Coronavirus updates April 2022

[Gloria27]

Let me try to explain this as simply as I can. No attitude from me at all. Just truly want to try to help you understand.

1. If everyone got vaccinated the virus would have died out.
2. Because so many did not get vaccinated the virus was able to survive and mutate.
3. Getting vaccinated helps lower the risk of getting Covid and then transferring it to others.

You wrote: "I don't need reasons not to get vaxxed, I need reasons to get vaxxed."
I thought you said you couldn't get vaccinated for medical reasons. But now the truth comes out. No offense to anyone who actually could not get vaccinated for medical reasons. The pandemic lives because of those who selfishly refused to get vaccinated. Not because of those who have a valid medical reason.

Anyway, I do not care why you did not get vaccinated. It is none of my business. You brought it up. I just don't want misinformation being spread. This thread exists to share info and facts.

1. You literally cannot vaccinate the whole globe at once, it is logistically impossible. As you know there weren't enough vaccines to go around at first so people had to wait for them to be made. By the time everyone had access, the virus mutated!

2. Some people cannot get vaccinated at all because of various disease including clotting diseases like ET or a million others.

3.Getting vaccinated helps- AGREED! but it comes with a risk, risk that some people might not want to take. There are plenty who are learning to walk again after getting vaxxed, and plenty who suffer from Covid long haul, it should be a choice.

I have a medical reason not to get vaxxed but also don't want to. The lack of transparency and how everything was handled since it began just put me off.

 

[missy]

We're Toying With a Ruinous End to COVID Travel Masking​

— CDC's powers to protect the public during health emergencies hangs in the balance​

by Lawrence O. Gostin, JD April 20, 2022

On Feb. 2, 2021, near the height of the COVID-19 pandemic, the CDC issued a public health order requiring masks in interstate transportation and at transit hubs, including airplanes, trains, and mass transit. The Transportation Security Administration (TSA) issued a security directive to enforce CDC's order. Ever since, CDC has extended the mandate, with the most recent extension setting the mandate to expire on May 3. The agency was not expected to renew it after that, so long as the current BA.2 surge does not cause significant spikes in hospitalizations and deaths, as occurred in the U.K.

But on April 18, a federal judge struck down CDC's latest order. The TSA immediately stopped enforcement while airlines abandoned masking rules, creating confusion and chaos at the nation's transportation hubs. I can't think of a more ruinous way for COVID-19 era travel masking to end then at the hand of a single federal judge in Florida. First let's talk about that judge before discussing the implications for CDC and the nation's health.
The Judge's Ruling
President Trump appointed Judge Kathryn Kimball Mizelle in late 2020 and the Senate confirmed her on a strict party-line vote, despite the American Bar Association rating her "not qualified." Judge Mizelle's recent ill-informed opinion further demonstrates her lack of qualifications. She gratuitously adds fuel to the COVID-19 culture wars in saying unmasked passengers are "forcibly removed from their airplane seats, denied boarding at the bus stop, and turned away at the train station door." She said it was akin to a "quarantine" which CDC has no power to do.

But of course, the agency has that power. The CDC regulations -- which it has implemented for a half century -- are known as the "quarantine rule." Under those regulations, the agency has long exercised powers to detain persons who are infected or exposed. It has exercised that authority without challenge for multiple health threats, including smallpox, tuberculosis, Ebola, and COVID-19 on airlines and cruise ships.
In the last couple days I've often been asked, does this judge have such awesome power and shouldn't the Biden administration simply refuse to comply? She does have that power unless the Justice Department gets the order stayed on appeal. Until that happens, the CDC should comply with the judge's order. Why? Well, we have been down this road before. When CDC's housing eviction moratorium first came before the Supreme Court, it was due to expire. The Justices upheld the order, but warned CDC not to test it by extending the moratorium. Biden should have complied, but instead he extended the moratorium. That led the Court to strike down the eviction moratorium, taking that tool out of CDC's toolbox forever. Whatever we think of a judge's decision, it is the rule of law -- so we must swallow hard and comply.

Waiting on a White House Response
The White House has a tough legal and political calculation to make. The White House just announced if CDC deems a mask mandate necessary, the Justice Department will appeal Judge Mizelle's ruling. If it appeals to the 11th Circuit, there is a risk of an adverse result, which sets an even worse precedent. Ultimately, I think the Supreme Court might narrowly uphold the order, but a conservative 6-3 supermajority could significantly narrow CDC's powers under the Public Health Services Act. So, the White House would be taking a legal risk. President Biden also faces a political risk. The transit mask requirement was likely to expire on May 3, and an appeal would create blowback from governors, the public, and the airline industry. The path of least resistance is to let it drop.
But I advise the White House to fight. Don't let an ethically and legally erroneous decision stand unchallenged. Why? This opinion literally handcuffs the CDC, making it less able to end the COVID-19 pandemic and, more importantly, to act nimbly and decisively when the next health crisis hits -- and it will. The CDC will forever be looking over its shoulder, gun-shy and reluctant to rapidly and firmly respond. Conservatives should be careful what they wish for. Americans will look to the CDC to protect them from the next dreaded outbreak and they will want a strong and vibrant public health agency.

A Dangerous Limit on CDC's Power
Let's dig in deeper. There is a conversation to be had as to whether the CDC has the power to reach into a state and regulate individuals or businesses, which it did with the housing eviction moratorium. But the CDC has an undisputed legal and constitutional mandate to prevent the spread of a dangerous virus across state lines or international borders. CDC's mask mandate was a textbook case of a power at the core of CDC's authority. If it can't require an unintrusive health measure on a flight from, say, New York to Los Angeles, then it literally can't do anything -- other than to issue voluntary recommendations. What if a person with multidrug-resistant tuberculosis boards a flight and exposes passengers? Surely CDC could conduct surveillance, contact tracing, and isolate or quarantine infected or exposed passengers. In fact, CDC did just that during the Ebola epidemic originating from West Africa.

The Public Health Service Act (42 USC § 264) authorizes the HHS Secretary "to prevent the entry and spread of communicable diseases from foreign countries into the United States and between states." That broad power includes "inspection, fumigation, disinfection, sanitation, pest extermination ... and other measures, as in his judgment may be necessary."
Judge Mizelle read that statute so narrowly that it limits CDC to basic sanitation, which is virtually useless against SARS-CoV-2. But it's vital that CDC should have the powers it deems necessary to protect the public's health. If Judge Mizelle's decision is allowed to stand unchallenged, it means that when the next variant hits, say this winter, the CDC won't be able to require masking or literally any other effective measure. Do we really want to curb CDC's powers so that it has to fight health emergencies with its hands tied behind its back?
Lawrence O. Gostin, JD, is a University Professor, Georgetown University's highest academic rank, where he directs the O'Neill Institute for National & Global Health Law. He is also director of the World Health Organization Collaborating Center on National & Global Health Law. He is the author of the book, Global Health Security: A Blueprint for the Future.

 

[missy]

BA.2 Variants Dominant in U.S.; USPSTF Nixes Hormone Tx; More Child Hepatitis Cases​

— A daily roundup of news on COVID-19 and the rest of medicine​

by Joyce Frieden, Washington Editor, MedPage Today April 20, 2022

Note that some links may require registration or subscription.
Two BA.2 variants -- the original lineage and BA.2.12.2 -- now account for 93%of COVID-19 cases in the U.S., according to the CDC.
The CDC has launched a new center for forecasting infectious diseases. (ABC News)
The FDA warned 12 companies that their skin lightening products containing hydroquinone are not "generally recognized as safe and effective" (GRASE) and therefore can't be sold over the counter.

In other FDA news, the agency released a final rule for the addition of fluoride to bottled water, amending the allowable level for fluoride to 0.7 mg/L.
COVID spread can be prevented with better ventilation, but that strategy is not getting much attention. (Kaiser Health News)
As of Wednesday at 8 a.m. EDT, the unofficial COVID toll in the U.S. reached 80,769,604 cases and 990,629 deaths, increases of 42,563 and 362, respectively, since this time yesterday.
In new draft guidelines, the U.S. Preventive Services Task Force is still recommending against hormone therapy to prevent chronic conditions in postmenopausal persons.
Researchers are hoping that a project that involves going house-to-house in some low-income countries to record the cause of deaths will help reduce preventable fatalities. (New York Times)
Sutter Health hospitals in Northern California are locking out thousands of nurses who staged a recent 1-day strike. (San Francisco Chronicle)

"We're done with dead kids. We're done with accidental overdoses." -- Bars in the U.S. are starting to dole out fentanyl testing strips for injection-drug users. (Reuters)
More cases of hepatitis among children have been detected in four European countries, the European Centre for Disease Prevention and Control said. (CBS News)
An avian flu outbreak on a farm in Lancaster County, Pennsylvania forced authorities there to order the killing of 1.4 million chickens. (Lancaster Online)
Delta Airlines was forced to revise its statement saying it had dropped its COVID-19 mask mandate because the coronavirus was now "an ordinary, seasonal virus." (NPR)

 

[missy]

‘Not how to stop a pandemic’​

Masks will no longer be required on (most) planes, trains and automobiles in the U.S. after a Florida judge ruled this week that the country’s top public health agency overstepped its federal authority to extend a mandate for public transit. Major airline carriers were quick to follow suit. “We are relieved to see the U.S. mask mandate lift to facilitate global travel as COVID-19 has transitioned to an ordinary seasonal virus,” Delta Air Lines said in a memo to customers Monday evening announcing the carrier’s switch to mask-optional travel. But after fielding blowback for calling Covid an “ordinary seasonal virus” Delta updated its memo the following day: “We are relieved to see the U.S. mask mandate lift to facilitate global travel as COVID-19 transitions to a more manageable respiratory virus — with better treatments, vaccines and other scientific measures to prevent serious illness.” Although airplanes tend to have enhanced air filtration system, the risk of airborne transmission remains, especially for those who are immunocompromised. Photographer: Bing Guan/Bloomberg As Americans are again divided over pandemic protocol, one thing is certain: Covid is most definitely not an ordinary seasonal virus — at least not yet. And based on what we know about the pathogen’s ability to spread through inhalation of aerosol particles (which can carry SARS-CoV-2), there’s reason to exercise caution as mask mandates drop. When outdoors, aerosol particles are easily diluted, but indoors, especially in poorly ventilated spaces, they can linger in the air and be inhaled by others sharing the area. The Centers for Disease Control and Prevention says the particles can stay suspended in air for minutes — or even hours. “This is not the right time to get rid of masks,” says Abraar Karan, an infectious disease physician at Stanford University. Karan says that placing the onus of mitigating risk on individuals is “not how to stop a pandemic.” Although airplanes tend to have enhanced air-filtration systems — some scientists are even studying how well these filters catch Covid — risk of airborne transmission remains, especially for those who are immunocompromised. Karan says that risk is even higher in crowded subway cars or packed buses where ventilation may not be as good. Though not effective as a public health strategy, one-way masking does have some benefit, Karan says. He recommends a well-fitting respirator-style mask, such as a KN95 or N95, and replacing it when no longer viable. It’s important to ensure the mask fits snugly over both your face and mouth. — Madison Muller

​ ​ ​ ​ Track the recovery​

New Zealand Tourism to Take Years to Recover​ New Zealand expects the international tourism market to take more than three years to recover to pre-Covid levels as it gradually dismantles some of the world’s strictest pandemic border controls. Global airlines will take some time to resume operations and some people will be cautious about traveling again because of high costs, Rene de Monchy, chief executive officer of Tourism New Zealand, said in an interview. Read the full story here.

 

[missy]

"

SARS-CoV-2 transmission on planes​

Katelyn Jetelina April 20, 2022

On Monday, a Florida judge voided the U.S. mandate for public transit, which includes planes, trains, and buses. Several airlines immediately announced they dropped masks. And, in true pandemic fashion, an intense debate about masks ensued.
There are health equity concerns. There are legal concerns, like setting the precedent that the CDC doesn’t have authority during a public health emergency. And there are epidemiological concerns.
In particular, I’ve noticed dangerous rhetoric around the perceived lack of transmission on planes. This misinformation stemmed from the Senate Committee hearing when several airline CEOs said “99.97 of airborne pathogens are captured by filters” so “masks serve no purpose.” While the first claim may be true, the second is not.
Here is a review of the scientific evidence.

Modes of transmission​

Like I’ve written before, filtration and ventilation are powerful layers of protection against SARS-CoV-2 and other viruses. Airplanes, in particular, have fantastic systems with an estimated 10-20 air changes per hour (for context, a hospital has 6 air changes per hour). A Department of Defense report found plane ventilation and filtration systems reduced the risk of airborne SARS-CoV-2 exposure by 99%. Because of this, transmission occurs less frequently than one might intuitively expect given lots of people in close quarters with shared air. A scientific group reviewed 18 peer-reviewed studies or public health reports of flights published between January 24, 2020 to 21 September 21, 2020 and concluded that “transmission of SARS-CoV-2 can occur in aircrafts but is a relatively rare event.”
But, like any mitigation layer, ventilation/filtration isn’t perfect in stopping transmission. This is because of two things:

1. You need to get to the airplane, and many spaces, like crowded boarding areas, don’t have great ventilation. Also, filtrations systems are not turned on during the boarding process. One of my favorite aerosol scientists, Jose-Luis Jimenez, documented CO2 levels on his recent international plane trip. The highest CO2 level (the higher the value, the worse ventilation) was while boarding and taxiing to the runway.
   

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   Jose-Luis Jimenez Twitter
2. SARS-CoV-2 is spread through aerosols and droplets. Filtration is great for aerosols, which float and suspend in the air for hours. But the air actually has to get filtered first. You can inhale SARS-CoV-2 aerosols before they reach the filter. Also, filtration isn’t effective for larger droplets, which can travel up to 6 feet, but then fall to the ground due to gravity. Masks help with droplets.

Proximity matters​

Because modes of transmission differ, scientific studies have shown that proximity to the index case (i.e., person originally infected before boarding) on a plane impacts risk of infection during a trip. A very extensive studytraced all 217 passengers and crew from a 10-hour flight from London → Vietnam in March 2020. At the time, masks were not mandatory nor widely used. The index case was in business class and symptomatic (fever and cough). The scientists found 16 cases were acquired in-flight (i.e., secondary cases), 12 of which were in business class. This equated to a 75% attack rate in business class. Two cases were in economy class and another case was a staff member.

[IMG alt="An external file that holds a picture, illustration, etc. Object name is 20-3299-F1.jpg"]https://ecp.yusercontent.com/mail?url=https%3A%2F%2Fcdn.substack.com%2Fimage%2Ffetch%2Fw_1200%2Cc_limit%2Cf_auto%2Cq_auto%3Agood%2Cfl_progressive%3Asteep%2Fhttps%253A%252F%252Fbucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com%252Fpublic%252Fimages%252F1c3c3be6-22d8-422a-8278-6e23aa29eaf7_600x168.jpeg&t=1650536081&ymreqid=5ff2e1e5-7893-c4e5-1c5e-6a0000012000&sig=0k1BvGZbOSuq5F6OikH9XQ--~D[/IMG]​

Figure source: DOI 10.3201/eid2611.203299
Another study assessed a flight from Israel → Germany in March 2020 with no masks. They found secondary cases were two rows away from the index case.

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Figure source: DOI10.1001/jamanetworkopen.2020.18044
The importance of proximity is consistent with other viral outbreaks on planes. In a review of 14 studies, researchers found an overall influenza attack rate of 7.5%, but 42% of the cases were seated within two rows of the index case. A similar finding was documented with SARS on a flight: 34% attack rate within 3 rows of the index case compared to 11% attack rate among persons seated elsewhere.
It’s important to note that there are many examples of secondary cases not in close proximity. In the London to Vietnam study, 2 cases were not in business class, but instead 15 rows behind in economy and another was a staff member at the back of the plane. Another study found that 11 people who contracted the virus on the plane were outside the usual parameters (2 rows in front and behind).

That’s because people move a lot on planes​

Before the pandemic, a scientific group traveled on 10 intercontinental flights to assess the behaviors and movements of people on planes and the impact on viral transmission. Of the 1,296 passengers observed, 38% left their seat once, 13% left twice, and 11% left more than two times. In total, 84% of passengers had a close contact with an individual seated beyond a 1-meter radius from them. People with the most contacts were seated in the aisle compared to the window.

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Percent of contacts by seating position across all flights. Figure Source: DOI: 10.1073/pnas.1711611115 found here
One would hypothesize, then, that aisle seat passengers have a higher risk of infection. But a SARS-CoV-2 study found the exact opposite. The attack rate was higher for passengers in window seats (7 cases/28 passengers) compared to non-window seats (4/83). Importantly, the 7 window passengers said they never left their seat too. In another modeling study, scientists found that you definitely don’t want to sit next to an infected person. Beyond that, you just don’t want to sit behind them. But you may not be able to decide what seat to take.

