Covid19-Sources

To establish a novel SARS-CoV-2 human challenge model, 36 volunteers aged 18-29 years without evidence of previous infection or vaccination were inoculated with 10 TCID50 of a wild-type virus (SARS-CoV-2/human/GBR/484861/2020) intranasally. Two participants were excluded from per pr...

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Recently, the Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been described as immune escape variant. Here, we analyzed samples from BA.1 (Omicron) convalescent patients with different constellations of prior SARS-CoV-2 immunity regarding vaccination and previous infection with a non-Omicron variant and determined titers of neutralizing antibodies against different SARS-CoV-2 variants (D614G, Alpha, Beta, Delta, Gamma, Omicron). We found high neutralizing antibody titers against all variants for vaccinated individuals after BA.1 breakthrough infection or for individuals after infection with a pre-omicron variant followed by BA.1 infection. In contrast, samples from naive unvaccinated individuals after BA.1 infection mainly contained neutralizing antibodies against BA.1 but only occasionally against the other variants. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any 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: The ethics committee (EC) of the Medical University of Innsbruck has approved the study with EC numbers 1064/2021 and 1191/2021. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the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.

SARS-CoV-2 Delta and Omicron strains are the most globally relevant variants of concern (VOCs). While individuals infected with Delta are at risk to develop severe lung disease[1][1], Omicron infection causes less severe disease, mostly upper respiratory symptoms[2][2],[3][3]. The question arises whether rampant spread of Omicron could lead to mass immunization, accelerating the end of the pandemic. Here we show that infection with Delta, but not Omicron, induces broad immunity in mice. While sera from Omicron-infected mice only neutralize Omicron, sera from Delta-infected mice are broadly effective against Delta and other VOCs, including Omicron. This is not observed with the WA1 ancestral strain, although both WA1 and Delta elicited a highly pro-inflammatory cytokine response and replicated to similar titers in the respiratory tracts and lungs of infected mice as well as in human airway organoids. Pulmonary viral replication, pro-inflammatory cytokine expression, and overall disease progression are markedly reduced with Omicron infection. Analysis of human sera from Omicron and Delta breakthrough cases reveals effective cross-variant neutralization induced by both viruses in vaccinated individuals. Together, our results indicate that Omicron infection enhances preexisting immunity elicited by vaccines, but on its own may not induce broad, cross-neutralizing humoral immunity in unvaccinated individuals. ### Competing Interest Statement A.M.S. and J.A.D. are inventors on a patent application filed by the Gladstone Institutes and the University of California that covers the method and composition of SARS-CoV-2 VLP preparations for RNA transduction and expression in cells. J.A.D. is a cofounder of Caribou Biosciences, Editas Medicine, Scribe Therapeutics, Intellia Therapeutics, and Mammoth Biosciences. J.A.D. is a scientific advisory board member of Vertex, Caribou Biosciences, Intellia Therapeutics, eFFECTOR Therapeutics, Scribe Therapeutics, Mammoth Biosciences, Synthego, Algen Biotechnologies, Felix Biosciences, The Column Group, and Inari. J.A.D. is a director at Johnson & Johnson and Tempus and has research projects sponsored by Biogen, Pfizer, AppleTree Partners, and Roche. C.Y.C. is the director of the UCSF-Abbott Viral Diagnostics and Discovery Study and receives research support from Abbott Laboratories. C.Y.C. also receives support for SARS-CoV-2 research unrelated to this study from Mammoth Biosciences. ### Funding Statement This research is funded by grants from the National Institutes of Health: NIAID R37AI083139 to M.O., NIH/NIAID (F31 AI164671-01) to I.P.C., NHLBI U54HL147127 to M.M. A.M.S is supported by Natural Sciences and Engineering Research Council of Canada (NSERC PDF-533021-2019). M.O. and W.C.G also received support from the Roddenberry Foundation and M.O. received a gift from Pam and Ed Taft. J.A.D. acknowledges support from the National Institutes of Health (R21AI59666) and support from the Howard Hughes Medical Institute and the Gladstone Institutes. N.R. acknowledges support from the Van Auken Private Foundation, David Henke, and Pamela and Edward Taft; and Awards #2164 and #2208 from Fast Grants, a part of Emergent Ventures at the Mercatus Center, George Mason University. CYC acknowledges support by the Innovative Genomics Institute (IGI) at UC Berkeley and UC San Francisco, US Centers for Disease Control and Prevention contract 75D30121C10991, Abbott Laboratories, and the Sandler Program for Breakthrough Biomedical Research at UCSF. The group also acknowledges support from the James B. Pendleton Charitable Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### 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: Ethics committee/IRB of Advarra and UCSF gave 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 work are contained in the manuscript [1]: #ref-1 [2]: #ref-2 [3]: #ref-3

Scientific Reports - COVID-19 reinfections among naturally infected...

