Covid19-Sources

Correspondence from The New England Journal of Medicine — Effects of Vaccination and Previous Infection on Omicron Infections in Children

Scientific Reports - Reevaluation of antibody-dependent enhancement of infection in anti-SARS-CoV-2 therapeutic antibodies and mRNA-vaccine antisera using FcR- and ACE2-positive cells

The latest from our team in @NatureMedicineThe long-term neurologic consequences of #COVID19A thread 🧵https://t.co/jmQMBvHAQnby @evanjxu @Biostayan @zalaly— Ziyad Al-Aly, MD (@zalaly) September 22, 2022

GeroScience - Severe cases of COVID-19 are characterized by an inflammatory burst, which is accompanied by multiorgan failure. The elderly population has higher risk for severe or fatal outcome for...

Anti-cardiac troponin antibodies have been studied in different types of clinical diseases and in healthy populations. A systematic review of published data on anti-troponin antibodies was carried out (search performed on PubMed, ISI Web of Knowledge ...

The emergence of SARS-CoV-2 variants in the Omicron lineage with large number of substitutions in the spike protein that can evade antibody neutralization has resulted in diminished vaccine efficacy and persistent transmission. One strategy to broaden vaccine-induced immunity is to administer bivalent vaccines that encode for spike proteins from both historical and newly-emerged variant strains. Here, we evaluated the immunogenicity and protective efficacy of two bivalent vaccines that recently were authorized for use in Europe and the United States and contain two mRNAs encoding Wuhan-1 and either BA.1 (mRNA-1273.214) or BA.4/5 (mRNA-1273.222) spike proteins. As a primary immunization series in BALB/c mice, both bivalent vaccines induced broader neutralizing antibody responses than the constituent monovalent vaccines (mRNA-1273 [Wuhan-1], mRNA-1273.529 [BA.1], and mRNA-1273-045 [BA.4/5]). When administered to K18-hACE2 transgenic mice as a booster at 7 months after the primary vaccination series with mRNA-1273, the bivalent vaccines induced greater breadth and magnitude of neutralizing antibodies compared to an mRNA-1273 booster. Moreover, the response in bivalent vaccine-boosted mice was associated with increased protection against BA.5 infection and inflammation in the lung. Thus, boosting with bivalent Omicron-based mRNA-1273.214 or mRNA-1273.222 vaccines enhances immunogenicity and protection against currently circulating SARS-CoV-2 strains. ### Competing Interest Statement M.S.D. is a consultant for Inbios, Vir Biotechnology, Senda Biosciences, Moderna, and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Vir Biotechnology, Emergent BioSolutions, and Moderna. G.-Y.C., G.S.-J., A.N., K.W., D.L., D.M.B., L.A., H.J., P.M., N.J.A., A.C., S.E. and D.K.E. are employees of and shareholders in Moderna Inc.

Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge currently available coronavirus disease 2019 vaccines and monoclonal antibody therapies through epitope change on the receptor binding domain of the viral spike glycoprotein. Hence, there is a specific urgent need for alternative antivirals that target processes less likely to be affected by mutation, such as the membrane fusion step of viral entry into the host cell. One such antiviral class includes peptide inhibitors, which block formation of the so-called heptad repeat 1 and 2 (HR1HR2) six-helix bundle of the SARS-CoV-2 spike (S) protein and thus interfere with viral membrane fusion. We performed structural studies of the HR1HR2 bundle, revealing an extended, well-folded N-terminal region of HR2 that interacts with the HR1 triple helix. Based on this structure, we designed an extended HR2 peptide that achieves single-digit nanomolar inhibition of SARS-CoV-2 in cell-based and virus-based assays without the need for modifications such as lipidation or chemical stapling. The peptide also strongly inhibits all major SARS-CoV-2 variants to date. This extended peptide is ∼100-fold more potent than all previously published short, unmodified HR2 peptides, and it has a very long inhibition lifetime after washout in virus infection assays, suggesting that it targets a prehairpin intermediate of the SARS-CoV-2 S protein. Together, these results suggest that regions outside the HR2 helical region may offer new opportunities for potent peptide-derived therapeutics for SARS-CoV-2 and its variants, and even more distantly related viruses, and provide further support for the prehairpin intermediate of the S protein.