Masks help​

Regardless of where you sit on the plane, evidence shows that masks help reduce transmission. Because randomized control trials are not feasible, we’ve had to rely on descriptive and modeling studies to assess the impact of masks on planes.
In a scientific review of studies early in the pandemic, two public health reports extensively assessed transmission rates in the presence of rigid masking. The results affirmed low transmission with masking:

• The first flight had 25 index cases but only 2 secondary cases. One of which was seated next to a row with 5 index cases.
• On 5 Emirates Airlines (served food onboard) flights with more than 1500 passengers found no secondary cases identified despite 58 index cases

A great modeling study was published in 2021 with a few very interesting findings, too:

• During a 2-hour flight with no masks, the average probability of infection was 2%. But if one sat next to an index case, the probability rose to 60%.
• During a 12-hour flight with no masks, the average probability of infection is 10% (or 1 in 10). If one sat next to an index case, the probability rose to 99%.
  • If everyone wore high efficiency masks the whole time, the probability was reduced by 73%. If everyone wore low efficiency masks, the probability was reduced by 32%.
  • If face masks were worn by all passengers except during a one-hour meal service, the probability was decreased by 59% (high efficiency masks) or 8% (low efficiency masks).

Another modeling study found the impact of masks increased with passenger count on a Boeing 737. With small passenger counts, few passengers were near each other, so mask wearing didn’t make a big impact. But as the plane filled, more passengers were forced closer together, and risk accelerated. So the impact of masks was more apparent.

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Source: https://doi.org/10.1016/j.jairtraman.2021.102175

Community spread​

Transmission on a plane doesn’t just impact those on the plane: infections will spill over and drive community transmission, too. One study assessed an outbreak on an international flight that landed in Ireland in the summer of 2020. Despite low occupancy on the plane, 13 secondary cases occurred equating to a 9.8-17.8% attack rate. Onward transmission resulted in spread to 59 cases in six of eight health regions in Ireland, which required national oversight.

[IMG alt="An external file that holds a picture, illustration, etc. Object name is 2001624-f3.jpg"]https://ecp.yusercontent.com/mail?url=https%3A%2F%2Fcdn.substack.com%2Fimage%2Ffetch%2Fw_346%2Cc_limit%2Cf_auto%2Cq_auto%3Agood%2Cfl_progressive%3Asteep%2Fhttps%253A%252F%252Fbucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com%252Fpublic%252Fimages%252Fb456dac2-d10f-4aed-8a9f-d359db9a6a2b_674x899.jpeg&t=1650536081&ymreqid=5ff2e1e5-7893-c4e5-1c5e-6a0000012000&sig=pCPtfesTS9Io_prKc2Ii7w--~D[/IMG]​

Figure source: DOI 10.2807/1560-7917.ES.2020.25.42.2001624

Bottom line​

Planes have great filtration/ventilation systems and vaccines are highly effective, but no mitigation measure is perfect. Wear your mask while traveling, especially with increasing case trends. The layered approach will help reduce your individual-level risk, but perhaps more importantly will help travelers who are high risk and the greater community. To me, wearing a mask is just not that big of an inconvenience for good health.

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[missy]

SARS-CoV-2 Vaccination and Myocarditis in a Nordic Cohort Study of 23 Million Residents

This cohort study conducted using nationwide registers assesses the risks of myocarditis and pericarditis after SARS-CoV-2 messenger RNA vaccinations in a combined population of 23.1 million individuals across Denmark, Finland, Norway, and Sweden.

jamanetwork.com

"
April 20, 2022

SARS-CoV-2 Vaccination and Myocarditis in a Nordic Cohort Study of 23 Million Residents​

JAMA Cardiol. Published online April 20, 2022. doi:10.1001/jamacardio.2022.0583
COVID-19 Resource Center

• https://jamanetwork.com/journals/jamacardiology/fullarticle/2791257
  

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Key Points
Question Is SARS-CoV-2 messenger RNA (mRNA) vaccination associated with risk of myocarditis?
Findings In a cohort study of 23.1 million residents across 4 Nordic countries, risk of myocarditis after the first and second doses of SARS-CoV-2 mRNA vaccines was highest in young males aged 16 to 24 years after the second dose. For young males receiving 2 doses of the same vaccine, data were compatible with between 4 and 7 excess events in 28 days per 100 000 vaccinees after second-dose BNT162b2, and between 9 and 28 per 100 000 vaccinees after second-dose mRNA-1273.
Meaning The risk of myocarditis in this large cohort study was highest in young males after the second SARS-CoV-2 vaccine dose, and this risk should be balanced against the benefits of protecting against severe COVID-19 disease.
Abstract
Importance Reports of myocarditis after SARS-CoV-2 messenger RNA (mRNA) vaccination have emerged.
Objective To evaluate the risks of myocarditis and pericarditis following SARS-CoV-2 vaccination by vaccine product, vaccination dose number, sex, and age.
Design, Setting, and Participants Four cohort studies were conducted according to a common protocol, and the results were combined using meta-analysis. Participants were 23 122 522 residents aged 12 years or older. They were followed up from December 27, 2020, until incident myocarditis or pericarditis, censoring, or study end (October 5, 2021). Data on SARS-CoV-2 vaccinations, hospital diagnoses of myocarditis or pericarditis, and covariates for the participants were obtained from linked nationwide health registers in Denmark, Finland, Norway, and Sweden.
Exposures The 28-day risk periods after administration date of the first and second doses of a SARS-CoV-2 vaccine, including BNT162b2, mRNA-1273, and AZD1222 or combinations thereof. A homologous schedule was defined as receiving the same vaccine type for doses 1 and 2.
Main Outcomes and Measures Incident outcome events were defined as the date of first inpatient hospital admission based on primary or secondary discharge diagnosis for myocarditis or pericarditis from December 27, 2020, onward. Secondary outcome was myocarditis or pericarditis combined from either inpatient or outpatient hospital care. Poisson regression yielded adjusted incidence rate ratios (IRRs) and excess rates with 95% CIs, comparing rates of myocarditis or pericarditis in the 28-day period following vaccination with rates among unvaccinated individuals.
Results Among 23 122 522 Nordic residents (81% vaccinated by study end; 50.2% female), 1077 incident myocarditis events and 1149 incident pericarditis events were identified. Within the 28-day period, for males and females 12 years or older combined who received a homologous schedule, the second dose was associated with higher risk of myocarditis, with adjusted IRRs of 1.75 (95% CI, 1.43-2.14) for BNT162b2 and 6.57 (95% CI, 4.64-9.2 for mRNA-1273. Among males 16 to 24 years of age, adjusted IRRs were 5.31 (95% CI, 3.68-7.6 for a second dose of BNT162b2 and 13.83 (95% CI, 8.08-23.6 for a second dose of mRNA-1273, and numbers of excess events were 5.55 (95% CI, 3.70-7.39) events per 100 000 vaccinees after the second dose of BNT162b2 and 18.39 (9.05-27.72) events per 100 000 vaccinees after the second dose of mRNA-1273. Estimates for pericarditis were similar.
Conclusions and Relevance Results of this large cohort study indicated that both first and second doses of mRNA vaccines were associated with increased risk of myocarditis and pericarditis. For individuals receiving 2 doses of the same vaccine, risk of myocarditis was highest among young males (aged 16-24 years) after the second dose. These findings are compatible with between 4 and 7 excess events in 28 days per 100 000 vaccinees after BNT162b2, and between 9 and 28 excess events per 100 000 vaccinees after mRNA-1273. This risk should be balanced against the benefits of protecting against severe COVID-19 disease.

