Covid19-Sources

Novel intranasal COVID-19 vaccine, CoviLivTM, induced strong cellular immune response in healthy adults against many conserved proteins in known variants of SARS-CoV-2, in particular, a peptide pool 99% Omicron BA.2. Spike protein focused vaccines have shown lower protection against viral mutants.1 Unlike other spike-only vaccine approaches that may need to re-formulate as COVID evolves, this…

SARS-CoV-2 infection is associated with a surprising number of morbidities. Uncanny similarities with amyloid-disease associated blood coagulation and fibrinolytic disturbances together with neurologic and cardiac problems led us to investigate the amyloidogenicity of the SARS-CoV-2 spike protein (S-protein). Amyloid fibril assays of peptide library mixtures and theoretical predictions identified seven amyloidogenic sequences within the S-protein. All seven peptides in isolation formed aggregates during incubation at 37 °C. Three 20-amino acid long synthetic spike peptides (sequence 192–211, 601–620, 1166–1185) fulfilled three amyloid fibril criteria: nucleation dependent polymerization kinetics by ThT, Congo red positivity, and ultrastructural fibrillar morphology. Full-length folded S-protein did not form amyloid fibrils, but amyloid-like fibrils with evident branching were formed during 24 h of S-protein coincubation with the protease neutrophil elastase (NE) in vitro. NE efficiently cleaved S-protein, rendering exposure of amyloidogenic segments and accumulation of the amyloidogenic peptide 194–203, part of the most amyloidogenic synthetic spike peptide. NE is overexpressed at inflamed sites of viral infection. Our data propose a molecular mechanism for potential amyloidogenesis of SARS-CoV-2 S-protein in humans facilitated by endoproteolysis. The prospective of S-protein amyloidogenesis in COVID-19 disease associated pathogenesis can be important in understanding the disease and long COVID-19.

The rising case numbers of the SARS-CoV-2 Omicron BA.4, BA.5, and BA.2.12.1 subvariants has generated serious concern about the course of the pandemic. Here we examine the neutralization resistance, infectivity, processing, and fusogenicity of spike from the BA.4/5 and BA.2.12.1 SARS-CoV-2 variants compared with other Omicron subvariants and Delta. Critically, we found that the new Omicron subvariants BA.4/5 and BA.2.12.1 were more resistant to neutralization by mRNA-vaccinated and boosted health care worker sera and Omicron-BA.1-wave patient sera than were the BA.1 and BA.2 variants. Interestingly, Delta-wave patient sera neutralized more efficiently against not only Delta but also BA.4/5 and BA.2.12.1 variants that also contain substitutions at position L452, similar to Delta. The BA.4/5 and BA.2.12.1 variants also exhibited higher fusogenicity, and increased spike processing, dependent on the L452 substitution. These results highlight the key role of the L452R and L452Q mutations in BA.4/5 and BA.2.12.1 subvariants. ### Competing Interest Statement The authors have declared no competing interest.

Derzeit haben in Deutschland erst 5,8% der Bevölkerung eine vierte Impfung erhalten, und auch bei den über 60-jährigen sind es gerade mal 17,5%.Vor diesem Hintergrund hier ein Thread mit einem Überblick…#ImpfenSchuetzt#COVID19#LongCovid#coronavirushttps://t.co/epYiNhiYIt pic.twitter.com/dUROI7Wdd3— Ralf Wittenbrink (@RWittenbrink) May 21, 2022