SARS-CoV-2 infects less than 1% of cells in the human body, yet it can cause severe damage in a variety of organs. Thus, deciphering the non-cell autonomous effects of SARS-CoV-2 infection is imperative for understanding the cellular and molecular disruption it elicits. Neurological and cognitive defects are among the least understood symptoms of COVID-19 patients, with olfactory dysfunction being their most common sensory deficit. Here, we show that both in humans and hamsters SARS-CoV-2 infection causes widespread downregulation of olfactory receptors (OR) and of their signaling components. This non-cell autonomous effect is preceded by a dramatic reorganization of the neuronal nuclear architecture, which results in dissipation of genomic compartments harboring OR genes. Our data provide a potential mechanism by which SARS-CoV-2 infection alters the cellular morphology and the transcriptome of cells it cannot infect, offering insight to its systemic effects in olfaction and beyond.

Characteristics of people testing positive for COVID-19 from the Coronavirus (COVID-19) Infection Survey.

Introduction During the course of the COVID-19 pandemic, there have been suggestions that various techniques could be employed to improve the fit and, therefore, the effectiveness of face masks. It is well recognized that improving fit tends to improve mask effectiveness, but whether these fit modifiers are reliable remains unexplored. In this study, we assess a range of common “fit hacks” to determine their ability to improve mask performance. Methods Between July and September 2020, qualitative fit testing was performed in an indoor living space. We used quantitative fit testing to assess the fit of both surgical masks and KN95 masks, with and without ‘fit hacks’, on four participants. Seven fit hacks were evaluated to assess impact on fit. Additionally, one participant applied each fit hack multiple times to assess how reliable hacks were when reapplied. A convenience of four participants took part in the study, three females and one male with a head circumference range of 54 to 60 centimetres. Results and discussion The use of pantyhose, tape, and rubber bands were effective for most participants. A pantyhose overlayer was observed to be the most effective hack. High degrees of variation were noted between participants. However, little variation was noted within participants, with hacks generally showing similar benefit each time they were applied on a single participant. An inspection of the fit hacks once applied showed that individual facial features may have a significant impact on fit, especially the nose bridge. Conclusions Fit hacks can be used to effectively improve the fit of surgical and KN95 masks, enhancing the protection provided to the wearer. However, many of the most effective hacks are very uncomfortable and unlikely to be tolerated for extended periods of time. The development of effective fit-improvement solutions remains a critical issue in need of further development.

Biological researchers in Switzerland released a preprint in late December providing very useful information about the immune escape properties of Omicron vs. previous infection and/or vaccination with respect to neutralizing antibodies titers. In this blog post, I summarize the key results. They looked at neutralizing antibody titers (Nabs) for convalescent plasma from people previously infected with Delta, Gamma, Beta, Alpha, and from 2020 "wild type" versions of the virus (non-VOC) vs. each v