Introduction
The European Medicines Agency and European Commission have, by October 2021, approved 4 vaccines against SARS-CoV-2: BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), AZD1222 (AstraZeneca), and Ad26.COV2.S (Janssen). The Nordic countries have primarily used the 2 messenger RNA (mRNA) vaccines BNT162b2 and mRNA-1273. These vaccines have been shown to be efficient and safe, although cases of myocarditis or pericarditis during the first weeks after vaccination have been reported.1
Case reports, surveillance data, and other reports from the US, Israel, and Canada indicate an increased risk of myocarditis after vaccination with SARS-CoV-2 mRNA vaccines, higher after the second dose, especially in younger men.2-9 Data from Canada and France indicate more cases of myocarditis after mRNA-1273 than after BNT162b2, but this remains to be elucidated.10,11
In nationwide cohort studies in Denmark, Finland, Norway, and Sweden, we evaluated the risks of myocarditis and pericarditis following SARS-CoV-2 vaccination in a combined population of 23.1 million individuals. High-quality nationwide registers enabled us to evaluate the risk by vaccine product, vaccination dose number, sex, and age.
Methods
Setting and Data Sources
We conducted population-based cohort studies in 4 Nordic countries (Denmark, Finland, Norway, and Sweden) using linked data from nationwide health registers on SARS-CoV-2 vaccination, myocarditis and pericarditis diagnoses, and other covariates (eMethods in the Supplement). All Nordic residents are assigned a unique personal identifier at birth or immigration, enabling deterministic linkage between registers. These countries have universal and tax-financed health care systems, and reporting to national registers is mandatory, providing near-complete follow-up of all residents over time.12,13 Each cohort study was analyzed separately according to a common protocol, and the results were combined by meta-analyses. On the basis of current law in each of the countries, this register-based research was conducted according to the laws, regulations, and authority permits, and informed consent from individuals was not applicable (eMethods in the Supplement).14 The requirement for obtaining informed consent was waived because all data are publicly available. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
Study Population
We included all persons who turned 12 years or older in 2021, were residents on January 1, 2017, and were alive and still residing within the country on December 27, 2020. We excluded 20 211 persons with any myocarditis or pericarditis in inpatient or outpatient hospital care from January 1, 2017, to December 26, 2020 (eMethods in the Supplement).
SARS-CoV-2 Vaccination
The Nordic countries implemented national vaccination campaigns against SARS-CoV-2 from December 27, 2020, providing free vaccinations to all residents. Phased distribution plans were implemented, prioritizing vaccination of individuals at highest risk of COVID-19 complications (ie, nursing home residents, health care workers, and older adults). Denmark, Finland, and Norway almost exclusively used mRNA vaccines after full or partial discontinuation of AZD1222 in March 2021 because of serious but rare events of thrombosis with thrombocytopenia.15,16 Sweden used AZD1222 for a majority of the population older than 64 years and mRNA vaccines in other age groups. The vaccine Ad26.COV2.S had very limited use. The Nordic countries vaccinated approximately 6 times more individuals with BNT162b2 than with mRNA-1273 because of higher availability of the former vaccine. We studied risk of myocarditis and pericarditis in 28-day risk periods after the administration date of the first and second dose with BNT162b2, mRNA-1273, and AZD1222 (Figure 1). A homologous schedule was defined as receiving the same vaccine type for doses 1 and 2.
Myocarditis and Pericarditis
We defined incident outcome events as the date of first hospital admission for myocarditis or pericarditis from December 27, 2020, onward. The primary outcome was a main or secondary diagnosis of myocarditis at discharge from inpatient hospital care. Secondary outcomes were a main or secondary diagnosis of pericarditis (inpatient hospital care) and a main or secondary diagnosis of either condition (myocarditis or pericarditis) combined from either inpatient or outpatient hospital care (eTable 1 in the Supplement).
Covariates
We used the following covariates for adjustment and stratification: sex, age, calendar period, health care worker status, nursing home resident, and 5 comorbidities (pulmonary disease, kidney disease, autoimmune disease, cardiovascular disease or diabetes, and cancer) defined by diagnoses before the start of follow-up (eTable 2 in the Supplement). We also adjusted for verified SARS-CoV-2 infection before December 27, 2020, whereas infection after this date was a censoring event. We defined having SARS-CoV-2 as the sample date of a positive reverse transcriptase–polymerase chain reaction or lateral flow test.
Statistical Analysis
We took advantage of the longitudinal information in our national cohorts to calculate exact unvaccinated and vaccinated person-time at risk for each individual (Figure 1). We started follow-up on December 27, 2020. Each individual was followed up until first outcome event of interest or a censoring event, defined as first occurrence of a positive test result for SARS-CoV-2 infection, receiving Ad26.COV2.S vaccine, receiving a third dose of any SARS-CoV-2 vaccine, emigration, death, or country-specific study end (latest October 5, 2021). Individuals contributed person-time as unvaccinated until the first vaccination. After each first or second dose, individuals contributed person-time in a main risk period of interest defined as day 0 up to and including day 28 (Figure 1). The resulting follow-up periods and numbers of myocarditis and pericarditis cases were aggregated for all individuals according to vaccination status (ie, unvaccinated, risk period after first dose, and risk period after second dose).
We used Poisson regression for the number of events to estimate incidence rate ratios (IRRs) with 95% CIs, comparing rates in the risk periods after vaccination with rates in unvaccinated periods. We took potential confounding factors into account by adjustment in 3 models. Model 1 included adjustment for sex and age group (12-15, 16-19, 20-24, 25-29, 30-39, 40-64, and ≥65 years). Model 2 included adjustment as in model 1 and for health care worker status, nursing home resident, and the aforementioned comorbidities. Model 3 included adjustment as in model 2 and for calendar periods (December through March, April through June, and July to the study end). We used model 2 in the main analyses, whereas models 1 and 3 were used for sensitivity analyses. We included subgroup results according to sex and age (12-15, 16-24, 25-39, and ≥40 years). Analyses were conducted in Denmark and Sweden with SAS, version 9.4 (SAS Institute Inc), in Finland with R, version 3.6.3 (R Foundation for Statistical Computing), and in Norway with Stata, version 16.0 (StataCorp LLC).
Meta-analyses
Meta-analyses of the IRR estimates were based on random-effects models implemented using the mixmeta package17 of R.18 We tested the homogeneity of country-specific estimates using the Cochran Q test,19 calculated the pooled incidence rates using the sum of events and person-years in the countries, and calculated the pooled excess rates using the pooled incidence rates and IRR estimates. For the CIs, we used the delta method, assuming independence of the incidence rates and IRR estimates.
Supplementary Analyses
In a complementary analysis, we studied incident myocarditis within 28 days following SARS-CoV-2 infection from August 1, 2020, to end of study. We also studied risk of myocarditis or pericarditis in a shorter 7-day risk period. Furthermore, among myocarditis cases, we estimated the proportion of patients discharged on day 4 or later and the proportion of cases in which the patient died within 28 days of the admission date, using the Kaplan-Meier estimator. Among myocarditis cases after vaccination, we calculated the median time from vaccination to outcome (hospital admission date).
Results
Across 4 Nordic countries, 23 122 522 residents (49.8% male and 50.2% female) were followed up from December 27, 2020, to October 5, 2021, at the latest. By study end, 17 129 982 residents (74%) had received 2 doses and 1 681 930 residents (7%) had received 1 dose of SARS-CoV-2 vaccines. By study end, 487 751 of 1 238 004 persons (39%) aged 12 to 15 years, 2 009 995 of 2 675 558 persons (75%) aged 16 to 24 years of age, 3 736 517 of 5 046 164 persons (74%) aged 25 to 39 years, and 12 579 805 of 14 162 796 persons (89%) aged 40 years or older had received at least 1 dose of a SARS-CoV-2 vaccine (Table 1; eTable 3 in the Supplement).
Myocarditis and Pericarditis During Follow-up
During the 28-day risk periods following vaccination and during unvaccinated periods (13 million person-years in total), we observed 1077 incident myocarditis cases and 1149 incident pericarditis cases. Incidence rates of myocarditis during the unvaccinated period were 9.7 per 100 000 person-years for males and 4.3 per 100 000 person-years for females (Table 2). Among individuals aged 16 to 24 years, incidence rates were 18.8 per 100 000 person-years for males and 4.4 per 100 000 person-years for females. Incidence rates of pericarditis increased with age (eTable 4 in the Supplement).
Vaccination and Myocarditis
During the 28-day risk period, we observed 105 myocarditis cases following administration of the first dose of BNT162b2 and 115 myocarditis cases following the second dose. We also observed 15 myocarditis cases following administration of the first dose of mRNA-1273 and 60 myocarditis cases following the second dose.
Adjusted IRRs comparing the 28-day risk periods following first and second doses compared with unvaccinated periods were 1.38 (95% CI, 1.12-1.69) for the first dose of BNT162b2 and 1.75 (95% CI, 1.43-2.14) for the second dose, and 1.16 (95% CI, 0.69-1.93) for the first dose of mRNA-1273 and 6.57 (95% CI, 4.64-9.2 for the second dose. Among males, after the first and second doses, adjusted IRRs were 1.40 (95% CI, 1.09-1.80) for the first dose of BNT162b2 and 2.04 (95% CI, 1.61-2.5 for the second dose, and 1.45 (95% CI, 0.84-2.52) for the first dose of mRNA-1273 and 8.55 (95% CI, 6.40-11.41) for the second dose. Among females, following the first and second doses, adjusted IRRs were 1.46 (95% CI, 1.01-2.11) for the first dose of BNT162b2 and 1.25 (95% CI, 0.77-2.05) for the second dose, and 1.45 (95% CI, 0.35-5.97) for the first dose of mRNA-1273 and 2.73 (95% CI, 1.27-5.87) for the second dose.
Among males 16 to 24 years of age, the adjusted IRRs for myocarditis were 5.31 (95% CI, 3.68-7.6 for a second dose of BNT162b2 and 13.83 (95% CI, 8.08-23.6 for a second dose of mRNA-1273. For females, the comparative adjusted IRRs were lower (Table 2, Figure 2, Figure 3; eFigure 1 in the Supplement).
We also estimated the excess numbers of myocarditis events per 100 000 vaccinees in the 28-day risk periods. Among all males, these numbers were 0.27 (95% CI, 0.09-0.46) events after the first dose of BNT162b2 and 0.67 (95% CI, 0.46-0.8 events after the second dose, and 0.33 (95% CI, −0.11 to 0.7 events after the first dose of mRNA-1273 and 4.97 (95% CI, 3.62-6.32) events after the second dose. Among all females, the excess numbers of events per 100 000 vaccinees in the 28-day risk periods were 0.15 (95% CI, 0.02-0.2 events after the first dose of BNT162b2 and 0.09 (95% CI, −0.09 to 0.26) events after the second dose, and 0.05 (95% CI, −0.13 to 0.23) events after the first dose of mRNA-1273 and 0.48 (95% CI, 0.07-0.89) events after the second dose (Table 2).
Among males 16 to 24 years of age, the excess number of myocarditis events per 100 000 vaccinees in the 28-day risk periods after the first dose of BNT162b2 was 1.55 (95% CI, 0.70-2.39) events and after the second dose was 5.55 (95% CI, 3.70-7.39) events, and it was 1.75 (95% CI, −0.20 to 3.71) events after the first dose of mRNA-1273 and 18.39 (95% CI, 9.05-27.72) events after the second dose (Table 2).
For a heterologous schedule (1 dose with BNT162b2 and the other dose with mRNA-1273), 38 myocarditis cases (34 males) occurred following the second dose, with an excess number of events in males of 10.34 (95% CI, 6.86-13.83) events. In males aged 16 to 24 years, 17 myocarditis cases occurred, with an excess number of events of 27.49 (95% CI, 14.41-40.56) events (Table 2).
Vaccination and Pericarditis
Pericarditis in males followed a pattern similar to myocarditis by vaccine product and age but with lower IRRs. Pericarditis was rare in females aged 12 to 39 years. Among males aged 16 to 24 years of age, the excess number of pericarditis events within the 28-day risk period was 7.39 per 100 000 vaccinees (95% CI, 1.46-13.32) events for the second dose of mRNA-1273 (eTables 4 and 5 in the Supplement).
Vaccination and Myocarditis or Pericarditis Combined
The IRRs of myocarditis or pericarditis combined among males aged 16 to 24 years were slightly higher than those of myocarditis (Table 3). In males aged 25 to 39 years, the IRRs were generally lower. Among females aged 16 to 24 years, the IRRs were similar to those for males but with fewer events. Among males aged 12 to 15 years, the crude IRR was based on very few events among the vaccinated population (eTable 6 in the Supplement).
SARS-CoV-2 Infection and Myocarditis
During the 28-day risk period after a positive SARS-CoV-2 test, there were 73 myocarditis cases. Excess events of myocarditis were 3.26 (95% CI, 1.90-4.61) events per 100 000 individuals with a positive test result among all males, and 1.37 (95% CI, −0.14 to 2.87) events per 100 000 individuals with a positive test result among males aged 16 to 24 years (eTable 7 in the Supplement).
Supplementary Analyses
The IRRs and excess rates were slightly attenuated when model 1 was complemented by other covariates (model 2) and further attenuated when calendar period was added (model 3) (eFigure 2 and eTable 5 in the Supplement). Among males aged 16 to 24 years, adjustment for calendar period (model 3) yielded unstable point estimates with wide CIs for the second dose of mRNA-1273. Heterogeneity of the analyses across countries was not statistically significant (eFigure 2 in the Supplement); thus, we present the results as pooled 4-country estimates of IRRs and excess rates.
Of the 213 myocarditis cases in the 28-day risk window after a second dose of SARS-CoV-2 mRNA vaccination, 135 events occurred within the first week, yielding higher IRRs in the 7-day risk period (Table 2; eTable 8 in the Supplement). Among males aged 16 to 24 years, the adjusted IRRs were 12.50 (8.24-18.96) for a second dose of BNT162b2 and 38.29 (21.95-66.80) for a second dose of mRNA-1273.
For males aged 12 to 39 years, country-specific median time to hospital admission for myocarditis cases was 3 to 7 days (eTable 9 in the Supplement). Comorbid conditions did not differ markedly between vaccinated and unvaccinated myocarditis cases (eTable 10 in the Supplement). Median hospital length of stay was 4 to 5 days for both vaccinated and unvaccinated cases (eTable 11 in the Supplement). For all age groups, the 28-day mortality of the unvaccinated cases with myocarditis was 0.8% (95% CI, 0.3%-2.0%) and ranged from 0.2% (95% CI, 0.0%-0.4%) after the second dose of BNT162b2 to 4.5% (95% CI, 0.0%-13.2%) after the second dose of mRNA-1273; there were no deaths among cases for patients younger than 40 years (eTable 11 in the Supplement).
Discussion
This cohort study of 23.1 million residents across 4 Nordic countries showed higher rates of myocarditis and pericarditis within 28 days after being vaccinated with SARS-CoV-2 mRNA vaccines compared with being unvaccinated. The risks of myocarditis and pericarditis were highest within the first 7 days of being vaccinated, were increased for all combinations of mRNA vaccines, and were more pronounced after the second dose. A second dose of mRNA-1273 had the highest risk of myocarditis and pericarditis, with young males aged 16 to 24 years having the highest risk.
Myocarditis after mRNA vaccination was rare in this study cohort and even among young males. The risk of myocarditis following the mRNA vaccines has been evaluated by the US Food and Drug Administration, which concluded that the benefits of vaccination outweigh the risks and fully authorized the use of mRNA-1273 in persons 18 years or older and BNT162b2 in persons 16 years or older. In addition, BNT162b2 is authorized for emergency use in children 5 years or older.20,21 The European Medicines Agency concluded that the benefits of vaccination outweigh the risks and approved mRNA-1273 for use in persons 12 years or older and BNT162b2 for those 5 years or older.22,23 In addition, a comment published by the American College of Cardiology24 evaluated vaccine-associated myocarditis risk and concluded that the benefits of vaccination outweigh the risks. As of January 2022, there have been nearly 5.8 million deaths associated with COVID-19 worldwide since the start of the pandemic.25 All currently available SARS-CoV-2 mRNA vaccines are highly effective against severe COVID-19 and provide some protection against transmission and infection.26-28 There is some evidence that the mRNA-1273 vaccine, possibly owing to its higher concentration of mRNA, is associated with increased immunogenicity and effectiveness.29,30 This more profound immune response could be one reason for the higher risk of myocarditis, but this hypothesis needs to be investigated further.
Our findings are consistent with higher risk after the second dose and higher risk in young males.2,3,10,11,31-36 Excess events within 28 days in males aged 16 to 24 years of 5.55 events per 100 000 vaccinees after the second dose with BNT162b2 and 18.39 events per 100 000 vaccinees after the second dose with mRNA-1273 are among the highest reported.3,4,32,33Our finding of a higher risk of myocarditis after mRNA-1273 than after BNT162b2 in this group is in line with data from the US, Canada, France, and England.5,10,11,33,35 In comparison with previous studies, we had the advantage of data analyzed according to a common protocol from 4 different countries, and that showed similar directions of associations, despite considerable differences in prior SARS-CoV-2 infection levels and lockdown policies.
Strengths and Limitations
The main strengths of our study include the population-based cohort design in 4 Nordic countries, large sample size, near-complete follow-up, and independent ascertainment of vaccinations and diagnoses from nationwide registers with mandatory reporting. The findings in the meta-analyses were supported by consistent findings across all 4 countries, despite some country-specific differences in data sources, SARS-CoV-2 transmission, testing activities, and vaccination schedules.
There are also some limitations of the study. We defined events as an inpatient hospital admission with a corresponding main or secondary discharge diagnosis of myocarditis or pericarditis. Diagnostic codes have been shown to have 85% positive predictive value among patients younger than 60 years.37 Thus, without access to data on clinical measures, such as troponin levels, diagnostic imaging results, and endomyocardial biopsy, we studied myocarditis as diagnosed in clinical practice and could therefore not assess how many of these patients fulfilled all criteria for receiving a myocarditis diagnosis.38 However, the median hospital length of stay was 4 to 5 days for both unvaccinated and vaccinated patients, enabling sufficient time for adequate diagnostic procedures and indicative of no difference in disease severity between vaccinated and unvaccinated cases. Deaths were rare, with no deaths of persons younger than 40 years. Our findings in children aged 12 to 15 years were limited to relatively few exposed individuals because vaccination in this age group only recently started in most countries.
Surveillance bias, whereby increased focus and media attention on myocarditis as an adverse event after vaccination39 resulted in more subclinical cases being diagnosed, cannot be ruled out. Hence, all studies including data on vaccination and myocarditis after April 25, 2021, are likely prone to this potential surveillance bias. However, in our study, surveillance bias is unlikely to fully explain the differences between the first and second dose, between the 2 mRNA vaccines, and between age groups. Denmark and Norway had lower background incidence rates of myocarditis than Finland and Sweden.
We studied rates of myocarditis after a positive test result for SARS-CoV-2 infection. However, SARS-CoV-2 infection is associated with acute and postacute events other than myocarditis, including hospitalizations, intensive care unit admissions, and death.40 The present study showed increased risk of myocarditis after a positive test result for SARS-CoV-2 infection, and the risk was highest in the older age groups, whereas the risk of myocarditis after vaccination was highest in the younger age groups. However, the estimated risk of any outcome after SARS-CoV-2 infection will be dependent on the testing strategy. If only severe COVID-19 cases are tested, the association with other events will be strengthened owing to selection bias. Therefore, to reduce selection bias in our analyses of myocarditis after SARS-CoV-2 infection, we included only the period from August 2020 onward, when testing was widely available in the Nordic countries.
The 2 mRNA vaccines were used in the Nordic countries according to availability during 2021, and supply was limited during the first months of 2021. Furthermore, vaccination was first provided for older adults. The availability has thus varied across age, calendar months, and countries. The background incidence rate of myocarditis fluctuates with infectious disease burden, being typically higher during the fall and winter.41 Moreover, differences in lockdown measures affecting the spread of SARS-CoV-2 and other viruses could also affect the background incidence rate in both unvaccinated and vaccinated persons. Most of the younger age groups were vaccinated from July to September 2021, and very few during the spring. However, our supplementary model 3 with adjustment for calendar period resulted in wider CIs but did not substantially change the point estimates.
The observed risks of myocarditis and pericarditis are applicable to the current SARS-CoV-2 pandemic situation in the Nordic countries. In other settings, the background incidence of myocarditis and pericarditis and risks following vaccination may differ. Furthermore, we cannot draw conclusions from the study results to predict myocarditis and pericarditis after a third dose or for children younger than 12 years. We captured all hospitalizations for myocarditis and pericarditis in the Nordic countries during the study period; however, without access to data on clinical measures and diagnostic imaging results, future adjudication must assess how many of these patients fulfill all criteria for a myocarditis diagnosis. Although studies on the long-term prognosis of vaccine-associated cases of myocarditis are lacking and are urgently needed, some evidence suggests that the 28-day risk of death, hospital readmission rates, and development of heart failure appear low, especially in the younger age groups.34
Conclusions
In this cohort study of 23.1 million Nordic residents aged 12 years or older, the risk of myocarditis was higher within 28 days of vaccination with both BNT162b2 and mRNA-1273 compared with being unvaccinated, and higher after the second dose of vaccine than the first dose. The risk was more pronounced after the second dose of mRNA-1273 than after the second dose of BNT162b2, and the risk was highest among males aged 16 to 24 years. Our data are compatible with 4 to 7 excess events within 28 days per 100 000 vaccinees after a second dose of BNT162b2, and 9 to 28 excess events within 28 days per 100 000 vaccinees after a second dose of mRNA-1273. The risk of myocarditis associated with vaccination against SARS-CoV-2 must be balanced against the benefits of these vaccines.
"

 

[missy]

"

Mask Mandates Return to US College Campuses as Cases Rise​

Heather Hollingsworth and Ashraf Khalil, Associated Press
April 22, 2022

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.
The final weeks of the college school year have been disrupted yet again by COVID-19 as universities bring back mask mandates, switch to online classes and scale back large gatherings in response to upticks in coronavirus infections.
Colleges in Washington, D.C., New York, Pennsylvania, Massachusetts, Connecticut and Texas have reimposed a range of virus measures, with Howard University moving to remote learning amid a surge in cases in the nation's capital.
This is the third straight academic year that has been upended by COVID-19, meaning soon-to-be seniors have yet to experience a normal college year.

"I feel like last summer it was everyone was like, 'Oh, this is it. We're nearing the tail end,'" recalled Nina Heller, a junior at American University in Washington D.C., where administrators brought back a mask mandate about a month after lifting it. "And then that didn't quite happen, and now we're here at summer again, and there's kind of no end."

Mandates were shed widely in the wake of spring break as case numbers dropped following a winter surge fueled by the omicron variant. But several Northeast cities have seen a rise in cases and hospitalizations in recent weeks, as the BA.2 subvariant of the omicron variant continues to rapidly spread throughout the U.S.
"As much as we would like to move on and think that the pandemic is over, and I think we all would like that to happen at this point, it's wishful thinking," said Anita Barkin, co-chair of a COVID-19 task force for the American College Health Association. "The pandemic is still with us."
COVID-19 had eased so much at Williams College that the private liberal arts school in Massachusetts allowed professors to decide whether to require masks in their classes early last week. But just days later, with cases rising, it reinstated an indoor mask mandate, which was even stricter than what had been in place before.

"I think students are really feeling like people they know are dropping like flies," said junior Kitt Urdang, who's had a half-dozen friends test positive in recent days. "There's definitely been a lot more uncertainty than there's been on campus since COVID hit."
Philadelphia recently brought back its mask mandate, leading the University of Pennsylvania and Temple University to again require them starting Monday. Although the city ended the mandate Thursday, the colleges haven't made any changes.
In Washington, D.C., Howard University's main campus, affectionately dubbed "The Hilltop" by students and alums, was largely quiet this week, with many students taking classes and exams from home. The academic year is coming to a muted end as rising virus numbers prompted administrators to abruptly shift back to online education.

The city's COVID infection rate has more than doubled in April. Besides American, Georgetown and George Washington University also reinstated their indoor mask mandates. But Howard is the only one that has moved away from in-person instruction. The spring semester ends Friday, with final exams for most students starting next week. Administrators have promised an update on what this means for the May 7 commencement ceremony.

"I don't think people are super unhappy about wearing masks," said Lia DeGroot, a George Washington senior who never shed her mask during the single week the mandate was lifted at her school. "Of all of the things that the pandemic has disrupted, I think wearing masks is, you know, a relatively small thing to do. I think that's kind of the mindset that a lot of students have."

In nearby Baltimore, Maryland, Johns Hopkins University announced this month that it was testing all undergraduate students twice weekly through Friday, noting a steep rise in cases. The school also said masks would be required not just in classrooms, but in places like residence hall common areas.

In Houston, Rice University announced earlier this month that students should resume wearing masks in classrooms, citing an uptick in cases on campus. Large college parties also were canceled.

New Mexico State University took a different tack, announcing Monday that all students on campus must be fully vaccinated against COVID-19 by July 1, ending the option of submitting weekly tests as an alternative.

One of the few counties still identified by the CDC as having high spread is home to New York's Syracuse University, which announced Monday that it would again require masks in classrooms.

J. Michael Haynie, the school's vice chancellor for strategic initiatives and innovation, said in a letter that "it is important that we take reasonable action to minimize the impact of COVID infections" with finals and commencement fast approaching.
The University of Rochester in upstate New York, the University of Connecticut, Bowdoin College in Brunswick, Maine, and Columbia University in New York City took a similar approach. Many, like Columbia, noted that their surveillance testing programs were finding more cases.

While many students were eager to mask up, grumbling was emerging.

"We're to the point where we're tired of masks," said Neeraj Sudhakar, a Columbia grad student studying financial engineering. "We probably have a 99% vaccination rate, so at this point I think we just need to move on with the pandemic and treat it as endemic rather than going back to what we were doing the past two years."

Tammy Webber in Fenton, Michigan, and Robert Bumsted in New York, contributed to this report.