We conducted a distributed network cohort study using primary care records from the Netherlands, Italy, Spain, and the UK, and outpatient specialist records from Germany. The Spanish database was linked to hospital admissions. Participants were followed up from the date of a diagnosis of COVID-19 or positive RT-PCR test for SARS-CoV-2 (index date) for 90 days. The primary study outcomes were venous thromboembolic events, arterial thromboembolic events, and death, all over the 90 days from the index date. We estimated cumulative incidences for the study outcomes. Multistate models were used to calculate adjusted hazard ratios (HRs) for the association between venous thromboembolism or arterial thromboembolism occurrence and risks of hospitalisation or COVID-19 fatality. Findings Overall, 909 473 COVID-19 cases and 32 329 patients hospitalised with COVID-19 on or after Sept 1, 2020, were studied. The latest index dates across the databases ranged from Jan 30, 2021, to July 31, 2021. Cumulative 90-day incidence of venous thromboembolism ranged from 0·2% to 0·8% among COVID-19 cases, and up to 4·5% for those hospitalised. For arterial thromboembolism, estimates ranged from 0·1% to 0·8% among COVID-19 cases, increasing to 3·1% among those hospitalised. Case fatality ranged from 1·1% to 2·0% among patients with COVID-19, rising to 14·6% for hospitalised patients. The occurrence of venous thromboembolism in patients with COVID-19 was associated with an increased risk of death (adjusted HRs 4·42 [3·07–6·36] for those not hospitalised and 1·63 [1·39–1·90] for those hospitalised), as was the occurrence of arterial thromboembolism (3·16 [2·65–3·75] and 1·93 [1·57–2·37]). Interpretation Risks of venous thromboembolism and arterial thromboembolism were up to 1% among COVID-19 cases, and increased with age, among males, and in those who were hospitalised. Their occurrence was associated with excess mortality, underlying the importance of developing effective treatment strategies that reduce their frequency.

It's not a problem entirely solved by highly vaccinated population or Omicron though - over 400,000 people developed Long Covid from Omicron (and that's not including the big March wave!). 5/8 pic.twitter.com/EwKkKwXXxe— Prof. Christina Pagel 🇺🇦 (@chrischirp) May 17, 2022

Background. A growing number of long COVID cases after infection have been reported. By definition, long COVID is the condition whereby affected individ

Omicron s escape to vaccine-induced systemic antibody responses has been shown in several studies in Omicron-infected patients and vaccine controls. In the present study we compared mucosal antibody response to Omicron to mucosal antibody response to ancestral strain and Delta variant. This was done on nasal epithelial lining fluid (NELF) prospectively collected in 84 otherwise healthy healthcare workers who had never exhibited PCR-documented COVID-19 and had received three doses of the Pfizer-BioNTech COVID-19 mRNA vaccine. NELF was collected prior to Omicron detection in the geographical area of inclusion. We show that NELF antibodies from vaccinated individuals were less efficient at inhibiting the binding of the Omicron Spike protein to ACE-2 compared to those of Delta or the ancestral strain. These findings may explain the increased risk of onward transmission of Omicron, consistent with its successful global displacement of Delta in countries with a high vaccination coverage. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Research reported in this publication was supported by grants from the Conseil Departemental des Alpes Maritimes, the Metropole Nice Cote dAzur. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the CPP Sud Mediterranee V ethics committee I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

The World Health Organisation (WHO) has been tracking the impact of COVID-19 as the pandemic has evolved over time. Aggregate case and death numbers are being reported to the WHO and the data have been made publicly available at https://covid19.who.int/. For a number of reasons, these data do not provide a complete picture of the health burden attributable to COVID-19, nor of how many lives have been lost due to the pandemic. Some deaths that are attributable to COVID-19 have not been certified as such because tests had not been conducted prior to death. There have also been variations in the death certification rules countries have applied in regards to COVID-19 (Riffe and Acosta, 2021). The impact of the pandemic is far reaching. Beyond the deaths directly attributable to it are those that can be linked to the conditions that have prevailed since the pandemic began and have led to some health systems being overwhelmed or some patients avoiding healthcare. In countries where COVID-19 spread was limited, due to lockdown measures or otherwise, some potential causes of death have decreased, such as those attributable to air pollution, or traffic accidents, or from other communicable diseases such as influenza like illness, resulting in negative excess or deficit deaths (Kung, Doppen, Black, Hills, and Kearns, 2020; Karlinsky and Kobak, 2021).

Risk Factors for SARS-CoV-2 in Cats and Dogs

Berlin – In Deutschland haben sich nach Schätzungen der Bundesregierung schon 50 Millionen Menschen mit dem Coronavirus SARS-CoV-2 infiziert. Bundesweit sind... #Coronainfektionen #Deutschland

Early anecdotes about Paxlovid’s effects on long COVID are intriguing, but no one’s testing them in clinical trials yet.

