The Correlation of Neutralizing Antibody Responses with SARS-CoV-2 Virus Clearance and Lung Disease Prognosis: Implication from a Family Cluster Study

Abstract

Background: A novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing pneumonia-associated respiratory disease pandemic across the world. Until now, the viral prevalence patterns, radiological characters, and antibody responses at initial stage of SARS-CoV-2 infection have been reported. The prolonged viral RNA shedding and coexistence with viral specific IgG antibody in discharged patients have also been reported recently. To date, however, correlations among viral specific RNA shedding, radiological pattern shift, and serum neutralizing antibody response covering the whole acute- and convalescent- phase in patients infected with SARS-CoV-2 are unknown. Focusing on a family cluster, present study is aim to give a bird view on the correlation of neutralizing antibody responses with viral clearance and lung disease prognosis from acute to convalescent phases. Methods: We conducted a surveillance study on a familial cluster of COVID-19 patients from Jan 17 to Apr 27 (99 days), 2020, in Guangzhou, Guangdong province, China. Epidemiological study was performed to clarify the virus transmission inside a family. NPAs, stool, and serum samples were collected and conducted RT-PCR to test the presence of SARS-CoV-2. Serum was used to perform neutralizing antibody tests to determine dynamic levels of neutralizing antibody. Radiological images as well as high-resolution CT scans for each patients were continually recorded to monitor outcomes of lung recovery. Findings: In this family cluster, three members (P2, P3, P4) in Guangzhou were infected by SARS-CoV-2 due to a close contact with P1 (index), who came back Guangzhou from Wuhan on Jan, 17, 2020, while another two members (H1 and H2) were unsusceptible and negative to SARS-CoV-2 test. The patients (P1, P2, P3) presented varying degrees of clinical symptoms on admission including recurrent fever, cough, and dyspnea, while P4 was asymptomatic. CT images showed ground-glass opacities in lungs of P1-3. The median length from illness onset to discharge for four-confirmed cases was 21.3 (4.7) days (range from 15 to 26). However, all patients returned positive for SARS-CoV-2 in follow-up investigation. The mean time for RNA shedding was 36.5 (3.2) days in P1, P2, and P4. The neutralizing antibody of P1, P2, and P4 was detectable during illness day 16 to 22. Then, the level was apparently ascent to a relative high titer and remained stable during 34-40, 31-41, and 35 days of illness onset for P1, P2, and P4, respectively, while declined gradually with time. The last positive time for SARS-CoV-2 test for P1, P2, and P4 was 40, 35, and 34 days of illness onset, respectively. Follow-up chest CT showed good prognosis in lung disease of P1 and P2, and CT scan was normal for P4. P3 was an exceptional case in this family cluster, who experienced the longest RNA shedding time (up to 68 days) as well as lung disease. In particular, radiological worsen was observed at day 34 of illness onset, high-resolution CT image revealed a glass-ground opacity in middle segment of right lung since day 45 to 99 of illness onset. The neutralizing antibody level in P3 was low during the entire study and significantly lower than that in other patients. Interpretation: The efficiency of SARS-CoV-2 virus clearance and lung disease prognosis were closely related to the levels of neutralizing antibody in COVID-19 patients. Viral clearance was observed along with high level of neutralizing antibody in P1, P2, and P4. However, the level of neutralizing antibody in P3 was not high enough to clear the virus completely, leading a prolong RNA shedding and lung disease. We proposed that high level of neutralizing antibody was essential for viral clearance and lung recovery, and virus was thoroughly eliminated during the period when neutralizing antibody reached high level in serum. Funding Statement: This work was supported by grants from the Guangzhou Science and Technology Program (201904010012), Guangdong Provincial Science and Technology Program (2018B020207006), Guangdong Provincial Novel Coronavirus Scientific and Technological Project (2020111107001). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study was approved by the Institutional Review Board of the Guangdong Second Provincial General Hospital. All patients involved in this study signed the clinical research informed consent.