Objective: This study aimed to investigate the clinical characteristics of COVID-19 patients with recurrent SARS-CoV-2 positivity after hospital discharge. Methods: This retrospective study included COVID-19 patients who were readmitted for recurrence of positive SARS-CoV-2 RNA. Univariate and multivariate analyses were performed to assess the risk factors associated to the duration of recurrent RNA positivity. Results: Among the 287 discharged COVID-19 patients, 33 (11.5%) patients with recurrent PCR positivity were included. Among these patients, 21 (63.7%) patients were female, their mean age was 48.7 (±19.7) years old. 22 (66.7%) patients were asymptomatic. The following clinical features were presented in other patients: cough, fatigue, sore throat, fever and expectoration. The chest CT ndings revealed that 8 (24.2%) patients were characterized by deterioration compared to the previous results. The median duration of recurrent RNA positivity was 9.0 days (IQR, 6.0, 15.0). We found that increased serum SARS-CoV-2-speci c IgG antibody titer, elevated serum creatinine level, and female gender were the risk factors for the prolonged duration of recurrent RNA positivity. Conclusion: SARS-CoV-2 turned positive in a minority of discharged patients with COVID-19. Most patients experienced mild clinical course. Increased IgG antibody titer, creatinine and female gender were correlated to the prolonged RNA clearance time.

Serological and plasmablast responses and plasmablast-derived IgG monoclonal antibodies (MAbs) have been analysed in three COVID-19 patients with different clinical severities. Potent humoral responses were detected within 3 weeks of onset of illness in all patients and the serological titre was elicited soon after or concomitantly with peripheral plasmablast response. An average of 13.7% and 13.0% of plasmablast-derived MAbs were reactive with virus spike glycoprotein or nucleocapsid, respectively. A subset of anti-spike (10 of 32) and over half of anti-nucleocapsid (19 of 35) antibodies cross-reacted with other betacoronaviruses tested and harboured extensive somatic mutations, indicative of an expansion of memory B cells upon SARS-CoV-2 infection. Fourteen of 32 anti-spike MAbs, including five anti-receptor-binding domain (RBD), three anti-non-RBD S1 and six anti-S2, neutralised wild-type SARS-CoV-2 in independent assays. Anti-RBD MAbs were further grouped into four cross-inhibiting clusters, of which six antibodies from three separate clusters blocked the binding of RBD to ACE2 and five were neutralising. All ACE2-blocking anti-RBD antibodies were isolated from two recovered patients with prolonged fever, which is compatible with substantial ACE2-blocking response in their sera. At last, the identification of non-competing pairs of neutralising antibodies would offer potential templates for the development of prophylactic and therapeutic agents against SARS-CoV-2.

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