key: cord-0690518-ln4xclav authors: Saurabh, Suman; Kumar, Ritesh; Gupta, Manoj Kumar; Bhardwaj, Pankaj; Nag, Vijaya Lakshmi; Garg, Mahendra Kumar; Misra, Sanjeev title: Prolonged persistence of SARS-CoV-2 in the upper respiratory tract of asymptomatic infected individuals date: 2020-07-01 journal: QJM DOI: 10.1093/qjmed/hcaa212 sha: d441433e6caca18ea66f439e3a9922f3842e6e6f doc_id: 690518 cord_uid: ln4xclav BACKGROUND: Duration of persistence of SARS-CoV-2 in the upper respiratory tract of infected individuals has important clinical and epidemiological implications. AIM: We aimed to establish the duration and risk factors for persistence of SARS-CoV-2 in the upper respiratory tract of asymptomatic infected individuals. METHODS: Data of repeat rRT-PCR test done for SARS-CoV-2 infected individuals at our institute at Jodhpur, India was analysed from 19 March- 21 May 2020. Duration of virus persistence was estimated with parametric regression models based on Weibull, Log-normal, Log-logistic, Gamma and Generalized Gamma distributions. Factors associated with prolonged viral persistence were analysed with the best fitting model. RESULTS: 51 SARS-CoV-2 infected individuals with repeat rRT-PCR test were identified with 44 asymptomatics. The asymptomatic individuals had median virus persistence duration of 8.87 days (95%CI: 7.65 – 10.27) and 95 percentile duration of 20.70 days (95% CI: 16.08 -28.20). The overall median virus persistence including both symptomatic and asymptomatic individuals was found to be 9.18 days (95 CI 8.04 – 10.48). Around one-fourth asymptomatics (10/44) demonstrated SARS-CoV-2 persistence beyond 2 weeks. Age < 60 years and local transmission were found to be significantly associated with longer virus persistence among asymptomatic individuals on univariate regression but not in multivariate analysis. CONCLUSION: Recommended home isolation duration for SARS-CoV-2 infected individuals in India should be extended from 17 days to at least three weeks. Prolonged persistence of SARS-CoV-2 in a proportion of asymptomatic individuals merits attention with regard to ensuring universal infection prevention precautions irrespective of symptomatic status. 3 of 20.70 days (95% CI: 16 .08 -28.20). The overall median virus persistence including both symptomatic and asymptomatic individuals was found to be 9.18 days (95 CI 8.04 -10.48). Around one-fourth asymptomatics (10/44) demonstrated SARS-CoV-2 persistence beyond 2 weeks. Age < 60 years and local transmission were found to be significantly associated with longer virus persistence among asymptomatic individuals on univariate regression but not in multivariate analysis. Recommended home isolation duration for SARS-CoV-2 infected individuals in India should be extended from 17 days to at least three weeks. Prolonged persistence of SARS-CoV-2 in a proportion of asymptomatic individuals merits attention with regard to ensuring universal infection prevention precautions irrespective of symptomatic status. SARS-CoV-2, COVID-19, persistence, viral shedding, Log-logistic, rRT-PCR As on 21 June 2020, COVID-19 has resulted in 8.7 million cases and 0.46 million deaths. 1 India has become the fourth most affected country worldwide with around 0.41 million confirmed COVID-19 cases. 1 The persistence of SARS-CoV-2 in body fluids has important clinical and epidemiological implications. A negative rRT-PCR result had been considered as a surrogate marker of non-infectiousness of the individual. Consequently, it had been required for discharge of individuals undergoing treatment or hospital isolation in India until 8 May 2020, when testing prior to discharge had been discontinued under the revised strategy. 2,3 Also, the https://mc.manuscriptcentral.com/qjm recommended duration of home isolation for both health workers and general public is being guided by expectation of viral negativity at the end of the isolation period. 3 Both oropharyngeal and nasopharyngeal swab specimens were taken from the individuals meeting suspect case definition for COVID-19 at our institute in Jodhpur, India. 4 Regression analysis for asymptomatic individuals was conducted with the best-fitting Log-logistic model. Upon univariate analysis, age < 60 years and local transmission were found to be significantly associated with longer persistence of SARS-CoV-2 in the upper respiratory tract ( Table 3) . None of the co-variates were found significantly associated with prolonged virus persistence when age, gender and type of transmission were taken together in the multivariate model (Table 3) . Prior to introduction of home isolation strategy on 10 May 2020 7 , India had adopted the policy of universal health-facility based isolation of all SARS-CoV-2 infected individuals irrespective of symptomatic status. This provided us with a unique opportunity to study the virus persistence among the asymptomatic individuals admitted at our institute. Longer virus persistence has been demonstrated in severe illness as compared to mild COVID-19. 8 However, we didn't find a statistically significant difference in virus persistence based on symptomatic status. Our finding of median duration of virus persistence of 9.18 days among all infected individuals was comparable to the estimate of 10 days as per laboratory surveillance data from India 3 and 10-12 days reported from China. 9-10 It was however, lower than the 15 days reported from South Korea. 11 Considering only asymptomatic individuals, the median virus persistence of 8.87 days reported by us nearly matched that of 9 days reported from the Diamond Princess ship, indicating similar transmission dynamics. 12 The present study adds to the evidence of prolonged persistence of SARS-CoV-2 in upper respiratory tract in a considerable proportion of infected individuals. 8, 9, 11, 13 Association of local transmission with longer virus persistence on univariate analysis could have been confounded by the locally infected individuals being significantly younger than those evacuated from abroad. Possible association of younger age and variation in transmission pattern with prolonged virus persistence merits further exploration. Although virus persistence measured through positive rRT-PCR of swab samples doesn't necessarily mean that the individual is infective, greater viral load indicated by lower cyclic threshold values correlates with cell culture infectivity. 13 Therefore, the finding of prolonged virus persistence even among asymptomatic individuals has important public health implications when large number of individuals with varying viral loads are considered in the community. A study from the United States had recommended that people infected with SARS-CoV-2 should cease infection prevention precautions and should return to work only after 33 days of symptom onset or a negative test result. 14 Furthermore, the finding of prolonged and intermittent viral shedding also helps explain why earlier many 'recovered' patients had re-tested positive after being discharged from hospital. 15, 16 These findings reset the expectation of viral shedding to a longer duration, especially for asymptomatic SARS-CoV-2 infected individuals. Our estimates could be generalizable to settings wherein large proportion of infected individuals remain asymptomatic. We had the limitation that we couldn't separately estimate the duration of virus persistence in nasopharynx and oropharynx as both the swap tips were inserted together in the viral transport medium to increase the possibility of SARS-CoV-2 detection. Based on our findings, a prolongation of current home isolation guidance from 17 Funding-The authors declare that no funding was received from any source for the study and preparation of this article. Ministry of Health and Family Welfare, Government of India Ministry of Health and Family Welfare, Government of India Indian Council of Medical Research Operating Procedure for Detection of 2019-nCoV in suspected human cases by rRT-PCR. Indian Council of Medical Research -National Institute of Virology R: A language and environment for statistical computing. 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