Determinants and Dynamics of SARS-CoV-2 Infection in a Diverse Population: 6-Month Evaluation of a Prospective Cohort Study

Abstract

Background: We studied risk factors, antibodies, and symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a diverse, ambulatory population.

Methods: A prospective cohort (n = 831) previously undiagnosed with SARS-CoV-2 infection underwent serial testing (SARS-CoV-2 polymerase chain reaction, immunoglobulin G [IgG]) for 6 months.

Results: Ninety-three participants (11.2%) tested SARS-CoV-2-positive: 14 (15.1%) asymptomatic, 24 (25.8%) severely symptomatic. Healthcare workers (n = 548) were more likely to become infected (14.2% vs 5.3%; adjusted odds ratio, 2.1; 95% confidence interval, 1.4-3.3) and severely symptomatic (29.5% vs 6.7%). IgG antibodies were detected after 79% of asymptomatic infections, 89% with mild-moderate symptoms, and 96% with severe symptoms. IgG trajectories after asymptomatic infections (slow increases) differed from symptomatic infections (early peaks within 2 months). Most participants (92%) had persistent IgG responses (median 171 days). In multivariable models, IgG titers were positively associated with symptom severity, certain comorbidities, and hospital work. Dyspnea and neurologic changes (including altered smell/taste) lasted ≥ 120 days in ≥ 10% of affected participants. Prolonged symptoms (frequently more severe) corresponded to higher antibody levels.

Conclusions: In a prospective, ethnically diverse cohort, symptom severity correlated with the magnitude and trajectory of IgG production. Symptoms frequently persisted for many months after infection.Clinical Trials Registration. NCT04336215.

Keywords: COVID-19; SARS-CoV-2 infection; humoral immunity; longitudinal data analysis; postacute sequelae of COVID-19; prospective cohort; risk factors; symptoms.

© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Factors associated with SARS-CoV-2 infection. Forest plots show factors associated with infection in (A) Rutgers Corona Cohort participants (n = 831) and (B) the subset of healthcare workers (n = 548) as measured by positive SARS-CoV-2 PCR or antibody testing. Results reflect aORs from multivariable logistic regression models fitted with elastic net penalty for regularization and variable selection from among variables listed in Table 1. Reference groups included: age < 40 years (versus ≥ 60 years), white race (versus Asian race), and attending physician (vs nursing). Abbreviations: aOR, adjusted odds ratio; CI, confidence interval; ICU, intensive care unit; OR, operating room; PCR, polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 2.

Average antibody levels over time among SARS-CoV-2–infected Rutgers Corona Cohort participants, stratified by symptom severity. Plots show estimated average levels of (A) total antibody and (B) IgG over time with 95% confidence intervals based on symptom severity. Curves and 95% confidence bands were estimated for different levels of symptom severity by fitting a model with a spline function for time and a random intercept to account for repeated measures. Abbreviations: Ig, immunoglobulin; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 3.

Factors associated with IgG titer among SARS-CoV-2–infected Rutgers Cohort participants (n = 81). Estimates reflect coefficients for factors in association with log-transformed IgG titer over time from a generalized additive mixed model, fitted with a spline for time. Factors reflect baseline values except disease severity (global assessment), cell counts (updated over time), and selected variables reflecting exposure in the first month of follow-up but excluding any values after SARS-CoV-2–positive testing (unprotected exposures to infected persons, worked on site). See “Methods” for details. Reference groups not shown are no symptoms, white race, and never smoker. Other chronic disease includes diabetes mellitus, cardio/cerebrovascular disease, cancer, chronic kidney disease, autoimmune disease, or immunosuppressant use. Chronic respiratory disease includes asthma, chronic obstructive pulmonary disease, or other chronic lung disease. Abbreviations: ALC, absolute lymphocyte count; ALT, alanine transaminase; ANC, absolute neutrophil count; CI, confidence interval; GFR, glomerular filtration rate; IgG, immunoglobulin G; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 4.

Duration of selected symptoms in infected RCC participants. Kaplan-Meier plots show prevalence and time course (in days) of 4 selected symptoms among infected RCC participants from infection to resolution: (A) fatigue; (B) loss of taste; (C) shortness of breath; and (D) neurologic changes besides altered taste or smell, eg, altered cognition or visual changes. Symptoms are shown in decreasing order of overall prevalence (A–D). Median, 75th, and 90th percentiles are indicated for each symptom among those who reported the symptom. Abbreviations: %ile, percentile; RCC, Rutgers Corona Cohort.

Figure 5.

Average antibody levels over time among SARS-CoV-2–infected Rutgers Corona Cohort participants, stratified by symptom duration. Plots show estimated average levels of IgG over time with 95% confidence intervals based on symptom duration. Curves and 95% confidence bands were estimated for different durations of symptoms by fitting a model with a spline function for time and a random intercept to account for repeated measures. Abbreviations: IgG, immunoglobulin G; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.