"

 

[missy]

"

Kids shots are coming. Who will get them?​

The pediatric Covid vaccine got some much-needed validation this past week. Turns out, as the omicron variant spread between mid-December and March, some 9 out of 10 children over age 5 who were hospitalized hadn’t been vaccinated. That helped show that the shots were working as intended to prevent the most severe Covid outcomes in kids. Getting American kids vaccinated hasn't been easy. Only 28% of children age 5 to 11 are fully vaccinated, according to data from the Centers for Disease Control and Prevention. A similar percentage of parents with kids in that age group said in a Kaiser Family Foundation survey that they “definitely” wouldn't get their child immunized against Covid. Blame mistrust in government, apathy and partisan politics. Yet vaccination of children is critical to preventing severe outcomes from Covid, the CDC report said, and unvaccinated kids are twice as likely to end up in the hospital. The agency's plea for widespread vaccination has consistently fallen flat. Even as omicron has continued to spread, momentum for getting shots into children's arms has tapered off. It's the same story with booster uptake in the 12-to-17 age group: Just 25% have gotten a third shot. Vaccination of children is critical to preventing severe outcomes from Covid, U.S. health officials say. Photographer: Cole Burston/Bloomberg So will there even be demand for shots for children under 5? We may soon know the answer. Pfizer is preparing to share the results of its three-dose vaccine trial among the youngest children. So far there's been data to show that it significantly increased antibodies against the omicron strain. (Meanwhile, Moderna's shot has also showed a strong immune response in children under 6, though efficacy was underwhelming.) The winter wave of omicron cases complicated and delayed Pfizer’s study of children under age of 5, as the highly transmissible variant decreased the two-shot regimen’s protection against infection. The earliest findings of Pfizer's shot in kids weren't that encouraging, so the drugmaker decided to test three doses instead. Pfizer has already seen a third-dose booster restore protection for adults. Following that line of thinking, the drugmaker just wrapped up a third-dose study in elementary school- age kids that it says boosted antibodies in that group. It's seeking authorization for a regimen that includes that additional boost. Within weeks, we'll likely know whether an extra dose of Pfizer's vaccine provides sufficient protection for children under 5. Some parents with kids in this age group have been eagerly awaiting this moment: One in 5 said they'd get a vaccine for their child right away if cleared, according to Kaiser. The next challenge will be persuading the reluctant and unsure parents to do the same. —Riley Ray Griffin "

 

[Gloria27]

"

​

Kids shots are coming. Who will get them?​

The pediatric Covid vaccine got some much-needed validation this past week. Turns out, as the omicron variant spread between mid-December and March, some 9 out of 10 children over age 5 who were hospitalized hadn’t been vaccinated. That helped show that the shots were working as intended to prevent the most severe Covid outcomes in kids. Getting American kids vaccinated hasn't been easy. Only 28% of children age 5 to 11 are fully vaccinated, according to data from the Centers for Disease Control and Prevention. A similar percentage of parents with kids in that age group said in a Kaiser Family Foundation survey that they “definitely” wouldn't get their child immunized against Covid. Blame mistrust in government, apathy and partisan politics. Yet vaccination of children is critical to preventing severe outcomes from Covid, the CDC report said, and unvaccinated kids are twice as likely to end up in the hospital. The agency's plea for widespread vaccination has consistently fallen flat. Even as omicron has continued to spread, momentum for getting shots into children's arms has tapered off. It's the same story with booster uptake in the 12-to-17 age group: Just 25% have gotten a third shot. Vaccination of children is critical to preventing severe outcomes from Covid, U.S. health officials say. Photographer: Cole Burston/Bloomberg So will there even be demand for shots for children under 5? We may soon know the answer. Pfizer is preparing to share the results of its three-dose vaccine trial among the youngest children. So far there's been data to show that it significantly increased antibodies against the omicron strain. (Meanwhile, Moderna's shot has also showed a strong immune response in children under 6, though efficacy was underwhelming.) The winter wave of omicron cases complicated and delayed Pfizer’s study of children under age of 5, as the highly transmissible variant decreased the two-shot regimen’s protection against infection. The earliest findings of Pfizer's shot in kids weren't that encouraging, so the drugmaker decided to test three doses instead. Pfizer has already seen a third-dose booster restore protection for adults. Following that line of thinking, the drugmaker just wrapped up a third-dose study in elementary school- age kids that it says boosted antibodies in that group. It's seeking authorization for a regimen that includes that additional boost. Within weeks, we'll likely know whether an extra dose of Pfizer's vaccine provides sufficient protection for children under 5. Some parents with kids in this age group have been eagerly awaiting this moment: One in 5 said they'd get a vaccine for their child right away if cleared, according to Kaiser. The next challenge will be persuading the reluctant and unsure parents to do the same. —Riley Ray Griffin "

Who is the author, what is his background and is there a peer reviewed study about what this article claims?

Is there any data and if yes, where is it coming from?

 

[missy]

Who is the author, what is his background and is there a peer reviewed study about what this article claims?

Is there any data and if yes, where is it coming from?

Hit the links in blue and it will take you to the source.

 

[Gloria27]

Bloomberg, Bloomberg, Bloomberg, Pfizer, Pfizer, Pfizer, Pfizer stocks...Pfizer.

Gotcha.

 

[missy]

Bloomberg, Bloomberg, Bloomberg, Pfizer, Pfizer, Pfizer, Pfizer stocks...Pfizer.

Gotcha.

You’re welcome Gloria

 

[Gloria27]

You’re welcome Gloria

it's actually a funny reply

 

[mellowyellowgirl]

I've been wanting to post this but was hesitant because of how pro vaccine this forum is.

I'm not sure how I feel about the vaccine for kids. I very grudgingly gave my kid one shot, he was fine but develops these red patches on his hands when he plays on play equipment. He plays on that same equipment every week and was able to do 7 run throughs with no marks. After the vaccine marks develop after 3 run throughs.

It's not anything that has affected him but I'm uncomfortable so he will not be receiving a second shot and to be honest I feel guilty about the first shot.

That said he caught Covid and breezed through it happily (was significantly milder than a cold) so maybe we could attribute that to the one shot or maybe he would have been fine anyway. Again I don't know. But lots of guilt.

My friend's child was diagnosed with ITP yesterday. My friend is a doctor and her kids received their shots right on schedule as recommended by the government. They're going to see more paediatricians and haematologists next week. The timing is uncomfortably suspect. Of course it could be other causes but my friend is adamant the bruises were noticeable a few months ago, possibly around the same time as the vaccine. I'm feeling antsy because my very pro vaccine, medical professional friend is now questioning whether the vaccine has anything to do with it.

So much guilt.

 

[DutchJackie]

Hi @missy , I’m so happy you’re still giving info about Covid-19 and it’s various variants. In the Netherlands the news cycle has changed to war and French elections and lots of other news. Well French election is done now, but I doubt Covid will get more coverage. We know so many sick people. It’s good to have a place with info that shows it’s not over yet…

 

[Gloria27]

I've been wanting to post this but was hesitant because of how pro vaccine this forum is.

I'm not sure how I feel about the vaccine for kids. I very grudgingly gave my kid one shot, he was fine but develops these red patches on his hands when he plays on play equipment. He plays on that same equipment every week and was able to do 7 run throughs with no marks. After the vaccine marks develop after 3 run throughs.

It's not anything that has affected him but I'm uncomfortable so he will not be receiving a second shot and to be honest I feel guilty about the first shot.

That said he caught Covid and breezed through it happily (was significantly milder than a cold) so maybe we could attribute that to the one shot or maybe he would have been fine anyway. Again I don't know. But lots of guilt.

My friend's child was diagnosed with ITP yesterday. My friend is a doctor and her kids received their shots right on schedule as recommended by the government. They're going to see more paediatricians and haematologists next week. The timing is uncomfortably suspect. Of course it could be other causes but my friend is adamant the bruises were noticeable a few months ago, possibly around the same time as the vaccine. I'm feeling antsy because my very pro vaccine, medical professional friend is now questioning whether the vaccine has anything to do with it.

So much guilt.

Yes, if you go against the mainstream you'll be accused of having an agenda, etc.
It's like they can't comprehend that some people might actually have a different opinion than theirs.

Nobody should feel pressured into doing anything.

My philosophy is simple: you do you and I do me, and I don't give a rat's &$$ about your feelings.

 

[missy]

I've been wanting to post this but was hesitant because of how pro vaccine this forum is.

I'm not sure how I feel about the vaccine for kids. I very grudgingly gave my kid one shot, he was fine but develops these red patches on his hands when he plays on play equipment. He plays on that same equipment every week and was able to do 7 run throughs with no marks. After the vaccine marks develop after 3 run throughs.

It's not anything that has affected him but I'm uncomfortable so he will not be receiving a second shot and to be honest I feel guilty about the first shot.

That said he caught Covid and breezed through it happily (was significantly milder than a cold) so maybe we could attribute that to the one shot or maybe he would have been fine anyway. Again I don't know. But lots of guilt.

My friend's child was diagnosed with ITP yesterday. My friend is a doctor and her kids received their shots right on schedule as recommended by the government. They're going to see more paediatricians and haematologists next week. The timing is uncomfortably suspect. Of course it could be other causes but my friend is adamant the bruises were noticeable a few months ago, possibly around the same time as the vaccine. I'm feeling antsy because my very pro vaccine, medical professional friend is now questioning whether the vaccine has anything to do with it.

So much guilt.

I'm sorry to hear this @mellowyellowgirl and hope your friend's son makes a full recovery.

Hi @missy , I’m so happy you’re still giving info about Covid-19 and it’s various variants. In the Netherlands the news cycle has changed to war and French elections and lots of other news. Well French election is done now, but I doubt Covid will get more coverage. We know so many sick people. It’s good to have a place with info that shows it’s not over yet…

Thank you @DutchJackie. I appreciate that.
Praying for peace for everyone. It's such a challenging time.

Some here (and she knows who she is though perhaps self aware is not a term we can use to describe this person) can only complain and add nothing to the conversation.
From this point forward I shall be ignoring @Gloria27 's posts. You do not deserve the courtesy of any more replies from me.

I post for those who are intellectually curious and want to read and learn as much as they can about this disease.

 

[missy]

Fractionating COVID-19 Vaccine Doses May Save Lives

Administering smaller doses of COVID-19 vaccines could be economically viable and could save more lives than either full-dose vaccination or no vaccination in low- and middle-income countries (LMICs)—even with the emergence of new, more highly transmissible variants, according to a...

jamanetwork.com

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Fractionating COVID-19 Vaccine Doses May Save Lives​

Howard D. Larkin
JAMA. 2022;327(15):1438. doi:10.1001/jama.2022.5655
COVID-19 Resource Center

Administering smaller doses of COVID-19 vaccines could be economically viable and could save more lives than either full-dose vaccination or no vaccination in low- and middle-income countries (LMICs)—even with the emergence of new, more highly transmissible variants, according to a cost-effectiveness modeling study.
Assuming a vaccine supply shortage, the study estimated the costs of hospitalization and vaccination and the economic benefits of averting COVID-19 deaths that would accrue if lower doses were administered in India. Shortages are most likely to occur in LMICs, where about 82% of the world’s population resides; the vaccination rate was 11% for low-income countries and 47% for middle-income countries in mid-January of this year.
Reducing the vaccine dose increased net monetary benefit under a wide range of transmission and vaccine efficacy assumptions in the modeling study. A ⅛ dose is the optimal strategy regardless of transmission rate, the study found. During high community transmission, the approach could save an estimated 4 million life-years at a cost of $10.63 billion. During times of low transmission, 11.34 million life-years could be saved at a cost of $8.8 billion.
Although fractional-dose strategies have potential for mitigating the public health and economic burdens of vaccine shortages, their adoption will depend on many factors, including ethical considerations and acceptability in specific country settings. Further clinical, policy, and operational research is needed, the authors wrote.
However, they noted that fractional vaccine doses already have been used for young children and for booster doses. Fractional doses might be most suitable for patients who were previously infected or vaccinated, according to the authors.
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[missy]

COVID-19 Vaccination and Estimated Public Health Impact in California

This decision analytical model estimates the number of COVID-19 cases, hospitalizations, and deaths averted because of COVID-19 vaccination in California.

jamanetwork.com

"
Original Investigation
Infectious Diseases
April 22, 2022

COVID-19 Vaccination and Estimated Public Health Impact in California​

Sophia T. Tan, BA1; Hailey J. Park1; Isabel Rodríguez-Barraquer, MD, PhD1,2; et alGeorge W. Rutherford, MD3; Kirsten Bibbins-Domingo, MD, PhD2,3; Robert Schechter, MD, MSc4; Nathan C. Lo, MD, PhD1,2
Author Affiliations Article Information
JAMA Netw Open. 2022;5(4):e228526. doi:10.1001/jamanetworkopen.2022.8526
COVID-19 Resource Center

Key Points
Question How many COVID-19 cases, hospitalizations, and deaths were averted because of COVID-19 vaccination in California?
Findings In this modeling study using data from the California Department of Public Health, COVID-19 vaccination was estimated to have prevented more than 1.5 million COVID-19 cases, 72 000 hospitalizations, and 19 000 deaths during the first 10 months of vaccination, through October 16, 2021.
Meaning These findings suggest that COVID-19 vaccination had a large public health benefit in California, which can be generalized across the United States.
Abstract
Importance Despite widespread vaccination against COVID-19 in the United States, there are limited empirical data quantifying their public health impact in the population.
Objective To estimate the number of COVID-19 cases, hospitalizations, and deaths directly averted because of COVID-19 vaccination in California.
Design, Setting, and Participants This modeling study used person-level data provided by the California Department of Public Health (CDPH) on COVID-19 cases, hospitalizations, and deaths as well as COVID-19 vaccine administration from January 1, 2020, to October 16, 2021. A statistical model was used to estimate the number of COVID-19 cases that would have occurred in the vaccine era (November 29, 2020, to October 16, 2021) in the absence of vaccination based on the ratio of the number of cases among the unvaccinated (aged <12 years) and vaccine-eligible groups (aged ≥12 years) before vaccine introduction. Vaccine-averted COVID-19 cases were estimated by finding the difference between the projected and observed number of COVID-19 cases. Averted COVID-19 hospitalizations and deaths were assessed by applying estimated hospitalization and case fatality risks to estimates of vaccine-averted COVID-19 cases. As a sensitivity analysis, a second independent model was developed to estimate the number of vaccine-averted COVID-19 outcomes by applying published data on vaccine effectiveness to data on COVID-19 vaccine administration and estimated risk of COVID-19 over time.
Exposure COVID-19 vaccination.
Main Outcomes and Measures Number of COVID-19 cases, hospitalizations, and deaths estimated to have been averted because of COVID-19 vaccination.
Results There were 4 585 248 confirmed COVID-19 cases, 240 718 hospitalizations, and 70 406 deaths in California from January 1, 2020, to October 16, 2021, during which 27 164 680 vaccine-eligible individuals aged 12 years and older were reported to have received at least 1 dose of a COVID-19 vaccine in the vaccine era (79.5% of the eligible population). The primary model estimated that COVID-19 vaccination averted 1 523 500 (95% prediction interval [PI], 976 800-2 230 800) COVID-19 cases in California, corresponding to a 72% (95% PI, 53%-91%) relative reduction in cases because of vaccination. COVID-19 vaccination was estimated to have averted 72 930 (95% PI, 53 250-99 160) hospitalizations and 19 430 (95% PI, 14 840-26 230) deaths during the study period. The alternative model identified comparable findings.
Conclusions and Relevance This study provides evidence of the public health benefit of COVID-19 vaccination in the United States and further supports the urgency for continued vaccination.