There is ample evidence that masking and social distancing are effective in reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. However, due to the complexity of airborne disease transmission, it is difficult to quantify their effectiveness, especially in the case of one-to-one exposure. Here, we introduce the concept of an upper bound for one-to-one exposure to infectious human respiratory particles and apply it to SARS-CoV-2. To calculate exposure and infection risk, we use a comprehensive database on respiratory particle size distribution; exhalation flow physics; leakage from face masks of various types and fits measured on human subjects; consideration of ambient particle shrinkage due to evaporation; and rehydration, inhalability, and deposition in the susceptible airways. We find, for a typical SARS-CoV-2 viral load and infectious dose, that social distancing alone, even at 3.0 m between two speaking individuals, leads to an upper bound of 90% for risk of infection after a few minutes. If only the susceptible wears a face mask with infectious speaking at a distance of 1.5 m, the upper bound drops very significantly; that is, with a surgical mask, the upper bound reaches 90% after 30 min, and, with an FFP2 mask, it remains at about 20% even after 1 h. When both wear a surgical mask, while the infectious is speaking, the very conservative upper bound remains below 30% after 1 h, but, when both wear a well-fitting FFP2 mask, it is 0.4%. We conclude that wearing appropriate masks in the community provides excellent protection for others and oneself, and makes social distancing less important.

2 ABSTRACT1 None of the available evaluations of the inhaled air carbon dioxide (CO 2) concentration, while wearing face2 masks, used professional, real-time capnography with water-removal tubing. We measured the end-tidal CO2 using professional side-stream capnography, with water-removing tubing (Rad-97™ capnograph), at rest, (1) without masks, (2) wearing a surgical mask, and (3) wearing a FFP2 respirator, in 102 healthy volunteers aged 10-90 years, from the general population of Ferrara province, Italy. The inhaled air CO2 concentration was then computed as: ((mask volume × end-tidal CO 2) + ((tidal volume - mask volume) × ambient air CO 2 )) / tidal volume). The mean CO 2 concentration was 4965±1047 ppm with surgical masks, and 9396±2254 ppm with FFP2 respirators. The proportion of the sample showing a CO2 concentration higher than the 5000 ppm acceptable exposure threshold recommended for workers was 40.2% while wearing surgical masks, 99.0% while wearing FFP2 respirators. The mean blood oxygen saturation remained 96%, and the mean end-tidal CO2 33 mmHg. Adjusting for age, gender, BMI, and smoking, the inhaled air CO2 concentration significantly increased with increasing respiratory rate (with a mean of 10,143±2782 ppm among the participants taking 18 or more breaths per minute, while wearing FFP2 respirators), and was higher among the minors, who showed a mean CO2 concentration of 12,847±2898 ppm, while wearing FFP2 respirators. If these results will be confirmed, the current guidelines on mask-wearing could be updated to integrate recommendations for slow breathing and a more targeted use when contagion risk is low.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes coronavirus disease (COVID-19) is one of the most serious global health crises in recent history. COVID-19 patient symptoms range from life-threatening to mild and asymptomatic, which presents unique problems in identifying, q …

Bei schweren COVID-19-Verläufen kommt es zu einer Überreaktion des Immunsystems mit einer unkontrollierten Überproduktion an Entzündungsmediatoren, einem sogenannten Zytokinsturm (Chen et al., 2020).

Several independent datasets suggest blood type A is over-represented and type O under-represented among COVID-19 patients. However, blood group antig…

Three COVID-19 vaccines in the US have been released for sale by the FDA under Emergency Use Authorization (EUA) based on a clinical trial design employing a surrogate primary endpoint for health, severe infections with COVID-19. This clinical trial design has been proven dangerously misleading. Many fields of medicine, oncology for example, have abandoned the use of disease specific endpoints for the primary endpoint of pivotal clinical trials (cancer deaths for example) and have adopted “all cause mortality or morbidity” as the proper scientific endpoint of a clinical trial. Pivotal clinical trial data from the 3 marketed COVID-19 vaccines was reanalyzed using “all cause severe morbidity", a scientific measure of health, as the primary endpoint. “All cause severe morbidity” in the treatment group and control group was calculated by adding all severe events reported in the clinical trials. Severe events included both severe infections with COVID-19 and all other severe adverse events in the treatment arm and control arm respectively. This analysis gives reduction in severe COVID-19 infections the same weight as adverse events of equivalent severity. Results prove that none of the vaccines provide a health benefit and all pivotal trials show a statically significant increase in “all cause severe morbidity" in the vaccinated group compared to the placebo group. The Moderna immunized group suffered 3,042 more severe events than the control group (p=0.00001). The Pfizer data was grossly incomplete but data provided showed the vaccination group suffered 90 more severe events than the control group (p=0.000014), when only including “unsolicited” adverse events. The Janssen immunized group suffered 264 more severe events than the control group (p=0.00001). These findings contrast the manufacturers’ inappropriate surrogate endpoints: Janssen claims that their vaccine prevents 6 cases of severe COVD-19 requiring medical attention out of 19,630 immunized; Pfizer claims their vaccine prevents 8 cases of severe COVID-19 out of 21,720 immunized; Moderna claims its vaccine prevents 30 cases of severe COVID-19 out of 15,210 immunized. Based on this data it is all but a certainty that mass COVID-19 immunization is hurting the health of the population in general. Scientific principles dictate that the mass immunization with COVID-19 vaccines must be halted immediately because we face a looming vaccine induced public health catastrophe.

