Covid19-Sources

Deaths reported within 28 days of testing positive were 61% (95% confidence interval: 56% to 65%) lower in suspected COVID-19 reinfection than primary infection cases. In the unvaccinated cohort, reinfections were associated with 49% (37% to 58%) lower odds of hospital admission in cases aged 50 to 65 years in the population not identified at risk of complication for COVID-19, and 34% (17% to 48%) in those at risk. ICU admission at reinfection compared to primary infection decreased 76% (55% to 87%). Individuals at risk and those aged below 50 years, who received at least 1 dose of vaccine against COVID-19, were 62% (39% to 74%) and 58% (24% to 77%) less likely to get admitted to hospital at reinfection, respectively.

Eine neue Studie soll zeigen, dass #SARSCoV2 auch T-Zellen infiziert und tötet. Aus immunologischer Sicht gibt es allerdings Probleme, die diesen Schluss nicht zulassen.#COVID19 ist eine ernste Erkrankung, aber kein "Airborne AIDS". Kurzer🧵1/nhttps://t.co/9RmC3KZuUv— Alexander Schäfer 🇪🇺🇺🇦 (@Immuno_Alex) March 14, 2022

AbstractBackground. Case series without control groups suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may result in cogniti

I spoke with @LaurenPelley about a new preprint comparing survival of Omicron vs. ancestral strain on surfaces. TLDR Omicron is more stable (probably in aerosols too, may contribute to greater transmissibility, my graph of their data👇) /1 pic.twitter.com/ECR8nrhjuP— Linsey Marr (@linseymarr) March 11, 2022

Figures have soared by 1.2m in two years of pandemic as long Covid takes its toll

Cross-Variant Neutralizing Antibodies after SARS-CoV-2 Breakthrough Infections

Nature Medicine - Individuals with COVID-19 are at increased long-term risk for a wide range of cardiovascular disorders, even for individuals who were not hospitalized during the acute phase of...

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2–3 months later), integrated with clinical data and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific auto-antibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes, exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time, leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly replaced the Delta variant as a dominating SARS-CoV-2 variant because of natural selection, which favors the variant with higher infectivity and stronger vaccine breakthrough ability. Omicron has three lineages or subvariants, BA.1 (B.1.1.529.1), BA.2 (B.1.1.529.2), and BA.3 (B.1.1.529.3). Among them, BA.1 is the currently prevailing subvariant. BA.2 shares 32 mutations with BA.1 but has 28 distinct ones. BA.3 shares most of its mutations with BA.1 and BA.2 except for one. BA.2 is found to be able to alarmingly reinfect patients originally infected by Omicron BA.1. An important question is whether BA.2 or BA.3 will become a new dominating “variant of concern”. Currently, no experimental data has been reported about BA.2 and BA.3. We construct a novel algebraic topology-based deep learning model trained with tens of thousands of mutational and deep mutational data to systematically evaluate BA.2’s and BA.3’s infectivity, vaccine breakthrough capability, and antibody resistance. Our comparative analysis of all main variants namely, Alpha, Beta, Gamma, Delta, Lambda, Mu, BA.1, BA.2, and BA.3, unveils that BA.2 is about 1.5 and 4.2 times as contagious as BA.1 and Delta, respectively. It is also 30% and 17-fold more capable than BA.1 and Delta, respectively, to escape current vaccines. Therefore, we project that Omicron BA.2 is on its path to becoming the next dominating variant. We forecast that like Omicron BA.1, BA.2 will also seriously compromise most existing mAbs, except for sotrovimab developed by GlaxoSmithKline.

The frequency and extent of persistent sequelae in children and adolescents after infection with SARS-CoV-2 still needs to be comprehensively determined. In this cross-sectional clinical trial, we used non-invasive, label-free morphologic and free-breathing phase-resolved functional low-field magnetic resonance imaging (LF-MRI) to identify pulmonary changes in children and adolescents from 5 to

Nature - SARS-CoV-2 is associated with changes in brain structure in UK Biobank

Brain scans before and after infection showed more loss of gray matter and tissue damage, mostly in areas related to smell, in people who had Covid than in those who did not.

