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Influence of Prior SARS-CoV-2 Infection on COVID-19 Severity: Evidence from the National COVID Cohort Collaborative
Influence of Prior SARS-CoV-2 Infection on COVID-19 Severity: Evidence from the National COVID Cohort Collaborative
Background As SARS-CoV-2 has transitioned from a pandemic to endemic disease, the majority of new infections have been among previously infected individuals. To manage the risks and benefits of ongoing COVID-19 policies, it is important to understand whether prior infection modifies the severity of subsequent infections. Methods We used data from first and second COVID-19 episodes in the National COVID Cohort Collaborative (N3C), a collection of health systems who provide de-identified electronic health records for research purposes. Our analysis was a sequential series of nested trial emulations. In the first of two analytic stages, we created a month-specific model of the probability of prior infection for each individual. In the second stage, we used an ordinal logistic regression with inverse probability weights calculated in the first stage to simulate a series of monthly trials comparing severity between the cohorts of first and second infections. In addition to cohort-wide effect estimates, we also conducted analyses among race/ethnicity, sex, and age subgroups. Results From an initial cohort of 7,446,481 combined first and second infections, we identified a cohort of 2,227,484 infections, among which 7.6% were second infections. Ninety-four percent of patients with two recorded infections experienced mild disease for both. The overall odds ratio (OR) for more severe disease with prior infection was 1.06 (95% confidence interval [CI]: 1.03 – 1.10). Monthly point estimates of the OR ranged from 0.56 (95% CI: 0.37 – 0.84) in October 2020 to 1.64 (95% CI: 1.33 – 2.00) in February 2023. In most subgroups, the effect of prior infection was significant. In 8 out of 10 subgroups, the maximum monthly OR occurred after the minimum monthly OR, suggesting that protection has waned throughout the pandemic. Conclusion Overall, prior infection was associated with a significant slightly elevated risk of severe disease. This effect varied month to month. As the pandemic proceeded, the effect of prior infection tended to evolve from generally protective during the pre-Omicron era to unprotective during the Omicron era. This points to the need for continued strategies to avert and minimize the harms of COVID-19, rather than relying upon immunity acquired through previous infection. Question Does prior infection with SARS-CoV-2 affect the severity of subsequent COVID-19 episodes? Findings We observed a mild protective effect of prior infection during the early and mid-stages of the pandemic that waned after the rise of the Omicron variants, ultimately resulting in loss of protection or a tendency toward more severe second infections. Meaning Prior infection alone is likely not enough to avert the worst public health harms of endemic SARS-CoV-2. Interventions to avoid infection and reduce the severity of COVID-19 will still be important in the post-pandemic era. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This project was sponsored by an award from the National COVID Cohort Collaborative's Public Health Answers to Speed Tractable Results (PHASTR) program and the National Center for Advancing Translational Sciences (Award #NCATS-P00438-E-2). ### 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 design was exempted from human subjects research review by the American Academy of Family Medicine institutional review board. 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, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data are available online through the National COVID Cohort Collaborative () with signed data use agreement and project approval.
Conclusion Overall, prior infection was associated with a significant slightly elevated risk of severe disease. This effect varied month to month. As the pandemic proceeded, the effect of prior infection tended to evolve from generally protective during the pre-Omicron era to unprotective during the Omicron era. This points to the need for continued strategies to avert and minimize the harms of COVID-19, rather than relying upon immunity acquired through previous infection.
·medrxiv.org·
Influence of Prior SARS-CoV-2 Infection on COVID-19 Severity: Evidence from the National COVID Cohort Collaborative
No evidence IV vitamin C aids critically ill COVID-19 patients
No evidence IV vitamin C aids critically ill COVID-19 patients
The median number of organ support–free days was 7 for the vitamin C group, compared with 10 for the control group (adjusted proportional odds ratio [OR], 0.88 [95% credible interval [CrI], 0.73 to 1.06]), and the posterior probabilities were 8.6% (efficacy), 91.4% (harm), and 99.9% (futility), the authors said. For patients who were not critically ill and received vitamin C, the median number of organ support–free days was 22, the same as the placebo group.
