Coronavirus updates December 2022

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Higher BMI a Risk Factor for Long COVID Symptoms​

— Female sex was another independent risk factor, U.K. study showed​

by Kristen Monaco, Staff Writer, MedPage Today November 30, 2022

When it comes to developing long COVID, certain people may have a higher risk than others, researchers reported.
According to an online survey of people who tested positive in 2020, 52.1% said they experienced post-COVID syndrome symptoms, said Vassilios Vassiliou, PhD, of the University of East Anglia in Norwich, England, and colleagues.
One of the top predictors of exactly who might develop these long COVID symptoms was body mass index (BMI), the team reported in PLOS Global Public Health. More specifically, every 1 kg/m2 more of BMI was tied with a 3% higher relative risk for the condition (RR 1.031, 95% CI 1.016-1.047).

Female sex also appeared to be another risk factor. Compared with females, male sex was linked with a significantly lower relative risk for developing post-COVID symptoms (RR 0.748, 95% CI 0.605-0.924).
"This is really important because information like this can be used to profile those people who are 'at risk' of developing long COVID," Vassiliou explained in a statement.
The researchers also discovered that of the 25.4% of patients who utilized healthcare services after their initial COVID infection, 73.2% were experiencing symptoms of long COVID. This translated to more than a three-fold higher relative risk for people with long COVID symptoms using healthcare services (RR 3.280, 95% CI 2.540-4.262).
Similarly, males were significantly less likely to be utilizing these health services after testing positive (RR 0.618, 95% CI 0.464-0.81. On the other hand, the same positive association with BMI was still seen (RR 1.027, 95% CI 1.009-1.046).
The researchers said there was a slight trend for age per year as an independent risk factor for post-COVID symptoms, but it was not statistically significant (RR 1.003, 95% CI 0.998-1.009 per 1 year older).

"Based on the above, it can be estimated that for a man to have the same probability as a female of the same age with normal BMI, they have to have a BMI over 35 kg/m2," the researchers said.
Vassiliou added that his group hopes the study can aid policymakers in planning local COVID services, as well as inform the general public of the magnitude of the long COVID pandemic.
"Long COVID is a complex condition that develops during or after having COVID, and it is classified as such when symptoms continue for more than 12 weeks," he explained. "Just over two million people in the U.K. are thought to suffer with long COVID, and it affects people in different ways. Breathlessness, cough, heart palpitations, headaches, and severe fatigue are among the most prevalent symptoms.
"Other symptoms may include chest pain or tightness, brain fog, insomnia, dizziness, joint pain, depression and anxiety, tinnitus, loss of appetite, headaches, and changes to sense of smell or taste," Vassiliou added.

A total of 1,487 individuals residing in East England completed the online survey. Post-COVID syndrome was defined as individuals who selected one or more new self-reported symptoms from the questionnaire following COVID illness. A total of 61% of the cohort were females, average age was 50, and average BMI was 28.4.
Because the study included only individuals with a confirmed COVID-19 infection between the start of the pandemic through December 6, 2020, the vast majority of participants were unvaccinated at the time of infection, the researchers noted. Only 11 participants had received their first vaccine dose.
"All of these people were infected in the months before the COVID vaccination program was rolled out and they suffered from numerous new symptoms that were not present before their COVID infection," said Vassiliou.

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  Kristen Monaco is a staff writer, focusing on endocrinology, psychiatry, and nephrology news. Based out of the New York City office, she’s worked at the company since 2015.

Disclosures
Vassiliou and co-authors reported no disclosures.
Primary Source
PLOS Global Public Health
Source Reference: Debski M, et al "Post-COVID-19 syndrome risk factors and further use of health services in East England" PLOS Glob Public Health 2022; DOI: 10.1371/journal.pgph.0001188.
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Omicron's Birthday: A Look at the Pandemic's Most Enduring Variant​

Lisa O'Mary

The COVID-19 variant Omicron is celebrating a birthday of sorts. One year ago today, it was labeled "a variant of concern" by the World Health Organization.
There have been no additional VOCs named by the WHO since then – just subvariants of Omicron with a jumble of letters, periods and numbers to identify them. The current prevalent ones are BQ.1 and BQ.1.1, sometimes called "the BQs."
Omicron's impact on public health and lifestyles worldwide has been so profound that its official naming is now commemorated in a widely distributed "Today in History" column.

"The United States, Canada, Russia and a host of other countries joined the European Union in restricting travel for visitors from southern Africa" in response to Omicron's emergence, The Associated Press history column says.
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Initially identified in Botswana and South Africa, scientists later realized the earliest known cases of Omicron occurred in The Netherlands, Yale Medicinesummarized. The CDC confirmed the first U.S. case in California on December 1, 2021.
Many researchers hypothesize that Omicron "arose in a single person, perhaps with a compromised immune system, who had a chronic case of Covid that lasted months," The New York Times reported. Another theory the Times noted was that an early form of coronavirus in mice evolved into Omicron and then moved from mice back to humans.
From December 2021 into the new year, the high transmissibility of Omicron fueled cases to record levels.

"Countries which had so far been successful in keeping COVID-19 at bay through public health and social measures now found themselves struggling," the WHO summarized in a retrospective article on Omicron. "For individuals, the greatest price was paid by those who were at risk of severe disease but not vaccinated, and we saw hospitalizations and deaths rise in a number of places around the world."
The sheer number of cases created many opportunities for the virus to evolve. Today, there are more than 500 known sublineages of Omicron.
COVID-19 experts told the Times they are hopeful that lessons learned by the scientific and public health communities position the world to be well-equipped to handle whatever the virus has in store, and perhaps even predict its next moves.
"It has made me very hopeful for the future as a paradigm," German computational biologist Moritz Gerstung told the Times. "It's an instance of how one could basically get ahead of the game."

Sources​

The Associated Press: "Today in History."

Yale Medicine: "Omicron and the BQs: A Guide to What We Know."

The New York Times: "Happy Birthday, Omicron."

World Health Organization: "One year since the emergence of COVID-19 virus variant Omicron."

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Acute and Chronic Neurological Disorders in COVID-19​

Potential Mechanisms of Disease​

Erin F. Balcom; Avindra Nath; Christopher Power
DISCLOSURES
Brain. 2022;144(12):3576-3588.

December 1, 2022

Abstract and Introduction​

Abstract​

Coronavirus disease 2019 (COVID-19) is a global pandemic caused by SARS-CoV-2 infection and is associated with both acute and chronic disorders affecting the nervous system. Acute neurological disorders affecting patients with COVID-19 range widely from anosmia, stroke, encephalopathy/encephalitis, and seizures to Guillain–Barré syndrome. Chronic neurological sequelae are less well defined although exercise intolerance, dysautonomia, pain, as well as neurocognitive and psychiatric dysfunctions are commonly reported. Molecular analyses of CSF and neuropathological studies highlight both vascular and immunologic perturbations. Low levels of viral RNA have been detected in the brains of few acutely ill individuals. Potential pathogenic mechanisms in the acute phase include coagulopathies with associated cerebral hypoxic-ischaemic injury, blood–brain barrier abnormalities with endotheliopathy and possibly viral neuroinvasion accompanied by neuro-immune responses. Established diagnostic tools are limited by a lack of clearly defined COVID-19 specific neurological syndromes. Future interventions will require delineation of specific neurological syndromes, diagnostic algorithm development and uncovering the underlying disease mechanisms that will guide effective therapies.

Introduction​

Since its discovery in Wuhan, China in late 2019, coronavirus disease 2019 (COVID-19), the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 3 million deaths (https://covid19.who.int/) and placed unprecedented pressure on social, economic and health care systems worldwide. Many survivors of the acute infection experience persistent and incapacitating neurological symptoms, which can have socio-economic and personal consequences.[1] It is thus imperative that there is a thorough understanding of the evolving clinical syndromes and the underlying pathophysiological mechanisms, enabling rational therapeutic interventions to be expeditiously deployed.

Retrospective cohort studies from around the world report neurological signs and symptoms such as headache, altered mental status, seizures and stroke, in over a third of patients during the acute phase of the illness,[2–4]positioning SARS-CoV-2 as an emerging neuro-pathogen. A similar proportion of infected individuals develop a post-infectious viral syndrome with diverse neuropsychiatric manifestations. Viral infections cause neurological impairments through multiple mechanisms,[5] including direct infection of neurons, glia or endothelial cells within the nervous system resulting in acute cell death, as observed in herpes simplex virus type-1 (HSV-1) encephalitis.[6] Alternatively, viruses, e.g. the human immunodeficiency virus type-1 (HIV-1), can persist in cellular reservoirs within the central (CNS) and perhaps peripheral (PNS) nervous system resulting in chronic inflammation and insidious progressive neurological damage.[7]Among non-neurotropic viruses such as influenza and other respiratory viruses, systemic infection is associated with inflammation, metabolic and hormonal derangements, with vascular injury resulting in neurological disease.[8] The host immune responses triggered during or following viral infections can also result in autoimmune damage of neural tissues, as observed in the PNS [e.g. Guillain–Barré syndrome (GBS)] and in the CNS [e.g. acute disseminated encephalomyelitis (ADEM) or acute transverse myelitis (ATM)]. Each of these mechanisms are implicated in SARS-CoV-2 infection and are addressed next. Of note, a multisystem inflammatory syndrome in children (MIS-C) has been described in paediatric cohorts with COVID-19; several cohort studies of children infected with SARS-CoV-2 report neurological disorders resembling those observed in adults including headache, encephalopathy, demyelinating disorders and stroke.[9–13] This review provides an update on neurological manifestations of COVID-19 that concentrates on adults while also examining contemporary evidence for the neuropathogenic mechanisms implicated in SARS-CoV-2 infection (Figure 1) and their relationship to current and potential therapies (Table 1).

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Figure 1.
Potential mechanisms of acute neurological disease in COVID-19. (A) Multiple pathogenic processes result in injury to the brain during COVID-19 including vascular abnormalities resulting in thromboembolism, microhaemorrhage and endotheliopathy with associated antiphospholipid antibodies (αPL) and disruption of the blood–brain barrier (BBB) leading to bioenergy failure, autoantibodies (e.g. αGQ1b, α-NMDA-R, α-CASPR2 and αLGI2) that target a range of neural antigens, and neuroinvasion with infection of neurons and astrocytes via ACE2 as well as associated systemic inflammation and innate neuroimmune responses (cytokine, chemokine, protease and reactive oxygen species production and release by microglia and astrocytes). Therapeutic interventions that have been reported or proposed are indicated with an asterisk. (B) In the PNS and spinal cord, GBS associated with anti-glycan antibodies (αGL), T-cell mediated transverse myelitis, as well as myositis have been reported in patients with COVID-19 that may be responsive to different therapies. PLEX = plasma exchange.

Acute Neurological Syndromes​

Anosmia and ageusia were among the first focal neurological symptoms described in COVID-19, and generated interest in SARS-CoV-2's potential neurotropism.[40] Anosmia was reported in 5–35% of hospitalized patients, and may be higher among non-hospitalized patients with COVID-19.[41] In some cases, it is the sole reported symptom, or persists far beyond the acute respiratory symptoms, negatively influencing the quality of life of survivors. Infection of the nasal mucosa and sustentacular cells with dissemination throughout olfactory nerve projections is one proposed mechanism of neuropathogenesis in COVID-19.[14] Viral RNA has also been found in the olfactory bulb at post-mortem of some patients, although its association with neurological injury is not established.[14]

Altered mental status is a commonly reported neurological finding associated with COVID-19 hospitalization. Abnormalities in EEG in COVID-19 related encephalopathy correlate with disease severity.[26] Frontal slowing is the most common pattern observed and has been proposed as a biomarker for COVID-19 encephalopathy.[26] Seizures are uncommon among COVID-19 patients; in a retrospective cohort of 1043 patients, 0.7% developed seizures in hospital and an even smaller proportion of those seizures occurred outside the context of pre-existing epilepsy[42] although a recent retrospective study indicated that epileptiform abnormalities are frequently detected (48.7%) of hospitalized patients with COVID-19.[28] Altered mental status, coma and seizures in COVID-19 are almost certainly multifactorial but can be stratified into metabolic/non-inflammatory versus inflammatory (e.g. encephalitis) categories.

Non-inflammatory Encephalopathy​

Many patients with COVID-19 and altered mental status (e.g. lethargy, confusion, coma) have clinical courses complicated by hypoxia, renal failure, electrolyte disturbances, sedating medications and underlying comorbidities. A third of critically ill patients with COVID-19 present with encephalopathy, often with frontal lobe-associated features,[43,44] either at the onset of illness or during the course of hospitalization, and encephalopathy is associated with increased mortality and poor functional outcome.[37,45,46] Although encephalopathy has been reported in COVID-19 patients at all ages, patients beyond the sixth decade of life and those with pre-existing neurologic conditions (stroke, dementia, Parkinson's disease) are most affected, particularly in the context of severe respiratory illness.[45,47] While encephalopathy in the aforementioned circumstances is probably multifactorial, reports of patients with encephalopathy in the absence of severe respiratory illness suggest other possible mechanisms including bioenergetic failure and vascular dysfunction in SARS-CoV-2 infection.[48] The association between encephalopathy and morbidity exists independently of respiratory disease, similar to that observed in sepsis-associated encephalopathy.[49] Encephalopathy in non-COVID-19 patients is attributed to mitochondrial dysfunction, excitotoxicity and macro- or micro-ischaemic injury.[49] One recent post-mortem analysis in New York revealed cerebral microthrombi in a subset of 67 hospitalized, deceased COVID-19 patients.[25] Small, subcortical ischaemic events may result in confusion and cognitive dysfunction.[25] Patients can also manifest multifocal cerebral microhaemorrhages or vascular leakage (Figure 2) due to compromise of the cerebral endothelial cells.[50,51] Radiographic findings in COVID-associated encephalopathy include non-specific white matter hyperintensities, diffusion restriction, microhaemorrhage and leptomeningeal enhancement.[50,52] In one study of intensive care unit (ICU) patients with COVID-19 and encephalopathy, bilateral frontotemporal hypoperfusion was evident in all patients who underwent perfusion imaging for altered mental status,[53]although this finding was disputed and has not been replicated.[54]Surprisingly, brain MRI was normal in up to 46% of patients with COVID-19 and associated encephalopathy.[52] In another study, patients with COVID-19 and cognitive impairment showed decreased metabolism in the fronto-parietal regions on fluorodeoxyglucose (FDG)-PET scans.[46] Indeed, correlations between neuropathology and brain MRI findings (including normal imaging) have yet to be established.

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Figure 2.
Microvascular diseases with COVID-19. (A) Multiple congested blood vessels and microhaemorrhages are observed in the basal ganglia at post-mortem. (B) MRI of the same block of tissue shows hyper and hypointense signals corresponding to the blood vessels in A. The hyperintense signals represent fibrin clots while the hypointense signals are microhaemorrhages. (C) MRI of the pons shows similar punctate hypointense signals (arrows).

