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1.
PLoS Biol ; 20(2): e3001531, 2022 02.
Article in English | MEDLINE | ID: covidwho-1686076

ABSTRACT

Identifying the potential for SARS-CoV-2 reinfection is crucial for understanding possible long-term epidemic dynamics. We analysed longitudinal PCR and serological testing data from a prospective cohort of 4,411 United States employees in 4 states between April 2020 and February 2021. We conducted a multivariable logistic regression investigating the association between baseline serological status and subsequent PCR test result in order to calculate an odds ratio for reinfection. We estimated an odds ratio for reinfection ranging from 0.14 (95% CI: 0.019 to 0.63) to 0.28 (95% CI: 0.05 to 1.1), implying that the presence of SARS-CoV-2 antibodies at baseline is associated with around 72% to 86% reduced odds of a subsequent PCR positive test based on our point estimates. This suggests that primary infection with SARS-CoV-2 provides protection against reinfection in the majority of individuals, at least over a 6-month time period. We also highlight 2 major sources of bias and uncertainty to be considered when estimating the relative risk of reinfection, confounders and the choice of baseline time point, and show how to account for both in reinfection analysis.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Reinfection/immunology , Adolescent , Adult , Aged , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing , Humans , Logistic Models , Middle Aged , Polymerase Chain Reaction , Prospective Studies , Reinfection/prevention & control , SARS-CoV-2/immunology , Seroepidemiologic Studies , Time Factors , United States/epidemiology , Workplace/statistics & numerical data , Young Adult
2.
Viruses ; 13(11)2021 11 06.
Article in English | MEDLINE | ID: covidwho-1502534

ABSTRACT

Obesity is a key correlate of severe SARS-CoV-2 outcomes while the role of obesity on risk of SARS-CoV-2 infection, symptom phenotype, and immune response remain poorly defined. We examined data from a prospective SARS-CoV-2 cohort study to address these questions. Serostatus, body mass index, demographics, comorbidities, and prior COVID-19 compatible symptoms were assessed at baseline and serostatus and symptoms monthly thereafter. SARS-CoV-2 immunoassays included an IgG ELISA targeting the spike RBD, multiarray Luminex targeting 20 viral antigens, pseudovirus neutralization, and T cell ELISPOT assays. Our results from a large prospective SARS-CoV-2 cohort study indicate symptom phenotype is strongly influenced by obesity among younger but not older age groups; we did not identify evidence to suggest obese individuals are at higher risk of SARS-CoV-2 infection; and remarkably homogenous immune activity across BMI categories suggests immune protection across these groups may be similar.


Subject(s)
Antibodies, Viral/blood , COVID-19/complications , COVID-19/immunology , Obesity/complications , Obesity/immunology , Spike Glycoprotein, Coronavirus/immunology , Adolescent , Adult , Age Factors , Body Mass Index , COVID-19/epidemiology , COVID-19/physiopathology , Female , Humans , Immunoglobulin G/blood , Male , Middle Aged , Risk Factors , SARS-CoV-2/immunology , Young Adult
3.
Nat Commun ; 12(1): 1018, 2021 02 15.
Article in English | MEDLINE | ID: covidwho-1085426

ABSTRACT

Antibodies serve as biomarkers of infection, but if sustained can confer long-term immunity. Yet, for most clinically approved vaccines, binding antibody titers only serve as a surrogate of protection. Instead, the ability of vaccine induced antibodies to neutralize or mediate Fc-effector functions is mechanistically linked to protection. While evidence has begun to point to persisting antibody responses among SARS-CoV-2 infected individuals, cases of re-infection have begun to emerge, calling the protective nature of humoral immunity against this highly infectious pathogen into question. Using a community-based surveillance study, we aimed to define the relationship between titers and functional antibody activity to SARS-CoV-2 over time. Here we report significant heterogeneity, but limited decay, across antibody titers amongst 120 identified seroconverters, most of whom had asymptomatic infection. Notably, neutralization, Fc-function, and SARS-CoV-2 specific T cell responses were only observed in subjects that elicited RBD-specific antibody titers above a threshold. The findings point to a switch-like relationship between observed antibody titer and function, where a distinct threshold of activity-defined by the level of antibodies-is required to elicit vigorous humoral and cellular response. This response activity level may be essential for durable protection, potentially explaining why re-infections occur with SARS-CoV-2 and other common coronaviruses.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , COVID-19/blood , Female , Humans , Immunity, Humoral/immunology , Immunoglobulin G/immunology , Male , Middle Aged , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology , Viral Vaccines/immunology , Young Adult
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