Epidemiological feature, viral shedding, and antibody seroconversion among asymptomatic SARS-CoV-2 carriers and symptomatic/ presymptomatic COVID-19 patients (preprint)

Background Novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pandemic. However, data concerning the epidemiological features, viral shedding, and antibody dynamics between asymptomatic SARS-CoV-2 carriers and COVID-19 patients remain controversial.Methods A total of 193 subjects in Ningbo and Zhoushan, Zhejiang, China, were enrolled in this study from January 21 to March 6, 2020. All subjects were tested positive for SARS-CoV-2 genomic RNA by quantitative reverse transcription PCR and then followed up to monitor the dynamics of serum antibody immunoglobulin M (IgM) and immunoglobulin G (IgG) against SARS-CoV-2 using enzyme-linked immunosorbent assays. Scatter diagram to demonstrate the distribution of IgM and IgG among asymptomatic carriers and COVID-19 patients were generated by R.Results Of the 193 subjects, 31 were asymptomatic SARS-CoV-2 carriers, 149 were symptomatic COVID-19 patients, and 14 were COVID-19 patients during the incubation. Compared to symptomatic COVID-19 patients, asymptomatic SARS-CoV-2 carriers were younger and had higher levels of white blood cell and lymphocyte, lower levels of C-reactive protein (CRP) and viral load, and shorter viral shedding time. Seroconversion of IgM against SARS-CoV-2 from positive to negative in asymptomatic carriers took 7.50 (IQR, 4.75–11.50) days, which was significantly shorter than 25.50 (IQR, 6.75–56.75) days in COVID-19 patients (P = 0.030). The proportion of those persistently seropositive for IgG against SARS-CoV-2 was higher in COVID-19 patients than in asymptomatic carriers (66.1% vs. 33.3%, P = 0.037). Viral load was higher in symptomatic than presymptomatic COVID-19 patients. Viral shedding was longer in presymptomatic COVID-19 patients than in asymptomatic carriers. In 4 familial clusters of SARS-CoV-2 infection, asymptomatic carriers were mainly children and young adults while severe COVID-19 was mainly found in family members older than 60 years with underlying diseases. Asymptomatic carriers acquired infection more from intra-familial transmission than did COVID-19 patients (89% vs. 61%, P = 0.028).Conclusion Asymptomatic carriers might have a higher antiviral immunity to clear SARS-CoV-2 than symptomatic COVID-19 patients and this antiviral immunity might not be contributable to humoral immunity. The severity of COVID-19 is associated with older age and underlying diseases in familial clustering cases.

Presymptomatic Transmission and Diverse Progression of Familial Clustering Covid-19 Cases in Zhoushan, China (preprint)

Background Novel coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-caused emerging infectious disease, firstly identified in Wuhan (Hubei, China), is pandemic. However, data concerning presymptomatic SARS-CoV-2 transmission and disease diversity among family members are limited. Herein, We investigated the epidemiological and clinical characteristics of presymptomatic transmission-caused familial clustering cases of SARS-CoV-2 infection in Zhoushan island, China.Methods All family members were tested for SARS-CoV-2 genomic RNA by quantitative reverse transcription PCR in 3 different samples and serum antibody immunoglobin M (IgM) and IgG against SARS-CoV-2. Exposure identification, laboratory test, and imaging were performed according to the national guideline of COVID-19 (7th edition, China).Results Of the 6 cases, index case who ever met his relative with COVID-19 from Xianning, Hubei on January 26–31, 2020, transmitted SARS-CoV-2 to his family members in Zhoushan via visiting family during January 31 and February 3, 2020. The index was identified as common-type COVID-19 on February 6, 2020. All 5 family members were infected with SARS-CoV-2. Of those, a 7-year-old girl was an asymptomatic carrier whereas her grandparents, especially her grandfather, were very sick. Case 6 (grandfather) remained positive for SARS-CoV-2 RNA in his sputum specimen in subsequent 2 months. Case 2 (mother) tested negative for SARS-CoV-2 RNA in all samples but positive for IgM and IgG to SARS-CoV-2 since February 9, 2020.Conclusions Presymptomatic transmission of SARS-CoV-2 causes familial cluster of COVID-19. Exposed to the same source of infection, family members present their differences in disease severity and viral clearance.