Inflammatory Encephalitis​

A minority of patients with COVID-19 encompass established diagnostic criteria for infectious encephalitis.[23] There are convincing reports of encephalitis-like presentations associated with elevated levels of soluble IL-6, IL-18, TNF-α, CXCL10 and markers of glial and astrocyte activation in CSF.[20,24,55,56] Radiological findings associated with COVID-19 meningoencephalitis include mesial temporal lobe T2/FLAIR hyperintensities, varying from punctate to diffuse in subcortical white matter, the brainstem and claustrum, often accompanied by cerebral oedema.[57–59]Case reports indicate that COVID-19 can present with an ADEM phenotype,[52,60] including oculomotor dysfunction, seizures and coma. Others have reported cases of acute necrotizing haemorrhagic encephalopathy that present initially with symmetric lesions in the thalami and are thought to be cytokine mediated.[61] Some patients may present with isolated pseudotumor cerebri/benign intracranial hypertension presumably from meningitis.[62,63] Opsoclonus-myoclonus syndrome, which has been observed in association with infections such as Epstein–Barr virus (EBV), chikungunya and Mycoplasma pneumoniae, has also been reported in patients with COVID-19, including those with mild respiratory disease.[64]Most patients with COVID-19 and opsoclonus-myoclonus syndrome had partial recovery at 4 weeks after treatments including pulse steroids, intravenous immunoglobulin (IVIg) and anti-epileptic medications.[64–66]

For presumed COVID-19 associated encephalitis, favourable therapeutic responses to corticosteroids and plasma exchange (PLEX) were observed in a subset of patients, although factors predicting a beneficial therapeutic response remain to be defined.[21,67] Whether the neuroinflammation observed clinically, neuroradiologically and neuropathologically is due to direct viral invasion, para-infectious or autoimmune processes remains unknown. In most COVID-19 cases with encephalitis, SARS-CoV-2 RNA is not detectable in CSF via PCR with reverse transcription (RT-PCR), favouring an immune-mediated mechanism of disease.[21,22,55,68]

Cerebrovascular Disease​

Patients with COVID-19 have an increased rate of stroke compared to other disease cohorts, with higher NIHSS scores compared to non-COVID-19 associated stroke.[16] Over half of strokes among patients with COVID-19 are cryptogenic, with a higher proportion of large vessel occlusions.[18] Some series have reported higher than expected rates of posterior circulation strokes (35.3%).[16,18] Hypercoagulability induced by systemic and focal inflammation has been implicated in COVID-19 associated strokes that include both arterial and venous thromboembolic events.[69] Cerebral venous sinus thrombosis (CVST) among patients with COVID-19 can also occur with an abnormally activated prothromboplastin time (aPTT) and elevated D-dimer levels.[70,71] COVID-19 associated CVST has an estimated in-hospital mortality of 40% in a cohort that included non-ventilated patients.[70] In fact, CVST represents 4% of cerebrovascular complications in COVID-19 with an estimated frequency of 0.08% among hospitalized patients.[70] In comparison, CVST accounts for 0.5–1% of all strokes among non-COVID-19 patients and occurs in ~2–5 per million people each year (0.0002–0.0005%).[72] Elevated D-dimer levels are more common among COVID-19 patients presenting with both ischaemic and haemorrhagic stroke and are associated with higher all-cause mortality.[18] As there is an increased risk of thromboembolism during COVID-19, multiple studies have compared standard dose thromboprophylaxis to high and intermediate-dose prophylactic anticoagulation in hospitalized patients with COVID-19. The largest of these trials, INSPIRATION randomized clinical trial found no difference in all-cause mortality or venous thromboembolic events in patients treated with standard versus intermediate-dose thromboprophylaxis in critically ill patients with COVID-19,[73] in contrast to earlier retrospective studies showing potential benefit in ICU patients.[74] Interim unpublished results of the multiplatform merged randomized control trial (mpRCT) ATTACC/REMAP-CAP/ACTIV-4A found similar results in the critically ill cohort as well as a signal towards harm with therapeutic anticoagulation.[75]Interestingly, this study found improved survival in moderately ill patients with COVID-19 treated with intermediate-dose anticoagulation, suggesting severity of disease may be important in determining appropriate thromboprophylaxis in hospitalized patients.[76,77] Further studies are required to determine whether prophylactic anticoagulation specifically reduces the risk of stroke in COVID-19, particularly because of reports of haemorrhagic stroke in hospitalized patients while receiving therapeutic anticoagulation.[78] Indeed, the risk of haemorrhagic stroke is higher than predicted among COVID-19 patients[79] and is associated with elevated serum ferritin.[16] Similarly, microhemorrhages[50] and acute haemorrhagic necrotizing encephalitis have been reported in patients with COVID-19.[61]Outcomes including risk of death and duration of hospitalization following intracerebral or subarachnoid haemorrhages are worse among patients with COVID-19.[80]

Recent reports of vaccine-induced thrombotic thrombocytopaenia (VITT) following administration of adenovirus vector-based COVID-19 vaccines have raised concern.[81–83] As of 4 April 2021, there had been 169 cases of VITT-CVST reported to the European Medicines Agency out of 34 million doses administered of the ChAdOx1 nCoV-19 (AstraZeneca) vaccine, with an incidence of VITT estimated at 1 per 100 000 exposures.[81] The reported rate of VITT-CVST after administration of 6.86 million doses of the Ad26.COV2.S adenoviral vector vaccine (Johnson & Johnson/Janssen) was 0.87 cases per million (0.000087%).[84,85] Most cases occurred in females <50 years of age, and most patients displayed high levels of antibodies to platelet factor 4 (PF4)-polyanion complexes, prompting comparisons to heparin-induced thrombotic thrombocytopaenia.[86] The precise pathophysiology of VITT is unknown to date; simultaneous thrombosis and thrombocytopaenia in VITT has only been reported for adenoviral vector vaccines although there have been five possible reports of CVST with normal platelet counts among 4 million doses of the Moderna mRNA vaccine.[87] Among 54 million doses of the Pfizer-BioNTech mRNA vaccine, there have been 35 reports of CNS thrombosis without thrombocytopaenia (0.00006%).[87] CSVT is a serious but rare condition associated with SARS-CoV-2 vaccination,[88] but there remains a consensus among health authorities that the benefits of widespread vaccination outweigh the potential risks, particularly when one considers the rate of thrombosis in COVID-19 infection.

Acute PNS Disorders​

Autoimmune polyradiculoneuropathies such as GBS or Miller-Fisher syndrome have been reported in patients with SARS-CoV-2 infection, with and without respiratory symptoms.[89] These disorders can be triggered by systemic infections and have been reported in patients with other coronavirus infections such as Middle East respiratory syndrome (MERS) and SARS-CoV-1.[30] Most case reports of GBS in COVID-19 describe the common syndrome of ascending weakness, areflexia with supporting CSF and nerve conduction studies, and are of the acute inflammatory demyelinating polyneuropathy (AIDP) type. Disease onset is between 5 and 10 days after acute COVID-19 symptoms (including anosmia, respiratory and gastrointestinal symptoms), which in the ICU settings helps distinguish GBS from critical illness neuropathy that appears later in disease course.[20,30,90]Patients with COVID-19-associated GBS respond to standard treatments (e.g. IVIg, PLEX) although how COVID-19 affects treatment responsiveness remains uncertain.[30] Of note, a UK epidemiological cohort study showed rates of GBS have fallen during the current pandemic,[91] probably resulting from increased public health efforts that have reduced transmission of more common infectious triggers.


Myalgia and weakness occur in 30–50% of hospitalized patients with COVID-19,[92,93] and are frequently reported by non-hospitalized patients.[94] While myalgia is a common symptom during many viral illnesses, the mechanism by which SARS-CoV-2 infection causes debilitating muscle pain and weakness is unknown. Myositis and rhabdomyolysis as a complication of COVID-19 are well recognized with elevated serum creatine kinase (>10 000) levels as a common finding which correlates with mortality in hospitalized patients.[92] There have also been multiple reports of muscle oedema demonstrated on MRI.[32,33] While other viruses such as influenza are known to directly invade skeletal myocytes in vitro,[95] to date there is no evidence for infection of skeletal myocytes with SARS-CoV-2.[29,33]Myositis in COVID-19 could be triggered by host immune responses to the virus. Muscle biopsies from COVID-19 patients show perivascular inflammation[33] including a case of type 1 interferonopathy associated myopathy in a young patient with SARS-CoV-2 infection.[96] There are reports of COVID-19 patients with elevated creatine kinase levels and muscle weakness who respond to immunosuppression including high dose glucocorticoids[33] as well as IVIg,[30] prompting comparisons to immune-mediated myositis. There is also a recent report of a patient with proximal and bulbar weakness in COVID-19 with positive anti-SSA and SAE-1 antibodies who was successfully treated with the humanized monoclonal antibody against the IL-6 receptor, tocilizumab.[33] While these neurological syndromes are observed in the acute setting, they have the capacity to exert long-term effects, as described next.


Patients who develop severe COVID-19 pneumonia often require prolonged ICU care. As expected, critical illness polyneuropathy (CIP)[29] and myopathy (CIM)[97] have been reported as complications of SARS-CoV-2 infection. While the pathophysiological mechanisms underlying CIM and CIP are unknown, both disorders are assumed to result from microcirculatory and metabolic changes brought on by severe physiological stress.[98] Based on electrophysiological and pathological studies, there is no evidence that COVID-19 associated CIP/CIM has distinctive features, and treatment to date has been supportive.[29] In fact, the lasting neurological consequences of prolonged hospitalization with or without intensive care and the associated interventions for patients with COVID-19 remain unclear.

Chronic Neurological Sequelae​

The long-term neurological impact of COVID-19 is uncertain, but it is already apparent that a range of signs and symptoms emerge among patients hospitalized with COVID-19 while non-hospitalized patients also exhibit neurological disorders that arise after the acute COVID-19 illness phase (Figure 3). The lingering or delayed neurological syndromes have been termed long COVID or post-acute sequelae of SARS-CoV-2 (PASC)[99] and are composed of a wide range of symptoms and signs including neurocognitive symptoms with associated impaired performance on neuropsychological testing.[100] Of note, neurocognitive and mood alterations among ICU survivors are well recognized phenomena, often attributed to sedating medications as well as systemic inflammation and neuronal injury.[34] Notably, these ICU-related effects can confound the evaluation of chronic sequelae among survivors of severe acute COVID-19. A study evaluating patients with COVID-19 at 2–3 months post-hospitalization (approximately a third of patients required ICU) reported that those patients reported significantly higher rates of depressive symptoms and decreased quality of life compared to age- and comorbidity-matched controls.[35] Moreover, abnormalities in visuospatial and executive function were detected among COVID-19 survivors compared to controls when assessed by the Montreal Cognitive Assessment tool (MoCA), recapitulating clinical experience of patients with post-COVID-19 who report apathy, short-term/working memory difficulties and 'brain fog' after SARS-CoV-2 infection.[39,101] A recent study of patients post-COVID-19 without hospitalization reported 'brain fog', headache, anosmia, dysgeusia and myalgia as the predominant persisting symptoms.[102] Over half of hospitalized COVID-19 patients report significant fatigue months after discharge, particularly among those who required admission to the ICU.[35] Similarly, persistent psychological distress is reported by half of hospitalized patients with COVID-19-related ICU admission as well as those COVID-19 patients not requiring the ICU.[103] A retrospective cohort analysis of over 200 000 patients in the UK found that 12.8% of patients with COVID-19 received a new neurological or psychiatric diagnosis in the 6 months after initial infection.[104] In the same study, nearly half of ICU-COVID-19 survivors had a neurological or psychiatric illness at 6-month follow-up, of which half were new diagnoses. Of note, frontotemporal FDG hypometabolism reported for acute COVID-19, discussed previously, was also observed among COVID-19 patients with cognitive symptoms >3 weeks after initial illness, accompanied by brainstem and thalamus hypometabolism in 'long COVID' patients, compared to controls.[38] A separate study of eight patients in the subacute and chronic stages of recovery from COVID-19 observed a similar pattern of bilateral frontoparietal hypometabolism, which resolved at the 6-month follow-up assessment and was accompanied by improved MoCA scores.[37]FDG-PET imaging is a potentially useful research tool although it is not validated for diagnosis of COVID-19 related neurocognitive impairments, which require clinical evaluation. Future studies of cognitive impairment in COVID-19 survivors must take into account the fact that hospitalization for any infection is associated with an increased 10-year risk of dementia, particularly vascular dementia and Alzheimer's disease.[105]

(Enlarge Image)
Figure 3.
Chronic neurological sequelae of COVID-19. Several long-term neurological syndromes result from SARS-CoV-2 among hospital- and community-treated patients, termed long COVID or post-acute sequelae of COVID-19 (PASC). These syndromes include neurocognitive, mood and sleep disorders, dysautonomia, diverse pain syndromes, as well as marked exercise intolerance and fatigue. These protracted syndromes remain to be fully defined in longitudinal cohort studies.
Patients with COVID-19 also develop autonomic instability that manifests as tachycardia, postural hypotension, hypertension, postural orthostatic tachycardia syndrome, low-grade fever with associated bowel, bladder or sexual dysfunctions.[106,107] Cardiac MRI of COVID-19 survivors at 2–3 months after symptom onset showed evidence of fibrosis and inflammation, which was correlated with serum inflammatory markers (e.g. CRP, calcitonin),[35] possibly accounting for the exercise intolerance reported by patients.


The spectrum of symptoms described in long COVID has prompted comparisons with myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS). Indeed, the overlap in symptoms between post-acute COVID-19 syndromes and ME/CFS is remarkable for the shared symptomatology including fatigue, autonomic instability, post-exertional myalgia or weakness as well as neurocognitive impairments.[36,102,108] Nonetheless, other viral illnesses (e.g. Dengue, West Nile disease, mononucleosis) are also associated with substantial disabilities that resemble the previous symptom complex. The precise diagnosis and management of neurological symptoms in long COVID is an emerging area of study, which is in evolution as more studies become available. Important caveats in considering persistent or delayed neurological disorders related to COVID-19 include the contribution of comorbid illnesses and their associated therapies to neurological disease as well as the potential for uncovering previously unrecognized illnesses.[109]

Laboratory Analyses of Nervous System Tissues and Fluids​

Analyses of CSF from patients with COVID-19 vary widely depending on the associated neurological disorder although pleocytosis, especially lymphocytic, and elevated protein[110] are common findings, particularly among patients with other features of encephalitis. The IgG index is increased in many patients with COVID-19 together with the presence of antiviral and antiviral receptor (e.g. ACE2) antibodies, indicative of intrathecal synthesis.[20,111] In contrast, viral RNA is infrequently detected in CSF using standard RT-PCR protocols,[110,112] although the timing of the CSF collection in relation onset is often not reported. Host innate immune responses were also apparent in CSF from patients with COVID-19 based on reports of neopterin and β2-microglobulin detection in CSF.[113] Similarly, several chemokines and cytokines in CSF have shown to be associated with COVID-19-related neurological disease (e.g. encephalitis) including IL-8, TNF-α, IL-6 as well as neural cell type-specific markers (e.g. GFAP, neurofilament and tau).[24] However, a specific diagnostic profile in CSF for COVID-19 associated neurological disease awaits definition. Antibodies associated with autoimmune encephalitis have been reported concurrently with SARS-CoV-2 infection, including anti-GD1b, -NMDA-R[22,114,115] and -CASPR2.[22]While these reports are intriguing, a direct link between SARS-CoV-2 infection and the development of these autoantibodies has not been established. Interestingly, there are emerging reports of non-neurological autoimmune disorders including psoriatic arthritis,[116] rheumatoid arthritis[117]and immune thrombocytopenic purpura[118] developing after COVID-19.[119]Possible explanations for this phenomenon include transient immunosuppression during acute viral illness, including suppression of regulatory T and B cells resulting in impaired self-tolerance, as has been suggested in other viral infections.[120] In susceptible individuals, the process of immune reconstitution following COVID-19 may 'unmask' autoimmune conditions, including multiple sclerosis and neuromyelitis optica spectrum disorders.[121,122] In contrast, other groups have proposed that T-cell exhaustion might contribute to autoimmune neuropathogenesis in COVID-19.[123]

As with CSF studies, autopsy-based neuropathological findings are diverse. Several variables need to be considered in interpreting the neuropathological findings including the presence and severity of prior or concurrent comorbidities, duration in ICU and ventilator support, concomitant therapies and the circumstances of death. Moreover, for many neuropathological reports of COVID-19, a corresponding clinical phenotype was not observed or reported. Nevertheless, reports range from the findings of absent neuropathology[124] to hypoxic/ischaemia changes, acute infarction and haemorrhagic lesions with endotheliitis.[51] ADEM- and ATM-like findings have been observed in select cases.[60,125] Post-mortem studies of patients with ADEM-associated COVID-19 report periventricular inflammation, characterized by foamy macrophages and axonal injury.[60,126]Conversely, other neuropathological studies have identified lymphocyte-predominant inflammation in the meninges, brainstem and perivascular spaces[27] with significant neuronal and axonal loss.[127]Meningoencephalitis, haemorrhagic posterior reversible encephalopathy syndrome, as well as diffuse leukoencephalopathy and microhaemorrhages have also been reported.[51,128,129] While a number of post-mortem studies indicate there is a paucity of immune cell infiltration within the neuroaxis,[47,51,130] recent studies have found marked microglial activation and CD8+ T cells in the brainstem and cerebellum.[68,131] In fact, one study reported pan-encephalitis in a cohort of patients with severe pulmonary-associated COVID-19.[127] Microscopy in larger studies (n = 43) have described diverse findings including astrogliosis with activated microglia and infiltrating T cells in brain parenchyma, together with ischaemic lesions in a subset of patients.[68,132,133] In one post-mortem study using imaging mass cytometry, distinct neuropathological features within the brainstem and olfactory bulb of COVID-19 patients were identified, including microglial nodules, CD8+ T-cell infiltration, and increased ACE2 expression in blood vessels.[131] These findings were not as pronounced in control patients who had been on ECMO but did not have COVID-19. Nevertheless, some authors have commented that collectively the neuropathological findings, especially microglia activation in COVID-19 resemble that observed in patients with hypoxia and sepsis.[132,134]

Mechanisms of Neurological Disease​

Multiple putative mechanisms of disease have been proposed for COVID-19 induced nervous system disorders[135] including coagulopathies as well as virus-associated host responses. Indeed, it is probable that specific pathogenic processes underlie the individual neurological presentations associated with COVID-19 in both the CNS (Figure 1A) and the PNS (Figure 1B). We review the different proposed mechanisms next.