Nature Microbiology - A longitudinal analysis of viral expansion and clearance rates in 60 individuals sampled daily during acute infection reveals high inter-individual variation in...

I'm very concerned that we are seeing rebound of active, replicating and likely infectious virus occurring frequently after COVID-19 oral treatmentThis may call for a 8 or 10 day course of treatment rather than 5 daysHere's what I think is happening and what we should do1/— Michael Mina (@michaelmina_lab) May 2, 2022

Many studies have shown that patients with Coronavirus disease 2019 (COVID-19) have different degrees of liver injury. However, the mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invasion into the liver are still not fully ...

Background Most patients with coronavirus disease 2019 demonstrate liver function damage. In this study, the laboratory test data of patients with moderate coronavirus disease 2019 were used to establish and evaluate an early prediction model to assess the risk of liver function damage. Methods Clinical data and the first laboratory examination results of 101 patients with moderate coronavirus disease 2019 were collected from four hospitals’ electronic medical record systems in Jilin Province, China. Data were randomly divided into training and validation sets. A logistic regression analysis was used to determine the independent factors related to liver function damage in patients in the training set to establish a prediction model. Model discrimination, calibration, and clinical usefulness were evaluated in the training and validation sets. Results The logistic regression analysis showed that plateletcrit, retinol-binding protein, and carbon dioxide combining power could predict liver function damage (P

Liver function derangements have been reported in COVID-19, but reported rates are variable. Treatment in intensive care units (ICU) has become a major challenge; therefore, early recognition of severe and critical cases is absolutely essential for timely triaging of patients. Objectives: to review incidence of acute liver injury in patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Patients and methods: obtaining clinical records and laboratory results prospectively from one hundred patients with PCR-confirmed or radiography-confirmed COVID-19, who are admitted to the isolation wards and emergency departments of three different hospitals in Baghdad from 1st of December 2020 to 31st of March 2021. Results: The mean age group of study sample was (61.2±12.36) years, males formed 59%. GI manifestations were recorded in 47% of total cases, and were statistically correlated with disease severity (P value 0.001). Wide range of LFT abnormalities are found in patients with COVID-19, but none of which showed statistical significance in relation to disease severity. When LFT results were reviewed in relation to previous comorbidities, GGT was found to be statistically correlated with the underlying CLD (P value 0.001), and ALP with both underlying CLD and DM (P values 0.001 and 0.029, respectively) and even in the absence of underlying comorbidity (P value 0.006). Conclusion: Liver enzyme derangements are increasingly reported in patients with COVID-19, but are not necessarily correlate with disease severity. Cholestatic picture of liver enzyme derangement is a more commonly recorded manifestation.

Fever and cough are the most common clinical symptoms of coronavirus disease 2019 (COVID-19), but complications (such as pneumonia, respiratory distress syndrome, and multiorgan failure) can occur in people with additional comorbidities. COVID-19 may ...

