key: cord-266996-knwpkyg6 authors: Kipkorir, Vincent; Cheruiyot, Isaac; Ngure, Brian; Misiani, Musa; Munguti, Jeremiah title: Prolonged SARS‐Cov‐2 RNA Detection in Anal/Rectal Swabs and Stool Specimens in COVID‐19 Patients After Negative Conversion in Nasopharyngeal RT‐PCR Test date: 2020-05-13 journal: J Med Virol DOI: 10.1002/jmv.26007 sha: doc_id: 266996 cord_uid: knwpkyg6 Coronavirus disease 2019 (COVID‐19) is a rapidly escalating pandemic that has spread to many parts of the world. Current data available on COVID‐19 would suggest that SARS‐CoV‐2 virus is shed through the gastrointestinal system via feces. Some reports further indicate that a subset of COVID‐19 patients may continue to have positive SARS‐CoV‐2 anal/rectal swab and stool test after negative conversion of nasopharyngeal test. This paper analyses current literature to so as to shed some light on this issue. This article is protected by copyright. All rights reserved. Since the initial cases in late 2019 in Wuhan, China, the coronavirus disease 2019 (COVID- 19) has spread rapidly across the world. As of 6 th May 2020, there had been more than 3,588,773 confirmed cases, with >247,503 fatalities. 1 Current evidence suggests that COVID-19 is mainly spread through respiratory droplets and by fomites. 2 Recently, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has also been isolated from anal/rectal swabs and stool specimens 3, 4 , raising concerns of potential alternative routes of viral transmission. In previous epidemics such as the Zika and Ebola virus, the persistence of the virus in various body fluids was noted to occur in convalescing patients. 5, 6 It is however unclear as to whether this phenomenon is also present in the COVID-19 pandemic. We, therefore, systematically analyzed current literature to identify any evidence of prolonged SARS-CoV-2 detection in anal/ rectal This article is protected by copyright. All rights reserved. swabs and stool specimens in COVID-19 patients after negative conversion in nasopharyngeal RT-PCR test. A systematic electronic search was carried out in Medline (PubMed interface) and China National Knowledge Infrastructure (CNKI) using the search strategy (1) "COVID-19" OR "SARS-CoV-2" OR "2019-nCOV"; (2) "Feces" OR "Rectal Swab" OR "Anal Swab"; (table 1) . Thereafter, a pooled analysis incorporating only cohort studies or case series with sample ≥10 patients was conducted to calculate pooled prevalence estimates (PPE) of prolonged SARS-CoV-2 RNA detection in anal/rectal swabs and stool samples after negative conversion in nasopharyngeal RT-PCR using the MetaXL (software Version 5.3, EpiGear International Pty Ltd., Sunrise Beach, Australia). A random effects model was applied due to the heterogeneity displayed by the data. The magnitude of heterogeneity among the included studies was assessed using the chi-squared test (Chi 2 ) and I-squared statistic (I 2 ). For the Chi 2 test, a Cochrane's Q p value of <0.10 was considered significant. The study was carried out in accordance with the declaration of Helsinki. As data were publicly available, no ethical approval was required. The initial search produced 49 potentially relevant articles. Following primary screening and assessment by full text for eligibility in the meta-analysis, 37 articles were excluded since they were review articles (n=11), commentaries, or other editorial materials (n = 8), or did not contain data on prolonged viral detection in anal/rectal swabs or stool specimens in COVID-19 patients (n=18). (Table 1 ). Overall, 107 had a positive rectal/anal/stool SARS-CoV-2 test after negative conversion of the nasopharyngeal RT-PCR test. The reported duration of test positivity ranged from 5 to 35 days (Table 1 ). In the pooled analysis of 8 cohort studies/ case series (n= 315), the pooled prevalence estimate (PPE) for prolonged rectal/anal/stool SARS-CoV-2 RNA was 32% (95% CI 22-44) (Figure 1 ). There was a high level of inter-study heterogeneity (I 2 = 75%). There was insufficient data to perform meta-regression analysis to identify any moderators for the pooled prevalence. Nonetheless, no significant difference was observed in the leave-oneout sensitivity analysis. Therefore, there is some evidence of the persistence of SARS-This article is protected by copyright. All rights reserved. CoV-2 in body secretion in convalescing COVID-19 patients. It is noteworthy that a significant proportion of these patients are within the pediatric age-group (Table 1) . Further, the study by Jiang and colleagues highlight the potential of gastro-intestinal shedding of the virus even in asymptomatic patients 17 . That being said, reverse transcriptase polymerase chain reaction (RT-PCR) does not usually distinguish between the infectious virus and non-infectious nucleic acid 18 , and therefore viral isolation in stool may not necessarily imply potential for transmission or infectivity. However, Wang and colleagues recently cultured four SARS-CoV-2-positive fecal specimens with high copy numbers, and successfully demonstrated live virus using electron microscopy in two specimens 19 . These findings however need to be further investigated in larger cohorts of patients. This article is protected by copyright. All rights reserved. Table Table 1 Coronavirus disease 2019 (COVID-19) Situation Report -107. 2020. Accessed 7th The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology Prolonged presence of SARS-CoV-2 viral RNA in faecal samples. The lancet Gastroenterology & hepatology Persistence of Ebola virus in various body fluids during convalescence: evidence and implications for disease transmission and control Persistence of Zika Virus in Body Fluids-Final Report The Presence of SARS-CoV-2 RNA in Feces of COVID-19 Patients A report of three COVID-19 cases with prolonged viral RNA detection in anal swabs Anal swab findings in an infant with COVID-19. Pediatric Investigation Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients. Chinese medical journal Evaluation of SARS-CoV-2 RNA shedding in clinical specimens and clinical characteristics of 10 patients with COVID-19 in Macau Do children need a longer time to shed SARS-CoV-2 in stool than adults? Prolonged viral shedding in feces of pediatric patients with coronavirus disease 2019 Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding Detectable SARS-CoV-2 Viral RNA in Feces of Three Children during Recovery Period of COVID-19 Pneumonia Online ahead of print CoV-2 infected case with viral detection positive in stool but negative in nasopharyngeal samples lasts for 42 days SARS-CoV-2 shedding and infectivity. The Lancet Detection of SARS-CoV-2 in different types of clinical specimens