Dynamics and Correlation Among Viral Positivity, Seroconversion, and Disease Severity in COVID-19 : A Retrospective Study

Ann Intern Med. 2021 Apr;174(4):453-461. doi: 10.7326/M20-3337. Epub 2020 Dec 8.

Abstract

Background: The understanding of viral positivity and seroconversion during the course of coronavirus disease 2019 (COVID-19) is limited.

Objective: To describe patterns of viral polymerase chain reaction (PCR) positivity and evaluate their correlations with seroconversion and disease severity.

Design: Retrospective cohort study.

Setting: 3 designated specialty care centers for COVID-19 in Wuhan, China.

Participants: 3192 adult patients with COVID-19.

Measurements: Demographic, clinical, and laboratory data.

Results: Among 12 780 reverse transcriptase PCR tests for severe acute respiratory syndrome coronavirus 2 that were done, 24.0% had positive results. In 2142 patients with laboratory-confirmed COVID-19, the viral positivity rate peaked within the first 3 days. The median duration of viral positivity was 24.0 days (95% CI, 18.9 to 29.1 days) in critically ill patients and 18.0 days (CI, 16.8 to 19.1 days) in noncritically ill patients. Being critically ill was an independent risk factor for longer viral positivity (hazard ratio, 0.700 [CI, 0.595 to 0.824]; P < 0.001). In patients with laboratory-confirmed COVID-19, the IgM-positive rate was 19.3% in the first week, peaked in the fifth week (81.5%), and then decreased steadily to around 55% within 9 to 10 weeks. The IgG-positive rate was 44.6% in the first week, reached 93.3% in the fourth week, and then remained high. Similar antibody responses were seen in clinically diagnosed cases. Serum inflammatory markers remained higher in critically ill patients. Among noncritically ill patients, a higher proportion of those with persistent viral positivity had low IgM titers (<100 AU/mL) during the entire course compared with those with short viral positivity.

Limitation: Retrospective study and irregular viral and serology testing.

Conclusion: The rate of viral PCR positivity peaked within the initial few days. Seroconversion rates peaked within 4 to 5 weeks. Dynamic laboratory index changes corresponded well to clinical signs, the recovery process, and disease severity. Low IgM titers (<100 AU/mL) are an independent risk factor for persistent viral positivity.

Primary funding source: None.