It's early days yet. But growing evidence suggests COVID causes changes to your immune system that may put you at risk of other infectious diseases, writes Lara Herrero.

Excess mortality compared with pre-pandemic mortality patterns

Dozens of intranasally delivered vaccines targeting SARS-CoV-2 are in development. Could they pave the way for widespread nasal vaccination in the future?

The immune cells of patients who received hospital care for COVID-19 early in the pandemic were still affected six months later, shows a study conducted by researchers at Linköping University.

SARS-CoV-2 causes a wide spectrum of clinical manifestations and significant mortality. Studies investigating underlying immune characteristics are needed to understand disease pathogenesis and inform vaccine design. In this study, we examined immune cell subsets in hospitalized and nonhospitalized individuals. In hospitalized patients, many adaptive and innate immune cells were decreased in frequency compared with those of healthy and convalescent individuals, with the exception of an increase in B lymphocytes. Our findings show increased frequencies of T cell activation markers (CD69, OX40, HLA-DR, and CD154) in hospitalized patients, with other T cell activation/exhaustion markers (PD-L1 and TIGIT) remaining elevated in hospitalized and nonhospitalized individuals. B cells had a similar pattern of activation/exhaustion, with increased frequency of CD69 and CD95 during hospitalization followed by an increase in PD1 frequencies in nonhospitalized individuals. Interestingly, many of these changes were found to increase over time in nonhospitalized longitudinal samples, suggesting a prolonged period of immune dysregulation after SARS-CoV-2 infection. Changes in T cell activation/exhaustion in nonhospitalized patients were found to positively correlate with age. Severely infected individuals had increased expression of activation and exhaustion markers. These data suggest a prolonged period of immune dysregulation after SARS-CoV-2 infection, highlighting the need for additional studies investigating immune dysregulation in convalescent individuals.

Author summary Dendritic cells (DCs) recognize viral infections and trigger innate and adaptive antiviral immunity. COVID-19 severity is greatly influenced by the host immune response and modulation of DC generation and function after SARS-CoV-2 infection could play an important role in this disease. This study identifies a long-lasting reduction of DCs in the blood of COVID-19 patients and a functional impairment of these cells. Downregulation of costimulatory molecule CD86 and upregulation of inhibitory molecule PD-L1 in conventional DCs correlated with disease severity and were accompanied by a reduced ability to stimulate T cells. A higher frequency of CD163+ CD14+ cells in the DC3 subpopulation correlated with systemic inflammation suggesting that these cells may play a role in inflammatory responses of COVID-19 patients. Depletion and functional impairment of DCs beyond the acute phase of the disease may have consequences for susceptibility to secondary infections and clinical management of COVID-19 patients.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious respiratory virus which is responsible for the coronavirus disease 2019 (COVID-19) pandemic. It is increasingly clear that recovered individuals, even those who had mild COVID-19, can suffer from persistent symptoms for many months after infection, a condition referred to as “long COVID”, post-acute sequelae of COVID-19 (PASC), post-acute COVID-19 syndrome, or post COVID-19 condition. However, despite the plethora of research on COVID-19, relatively little is known about the molecular underpinnings of these long-term effects. Methods We have undertaken an integrated analysis of immune responses in blood at a transcriptional, cellular, and serological level at 12, 16, and 24 weeks post-infection (wpi) in 69 patients recovering from mild, moderate, severe, or critical COVID-19 in comparison to healthy uninfected controls. Twenty-one of these patients were referred to a long COVID clinic and  50% reported ongoing symptoms more than 6 months post-infection. Results Anti-Spike and anti-RBD IgG responses were largely stable up to 24 wpi and correlated with disease severity. Deep immunophenotyping revealed significant differences in multiple innate (NK cells, LD neutrophils, CXCR3+ monocytes) and adaptive immune populations (T helper, T follicular helper, and regulatory T cells) in convalescent individuals compared to healthy controls, which were most strongly evident at 12 and 16 wpi. RNA sequencing revealed significant perturbations to gene expression in COVID-19 convalescents until at least 6 months post-infection. We also uncovered significant differences in the transcriptome at 24 wpi of convalescents who were referred to a long COVID clinic compared to those who were not. Conclusions Variation in the rate of recovery from infection at a cellular and transcriptional level may explain the persistence of symptoms associated with long COVID in some individuals.