Cerebrovascular Disease/Bioenergy Failure​

Microvascular injury characterized by thinning of the basal lamina of endothelial cells, fibrinogen leakage and microhaemorrhages has been described in the brainstem and olfactory bulb of deceased COVID-19 patients corresponding to visible MRI changes.[27] These observations are also complemented by other neuroimaging studies in which cerebral infarction was the most common finding on conventional brain MRI.[50] Most post-mortem analyses have shown signs of thrombotic microangiopathy and endothelial injury with minimal evidence of prototypic vasculitis.[16] This pattern is suggestive of endotheliitis. Although there have been several case reports of CNS vasculitis associated with COVID-19, none have confirmed the diagnosis histologically.[136] A cohort of patients with stroke and COVID-19 in Wuhan, China, showed elevated serum levels of IL-6,[137] IL-8 and TNF-α, a finding that has been replicated in several subsequent studies.[18] Both IL-8 and TNF-α promote the release of von Willebrand factor, a marker of endothelial damage that is elevated in both ICU and non-ICU patients with COVID-19,[17] while IL-6 inhibits cleavage of von Willebrand factor leading to accumulation of multimers that promote platelet aggregation.[16] These changes are bolstered by findings of damaged cerebral blood vessels or endotheliitis that was associated with extravasation of fibrinogen.[27] These mechanisms of disease are highly plausible because of the frequency of coagulation-related events during COVID-19. Indeed, neuroimaging studies point to abnormal energy metabolism, shown by reduced FDG detection in frontal lobes of patients with acute COVID-19.[138]

Viral Neuroinvasion​

SARS-CoV-2 infects respiratory cells via engagement of the angiotensin-converting enzyme 2 (ACE2) receptor,[15,139,140] with a higher binding affinity than other coronaviruses such as SARS-CoV-1. The ACE2 receptor is present on type II alveolar and respiratory epithelial cells, cardiomyocytes, neurons[141] and astrocytes.[140,142] This receptor is also present in pericytes and smooth muscle cells of cerebral blood vessels and is expressed in the thalamus, cerebellum and brainstem nuclei of humans.[143–145] After binding to ACE2, cleavage of the spike (S) protein of SARS-CoV-2 by transmembrane serine protease 2 (TMPRSS2) facilitates cell entry.[146] Alternative docking receptors including neuropilin-1 (NRP1)[147] and basigin (BSG)/CD147[148] are found at higher levels in the CNS. Similarly, alternative proteases including furin and cathepsin might permit viral entry in cells with low levels of TMPRSS2 expression (e.g. brain).[149]

Several anatomic routes of neuroinvasion by SARS-CoV-2 have been proposed. The integrity of the blood–brain barrier is compromised in multiple conditions associated with mortality in COVID-19, including hypertension, diabetes, smoking and stroke.[150] Areas of increased vascular permeability or lack of blood–brain barrier, such as the pituitary and median eminence of the hypothalamus are also rich in ACE2, NRP1 and TMPRSS2, thus representing possible portals of entry into the CNS.[19] SARS-CoV-2 infects nasal epithelium and perhaps olfactory bulb cells, presenting another entry portal to the CNS, as suggested for other coronaviruses.[151,152] A recent post-mortem analysis of humans with COVID-19 detected SARS-CoV-2 by RT-PCR in neuroepithelium, the olfactory bulb, trigeminal ganglion and brainstem, albeit at low levels.[14] Interestingly, olfactory nerves terminate in the frontal cortex as well as the hypothalamus and amygdala, structures that are implicated clinically, radiographically and electrographically in the neurological sequelae of COVID-19.[19] The importance of the choroid plexus in the development of COVID-19 associated neurological disease in conjunction with neuroinflammation has been highlighted recently in a large study predicated on RNA deep sequencing of brain-derived single cell nuclei transcriptomes.[153] The lack of evidence for productive infection of trafficking immune cells by SARS-CoV-2 to date makes a Trojan horse mechanism of neuroinvasion less likely. Nonetheless, viral proteins and RNA have been detected in CD68+ macrophages isolated from bronchoalveolar lavage of COVID-19 patients.[154] SARS-CoV-2 RNA levels in brain tissue detected by RT-PCR are low and seemingly independent of the presence or absence of apparent neurological dysfunction and histopathological alterations.[14,132] Immunodetection of SARS-Cov-2 viral antigens in neurons from autopsied patients with COVID-19 underscores the potential for direct viral invasion as an important disease determinant.[155]
Remdesivir, a nucleoside analogue that inhibits RNA-dependent replication of SARS-CoV-2, is the only direct antiviral agent approved for COVID-19 treatment despite preliminary results showing no impact on mortality or progression to mechanical ventilation.[156] Molnupiravir is orally available nucleoside analogue that induces coronavirus lethal mutagenesis and is in phase 2 and 3 trials for treatment of COVID-19.[157] A recent randomized control trial of the TMPRSS2 inhibitor, camostat mesylate, in hospitalized patients with COVID-19 did not have any impact on recovery, progression to ICU or mortality.[158]
SUGGESTED FOR YOU

Host Neuroimmune Responses​

Post-infectious neuro-inflammation triggered by expression of viral antigens into the CNS is another proposed mechanism of encephalitis in COVID-19. While human data supporting this hypothesis are limited, a recently published study using a murine model showed a subunit of the SARS-CoV-2 spike protein (S1) crosses the BBB via absorptive transcytosis when administered intravenously and intra-nasally.[159] Indeed, neuropathological studies demonstrate glia activation and occasional leucocyte infiltrates in patients with COVID-19 although the associated molecular pathways (e.g. cytokine, protease, or free radical release) induced are unclear. CSF studies suggest activation of innate immune responses with elevated levels of β2-microglobulin and neopterin and the presence of dedifferentiated monocytes.[113,123] This is associated with increased levels of neurofilament suggesting neuronal injury.[113] Autoimmune mechanisms including both antibody- as well as cell-mediated immune injury of neural tissue are also plausible, given the recognition of autoimmune processes in the systemic COVID-19 pathogenesis. The injury and loss of endothelial cells in arterioles, venules and capillaries represents another neuropathogenic avenue via disruption on the blood–brain barrier and through endothelia production of immune molecules[160] in the lung, kidney and heart of patients with COVID-19. These latter events can be initiated by systemic immune activation as well as a coagulation diathesis. An important qualification to these mechanisms is that concurrent clinical events including systemic hypoxia-ischaemia might affect immune processes within the nervous system. Among patients with COVID-19 associated cerebrovascular disease, autoimmune processes have been directly implicated. For example, the contribution of antiphospholipid antibodies to ischaemic stroke in patients with COVID-19 is controversial. Zhang et al.[161] described three COVID-19 patients with coagulopathy and multi-territory infarcts and anticardiolipin and anti-β2 microglobulin antibodies. Subsequent studies have reported lupus anticoagulant positivity in more than half of COVID-19 patients.[162] Most case reports of antiphospholipid antibodies in COVID-19 do not include repeat assays 12 weeks apart, which is required for the diagnosis of antiphospholipid antibody syndrome. Transient elevation of lupus anticoagulant during systemic inflammation is common, and several infections are associated with false positive antiphospholipid assays, including HIV, hepatitis C virus and syphilis, making current reports of antiphospholipid antibodies in COVID-19 difficult to interpret.[163]
Similarly, autoimmunity is also incriminated in COVID-19 associated GBS; anti-ganglioside antibodies implicated in autoimmune polyradiculoneuropathies such as anti-Gq1b, -GM1[164] and -GD1b antibodies have been reported in patients with COVID-19 presenting with cranial neuropathies, weakness, areflexia and sensory ataxia.[22] Anti-ganglioside antibodies are most strongly associated with more aggressive axonal motor neuropathies and poorer functional outcomes compared to AIDP.[165] The rare presence of these antibodies raises concern about potential molecular mimicry mediated by SARS-CoV-2 that could trigger autoimmune responses with important implications for vaccine safety. The spike (S) protein of SARS-CoV-2 is highly glycosylated; thus, the development of anti-glycan antibodies may be essential for an effective host immune response in COVID-19. In a microarray study of 800 human carbohydrate antigens, levels of anti-glycolipid antibodies associated with GBS, including GM1a, GD1a and GD1b significantly higher in COVID-19 patients compared to healthy controls. In this latter study, there was no direct correlation with antibody titre and clinical features of GBS. Anti-glycan antibodies are also observed in other viral and bacterial infections (HIV, EBV, Neisseria meningitidis[31,165]) as well as autoimmune diseases such as Crohn's disease,[166] and thus may merely be a marker of systemic inflammation. Of relevance, there were no reported cases of GBS in the three major COVID-19 vaccine trials.[167–169]
While randomized control trials demonstrate dexamethasone and tocilizumab improve respiratory outcomes in hospitalized patients, their effects on neurological disease in COVID-19 is presently supported only by case reports.[67,170–172] A subset of COVID-19 associated encephalopathies are responsive to steroids and IVIg, and there is a single report of a young patient with encephalitis and SARS-CoV-2 (based on CSF lymphocytosis and T2/FLAIR hyperintensities on MRI), which resolved after treatment with IVIg and tocilizumab.[173] In most cases with a positive response to immunosuppressive or modulatory therapy, SARS-CoV-2 was not detected in CSF, further supporting a para-infectious/immune-mediated basis for disease.

Future Perspectives​

Given the mounting impact of SARS-CoV-2 infection globally together with the increasing recognition of associated neurological disorders, it is imperative to define the types of COVID-19 related neurological syndrome, including those caused directly by viral infection versus those arising from systemic illness, the impact of different viral variants on neurological disease, as well as identifying informative diagnostic tools and effective therapies. GWAS studies have identified susceptibility genes for severe respiratory illness with COVID.[174,175] Similar studies to identify host factors associated with neurological complications would also be useful. The long-term neurological sequelae of COVID-19 remain unclear and await delineation in longitudinal studies. The neurodevelopmental impacts of COVID-19 are also unknown in utero as well as in infants or adolescents; this issue could have substantial lasting effects that require further investigation. Finally, a more comprehensive understanding of the pathogenic mechanisms underpinning the neurological syndromes associated with COVID-19 will advance therapeutic options for affected patients.

Literature Search Strategy and Selection Criteria​

Studies were selected from the peer-reviewed literature using NCBI and Google Scholar. We searched the databases using the following keywords: central and peripheral nervous systems, COVID-19, SARS-CoV-2, coronavirus, stroke, encephalopathy, neurocognitive impairment, hypercoagulability, encephalitis, neurologic infection, seizure and neuroinflammation. We also reviewed bibliographies of relevant articles. Non-peer-reviewed studies and single case reports were not included as references unless they were highly informative.

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Medical Masks Versus N95 Respirators for Preventing COVID-19 Among Health Care Workers: A Randomized Trial: Annals of Internal Medicine: Vol 0, No 0

Background: It is uncertain if medical masks offer similar protection against COVID-19 compared with N95 respirators. Objective: To determine whether medical masks are noninferior to N95 respirators to prevent COVID-19 in health care workers providing routine care. Design: Multicenter...

www.acpjournals.org

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Medical Masks, N95s May Offer Similar Prevention vs COVID: Study​

Lisa O'Mary



Regular medical masks might provide protection similar to that of N95 respirators in preventing SARS-CoV-2 infection among healthcare workers, according to the first randomized trial that tested the two types of masks head to head in the COVID-19 era.
Owing to limitations in the study, however, the authors were only formally able to conclude that healthcare workers who wore medical masks while treating COVID-19 patients were not twice as likely to contract the virus as workers wearing N95 respirators.
"Nonetheless, this trial provides the best evidence to date on comparative effectiveness of mask types in preventing SARS-CoV-2 infection in health care workers providing routine patient care," writes Roger Chou, MD, in an editorialpublished with the study.

In summarizing, Chou said that "the results indicate that medical masks may be similar to N95 respirators in Omicron-era settings with high COVID-19" rates, but the researchers set a low bar for establishing whether one is more effective than the other.







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The latest​

Most people dying of the coronavirus are 65 and older, my colleagues Ariana Eunjung Cha and Dan Keating report. While much of our society has moved on from masking, vaccine mandates and other mitigation efforts, older people and those with compromised immune systems remain at elevated risk from the virus.

According to Cha and Keating, people in this age cohort are dying at “roughly two to three times the rate at which people die of the flu.”

“Some epidemiologists and demographers predict the trend of older, sicker and poorer people dying at disproportionate rates will continue, raising hard questions about the trade-offs Americans are making in pursuit of normalcy — and at whose expense,” Cha and Keating write.

The Food and Drug Administration announced Wednesday it is pulling emergency use authorization for the monoclonal antibody treatment bebtelovimab because “it is not expected to neutralize Omicron subvariants BQ. 1 and BQ. 1.1.,” the agency said in a statement.

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The therapy, authorized in February by the FDA, was used to treat patients ages 12 and older who have mild to moderate symptoms associated with covid-19.

Manufacturer Eli Lilly has halted commercial distribution of bebtelovimab, and the federal government’s Administration for Strategic Preparedness and Response has stopped fulfilling pending requests for the drug.

The FDA recommends that health-care providers use other approved or authorized remedies for treating covid-19, such as the antiviral pill Paxlovid.

Other important news​

Former president Bill Clinton tested positive for the coronavirus. On Wednesday, he tweeted that his symptoms were mild and that he was “grateful to be vaccinated and boosted, which has kept my case mild, and I urge everyone to do the same, especially as we move into the winter months.”

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Twitter has stopped enforcing its coronavirus misinformation policy. “Effective November 23, 2022, Twitter is no longer enforcing the COVID-19 misleading information policy,” the company wrote.


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Your questions, answered​

Is it safe, or advisable, to take Paxlovid and monoclonal antibodies at the same time?

No studies or data support using an antiviral treatment such as Paxlovid and monoclonal antibodies together, according to Charles S. Dela Cruz, a pulmonologist at the Yale School of Medicine. He said many people who use antibody treatments are often prescribed them when they cannot tolerate antiviral treatments. This could include patients with kidney or severe liver disease.

The Food and Drug Administration authorized Paxlovid in December 2021, and it is used to treat mild to moderate symptoms in people 12 and older. Research has shown that it reduces the risk of severe illness and hospitalization if taken within five days of symptoms appearing. And new data suggests it could help minimize long covid.

Monoclonal antibody treatments such as Evusheld, which is used as a pre-exposure prophylaxis, meaning it is given before someone is infected, are for people at high risk of developing severe illness and those who are unable to get the coronavirus vaccine. In many respects, the question of combining an antiviral pill with a monoclonal antibody is increasingly moot: Many of the monoclonal antibodies are proving ineffective against subvariants of omicron.

Dela Cruz said monoclonals were the first outpatient treatment option when the pandemic began, but as more research has emerged and with the development of new antivirals such as Paxlovid, he said that “the oral antivirals are more practical for patients” because they are easier to administer.
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China Launches Elderly Vaccination Drive but Health Fears Linger​

By David Stanway and Xihao Jiang
December 01, 2022




SHANGHAI (Reuters) - As China works to raise COVID-19 vaccination rates among its elderly, essential if the country is to open up again and live with COVID, many older people remain fearful that the treatment will make them sick.
"If I were fit for vaccination, I would definitely get it," said Cai Shiyu, a 70-year-old retiree in Shanghai.
"But I've had a heart stent, and I have heart disease, and high blood pressure: what if something happens?"
Shanghai resident Yang Zhijie, 76, said she was scared of being vaccinated.

"Without the vaccination, I already have so many diseases, and after I do it I'm scared the diseases will become more serious," she said.




Vaccinating the vulnerable has long been seen as a crucial requirement in China's plans to open up after nearly three years of disruptive and economically damaging zero-COVID restrictions.
China's health authority said on Wednesday that it would aim to improve accessibility and launch targeted programmes in nursing homes and leisure facilities as part of a new vaccination drive among the over-60s.
It also pledged to make renewed efforts to publicise the benefits of vaccination.

Ye Weifang, an unvaccinated 83-year-old Shanghai resident, told Reuters that she would need to be reassured by her doctor before receiving the jab.
"I look like I'm in good health now, but I have a pretty serious illness," she said. "If the doctor thinks I can get vaccinated, I will do it."
China has offered vaccinations for the elderly since April 2021, but the take-up rate slowed noticeably this year.
By November, the proportion of people aged 60 and above to be fully vaccinated reached 86.4%, barely changing from 85.6% in August. Those who have received a booster jab increased to 68.2% from 67.8% over the period.

