scholarly journals Understanding viral shedding of severe acute respiratory coronavirus virus 2 (SARS-CoV-2): Review of current literature

Author(s):  
Lauren M. Fontana ◽  
Angela Holly Villamagna ◽  
Monica K. Sikka ◽  
Jessina C. McGregor

Abstract Objective: Transmission of SARS-CoV-2 has significant implications for hospital infection prevention and control, discharge management, and public health. We reviewed available literature to reach an evidenced-based consensus on the expected duration of viral shedding. Design: We queried 4 scholarly repositories and search engines for studies reporting SARS-CoV-2 viral shedding dynamics by PCR and/or culture available through September 8, 2020. We calculated the pooled median duration of viral RNA shedding from respiratory and fecal sources. Results: The review included 77 studies on SARS-CoV-2. All studies reported PCR-based testing and 12 also included viral culture data. Among 28 studies, the overall pooled median duration of RNA shedding from respiratory sources was 18.4 days (95% CI, 15.5–21.3; I2 = 98.87%; P < .01). When stratified by disease severity, the pooled median duration of viral RNA shedding from respiratory sources was 19.8 days (95% CI, 16.2–23.5; I2 = 96.42%; P < .01) among severely ill patients and 17.2 days (95% CI, 14.0–20.5; I2 = 95.64%; P < .01) in mild-to-moderate illness. Viral RNA was detected up to 92 days after symptom onset. Viable virus was isolated by culture from −6 to 20 days relative to symptom onset. Conclusions: SARS-COV-2 RNA shedding can be prolonged, yet high heterogeneity exists. Detection of viral RNA may not correlate with infectivity since available viral culture data suggests shorter durations of shedding of viable virus. Additional data are needed to determine the duration of shedding of viable virus and the implications for risk of transmission.

Author(s):  
Yves Longtin ◽  
Hugues Charest ◽  
Caroline Quach ◽  
Patrice Savard ◽  
Mariana Baz ◽  
...  

Abstract We performed viral culture of respiratory specimens in 118 severe acute respiratory coronavirus virus 2 (SARS-CoV-2)–infected healthcare workers (HCWs), ∼2 weeks after symptom onset. Only 1 HCW (0.8%) had a positive culture. No factors for prolonged viral shedding were identified. Infectivity is resolved in nearly all HCWs ∼2 weeks after symptom onset.


2020 ◽  
Author(s):  
Mahir Kapmaz ◽  
Ozlem Dogan ◽  
Hacer Akturk ◽  
Berna Ozer ◽  
Elif Nurtop ◽  
...  

Abstract We report infectivity of adult and pediatric COVID-19 patients in presence of viral shedding and anti-SARS-CoV-2 antibody response A total of 408 consequent samples from eleven adult and five pediatric patients with SARS-CoV-2 infection were included. The samples every second day from saliva, nasopharynx, feces, serum, urine, tear were studied by RT-PCR and viral culture. Anti-SARS-CoV-2 antibodies were measured. The median duration of RNA shedding in all specimens was 7(2-15) days in adults and 5(3-19) days in children. The median duration from onset of symptoms to admission was three days.The viral RNA was positive in 44.7 % of the nasopharynx and 37.6% of saliva samples up 16 days in adults and 19 days in chldren. The latest viral culture positivity was detected on day 8 of symptoms in nasopharynx. The viral RNA was found in 6.1% of feces, 4.4% ofserum, 4.3 % of tear, 2.9% of urine. The earliest seroconversion was the 7th day for adults and 8th day for children. Atthe 14th day, total antibody positivity was 78% in adults, and 80% in children. After seroconversion, the viral RNA was still detected in the nasopharynx and saliva of three patients, however, the infectious virus was not present. Earlier hospital admission could be associated with shorter SARS-CoV-2 RNA shedding. The infectivity of patient is very low after 8 days of symptoms. The risk of fecal-oral transmission is very low, and strict hand hygiene measures could be preventive. The positive antibody test result could be used as a discharge criterion.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Joshua L. Santarpia ◽  
Danielle N. Rivera ◽  
Vicki L. Herrera ◽  
M. Jane Morwitzer ◽  
Hannah M. Creager ◽  
...  

Abstract The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan, China in late 2019, and its resulting coronavirus disease, COVID-19, was declared a pandemic by the World Health Organization on March 11, 2020. The rapid global spread of COVID-19 represents perhaps the most significant public health emergency in a century. As the pandemic progressed, a continued paucity of evidence on routes of SARS-CoV-2 transmission has resulted in shifting infection prevention and control guidelines between classically-defined airborne and droplet precautions. During the initial isolation of 13 individuals with COVID-19 at the University of Nebraska Medical Center, we collected air and surface samples to examine viral shedding from isolated individuals. We detected viral contamination among all samples, supporting the use of airborne isolation precautions when caring for COVID-19 patients.


