Dynamics of Viral Load and Antibodies in First 8 Weeks of Infection by SARS-CoV-2: An Observational Cohort Study

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread worldwide. Reports about the profile of SARS-CoV-2 viral load and serological responses are limited even in relatively short periods. We aimed to investigate profiles of viral RNA, IgM, and IgG in patients with SARS-CoV-2 pneumonia in an 8-week period. Methods: A cohort of 33 patients with confirmed SARS-CoV-2 pneumonia admitted to Wenzhou Sixth People’s Hospital from January 27 to February 13, 2020, were enrolled in this study. Samples of throat swab, sputum, stool, and blood were collected and viral load was measured by reverse transcription PCR (RT-PCR). Specific IgM and IgG against spike protein (S), spike protein receptor binding domain (RBD), and nucleocapsid (N) were analyzed by a chemiluminescence assay. Findings: At the early stage of symptom onset, SARS-CoV-2 viral load is higher in throat swab and sputum, but lower in stool. The median (IQR) time of undetectable viral RNA in throat swab, sputum, and stool was 18·5 (13·25-22) days, 22 (18·5-27·5) days, and 17 (11·5-32) days, respectively. In sputum, 17 (51·5%) patients had undetectable viral RNA within 22 days (short persistence), and 16 (48·5%) had persistent viral RNA more than 22 days (long persistence). Three (9·1%) patients were detected relapse of viral RNA in sputum in two weeks after discharge from hospital. One patient had persistent viral RNA for 59 days or longer. The median (IQR) seroconversion time of anti-S IgM, anti-RBD IgM, and anti-N IgM was 10·5 (7·75-15·5), 14 (9-24), and 10 (7-14) days, respectively. The median (IQR) seroconversion time of anti-S IgG, anti-RBD IgG, and anti-N IgG was 10 (7·25-16·5), 13 (9-17), and 10 (7-14) days, respectively. In week 8 after symptom onset, IgM were negative in many of the previously positive patients, IgG levels remained less than 50% of the peak levels in more than 20% of the patients. SARS-CoV-2 RNA coexisted with antibodies for more than 50 days. Anti-RBD IgM and IgG levels, anti-RBD IgM levels at presentation and peak time, were significantly higher in viral RNA short persistence patients than in long persistence patients. Interpretation: In both sputum and stool, SARS-CoV-2 RNA persists for a long time. Seroconversion time and the peak level of anti-RBD are important for viral RNA clearance. Specific anti-RBD may be a potential protective antibody against SARS-CoV-2 infection. Funding Statement: This study was supported by The Research Project for Emergent prevention of Novel Coronavirus Infected Pneumonia of The Bureau of Science and Technology, Wenzhou City, Zhejiang Province (ZY202004). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved by the Ethics Commission of Wenzhou Central Hospital (L2020-01-036). Written informed consent was signed by patients themselves.