key: cord-0781660-y6a4u0vh
authors: Wang, Bin; Wang, Li; Kong, Xianggen; Geng, Jin; Xiao, Di; Ma, Chunhong; Jiang, Xue‐Mei; Wang, Pei‐Hui
title: Long‐term coexistence of SARS‐CoV‐2 with antibody response in COVID‐19 patients
date: 2020-05-05
journal: J Med Virol
DOI: 10.1002/jmv.25946
sha: ae91e932a47e9844010e6cd01352f2949f3e1e8e
doc_id: 781660
cord_uid: y6a4u0vh

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection causing coronavirus disease 2019 (COVID‐19) has spread worldwide. Whether antibodies are important for the adaptive immune responses against SARS‐CoV‐2 infection needs to be determined. Here, 26 cases of COVID‐19 in Jinan, China, were examined and shown to be mild or with common clinical symptoms, and no case of severe symptoms was found among these patients. Strikingly, a subset of these patients had SARS‐CoV‐2 and virus‐specific IgG coexist for an unexpectedly long time, with two cases for up to 50 days. One COVID‐19 patient who did not produce any SARS‐CoV‐2–bound IgG successfully cleared SARS‐CoV‐2 after 46 days of illness, revealing that without antibody‐mediated adaptive immunity, innate immunity alone may still be powerful enough to eliminate SARS‐CoV‐2. This report may provide a basis for further analysis of both innate and adaptive immunity in SARS‐CoV‐2 clearance, especially in nonsevere cases.

The first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak was reported in December 2019, and the virus has rapidly spread worldwide within 3 months. 1 Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has become pandemic. Most COVID-19 patients show mild or moderate symptoms.

Severe cases of COVID-19 might eventually develop acute respiratory distress syndrome, septic shock, multiple organ failure, bleeding, and coagulation dysfunction 2,3 ; and is featured by pneumonia, lymphopenia, exhausted lymphocytes, and elevated serum levels of proinflammatory cytokines characterized as a cytokine storm. 3, 4 Therefore, the host immune system is thought to have participated in the pathogenesis of COVID-19. The importance of innate and adaptive immunity in the defense against SARS-CoV-2 needs to be urgently determined. 5 To fulfill the pressing need, we examined antibody generation and virus clearance in 26 patients with SARS-CoV-2-induced COVID-19.

Specimens from sputum, stool, and nasopharyngeal swabs were collected throughout the illness from 30 January 2020 to 5 April 2020. Viral RNA was extracted from clinical specimens, and real-time reverse-transcription polymerase chain reaction was performed to test the presence of SARS-CoV-2 using "Novel (Table 1) . No SARS-CoV-2-specific IgG and IgM antibodies were detected in the patient's serum until the last sample collection day, which was the 66th day post illness. Although we did not collect data about virus-specific cellular immunity, it is known that cellular immunity is generated concomitantly with humoral immunity, so we could preliminarily exclude the potential role of cellular immunity in SARS-CoV-2 elimination in this case. Thus, this is the first report to state that innate immunity plays an essential role in SARS-CoV-2 clearance, which The disease severity and fatality were increased with age in COVID-19 patients, which may be explained by the augmentation of proinflammatory responses and the reduction of antiviral cytokines in elder individuals. 10 In our study, the younger patients clear SARS-CoV-2 faster, thus, whether the antiviral immunity such as type I interferon responses were maximized and proinflammatory responses were minimized in these patients is of great interest; and the molecular mechanism involved in the process would be fundamental to our understanding of the immune system.

Taken together, we showed that SARS-CoV-2 could coexist with virus-specific IgG antibodies in COVID-19 patients for an unexpectedly long time and, without adaptive immunity, innate immunity may still be powerful enough to eliminate SARS-CoV-2. The long-term coexistence of IgG with SARS-CoV-2 in the human body raises the question of whether patients with antibodies are still at risk for reinfection, which may make COVID-19 "immunity passports"

unfeasible. Our follow-up studies may answer this question and would, therefore, be beneficial to vaccine development.

A novel coronavirus from patients with pneumonia in China

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Increasing host cellular receptor-angiotensinconverting enzyme 2 (ACE2) expression by coronavirus may facilitate 2019-nCoV infection

Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19

Neutralizing antibodies and pathogenesis of hepatitis C virus infection

Don't rush to deploy COVID-19 vaccines and drugs without sufficient safety guarantees

Timely development of vaccines against SARS-CoV-2

Therapeutic targeting of RIG-I and MDA5 might not lead to the same Rome

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Long-term coexistence of SARS-CoV-2 with antibody response in COVID-19 patients

We thank the physicians and nurses in Jinan infectious diseases hospital who cared for these patients and made this study possible.This study was supported by grants from COVID-19 emergency tackling research project of Shandong University (Grant No.2020XGB03 to P-HW).

The authors declare that there are no conflict of interests.

XMJ and P-HW conceptualized the study and analyzed the data. CM