Low transmission risk of 9 asymptomatic carriers tested positive for both SARS-CoV-2 nucleic acid and serum IgG
Authors: Fenghua Chen, Daan Fu, Qianqian Yang, Zhi Geng, Jiahong Xia, Zheng Wang, Lin Wang
Journal: Journal of Infection (2020)

•Asymptomatic carriers (RT-PCR+ and serum IgG+) are unable to transmit virus.•Such a low transmission risk might be partly associated with high Ct values.•A new pattern in SARS-CoV-2 infected patients might have emerged. We read with interest a recent prospective contact-tracing study in this Journal by Huang et al.1Huang L. Zhang X. Zhang X. Wei Z. Zhang L. Xu J. et al.Rapid asymptomatic transmission of COVID-19 during the incubation period demonstrating strong infectivity in a cluster of youngsters aged 16–23 years outside Wuhan and characteristics of young patients with COVID-19: a prospective contact-tracing study.J Infect. 2020; 80: e1‐e13https://doi.org/10.1016/j.jinf.2020.03.006Abstract Full Text Full Text PDF PubMed Scopus (250) Google Scholar, who reported a rapid asymptomatic transmission of COVID-19 during the incubation period demonstrating strong infectivity in a cluster of youngsters aged 16–23 years outside Wuhan. The COVID-19 pandemic has affected millions of lives worldwide partly due to its high contagiousness.2WHO. Novel coronavirus (COVID-19) situation. Updated May 30, 2020. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200530-covid-19-sitrep-131.pdf?sfvrsn=d31ba4b3_2.Google Scholar,3Chan J.F. Yuan S. Kok K.H. To K.K. Chu H. Yang J. et al.A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster.Lancet. 2020; 395: 514‐523https://doi.org/10.1016/S0140-6736(20)30154-9Abstract Full Text Full Text PDF PubMed Scopus (6241) Google Scholar Thus far, the growing amount of evidence suggests that asymptomatic carriers are capable of transmitting SARS-CoV-2.4Bai Y. Yao L. Wei T. Tian F. Jin D.Y. Chen L. et al.Presumed asymptomatic carrier transmission of COVID-19 [published online ahead of print, 2020 Feb 21].JAMA. 2020; 323: 1406‐1407https://doi.org/10.1001/jama.2020.2565Crossref Scopus (3088) Google Scholar,5Hu Z. Song C. Xu C. Jin G. Chen Y. Xu X. et al. Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China.Sci China Life Sci. 2020; 63: 706‐711https://doi.org/10.1007/s11427-020-1661-4Crossref PubMed Scopus (948) Google Scholar Here we report clinical characteristics of nine confirmed COVID-19 asymptomatic carriers, who were tested positive both for SARS-CoV-2-specific nucleic acid and IgG, but appeared to be unable to transmit the virus. Of 4973 SARS-CoV-2 nucleic acid positive results in Union hospital, Wuhan throughout the COVID-19 outbreak (from January 25 to May 14, 2020), we found nine asymptomatic carriers who were tested positive both for SARS-CoV-2-specific nucleic acid and IgG between Mar 28 and May 12, 2020. The SARS-CoV-2 nucleic acid was tested using throat swab specimens through real-time PCR (RT-PCR) to amplify the ORF1ab gene and N gene of SARS-CoV-2 (BioGerm, Shanghai, China).The primers for ORF1ab gene and corresponding detecting products: forward primer 5′-CCCTGTGGGTTTTACACTTAA-3′, reverse primer 5′-ACGATTGTGCATCAGCTGA-3′, fluorescence probe 5′-FAM-CCGTCTGCGGTATGTGGAAAGGTTATGC-BHQ1-3′; for N gene and corresponding detecting products, forward primer 5′-GGGGAACTTCTCCTGCTAGAAT-3′, reverse primer 5′-CAGACATTTTGCTCTCAAGCTG-3′, fluorescence probe 5′-FAM-TTGCTGCTGCTTGACAGATT-TAMRA-3′. If the cycle threshold (Ct) value < 35 (or > 35 but less than 40 for two times), the specimens are defined as positive. Specific IgG against SARS-CoV-2 was detected using commercially available kit (#C86095G, YHLO biotechnology Co., LTD, Shenzhen, China) in an iFlash 3000 chemiluminescent immune analyzer (YHLO biotechnology Co., LTD, Shenzhen, China) through chemiluminescent microparticle immunoassay. This study was reviewed and approved by the Medical Ethical Committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. Nine confirmed asymptomatic carriers who were tested positive for both SARS-CoV-2-specific nucleic acid and IgG (Patient 1–3 positive for IgG and IgM, and the others positive for IgG but negative for IgM) were retrospectively analyzed (Fig. 1). These patients were enrolled from outpatient population or general population requesting regular physical check-up. They have an average age of 47y (range18–77y), five of which were male and four were female. Only one of them had comorbidity (Patient 8 with hypertension and diabetes). None of them received chest CT probably because of their lack of COVID-19 associated symptoms (Table 1). Two patients (Patient 1 and 3) were subject to in-hospital quarantine for 29 days, and then discharged because SARS-CoV-2 nucleic acid testing turned negative; the others remained quarantined in hospitals at the time of follow-up on May 12, 2020. The average Ct value of SARS-CoV-2nucleic acid testing in nine patients were 36.42 ± 2.06 (ORF1ab gene, range 31.27–38.89) and 34.87 ± 3.73 (N gene, range 27.30–39.47). From the moment of Wuhan City lockdown (January 23, 2020) to the time of being admitted for