·cidrap.umn.edu·
No evidence IV vitamin C aids critically ill COVID-19 patients
Incidence of Type 1 Diabetes in Children and Adolescents During the COVID-19 Pandemic in Germany: Results From the DPV Registry
Incidence of Type 1 Diabetes in Children and Adolescents During the COVID-19 Pandemic in Germany: Results From the DPV Registry
OBJECTIVE. The aim of this study was to investigate the incidence of type 1 diabetes in children and adolescents during the coronavirus disease 2019 (COVID-19)
·diabetesjournals.org·
Incidence of Type 1 Diabetes in Children and Adolescents During the COVID-19 Pandemic in Germany: Results From the DPV Registry
SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas - PubMed
SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas - PubMed
Infection-related diabetes can arise as a result of virus-associated β-cell destruction. Clinical data suggest that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19), impairs glucose homoeostasis, but experimental evidence that SARS-CoV …
·pubmed.ncbi.nlm.nih.gov·
SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas - PubMed
A single-dose of intranasal vaccination with a live-attenuated SARS-CoV-2 vaccine candidate promotes protective mucosal and systemic immunity
A single-dose of intranasal vaccination with a live-attenuated SARS-CoV-2 vaccine candidate promotes protective mucosal and systemic immunity
npj Vaccines - A single-dose of intranasal vaccination with a live-attenuated SARS-CoV-2 vaccine candidate promotes protective mucosal and systemic immunity
·nature.com·
A single-dose of intranasal vaccination with a live-attenuated SARS-CoV-2 vaccine candidate promotes protective mucosal and systemic immunity
Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA suggest prolonged gastrointestinal infection
Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA suggest prolonged gastrointestinal infection
Natarajan et al. perform a longitudinal study of fecal SARS-CoV-2 RNA shedding in patients with mild to moderate COVID-19, revealing that patients can shed RNA for up to 7 months after infection, that shedding is associated with gastrointestinal symptoms, and that the gastrointestinal tract may be infected even after the respiratory infection has cleared.
·cell.com·
Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA suggest prolonged gastrointestinal infection
Intranasal mRNA-LNP vaccination protects hamsters from SARS-CoV-2 infection
Intranasal mRNA-LNP vaccination protects hamsters from SARS-CoV-2 infection
Intranasal vaccination represents a promising approach for preventing disease caused by respiratory pathogens by eliciting a mucosal immune response in the respiratory tract that may act as an early barrier to infection and transmission. This study investigated immunogenicity and protective efficacy of intranasally administered messenger RNA (mRNA)–lipid nanoparticle (LNP) encapsulated vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Syrian golden hamsters. Intranasal mRNA-LNP vaccination systemically induced spike-specific binding [immunoglobulin G (IgG) and IgA] and neutralizing antibodies. Intranasally vaccinated hamsters also had decreased viral loads in the respiratory tract, reduced lung pathology, and prevented weight loss after SARS-CoV-2 challenge. Together, this study demonstrates successful immunogenicity and protection against respiratory viral infection by an intranasally administered mRNA-LNP vaccine.
