Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections

The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described. We studied 37 asymptomatic individuals in the Wanzhou District who were diagnosed with RT–PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization. Asymptomatic individuals were admitted to the government-designated Wanzhou People’s Hospital for centralized isolation in accordance with policy 1 . The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15–26 d). The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P  = 0.028). The virus-specific IgG levels in the asymptomatic group (median S/CO, 3.4; IQR, 1.6–10.7) were significantly lower ( P  = 0.005) relative to the symptomatic group (median S/CO, 20.5; IQR, 5.8–38.2) in the acute phase. Of asymptomatic individuals, 93.3% (28/30) and 81.1% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 96.8% (30/31) and 62.2% (23/37) of symptomatic patients. Forty percent of asymptomatic individuals became seronegative and 12.9% of the symptomatic group became negative for IgG in the early convalescent phase. In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines. These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection. The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys. A cohort of asymptomatic patients infected with SARS-CoV-2 had significantly lower levels of virus-specific IgG antibodies compared to a cohort of age- and sex-matched symptomatic infected patients.

[1]  G. Gao,et al.  Persistent shedding of viable SARS-CoV in urine and stool of SARS patients during the convalescent phase , 2005, European Journal of Clinical Microbiology and Infectious Diseases.

[2]  W. Cao,et al.  Disappearance of antibodies to SARS-associated coronavirus after recovery. , 2007, The New England journal of medicine.

[3]  Lin‐Fa Wang,et al.  Duration of Antibody Responses after Severe Acute Respiratory Syndrome , 2007, Emerging infectious diseases.

[4]  P. Marik,et al.  A Descriptive Study , 2015 .

[5]  S. Park,et al.  Viral Load Kinetics of MERS Coronavirus Infection. , 2016, The New England journal of medicine.

[6]  A. Tamin,et al.  Persistence of Antibodies against Middle East Respiratory Syndrome Coronavirus , 2016, Emerging infectious diseases.

[7]  Kyoung-Ho Song,et al.  MERS-CoV Antibody Responses 1 Year after Symptom Onset, South Korea, 2015 , 2017, Emerging infectious diseases.

[8]  Dennis Andersson,et al.  A retrospective cohort study , 2018 .

[9]  Yan Zhao,et al.  Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. , 2020, JAMA.

[10]  J. Low,et al.  Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. , 2020, JAMA.

[11]  N. Linton,et al.  Estimation of the asymptomatic ratio of novel coronavirus infections (COVID-19) , 2020, International Journal of Infectious Diseases.

[12]  Ting Yu,et al.  Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study , 2020, The Lancet.

[13]  S. Lo,et al.  A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster , 2020, The Lancet.

[14]  M. Lipsitch,et al.  Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period , 2020, Science.

[15]  Shashwat Shivam,et al.  Modeling shield immunity to reduce COVID-19 epidemic spread , 2020, Nature Medicine.

[16]  Quanyi Wang,et al.  Neutralizing Antibodies Responses to SARS-CoV-2 in COVID-19 Inpatients and Convalescent Patients , 2020, medRxiv.

[17]  Mengfeng Li,et al.  Long-Term Persistence of IgG Antibodies in SARS-CoV Infected Healthcare Workers , 2020, medRxiv.

[18]  Wenzhen Zhu,et al.  Clinical and High-Resolution CT Features of the COVID-19 Infection: Comparison of the Initial and Follow-up Changes , 2020, Investigative radiology.

[19]  Jun Yuan,et al.  Antibody responses to SARS-CoV-2 in patients with COVID-19 , 2020, Nature Medicine.

[20]  Philip L. Felgner,et al.  A serological assay to detect SARS-CoV-2 seroconversion in humans , 2020, medRxiv.

[21]  Jian-ming Wang,et al.  Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China , 2020, Science China Life Sciences.

[22]  O. F. Norheim Protecting the population with immune individuals , 2020, Nature Medicine.

[23]  J. Xiang,et al.  Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study , 2020, The Lancet.

[24]  G. Chowell,et al.  Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020 , 2020, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[25]  Kari Stefansson,et al.  Spread of SARS-CoV-2 in the Icelandic Population , 2020, The New England journal of medicine.

[26]  Y. Wen,et al.  Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications , 2020, medRxiv.

[27]  Xinquan Wang,et al.  Detection of SARS-CoV-2-Specific Humoral and Cellular Immunity in COVID-19 Convalescent Individuals , 2020, Immunity.

[28]  Vineet D. Menachery,et al.  Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients , 2020, Cell Reports Medicine.

[29]  Steven Y. C. Tong,et al.  Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19 , 2020, Nature Medicine.

[30]  Jian-ming Wang,et al.  Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China , 2020, Science China Life Sciences.

[31]  E. Petersen,et al.  SARS-CoV-2 shedding and infectivity , 2020, The Lancet.

[32]  Yan Bai,et al.  Presumed Asymptomatic Carrier Transmission of COVID-19. , 2020, JAMA.

[33]  A. Phelan,et al.  COVID-19 immunity passports and vaccination certificates: scientific, equitable, and legal challenges , 2020, The Lancet.