The Omicron SARS-CoV-2 variant of concern (VOC lineage B.1.1.529), which became dominant in many countries during early 2022, includes several subvariants with strikingly different genetic characteristics. Several countries, including Denmark, have observed the two Omicron subvariants: BA.1 and BA.2. In Denmark the latter has rapidly replaced the former as the dominant subvariant. Based on nationwide Danish data, we estimate the transmission dynamics of BA.1 and BA.2 following the spread of Omicron VOC within Danish households in late December 2021 and early January 2022. Among 8,541 primary household cases, of which 2,122 were BA.2, we identified a total of 5,702 secondary infections among 17,945 potential secondary cases during a 1-7 day follow-up period. The secondary attack rate (SAR) was estimated as 29% and 39% in households infected with Omicron BA.1 and BA.2, respectively. We found BA.2 to be associated with an increased susceptibility of infection for unvaccinated individuals (Odds Ratio (OR) 2.19; 95%-CI 1.58-3.04), fully vaccinated individuals (OR 2.45; 95%-CI 1.77-3.40) and booster-vaccinated individuals (OR 2.99; 95%-CI 2.11-4.24), compared to BA.1. We also found an increased transmissibility from unvaccinated primary cases in BA.2 households when compared to BA.1 households, with an OR of 2.62 (95%-CI 1.96-3.52). The pattern of increased transmissibility in BA.2 households was not observed for fully vaccinated and booster-vaccinated primary cases, where the OR of transmission was below 1 for BA.2 compared to BA.1. We conclude that Omicron BA.2 is inherently substantially more transmissible than BA.1, and that it also possesses immune-evasive properties that further reduce the protective effect of vaccination against infection, but do not increase its transmissibility from vaccinated individuals with breakthrough infections. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Frederik Plesner Lyngse: Independent Research Fund Denmark (Grant no. 9061-00035B.); Novo Nordisk Foundation (grant no. NNF17OC0026542); the Danish National Research Foundation through its grant (DNRF-134) to the Center for Economic Behavior and Inequality (CEBI) at the University of Copenhagen. Laust Hvas Mortensen is supported in part by grants from the Novo Nordisk Foundation (grant no. NNF17OC0027594, NNF17OC0027812). ### 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 national registers only. According to Danish law, ethics approval is not needed for this type of research. All data management and analyses were carried out on the Danish Health Data Authority's restricted research servers with project number FSEID-00004942. The study only contains aggregated results and no personal data. The study is, therefore, not covered by the European General Data Protection Regulation (GDPR). 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 used in this study are available under restricted access due to Danish data protection legislation. 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. We performed no data collection or sequencing specifically for this study. Consensus genome data from the Danish cases are routinely shared publicly at GISAID (www.gisaid.org).

Brain fog, headaches, blood pressure swings are being probed by NIH and other researchers

German scientists are researching nasal spray vaccines against coronavirus, which they hope will provide better protection than traditional vaccines.

The following is a summary of some recent studies on COVID-19. They include research that warrants further study to corroborate the findings and that has yet to be certified by peer review.

The Hyderabad-based vaccine maker conducted phase 2 trials on 650 volunteers

Background: Excess mortality quantifies the overall mortality impact of a pandemic. Mortality data have been accessible for many countries in recent decades, but few continuous data have been available for longer periods. Objective: To assess the historical dimension of the COVID-19 pandemic in 2020 for 3 countries with reliable death count data over an uninterrupted span of more than 100 years. Design: Observational study. Setting: Switzerland, Sweden, and Spain, which were militarily neutral and not involved in combat during either world war and have not been affected by significant changes in their territory since the end of the 19th century. Participants: Complete populations of these 3 countries. Measurements: Continuous series of recorded deaths (from all causes) by month from the earliest available year (1877 for Switzerland, 1851 for Sweden, and 1908 for Spain) were jointly modeled with annual age group–specific death and total population counts using negative binomial and multinomial models, which accounted for temporal trends and seasonal variability of prepandemic years. The aim was to estimate the expected number of deaths in a pandemic year for a nonpandemic scenario and the difference in observed and expected deaths aggregated over the year. Results: In 2020, the number of excess deaths recorded per 100 000 persons was 100 (95% credible interval [CrI], 60 to 135) for Switzerland, 75 (CrI, 40 to 105) for Sweden, and 155 (CrI, 110 to 195) for Spain. In 1918, excess mortality was 6 to 7 times higher. In all 3 countries, the peaks of monthly excess mortality in 2020 were greater than most monthly excess mortality since 1918, including many peaks due to seasonal influenza and heat waves during that period. Limitation: Historical vital statistics might be affected by minor completeness issues before the beginning of the 20th century. Conclusion: In 2020, the COVID-19 pandemic led to the second-largest infection-related mortality disaster in Switzerland, Sweden, and Spain since the beginning of the 20th century. Primary Funding Source: Foundation for Research in Science and the Humanities at the University of Zurich, Swiss National Science Foundation, and National Institute of Allergy and Infectious Diseases.