·science.org·
Intranasal mRNA-LNP vaccination protects hamsters from SARS-CoV-2 infection
Fortschritte in der Erforschung der SARS-CoV-2-Infektionen
Fortschritte in der Erforschung der SARS-CoV-2-Infektionen
DMZ – FORSCHUNG ¦ Lena Wallner ¦ Die kürzlich veröffentlichte Studie "Viral kinetics of sequential SARS-CoV-2 infections" hat uns spannende Erkenntnisse darüber geliefert, wie aufeinanderfolgende SARS-CoV-2-Infektionen verlaufen. Ein Team von Forschern, darunter Stephen M. Kissler, James A. Hay, Joseph R. Fauver, Christina Mack, Caroline G. Tai, Deverick J. Anderson, David D. Ho, Nathan D. Grubaugh und Yonatan H. Grad, hat diese bemerkenswerte Arbeit durchgeführt. Die Studie konzentrierte sich hauptsächlich darauf, wie sich eine vorherige SARS-CoV-2-Infektion auf den Verlauf späterer Infektionen auswirkt. Die Forscher analysierten beeindruckende 94.812 longitudinale RT-qPCR-Messungen von Abstrichen aus den Nasenvorhöfen und dem Oropharynx. Dabei stießen sie auf 71 Personen, die zwischen dem 11. März 2020 und dem 28. Juli 2022 zwei gut dokumentierte SARS-CoV-2-Infektionen erlebten. Die Ergebnisse dieser Studie sind äußerst aufschlussreich. Im Vergleich zur ersten Infektion zeigte sich, dass die zweite Infektion in der Regel eine kürzere Clearance-Zeit aufwies. Dies bedeutet, dass der Körper das Virus schneller beseitigte. Interessanterweise blieb das relative Verhältnis der Clearance-Zeit einer Person im Vergleich zu anderen, die mit derselben Virusvariante infiziert waren, in beiden Infektionen etwa gleich. Diese Ergebnisse deuten darauf hin, dass eine frühere SARS-CoV-2-Infektion, ähnlich wie eine Impfung, die Dauer nachfolgender akuter SARS-CoV-2-Infektionen hauptsächlich durch die Verkürzung der Clearance-Zeit verkürzt. Darüber hinaus scheint es ein inhärentes Element der Immunantwort oder einen anderen Faktor im Wirtsorganismus zu geben, der die Fähigkeit einer Person zur SARS-CoV-2-Clearance beeinflusst und über aufeinanderfolgende Infektionen hinweg bestehen bleibt. Diese Erkenntnisse sind von großer Bedeutung, da sie unser Verständnis darüber vertiefen, wie Immunität gegen SARS-CoV-2 funktioniert und wie dies den Verlauf von Infektionen beeinflussen kann. Sie könnten auch wichtige Auswirkungen auf klinische und öffentliche Gesundheitsrichtlinien haben. Dennoch müssen wir einige Einschränkungen dieser Studie berücksichtigen. Die untersuchte Kohorte war größtenteils jung, männlich und gesund. Es wurden keine Daten zu anderen Gesundheitsfaktoren erfasst, und die Ergebnisse könnten sich in verschiedenen Bevölkerungsgruppen unterscheiden. Die Forscher betonen die Notwendigkeit weiterer Studien, um ihre Ergebnisse zu bestätigen und die zugrunde liegenden Mechanismen besser zu verstehen. Trotzdem bietet diese Studie wertvolle Einblicke in die Dynamik aufeinanderfolgender SARS-CoV-2-Infektionen und deren Auswirkungen auf die Clearance-Zeit des Virus im Körper. Es wird spannend sein zu sehen, wie diese Erkenntnisse die Entwicklung von Impf- und Behandlungsstrategien beeinflussen werden. Wir können sicher sein, dass weitere Forschung folgen wird, um die Details dieser faszinierenden Entdeckungen zu klären.
·dmz-news.eu·
Fortschritte in der Erforschung der SARS-CoV-2-Infektionen
The effectiveness of COVID-19 vaccine in the prevention of post-COVID conditions: a systematic literature review and meta-analysis of the latest research | Antimicrobial Stewardship & Healthcare Epidemiology | Cambridge Core
The effectiveness of COVID-19 vaccine in the prevention of post-COVID conditions: a systematic literature review and meta-analysis of the latest research | Antimicrobial Stewardship & Healthcare Epidemiology | Cambridge Core
The effectiveness of COVID-19 vaccine in the prevention of post-COVID conditions: a systematic literature review and meta-analysis of the latest research - Volume 3 Issue 1
·cambridge.org·
The effectiveness of COVID-19 vaccine in the prevention of post-COVID conditions: a systematic literature review and meta-analysis of the latest research | Antimicrobial Stewardship & Healthcare Epidemiology | Cambridge Core
Assessing and improving the validity of COVID-19 autopsy studies - A multicentre approach to establish essential standards for immunohistochemical and ultrastructural analyses
Assessing and improving the validity of COVID-19 autopsy studies - A multicentre approach to establish essential standards for immunohistochemical and ultrastructural analyses
Since detection of SARS-CoV-2 in human autopsy tissues by IHC and EM is difficult and frequently incorrect, we propose criteria for a re-evaluation of available data and guidance for further investigations of direct organ effects by SARS-CoV-2.