The vaccination and booster rates in Japan, by contrast, were both at more than 90%.

"Concerns about safety and the lack of effectiveness probably are the major reasons why older adults refuse or delay vaccination," said Florence Zhang, a researcher at the School of Medicine at China's Jinan University, who has conducted studies into vaccine hesitancy among China's elderly.

Public health experts say studies show that besides vaccination scepticism, the elderly have also been slow to take up the jab due to health, mobility and access.

The National Health Commission said it would take the vaccination campaign directly to residents of nursing homes and retirement facilities, though they only account for around 3% of China's elderly population, according to a research paper by Shanghai's Fudan University in September.

It would also deliver door-to-door vaccination services to those who are disabled or housebound and deploy specialist vaccination vehicles and temporary vaccination stations.

China has also been slowly rolling out vaccine insurance to reassure those who are worried about dangerous side-effects.

A survey of over-60s conducted by the Fudan University researchers showed that 51% of vaccine-hesitant respondents said they would be more likely to get jabbed if more insurance was available.

Anger over China's zero-COVID policy, which has the world's toughest restrictions, has sparked protests across the country and prompted authorities to start easing some curbs.

"I will be pretty worried (if curbs are eased). Especially for the elderly who haven't been vaccinated," said Shanghai resident Ye, who did not get vaccinated due to concerns over her health.

(Reporting by David Stanway and Xihao Jiang; Editing by Michael Perry)

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FDA Pulls US Authorization for Eli Lilly's COVID Drug Bebtelovimab​

Reuters staff
December 01, 2022




(Reuters) -Eli Lilly and Co's COVID-19 drug bebtelovimab is not currently authorized for emergency use in the United States, the Food and Drug Administration said, citing it is not expected to neutralize the dominant BQ.1 and BQ.1.1 subvariants of Omicron.
Wednesday's announcement takes away authorization from the last COVID-19 monoclonal antibody treatment, leaving Pfizer Inc's antiviral drug Paxlovid, Merck's Lagevrio and Gilead Sciences' Veklury as treatments for the disease, besides convalescent plasma for some patients.
AstraZeneca Plc's monoclonal antibody Evusheld is also authorized for protection against COVID-19 infection in some people.
Eli Lilly and its authorized distributors have paused commercial distribution of the monoclonal antibody until further notice from the agency, while the U.S. government has also paused fulfillment of any pending requests under its scheme to help uninsured and underinsured Americans access the drug.

The drug, which was discovered by Abcellera and commercialized by Eli Lilly, received an authorization from the FDA in February.




BQ.1 and BQ.1.1 have become the dominant strains in the United States after a steady increase in prevalence over the last two months, surpassing Omicron's BA.5 sub-variant, which had driven cases earlier in the year.
The subvariants accounted for around 57% of the cases nationally, as per government data last week.
(Reporting by Leroy Leo in Bengaluru; Editing by Sriraj Kalluvila)
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COVID Hit HIV Detection in Europe, Threatens Eradication Progress​

Reuters staff
December 01, 2022




LONDON (Reuters) - The number of people in Europe with undiagnosed HIV has risen as testing rates fell during the COVID-19 pandemic, threatening a global goal of ending the disease by 2030, a report said.
The joint World Health Organization (WHO) and European Centre for Disease Prevention and Control (ECDC) report said that in 2021 a quarter fewer HIV diagnoses were recorded compared to pre-pandemic levels in the WHO's European region.
This region includes Russia and Ukraine, which have the area's highest rates of HIV infection.
This setback was likely because services related to HIV, including testing, were sidelined in many European countries during the two years of the pandemic, the report found.

"It's likely that reduced testing and extra demands due to the COVID-19 pandemic on clinical sectors and also on public health institutes did impact case detection in 2020 and 2021 and we do believe that this is still continuing even today," ECDC HIV expert Anastasia Pharris told a news briefing on Wednesday.

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European Women's Work-Life Balance Worsened Since COVID Outbreak: Study​

By Dina Kartit
December 01, 2022




(Reuters) - European women's work-life balance has worsened since the start of the COVID-19 pandemic in 2020, a European Institute for Gender Equality (EIGE) report shows.
The EIGE's Gender Equality Index 2022, which has a thematic focus on care, showed that the pandemic has increased informal and unpaid care at home, particularly pressuring women.
Women in the survey were more likely to face interruptions while teleworking than men, the report said. On average 20% of teleworking mothers unable to work for an hour without being interrupted by children, compared with 15% of teleworking fathers.
The disruption to childcare provision also hit women's income. They were more likely to cut back on working hours, miss work, take unpaid time-off, or quit the workforce altogether.

"While the full extent of the social and economic impact is still unfolding, before and throughout the pandemic women were more likely to be unemployed or to work fewer hours than they wished," the report published on Wednesday said.




Nonetheless, the index, which measures gender equality progress in the European Union, slightly increased to 68.6 points out of 100, 5.5 points higher than in 2010.
Sweden, Denmark and the Netherlands were the top performers, while Greece, Romania and Hungary ranked at the bottom.
Women in positions of authority has largely driven this modest growth, although they remain underrepresented in politics, making up just over a third of members of regional and local/municipal legislatures and 33% of members of national parliaments, EIGE said.

There is a persisting gender gap among key decision-makers in major corporations and financial institutions in the EU, with women accounting for 8% of CEOs, 21% of executives, and 34% of non-executives in the first half of 2022, EIGE said.
(Reporting by Dina Kartit; Editing by Alison Williams)


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Two Chinese Cities Ease COVID Curbs After Protests Spread​

By Brenda Goh and Martin Quin Pollard
December 01, 2022




SHANGHAI/BEIJING (Reuters) - The giant Chinese cities of Guangzhou and Chongqing announced an easing of COVID curbs on Wednesday, a day after demonstrators in southern Guangzhou clashed with police amid a string of protests against the world's toughest coronavirus restrictions.
The demonstrations, which spread over the weekend to Shanghai, Beijing and elsewhere, have become a show of public defiance unprecedented since President Xi Jinping came to power in 2012.
The southwestern city of Chongqing will allow close contacts of people with COVID-19, who fulfil certain conditions, to quarantine at home, a city official said.
Guangzhou, near Hong Kong, also announced an easing of curbs, but with record numbers of cases nationwide, there seems little prospect of a major U-turn in "zero-COVID" policy that Xi has said is saving lives and has proclaimed as one of his political achievements.

Some protesters and foreign security experts believe Wednesday's death of former President Jiang Zemin, who led the country for a decade of rapid economic growth after the Tiananmen crackdown in 1989, might become a new rallying point for protest after three years of pandemic.




Shanghai medical company worker Ray Lei, in his 20s, said Jiang was sometimes compared positively to Xi, given his skills on the international stage and relative openness to the West.
"So as for Jiang Zemin's death, we feel a sense of tragedy towards the future of China's leadership," said Lei, who took part in protests in Shanghai on Sunday.
Jiang's legacy was being debated on protesters' Telegram groups, with some saying it gave them a legitimate reason to gather.

"How similar is history," read one protester's post, referring to former party General Secretary Hu Yaobang, whose death in April 1989 was seen as one of the drivers of the nationwide protests that year.
"We can all go onto the streets today and lay chrysanthemums," another said.
Announcing the lifting of lockdowns in parts of Guangzhou, a city hard-hit by the recent wave of infections, authorities did not mention the protests, and the district where Tuesday's violence flared remained under tight control.

In one video of those clashes posted on Twitter, dozens of riot police clad in white protective suits and holding shields over their heads, advanced in formation over what appeared to be torn down lockdown barriers as objects flew at them.


Police were later seen escorting away a row of people in handcuffs.


Another video clip showed people throwing objects at police, while a third showed a tear gas canister landing in a small crowd on a narrow street, sending people running to escape the fumes.


Reuters verified that the videos were filmed in Guangzhou's Haizhu district, the scene of COVID-related unrest two weeks ago, but could not determine when the clips were taken or the exact sequence of events and what sparked the clashes.


Social media posts said the clashes took place on Tuesday night and were caused by a dispute over lockdown curbs.





The government of Guangzhou did not immediately respond to a request for comment.


China Dissent Monitor, run by U.S. government-funded Freedom House, estimated at least 27 demonstrations took place across China from Saturday to Monday. Australia's ASPI think tank estimated 43 protests in 22 cities.


EASING CURBS


As well as the easing of curbs in Guangzhou and Chongqing, officials in Zhengzhou, the site of a big Foxconn factory making Apple iPhones that has been the scene of worker unrest over COVID, announced the "orderly" resumption of businesses, including supermarkets, gyms and restaurants.


Earlier national health officials said China would respond to "urgent concerns" raised by the public and that COVID rules should be implemented more flexibly, according to a region's conditions.


But while the easing of some measures appears to be an attempt to appease the public, authorities have also begun to seek out those who have been at the protests.


"Police came to my front door to ask me about it all and get me to complete a written record," a Beijing resident who declined to be identified told Reuters on Wednesday.


Another resident said some friends who posted videos of protests on social media were taken to a police station and asked to sign a promise they "would not do that again".


Several people gave similar accounts to Reuters on Tuesday.


It was not clear how authorities identified the people they wanted to question, nor how many such people authorities contacted.


Beijing's Public Security Bureau did not comment.


In a statement that did not refer to the protests, the Communist Party's top body in charge of law enforcement agencies said on Tuesday that China would crack down on "the infiltration and sabotage activities of hostile forces".


The Central Political and Legal Affairs Commission also said "illegal and criminal acts that disrupt social order" would not be tolerated.


The foreign ministry has said rights and freedoms must be exercised lawfully.


COVID has spread despite China largely isolating itself from the world and demanding sacrifices from hundreds of millions to comply with relentless testing and isolation.


While infections and death numbers are low by global standards, analysts say that a reopening before increasing vaccination rates could lead to widespread illness and deaths.


The lockdowns have hammered the economy, disrupting global supply chains and roiling financial markets.


Data on Wednesday showed China's manufacturing and services activity for November posting the lowest readings since Shanghai's two-month lockdown began in April.


(Additional reporting by Eduardo Baptista and Yew Lun Tian in Beijing; Writing by Marius Zaharia, John Geddie and Greg Torode; Editing by Michael Perry, Robert Birsel)

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Which Respiratory Virus Do I Have?​

— There's a range of possibilities, and it's not easy to tell them apart​

by Kristina Fiore, Director of Enterprise & Investigative Reporting, MedPage Today December 1, 2022

It started with a tickle in your throat. Then, it evolved into congestion, and maybe a little cough. Perhaps you lost your voice.
You might have had a slight fever that went away with ibuprofen, but you never felt bad enough to stay in bed all day.
So, which respiratory virus was invading your cells?
There are several types of viruses that could be the culprit: respiratory syncytial virus (RSV), influenza, parainfluenza viruses, metapneumovirus, rhinoviruses, coronaviruses, enteroviruses, and adenoviruses are among the most common.

However, most people who are infected will probably never know which one rallied their immune system.
"They are hard to distinguish one from the next because they all have similar respiratory symptoms of congestion, cough, runny nose, fever. They all start that way," said Paul Offit, MD, of Children's Hospital of Philadelphia. "There's really no distinguishing them unless you test."
Testing isn't likely to happen unless you're hospitalized. A typical Quest Diagnostics respiratory panel, for example, includes adenovirus, influenza, parainfluenza, rhinovirus, enterovirus, metapneumovirus, and RSV.
"Typically what we see at Children's Hospital of Philadelphia in winter is RSV, number one; and right behind it is influenza," Offit said. "Then, you'll see things like human metapneumovirus, parainfluenza virus, adenovirus."
This year, he said, there seems to be more of a "bi-demic" rather than a "tri-demic" of winter respiratory illness, with RSV and influenza causing the most problems for hospitals. Luckily, SARS-CoV-2 hasn't caused a huge burden of illness this year, Offit said.

Outside of hospitalization, respiratory virus testing isn't as common because there are no at-home tests for any of those viruses except for SARS-CoV-2.
Without widespread testing, there's less surveillance data on infections, so it's hard to know just how much morbidity happens in any given year from any given virus.
"We do not track morbidity or mortality of all of these viruses," said William Schaffner, MD, professor of infectious diseases at Vanderbilt University Medical Center in Nashville, Tennessee. "We know in general that many of them are seasonal, increasing in late fall, winter, and into spring, and they provide the great background of viral infections with which every human on this planet is familiar -- the runny nose, the sore throat, feeling out of sorts for a day or 2 or 3 and then slowly getting better."
While all of these viruses typically prompt similar symptoms, there are a few known to have particular manifestations, such as parainfluenza being responsible for the majority of croup in children, and RSV being a frequent cause of bronchiolitis in infants.

Here are the key features and differences among each of the most common annual respiratory nuisances.
Respiratory Syncytial Virus
RSV is a single-stranded RNA virus in the Pneumoviridae family and the Orthopneumovirus genus. It was first isolated in 1955 from chimpanzees with respiratory illness at the Walter Reed Army Institute of Research, according to a report in Nature.
It's the most common cause of bronchiolitis in infants, and can be severe in older adults as well. Up to 10,000 adults die each year in the U.S. from RSV, Offit noted.
"RSV has this reputation as a pediatric virus, but over the last 15 years, we've accumulated data that people over 65, particularly those with underlying lung or heart disease, can be affected by RSV just as severely as influenza," Schaffner said. "And in some years the impact of RSV has been as serious as the impact of flu."

In most cases, however, symptoms are usually mild and resemble the common cold. These include congestion, runny nose, sneezing, dry cough, low-grade fever, and sore throat.
Influenza
Influenza is an RNA virus in the Orthomyxoviridae family and its most common subtypes are A and B. Infection typically leads to more severe symptoms than the common cold. These include fever, aches, fatigue, cough, and sore throat.
People infected with influenza are most contagious in the 3 to 4 days after the illness starts, according to the CDC.
The virus can be more severe in young children and in older adults, and the U.S. typically sees some 20,000 to 25,000 influenza deaths per year, though that number can reach as high as 60,000 annually, Offit said.
Parainfluenza Viruses
These single-stranded RNA viruses belong to the Paramyxoviridae family, and fall into two genera: Respirovirus and Rubulavirus, and overall there are four types (1-4) and two subtypes (4a and 4b), according to the CDC.

Parainfluenza viruses are the most common culprit in cases of croup, infamous for terrifying parents with the raspy sound of stridor.
By age 5, almost all children are seropositive, and people can be reinfected multiple times in their lifetime, resulting in mild illness with cold-like symptoms. Older adults and people who are immunocompromised have a higher risk of severe infection, according to the CDC.
Metapneumovirus
This single-stranded RNA virus in the Paramyxoviridae family was discovered in the Netherlands in 2001, but evidence suggests its been in circulation for at least 5 decades, according to the Encyclopedia of Microbiology.
Common symptoms include cough, fever, and congestion, but it can lead to more severe disease in young children, older adults, and people who are immunocompromised, according to the CDC.
Rhinoviruses
Rhinoviruses are the most common cause of the common cold, according to the CDC. These single-stranded RNA viruses belong to the Picornaviridaefamily and have three types: A, B, and C.

They were first isolated in the 1950s by Winston Price, MD, at Johns Hopkins University in Baltimore, during an effort to identify the cause of the common cold.
Coronaviruses
While coronaviruses are now widely known due to the pandemic of SARS-CoV-2, four subtypes previously had been responsible for respiratory disease in the U.S. Those include 229E, OC43, NL63, and HKU1, which have typically been associated with mild cold-like symptoms.
Two other coronaviruses, the original SARS-CoV and MERS-CoV, have caused more severe disease in humans.
These single-stranded RNA viruses are known for their distinct surface spikes, which give them a crown-like appearance.
Enteroviruses
Most people infected with an enterovirus have asymptomatic infections or only mild, cold-like illness. Of the more than 100 non-polio enteroviruses, the most common ones are EV-D68, EV-A71, and coxsackie virus A6 (CV-A6), according to the CDC.
EV-D68 more commonly causes respiratory illness, while EV-A71 and CV-A6 can cause hand, foot, and mouth disease. While EV-D68 is usually asymptomatic or causes only mild symptoms, it can in rare cases cause acute flaccid myelitis (AFM).