New evidence further strengthens the case for childhood vaccination against COVID-19

Nature Communications - Antibodies (Abs) targeting highly conserved epitopes are important tools against emerging virus variants. Here, the authors characterize Abs that recognize a cryptic epitope...

mRNA RBD S1 strategy

Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 μg group, 13 [65%] of 20 in the 10 μg group, 17 [85%] of 20 in the 15 μg group, 19 [95%] of 20 in the 20 μg group, 16 [100%] of 16 in the 25 μg group; p0·0001). The incidence of grade 3 systemic adverse events were none (0%) of 20 in the 5 μg group, three (15%) of 20 in the 10 μg group, six (30%) of 20 in the 15 μg group, seven (35%) of 20 in the 20 μg group, five (31%) of 16 in the 25 μg group, and none (0%) of 20 in the placebo group (p=0·0013). As expected, the majority of fever resolved in the first 2 days after vaccination for all groups. The incidence of solicited systemic adverse events was similar after administration of ARCoV as a first or second vaccination. Humoral immune responses including anti-RBD IgG and neutralising antibodies increased significantly 7 days after the second dose and peaked between 14 and 28 days thereafter. Specific T-cell response peaked between 7 and 14 days after full vaccination. 15 μg induced the highest titre of neutralising antibodies, which was about twofold more than the antibody titre of convalescent patients with COVID-19.

Prominently accountable for the upsurge of COVID-19 cases as the world attempts to recover from the previous two waves, Omicron has further threatened the conventional therapeutic approaches....

A Phase III Confirmatory Study of K-237 - Full Text View.

Viruses interact extensively with the host molecular machinery, but the underlying mechanisms are poorly understood. Bacteriophage T7 recruits the small protein thioredoxin of the Escherichia coli host as an essential processivity factor for the viral DNA polymerase. We challenged the phage t …

Knowing the age-specific rates at which individuals infected with SARS-CoV-2 develop severe and critical disease is essential for designing public policy, for epidemic modeling, and for individual risk evaluation. In this study, we present the first estimates of these rates using multi-country serology studies, and data on hospital admissions and mortality from early to mid-2020. We integrated data from those sources using a Bayesian model that accounts for the high heterogeneity between data sources and for the uncertainty associated to the estimates reported from each data source. Our results show that the risk of severe and critical disease increases exponentially with age, but much less steeply than the risk of fatal illness. Importantly, the estimated rate of severe disease outcome in adolescents is between one and two orders of magnitude larger than the reported rate of vaccine side-effects, showing how these estimates are relevant for health policy. Finally, we validate our results by showing that they are in close agreement with the estimates obtained from an indirect method that uses reported infection fatality rates estimates and hospital mortality data.

Compared to non-VOC SARS-CoV-2 strains, the adjusted elevation in risk associated with N501Y-positive variants was 52% (43-62%) for hospitalization; 89% (67-116%) for ICU admission; and 51% (30-74%) for death. Increases with Delta variant were more pronounced: 108% (80-138%) for hospitalization; 234% (164-331%) for ICU admission; and 132% (47-230%) for death. Interpretation: The progressive increase in transmissibility and virulence of SARS-CoV-240 VOCs will result in a significantly larger, and more deadly, pandemic than would have occurred41 in the absence of VOC emergence.

COVID-19 is characterized by excessive production of pro-inflammatory cytokines and acute lung damage associated with patient mortality. While multipl…

An in-depth analysis of IFNs in COVID-19 reveals differences in their roles based on anatomical location, viral load, age, and disease severity. In the upper respiratory tract, high levels of IFN-III are protective and result in mild disease in spite of higher SARS-CoV-2 viral burden, while the lower airways of patients with severe COVID-19 demonstrate elevated IFN-I and IFN-III, cell death, and a reduction in IFN-stimulated genes.