Evidence is growing there are changes to your immune system that may put you at risk of other infectious diseases.

Acute kidney injury (AKI) is associated with mortality in patients hospitalized with COVID-19, however, its incidence, geographic distribution, and temporal trends since the start of the pandemic are understudied. Methods: Electronic health record data were obtained from 53 health systems in the United States (US) in the National COVID Cohort Collaborative (N3C). We selected hospitalized adults diagnosed with COVID-19 between March 6th, 2020, and January 6th, 2022. AKI was determined with serum creatinine (SCr) and diagnosis codes. Time were divided into 16-weeks (P1-6) periods and geographical regions into Northeast, Midwest, South, and West. Multivariable models were used to analyze the risk factors for AKI or mortality. Results: Out of a total cohort of 306,061, 126,478 (41.0 %) patients had AKI. Among these, 17.9% lacked a diagnosis code but had AKI based on the change in SCr. Similar to patients coded for AKI, these patients had higher mortality compared to those without AKI. The incidence of AKI was highest in P1 (49.3%), reduced in P2 (40.6%), and relatively stable thereafter. Compared to the Midwest, the Northeast, South, and West had higher adjusted AKI incidence in P1, subsequently, the South and West regions continued to have the highest relative incidence. In multivariable models, AKI defined by either SCr or diagnostic code, and the severity of AKI was associated with mortality. Conclusions: Uncoded cases of COVID-19-associated AKI are common and associated with mortality. The incidence and distribution of COVID-19-associated AKI have changed since the first wave of the pandemic in the US.

India’s national COVID death totals remain undetermined. Using an independent nationally representative survey of 0.14 million (M) adults, we compared COVID mortality during the 2020 and 2021 viral waves to expected all-cause mortality. COVID constituted 29% (95% confidence interval, 28 to 31%) of deaths from June 2020 to July 2021, corresponding to 3.2 M (3.1 to 3.4) deaths, of which 2.7 M (2.6 to 2.9) occurred in April to July 2021 (when COVID doubled all-cause mortality). A subsurvey of 57,000 adults showed similar temporal increases in mortality, with COVID and non-COVID deaths peaking similarly. Two government data sources found that, when compared to prepandemic periods, all-cause mortality was 27% (23 to 32%) higher in 0.2 M health facilities and 26% (21 to 31%) higher in civil registration deaths in 10 states; both increases occurred mostly in 2021. The analyses find that India’s cumulative COVID deaths by September 2021 were six to seven times higher than reported officially.

Peer-reviewed finding is ‘the cherry on top’ for vaccines, which have already been shown to reduce infection and lower seriousness of illness, says researcher

Background: Emerging evidence suggests that worldwide, between 30% and 50% of those who are infected with COVID-19 experience long COVID (LC) symptoms. These symptoms create...