Introduction
COVID-19 has caused substantial morbidity, mortality, and socioeconomic disruption and disparity in the United States and globally. The COVID-19 vaccine has been a key tool for public health control of COVID-19, alongside public health measures for universal masking and social distancing.1,2 In the United States, implementation of COVID-19 vaccination took place in a phased approach, guided by recommendations from the Advisory Committee on Immunization Practices (ACIP) within the US Centers for Disease Control and Prevention. The ACIP recommendation prioritized vaccination based on risk of infection. Phase 1a of vaccination included health care personnel and residents of nursing facilities, phase 1b included frontline essential workers and adults 75 years or older, and phase 1c included adults 65 years or older and individuals with high-risk conditions. Phase 2 included vaccination of the general population 16 years or older.3 Initiation of phase 1a vaccination against COVID-19 began in December 2020,3,4 indicating the beginning of widespread vaccination in the United States.
Three vaccines are currently authorized in the United States: (1) BNT162b2 mRNA from Pfizer/BioNTech; (2) mRNA-1273 from Moderna; and (3) Ad26.COV2.S from Janssen. The landmark trials on these vaccines demonstrated high efficacy against clinical disease, hospitalization, and death. The efficacy of vaccine against symptomatic infection was 95%, 94%, and 66% for the BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines, respectively, with even greater efficacy against hospitalization and death.5-7 Furthermore, published data on the effectiveness in the general population have demonstrated similar protection against clinical outcomes, with some waning for the BNT162b2 and Ad26.COV2.S vaccines8 and some differential vaccine effectiveness by SARS-CoV-2 variant.9-13 However, despite widespread implementation of COVID-19 vaccinations in the United States, there are limited data to estimate the overall population-level public health outcomes of vaccination regarding averted cases, hospitalization, and deaths from COVID-19.
This article reports on the estimated public health impact of COVID-19 vaccination by estimating the number of COVID-19 cases, hospitalizations, and deaths directly averted in the first 10 months of vaccination. This analysis uses the representative case example of California given the large population, geographic size, and epidemiologic variation within the state.
Methods
We developed 2 independent statistical modeling approaches to estimate the number of averted COVID-19 cases because of direct effects of vaccination (ie, cases averted due to immunity) from the introduction of vaccine on November 29, 2020, to October 16, 2021. We applied estimated hospitalization and case fatality risks to estimate averted COVID-19 hospitalizations and deaths because of COVID-19 vaccination. In this analysis, we used person-level COVID-19 case data from the California Department of Public Health (CDPH) and public data on COVID-19 vaccination. The analytic code is available on GitHub.14 This project was approved by the institutional review board at the University of California, San Francisco. The requirement for informed consent was waived because the study relied on secondary data sets that were collected as part of public health surveillance. Study reporting followed the Consolidated Health and Economic Evaluation Reporting Standards (CHEERS) guidelines.15
Data
We obtained deidentified person-level case data, including outcomes of hospitalization and death, for confirmed COVID-19 cases in California from January 1, 2020, to October 16, 2021, from CDPH. A case of COVID-19 was defined as a person whose positive SARS-CoV-2 molecular test was reported to the state, including both symptomatic cases and asymptomatic infections.16 COVID-19 hospitalizations and deaths were defined as individuals with confirmed COVID-19 cases who were hospitalized or died due to COVID-19 based on reporting to CDPH by health care practitioners. We excluded data on persons with missing age data (<1%).
We obtained publicly available CDPH vaccine administration data in 4 age groups (12-17 years, 18-49 years, 50-64 years, and ≥65 years) from July 27, 2020, to October 16, 2021.17These age groupings were based on vaccine eligibility.18 We excluded vaccination in children aged 5 to 11 years old (vaccine coverage <0.01%) because they were ineligible during the study period.19,20 We additionally excluded vaccination that occurred before start of phase 1a of vaccination (<0.01%) or had missing age information (<0.02%). We aggregated both COVID-19 case and vaccination data from daily counts to weekly counts beginning January 1, 2020.
Study Outcomes
The primary study outcomes were estimated COVID-19 cases, hospitalizations, and deaths averted because of the direct effects of COVID-19 vaccination. We estimated the relative reduction in COVID-19 cases because of vaccination, adjusting for vaccine coverage over time given initial periods of low vaccine coverage. We also provide alternative definitions for the relative reduction estimates (eAppendix in the Supplement). Secondary study outcomes include estimated averted COVID-19 outcomes and relative reduction in outcomes by age group. Study outcomes were chosen based on public health relevance.
Statistical Analysis
We used 2 independent modeling approaches to estimate the number of averted COVID-19 cases because of vaccination in the vaccine era from November 29, 2020 to October 16, 2021. We defined the start of the vaccine era based on the approximate start of phase 1a of COVID-19 vaccination in California.4 We developed multiple estimation procedures that relied on different assumptions to improve the reliability and robustness of our study findings. All analyses were conducted in R version 3.6.0 (R Project for Statistical Computing).
Primary Statistical Model for COVID-19 Cases
In the primary model, we estimated the number of COVID-19 cases that would have otherwise occurred over time if vaccines were never available. This modeling approach used the unvaccinated population as a proxy for overall force of infection over time in the vaccine-eligible population. We defined our unvaccinated population as all children younger than 12 years, as they were ineligible for vaccination over the entire study period.
We used quasi-Poisson regression models to estimate the ratio between the log-transformed number of weekly COVID-19 cases in the unvaccinated population (<12 years) and the number of weekly cases in each of the 4 vaccine-eligible populations (aged 12-17 years, 18-49 years, 50-64 years, and ≥65 years) during the prevaccine era at the state level. The prevaccine era was defined as May 31 to November 28, 2020, to provide 6 months of data for model calibration. We fit separate models for each of the 4 age groups of the vaccine-eligible population.
We then applied each calibrated model to the observed COVID-19 cases in the unvaccinated population (<12 years) in the vaccine era (November 29, 2020, to October 16, 2021) to estimate the number of COVID-19 cases that would have occurred in each vaccine-eligible age group in the absence of vaccination. We computed the weekly difference between the projected number of COVID-19 cases in absence of vaccination with the observed number of COVID-19 cases from the CDPH data set (eAppendix in the Supplement). We summed the differences across age groups to estimate the total number of averted COVID-19 cases because of the direct protection of COVID-19 vaccination in California. We reported 95% prediction intervals (PIs) for study estimates. This model assumed that the relative risk of COVID-19 diagnosis remained constant over time between the unvaccinated population (<12 years) and vaccine-eligible age groups. This model did not explicitly account for person-level vaccination.
Alternative Statistical Model for COVID-19 Cases
In the second model, we used published data on vaccine effectiveness and estimated risk of COVID-19 in the vaccine era (November 29, 2020, to October 16, 2021) to estimate the number of COVID-19 cases averted because of the direct protection of vaccination. First, we estimated state-level weekly incidence of COVID-19 cases (defined as total cases per 100 000 susceptible persons) beginning January 1, 2020 (earliest available data for COVID-19 in California), in each of the 4 vaccine-eligible populations (aged 12-17 years, 18-49 years, 50-64 years, ≥65 years). We estimated the fraction of the population susceptible to infection over time by age group based on natural infection and/or vaccination. For natural immunity, we used data on reported COVID-19 cases and applied published estimates of age-specific clinical fractions to estimate the total number of infections (including subclinical infections) (Table 1; eAppendix in the Supplement).6-8,22,23 We made the simplifying assumption that natural infection provided perfect immunity, although we varied this in a sensitivity analysis. For vaccine-induced immunity, we used data on vaccine administration and published data on vaccine effectiveness.5-8 We estimated vaccine-induced immunity and waning specific to each of the COVID-19 vaccines (BNT162b2, mRNA-1273, and Ad26.COV2.S) over time (Table 1; eAppendix in the Supplement).
We applied the age-specific estimated risk of COVID-19 to the fraction of the corresponding age group susceptible to infection, removing vaccine-induced protection and thus simulating a scenario without vaccination. This estimation was conducted in the vaccine era (November 29, 2020, to October 16, 2021). We estimated 95% uncertainty intervals (UIs), which incorporated uncertainty in estimates of vaccine effectiveness over time and the age-specific clinical fraction generated through Monte Carlo simulation (eAppendix in the Supplement). This approach did not assume a fixed relationship in COVID-19 cases between the unvaccinated and vaccine-eligible groups. This model did assume complete reporting of both case and vaccination data and a constant clinical fraction among infections over time.
Statistical Analysis for Hospitalizations and Deaths
We estimated age-specific monthly risk of hospitalization and death among COVID-19 cases over time, as the severity of clinical outcome may have changed over time owing to clinical experience and COVID-19 directed therapies (eFigure 1 and eAppendix in the Supplement). We estimated averted COVID-19 hospitalizations and deaths by applying these hospitalizations and death risk estimates to vaccine-averted COVID-19 cases in the 3 vaccine-eligible age groups aged 18 years or older (18-49 years, 50-64 years, and ≥65 years). We also compared this estimate with published literature values in sensitivity analysis. We did not estimate these outcomes in younger age groups given their lower risk of hospitalization and death.
Sensitivity Analyses
We conducted several sensitivity analyses to evaluate varying assumptions and parameters in the model. We estimated the relative reduction in COVID-19 cases because of vaccination with alternative definitions, including no adjustment for vaccine coverage over time and considering different start dates for widespread vaccination based on age-specific vaccine eligibility (eAppendix in the Supplement).
In the primary model, we varied the calibration period and used other age group definitions for the unvaccinated population. We simulated changing risk of infection among children younger than 12 years from the Delta variant (eAppendix in the Supplement). In the alternative model, we varied vaccine effectiveness estimates to simulate the study findings under reduced vaccine effectiveness to the Delta variant and relaxed model assumptions of perfect immunity from natural infection to assess waning natural immunity on study outcomes (eAppendix in the Supplement). We ran the alternative model using literature estimates of vaccine effectiveness against hospitalization and death rather than estimates based on CDPH data (eAppendix in the Supplement).
Results
Descriptive Data
There were 4 588 146 reported COVID-19 cases in California from January 1, 2020, to October 16, 2021. We included 4 585 248 COVID-19 cases and excluded 2898 (0.06%) because of missing age data. A total of 3 276 260 COVID-19 cases occurred after November 28, 2020 (phase 1a of COVID-19 vaccination in California). There were 899 510 confirmed cases of COVID-19 after the Delta variant became a prominent circulating strain of SARS-CoV-2 in June 2021 (Figure 1).24
Among COVID-19 cases included in this analysis, there were 240 718 reported hospitalizations and 70 406 reported deaths (Figure 1). Both risk of hospitalization and risk of death varied over time and across age groups and was highest in the population aged 65 years or older (21.6% of reported cases resulted in hospitalization and 10.8% of reported cases resulted in death) (eFigure 1 in the Supplement). Overall estimates of the hospitalization and death risks (5% and 1.5%, respectively) were comparable with literature estimates (6% and 1%, respectively).25
Between November 29, 2020, and October 16, 2021, 27 164 680 persons aged 12 years and older (79.5%) were reported to have received at least 1 dose of a COVID-19 vaccine in California. We excluded 2022 individuals (<0.01%) who received vaccines before November 29, 2020 (Figure 1). Approximately 57% of vaccine-eligible individuals received the BNT162b2 vaccine, 36% received the mRNA-1273 vaccine, and 7% received the Ad26.COV2.S vaccine. We excluded 3924 individuals (<0.02%) with missing age from the vaccination data.
COVID-19 Cases
Primary Model Results
We observed good model fit over the calibration period for the primary model in the prevaccine era (May 31 to November 28, 2020) (eFigure 2 in the Supplement). We estimated that 1 523 500 (95% PI, 976 800-2 230 800) COVID-19 cases were averted because of COVID-19 vaccination (Table 2 and Figure 2), which corresponded with a 72% (95% PI, 53%-91%) reduction in cases in the vaccine-eligible population after the start of phase 1a of vaccination (Table 2) and an 86% (95% PI, 81%-92%) reduction in cases when taking into account age-specific differences in vaccine eligibility (eTable 1 in the Supplement). The populations aged 12 to 17 years, 18 to 49 years, 50 to 64 years, and 65 years and older were estimated to have experienced 57%, 83%, 66%, and 49% reductions, respectively, in COVID-19 cases after the start of phase 1a of vaccination (Table 2; eFigures 3-6 in the Supplement), and these estimated reductions were greater when accounting for age-specific eligibility over time (eTable 1 in the Supplement). Approximately 1 005 500 (95% PI, 809 300-1 230 450) COVID-19 cases (66% of total cases averted) were estimated to have been averted after the Delta variant became the dominant strain of SARS-CoV-2 circulating in California in June 2021.24
We performed sensitivity analyses on the primary model, including varying date to define vaccine introduction (eTable 3 in the Supplement), testing alternative age definitions for the vaccine-eligible population (eTable 2 in the Supplement), and changing transmission dynamics due to the Delta variant (eTable 4 in the Supplement). The findings of these sensitivity analyses were overall similar to the main results.
Alternative Model Results
In the alternative modeling approach, we estimated that 1 402 100 (95% UI, 1 192 100-1 615 600) cases were averted because of COVID-19 vaccination from November 29, 2020, to October 16, 2021 (Table 2 and Figure 3). We estimated that vaccination contributed to a 68% (95% UI, 61%-75%) reduction in cases in the population aged 12 years or older after the start of vaccination when adjusting for vaccine coverage (Table 2) and 93% (95% UI, 86%-99%) reduction in cases when accounting for age-specific differences in vaccine eligibility (eTable 1 in the Supplement). The populations aged 12 to 17 years, 18 to 49 years, 50 to 64 years, and 65 years or older were estimated to have experienced 97%, 71%, 68%, and 61%, respectively, reductions in COVID-19 cases after the start of phase 1a of vaccination (Table 2; eFigures 3-6 in the Supplement), and these estimated reductions in cases were greater when accounting for differences in vaccine eligibility (eTable 1 in the Supplement). We estimated that 90% of averted cases were prevented after the introduction of the Delta variant.
In sensitivity analysis, we obtained comparable results when accounting for the possibility of reduced vaccine effectiveness against the Delta variant; we estimated that 1 106 300 (95% UI, 913 300-1 308 650) cases were prevented, and there was an estimated 58% (95% UI, 50%-65%) reduction in cases (eTable 5 in the Supplement). In this sensitivity analysis, 87% of estimated averted COVID-19 cases were prevented during widespread transmission of the Delta variant. We additionally found similar results when relaxing the assumption that natural infection provided full immunity (eTable 6 in the Supplement).
COVID-19 Hospitalizations and Deaths
Using estimates of averted COVID-19 cases from the primary model, we estimated that 72 930 (95% PI, 53 250-99 150) hospitalizations and 19 430 (95% PI, 14 840-26 230) deaths were averted in the population aged 18 years or older because of COVID-19 vaccination (Table 2 and Figure 2). From the alternative model of cases, we estimated there were 84 330 (95% UI, 71 760-97 510) hospitalizations and 22 620 (95% UI, 19 280-26 190) deaths prevented because of vaccination (Table 2 and Figure 3). We found similar results for both hospitalizations and deaths across all sensitivity analyses (eTables 1-8 in the Supplement).
Discussion
In this study, we estimated that COVID-19 vaccination had a large public health benefit by averting COVID-19 cases and related hospitalizations and deaths, which likely generalizes across the United States. More than 1.5 million COVID-19 cases were estimated to have been prevented because of protection by COVID-19 vaccination programs during the first 10 months of widespread vaccination in California. We additionally estimated that there were more than 72 000 vaccine-averted hospitalizations and at least 19 000 vaccine-averted deaths. Vaccination contributed to an estimated greater than 70% reduction in cases. These study findings are strengthened by our second modeling approach, which had comparable findings despite relying on distinct assumptions. Furthermore, our study likely provides a lower bound for the estimated public health impact of COVID-19 vaccination given we only estimated the direct effects of vaccination.
Our findings suggest that COVID-19 vaccination had especially invaluable benefit for mitigating the surge of COVID-19 cases due to the Delta variant, which is more infectious than other previously identified variants of SARS-CoV-2 during the first 2 years of the pandemic.23 A large number of COVID-19 outcomes were estimated to have been prevented after the introduction of the SARS-CoV-2 Delta variant in California. The primary model and alternative model estimated that more than 65% to 90% of averted COVID-19 cases occurred after the Delta variant became the prominent variant of SARS-CoV-2 circulating in California, with similar estimates of averted hospitalizations and deaths. The burden of COVID-19 cases and more severe outcomes would have been significantly greater in the absence of vaccination (Figure 2 and Figure 3), including in the Omicron surge. We found similar estimates for vaccination in averting severe clinical outcomes when additionally considering increased infectiousness of the Delta variant in the primary model and reduced effectiveness of vaccines against the Delta variant in the alternative model.
We estimated a 72% reduction in COVID-19 cases in the vaccine-eligible population in California from the start of phase 1a of vaccination when adjusting for the average vaccine coverage. This provided a conservative estimate of the true reduction given that vaccine eligibility across age groups varied over time. Other factors associated with this estimate not being larger include imperfect vaccine effectiveness and waning immunity. When accounting for differences in vaccine eligibility by age, we found an estimated 86% reduction in COVID-19 cases. However, this still likely represents an underestimate, as early vaccine eligibility was determined by occupational and health risk, which our data was unable to fully capture. Other model-based analyses on the population-level outcomes of vaccination have been previously undertaken, and in comparison, support the large public health benefit of COVID-19 vaccination.26
A key strength of the analysis is the development of 2 distinct modeling approaches to improve reliability of the study findings. While each analysis of estimating averted COVID-19 cases relied on limiting assumptions, the assumptions were nonoverlapping, and overall findings for all study outcomes were similar. Notably, the primary modeling approach estimated a greater number of outcomes averted early in the vaccine era. The alternative modeling approach estimated greater vaccine benefit after the widespread circulation of the Delta variant (Figure 2 and Figure 3). The alternative modeling approach estimated more cases averted in the populations aged 12 to 17 years and 65 years or older than the primary modeling approach and more hospitalizations and deaths averted in the populations aged 50 to 64 years and 65 years or older (Table 2). The PIs from the primary modeling approach include larger uncertainty than the UIs of the alternative modeling approach, although these intervals represent different statistical entities and are broadly overlapping.
Limitations
Our study has limitations. We report predominately on the estimated direct effects of vaccination and were not able to capture the indirect effects of vaccination (ie, averted outcomes due to reduced SARS-CoV-2 transmission), meaning the overall benefits of vaccination, which includes both direct and indirect effects of vaccination, is likely much larger than estimated.
Our primary modeling approach for cases relied on the key assumption that COVID-19 cases in the unvaccinated population (aged <12 years) remained a robust indicator of cases in each vaccine-eligible group over time. We assumed that the relative risk of SARS-CoV-2 infection between the vaccine-ineligible (aged <12 years) and vaccine-eligible (aged ≥12 years) populations was stable over time, as well as stable testing practices within and between these age groups. Relative risk and testing practices likely changed over time and differentially between groups, especially as children returned to schools and had access to increased SARS-CoV-2 testing in the fall of 2021.27 To address this, we developed the alternative modeling approach that did not make this assumption and ultimately had similar study findings.
Our alternative modeling approach used the susceptibility profile of the vaccine-eligible population over time to estimate the COVID-19 cases prevented by vaccination. The key assumption in the alternative model was complete reporting of COVID-19 cases and vaccination, although this assumption was relaxed for estimating the relative reduction outcome. Similarly, we assumed the symptomatic fraction of reported SARS-CoV-2 infections remained constant over time, even with the introduction of vaccines (eAppendix in the Supplement). An increase in asymptomatic screening over time would bias the study to overestimate the public health benefit of vaccination, while an increase in the asymptomatic fraction of infection over time due to vaccine effectiveness would bias the study to underestimate the public health impact of vaccination.
Our approach to estimating hospitalizations and deaths prevented by COVID-19 vaccination has limitations. We were unable to estimate age-specific risks of hospitalization and death among cases solely in the unvaccinated population. Our estimates of the risk of severe outcomes reflect overall risk of hospitalization and death among both vaccinated and unvaccinated individuals in the vaccine-eligible population, which suggests that our results likely underestimate the direct effects of vaccination on severe COVID-19 outcomes, although these estimates were similar to published values elsewhere.
Conclusions
In this study, our estimates suggest that COVID-19 vaccination had a substantial public health benefit by reducing COVID-19 cases, hospitalizations, and deaths in California, especially during widespread transmission of the Delta variant. The value of vaccination is likely to be larger with the emergence of more transmissible variants, such as the Omicron variant. This study provides evidence on the public health benefit of COVID-19 vaccination in the United States and further supports the urgency for continued vaccination.
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[missy]