Adenoviruses
These DNA viruses in the family Adenoviridae are frequently accompanied by small, single-stranded DNA parvoviruses known as adeno-associated viruses, that don't seem to cause any specific disease. In fact, most experimental gene therapies have switched from using adenoviruses to these adeno-associated viruses to mitigate some of the side effects.
Most adenovirus infections are asymptomatic, and when they do cause symptoms, these are mostly mild. They can also range widely in the type of disease they cause.
"Adenoviruses are interesting. Some are directed more at the respiratory tract, while some have more intestinal symptoms and others like to give us pink eye," Schaffner said. "That viral family is very diverse and often the major impact is quite strain-specific."

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  Kristina Fiore leads MedPage’s enterprise & investigative reporting team. She’s been a medical journalist for more than a decade and her work has been recognized by Barlett & Steele, AHCJ, SABEW, and others. Send story tips to [email protected].
  "

 

[missy]

"

COVID Vax Prevents Death in Children Regardless of Variant​

Heidi Splete
December 02, 2022



COVID-19 vaccines retained the ability to prevent deaths from COVID-19 in children and adolescents regardless of the dominant circulating variant, in a new study.

The vaccine's effectiveness against infection in the short term has been established, as has the waning effectiveness of the vaccine over time, wrote Juan Manuel Castelli, MD, of the Ministry of Health of Argentina, Buenos Aires, and colleagues, in the British Medical Journal.

However, data on the impact of vaccine effectiveness on mortality in children and adolescents are limited, especially during periods of omicron variant dominance, the researchers said.


In their new study, the researchers reviewed data from 844,460 children and adolescents aged 3-17 years from the National Surveillance System and the Nominalized Federal Vaccination Registry of Argentina, during a time that included a period of omicron dominance.




Argentina began vaccinating adolescents aged 12-17 years against COVID-19 in August 2021 and added children aged 3-11 years in October 2021. Those aged 12-17 years who were considered fully vaccinated received two doses of either Pfizer-BioNTech and/or Moderna vaccines, and fully-vaccinated 3- to 11-year-olds received two doses of Sinopharm vaccine.

The average time from the second vaccine dose to a COVID-19 test was 66 days for those aged 12-17 years and 54 days for 3- to 11-year-olds. The researchers matched COVID-19 cases with uninfected controls, and a total of 139,321 cases were included in the analysis.

Overall, the estimated vaccine effectiveness against COVID-19 was 64.2% during a period of delta dominance (61.2% in children aged 3-11 years and 66.8% in adolescents aged 12-17 years).


During a period of omicron dominance, estimated vaccine effectiveness was 19.9% across all ages (15.9% and 26.0% for younger and older age groups, respectively).

Effectiveness of the vaccine decreased over time, regardless of the dominant variant, but the decline was greater during the omicron dominant period, the researchers noted. During the omicron period, effectiveness in children aged 3-11 years decreased from 37.6% at 15-30 days postvaccination to 2.0% at 60 days or longer after vaccination. In adolescents aged 12-17 years, vaccine effectiveness during the omicron period decreased from 55.8% at 15-30 days postvaccination to 12.4% at 60 days or longer after vaccination.

Despite the waning protection against infection, the vaccine's effectiveness against death from COVID-19 was 66.9% in children aged 3-11 years and 97.6% in adolescents aged 12-17 during the period of omicron dominance, the researchers noted.

The results are consistent with similar studies showing a decreased vaccine effectiveness against infection but a persistent effectiveness against deaths over time, the researchers wrote in the discussion section of their paper.


"Our results suggest that the primary vaccination schedule is effective in preventing mortality in children and adolescents with COVID-19 regardless of the circulating SARS-CoV-2 variant," the researchers said.

Study Limitations and Strengths​

The study was limited by several factors including the incomplete data on symptoms and hospital admissions, the possible impact of unmeasured confounding variables, and the observational design that prevents conclusions of causality, the researchers noted. However, the results were strengthened by the large sample size and access to detailed vaccination records, they said.


Both heterologous and homologous mRNA vaccine schedules showed similar effectiveness in preventing short-term infection and mortality from COVID-19 during periods of differing dominant variants, they noted.





The study findings support the vaccination of children against COVID-19 as an important public health measure to prevent mortality in children and adolescents, they concluded.

Data Support Value of Vaccination, Outside Experts Say​

"COVID vaccines may not be as effective over time as the gene variants in the SARS-CoV-2 virus change," Adrienne G. Randolph, MD, a pediatrician at Harvard Medical School and Boston Children's Hospital, said in an interview. "Therefore, it is essential to assess vaccine effectiveness over time to look at effectiveness against variants and duration of effectiveness." Randolph, who was not involved in the study, said she was not surprised by the findings, which she described as consistent with data from the United States. "COVID vaccines are very effective against preventing life-threatening disease, but the effectiveness against less severe illness for COVID vaccines is not as effective against Omicron," she noted.


The take-home message for clinicians is that it's important to get children vaccinated against COVID to prevent severe and life-threatening illness, said Randolph. "Although these cases are uncommon in children, it is not possible to predict which children will be the most severely affected by COVID," she emphasized.


However, "we need more data on the new COVID booster vaccines in children that are designed to be more effective against Omicron's newer variants," Randolph said in an interview. "We also need more data on COVID vaccine effectiveness in the youngest children, under 5 years of age, and data on vaccinating mothers to prevent COVID in infants," she said.


Tim Joos, MD, a Seattle-based clinician who practices a combination of internal medicine and pediatrics, agreed that future research should continue to assess how the new COVID boosters are faring against new variants, noting that the current study did not include data from children who received the new bivalent vaccine.


"The methodology of this study uses a test negative case control design which is common for estimating vaccine effectiveness post-release of a vaccine, but is subject to biases," Joos explained. "These are not the clean effectiveness numbers of the prospective randomized control trials that we are used to hearing about when a vaccine is first being approved."


"Nevertheless, the study reinforces the initial manufacturers' studies that the vaccines are effective at preventing infection in the pediatric population," Joos said in an interview. The current study also reinforces the effectiveness of vaccines in preventing "the rare but devastating mortality from COVID-19 in the pediatric population."


Commenting on other research showing an increasing ratio of COVID deaths among vaccinated individuals compared to total COVID deaths, he noted that this finding is "likely reflecting a denominator effect of rapidly declining COVID deaths overall," partly from the vaccines and partly from immunity after previous natural infection.


The study received no outside funding. The researchers, Randolph, and Joos had no financial conflicts to disclose. Joos serves on the Editorial Advisory Board of Pediatric News.


This article originally appeared on MDedge.com, part of the Medscape Professional Network.

"

 

[ItsMainelyYou]

@missy I just want to let you know, again, I read all of these. Every month. You're doing a great public service for this board and everyone who comes to it. I'm very appreciative of your effort and care.

 

[missy]

@missy I just want to let you know, again, I read all of these. Every month. You're doing a great public service for this board and everyone who comes to it. I'm very appreciative of your effort and care.

Thank you so much @ItsMainelyYou I appreciate the feedback and am pleased it is helpful, thank you.



"

​

On the (Paxlovid) rebound​

The headline offers a clue... Biden, Walensky and Fauci all experienced a rebound after taking a five-day course of Paxlovid for Covid-19. Their cases and scores of similar anecdotes were widely reported, fueling suspicions that Pfizer Inc.’s antiviral medication caused recurrences or prolonged infections more often in real life than in clinical studies. (A rebound of coronavirus occurred in 2.3% of patients on Paxlovid versus 1.7% receiving placebo in a late-stage trial, Pfizer scientists said in September.) Concern about protracted illness is undermining use of the treatment that appears to have multiple benefits. Before I explain, my 18-year-old daughter will tell you (from the isolated confines of her bedroom) that a drawn-out bout of Covid is a huge annoyance. She didn’t take Paxlovid, but a rapid antigen test was still coming back positive 11 days after she fell ill -- something seen in a small fraction of vaccinated college students. It’s difficult to know why, but newer omicron variants and fluctuating levels of infection- and vaccine-induced immunity have led to different disease patterns across epidemic waves. The extent to which Paxlovid has added to the mix hasn’t been clear. So Jay Pandit at Scripps Research Translational Institute and former Harvard epidemiologist Michael Minaconducted an independent trial over four months to study rates of rebound. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, at the White House on Nov. 22, 2022. Photographer: Ken Cedeno/UPI Participants tested themselves every other day and recorded their symptoms over 16 days. The protocol was completed by 170 people, comprising 127 who took Paxlovid and 43 who didn’t. Almost all of participants had received at least one dose of vaccine. Viral rebound, as indicated by a positive test after recovering from an earlier infection, occurred in 14.2% of patients taking Paxlovid and 9.3% of controls. Symptoms returned in 18.9% of those on treatment, compared with just 7% of those who weren’t taking the drug. The rates were higher than what was seen in clinical trial data, but considerably lower than what the researchers anticipated. “We expected the rate of Paxlovid rebound (excess compared with controls) might be 30% or higher,” Eric Topol, Scripps’ founder, wrote in a blog post. Although more studies are needed to replicate and extend the findings, as well as figure out why rebound occurs, the research highlights the pitfalls of relying on anecdotal data disseminated on social media, Topol says. “The only way to know is to conduct a prospective, systematic clinical trial, with controls, which our group did, to shed light on the frequency of this Paxlovid problem,” he says. “I hope the new Scripps Research study will help alleviate some concerns about excessive rebound and get the right balance for decisions for treating with Paxlovid.” More information is coming on other benefits of Paxlovid. A study last month showed hospitalization rates were 51% lower among patients who took it for mild-to-moderate Covid, compared to those who didn’t. That supports a national TV campaign urging older Americans to ask about treatment if they catch the virus. Paxlovid is slated to be studied as a treatment for long Covid after a study found it was associated with a 26% reduction in the risk of lingering symptoms. There’s also accumulating evidence that it could stem the evolution of immune-evasive variants in a minority of patients whose bodies fail to clear the virus, leaving them chronically infected. — Jason Gale "

 

[dk168]

Not much to update except to say the bench I use in China is currently affected by Covid, and their government is easing the restrictions, as the latest strain is more like flu etc...!

And my usual contact did not join in the demonstrations against straight Covid restrictions.

DK

 

[missy]

Not much to update except to say the bench I use in China is currently affected by Covid, and their government is easing the restrictions, as the latest strain is more like flu etc...!

And my usual contact did not join in the demonstrations against straight Covid restrictions.

DK

I am sorry to hear this @dk168

I will share what my pulmonologist told me during our telemedicine call last week.
She said (as we all know) Covid is here to stay.

She said the best way to deal with this is always test (rapid testing) before getting together with anyone. She said have your friends/family test in front of you to make sure they are doing it correctly and then if everyone is negative plans can proceed. If anyone is positive obviously they leave.

In the USA we are entitled to 8 free rapid tests a month with most insurances. In fact I just ordered and picked up my free 8 tests yesterday. It was very easy to do. I ordered online at Walgreens and they texted me it was ready in one hour. On a Sunday. This way we are ready to socialize in small groups and I will have sufficient tests on hand for everyone. To test in front of me.

I have no social plans as of yet but for seeing my parents soon and we will all do a rapid test that day. Is it a perfect test? No. But perfect can be the enemy of good enough.

Hope you find this helpful and this is, IMO, the way forward. Since Covid is here to stay.

 

[missy]

"

The latest​

U.S. hospitals are reporting a post-Thanksgiving rise in coronavirus patients. More than 35,000 patients are being treated, with most states reporting increases, Washington Post reporters Fenit Nirappil and Jacqueline Dupree write.

The uptick began right before the holiday, and health officials are concerned that a continued increase would further tax the nation’s already overburdened health-care system as other viral illnesses, such as RSV (respiratory syncytial virus) and influenza, swarm.

Yeganeh Torbati and Ope Adetayo write in The Post about how an ex-Nigerian official, Abidemi Rufai, defrauded American taxpayers.He stole hundreds of thousands of dollars in coronavirus pandemic relief funds in 2020 by using the identities of unsuspecting residents in Washington state.

Rufai is not the only case of pandemic government fraud; the United States has spent more than $5 trillion on the pandemic — helping families and businesses. “But billions of dollars were stolen, and no one is sure, even now, exactly how much has disappeared,” the authors write.


This year, Rufai was sentenced to five years in prison and ordered to repay more than $600,000.

Other important news​

Pfizer and its German partner, BioNTech, submitted an emergency use authorization application Monday to the Food and Drug Administration for their omicron-targeting coronavirus booster for children younger than 5.

Financial technology firms are accused of overlooking signs of fraud related to coronavirus relief funds when they review applications for small businesses that applied for loans.

"

"

Your questions, answered​

Do coronavirus tests expire? If so, what is their shelf life?

Testing for the coronavirus can be done at home using a Food and Drug Administration-authorized test, but adhering to the manufacturer’s instructions is important to ensure accuracy of results.

The most common type of home diagnostic is a self-administered antigen test, which uses the surface cells in a person’s nasal passage to detect viral proteins. Many of these rapid tests have a shelf-life of six to 24 months.

Health experts do not recommend using at-home tests if the expiration date has passed.

“We cannot rely on results from expired coronavirus tests since the components of the test may be faulty, such as the liquid reagent drying up and not reacting as it should,” Scott Roberts, an infectious-disease specialist at the Yale School of Medicine, told The Washington Post.

“I would only use tests that are not expired even by one day,” Roberts said.

The federal government stopped its free coronavirus test distribution program in August. The FDA has a full list of authorized home tests that can be purchased here: At-Home OTC COVID-19 Diagnostic Tests.

"

But the FDA has extended some rapid home tests the expiration dates.
I am going to try sharing the graphs. If I cannot the link is below

At-Home OTC COVID-19 Diagnostic Tests

Expiration dates and more about authorized at-home OTC COVID-19 diagnostic tests information.

www.fda.gov

"
To see if the expiration date for your at-home OTC COVID-19 test has been extended, first find the row in the below table that matches the manufacturer and test name shown on the box label of your test.

• If the Expiration Date column says that the shelf-life is "extended," there is a link to "updated expiration dates" where you can find a list of the original expiration dates and the new expiration dates. Find the original expiration date on the box label of your test and then look for the new expiration date in the "updated expiration dates" table for your test.
• If the Expiration Date column does not say the shelf-life is extended, that means the expiration date on the box label of your test is still correct. The table will say "See box label" instead of having a link to updated expiration dates.

The FDA will update this table as additional shelf-life extensions are authorized.

To see complete information on smaller screens, select the blue plus (+) button beside the test name.