Scientific Reports - mRNA vaccine-induced antibodies more effective than natural immunity in neutralizing SARS-CoV-2 and its high affinity variants

COVID-19: Testicular Damage & Reduced Sperm CountThe first study looked at the testicular damage and reduced fertility caused by COVID-19 ( https://t.co/NdVlf7KB8c ). H/T: @__philipn__ 🧵1/— Dr. Jeff Gilchrist (@jeffgilchrist) March 7, 2022

We compared the risk of severe COVID-19 during two periods 2021 and 2022 when Delta and Omicron, respectively, were the dominating virus variants in Scania county, Sweden. We adjusted for differences in sex, age, comorbidities, prior infection and vaccination. Risk of severe disease from Omicron was markedly lower among vaccinated cases. It was also lower among the unvaccinated but remained high ( 5%) for older people and middle-aged men with two or more comorbidities. Efforts to increase vaccination uptake should continue.

Importance: There is limited evidence on the effectiveness of the BNT162b2 vaccine for children, particularly those 5-11 years and after the Omicron variant's emergence. Objective: To estimate BNT162b2 vaccine effectiveness against COVID cases and hospitalizations among children 5-11 years and 12-17 years during December, 2021 and January, 2022. Design: Analyses of cohorts constructed from linked statewide immunization, laboratory testing, and hospitalization databases. Setting/Participants: New York State children 5-17 years. Main outcomes/measures: New laboratory-confirmed COVID-19 cases and hospitalizations. Comparisons were made using the incidence rate ratio (IRR), comparing outcomes by vaccination status, and estimated vaccine effectiveness (VE: 1-[1/IRR]). Results: From December 13, 2021 to January 30, 2022, among 852,384 fully-vaccinated children 12-17 years and 365,502 children 5-11 years, VE against cases declined from 66% (95% CI: 64%, 67%) to 51% (95% CI: 48%, 54%) for those 12-17 years and from 68% (95% CI: 63%, 72%) to 12% (95% CI: 6%, 16%) for those 5-11 years. During the January 24-30 week, VE for children 11 years was 11% (95%CI -3%, 23%) and for those age 12 was 67% (95% CI: 62%, 71%). VE against hospitalization declined changed from 85% (95% CI: 63%, 95%) to 73% (95% CI: 53%, 87%) for children 12-17 years, and from 100% (95% CI: -189%, 100%) to 48% (95% CI: -12%, 75%) for those 5-11 years. Among children newly fully-vaccinated December 13, 2021 to January 2, 2022, VE against cases within two weeks of full vaccination for children 12-17 years was 76% (95% CI: 71%, 81%) and by 28-34 days it was 56% (95% CI: 43%, 63%). For children 5-11, VE against cases declined from 65% (95% CI: 62%, 68%) to 12% (95% CI: 8%, 16%) by 28-34 days. Conclusions and Relevance: In the Omicron era, the effectiveness against cases of BNT162b2 declined rapidly for children, particularly those 5-11 years. However, vaccination of children 5-11 years was protective against severe disease and is recommended. These results highlight the potential need to study alternative vaccine dosing for children and the continued importance layered protections, including mask wearing, to prevent infection and transmission. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any external funding. ### 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: Institutional Review Board (IRB) of the New York State Department of Health determined this surveillance activity to be necessary for public health work, and therefore, waived the need for ethical approval for this work. 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