Assessment of T-cell Reactivity to the SARS-CoV-2 Omicron Variant by Immunized Individuals

This cohort study assesses T-cell reactivity to the Omicron variant of SARS-CoV-2 in individuals vaccinated against SARS-CoV-2.

jamanetwork.com

"
Original Investigation
Immunology
April 22, 2022

Assessment of T-cell Reactivity to the SARS-CoV-2 Omicron Variant by Immunized Individuals​

Lorenzo De Marco, MSc1; Silvia D’Orso, MSc1; Marta Pirronello, MSc1; et alAlice Verdiani, MSc1; Andrea Termine, MSc2; Carlo Fabrizio, MSc2; Alessia Capone, PhD3; Andrea Sabatini, MSc3; Gisella Guerrera, PhD1; Roberta Placido, PhD1; Manolo Sambucci, PhD1; Daniela F. Angelini, PhD1; Flavia Giannessi, PhD1; Mario Picozza, PhD1; Carlo Caltagirone, MD, PhD4; Antonino Salvia, MD5; Elisabetta Volpe, PhD3; Maria Pia Balice, PhD6; Angelo Rossini, MD5; Olaf Rötzschke, PhD7; Emiliano Giardina, PhD8,9; Luca Battistini, MD, PhD1; Giovanna Borsellino, MD, PhD1
Author Affiliations Article Information
JAMA Netw Open. 2022;5(4):e2210871. doi:10.1001/jamanetworkopen.2022.10871
COVID-19 Resource Center

Key Points
Question What is the cellular immunity associated with the Omicron variant of SARS-CoV-2 among immunized individuals?
Findings In this cohort study among 61 individuals who had been vaccinated against COVID-19, cellular responses to the mutated regions of the Omicron spike protein were detected in 80% of participants. The mutations were associated with significantly reduced T-cell recognition compared with the vaccine strain, while reactivity to the whole spike protein was present in 100% of participants, and the proportion of remaining immunity to SARS-CoV-2 was estimated to be 87%.
Meaning These findings suggest that cellular immunity to the Omicron variant was maintained despite the mutations in its spike protein; thus, immunization may confer protection from severe COVID-19 from the Omicron variant.
Abstract
Importance The emergence of the highly contagious Omicron variant of SARS-CoV-2 and the findings of a significantly reduced neutralizing potency of sera from individuals with previous SARS-CoV-2 infection or vaccination highlights the importance of studying cellular immunity to estimate the degree of immune protection to the new SARS-CoV-2 variant.
Objective To determine T-cell reactivity to the Omicron variant in individuals with established (natural and/or vaccine-induced) immunity to SARS-CoV-2.
Design, Setting, and Participants This was a cohort study conducted between December 20 and 21, 2021, at the Santa Lucia Foundation Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy, among health care worker and scientist volunteers. Lymphocytes from freshly drawn blood samples were isolated and immediately tested for reactivity to the spike protein of SARS-CoV-2.
Main Outcomes and Measures The main outcomes were the measurement of T-cell reactivity to the mutated regions of the spike protein of the Omicron BA.1 SARS-CoV-2 variant and the assessment of remaining T-cell immunity to the spike protein by stimulation with peptide libraries.
Results A total of 61 volunteers (mean (range) age, 41.62 (21-62) years; 38 women [62%]) with different vaccination and SARS-CoV-2 infection backgrounds were enrolled. The median (range) frequency of CD4+ T cells reactive to peptides covering the mutated regions in the Omicron variant was 0.039% (0%-2.356%), a decrease of 64% compared with the frequency of CD4+ cells specific for the same regions of the ancestral strain (0.109% [0%-2.376%]). Within CD8+ T cells, a median (range) of 0.02% (0%-0.689%) of cells recognized the mutated spike regions, while 0.039% (0%-3.57%) of cells were reactive to the equivalent unmutated regions, a reduction of 49%. However, overall reactivity to the peptide library of the full-length protein was largely maintained (estimated 87%). No significant differences in loss of immune recognition were identified between groups of participants with different vaccination or infection histories.
Conclusions and Relevance This cohort study of immunized adults in Italy found that despite the mutations in the spike protein, the SARS-CoV-2 Omicron variant was recognized by the cellular component of the immune system. It is reasonable to assume that protection from hospitalization and severe disease will be maintained.

Introduction
Far from being weakened, the COVID-19 pandemic has found new strength in another wave of infections with the Omicron variant of SARS-CoV-2.1 Mutations in the receptor-binding domain region correlate with lower neutralization potency of sera collected from individuals with immunity from previous infection or vaccination,2 setting the stage for immune evasion by the mutated virus. Conveniently, T-cell responses are characterized by vast cross-reactivity,3 and cellular immunity is maintained in the face of mutations that may escape antibody recognition.4 Still, infection in an immunized individual with a slightly different version of the immunizing pathogen occurs in a context of preexisting immunity, mostly mediated by the cellular component of the immune response. This raises the question of whether the intrinsic cross-reactivity of the spike-specific T cells induced by vaccination or infection will confer a broad enough repertoire for T cells to respond to emerging variants of SARS-CoV-2. Studies on the fine specificity and persistence of spike-specific T cells in individuals with previous SARS-CoV-2 infection have indicated that the cellular response to SARS-CoV-2 offers broad reactivity against spike epitopes,5,6 and induction of broadly reactive CD4+ and CD8+ memory cells has been shown to occur after vaccination as well.7 In this study, we investigate the T-cell response to the mutated regions of the spike protein from the Omicron BA.1 variant in 61 individuals who received COVID-19 vaccinations and/or with immunity from previous SARS-CoV-2 infection. By also measuring reactivity to the equivalent regions from the ancestral vaccine strain and to the whole spike protein, we estimate the degree of remaining immunity to the SARS-CoV-2 spike protein.
Methods
Study Design and Participants
This cohort study was approved by the ethics committee at the Santa Lucia Foundation Hospital and conducted on December 20 to 21, 2021. All participants provided written informed consent. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
Volunteers from among the hospital workers and scientists of the Santa Lucia Foundation donated 15 mL of blood. To include individuals who had been previously infected with SARS-CoV-2, we queried the internal registry to select individuals with positive results on polymerase chain reaction (PCR) tests after periodic surveillance screenings. Participants were divided in 5 groups, based on their vaccination/infection history: (1) those with 2 doses of any 1 vaccine; (2) those with 3 doses of mRNA vaccine; (3) those with heterologous vaccination with adenoviral vector followed by an mRNA vaccine; (4) individuals who had been vaccinated and who had subsequently been infected with SARS-CoV-2; and (5) individuals who had contracted and recovered from SARS-CoV-2 and were subsequently vaccinated (Table).
T-cell Stimulation
Peripheral blood mononuclear cells were isolated and immediately tested in an in vitro assay, including incubation with 3 different peptide pools: an overlapping peptide pool spanning the entire spike protein from the ancestral vaccine strain (PoolS), a pool of 83 peptides covering only the mutated regions of the spike protein from the Omicron variant (PoolMut), and a peptide pool covering the same regions as the mutated Omicron regions but from the ancestral strain (PoolRef) (all pools 1 μg/mL each; Miltenyi Biotec). These peptides pools are 15 mers with 11 amino acid overlap and are ideal for CD4+ T-cell stimulation but suboptimal for presentation through major histocompatibility complex Class I, which preferentially binds shorter peptides (8-10 mers), thus CD8+ T-cell reactivity may be underestimated. After 18 hours, cells were stained with fluorochrome-conjugated monoclonal antibodies for the detection of the expression of surface activation induced markers (AIM) in CD4+ and CD8+ T-cell subsets (eTable in the Supplement), and supernatants were collected for measurement of interferon (IFN)-γ release by enzyme-linked immunoassay (Bio-Techne). Activated CD4+ cells were defined as activation of CD40 ligand+ and CD69+ cells, while the expression of CD137+ and CD69+ identified activated CD8+ cells, as previously described.8Following background subtraction of unstimulated cultures, negative values were set to zero. The threshold for positivity was set by calculating the 75th percentile minus the median of the values obtained.9 Samples were acquired on Aurora (Cytek) or on Cytoflex LS (Beckman Coulter) flow cytometers. In parallel, 50 μL of corresponding whole-blood samples were stained with anti-CD3, anti-CD4, and anti-CD8 for the determination of absolute cell counts as previously described.8 Data were analyzed with FlowJo version 10.8 (BD). Data were visualized using PRISM version 9 (GraphPad).
Estimation of Remaining Immunity
To estimate the remaining immunity, for each individual we subtracted the number of cells responding to the unmutated pool from the number of cells activated by the complete protein pool to obtain the number of cells specific for the other spike regions. To this, we added the number of cells responding to the mutated pool, corresponding to the cells that had maintained reactivity despite the mutations. Thus, remaining immunity can be estimated with the formula:

Statistical Analysis
The differences between groups in CD4+ and CD8+ activated T cells were assessed for each experimental condition (PoolS, PoolRef, and PoolMut) using multiple Kruskal-Wallis rank sum tests. Pairwise post hoc comparisons were performed using the Wilcoxon rank sum test with false discovery rate correction for multiple testing. Within-groups differences in CD4+ and CD8+ were assessed in PoolRef and PoolMut conditions using Friedman rank sum test with Omicron exposure as the fixed effect and participant ID as the random effect. Kendall W was used to compute effect size following the Cohen interpretation guidelines (small, 0.1 to <0.3; moderate, 0.3 to <0.5; large, ≥0.5). The obtained effect sizes were used in multiple 2-tailed post hoc power analyses for dependent means to estimate the obtained statistical power with α = .05. The slopes of the regression line between PoolRef and PoolMut were computed for CD4+ AIM and CD8+ AIM for each participant. The obtained slopes were compared between groups using multiple Kruskal-Wallis rank sum tests and Heteroscedastic 1-way analysis of variance for medians with false discovery rate correction. All the statistical analyses were performed using the lme4, lmerTest, and WRS2 libraries in R statistical software version 4.1.2 (R Project for Statistical Computing). Analyses were conducted on December 27, 2021.
Results
A total of 61 volunteers (mean [range] age, 41.62 [21-62] years; 38 [62%] women) with different vaccination and SARS-CoV-2 infection backgrounds each donated 15 mL of blood, which was immediately processed. Of these participants, 1 had recently completed chemotherapy, and 1 was undergoing treatment with monoclonal antibodies; the others reported no known health issue (Table).
First, we established T-cell responsiveness to the spike protein (Figure 1). All 61 participants showed CD4+ T-cell reactivity to PoolS, and 59 participants (97%) showed CD8+ T-cell reactivity to PoolS (Figure 2). For PoolMut, CD4+ T-cell reactivity was detected in 47 participants (77%), and CD8+ T-cell reactivity was detected in 29 participants (48%). For PoolRef, CD4+T cells were present in 59 participants (97%), and CD8+ T cells were present in 35 participants (57%). Within the different groups of participants, there was no significant difference in T-cell reactivity to PoolMut between individuals with the heterologous regimen of vaccination (CD4+: 10 of 11 participants [91%]; CD8+: 8 of 11 participants [73%]) and those who had received 2 doses of vaccine (CD4+: 7 of 10 participants [70%]; CD8+: 3 of 10 participants [30%]).
Overall, the proportion of T cells activated by PoolMut was significantly lower than that of T cells recognizing the same regions from the Wuhan strain used for vaccine design (median [range]: CD4+, 0.039% [0%-2.356%] vs 0.109% [0%-2.376%]; P < .001; CD8+, 0.02% [0%-0.689%] vs 0.039% [0%-3.57%]; P < .001) (Figure 3). The reduction in T cell numbers reactive to the Omicron variant was found to be significant in all groups of participants, regardless of vaccination and SARS-CoV-2 infection history (eFigure in the Supplement). Individuals who had been infected with SARS-CoV-2 after vaccination showed a lower reduction in the proportion of CD8+ T cells recognizing the mutated spike regions. CD8+ T-cell reactivity, when present, was more conserved compared with the CD4+ subset.
IFN-γ released in the cultures was also significantly reduced when cells were incubated with the peptide pools covering the mutated spike regions, compared with pools spanning the equivalent regions of the ancestral strain (Figure 3; eFigure in the Supplement). Thus, these data show that mutations of the spike protein carried by the Omicron variant were associated with decreased CD4+ and CD8+ T-cell activation and function.
While we observed a significant reduction in T-cell reactivity to the mutated regions of the spike protein from the Omicron variant, these account for a small proportion of the total protein. Using our Equation, we estimate that overall T-cell reactivity to the spike protein of the Omicron variant was maintained by 87% (CD4+: 83%; CD8+: 91%) (Figure 4), with no significant differences between the different groups of participants.
Discussion
This cohort study found that that T-cell responses against the mutated regions in Omicron were significantly reduced in immunized individuals. Compared with the Wuhan strain, the Omicron BA.1 variant carries more than 35 mutations in the spike protein. The impact of these mutations on antibody recognition has been shown to be substantial, with a significant loss of neutralizing activity in sera from individuals with immunity from previous infection or vaccination.2,10 In previous variants, although antibody neutralizing potency was decreased, T-cell responses were maintained.4,11 However, as these regions cover only a small proportion of the whole protein, the overall response against Omicron spike was largely preserved regardless of vaccination and/or infection history in our study, in line with other studies.12-16
Limitations
This study has some limitations. The main limitation is the small number of participants in each group, which resulted in low statistical power for the identification of differences in T-cell responses between groups. Also, we only measured T-cell responses in peripheral blood, which may not fully represent what happens in the respiratory tract and lymph nodes. Additionally, we did not use the whole spike protein from the Omicron variant in our peptide pool, since it was not available at the time of the study. Furthermore, we cannot exclude some distortion due to potential immunodominance effects of the individual peptide epitopes, although no major immunodominance was evident in significantly higher reactivity to the Omicron peptide pool.
Conclusions
This cohort study of 61 immunized adults in Italy found persisting and robust T-cell responses despite the mutations in the Omicron variant of SARS-CoV-2. These findings suggest that cellular immunity against this variant, together with protection from severe disease, will not be compromised.

"

 

[Gloria27]

Haha, funny thing, someone who did not have covid trying to explain this disease to someone who had it!
Like a man trying to explain to women how periods work/feel
You are free to ignore me, you were free to do it before, no need to brag about it, seems like you are complaining not me.

 

[missy]

Additional info about Covid vaccines and boosters.

Surveillance of Safety of 3 Doses of COVID-19 mRNA Vaccination Using EHR Data

This cohort study assesses adverse events associated with a third dose of mRNA COVID-19 vaccine using data from electronic health records (EHRs).

jamanetwork.com

Adverse Events After the Third Dose of the BNT162b2 mRNA Vaccine in Older Adults

This survey study assesses the occurrence of short-term adverse events in adults 60 years or older who received a booster dose of the BNT162B2 mRNA vaccine.

jamanetwork.com

Trends in COVID-19 Vaccine Administration and Effectiveness Through October 2021

This cohort study reports statewide trends in vaccine administration and vaccine effectiveness in Minnesota.

jamanetwork.com

And for those who wish to follow updates on their own:

Research and opinion articles on Coronavirus Disease 2019 (COVID-19) from JAMA Network

Read the latest on the COVID-19 outbreak, including new expert opinion and science on the epidemiology, diagnosis, management, and prevention of infection

jamanetwork.com

 

[missy]

@MamaBee

More Antibodies With Longer Intervals Between COVID Vaccine Doses

Antibody levels were also much higher in individuals who were previously infected with COVID-19.

www.medscape.com

“

More Antibodies With Longer Intervals Between COVID Vaccine Doses​

Becky McCall
April 24, 2022


LISBON, Portugal — An overall ninefold increase in COVID-19 antibody levels can be seen with a longer interval between first and second doses of the Pfizer/BioNTech (BNT162b2) vaccine in people without prior infection, according to data from the UK government's SIREN (SARS-CoV-2 Immunity and Reinfection Evaluation) study.
This interval-dependent antibody level varied by age, with those aged 45-54 years showing an 11-fold increase with a longer dosing interval (greater than 10 weeks vs 2-4 weeks). People younger than age 25 years showed a 13-fold increase with the longer interval, but participant numbers were low in this sub-group.
Overall antibody levels in infection-naive participants were 1268.72 Binding Antibody Units (BAU)/mL (1043.25 - 1542.91) in those with a 2-4-week interval compared to 11,479.73 BAU/mL (10,742.78 - 12,267.24) (P < .0001), in those with at least a 10-week interval between doses.

