Longitudinal Serology of SARS-CoV-2-Infected Individuals in India: A Prospective Cohort Study

Abstract

Clinical and epidemiological characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now widely available, but there are few data regarding longitudinal serology in large cohorts, particularly those from low-income and middle-income countries. We established an ongoing prospective cohort of 3,840 SARS-CoV-2-positive individuals according to RT-PCR in the Delhi-National Capital Region of India to document clinical and immunological characteristics during illness and convalescence. The immunoglobulin G (IgG) responses to the receptor binding domain (RBD) and nucleocapsid were assessed at 0 to 7 days, 10 to 28 days, and 6 to 10 weeks after infection. The clinical predictors of seroconversion were identified by multivariable regression analysis. The seroconversion rates during the postinfection windows of 0 to 7 days, 10 to 28 days, and 6 to 10 weeks were 46%, 84.7%, and 85.3%, respectively (N = 743). The proportion with a serological response increased with the severity of coronavirus disease 2019 (COVID-19). All participants with severe disease, 89.6% with mild to moderate infection, and 77.3% of asymptomatic participants had IgG antibodies to the RBD antigen. The threshold values for the nasopharyngeal viral RNA RT-PCR of a subset of asymptomatic and symptomatic seroconverters were comparable (P = 0.48) to those of nonseroconverters (P = 0.16) (N = 169). This is the first report of longitudinal humoral immune responses to SARS-CoV-2 over a period of 10 weeks in South Asia. The low seropositivity of asymptomatic participants and differences between assays highlight the importance of contextualizing the understanding of population serosurveys.

Figure 1.

Cumulative seropositivity for anti-nucleocapsid (anti-NC) and anti-receptor binding domain (anti-RBD) immunoglobulin G (IgG) antibodies among different categories of disease severity. The error bars indicate the 95% confidence interval (CI) of the signal/cutoff ratio during that window of follow-up. This figure appears in color at www.ajtmh.org.

Figure 2.

Longitudinal changes in the signal to cut-off ratios among different categories of disease severity. Anti-NC = anti-nucleocapsid; anti-RBD = anti-receptor binding domain; IgG = immunoglobulin G. This figure appears in color at www.ajtmh.org.