Prolonged detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and recurrence of PCR-positive tests have been widely reported in patients after recovery from COVID-19, but some of these patients do not appear to shed infectious virus. We investigated the possibility that SARS-CoV-2 RNAs can be reverse-transcribed and integrated into the DNA of human cells in culture and that transcription of the integrated sequences might account for some of the positive PCR tests seen in patients. In support of this hypothesis, we found that DNA copies of SARS-CoV-2 sequences can be integrated into the genome of infected human cells. We found target site duplications flanking the viral sequences and consensus LINE1 endonuclease recognition sequences at the integration sites, consistent with a LINE1 retrotransposon-mediated, target-primed reverse transcription and retroposition mechanism. We also found, in some patient-derived tissues, evidence suggesting that a large fraction of the viral sequences is transcribed from integrated DNA copies of viral sequences, generating viral–host chimeric transcripts. The integration and transcription of viral sequences may thus contribute to the detection of viral RNA by PCR in patients after infection and clinical recovery. Because we have detected only subgenomic sequences derived mainly from the 3′ end of the viral genome integrated into the DNA of the host cell, infectious virus cannot be produced from the integrated subgenomic SARS-CoV-2 sequences. Continuous or recurrent positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR tests have been reported in samples taken from patients weeks or months after recovery from an initial infection (1–17). Although bona fide reinfection with SARS-CoV-2 after recovery has recently been reported (18), cohort-based studies with subjects held in strict quarantine after they recovered from COVID-19 suggested that at least some “re-positive” cases were not caused by reinfection (19, 20). Furthermore, no replication-competent virus was isolated or spread from these PCR-positive patients (1–3, 5, 6, 12, 16), and the cause for the prolonged and recurrent production of viral RNA remains unknown. SARS-CoV-2 is a positive-stranded RNA virus. Like other beta-coronaviruses (SARS-CoV-1 and Middle East respiratory syndrome-related coronavirus), SARS-CoV-2 employs an RNA-dependent RNA polymerase to replicate its genomic RNA and transcribe subgenomic RNAs (21–24). One possible explanation for the continued detection of SARS-CoV-2 viral RNA in the absence of virus reproduction is that, in some cases, DNA copies of viral subgenomic RNAs may integrate into the DNA of the host cell by a reverse transcription mechanism. Transcription of the integrated DNA copies could be responsible for positive PCR tests long after the initial infection was cleared. Indeed, nonretroviral RNA virus sequences have been detected in the genomes of many vertebrate species (25, 26), with several integrations exhibiting signals consistent with the integration of DNA copies of viral mRNAs into the germline via ancient long interspersed nuclear element (LINE) retrotransposons (reviewed in ref. 27). Furthermore, nonretroviral RNA viruses such as vesicular stomatitis virus or lymphocytic choriomeningitis virus (LCMV) can be reverse transcribed into DNA copies by an endogenous reverse transcriptase (RT), and DNA copies of the viral sequences have been shown to integrate into the DNA of host cells (28–30). In addition, cellular RNAs, for example the human APP transcripts, have been shown to be reverse-transcribed by endogenous RT in neurons with the resultant APP fragments integrated into the genome and expressed (31). Human LINE1 elements (∼17% of the human genome), a type of autonomous retrotransposons, which are able to retro-transpose themselves and other nonautonomous elements such as Alu, are a source of cellular endogenous RT (32–34). Endogenous LINE1 elements have been shown to be expressed in aged human tissues (35) and LINE1-mediated somatic retrotransposition is common in cancer patients (36, 37). Moreover, expression of endogenous LINE1 and other retrotransposons in host cells is commonly up-regulated upon viral infection, including SARS-CoV-2 infection (38–40). In this study, we show that SARS-CoV-2 sequences can integrate into the host cell genome by a LINE1-mediated retroposition mechanism. We provide evidence that the integrated viral sequences can be transcribed and that, in some patient samples, the majority of viral transcripts appear to be derived from integrated viral sequences.