The work is the latest analysis from SIREN, which measured antibody levels in the blood from nearly 6000 healthcare workers from across the UK. Study lead Ashley Otter, PhD, technical lead for SIREN serology at the UK Health Security Agency (UKHSA), will present the work on Tuesday at this year's European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Lisbon.

In an interview with Medscape Medical News, Otter noted that, "it is important to remember that antibody levels are only one aspect of the immune response and in our recent vaccine effectiveness analysis we found that dosing intervals did not affect protection against infection."
The study, which appeared in the March issue of the New England Journal of Medicine, also found that after the second dose of vaccine, there was about a 2.5-fold difference in antibody levels between those who had prior infection 16.052 (14.071-18.312) BAU/mL compared with 7.050 (6.634 - 7.491) BAU/mL in infection-naive individuals (P < .0001).
Following the first dose only, antibody levels were up to 10 times higher in participants who were previously infected compared with infection-naive individuals. This effect lasted up to 8 months and then began to plateau.

Natural Infection Increased Antibody Levels​

Otter remarked that, "COVID-19 antibody levels are high in those people who were previously naturally infected and vaccinated, highlighting that vaccination provides an additional benefit to these individuals."

Medscape asked Charlotte Thålin, PhD, an immunologist from the Karolinska Institute, Stockholm, Sweden, to comment on the study. Thålin studies a cohort similar to SIREN, called the Swedish COMMUNITY healthcare worker cohort. "The new data from the SIREN emphasizes the importance of the number of antigenic exposures and the time interval between them, whether it be exposure through vaccination or exposure through infection."

"We see similar data in our Swedish COMMUNITY healthcare worker cohort," Thålin continued, "where infection prior to vaccination yields a more than twofold enhancement in antibodies, neutralizing breadth, and T-cell responses, and an even larger increase with a longer time interval between infection and vaccination."

However, she cautioned that they now see a high rate of Omicron vaccine breakthrough infections, and this is also true in people with previous infection and three vaccine doses.

"As we approach a second booster — a fourth vaccine dose — we need to consider that many individuals will have had up to five to six antigen exposures within a short period of time, sometimes within a year," she pointed out. "This is a whole new scenario, with a lot of different combinations of vaccine and infection-induced immunity. We do not yet know the impact of these frequent immune exposures, and we now need to monitor immune responses following Omicron and booster doses closely."

SIREN originally aimed to understand how much protection people got after developing a primary infection and why they might become reinfected with COVID-19. Following the rollout of the UK's vaccination program, the protective effects of vaccination against COVID-19 were investigated as well as why some people still become ill after being vaccinated, Otter explained.

In this latest analysis, Otter and colleagues assessed anti-spike binding antibodies in serum samples from a total of 5871 healthcare workers, with 3989 after one dose (at least 21 days) and 1882 two doses (at least 14 days).

Most participants were women (82.3%) and of white ethnicity (87%) and came from across the UK.

Participants were also categorized into those who had evidence of natural COVID-19 infection (confirmed by a PCR test or assumed because of their antibody profile) or those who were infection-naive. Almost all (>99%) of those who were infection-naive seroconverted after vaccination.
The primary outcome was anti-spike antibody levels assessed according to dose, previous infection, dosing interval, age, ethnicity, and comorbidities, including immunosuppressive disease such as immune system cancers, rheumatologic disease, chronic respiratory diseases, diabetes, obesity, and chronic neurologic disease.

In the infection-naive group, the mean antibody (anti-S titer) was 75.48 BAU/mL after the first vaccine dose one, and this rose to 7049.76 BAU/mL after the second dose.

The much higher antibody titer with the second dose in infection-naive individuals, "is what gives you the most protection, as your antibody titers are at their peak. They then start to gradually wane from this peak," said Otter.

In the post-infection group, antibody titers also rose (2111.08 BAU/mL after first dose and 16,052.39 BAU/mL after second dose), although less so than in the infection-naive group, because of the additional exposure of infection, added Otter.

Antibody levels also varied according to time elapsed between natural infection and dose 1 of vaccination. With a 3-month interval, antibody levels were 1970.83 (1506.01 - 2579.1) BAU/mL compared with 13,759.31 (8,097.78 - 23,379.09) BAU/mL after a 9-month interval. Antibody levels after one dose in those previously infected are higher than the infection-naive because "previous infection, then vaccination, is likely explained by T-cell expansion upon a boost with a second antigen exposure, and then a maturing memory B-cell response that has been demonstrated up to 6 months," explained Otter

Timing of Fourth Dose​

By March of this year, 86.2% of the UK population aged over 12 years had received at least two doses, but with rises in disease prevalence and the spread of variants of concern,


further work is ongoing to understand the waning of the immune response, level of protection, and why some individuals develop COVID-19 even when double-vaccinated.

Medscape asked Susanna Dunachie, BMChB, professor of infectious diseases, University of Oxford, UK, what the interval findings might mean for the timing of the fourth dose of vaccine across the UK population.

In the UK, fourth doses are being given to people who are 75 years and older, residents in care homes for older people, and those with weakened immune systems. "To make decisions about fourth doses for healthy people, we need to see how quickly antibody and T-cell responses drop," said Dunachie, who is part of the large SIREN study team but was not involved in the analysis led by Otter. "Current research suggests that the T-cell response may be better maintained than the antibody response, and less affected by variants like Omicron."

She explained the balance between antibody and T-cell responses to vaccination. "It is likely that antibodies that neutralize the virus are important for preventing any infection at all, and these unfortunately do fall in time, but T-cell responses are better sustained and help keep people out of [the] hospital," she said.

Dunachie added that it was necessary to wait and observe what happens next with SARS-CoV-2 evolution, as well as wait for longer follow-up after the third dose in healthy people. "On current evidence, my estimate is we postpone decisions on fourth doses in healthy people to late summer/autumn."

32nd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID): Abstract 250. To be presented April 26, 2022

”

 

[MamaBee]

@MamaBee

More Antibodies With Longer Intervals Between COVID Vaccine Doses

Antibody levels were also much higher in individuals who were previously infected with COVID-19.

www.medscape.com

“

More Antibodies With Longer Intervals Between COVID Vaccine Doses​

Becky McCall
April 24, 2022


LISBON, Portugal — An overall ninefold increase in COVID-19 antibody levels can be seen with a longer interval between first and second doses of the Pfizer/BioNTech (BNT162b2) vaccine in people without prior infection, according to data from the UK government's SIREN (SARS-CoV-2 Immunity and Reinfection Evaluation) study.
This interval-dependent antibody level varied by age, with those aged 45-54 years showing an 11-fold increase with a longer dosing interval (greater than 10 weeks vs 2-4 weeks). People younger than age 25 years showed a 13-fold increase with the longer interval, but participant numbers were low in this sub-group.
Overall antibody levels in infection-naive participants were 1268.72 Binding Antibody Units (BAU)/mL (1043.25 - 1542.91) in those with a 2-4-week interval compared to 11,479.73 BAU/mL (10,742.78 - 12,267.24) (P < .0001), in those with at least a 10-week interval between doses.

The work is the latest analysis from SIREN, which measured antibody levels in the blood from nearly 6000 healthcare workers from across the UK. Study lead Ashley Otter, PhD, technical lead for SIREN serology at the UK Health Security Agency (UKHSA), will present the work on Tuesday at this year's European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Lisbon.

In an interview with Medscape Medical News, Otter noted that, "it is important to remember that antibody levels are only one aspect of the immune response and in our recent vaccine effectiveness analysis we found that dosing intervals did not affect protection against infection."
The study, which appeared in the March issue of the New England Journal of Medicine, also found that after the second dose of vaccine, there was about a 2.5-fold difference in antibody levels between those who had prior infection 16.052 (14.071-18.312) BAU/mL compared with 7.050 (6.634 - 7.491) BAU/mL in infection-naive individuals (P < .0001).
Following the first dose only, antibody levels were up to 10 times higher in participants who were previously infected compared with infection-naive individuals. This effect lasted up to 8 months and then began to plateau.

Natural Infection Increased Antibody Levels​

Otter remarked that, "COVID-19 antibody levels are high in those people who were previously naturally infected and vaccinated, highlighting that vaccination provides an additional benefit to these individuals."

Medscape asked Charlotte Thålin, PhD, an immunologist from the Karolinska Institute, Stockholm, Sweden, to comment on the study. Thålin studies a cohort similar to SIREN, called the Swedish COMMUNITY healthcare worker cohort. "The new data from the SIREN emphasizes the importance of the number of antigenic exposures and the time interval between them, whether it be exposure through vaccination or exposure through infection."

"We see similar data in our Swedish COMMUNITY healthcare worker cohort," Thålin continued, "where infection prior to vaccination yields a more than twofold enhancement in antibodies, neutralizing breadth, and T-cell responses, and an even larger increase with a longer time interval between infection and vaccination."

However, she cautioned that they now see a high rate of Omicron vaccine breakthrough infections, and this is also true in people with previous infection and three vaccine doses.

"As we approach a second booster — a fourth vaccine dose — we need to consider that many individuals will have had up to five to six antigen exposures within a short period of time, sometimes within a year," she pointed out. "This is a whole new scenario, with a lot of different combinations of vaccine and infection-induced immunity. We do not yet know the impact of these frequent immune exposures, and we now need to monitor immune responses following Omicron and booster doses closely."

SIREN originally aimed to understand how much protection people got after developing a primary infection and why they might become reinfected with COVID-19. Following the rollout of the UK's vaccination program, the protective effects of vaccination against COVID-19 were investigated as well as why some people still become ill after being vaccinated, Otter explained.

In this latest analysis, Otter and colleagues assessed anti-spike binding antibodies in serum samples from a total of 5871 healthcare workers, with 3989 after one dose (at least 21 days) and 1882 two doses (at least 14 days).

Most participants were women (82.3%) and of white ethnicity (87%) and came from across the UK.

Participants were also categorized into those who had evidence of natural COVID-19 infection (confirmed by a PCR test or assumed because of their antibody profile) or those who were infection-naive. Almost all (>99%) of those who were infection-naive seroconverted after vaccination.
The primary outcome was anti-spike antibody levels assessed according to dose, previous infection, dosing interval, age, ethnicity, and comorbidities, including immunosuppressive disease such as immune system cancers, rheumatologic disease, chronic respiratory diseases, diabetes, obesity, and chronic neurologic disease.

In the infection-naive group, the mean antibody (anti-S titer) was 75.48 BAU/mL after the first vaccine dose one, and this rose to 7049.76 BAU/mL after the second dose.

The much higher antibody titer with the second dose in infection-naive individuals, "is what gives you the most protection, as your antibody titers are at their peak. They then start to gradually wane from this peak," said Otter.

In the post-infection group, antibody titers also rose (2111.08 BAU/mL after first dose and 16,052.39 BAU/mL after second dose), although less so than in the infection-naive group, because of the additional exposure of infection, added Otter.

Antibody levels also varied according to time elapsed between natural infection and dose 1 of vaccination. With a 3-month interval, antibody levels were 1970.83 (1506.01 - 2579.1) BAU/mL compared with 13,759.31 (8,097.78 - 23,379.09) BAU/mL after a 9-month interval. Antibody levels after one dose in those previously infected are higher than the infection-naive because "previous infection, then vaccination, is likely explained by T-cell expansion upon a boost with a second antigen exposure, and then a maturing memory B-cell response that has been demonstrated up to 6 months," explained Otter

Timing of Fourth Dose​

By March of this year, 86.2% of the UK population aged over 12 years had received at least two doses, but with rises in disease prevalence and the spread of variants of concern,


further work is ongoing to understand the waning of the immune response, level of protection, and why some individuals develop COVID-19 even when double-vaccinated.

Medscape asked Susanna Dunachie, BMChB, professor of infectious diseases, University of Oxford, UK, what the interval findings might mean for the timing of the fourth dose of vaccine across the UK population.

In the UK, fourth doses are being given to people who are 75 years and older, residents in care homes for older people, and those with weakened immune systems. "To make decisions about fourth doses for healthy people, we need to see how quickly antibody and T-cell responses drop," said Dunachie, who is part of the large SIREN study team but was not involved in the analysis led by Otter. "Current research suggests that the T-cell response may be better maintained than the antibody response, and less affected by variants like Omicron."

She explained the balance between antibody and T-cell responses to vaccination. "It is likely that antibodies that neutralize the virus are important for preventing any infection at all, and these unfortunately do fall in time, but T-cell responses are better sustained and help keep people out of [the] hospital," she said.

Dunachie added that it was necessary to wait and observe what happens next with SARS-CoV-2 evolution, as well as wait for longer follow-up after the third dose in healthy people. "On current evidence, my estimate is we postpone decisions on fourth doses in healthy people to late summer/autumn."

32nd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID): Abstract 250. To be presented April 26, 2022

”

Thanks @missy..Yes..That’s what you’ve been saying..I think that will be our timeline..end of summer..I do want to test my antibodies again in two months though. I know my T cells are probably at the ready anyway..but I really like knowing my antibodies are still high.

 

[missy]

"

JAMA

April 25, 2022

Oral Antiviral Medications for COVID-19​

Lindsay A. Petty, MD1; Preeti N. Malani, MD, MSJ1
Author Affiliations Article Information
JAMA. Published online April 25, 2022. doi:10.1001/jama.2022.6876


https://jamanetwork.com/journals/jama-health-forum/fullarticle/2790540



Two new oral antiviral medications are available for treatment of COVID-19.
Two new antiviral medications, ritonavir-boosted nirmatrelvir (Paxlovid, ie, nirmatrelvir-ritonavir) and molnupiravir (Lagevrio), are currently available in the US under emergency use authorization. These 2 drugs are authorized for treatment of patients with mild to moderate COVID-19 who are not currently hospitalized but are at high risk of developing severe disease. Nirmatrelvir-ritonavir and molnupiravir are approved for use only within 5 days of onset of COVID-19 symptoms.
Nirmatrelvir-ritonavir and molnupiravir should be considered for patients with symptoms of COVID-19 who test positive for SARS-CoV-2 and either are an older adult (aged 65 years or older) or are aged 12 years or older with an underlying condition that increases risk of severe outcomes of COVID-19 (such as cancer, heart disease, diabetes, and obesity).

How Do These Medications Work and How Effective Are They?
Nirmatrelvir-ritonavir and molnupiravir reduce the ability of SARS-CoV-2 to multiply and spread through the body. While these drugs may not shorten the duration of symptoms, they decrease the need for hospitalization and work best when taken early in the course of COVID-19.
Nirmatrelvir-ritonavir has been found to be substantially more effective against hospitalization and death than molnupiravir, so it is the preferred drug unless it is unavailable or cannot be given due to kidney or liver disease or certain drug interactions.
Nirmatrelvir-ritonavir cannot be given to people with severe kidney or liver disease and should not be taken with certain other drugs (such as amiodarone, colchicine, and statins). Doctors may stop or replace such medications temporarily while a patient is taking nirmatrelvir-ritonavir, or they may decrease the dose of a medication that interacts with nirmatrelvir-ritonavir. Patients should provide a complete list of medications, including over-the-counter and herbal products, to their doctor or pharmacist before starting this medication.
Molnupiravir should not be prescribed to patients who are pregnant or attempting to become pregnant. Men who have sexual contact with individuals of childbearing age should use a reliable method of contraception consistently while taking molnupiravir and for 3 months afterward. Use of molnupiravir is not authorized for patients younger than 18 years due to potential effects on bone and cartilage.
What to Expect While Taking the Medication
Both nirmatrelvir-ritonavir and molnupiravir are taken twice daily for 5 days. Altered taste, nausea, diarrhea, and dizziness are the most common side effects. Most patients feel better over several days to 2 weeks, but those who develop shortness of breath or other worrisome symptoms should notify their doctor without delay.
How Can Patients Get Oral Antiviral Medications for COVID-19?
People who develop symptoms of COVID-19 should get tested as early as possible. Those who test positive for SARS-CoV-2 and are at high risk of severe illness should contact their doctor to find out if they are eligible for treatment.
Nirmatrelvir-ritonavir and molnupiravir are provided to patients for free, although pharmacies may request insurance information for dispensing charges. To avoid spreading SARS-CoV-2, patients should use drive-through windows to pick up oral antiviral medications for COVID-19. Home delivery options may be available for patients who do not have transportation.