quarantine, all these patients had lived together with their family members for an average of 85 days (range 65–104 days). All these patients developed no symptoms associated with COVID-19 during their quarantine. Of note, none of the patients' close contacts (including all their family members who stayed with them) were RT-PCR tested positive for SARS-CoV-2, indicating they are not infected by these asymptomatic carriers despite of close contact.Table 1Characteristics of nine asymptomatic carriers with SARS-CoV-2-specific IgG positive.SexPatient 1Patient 2Patient 3Patient 4Patient 5Patient 6Patient 7Patient 8Patient 9MaleFemaleFemaleMaleMaleFemaleFemaleMaleMaleAge58y56y52y42y30y18y55y77y38yUnderlying diseasesNoNoNoNoNoNoNoHypertension, diabetesNoInitial symptoms associated with COVID-19NoNoNoNoNoNoNoNoNoCT evidence of pneumoniaNANANANANANANANANADate of positive for initial SARS-CoV-2 nucleic acid testingApr 13Mar 29Apr 10Apr 24Apr 13Apr 23Mar 28Apr 22Apr 15Ct value of ORF1ab gene for initial SARS-CoV-2 nucleic acid testing37.836.636.736.537.935.336.831.338.9Ct value of N gene for initial SARS-CoV-2 nucleic acid testing37.537.727.336.439.534.035.029.936.7Date of initial testing for SARS-CoV-2-specific IgG and IgMApr 13Mar 29Apr 10Apr 24Apr 13Apr 23Mar 14Apr 22Apr 15Result of initial testing for SARS-CoV-2-specific IgG and IgMIgG (+),IgG (+),IgG (+),IgG (+),IgG (+),IgG (+),IgG (+),IgG (+),IgG (+),IgM (+)IgM (+)IgM (+)IgM (−)IgM (−)IgM (−)IgM (−)IgM (−)IgM (−)Date of admissionApr 13Mar 29Apr 10Apr 25Apr 13Apr 24Mar 28Apr 22Apr 15Date of negative for initial SARS-CoV-2 nucleic acid testingApr 26May 10Apr 26May 2Apr 27Apr 28Apr 5*Apr 28Apr 26Date of dischargeMay 12NA**May 9NA**NA**NA**NA**NA**NA**Symptoms associated with COVID-19 during quarantineNoNoNoNoNoNoNoNoNoDays for patients living with their family members since Jan. 23, 2020 (Wuhan lockdown)8110478938192659083The status of SARS-CoV-2 nucleic acid testing for all close contactsNegativeNegativeNegativeNegativeNegativeNegativeNegativeNegativeNegative Open table in a new tab We observed a small group of asymptomatic carriers (positive for both SARS-CoV-2-specific nucleic acid and IgG) with very low transmission risk. Our observation is consistent with a recent report suggesting that low transmission risk in asymptomatic patients.6Wei W.E. Li Z. Chiew C.J. Yong S.E. Toh M.P. Lee V.J Presymptomatic Transmission of SARS-CoV-2 – Singapore, January 23–March 16, 2020.MMWR Morb Mortal Wkly Rep. 2020; 69 (Published 2020 Apr 10): 411‐415https://doi.org/10.15585/mmwr.mm6914e1Crossref PubMed Google Scholar Such a low transmission risk might be partly associated with relatively high Ct values. This is in accordance with the observation that compared with severe COVID-19 cases, significantly lower viral loads were found in mild COVID-19 patients.7Zheng S. Fan J. Yu F. Feng B. Lou B. Zou Q. et al.Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January–March 2020: retrospective cohort study.BMJ. 2020; 369 (Published 2020 Apr 21): m1443https://doi.org/10.1136/bmj.m1443Crossref PubMed Scopus (1089) Google Scholar The other possible reasons for low transmission risk: (1) the infectivity of the virus might be decreased in these confirmed asymptomatic carriers; (2) viral shedding might be ineffective without relevant symptoms, such as sneezing and coughing, thus reducing the risk of infections for close contacts.8Wang Y. Kang H. Liu X. Tong Z. Asymptomatic cases with SARS-CoV-2 infection [published online ahead of print, 2020 May 8].J Med Virol. 2020; (10.1002/jmv.25990)https://doi.org/10.1002/jmv.2599Crossref Google Scholar The analysis of this group of patients suggests that some asymptomatic carriers can be tested positive for SARS-CoV-2-specific nucleic acid and serum IgG, but they are of low transmission risk, which is different from previously-reported asymptomatic carriers5Hu Z. Song C. Xu C. Jin G. Chen Y. Xu X. et al. Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China.Sci China Life Sci. 2020; 63: 706‐711https://doi.org/10.1007/s11427-020-1661-4Crossref PubMed Scopus (948) Google Scholar, suggesting a new pattern may have emerged in SARS-CoV-2 infected patients and changes associated with viral load and virus infectivity. These have not been reported thus far. However, close monitoring of the asymptomatic patients is still required. This work was limited in several aspects: (1) the sample size is limited (n = 9); (2) further investigation such as virus isolation and culture would strengthen the study, but we are unable to provide the results at this point, given current limited medical resources and urgent situations. The findings of this work may provide useful information for helping improve understanding and management of asymptomatic carriers and facilitating restoration of normal medical services after COVID-19 pandemic. All authors participated in design, collected and analyzed data, drafted the manuscript and approved the final submitted version. Chen, Fu, and Yang contributed equally to the work. The authors declare no conflicts of interest.