Systemic Inflammatory Cytokines Associate With SARS-COV-2 Viral Shedding Time in Covid-19 Inpatients

Shi, Jing; Cheng, Chongsheng; Yu, Muqing; Li, Xiaochen; Wang, Ke; Tao, Yu; Zhou, Ying; Zhou, Min; Xu, Shuyun; Qin, Lü; Yang, Zhenyu; Zhang, Cong; Yue, Junqing; Liu, Xiansheng; Renz, Harald; Xie, Min

doi:10.21203/rs.3.rs-31556/v1

Cited by 2 publications

(7 citation statements)

References 22 publications

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“…20 studies evaluated duration of viral RNA shedding based on disease severity. 13 of these studies reported longer duration of viral shedding in patients with severe illness than in those with non-severe illness, 17 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 whereas five studies in upper respiratory tract samples 16 , 18 , 35 , 36 , 37 and one study in stool samples 38 reported similar shedding durations according to disease severity. One study reported shorter duration of viral shedding in moderate to severe illness than in mild to moderate illness.…”

Section: Resultsmentioning

confidence: 98%

“…350 articles were retrieved for full-text review. After reviewing the eligibility criteria, 79 studies (5340 individuals) on SARS-CoV-2, 2 , 3 , 4 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ,…”

Section: Resultsmentioning

confidence: 99%

“…All but one study 40 that examined the effect of age on SARS-CoV-2 shedding identified an association between older age (older than 60 years) and prolonged viral RNA shedding. 23 , 24 , 26 , 31 , 35 , 36 , 37 , 41 , 42 , 43 Three studies identified age as an independent risk factor for delayed viral clearance. 23 , 24 , 36 Male sex was also associated with prolonged shedding, 23 , 36 , 44 and the association remained significant even when patients were stratified based on illness severity.…”

Section: Resultsmentioning

confidence: 99%

“…Fang et al (2020) 29 Cai et al (2020) 24 Hu et al (2020) 35 Kim et al (2020) 4 Le et al (2020) 57 Lo et al (2020) 68 Ling et al (2020) 45 Qian et al (2020) 71 Wu et al (2020) 38 Xiao et al (2020) 43 Xu et al (2020) 36 Xu et al (2020) 12 Yongchen et al (2020) 34 Young et al (2020) 20 Zhou et al (2020) 40 Zhou et al (2020) 33 Zhu et al (2020) 82 Sakurai et al (2020) 41 To et al (2020) 58 Huang et al (2020) 49 Liang et al (2020) 47 Shi et al (2020) 31 Talmy et al (2020) 42 Chen et al (2020) 26 Hu et al (2020) 53 Song et al (2020) 75 Yang et al (2020) 54 Wu et al (2020) 79 Zhang et al (2020) 22 Fu et al (2020) 64 Tan et al (2020) 17 Kujawski et al (2020) 16 Yan et al (2020) 37 Yang et al (2020) 81 Xu et al (2020) 80 Huang et al (2020) 21 Chen et al (2020) 25 Chang et al (2020) 61 Li et al (2020) 66 Pongpirul et al (2020) 70 Tan et al (2020) 10 Wang et al (2020) 77 Zha et al (2020) 46 longer duration of viral shedding in patients with severe illness than in those with non-severe illness,…”

Section: Sementioning

confidence: 99%

“…23,24,36 Male sex was also associated with prolonged shedding, 23,36,44 and the association remained significant even when patients were stratified based on illness severity. 23,36 Corticosteroid treatment was associated with delayed viral clearance in four studies, 31,36,45,46 and one study that recruited 120 patients with critical illness found no difference between corticosteroid and control groups. 47 A randomised, placebo-controlled trial of remdesivir in adults with severe COVID-19 found a similar decline in viral load over time in remdesivir and control groups, as well as similar proportions of patients with undetectable viral RNA at 28 days.…”

Section: Overallmentioning

confidence: 99%

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SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis

et al. 2021

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Background Viral load kinetics and duration of viral shedding are important determinants for disease transmission. We aimed to characterise viral load dynamics, duration of viral RNA shedding, and viable virus shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in various body fluids, and to compare SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) viral dynamics. Methods In this systematic review and meta-analysis, we searched databases, including MEDLINE, Embase, Europe PubMed Central, medRxiv, and bioRxiv, and the grey literature, for research articles published between Jan 1, 2003, and June 6, 2020. We included case series (with five or more participants), cohort studies, and randomised controlled trials that reported SARS-CoV-2, SARS-CoV, or MERS-CoV infection, and reported viral load kinetics, duration of viral shedding, or viable virus. Two authors independently extracted data from published studies, or contacted authors to request data, and assessed study quality and risk of bias using the Joanna Briggs Institute Critical Appraisal Checklist tools. We calculated the mean duration of viral shedding and 95% CIs for every study included and applied the random-effects model to estimate a pooled effect size. We used a weighted meta-regression with an unrestricted maximum likelihood model to assess the effect of potential moderators on the pooled effect size. This study is registered with PROSPERO, CRD42020181914. Findings 79 studies (5340 individuals) on SARS-CoV-2, eight studies (1858 individuals) on SARS-CoV, and 11 studies (799 individuals) on MERS-CoV were included. Mean duration of SARS-CoV-2 RNA shedding was 17•0 days (95% CI 15•5-18•6; 43 studies, 3229 individuals) in upper respiratory tract, 14•6 days (9•3-20•0; seven studies, 260 individuals) in lower respiratory tract, 17•2 days (14•4-20•1; 13 studies, 586 individuals) in stool, and 16•6 days (3•6-29•7; two studies, 108 individuals) in serum samples. Maximum shedding duration was 83 days in the upper respiratory tract, 59 days in the lower respiratory tract, 126 days in stools, and 60 days in serum. Pooled mean SARS-CoV-2 shedding duration was positively associated with age (slope 0•304 [95% CI 0•115-0•493]; p=0•0016). No study detected live virus beyond day 9 of illness, despite persistently high viral loads, which were inferred from cycle threshold values. SARS-CoV-2 viral load in the upper respiratory tract appeared to peak in the first week of illness, whereas that of SARS-CoV peaked at days 10-14 and that of MERS-CoV peaked at days 7-10. Interpretation Although SARS-CoV-2 RNA shedding in respiratory and stool samples can be prolonged, duration of viable virus is relatively short-lived. SARS-CoV-2 titres in the upper respiratory tract peak in the first week of illness. Early case finding and isolation, and public education on the spectrum of illness and period of infectiousness are key to the effective containment of SARS-CoV-2. Funding None.

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Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Sementioning

confidence: 99%

Section: Overallmentioning

confidence: 99%

See 3 more Smart Citations

SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis

et al. 2021

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SARS-CoV-2, SARS-CoV-1 and MERS-CoV viral load dynamics, duration of viral shedding and infectiousness – a living systematic review and meta-analysis

Çevik

Tate

Lloyd

et al. 2020

Preprint

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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.

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Systemic Inflammatory Cytokines Associate With SARS-COV-2 Viral Shedding Time in Covid-19 Inpatients

Cited by 2 publications

References 22 publications

SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis

SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis

SARS-CoV-2, SARS-CoV-1 and MERS-CoV viral load dynamics, duration of viral shedding and infectiousness – a living systematic review and meta-analysis

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