For More Information​

• Centers for Disease Control and Prevention
  www.cdc.gov/coronavirus/2019-ncov/your-health/treatments-for-severe-illness.html
• Department of Health and Human Services
  aspr.hhs.gov/TestToTreat/Pages/default.aspx

The JAMA Patient Page is a public service of JAMA. The information and recommendations appearing on this page are appropriate in most instances, but they are not a substitute for medical diagnosis. For specific information concerning your personal medical condition, JAMA suggests that you consult your physician. This page may be downloaded or photocopied noncommercially by physicians and other health care professionals to share with patients. To purchase bulk reprints, email [email protected].
Article Information
Published Online: April 25, 2022. doi:10.1001/jama.2022.6876
Conflict of Interest Disclosures: None reported.
Source: Gandhi RT, Malani PN, del Rio C. COVID-19 therapeutics for nonhospitalized patients. JAMA. 2022;327(7):617-618. doi:10.1001/jama.2022.0335

"

 

[missy]

Even Mild Covid Can Change the Brain

"
A large study comparing brain scans from the same individuals before and after SARS-CoV-2 infection suggests that brain changes could be a lingering outcome of even mild COVID-19. Writing in Nature, researchers at Oxford University’s Wellcome Centre for Integrative Neuroimaging reported that several months after study participants had SARS-CoV-2 infections, they had more gray matter loss and tissue abnormalities, mainly in the areas of the brain associated with smell, and more brain size shrinkage than participants who hadn’t been infected with the virus.



Why It’s Important
Researchers, clinicians, and the public all are eager to learn more about COVID-19’s outcomes after the initial infection, especially for individuals with mild or asymptomatic disease, which represents most people with SARS-CoV-2 infection. Of particular interest are brain-related changes that could help explain commonly reported long-term symptoms including loss of smell and taste, headaches, and memory problems.

With nearly 800 volunteers, the new study is the largest COVID-19 brain imaging analyses to date. It’s also the first to focus on patients with mostly nonsevere illness and to include preinfection data from the same people. “The fact that we have the pre-infection scan helps us distinguish brain changes related to the infection from differences that may have pre-existed in their brains,” Stephen Smith, DPhil, the study’s senior author and a professor of biomedical engineering at the Nuffield Department of Clinical Neurosciences (NDCN) at Oxford, said in a statement.

In an email, JAMA Neurology Editor S. Andrew Josephson, MD, who was not involved with the work, called the report “an intriguing study that furthers our understanding of COVID-19 and the brain.”

The Design
The scans came from the UK Biobank—a research resource with data from half a million volunteers—where Smith is scientific lead for brain imaging. The baseline magnetic resonance imaging took place from 2014 through early March of 2020. For the UK Biobank COVID-19 Repeat Imaging study, the researchers invited hundreds of original volunteers aged 51 to 81 years back for a second round of scans between February and May of 2021. The current reimaging study analysis included:

• 401 cases—volunteers infected with SARS-CoV-2 between March 2020 and April 2021. Of this group, 15 people, or 4%, were hospitalized and 2 received critical care. The group underwent reimaging an average of 3 years after their baseline scans and 4.5 months after their COVID-19 diagnoses.
• 384 controls—volunteers without SARS-CoV-2 infection who were matched with the COVID-19 group for age, sex, ethnicity, the amount of time elapsed between scans, and risk factors such as blood pressure, obesity, smoking, socioeconomic status, and diabetes.

The researchers first estimated brain changes over time in each group and then looked for differences in these changes between the groups. They also compared the groups’ changes in cognitive decline based on differences in cognitive task scores. To investigate if other respiratory infections are associated with brain changes, the team compared imaging from separate groups of UK Biobank volunteers who had influenza or pneumonia not related to COVID-19.

What We’ve Learned
The brain scans and cognitive scores of participants who had been infected with SARS-CoV-2 showed changes between the 2 time points that differed from those seen in the control group, with greater differences among older participants. Although not everyone who became infected with SARS-CoV-2 had these differences, the prior-infection group on average had:

• greater loss of gray matter thickness in the orbitofrontal cortex and parahippocampal gyrus, areas associated with the sense of smell
• greater tissue damage in areas connected with the primary olfactory cortex, also linked with smell
• greater decrease in whole-brain volume and increase in cerebrospinal fluid volume
• greater decline in the ability to perform complex tasks, which on brain scans was associated with atrophy in crus II, an area of the cerebellum associated with cognition

Compared with the control group, volunteers with a prior SARS-CoV-2 infection had an additional 0.2% to 2% gray matter loss or tissue damage on average between their 2 sets of scans. For context, adults lose about 0.2% to 0.3% of gray matter in memory-related brain regions per year, according to Gwenaëlle Douaud, PhD, the study’s lead author and an associate professor at the NDCN.

The findings remained statistically significant when the patients hospitalized with COVID-19 were removed from the analysis.

Too few influenza cases occurred to draw comparisons, but brain differences among 11 volunteers who developed non–COVID-19 pneumonia between imaging sessions did not substantially overlap with brain regions implicated in the COVID-19 analysis. This could indicate that the study’s findings are specific to SARS-CoV-2 infection, not respiratory infection in general.

Possible Explanations
In their article, Douaud’s team offered several potential mechanisms by which SARS-CoV-2 infection might directly or indirectly alter brain structure, including

• reduced sensory input related to loss of smell
• neuroinflammation or immune reactions
• direct viral infection of brain cells

The Limitations

• The volunteers’ COVID-19 symptoms were not available to the researchers. They therefore could not connect brain changes with symptoms or with symptomatic vs asymptomatic infection.
• Most participants became infected before COVID-19 vaccines were available in the UK. Some were likely infected by the original SARS-CoV-2 strain but most probably contracted the Alpha variant, according to the authors. How vaccination or different variants such as Delta or Omicron might affect the findings isn’t known.
• The study volunteers were predominantly White and were all middle-aged or older adults. It’s unknown how the findings will translate to younger adults or to children. The researchers pointed out that the effects were greater in the study’s older participants.
• Although the researchers attempted to match the 2 groups as closely as possible, the COVID-19 group at baseline had a subtle pattern of lower cognitive abilities. These differences were not statistically significant and, according to the researchers, could not explain away the study findings.
• The COVID-19 group had structural differences in certain brain regions at baseline compared with the control group, but these regions did not overlap with those that were different in the longitudinal analysis.
• It’s possible that the volunteers in the COVID-19 group had subtle preexisting differences from the control group that predisposed them to acquiring SARS-CoV-2 and experiencing its damaging effects.

The Clinical Takeaway
Josephson said the study puts into context concerns about ongoing infections, including those that are mild. But he cautioned that despite the study’s cognitive findings, the clinical significance of the COVID-19 group’s additional brain changes is not clear.

It’s also too soon to know if the changes are reversible. The timeframe between SARS-CoV-2 infection and the second round of imaging was relatively short. “Whether this is a temporary effect, perhaps related to anosmia or inflammation, or an effect that is more long lasting and could be associated with the cognitive and other neurologic and psychiatric changes described in some with long COVID remains an ongoing area of study,” noted Josephson, who is a professor and chair of the Department of Neurology at the University of California, San Francisco.

A recent report in JAMA Neurology suggests that the cognitive changes observed among some patients with COVID-19 might endure, particularly for those with more severe disease. Investigators found a higher incidence of cognitive impairment among older adults in Wuhan, China, a year after COVID-19 hospitalization compared with their spouses who hadn’t been infected, even after adjusting for age, sex, educational level, body mass index, and comorbidities.

On the other hand, in a written FAQ provided to media, Douaud suggested that the damage observed in her team’s study might improve in due course: “Since the abnormal changes we see in the brain of the infected participants might be related to their loss of smell, it is possible that recovering their smell might lead to these brain abnormalities becoming less marked over time. Similarly, it is likely that the harmful effects of the virus (whether direct, or indirect via inflammation or immune reaction) decrease over time after infection.” She cited small previous studies indicating that issues detected on functional brain imaging may in part improve more than 6 months after SARS-CoV-2 infection.

The bottom line for now, in Josephson’s view: “Making sure we are vigilant and attentive to patients’ cognitive concerns post-COVID remains extremely important.”

Looking Ahead
The findings should be replicated in different populations before being considered definitive. Expect additional analyses from Douaud’s group, too. The team hopes to scan the UK Biobank COVID-19 Repeat Imaging study participants for a third time in a year or two.

How best to manage patients’ cognitive symptoms remains an area of robust study, according to Josephson. The current analysis, he said, “also emphasizes just how important it is to continue to work to understand the mechanisms of these neurological symptoms and whether vaccination or severity of illness modifies them.”

Some of the altered brain regions identified in the study also have memory-related functions. Although there were no signs of memory impairment, if the damage persists, there could be implications for later memory problems or even dementia. Down the line, insight should come from the Alzheimer’s Association and researchers from more than 30 countries, who have formed an international consortium to study SARS-CoV-2 infection’s effects on the central nervous system in the short- and long-term.


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[GemmaBella]

Thank you, @missy for these important updates. I for one, really appreciate them.

 

[missy]

Fauci: U.S. Out of Pandemic Phase; Pfizer Seeks Kids' Booster; Aspirin Advice Shifts​

— A daily roundup of news on COVID-19 and the rest of medicine​

by Judy George, Senior Staff Writer, MedPage Today April 27, 2022

“

NIAID Director Anthony Fauci, MD, said the U.S. is now "out of the pandemic phase." (Washington Post)

Vice President Kamala Harris tested positive for the coronavirus. (CNN)

Japan has detected its first probable case of the mysterious severe acute hepatitis that has so far affected at least 169 children, largely in Britain. (Bloomberg)

Canada's Public Health Agency said it is investigating reportsof severe acute hepatitis of unknown origin in young children, but provided no details about the number of cases. (CBC)



Pfizer/BioNTech asked the FDA to authorize their COVID-19 booster shot for children 5 through 11.

Meanwhile, agency official Peter Marks, MD, PhD, suggested the FDA hasn't cleared a primary COVID vaccine series for kids under 5 yet because manufacturers have not completed their applications for emergency authorization. (New York Times)

As of Wednesday at 8:00 a.m. EDT, the unofficial COVID tollin the U.S. reached 81,118,173 infections and 993,193 deaths, increases of 44,123 and 291, respectively, from this time yesterday.

The European Union is set to move away from the emergency phase of the pandemic amid a gradual drop in cases and a decreasing number of deaths linked with COVID-19. (Reuters)

Daily aspirin offered no net benefit for primary prevention of cardiovascular disease in people 60 and over, and a small net benefit in some people 40 to 59 years old, the U.S. Preventive Services Task Force said, consistent with its draft recommendations released last fall. (JAMA)

”

 

[missy]

Guillain-Barre Risk After COVID-19 Vaccines Low, Surveillance Data Show​

— But rates continue to be unusually high after Johnson & Johnson shot​

April 26, 2022
“

Risk of Guillain-Barré syndrome after COVID-19 vaccines was low overall, but unusually high after the Johnson & Johnson shot, surveillance data showed.

Among 15.1 million doses of COVID-19 vaccines included in the Vaccine Safety Datalink, the unadjusted incidence rate of confirmed Guillain-Barré syndrome 1 to 21 days after receiving the Johnson & Johnson vaccine was 32.4 per 100,000 person-years, significantly higher than the background rate, reported Nicola Klein, MD, PhD, of Kaiser Permanente Northern California in Oakland, and colleagues.



The unadjusted incidence rate of confirmed Guillain-Barré 1 to 21 days after mRNA vaccines was 1.3 per 100,000 person-years, similar to the background rate, they wrote in JAMA Network Open.

"The background rate for Guillain-Barré syndrome is known to be about one or two cases per 100,000 person-years," Klein told MedPage Today.

The findings confirm data seen in the Vaccine Adverse Event Reporting System (VAERS) that led to the FDA warning about the Johnson & Johnson vaccine in July 2021.

"The Vaccine Safety Datalink is an active surveillance system for vaccine safety events, complementary to VAERS but quite different," Klein noted.

"In the Vaccine Safety Datalink, eight integrated health systems contribute data in collaboration with the CDC," she said. "We have full access to complete medical records and we can actively survey for all sorts of medical encounters and health events after vaccination. We know our underlying population; we know who is in the denominator and we don't have to make estimates."



The study evaluated data from 7.9 million people, ages 12 and older, who received either the Johnson & Johnson shot or a Pfizer-BioNTech or Moderna vaccine (including mRNA vaccine doses 1 and 2) from December 2020 to November 2021. The outcome was Guillain-Barré syndrome with symptom onset after vaccination, confirmed by medical record review.

"We pre-specified that we would look at the charts of all the Guillain-Barré syndrome cases after vaccination," Klein said. "The charts were all reviewed and adjudicated by neurologists and other medical professionals."

Overall, 15,120,073 COVID-19 vaccine doses were administered to 7,894,989 individuals, including 483,053 Johnson & Johnson, 8,806,595 Pfizer, and 5,830,425 Moderna doses. Patients had a mean age of 46.5 and 53.8% of doses were received by women. Rate ratios (RRs) comparing Guillain-Barré risk after vaccination were adjusted for age, sex, race and ethnicity, site, and calendar day.

Eleven cases of Guillain-Barré syndrome were confirmed after the Johnson & Johnson shot. The adjusted RR in days 1 to 21 compared with days 22 to 42 after the Johnson & Johnson vaccine was 6.03 (95% CI 0.79-147.79).



Thirty-six cases of Guillain-Barré after mRNA vaccines were confirmed; the adjusted RR in days 1 to 21 versus days 22 to 42 was 0.56 (95% CI 0.21-1.4 for the mRNA vaccines.

A head-to-head comparison showed the Johnson & Johnson vaccine carried a 20% higher risk for Guillain-Barré than the mRNA shots (adjusted RR 20.56, 95% CI 6.94-64.66). Using a risk interval of 1 to 42 days, the adjusted RR dropped to 11.46 (95% CI 4.83-26.16, P<0.001).

The study had several limitations, the researchers acknowledged. Many fewer doses of the Johnson & Johnson vaccine were administered, leading to reduced statistical power and wide confidence intervals. People who received the Johnson & Johnson shot may have differed from others in ways that might affect Guillain-Barré risk. In addition, the incidence of confirmed Guillain-Barré during the COVID-19 pandemic has not been established and may differ from pre-pandemic background rates.

Surveillance for Guillain-Barré in the Vaccine Safety Datalink is ongoing, Klein noted. In December 2021, the CDC recommended Pfizer and Moderna's COVID-19 vaccines over Johnson & Johnson's for all adults.

”

 

[missy]

"

Long Covid and new variants​

How long the coronavirus spends in the body of Covid-19 patients has been a point of contention since the first months of the pandemic. Tests that look for viral antigens, called PCR, were positive repeatedly for weeks in some recovered patients, stoking concern that they remained infectious. But studies by researchers in South Korea in 2020 found those tests were detecting non-infectious viral remnants or debris, and the patients weren’t transmitting the virus anymore. The peace of mind that generated lasted until the emergence of more infectious strains, beginning with alpha in late 2020. Some scientists hypothesized that the contagious variant evolved in a chronically infected patient. Researchers have increasingly described persistent SARS-CoV-2 infections in a small minority of patients, most of whom can’t clear the virus because of HIV, cancer, organ transplantation or other conditions that weaken the immune system. Some believe that omicron and its sub-variants emerged from such a patient. In one case, a patient in London tested positive for 505 days, U.K. researchers told the European Congress of Clinical Microbiology & Infectious Diseases in Lisbon. The patient, who eventually died, was one of nine studied by doctors at King’s College London and Guy’s and St. Thomas’ NHS Foundation Trust. In some patients, the coronavirus or its remnants can linger for months in the body and aggravate the immune system. Photographer: Chan Long Hei/Bloomberg Their infections persisted for 73 days on average, but two had infections for longer than a year. Regular sampling and genetic analysis showed that virus isolated from five of the nine patients developed at least one mutation, and samples from some individuals developed multiple mutations associated with the alpha, delta and omicron variants. The virus from one individual contained 10 mutations seen in the alpha, gamma and omicron strains. “Immunocompromised patients with persistent infection have poor outcomes, and new treatment strategies are urgently needed to clear their infection,” said Gaia Nebbia, a virology consultant who worked on the research, in a statement. “This may also prevent the emergence of variants.” Autopsy findings and a growing awareness of a subset of Covid patients with long-haul symptoms and persistent immune activation also suggest that the coronavirus or its remnants may linger for months in the body and aggravate the immune system. In the largest study yet, scientists at California’s Stanford University found that about half of infected patients shed traces of the virus in their waste in the week after infection, and that almost 4% patients still emit them seven months later. The researchers also linked coronavirus RNA in feces to gastric upsets, and concluded that SARS-CoV-2 likely directly infects the gastrointestinal tract, where it may hide out. No one knows yet what causes the constellation of post-Covid symptoms, often termed long Covid. It’s possible that at least four different biological mechanisms lead to distinct conditions or subtypes of long Covid, Akiko Iwasaki, a professor of immunobiology and molecular, cellular, and developmental biology at Yale University, told me last month. In one of those forms, persistent SARS-CoV-2 may trigger a damaging immune response that leads to ailments that could be quelled with antiviral drugs or monoclonal antibodies that target the virus, Iwasaki said. Researchers are gearing up to conduct clinical trials to investigate that possibility, she said. — Jason Gale :