Author(s):  
Daniel Owusu ◽  
Mary A Pomeroy ◽  
Nathaniel M Lewis ◽  
Ashutosh Wadhwa ◽  
Anna R Yousaf ◽  
...  

Abstract Background To better understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding and infectivity, we estimated SARS-CoV-2 RNA shedding duration, described participant characteristics associated with the first negative rRT-PCR test (resolution), and determined if replication-competent viruses was recoverable ≥10 days after symptom onset. Methods We collected serial nasopharyngeal specimens from 109 individuals with rRT-PCR–confirmed COVID-19 in Utah and Wisconsin. We calculated viral RNA shedding resolution probability using the Kaplan-Meier estimator and evaluated characteristics associated with shedding resolution using Cox proportional hazards regression. We attempted viral culture for 35 rRT-PCR–positive nasopharyngeal specimens collected ≥10 days after symptom onset. Results The likelihood of viral RNA shedding resolution at 10 days after symptom onset was approximately 3%. Time to shedding resolution was shorter among participants aged &lt;18 years (adjusted hazards ratio [aHR], 3.01; 95% confidence interval [CI], 1.6–5.6) and longer among those aged ≥50 years (aHR, 0.50; 95% CI, .3–.9) compared to participants aged 18–49 years. No replication-competent viruses were recovered. Conclusions Although most patients were positive for SARS-CoV-2 for ≥10 days after symptom onset, our findings suggest that individuals with mild to moderate COVID-19 are unlikely to be infectious ≥10 days after symptom onset.


2020 ◽  
Vol 9 (9) ◽  
pp. 2924 ◽  
Author(s):  
Yujin Sohn ◽  
Su Jin Jeong ◽  
Won Suk Chung ◽  
Jong Hoon Hyun ◽  
Yae Jee Baek ◽  
...  

Background: The coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a major global public health issue. SARS-CoV-2 infection is confirmed by the detection of viral RNA using reverse transcription polymerase chain reaction (RT-PCR). Prolonged viral shedding has been reported in patients with SARS-CoV-2 infection, but the presence of viral RNA does not always correlate with infectivity. Therefore, the present study aimed to confirm the presence of viable virus in asymptomatic or mildly symptomatic patients in the later phase of the disease, more than two weeks after diagnosis. Method: Asymptomatic or mildly symptomatic COVID-19 patients who had been diagnosed with the disease at least two weeks previously and admitted to a community treatment center (CTC) from 15 March to 10 April 2020 were enrolled in this study. Nasopharyngeal and salivary swab specimens were collected from each patient. Using these specimens, RT-PCR assay and viral culture were performed. Result: In total, 48 patients were enrolled in this study. There were no significant differences in baseline characteristics between the asymptomatic and mildly symptomatic patient groups. RT-PCR assay and viral culture of SARS-CoV-2 were performed using nasopharyngeal and salivary swabs. The results of RT-PCR performed using salivary swab specimens, in terms of cycle threshold (Ct) values, were similar to those of RT-PCR using nasopharyngeal swab specimens. In addition, no viable virus could be cultured from swab specimens collected from the late-phase COVID-19 patients with prolonged viral RNA shedding. Conclusions: In conclusion, our study suggests that even if viral shedding is sustained in asymptomatic or mildly symptomatic patients with later phase of COVID-19, it can be expected that the transmission risk of the virus is low. In addition, saliva can be used as a reliable specimen for the diagnosis of SARS-CoV-2 infection.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 734-735
Author(s):  
Thilaka Arunachalam ◽  
Amit Singh ◽  
Kathleen Stellrecht ◽  
Sarah Elmendorf ◽  
Tarani K Barman ◽  
...  

Abstract Prolonged detection of SARS-CoV-2 viral RNA has been observed in hospitalized congregate care patients following resolution of clinical symptoms. It is unknown whether patients with persistent PCR positivity pose a risk for COVID-19 transmission. The purpose of this study was to examine the results of serial PCR testing, viral load, and viral culture in patients awaiting discharge prior to a negative PCR test. We sampled 14 patients who were admitted from skilled nursing and/or rehabilitation facilities to a large academic medical center, had clinical signs and symptoms of COVID-19, and had multiple PCR-positive tests separated by at least 14 days. PCR-positive nasopharyngeal swabs were obtained from each patient for viral load quantification and viral culture. The mean age of patients was 72.5 years (55 – 92), with a mean peak SOFA score of 5.6 (1 – 11). Patients were hospitalized for a mean of 37.0 days (25 – 60). RNA was detected by PCR for a mean of 32.9 days (19 – 47). Mean viral load for the first PCR-positive nasopharyngeal swab collected at our hospital was 5.81 genomic copies/mL (2.12 – 9.72). Viral load decreased significantly with days from clinical symptom onset (R = -0.69, 95% CI, -0.80 – -0.55). Four out of 28 samples grew active virus via culture, with no active virus isolates after 2 days of symptom onset. Our viral culture data suggests that persistent PCR positivity may not correlate with infectivity, which has important implications for COVID-19 infection control precautions among older congregate care patients.