Search:
Show 102550100All entries

Manufacturer and Test Name (Links to Instructions for Use)	Who can use this test: Symptoms	Who can use this test: Age	Other Details	Expiration Date
Abbott Diagnostics Scarborough, Inc.: BinaxNOW COVID-19 Ag Card Home Test https://www.fda.gov/media/160087/download	People with symptoms that began within the last 7 days People without symptoms. The test is to be performed two times over three days (serial testing)	Age 15 years and older Age 2 years and older when collected by an adult	Antigen test Nasal swab Requires supervision of a telehealth proctor and a smartphone or computer Results in 15 minutes	Shelf Life: 15 months (extended) Expiration Date: See link for list of updated expiration dates
Abbott Diagnostics Scarborough, Inc.: BinaxNOW COVID-19 Antigen Self Test https://www.fda.gov/media/160094/download	People with symptoms that began within the last 7 days People without symptoms. The test is to be performed two times over three days (serial testing)	Age 15 years and older Age 2 years and older when collected by an adult	Antigen test Nasal swab Smartphone optional Results in 15 minutes	Shelf Life: 15 months (extended) Expiration Date: See link for list of updated expiration dates
Access Bio, Inc.: CareStart COVID-19 Antigen Home Test Alternate brand name:	People with symptoms that began within the last 7 days People without symptoms. The test is to be performed two times over three days (serial testing)	Age 14 years and older Age 2 years and older when collected by an adult	Antigen test Nasal swab Smartphone optional Alternate brand name: On/go COVID-19 Antigen Self-Test Results in 10 minutes	Shelf Life: 15 months (extended) Expiration Date: See link for list of updated expiration dates
ACON Laboratories, Inc: Flowflex COVID-19 Antigen Home Test Alternate brand name:	People with symptoms that began within the last 7 days People without symptoms. The test is to be performed two times over three days (serial testing)	Age 14 years and older Age 2 years and older when collected by an adult	Antigen test Nasal swab Smartphone optional Alternate brand name: On/Go One COVID-19 Antigen Home Test Results in 15 minutes	Shelf Life: 21 months (extended) Expiration Date: See link for list of updated expiration dates
ANP Technologies, Inc.: NIDS COVID-19 Antigen Home Test	People with symptoms that began within the last 7 days. The test is to be performed two times over three days (serial testing). People without symptoms. The test is to be performed three times over five days (serial testing).	Age 14 years and older Age 2 years and older when collected by an adult	Antigen test Nasal swab Results in 15-30 minutes	Shelf Life: 11 months Expiration Date: See box label
Aptitude Medical Systems Inc.: Metrix COVID-19 Test	People with or without symptoms	Age 14 years and older Age 2 years and older when collected by an adult	Molecular test Nasal swab Saliva Requires a Metrix Reader (sold separately) Smartphone optional Results in 30 minutes	Shelf Life: 12 Months Expiration Date: See box label
Azure Biotech Inc.: Fastep COVID-19 Antigen Home Test	People with symptoms that began within the last 5 days. The test is to be performed two times over three days (serial testing). People without symptoms. The test is to be performed three times over five days (serial testing).	Age 14 years and older Age 2 years and older when collected by an adult	Antigen test Nasal swab Results in 15-30 minutes	Shelf Life: 24 months Expiration Date: See box label
Becton, Dickinson and Company (BD): BD Veritor At-Home COVID-19 Test	People with symptoms that began within the last 7 days People without symptoms. The test is to be performed two times over three days (serial testing)	Age 14 years and older Age 2 years and older when collected by an adult	Antigen test Nasal swab Requires a smartphone Results in 15 minutes	Shelf Life: 6 months Expiration Date: See box label
Beijing Hotgen Biotech Co., Ltd.: Hotgen COVID-19 Antigen Home Test	People with symptoms that began within the last 7 days. The test is to be performed two times over three days (serial testing). People without symptoms. The test is to be performed three times over five days (serial testing).	Age 14 years and older Age 2 years and older when collected by an adult	Antigen test Nasal swab Results in 15-30 minutes	Shelf Life: 6 months Expiration Date: See box label
Celltrion USA, Inc.: Celltrion DiaTrust COVID-19 Ag Home Test	People with symptoms that began within the last 7 days People without symptoms. The test is to be performed two times over three days (serial testing)	Age 14 years and older	Antigen test Mid-turbinate nasal swab Smartphone optional Results in 15 minutes	Shelf Life: 18 months (extended) Expiration Date: See link for updated expiration dates
CorDX, Inc.: CorDx COVID-19 Ag Test https://www.fda.gov/media/163450/download	People with symptoms that began within the last 7 days. The test is to be performed two times over three days (serial testing). People without symptoms. The test is to be performed three times over five days (serial testing).	Age 14 years and older Age 2 years and older when collected by an adult	Antigen test Nasal swab Results in 10-30 minutes	Shelf Life: 15 months Expiration Date: See box label
Cue Health Inc.: Cue COVID-19 Test for Home and Over The Counter (OTC) Use https://www.fda.gov/media/160102/download	People with or without symptoms	Age 18 years and older Age 2 years and older when collected by an adult	Molecular test Nasal swab Requires a Cue Cartridge Reader (sold separately) Requires a smartphone Results in 20 minutes	Shelf Life: 4 months Expiration Date: See box label
Detect, Inc.: Detect Covid-19 Test https://www.fda.gov/media/160103/download	People suspected of COVID-19 People without symptoms. The test is to be performed two times over three days (serial testing)	Age 14 years and older Age 2 years and older when collected by an adult	Molecular test Nasal swab Requires a Detect Hub (sold separately) Smartphone optional Results in 60 minutes	Shelf-Life: 8 months (extended) Expiration Date: See link for list of updated expiration dates
Ellume Limited: Ellume COVID-19 Home Test https://www.fda.gov/media/160104/download	People with symptoms that began within the last 7 days People without symptoms. The test is to be performed two times over three days (serial testing)	Age 16 years and older Age 2 years and older when collected by an adult	Antigen test Mid-turbinate nasal swab Requires a Smartphone Results in 15 minutes	Shelf Life: 12 months Expiration Date: See box label
Genabio Diagnostics Inc.: Genabio COVID-19 Rapid Self-Test Kit https://www.fda.gov/media/160105/download	People with symptoms that began within the last 7 days. People without symptoms. The test is to be performed two times over three days (serial testing)	Age 14 years and older Age 2 years and older when collected by an adult	Antigen test Nasal swab Results in 15-30 minutes	Shelf Life: 18 months Expiration Date: See box label
iHealth Labs, Inc.: iHealth COVID-19 Antigen Rapid Test https://www.fda.gov/media/160106/download	People with symptoms that began within the last 7 days People without symptoms. The test is to be performed two times over three days (serial testing)	Age 15 years and older Age 2 years and older when collected by an adult	Antigen test Nasal swab Smartphone optional Results in 15 minutes Alternate brand name: GoodToKnow COVID-19 Antigen Rapid Test	Shelf Life: 12 months (extended) Expiration Date: See link for list of updated expiration dates
InBios International Inc: SCoV-2 Ag Detect Rapid Self-Test https://www.fda.gov/media/160108/download	People with symptoms that began within the last 5 days People without symptoms. The test is to be performed two times over three days (serial testing)	Age 14 years and older Age 2 years and older when collected by an adult	Antigen test Nasal swab Results in 20 minutes	Shelf Life: 13 months (extended) Expiration Date: See link for list of updated expiration dates
Lucira Health, Inc: Lucira CHECK-IT COVID-19 Test Kit https://www.fda.gov/media/160109/download	People with or without symptoms	Age 14 years and older Age 2 years and older when collected by an adult	Molecular test Nasal swab Smartphone optional Results in 30 minutes	Shelf Life: 18 months (extended) Expiration Date: See link for list of updated expiration dates
Maxim Biomedical, Inc.: MaximBio ClearDetect COVID-19 Antigen Home Test https://www.fda.gov/media/160110/download	People with symptoms that began within the last 5 days People without symptoms. The test is to be performed two times over three days (serial testing)	Age 14 years and older Age 2 years and older when collected by an adult	Antigen test Nasal swab Results in 15 minutes	Shelf Life: 8 months (extended) Expiration Date: See link for list of updated expiration dates
OraSure Technologies, Inc.: InteliSwab COVID-19 Rapid Test https://www.fda.gov/media/160111/download	People with symptoms that began within the last 7 days People without symptoms. The test is to be performed two times over three days (serial testing)	Age 18 years and older Age 2 years and older when collected by an adult	Antigen test Nasal swab Smartphone optional Results in 30 minutes	Shelf Life: 12 months (extended) Expiration Date: See link for list of updated expiration dates
OSANG LLC: OHC COVID-19 Antigen Self Test https://www.fda.gov/media/161361/download Alternate brand name: https://www.fda.gov/media/161362/download	People with symptoms that began within the last 7 days. The test is to be performed two times over three days (serial testing). People without symptoms. The test is to be performed two times over three days (serial testing).	Age 14 years and older Age 2 years and older when collected by an adult	Antigen test Nasal swab Alternate brand name: QuickFinder COVID-19 Antigen Self Test Results in 15 minutes	Shelf Life: 12 months (extended) Expiration Date: See link for list of updated expiration dates
PHASE Scientific International, Ltd.: INDICAID COVID-19 Rapid Antigen At-Home Test https://www.fda.gov/media/160113/download	People with symptoms that began within the last 6 days People without symptoms. The test is to be performed two times over three days (serial testing)	Age 14 years and older Age 2 years and older when collected by an adult	Antigen test Nasal swab Results in 20 minutes	Shelf Life: 12 months Expiration Date: See box label
Quidel Corporation: QuickVue At-Home OTC COVID-19 Test https://www.fda.gov/media/162058/download	People with symptoms that began within the last 6 days People without symptoms. The test is to be performed two times over three days (serial testing)	Age 14 years and older Age 2 years and older when collected by an adult	Antigen test Nasal swab Results in 10 minutes	Shelf Life: 16 months (extended) Expiration Date: See link for updated expiration date
SD Biosensor, Inc.: Pilot COVID-19 At-Home Test 1 https://www.fda.gov/media/160115/download	People with symptoms that began within the last 6 days People without symptoms. The test is to be performed two times over three days (serial testing)	Age 14 years and older Age 2 years and older when collected by an adult	Antigen test Nasal swab Results in 20 minutes	Shelf Life: 12 months (extended) Expiration Date: See link for updated expiration date
Siemens Healthineers: CLINITEST Rapid COVID-19 Antigen Self-Test https://www.fda.gov/media/160116/download	People with symptoms that began within the last 7 days People without symptoms. The test is to be performed two times over three days (serial testing)	Age 14 years and older Age 2 years and older when collected by an adult	Antigen test Nasal swab Results in 15 minutes	Shelf Life: 24 months (extended) Expiration Date: See link for updated expiration date
Watmind USA: Speedy Swab Rapid COVID-19 Antigen Self-Test https://www.fda.gov/media/160117/download	People with symptoms that began within the last 6 days. The test is to be performed two times over three days (serial testing) People without symptoms. The test is to be performed two times over three days (serial testing)	Age 14 years and older Age 2 years and older when collected by an adult	Antigen test Nasal swab Results in 15 minutes	Shelf Life: 6 months Expiration Date: See box label
Xiamen Boson Biotech Co., Ltd.: Rapid SARS-CoV-2 Antigen Test Card https://www.fda.gov/media/160118/download	People with symptoms that began within the last 6 days. The test is to be performed two times over three days (serial testing). People without symptoms. The test is to be performed two times over three days (serial testing).	Age 14 years and older Age 2 years and older when collected by an adult	Antigen test Nasal swab Results in 15 minutes	Shelf Life: 6 months Expiration Date: See box label

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ETA I had to delete a number of images in the chart due to PS's limitation of 10 images per post. If you want to see the entire chart please click the link I provided above

 

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Flu Admissions Double; Pfizer Seeks EUA for Kid Omicron Shot; WHO's Variant Warning​

— Health news and commentary from around the Web gathered by MedPage Today staff​

by Shannon Firth, Washington Correspondent, MedPage Today December 5, 2022

The flu sent nearly 20,000 people to the hospital during Thanksgiving week -- close to twice the admissions over the prior week -- according to the latest CDC data. (CNN)

Pfizer/BioNTech are seeking emergency use authorization (EUA) for their Omicron-containing booster shot for kids under 5 years of age.

Children's Tylenol, Children's Motrin, and other fever-reducing medicines are getting harder to find, due to the nation's "tripledemic," but drugmaker Johnson & Johnson reports no shortages. (NPR)



Meanwhile, a shortage of pharmacists spurred CVS to test a remote system to fill prescriptions. (Wall Street Journal)

Poison center reports show an alarming spike in child and teen marijuana useover a 20-year period. (ABC News)

The former co-owner of a compounding pharmacy in Massachusetts was sentenced to 1 year in prison for his part in a 2012 fungal meningitis outbreak that sickened almost 800 people in 20 states. (CNN)

An Indiana judge said the state's attorney general broke the law in publicizing his investigation of a physician who gave an abortion to a 10-year-old rape victim; the judge stopped short of blocking the investigation, however. (The Hill)

HHS does not anticipate it will renew the public health emergency declarationfor monkeypox, or mpox, when it ends Jan. 31, 2023.

As of Monday at 8:00 a.m. ET, the unofficial COVID toll in the U.S. reached 98,972,411 cases and 1,081,431 deaths, increases of 401,199 and 2,224 respectively, since this time a week ago.



Billions of dollars in COVID aid went to hospitals that didn't need it. (Wall Street Journal)

A defense bill slated for release this week could undo the Pentagon's policy of booting troops for refusing the COVID vaccine. (Politico)

The World Health Organization (WHO) warned that receding COVID precautions could lead to deadly new variants. (Reuters)

Local health departments in Central Ohio are working with the Ohio Department of Health and hospitals there to contain a measles outbreak with vaccines, treatments, and tests. (WBNS)

Drug overdoses killed eight friends one after another in this small North Carolina city. (Washington Post)

Daniel Davidow, MD, the former medical director of Cumberland Hospital for Children and Adolescents in Virginia, has been charged with felony sex crimesfor abuse that happened at the facility, according to authorities. (AP)

The United Health Foundation and the American Nurses Foundation are launching a $3.1 million pilot program to address nurse stress and burnout. (Fierce Healthcare)



A healthcare marketing group is launching "Unf*ck Your Feelings," a suicide prevention strategy that targets younger men. (Fierce Pharma)

Can a new gene therapy stop Alzheimer's disease in its tracks? (New York Times)

Brazilian soccer legend, Pelé, who has colon cancer, stated on social media that he was feeling "strong" despite unconfirmed reports that he had been moved to palliative care. (The Guardian)

Jim Kolbe, a former Republican Congressman from Arizona and proponent of gay rights, died Saturday, at age 80. (AP via Politico)

Words for cancer surgeons to avoid? "We got it all." (New York Times)

James Farms frozen raspberries have been recalled over concerns of possible contamination with hepatitis A, the FDA announced.

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Do We Still Need to Quarantine With COVID?​

— While COVID still distinguishes itself from other illnesses, those days may be numbered​

by Jennifer Henderson, Enterprise & Investigative Writer, MedPage Today December 2, 2022

Before the pandemic, people often didn't think twice about going about their daily lives and heading into public spaces with a runny nose, sore throat, or even a bit of a cough.
Now, years into living with COVID-19 and with a herd of other respiratory viruses hitting hard, people may be questioning whether they should still subject themselves to quarantine or isolation if they contract COVID. Most people wouldn't do as much with an unidentified case of the sniffles, but is COVID still a different story?

Public health expert Leana Wen, MD, an emergency physician and professor at George Washington University in Washington, D.C., explained to MedPage Today that people should follow the CDC's guidelines for isolation when testing positive for COVID. Generally speaking, that means at least 5 days of isolation followed by 5 days of mask wearing.
That's because COVID is still being treated differently than other respiratory viruses, Wen said.
Not only is COVID a new illness unlike some of its circulating counterparts -- flu and respiratory syncytial virus (RSV) -- but people have "really feared it" throughout the pandemic, she noted. Many people "continue to feel strongly about wanting to avoid it," for reasons including severe outcomes and the possibility of long COVID.
Furthermore, she added, COVID is much more contagious than flu and RSV.
Perhaps the bigger question around whether COVID continues to be treated differently than other respiratory viruses is "what is the goal ... as a society?" Wen noted.

For now, the goal remains reducing infections, which is reflected in ongoing COVID protocols that are unlike those for other illnesses, she said. However, if the goal is to minimize severe disease from COVID, then isolation would not be the right strategy; instead, vaccination and prompt detection and treatment for those at risk of severe illness would be the way to go.
"I think there is an idea around COVID that may not be there for other illnesses," Wen said. "Out of respect for individuals who have such a strong desire to avoid COVID -- unless we as a society make that pivot -- we need to continue isolation."
Aubree Gordon, PhD, an associate professor of epidemiology at the University of Michigan School of Public Health in Ann Arbor, agreed that, at least for now, isolation is still a hallmark of COVID protocols.
For COVID, "the advice is certainly still to isolate," she said. The U.S. is still seeing some 300 deaths per day from COVID, "which is a really huge number."

"I think that's really where the difference lies," she added.
However, Gordon said that she believes the days of COVID being treated differently than other respiratory viruses are numbered, at least to some extent. "I do think we'll get to the point, eventually, where we won't need to isolate at home when we have COVID."
Public health experts continue to weigh that topic.
"There are discussions happening over cups of coffee in the public health environment, that there's so much Omicron out there and it is spreading even without symptoms," William Schaffner, MD, professor of infectious diseases at Vanderbilt University Medical Center in Nashville, Tennessee, explained to MedPage Today. "So they question the value of quarantine. What's the point, when this virus is infecting people left and right? Should we really take the few people with symptoms and ask them to lock themselves up? That probably doesn't have a noteworthy impact on transmission at all."

"This is very different from the beginning of the outbreak, when no one had any protection at all," Schaffner added. "Then, quarantine had a role. But now people are beginning to wonder, does quarantine have any role in reducing transmission of this virus?"
As challenging as the questions surrounding COVID may be, considerations concerning other respiratory viruses that are also rearing their heads can be even more nuanced.
"In an ideal world, of course you should not be around others while you could be infectious, but if you say, that's the blanket recommendation across the board, you'll have kids that will never go to school," Wen said.
However, there are certain symptoms that are more clear and potentially more problematic than others, she added. (Think nausea and vomiting, enough coughing to cause trouble breathing, and high fever.)
"Otherwise, we should be particularly careful when we're around vulnerable individuals," she noted.