Background Characteristics of laboratory findings of COVID-19 patients are of great significance for diagnosis and treatment. Studies that have analysed the variations in hepatic profile in correlation with the inflammatory markers in SARS-CoV-2 are limited. Methods We retrospectively analysed liver function tests and inflammatory markers of 170 admitted patients with confirmed COVID-19 in the tertiary care centre, Post Graduate Institute of Medical Education and Research (PGIMER), India, using Roche Cobas Autoanalyzer. Results Number of patients with normal liver enzyme levels were 63 (41.5%), while with raised levels of any of the liver enzymes were 89 (58.5%), out of which 43 (48.31%) had liver injury which manifested as increased severity in terms of intensive care unit (ICU) requirement (p=0.0005). Significantly raised levels of liver enzymes and liver injury were observed with age (p

Objective: While pediatric population has largely remained free of severe COVID-19, in some cases SARS-CoV-2 infection has been associated with complications like Multiple Inflammatory Syndrome in children (MIS-C). We mention another unique presentation subsequent to asymptomatic infection of SARS-CoV-2, a unique form of hepatitis designated by us as COVID-19 Associated Hepatitis in Children (CAH-C). The contrasting clinical presentations, temporal association and viral parameters of CAH-C cases, to the MIS-C cases are presented here. Methods: As a retrospective and follow-up observational study we reviewed all children testing positive for SARS-CoV-2 during study period. Children presenting with sudden onset of hepatitis, elevated transaminases, non-obstructive jaundice, lacking marked inflammatory responses and without evidence of (a) other known causes of acute hepatitis or previous underlying liver disease (b) multi-system involvement were classified as CAH-C, are described here. Results: Among 475 children who tested positive, 47 patients presented with hepatitis, 37 patients who had features of CAH-C, having symptoms of hepatitis only, with un-elevated inflammatory markers and uneventful recovery following supportive treatment. Whereas remaining 10 MIS-C hepatitis had protracted illness, multiple system involvement, required admission to critical care, and had mortality of 30%. Conclusion: With the emergence of newer variants of concern (VOC) including the Delta variant which predominated the second wave of infections in India and has now spread to more than 142 countries with changing presentations, CAH-C might be one of them. Cases of such new entities need to be identified early and differentiated from other emerging syndromes in children during the ongoing pandemic for preventing adversities by timely intervention. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement No external grant has been used for the study. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the IRB and the institutional human ethics committee, Bundelkhand Medical College, Sagar registration number ECR/1252/Inst/MP/2019. The follow-up and analysis work was performed after the ethical approval was granted by the institutional human ethics committee of our institute. Wide reference letter IEC/BMC/80/21. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data related to the manuscript is available with the author. [https://main.icmr.nic.in/sites/default/files/press\_realease\_files/ICMR\_PR\_IgG\_Elisa\_30052020.pdf][1] [1]: https://main.icmr.nic.in/sites/default/files/press_realease_files/ICMR_PR_IgG_Elisa_30052020.pdf

The likelihood of reporting long COVID symptoms four weeks after a first coronavirus (COVID-19) infection compatible with the Omicron BA.1 or BA.2 variants, compared with the Delta variant, using data from the COVID-19 Infection Survey.

SARS-CoV-2 variants of concern (VOCs) possess mutations that confer resistance to neutralizing antibodies within the Spike protein and are associated with breakthrough infection and reinfection. By contrast, less is known about the escape from CD8+ T cell-mediated immunity by VOC. Here, we demonstrated that VOCs retain similar MHC-I downregulation capacity compared to the ancestral virus. However, VOCs exhibit a greater ability to suppress type I IFN than the ancestral virus. Although VOCs possess unique mutations within the ORF8 gene, which suppresses MHC-I expression, none of these mutations enhanced the ability of ORF8 to suppress MHC-I expression. Notably, MHC-I upregulation was strongly inhibited after the ancestral SARS-CoV-2 infection in vivo . Collectively, our data suggest that the ancestral SARS-CoV-2 already possesses an intrinsically potent MHC-I evasion capacity, and that further adaptation by the variants was not observed. ### Competing Interest Statement The authors have declared no competing interest.

In this study, @MiyuMoriyama et al investigate how well SARS-CoV-2 variants of concern (VOC) suppress MHC I needed for recognition by cytotoxic T cells. This question is important to understand how well the virus limits CD8 killing 🧵(1/) @biorxivpreprint https://t.co/TLvnB7NotN pic.twitter.com/EkCq51MlfN— Prof. Akiko Iwasaki (@VirusesImmunity) May 7, 2022

Nature - Omicron relatives called BA.4 and BA.5 are behind a fresh wave of COVID-19 in South Africa, and could be signs of a more predictable future for SARS-CoV-2.