Presymptomatic transmission and diverse progression of familial clustering COVID-19 cases in Zhoushan, China (preprint)

Background Novel coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-caused emerging infectious disease, firstly identified in Wuhan (Hubei, China), is pandemic. However, data concerning presymptomatic SARS-CoV-2 transmission and disease diversity among family members are limited.Objectives To investigate the epidemiological and clinical characteristics of presymptomatic transmission-caused familial clustering cases of SARS-CoV-2 infection in Zhoushan island, China.Methods All family members were tested for SARS-CoV-2 genomic RNA by quantitative reverse transcription PCR in 3 different samples and serum antibody immunoglobin M (IgM) and IgG against SARS-CoV-2. Exposure identification, laboratory test, and imaging were performed according to the national guideline of COVID-19 (7th edition, China).Results Of the 6 cases, index case who ever met his relative with COVID-19 from Xianning, Hubei on January 26–31, 2020, transmitted SARS-CoV-2 to his family members in Zhoushan via visiting family during January 31 and February 3, 2020. The index was identified as common-type COVID-19 on February 6, 2020. All 5 family members were infected with SARS-CoV-2. Of those, a 7-year-old girl was an asymptomatic carrier whereas her grandparents, especially her grandfather, were very sick. Case 6 (grandfather) remained positive for SARS-CoV-2 RNA in his sputum specimen in subsequent 2 months. Case 2 (mother) tested negative for SARS-CoV-2 RNA in all samples but positive for IgM and IgG to SARS-CoV-2 since February 9, 2020.Conclusions Presymptomatic transmission of SARS-CoV-2 causes familial cluster of COVID-19. Exposed to the same source of infection, family members present their differences in disease severity and viral clearance.

Epidemiological and clinical features of COVID-19 patients with and without pneumonia in Beijing, China (preprint)

Background:SARS-CoV-2-caused coronavirus disease (COVID-19) is posinga large casualty. The features of COVID-19patients withand without pneumonia,SARS-CoV-2 transmissibility in asymptomatic carriers, and factors predicting disease progression remain unknown. Methods: We collected information on clinical characteristics, exposure history, andlaboratory examinations of all laboratory-confirmed COVID-19 patients admitted to PLA General Hospital. Cox regression analysis was applied to identify prognostic factors. The last follow-up was February 18, 2020. Results:We characterized 55 consecutive COVID-19 patients. The mean incubation was 8.42(95% confidence interval [CI], 6.55-10.29) days. The mean SARS-CoV-2-positive duration from first positive test to clearance was 9.71(95%CI, 8.21-11.22) days. COVID-19 course was approximately 2 weeks. Asymptomatic carriers might transmit SARS-CoV-2. Compared with patients without pneumonia, those with pneumonia were 15 years older and had a higher rate of hypertension, higher frequencies of having a fever and cough, and higher levels of interleukin-6 (14.61 vs. 8.06pg/mL, P=0.040), B lymphocyte proportion (13.0% vs.10.0%, P=0.024), low account (<190/L) of CD8+ T cells (33.3% vs. 0, P=0.019). Multivariate Cox regression analysis indicated that circulating interleukin-6 andlactate independently predicted COVID-19 progression, with a hazard ratio (95%CI) of 1.052 (1.000-1.107) and 1.082 (1.013-1.155), respectively. During disease course,T lymphocytes were generally lower,neutrophils higher, in pneumonia patients than in pneumonia-free patients. CD8+ lymphocytes did not increase at the 20th days after illness onset. Conclusion: The epidemiological features areimportant for COVID-19 prophylaxis. Circulating interleukin-6 and lactateare independent prognostic factors. CD8+ T cell exhaustion might be critical in the development of COVID-19.