RSV is an especially significant threat to very young children, Gordon said, and flu can be as well.
"For all those respiratory viruses, I'd really encourage people to stay home for a few days," Gordon advised. "We know you're most infectious for the first few days for all of these viruses [and] the amount of virus you shed potentially decreases over time."
She said she believes the amount of virus someone is exposed to and how they are exposed to it contributes to how sick they may ultimately get.
If a person is sick with a respiratory illness other than COVID, she recommended they consider wearing a mask if they need to be out in a public setting.
Another item on Gordon's wish list for combatting a scourge of respiratory viruses is at-home tests for flu and RSV that people could purchase at their local drugstore, just the same as for COVID.

Overall, "trying to cut down on that transmission can lead to a much less sharp peak," Gordon said.
"None of us want our child or us in a hospital bed, but if we need one, we want that bed to be available," she added, "and adequate care to be available."
Kristina Fiore contributed reporting to this article.
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Drop in COVID alertness could create deadly new variant - WHO
Published December 5, 2022 | Originally published on Health News Online Report


Lapses in strategies to tackle COVID-19 this year continue to create the perfect conditions for a deadly new variant to emerge, as parts of China witness a rise in infections, the head of the World Health Organization said on Friday.

The comments by WHO Director-General Tedros Adhanom Ghebreyesus mark a change in tone just months after he said that the world has never been in a better position to end the pandemic.

"We are much closer to being able to say that the emergency phase of the pandemic is over, but we're not there yet," Tedros said on Friday.

The global health agency estimates that about 90% of the world's population now has some level of immunity to SARS-COV-2 either due to prior infection or vaccination.

"Gaps in testing ... and vaccination are continuing to create the perfect conditions for a new variant of concern to emerge that could cause significant mortality," Tedros said.

COVID-19 infections are at record highs in China and have started to rise in parts of Britain after months of decline.

Further easing of COVID-19 testing requirements and quarantine rules in some Chinese cities was met with a mix of relief and worry on Friday, as hundreds of millions await an expected shift in national virus policies after widespread social unrest.

"While COVID-19 and flu can be mild infections for many, we must not forget that they can cause severe illness or even death for those most vulnerable in our communities", Mary Ramsay, director of public health programmes at the UK Health Security Agency, said.

The WHO urged governments globally to focus on reaching those at risk, such as people over the age of 60 and those with underlying conditions, for vaccination.

(Reporting by Bhanvi Satija and Manas Mishra in Bengaluru and Josephine Mason in London; Editing by Devika Syamnath and Shounak Dasgupta)

—Bhanvi Satija

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Scientists closer to understanding why COVID-19 affects people so differently
Published December 2, 2022 | Originally published on MedicalXpress Breaking News-and-Events


Researchers from the Institut Pasteur, Inserm, St. James's Hospital Dublin and Trinity are getting closer to understanding what makes some people so vulnerable to COVID-19-induced illness, which in turn may guide the development of new therapeutic strategies.

Their findings of a comprehensive study that yields fresh insights are published this week in the journal Nature Communications. Chief among their new discoveries is the link between very sick people and their difficulty or inability to produce a key anti-viral protein called type 1 interferon.

Earlier studies, several of which included members of the collaboration, had already shown that if type 1 interferon was compromised then viral infection would not be cleared. But the new work builds on this, and helps explain why simply administering type 1 interferon therapeutically has been largely ineffective.

This most recent French-Irish collaboration found that when type 1 interferon was added to the blood of patients with severe COVID-19, their immune cells were much more inflammatory as compared to people who had a much milder COVID-19.

Darragh Duffy from the Institut Pasteur is the senior investigator on the project. He says, "We have of course long known that people respond very differently to COVID-19—some remain relatively well or are even asymptomatic, while others get very sick and some tragically die. But we are still hunting for a more complete picture of why this the case. This latest research has added more layers to our understanding, and the results are exciting as they may help explain why therapeutic use of type 1 interferon late in infection has failed despite many studies showing how important this protein is in early infection."

The new findings support interferon testing much earlier in the disease time course and reinforce the need to screen individuals with compromised responses (either due to genetics, autoantibodies or treatments) for complications with COVID or other acute viral infections.

Nollaig Bourke, from Trinity, says, "This study reveals important new insights into why inadequate and inappropriate type I interferon responses can be so detrimental in severe COVID-19, which helps us to understand more about the early biological immune processes that go wrong in people with severe disease."

Cliona O'Farrelly, professor of comparative immunology at Trinity, who is based in the Trinity Biomedical Sciences Institute (TBSI), adds, "Novel useful clinical research like this that helps us understand how we are vulnerable to COVID-19 requires teams of people with different skills and expertise like the authors of this paper who come from diverse clinical and scientific backgrounds."

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Nanobody treatment shows promise against SARS-CoV-2 infection
Published December 2, 2022 | Originally published on MedicalXpress Breaking News-and-Events


A nanobody—an alternative class of antibody derived from alpaca or IIama protein fragments—developed by MassBiologics of UMass Chan Medical School, blocks SARS-CoV-2 infection in animal models and may be a new therapeutic in the growing number of biologics being explored to treat emerging COVID variants. As published in Frontiers in Immunology, a nasally delivered nanobody could be a noninvasive, low-cost and effective prophylaxis and post-exposure treatment for SARS-CoV-2 and other respiratory pathogens.

A division of UMass Chan, MassBiologics is the only nonprofit, FDA-licensed manufacturer of vaccines in the United States and is a pioneer in the development of human monoclonal antibody treatments for diseases important to public health. A 2020 study by MassBiologics was the first to show that an IgA antibody could successfully block SARS-Cov-2 infection. Nature Communications recently selected this work as one of the most impactful and innovative studies published in the journal since the COVID-19 pandemic.

"There is still a great need for therapeutics to counter emerging SARS-CoV-2 variants that cause COVID, particularly for resource-constrained populations," said principal investigator Yang Wang, MD, Ph.D., professor of medicine and deputy director of product discovery at MassBiologics.

"The challenge for antibody treatments for COVID, however, is that they have been very expensive to deliver because they have to be produced in mammalian cells and they take trained health professionals to administer intravenously. Even the mRNA vaccines require special storage and handling. Our nanobodies, in contrast, can be produced inexpensively in yeast cells and can be delivered simply in a nasal spray."

The MassBiologics nanobody, designated VHH-IgA, is a fusion of an antigen-binding fragment of the COVID spike protein and a human IgA antibody. When delivered nasally to animal models that had been previously exposed to the SARS-CoV-2 virus, the VHH-IgA effectively bonded to the SARS-CoV-2 spike protein, thereby inhibiting infection. These animals showed a marked reduction in viral loads.

Conversely, when treated prophylactically, animal models that were subsequently exposed to the SARS-CoV-2 virus showed lower levels of viral penetration, making the treatment potentially protective against COVID-19.

The VHH-IgA antibody treatment was equally effective against most variants of SARS-CoV-2, including the newer omicron variants. This suggests that a nanobody treatment may also be effective against emerging variants of concern.

"While the current mRNA vaccines and other monoclonal antibody treatments have been effective in curtailing COVID infection, there are multiple reasons why these options might not be readily available to all patients," said Dr. Wang. "It's necessary to have other options available, and our VHH-IgA molecule shows great promise as a complementary therapeutic that can neutralize existing infections and preventing new infections."

The next step for the team is to perform pre-clinical studies of the VHH-IgA biologic along with toxicology studies before embarking on clinical trials.

"Ultimately, our hope is to have a product that you can walk into and purchase, over-the-counter, from your local pharmacy," said Wang.


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Rising Flu Cases Drive Up US Hospitalizations, CDC Says​

By Susan Heavey and Caroline Humer
December 06, 2022



WASHINGTON (Reuters) - The United States is experiencing the highest levels of hospitalizations from influenza that it has seen in a decade for this time of year, the head of the U.S. Centers for Disease Control and Prevention (CDC) said on Monday, adding that 14 children have died so far this flu season.
CDC Director Rochelle Walensky added that U.S. hospital systems also continue to be stressed with a high number of patients with other respiratory illnesses such as respiratory syncytial virus (RSV) and COVID-19.
There have been at least 8.7 million illnesses, 78,000 hospitalizations, and 4,500 deaths from flu so far this season, according to CDC estimates. It urged people to get vaccinated.
"Especially for RSV and flu, these levels are higher than we generally see this time of year," Walensky told reporters in a telephone news briefing. She said flu season started earlier and "hospitalizations for flu continue to be the highest we have seen at this time of year in a decade."

Respiratory viruses are spreading as people gather indoors due to the colder weather. People also likely have weakened defenses after not being exposed to flu and RSV while working or schooling from home during the COVID-19 pandemic.




Vaccination rates for people at higher risk from the flu - those 65 and older, children and pregnant women - are also lower than at this time last year, Walensky added.
About 12% fewer pregnant women have been vaccinated so far this season compared to last season, and about 5% fewer children, Walensky said.
Between Oct. 1 and Nov. 26, the rate of hospitalization for flu in the United States was 16.6 per 100,000 people. In the past 10 years, the cumulative rate during the same week of the year typically range from 0.1 to 2 per 100,000.

COVID-19 cases have risen following the Thanksgiving holiday and COVID-related hospitalizations have also increased about 15% to 20% over the last week, Walensky said.
Walensky, joined by Dr. Sandra Fryhofer, an internist who chairs the American Medical Association board, urged people to get flu shots now - despite possibly being wary or tired of vaccinations - saying it was not too late.
"This year's flu season's off to a rough start," Fryhofer said. "It started early, and with COVID and RSV also circulating, it's a perfect storm for a terrible holiday season."
(Reporting by Susan Heavey and Caroline Humer; Editing by Bill Berkrot)

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China May Announce 10 New COVID Easing Steps on Wednesday: Sources​

By Julie Zhu and Kevin Huang
December 06, 2022




HONG KONG (Reuters) - China may announce 10 new COVID-19 easing measures as early as Wednesday, two sources with knowledge of the matter told Reuters, supplementing 20 unveiled in November that set off a wave of COVID easing steps nationwide.
Three years of zero-tolerance measures, from shuttered borders to frequent lockdowns, have battered China's economy, fuelling last month the mainland's biggest show of public discontent since President Xi Jinping took power in 2012.
Management of the disease may be downgraded as soon as January, to the less strict Category B from the current top-level Category A of infectious disease, the sources said on Monday, speaking on condition of anonymity.
The National Health Commission did not immediately respond to a Reuters fax message seeking comment.

Last week, Vice Premier Sun Chunlan said China was facing "a new situation" as pathogenicity of the Omicron virus weakened, becoming the first high-ranking official to publicly acknowledge that the new variant's disease-causing ability had diminished.




Many major cities have since started to lift wide lockdowns, reduce regular PCR testing and end checks for negative tests in public spaces, such as subway stations and parks.
The national health authority had earlier announced a score of new measures on Nov. 11, in the effort to improve COVID management and strike a better balance between epidemic control and shoring up the economy.
China will allow home quarantine for some of those testing positive, among the supplementary measures set to be announced, two sources told Reuters last week.

That would be a key change in strategy from earlier this year, when entire communities were locked down, sometimes for weeks, after just one positive case.
Last month, new, easier quarantine rules required just the lockdown of affected buildings.
Since January 2020, China has classified COVID-19 as a Category B infectious disease but managed it under Category A protocols, giving local authorities the power to quarantine patients and their close contacts and lock down regions.
Category A covers diseases such as bubonic plague and cholera, while Category B groups SARS, AIDS and anthrax, with diseases such as influenza, leprosy and mumps placed in Category C.

But more than 95% of China's cases are asymptomatic and mild, with few deaths. In such circumstances, sticking to the Category A strategy is not in line with science, state media outlet Yicai said on Sunday, citing an unidentified expert.

COVID-19 could be downgraded to Category B management or even Category C, the expert told Yicai.

(Writing by Ryan Woo; Editing by Alison Williams and Clarence Fernandez)

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China's COVID-19 Policy in Flux​

Reuters staff
December 06, 2022




BEIJING (Reuters) - China is set to announce new measures to further ease some of the world's toughest COVID-19 curbs as early as Wednesday, sources told Reuters, with investors cheering the prospect of changes after widespread protests and mounting economic damage.
The zero-COVID policy to stamp out transmission has become a global outlier as most countries seek to live with the disease, but 20 new measures to streamline controls came last month, amid rising public frustration.
After November's rare widespread protests across more than 20 cities, crucial planks of the policy, such as some compulsory tests, and even messaging on the deadliness of the virus, are changing.
Here are questions and answers about a key turning point in President Xi Jinping's signature policy:

Is China abandoning zero COVID?


Not yet, but it is making incremental adjustments, easing testing requirements and quarantine rules.
Changes varying by location have taken place even in cities such as southern Guangzhou and Beijing, the capital, despite recent record infections.
Officials told local governments not to use an earlier "one-size-fits-all" approach. Rather, cities have been closing off apartment buildings and single compounds after cases were found, instead of portions of city blocks.

More changes could come as early as Wednesday, Reuters has reported.
WHY MAKE CHANGES NOW?
Public fatigue with zero-COVID is growing, and a surge that triggered lockdowns in numerous cities last month, often unannounced, saw the anger boil over.
At the same time, the world's second-largest economy is being hammered by curbs that have squeezed consumption and travel and disrupted factory output and global supply chains.

The 20th Congress of the ruling Communist Party in October, where Xi secured a third five-year leadership team, had been seen as a milestone that could lead to an unwinding of the policy.

WHAT IS CHINA DOING TO PREPARE FOR EASING?

It recently announced efforts to boost vaccination among its vast elderly population. Some cities have rolled out a new inhalable COVID vaccine booster from CanSino Biologics.

But many experts have said China has not done enough.

It has not approved foreign mRNA vaccines that are more effective against COVID-19. A top U.S. intelligence official said Xi is unwilling to accept Western vaccines.

Some experts urge more vaccine booster doses and beefed up health services, as herd immunity is low after the virus was largely kept at bay during the pandemic's first two years.

Forecasts of deaths after eventual re-opening range from 1.55 million to more than 2 million, depending on vaccination levels and health care preparedness.

Yet the current tally of 5,235 COVID-related deaths is a tiny fraction of China's population of 1.4 billion, and extremely low by global standards.




HOW HAVE THE PUBLIC REACTED TO THE CHANGES?

With relief and worry. Many, especially in big cities, frustrated by the inconvenience, uncertainty, economic toll and travel curbs accompanying zero-COVID, would welcome its end.

But others, including the elderly, worry about the costs of a wide outbreak. Fear of the disease runs deep after heavy-handed control measures, while state media have played up deaths and chaos elsewhere, especially the United States.

The recent rule changes and their patchy application have also confused many.

WHAT DOES THIS MEAN FOR FULL RE-OPENING?

China has all but shut its borders to international travel for nearly three years. International flights are still at just a fraction of pre-pandemic levels and arrivals face eight days in quarantine.

Many analysts have said significant re-opening will only begin in March or April, after the winter flu season and the annual session of parliament that usually starts on March 5.

Bank Goldman Sachs said it expects gradual re-opening from April.

But Julian Evans-Pritchard, a senior China economist at Capital Economics, said a move away from zero-COVID was unlikely even in 2023, citing low vaccination rates for the elderly, among other factors.

JPMorgan analysts have warned the path to re-opening is likely to be bumpy.

(Reporting by Beijing and Shanghai newsroom, Writing by Bernard Orr; Editing by Clarence Fernandez)

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France Says Making Masks Mandatory in Transports Hinges on COVID Epidemic Situation​

Reuters staff
December 06, 2022




PARIS (Reuters) -The decision to make wearing face-masks in public transportation mandatory again to contain a new surge in the COVID-19 epidemic will depend on the evolution of the situation, French Health Minister Francois Braun said on Monday.
"I invite people to put on masks in public transportation even if it's not mandatory," he told reporters during a visit of French hospital.
"The decision (to make it mandatory) will depend on the evolution of the pandemic," Braun said, adding that option was "on the table".
As of last Friday, the seven-day moving average of daily new COVID infections stood at 54,824, a more than six-week high in France versus less than 25,000 in early November.

However, it is still well below levels of over 100,000 seen over March-April and in July, and a record of over 366,000 in January.




The number of people in intensive care units for COVID-19 has reached a peak since Aug 8, at 1,113 and total hospitalisations for the disease are close to 20,000 again for the first time since end October.
Last week, French Prime Minister Elisabeth Borne said she recommended that people wear masks in public transport and when they come in contact with vulnerable people.
(Reporting by Benoit Van Overstraeten; Editing by Dominique Vidalon)


Reuters Health Information © 2022

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NEJM December 7, 2022

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Efficacy of Antiviral Agents against Omicron Subvariants BQ.1.1 and XBB​

TO THE EDITOR:​

Three sublineages of the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have serially transitioned into globally dominant forms — first BA.1, then BA.2, and then BA.5. As of October 2022, most circulating omicron variants belong to BA.5. However, the prevalence of BQ.1.1 (a BA.5 subvariant) and XBB (a BA.2 subvariant) is increasing rapidly in several countries, including the United States and India. BA.2 and BA.5 variants have been shown to have less sensitivity to certain monoclonal antibodies than previously circulating variants of concern.1-5 Notably, as compared with BA.5 and BA.2, BQ.1.1 and XBB carry additional substitutions in the receptor-binding domain of the spike (S) protein, which is the major target for vaccines and therapeutic monoclonal antibodies for coronavirus disease 2019 (Covid-19). These subvariants may, therefore, be more immune-evasive than BA.5 and BA.2.
Figure 1.