BACKGROUND Waning of COVID-19 vaccine protection and emergence of SARS-CoV-2 Omicron (B.1.1.529) variant have expedited efforts to scale up booster vaccination. This study compared protection afforded by booster doses of the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines, compared to the primary series of only two doses in Qatar, during a large, rapidly growing Omicron wave. METHODS In a population of 2,232,224 vaccinated persons with at least two doses, two matched, retrospective cohort studies were implemented to investigate effectiveness of booster vaccination against symptomatic SARS-CoV-2 infection and against COVID-19 hospitalization and death, up to January 9, 2022. Association of booster status with infection was estimated using Cox proportional-hazards regression models. RESULTS For BNT162b2, cumulative symptomatic infection incidence was 2.9% (95% CI: 2.8-3.1%) in the booster-dose cohort and 5.5% (95% CI: 5.3-5.7%) in the primary-series cohort, after 49 days of follow-up. Adjusted hazard ratio for symptomatic infection was 0.50 (95% CI: 0.47-0.53). Booster effectiveness relative to primary series was 50.1% (95% CI: 47.3-52.8%). For mRNA-1273, cumulative symptomatic infection incidence was 1.9% (95% CI: 1.7-2.2%) in the booster-dose cohort and 3.5% (95% CI: 3.2-3.9%) in the primary-series cohort, after 35 days of follow-up. The adjusted hazard ratio for symptomatic infection was 0.49 (95% CI: 0.43-0.57). Booster effectiveness relative to primary series was 50.8% (95% CI: 43.4-57.3%). There were fewer cases of severe COVID-19 in booster-dose cohorts than in primary-series cohorts, but cases of severe COVID-19 were rare in all cohorts. CONCLUSIONS mRNA booster vaccination is associated with modest effectiveness against symptomatic infection with Omicron. The development of a new generation of vaccines targeting a broad range of variants may be warranted. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The authors are grateful for institutional salary support from the Biomedical Research Program and the Biostatistics, Epidemiology, and Biomathematics Research Core, both at Weill Cornell Medicine-Qatar, as well as for institutional salary support provided by the Ministry of Public Health, Hamad Medical Corporation, and Sidra Medicine. The authors are also grateful for the Qatar Genome Programme and Qatar University Biomedical Research Center for institutional support for the reagents needed for the viral genome sequencing. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the article. Statements made herein are solely the responsibility of the authors. ### 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: Hamad Medical Corporation and Weill Cornell Medicine-Qatar Institutional Review Boards approved this retrospective study with waiver of informed consent. 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 dataset of this study is a property of the Qatar Ministry of Public Health that was provided to the researchers through a restricted-access agreement that prevents sharing the dataset with a third party or publicly. Future access to this dataset can be considered through a direct application for data access to Her Excellency the Minister of Public Health (). Aggregate data are available within the manuscript and its Supplementary information.

Das Paul-Ehrlich-Institut hat in Zusammenarbeit mit der Universität Frankfurt am Main die Langzeit-Antikörperreaktion nach SARS-CoV-2-Infektion bei 828 Personen mit verschiedenen COVID-19-Schweregraden untersucht. Gemessen wurden bindende Antikörper gegen unterschiedliche SARS-CoV-2-Zielantigene, neutralisierende Antikörper und die Stärke der Antikörperbindung (Antikörperavidität). Sensitivität, Kinetik und Dauer des Antikörpernachweises waren abhängig von detektierter Antikörperklasse, Testdesign, Zielantigen des Anti-SARS-CoV-2-Antikörpertests sowie von Antikörperavidität und COVID-19-Schweregrad.

Background Prior studies have documented reliable associations between SARS-CoV-2 infection and adverse cognitive impact in older adults. The current study sought to determine whether SARS-CoV-2 infection and COVID-19 symptom severity are associated with cognitive dysfunction among young adults and middled-aged adults in the general population. Method The Canadian COVID-19 Experiences Project (CCEP) survey involves 1,958 adults with equal representation of vaccinated and vaccine hesitant adults between the ages of 18 and 54 years. The sample comprised 1,958 adults with a mean age of 37 years ( SD =10.4); 60.8% were female. The primary outcome was symptoms of cognitive dysfunction assessed via an abbreviated form of the Barkley Deficits in Executive Functioning Scale (BDEFS) and performance on a validated decision-making task. Results Young and middle-aged adults with a positive SARS-CoV-2 infection history reported a significantly higher number of symptoms of executive dysfunction ( M adj =1.89, SE =0.08, CI : 1.74, 2.04; n =175) than their non-infected counterparts ( M adj =1.63, SE =0.08, CI : 1.47,1.80; n =1,599; β=0.26, p =.001). Among those infected, there was a dose-response relationship between COVID-19 symptom severity and level of executive dysfunction, with moderate (β=0.23, CI : 0.003-0.46) and very/extremely severe (β= 0.69, CI : 0.22-1.16) COVID-19 symptoms being associated with significantly greater dysfunction, compared to asymptomatic. These effects remained reliable and of similar magnitude after controlling for age, sex, vaccination status, income, and geographic region, and after removal of those who had been intubated during hospitalization. Similar effects were found for the decision-making task. Conclusions Positive SARS-CoV-2 infection history and COVID-19 symptom severity are associated with executive dysfunction among young and middle-aged adults with no history of medically induced coma. These findings are evident on self-reported and task-related indicators of cognitive function. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was supported by an operating grant to P. Hall (PI), G. Fong (co-PI) and S. Hitchman (co-I) by the Canadian Institutes for Health Research (CIHR), Institute for Population and Public Health (GA3-177733). ### 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 protocol was reviewed by and received approval from the University of Waterloo Office of Research Ethics. 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