·thelancet.com·
Assessing and improving the validity of COVID-19 autopsy studies - A multicentre approach to establish essential standards for immunohistochemical and ultrastructural analyses
Endothelial cell infection and endotheliitis in COVID-19
Endothelial cell infection and endotheliitis in COVID-19
Cardiovascular complications are rapidly emerging as a key threat in coronavirus disease 2019 (COVID-19) in addition to respiratory disease. The mechanisms underlying the disproportionate effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on patients with cardiovascular comorbidities, however, remain incompletely understood.1,2
·thelancet.com·
Endothelial cell infection and endotheliitis in COVID-19
Dr. Gustavo Aguirre-Chang on Twitter
Dr. Gustavo Aguirre-Chang on Twitter
🇩🇪2023-PROTOKOLLEMIT ANTIMIKROBIELLEN/ANTIVIRALENFÜRLONG-COVID, POST-COVID-SYNDROMPOST-V-SYNDROMME/CFSFIBROMYALGIEPOTS, TACHYKARDIEDYSAUTONOMIEKOGNITIVE BEEINTRÄCHTIGUNG,DEMENZAUTOIMMUNERKRANKUNGUND ANDERE MIT CHRONISCHER MÜDIGKEIT UND SCHMERZENhttps://t.co/N46RJlcztR pic.twitter.com/JQuy18NwlN— Dr. Gustavo Aguirre-Chang (@Aguirre1Gustavo) September 11, 2023
·twitter.com·
Dr. Gustavo Aguirre-Chang on Twitter
Could SARS-CoV-2 Have Bacteriophage Behavior or Induce the Activity of Other Bacteriophages?
Could SARS-CoV-2 Have Bacteriophage Behavior or Induce the Activity of Other Bacteriophages?
SARS-CoV-2 has become one of the most studied viruses of the last century. It was assumed that the only possible host for these types of viruses was mammalian eukaryotic cells. Our recent studies show that microorganisms in the human gastrointestinal tract affect the severity of COVID-19 and for the first time provide indications that the virus might replicate in gut bacteria. In order to further support these findings, in the present work, cultures of bacteria from the human microbiome and SARS-CoV-2 were analyzed by electron and fluorescence microscopy. The images presented in this article, in association with the nitrogen (15N) isotope-labeled culture medium experiment, suggest that SARS-CoV-2 could also infect bacteria in the gut microbiota, indicating that SARS-CoV-2 could act as a bacteriophage. Our results add new knowledge to the understanding of the mechanisms of SARS-CoV-2 infection and fill gaps in the study of the interactions between SARS-CoV-2 and non-mammalian cells. These findings could be useful in suggesting specific new pharmacological solutions to support the vaccination campaign.
·mdpi.com·
Could SARS-CoV-2 Have Bacteriophage Behavior or Induce the Activity of Other Bacteriophages?
Viral kinetics of sequential SARS-CoV-2 infections
Viral kinetics of sequential SARS-CoV-2 infections
Nature Communications - In this study, the authors compare the viral kinetics of first and second SARS-CoV-2 infections using data from an occupational surveillance scheme in the National...
In individuals with multiple infections, second infections were cleared more quickly than first infections. Furthermore, one’s relative speed of clearing infection roughly persisted across infections. Those with a relatively fast clearance speed in their first infection tended to have a relatively fast clearance speed in their second infection, and vice versa. Thus, while prior infection and vaccination can modulate a person’s viral kinetics in absolute terms, there may also exist some further immunological mechanism, conserved across sequential infections, that determines one’s strength of immune response against SARS-CoV-2 relative to others in the population.
A consistent finding between this and other studies on SARS-CoV-2 viral kinetics is that prior antigenic exposure, through infection or vaccination, tends to speed up viral clearance, and thus to reduce the duration of test positivity5,11,15. The duration of viral positivity has various consequences both for clinical management and for public health surveillance. For clinical management, test results should be interpreted in the context of a patient’s immune history, which can modulate both the extent and expected duration of viral shedding5,16. It may also be possible to adjust the recommended duration of post-infection isolation based on infection history.
·nature.com·
Viral kinetics of sequential SARS-CoV-2 infections