In Vitro Efficacy of Therapeutic Monoclonal Antibodies and Antiviral Drugs against Omicron Subvariants.
We assessed the efficacy of therapeutic monoclonal antibodies against omicron BQ.1.1 (hCoV-19/Japan/TY41-796/2022; TY41-796) and XBB (hCoV-19/Japan/TY41-795/2022; TY41-795), which were isolated from patients. The BQ.1.1 isolate had three more substitutions (R346T, K444T, and N460K) in its receptor-binding domain than a BA.5 (hCoV-19/Japan/TY41-702/2022) isolate (Fig. S1A in the Supplementary Appendix, available with the full text of this letter at NEJM.org). The XBB isolate had nine more changes (G339H, R346T, L368I, V445P, G446S, N460K, F486S, F490S, and the wild-type amino acid at position 493) in its receptor-binding domain than a BA.2 (hCoV-19/Japan/UT-NCD1288-2N/2022) isolate (Fig. S1B). To examine the reactivity of monoclonal antibodies against these subvariants, we determined the 50% focus reduction neutralization test (FRNT50) titer of the monoclonal antibodies by using a live-virus neutralization assay. REGN10987 (marketed as imdevimab), REGN10933 (marketed as casirivimab), COV2-2196 (marketed as tixagevimab), COV2-2130 (marketed as cilgavimab), and S309 (the precursor of sotrovimab) did not neutralize the BQ.1.1 or XBB isolates even at the highest FRNT50 value (>50,000 ng per milliliter) tested (Figure 1A and Table S1). LY-CoV1404 (marketed as bebtelovimab), which effectively neutralizes1,3-5 omicron BA.1, BA.2, BA.4, and BA.5, had no efficacy against BQ.1.1 or XBB. Both combinations of monoclonal antibodies tested (i.e., imdevimab–casirivimab and tixagevimab–cilgavimab) failed to neutralize either BQ.1.1 or XBB. These results suggest that imdevimab–casirivimab, tixagevimab–cilgavimab, sotrovimab, and bebtelovimab may not be effective against BQ.1.1 or XBB in the clinical setting.
The Food and Drug Administration approved remdesivir (an inhibitor of the RNA-dependent RNA polymerase [RdRp] of SARS-CoV-2) for the treatment of Covid-19 and issued an emergency use authorization for molnupiravir (an RdRp inhibitor) and nirmatrelvir (an inhibitor of the main protease of SARS-CoV-2). We therefore tested these antiviral drugs by determining the in vitro 50% inhibitory concentration (IC50) of each compound against BQ.1.1 and XBB. Unlike the amino acid sequence of the reference strain Wuhan/Hu-1/2019, the BQ.1.1 and XBB isolates encode the P3395H substitution in their main protease (Fig. S1C and S1D). The BQ.1.1 and XBB isolates also have two (Y264H and P314L) and three (P314L, M659I, and G662S) substitutions in their RdRp, respectively. The susceptibilities of BQ.1.1 and XBB to the three compounds were similar to those of the ancestral strain (SARS-CoV-2/UT-NC002-1T/Human/2020/Tokyo). For BQ.1.1, the IC50 value was lower by a factor of 0.6 with remdesivir and higher by factors of 1.1 and 1.2 with molnupiravir and nirmatrelvir, respectively. For the XBB subvariant, the IC50 value was lower by a factor of 0.8 with remdesivir, lower by a factor of 0.5 with molnupiravir, and higher by a factor of 1.3 with nirmatrelvir (Figure 1B). These results suggest that remdesivir, molnupiravir, and nirmatrelvir are efficacious against both BQ.1.1 and XBB in vitro.
Our data suggest that the omicron sublineages BQ.1.1 and XBB have immune-evasion capabilities that are greater than those of earlier omicron variants, including BA.5 and BA.2. The continued evolution of omicron variants reinforces the need for new therapeutic monoclonal antibodies for Covid-19.
Masaki Imai, D.V.M., Ph.D.
Mutsumi Ito, D.V.M.
Maki Kiso, D.V.M., Ph.D.
Seiya Yamayoshi, D.V.M., Ph.D.
Ryuta Uraki, Ph.D.
University of Tokyo, Tokyo, Japan
Shuetsu Fukushi, Ph.D.
Shinji Watanabe, D.V.M., Ph.D.
Tadaki Suzuki, M.D., Ph.D.
Ken Maeda, D.V.M., Ph.D.
National Institute of Infectious Diseases, Tokyo, Japan
Yuko Sakai-Tagawa, Ph.D.
Kiyoko Iwatsuki-Horimoto, D.V.M., Ph.D.
University of Tokyo, Tokyo, Japan
Peter J. Halfmann, Ph.D.
University of Wisconsin–Madison, Madison, WI
Yoshihiro Kawaoka, D.V.M., Ph.D.
University of Tokyo, Tokyo, Japan
[email protected]
Supported by grants from the Center for Research on Influenza Pathogenesis and Transmission (75N93021C00014, to Dr. Kawaoka), funded by the National Institute of Allergy and Infectious Diseases; a Research Program on Emerging and Reemerging Infectious Diseases (JP21fk0108552 and JP21fk0108615, to Dr. Kawaoka); a Project Promoting Support for Drug Discovery (JP21nf0101632, to Dr. Kawaoka); the Japan Program for Infectious Diseases Research and Infrastructure (JP22wm0125002, to Dr. Kawaoka); and the Japan Agency for Medical Research and Development (JP223fa627001, to Dr. Kawaoka).
Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.
This letter was published on December 7, 2022, at NEJM.org.

Drs. Imai and Ito and Drs. Kiso and Yamayoshi contributed equally to this letter.



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Study uncovers inflammatory markers that may predict a response in certain patients to COVID-19 immunotherapies
Published December 6, 2022 | Originally published on ScienceDaily Top Health
Researchers at The Tisch Cancer Institute uncovered inflammatory markers that may predict which COVID-19 patients are more likely to respond to therapies like the anti-cancer drug pacritinib, according to phase 2 trial results published in JAMA Network Open in December.

Pacritinib, which has been approved as a cancer therapy by the Food and Drug Administration (FDA), is classified as a JAK2 inhibitor; it blocks messaging pathways in the immune system that promote inflammation. The researchers suggested that it could serve as a model to guide the selection of several other approved immunotherapies that have been shown to improve outcomes in patients with severe COVID-19, including the JAK2 inhibitor baricitinib and the IL-6 inhibitor tocilizumab.

"While we identified subtypes of COVID-19 patients with hyperinflammation who could actually benefit from pacritinib, our study failed to show superiority of pacritinib to standard-of-care management of hospitalized COVID-19 adults with acute respiratory distress syndrome for a variety of reasons," says senior author John Mascarenhas, MD, Professor of Medicine at the Icahn School of Medicine at Mount Sinai and Director of the Center of Excellence for Blood Cancers and Myeloid Disorders. "We believe one reason may have been that the study was limited by the early dropout of participants who actually improved with this agent and therefore did not feel it was necessary to continue treatment and these patients were not captured as responders in the analysis."

Dr. Mascarenhas believes that despite recent advances in immunomodulatory treatment, an unmet need still exists for therapeutic strategies to prevent disease progression in hospitalized patients. "Pacritinib showed an excellent safety profile in our trial," he notes, "which is why further studies are needed to show how pacritinib or other agents like it might be beneficial to certain populations of patients with hyperinflammation that are at significant risk for poor outcomes."

JAK inhibitors are a class of medicines that inhibit the activity of one or more of the Janus kinase enzymes (JAK1, JAK2, JAK3, and TYK2) that are known to promote inflammation. They do this by transmitting signals from proteins known as cytokines that attach to receptors on immune cells to produce pro-inflammatory cytokines. JAK inhibitors interfere with this process by blocking the enzyme signaling pathway and calming the body's immune system. Pacritinib is a selective JAK inhibitor, meaning it affects the enzymes JAK2 and IRAK1, but spares JAK1. This distinction is important because JAK1 is responsible for the differentiation and activity of immune cells that contribute to antiviral and antitumor responses. IRAK1 or IL-1 receptor associated kinase 1 is integral to an inflammatory signaling pathway that culminates in NFκB activation which also regulates expression of inflammatory cytokines.

The study, known as PRE-VENT, was launched in June 2020 across 21 centers with 200 patients in the early stage of the pandemic. It became the first to demonstrate that certain inflammatory markers like Interleukin 6 (IL-6), a cytokine thought to be a main driver of inflammation, may predict which COVID-19 patients are most likely to respond to immunotherapy. In May 2022, the JAK1/2 inhibitor baricitinib became the first immunomodulatory drug to win approval from the FDA for COVID-19 (in combination with remdesivir), and in June 2021 the IL-6 inhibitor tocilizumab was granted emergency use authorization (EUA) for the treatment of COVID-19. Both of these agents directly and indirectly target the IL-6 signaling pathway and thus support the PRE-VENT finding that IL-6 elevation could be an important biomarker for determining which COVID-19 patients are most likely to benefit from certain immunomodulatory agents.

Pacritinib has been primarily studied in outpatient oncology settings, and following the completion of PRE-VENT was approved by the FDA for the treatment of patients with myelofibrosis, a chronic leukemia that disrupts the body's production of blood cells. Moreover, it is being investigated for other hematologic malignancies, including acute myeloid leukemia (AML), according to Dr. Mascarenhas, who led the phase 3 study that resulted in the drug's approval for myelofibrosis.

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Study: COVID pandemic reversed ten years of progress in reducing cardiovascular deaths in US​

Published December 6, 2022 | Originally published on MedicalXpress Breaking News-and-Events

The COVID-19 pandemic reversed a decade's worth of progress in reducing mortality from cardiovascular disease in the U.S., new research has found.

The international research team, including Keele University's Professor Mamas Mamas, studied data from the U.S. Center for Disease Control's (CDC) WONDER database, spanning 21 years between 1999 and 2020.

They wanted to see how cardiovascular mortality rates had changed and study trends in the death rates over that time. They discovered that cardiovascular deaths in 2020 were 4.6% higher than they were in 2019—representing over 62,000 excess deaths.

The highest relative increase was in adults under 55, who had a higher rate of mortality from cardiovascular disease than adults 55–74, and 75 and over.

There were also significant differences between different ethnic groups, with black adults experiencing the largest percentage increase in mortality at 10.6% (15,477 excess deaths) versus a 3.5% increase (42,907 excess deaths) for white adults. Hispanic adults also experienced a 9.4% increase in CV mortality (7,400 excess deaths) versus 4.3% for non-Hispanic adults (56,760 excess deaths).

There were also increases in mortality rates from certain conditions between 2019 and 2020, including ischemic heart disease, hypertensive disease, and cerebrovascular disease. However, deaths from heart failure did decline in the same time.

Professor Mamas Mamas, Professor of Cardiology at Keele University said, "Data from the U.S. reflects what has happened globally, the decades of falling cardiovascular mortality has been reversed by the COVID pandemic, both directly through infection with COVID and indirectly through the impact of the pandemic on cardiovascular services. Analogous to what has happened in the U.K., the greatest impact of the COVID pandemic on cardiovascular mortality has been felt by minority ethnic populations."

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Pfizer partners with Clear Creek Bio to develop oral COVID-19 drug​

Published December 7, 2022 | Originally published on Health News Online Report

Pfizer Inc and Clear Creek Bio Inc on Tuesday announced a collaboration to identify a potential drug candidate and develop a new class of oral treatment against COVID-19, as Pfizer seeks to expand its anti-infective pipeline.

Charlotte Allerton, Pfizer's chief scientific officer, said COVID-19 has "the potential to remain a global health concern for years to come".

Pfizer already has a COVID antiviral pill Paxlovid, which the drugmaker expects to generate about $22 billion in revenue this year.

Pfizer has been making various deals to boost its portfolio. This year, it has announced acquisitions of Biohaven Pharmaceutical Holding Co and Global Blood Therapeutics for $11.6 billion and $5.4 billion, respectively, and also launched a company with Roivant Sciences focused on an experimental bowel disease treatment.Under the agreement with Clear Creek Bio, the pharmaceutical giant will pay an undisclosed amount upfront as well as make additional milestone payments along with royalties on future product sales.

(Reporting by Khushi Mandowara in Bengaluru; Editing by Krishna Chandra Eluri)



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Severe COVID-19 Linked With Molecular Signatures of Brain Aging
FeaturedNeurologyNeuroscience·December 6, 2022


Summary: Gene usage in the brains of those who suffered severe COVID-19 infections was similar to that observed in the aging brain. Researchers say COVID-19 is associated with molecular signatures of brain aging.



Source: BIDMC

Although COVID-19 is primarily a respiratory disease, neurological symptoms have been described in many COVID-19 patients, including in recovered individuals.

Patients report symptoms including brain fog or lack of focused thinking, memory loss and depression, and scientists have demonstrated that patients with severe COVID-19 exhibit a drop in cognitive performance that mimics accelerated aging. But, the molecular evidence for COVID-19’s aging effects on the brain is lacking.

In a series of experiments, scientists at Beth Israel Deaconess Medical Center (BIDMC), found that gene usage in the brains of patients with COVID-19 is similar to those observed in aging brains.

Using a molecular profiling technique called RNA sequencing to measure the levels of every gene expressed in a particular tissue sample, the scientists assessed changes in gene expression profiles in the brains of COVID-19 patients and compared them to those changes observed in the brains of uninfected individuals.

The team’s analysis, published in Nature Aging, suggested that many biological pathways that change with natural aging in the brain also changed in patients with severe COVID-19.

“Ours is the first study to show that COVID-19 is associated with the molecular signatures of brain aging,” said co-first and co-corresponding author Maria Mavrikaki, PhD, an instructor of pathology at BIDMC and Harvard Medical School. “We found striking similarities between the brains of patients with COVID-19 and aged individuals.”



Mavrikaki and colleagues analyzed a total of 54 postmortem human frontal cortex tissue samples from adults 22 to 85 years old. Of these, 21 samples were from severe COVID-19 patients and one from an asymptomatic COVID-19 patient who died. These samples were age- and sex-matched to uninfected controls with no history of neurological or psychiatric disease.

The scientists also included an age-and sex- matched uninfected Alzheimer’s disease case for analysis as a control to a COVID-19 case which had co-morbid Alzheimer’s disease, as well as an additional independent control group of uninfected individuals with a history of intensive care or ventilator treatment.

“We observed that gene expression in the brain tissue of patients who died of COVID-19 closely resembled that of uninfected individuals 71 years old or older,” said co-first author Jonathan Lee, PhD, a postdoctoral research fellow at BIDMC and Harvard Medical School.

“Genes that were upregulated in aging were upregulated in the context of severe COVID-19; likewise, genes downregulated in aging were also downregulated in severe COVID-19.


In a series of experiments, scientists at Beth Israel Deaconess Medical Center (BIDMC), found that gene usage in the brains of patients with COVID-19 is similar to those observed in aging brains.


“While we did not find evidence that the SARS-CoV-2 virus was present in the brain tissue at the time of death, we discovered inflammatory patterns associated with COVID-19. This suggests that this inflammation may contribute to the aging-like effects observed in the brains of patients with COVID-19 and long COVID.”

“Given these findings, we advocate for neurological follow-up of recovered COVID-19 patients,” said senior and co-corresponding author Frank Slack, PhD, director of the Institute for RNA Medicine at BIDMC and the Shields Warren Mallinckrodt Professor of Medical Research at Harvard Medical School.



“We also emphasize the potential clinical value in modifying the factors associated with the risk of dementia — such as controlling weight and reducing excessive alcohol consumption — to reduce the risk or delay the development of aging-related neurological pathologies and cognitive decline.”

Better understanding of the molecular mechanisms underlying brain aging and cognitive decline in COVID-19 could lead to the development of novel therapeutics to address cognitive decline observed in COVID-19 patients. The team is now trying to understand what drives the aging-like effects in the brains of COVID-19 patients.


Author: Chloe Meck
Source: BIDMC
Contact: Chloe Meck – BIDMC

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