Eine aktuelle Auswertung des Wissenschaftlichen Instituts der AOK (WIdO) zeigt, dass seit Pandemiebeginn mehr als jeder Fünfte durchgängig erwerbstätige AOK-Versicherte im Zusammenhang mit einer akuten COVID-19-Erkankung ausgefallen ist. In der Folge waren 3,8 Prozent dieser Personen aufgrund einer Long-COVID- oder Post-COVID-Symptomatik arbeitsunfähig. Das entspricht etwa 0,9 Prozent aller erwerbstätigen AOK-Versicherten. Während eine akute COVID-19-Infektion mit durchschnittlich 9,5 krankheitsbedingten beruflichen Ausfalltagen verbunden war, sind es bei Beschäftigten mit einer anschließenden Long-COVID- oder Post-COVID-Symptomatik fast sieben Wochen. Detaillierte Auswertungen zeigen große Unterschiede hinsichtlich der verschiedenen Virusvarianten. So waren in der jüngsten, seit Frühjahr 2022 durch die Omikron-Variante geprägten Krankheitswelle nur 2,1 Prozent der Beschäftigten wegen Long-COVID oder Post-COVID krankgeschrieben, während es beim Vorherrschen der Delta-Variante noch 6,3 Prozent waren. „Damit gibt es aktuell zwar ein geringeres Risiko für eine mögliche anschließende Long-COVID bzw. Post-COVID-Symptomatik. Die erkrankten Beschäftigten waren aber auch in der Omikron-Welle noch schwer beeinträchtigt und fehlten durchschnittlich mehr als fünf Wochen am Arbeitsplatz. Da aktuell nur wenig über die COVID-bedingten Langzeitfolgen bekannt ist, sollte weiterhin gelten, sich und andere bestmöglich vor einer COVID-19-Infektion zu schützen“, so Helmut Schröder, stellvertretender Geschäftsführer des WIdO.

Full-term infants born to mothers with SARS-CoV-2 infection may be at increased risk for neurodevelopmental delays at 16 to 18 months of life. Infants born to the mothers with mild symptoms had no differences in outcomes during developmental screening than those born to asymptomatic mothers wi...

Group O has shown a consistent relationship with PCS, characterised by a more intense inflammatory burden than the other blood groups. Blood group O could be part of the immunological link between acute COVID-19 and PCS.

The results of the present study suggest that while the blood group A might have a role in increased susceptibility to the COVID-19 infection, the blood group O might be somewhat protective. However, once infected, blood group type does not seem to influence clinical outcome.

COVID-19 is being extensively studied, and much remains unknown regarding the long-term consequences of the disease on immune cells. The different arms of the immune system are interlinked, with humoral responses and the production of high-affinity antibodies being largely dependent on T cell immunity. Here, we longitudinally explored the effect COVID-19 has on T cell populations and the virus-specific T cells, as well as neutralizing antibody responses, for 6-7 months following hospitalization. The CD8+ TEMRA and exhausted CD57+ CD8+ T cells were markedly affected with elevated levels that lasted long into convalescence. Further, markers associated with T cell activation were upregulated at inclusion, and in the case of CD69+ CD4+ T cells this lasted all through the study duration. The levels of T cells expressing negative immune checkpoint molecules were increased in COVID-19 patients and sustained for a prolonged duration following recovery. Within 2-3 weeks after symptom onset, all COVID-19 patients developed anti-nucleocapsid IgG and spike-neutralizing IgG as well as SARS-CoV-2-specific T cell responses. In addition, we found alterations in follicular T helper (TFH) cell populations, such as enhanced TFH-TH2 following recovery from COVID-19. Our study revealed significant and long-term alterations in T cell populations and key events associated with COVID-19 pathogenesis.

Survey indicates that getting reinfected worsens symptoms of Long COVID or triggers a recurrence of symptoms in people who have recovered.

Correspondence from The New England Journal of Medicine — Duration of Shedding of Culturable Virus in SARS-CoV-2 Omicron (BA.1) Infection

As of May 31, 2022, there were 6·9 million reported deaths and 17·2 million estimated deaths from COVID-19, as reported by the Institute for Health Metrics and Evaluation (IHME; throughout the report, we rely on IHME estimates of infections and deaths; note that the IHME gives an estimated range, and we refer to the mean estimate). This staggering death toll is both a profound tragedy and a massive global failure at multiple levels. Too many governments have failed to adhere to basic norms of institutional rationality and transparency, too many people—often influenced by misinformation—have disrespected and protested against basic public health precautions, and the world's major powers have failed to collaborate to control the pandemic.

npj Vaccines - Association between BNT162b2 vaccination and reported incidence of post-COVID-19 symptoms: cross-sectional study 2020-21, Israel

Abstract. We investigated Long Covid incidence by vaccination status in a random sample of UK adults from April 2020 to November 2021. Persistent symptoms were

The B.1.1.529 (omicron) variant has rapidly supplanted most other SARS-CoV-2 variants. Using microfluidics-based antibody affinity profiling (MAAP), w…