Author(s):  
Muge Cevik ◽  
Matthew Tate ◽  
Oliver Lloyd ◽  
Alberto Enrico Maraolo ◽  
Jenna Schafers ◽  
...  

Background Viral load kinetics and the duration of viral shedding are important determinants for disease transmission. We aim i) to characterise viral load dynamics, duration of viral RNA, and viable virus shedding of SARS-CoV-2 in various body fluids and ii) to compare SARS-CoV-2 viral dynamics with SARS-CoV-1 and MERS-CoV. Methods: Medline, EMBASE, Europe PMC, preprint servers and grey literature were searched to retrieve all articles reporting viral dynamics and duration of SARS-CoV-2, SARS-CoV-1 and MERS-CoV shedding. We excluded case reports and case series with < 5 patients, or studies that did not report shedding duration from symptom onset. PROSPERO registration: CRD42020181914. Findings: Seventy-nine studies on SARS-CoV-2, 8 on SARS-CoV-1, and 11 on MERS-CoV were included. Mean SARS-CoV-2 RNA shedding duration in upper respiratory tract, lower respiratory tract, stool and serum were 17.0, 14.6, 17.2 and 16.6 days, respectively. Maximum duration of SARS-CoV-2 RNA shedding reported in URT, LRT, stool and serum was 83, 59, 35 and 60 days, respectively. Pooled mean duration of SARS-CoV-2 RNA shedding was positively associated with age (p=0.002), but not gender (p = 0.277). No study to date has detected live virus beyond day nine of illness despite persistently high viral loads. SARS-CoV-2 viral load in the upper respiratory tract appears to peak in the first week of illness, while SARS-CoV-1 and MERS-CoV peak later. Conclusion: Although SARS-CoV-2 RNA shedding in respiratory and stool can be prolonged, duration of viable virus is relatively short-lived. Thus, detection of viral RNA cannot be used to infer infectiousness. High SARS-CoV-2 titres are detectable in the first week of illness with an early peak observed at symptom onset to day 5 of illness. This review underscores the importance of early case finding and isolation, as well as public education on the spectrum of illness. However, given potential delays in the isolation of patients, effective containment of SARS-CoV-2 may be challenging even with an early detection and isolation strategy. Funding: No funding was received.


2021 ◽  
pp. 097321792110656
Author(s):  
Chokkiyil Ponnambath Hafis Ibrahim ◽  
Amir Mohammed Abelshafy ◽  
Maqbool Qadir

The reported median duration of viral shedding after infection with SARS-CoV2 is between 12 and 20 days. It is now established that infected individuals can continue to shed viral ribonucleic acid (RNA) without shedding live virus. This has implications for quarantine and infection control practices. COVID in the acute phase seems to be milder in children, and the duration of viral RNA shedding is shorter in children compared to adults. SARS-CoV-2 infections in the newborn period is rare. Little is known about the duration of viral shedding in preterm infants with vertically acquired SARS-CoV-2. 3 of the 4 preterm infants cared for at our center had prolonged shedding up to 34 days with live viral shedding not seen beyond the second week when tested in 3 of them.


Author(s):  
Dan Yan ◽  
Xiao-Yan Liu ◽  
Ya-nan Zhu ◽  
Li Huang ◽  
Bi-tang Dan ◽  
...  

AbstractBackgroundThe duration of viral shedding is central to guide decisions around isolation precautions and antiviral treatment. However, studies about risk factors associated with prolonged SARS-CoV-2 shedding and the potential impact of Lopinavir/Ritonavir (LPV/r) treatment remain scarce.MethodsIn this retrospective study, data were collected from all SARS-CoV-2 infected patients who were admitted to isolation wards and had RT-PCR conversion at the NO.3 People’s hospital of Hubei province between 31 January and 09 March 2020. We compared clinical features and SARS-CoV-2 RNA shedding between patients with LPV/r treatment and those without. Logistic regression analysis was employed to evaluate risk factors associated with prolonged viral shedding.ResultsOf 120 patients, the median age was 52 years, 54 (45%) were male and 78 (65%) received LPV/r treatment. The median duration of SARS-CoV-2 RNA detection from symptom onset was 23 days (IQR, 18-32 days). Older age (odd ratio [OR] 1.03, 95% confidence interval [CI] 1.00-1.05, p=0.03) and lack of LPV/r treatment (OR 2.42, 95% CI 1.10-5.36, p=0.029) were independent risk factors for prolonged SARS-CoV-2 RNA shedding in multivariate logistic regression analysis. The median duration of viral shedding was shorter in the LPV/r treatment group (n=78) than that in no LPV/r treatment group (n=42) (median, 22 days vs. 28.5 days, p=0.02). Only earlier administration of LPV/r treatment (≤10 days from symptom onset) could shorten the duration of viral shedding.ConclusionsOlder age and lack of LPV/r treatment were independently associated with prolonged SARS-CoV-2 RNA shedding in patients with COVID-19. Earlier administration of LPV/r treatment could shorten viral shedding.Take home messageRisk factors for prolonged SARS-CoV-2 shedding included older age and lack of Lopinavir/Ritonavir treatment. Earlier administration of Lopinavir/Ritonavir treatment could shorten the duration of SARS-CoV-2 RNA shedding.