Preclinical studies of COVID-19 mRNA vaccine BNT162b2, developed by Pfizer and BioNTech, showed reversible hepatic effects in animals that received the BNT162b2 injection. Furthermore, a recent study showed that SARS-CoV-2 RNA can be reverse-transcribed and integrated into the genome of human cells. In this study, we investigated the effect of BNT162b2 on the human liver cell line Huh7 in vitro. Huh7 cells were exposed to BNT162b2, and quantitative PCR was performed on RNA extracted from the cells. We detected high levels of BNT162b2 in Huh7 cells and changes in gene expression of long interspersed nuclear element-1 (LINE-1), which is an endogenous reverse transcriptase. Immunohistochemistry using antibody binding to LINE-1 open reading frame-1 RNA-binding protein (ORFp1) on Huh7 cells treated with BNT162b2 indicated increased nucleus distribution of LINE-1. PCR on genomic DNA of Huh7 cells exposed to BNT162b2 amplified the DNA sequence unique to BNT162b2. Our results indicate a fast up-take of BNT162b2 into human liver cell line Huh7, leading to changes in LINE-1 expression and distribution. We also show that BNT162b2 mRNA is reverse transcribed intracellularly into DNA in as fast as 6 h upon BNT162b2 exposure.

Scientific Reports - Communicate hope to motivate the public during the COVID-19 pandemic

Geographical clustering of the earliest known COVID-19 cases and the proximity of positive environmental samples to live-animal vendors suggest that the Huanan Seafood Wholesale Market in Wuhan was the site of origin of the COVID-19 pandemic.

The newly found Omicron SARS-CoV-2 variant of concern has rapidly spread worldwide. Omicron carries numerous mutations in key regions and is associated with increased transmissibility and immune escape. The variant has recently been divided into four subvariants with substantial genomic differences, in particular between Omicron BA.1 and BA.2. With the surge of Omicron subvariants BA.1 and BA.2, a large number of reinfections from earlier cases has been observed, raising the question of whether BA.2 specifically can escape the natural immunity acquired shortly after a BA.1 infection. To investigate this, we selected a subset of samples from more than 1,8 million cases of infections in the period from November 22, 2021, until February 11, 2022. Here, individuals with two positive samples, more than 20 and less than 60 days apart, were selected. From a total of 187 reinfection cases, we identified 47 instances of BA.2 reinfections shortly after a BA.1 infection, mostly in young unvaccinated individuals with mild disease not resulting in hospitalization or death. In conclusion, we provide evidence that Omicron BA.2 reinfections do occur shortly after BA.1 infections but are rare. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Not applicable ### 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 conducted using data from the Danish COVID-19 surveillance. According to Danish law, ethics approval is not needed for this type of research but approved by the Legal Advisory Board at Statens Serum Institut, a Danish sector research institute under the auspices of the Danish Ministry of Health. The publication only contains aggregated results without personal data. Therefore, the publication is in compliance with the European General Data Protection Regulations. 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 The data are available for research upon reasonable request to the Danish Health Data Authority and Statens Serum Institut and within the framework of the Danish data protection legislation and any required permission from authorities. Consensus genome data from the Danish cases are routinely shared publicly at GISAID (www.gisaid.org), including information on reinfections.

New light is being shed on the colossal human impact of the pandemic, not from government health reports, but from the financial accounts of giant corporations.

Vaccine spike antigen and mRNA persist for two months in lymph node germinal centers...

Autopsies are an important tool in medicine, dissecting disease pathophysiology and causes of death. In COVID-19, autopsies revealed e.g., the effects…

But since I know some folks prefer their evidence in the format of an animated GIF, I'm happy to oblige. Sorry, it lacks the cutesy punch of an out-of-context scene from a Will Ferrell movie, but I'll just have to hope actual scientific evidence is equally entertaining. pic.twitter.com/lZB70oni0O— Dr. Angela Rasmussen (@angie_rasmussen) February 26, 2022

Scientific Reports - Prospective postmortem evaluation of 735 consecutive SARS-CoV-2-associated death cases

A national autopsy registry can provide multicentre quantitative information on COVID-19 deaths on a national level, supporting medical research, political decision-making and public discussion.

Nature - Massive study shows a long-term, substantial rise in risk of cardiovascular disease, including heart attack and stroke, after a SARS-CoV-2 infection.

The aim of this study was to determine clinical outcomes of older patients with coronavirus (COVID-19) who received a combination of vitamin D, magnes…

The vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID-19 progression especially by decreasing the Acute …