Author(s):  
Jeroen J.A. van Kampen ◽  
David A.M.C. van de Vijver ◽  
Pieter L.A. Fraaij ◽  
Bart L. Haagmans ◽  
Mart M. Lamers ◽  
...  

ABSTRACTBackgroundLong-term shedding of viral RNA in COVID-19 prevents timely discharge from the hospital or de-escalation of infection prevention and control practices. Key questions are the duration and determinants of infectious virus shedding. We assessed these questions using virus cultures of respiratory tract samples from hospitalized COVID-19 patients as a proxy for infectious virus shedding.MethodsClinical and virological data were obtained from 129 hospitalized COVID-19 patients (89 intensive care, 40 medium care). Generalized estimating equations were used to identify if viral RNA load, detection of viral subgenomic RNA, serum neutralizing antibody response, duration of symptoms, or immunocompromised status were predictive for a positive virus culture.FindingsInfectious virus shedding was detected in 23 of the 129 patients (17,8%). The median duration of shedding was 8 days post onset of symptoms (IQR 5 – 11) and the probability of detecting infectious virus dropped below 5% after 15,2 days post onset of symptoms (95% confidence interval (CI) 13,4 – 17,2). Multivariate analyses identified viral loads above 7 log10 RNA copies/mL (odds ratio [OR]; CI 14,7 (3,57-58,1; p<0,001) as independently associated with isolation of infectious SARS-CoV-2 from the respiratory tract. A serum neutralizing antibody titre of at least 1:20 (OR of 0,01 (CI 0,003-0,08; p<0,001) was independently associated with non-infectious SARS-CoV-2.InterpretationInfection prevention and control guidelines should take into account that patients with severe or critical COVID-19 may shed infectious virus for longer periods of time compared to what has been reported for in patients with mild COVID-19. Infectious virus shedding drops to undetectable levels below a viral RNA load threshold and once serum neutralizing antibodies are present, which warrants the use of quantitative viral RNA load assays and serological assays in test-based strategies to discontinue or de-escalate infection prevention and control precautions.Research in contextEvidence before this studyWe searched PubMed, bioRxiv, and medRxiv for articles that reported on shedding of infectious virus in COVID-19 patients using the search terms (“coronavirus” OR “SARS” OR “SARS-CoV-2” OR “COVID-19”) AND (“shedding” OR “infectivity” OR “infectious” OR “virus culture”) with no language or time restrictions. A detailed study on nine patients with mild COVID-19 reported that infectious virus could not be isolated after more than eight days of symptoms. The probability of isolating infectious virus was less than 5% when viral loads dropped below 6,51 Log10 RNA copies/mL. Similar results were obtained with a larger diagnostic sample set, but that study did not report on clinical parameters such as disease severity. Finally there is a report of a single patient shedding infectious virus up to 18 days after onset of symptoms. No published works were found on the shedding of infectious virus in patients with severe or critical COVID-19, and no published works were found on factors independently associated with shedding of infectious virus.Added value of this studyWe assessed the duration and determinants of infectious virus shedding in 129 patients with severe or critical COVID-19. The duration of infectious virus shedding ranged from 0 to 20 days post onset of symptoms (median 8 days, IQR 5 – 11). The probability of detecting infectious virus dropped below 5% after 15,2 days post onset of symptoms (95% confidence interval (CI) 13,4 – 17,2). Viral loads above 7 log10 RNA copies/mL were independently associated with detection of infectious SARS-CoV-2 from the respiratory tract (odds ratio [OR]; CI 14,7 (3,57-58,1; p<0,001). A serum neutralizing antibody titre of at least 1:20 (OR of 0,01 (CI 0,003-0,08; p<0,001) was independently associated with non-infectious SARS-CoV-2.Implications of all the available evidenceInfection prevention and control guidelines should take into account that patients with severe or critical COVID-19 may shed infectious virus for longer periods of time compared to what has been reported for in patients with mild COVID-19. Quantitative viral RNA load assays and serological assays should be used for test-based strategies to discontinue or de-escalate infection prevention and control precautions.


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