Duration of SARS-CoV-2 shedding and infectivity in the working age population: a systematic review and meta-analysis
Parole chiave:
SARS-CoV-2, shedding, infectivity, working age population, occupational, return to work, meta-analysis, COVID-19Abstract
Background: During the COVID-19 pandemic, working age individuals have been implicated in sustaining the resurgence of SARS-CoV-2 infections, and multiple outbreaks have been observed in several occupational settings. In this regard, Occupational Physicians play a crucial role in the management of infected workers, particularly in the safe return-to-work of subjects after clinical resolution. To this end, knowledge of the duration of the infective phase in the working age population is essential, taking into account previous evidence suggesting that PCR positivity does not coincide with virus viability. Methods: A systematic review and meta-analysis, searching major scientific databases, including PubMed/MEDLINE, Scopus and Web of Science, were performed in order to synthesize the available evidence regarding the mean and maximal duration of infectivity compared to the mean and maximal duration of viral RNA shedding. A subgroup analysis of the studies was performed according to the immunocompetent or immunocompromised immune status of the majority of the enrolled individuals. Results: Twenty studies were included in the final qualitative and quantitative analysis (866 individuals). Overall, a mean duration of RT-PCR positivity after symptom onset was found equal to 27.9 days (95%CI 23.3-32.5), while the mean duration of replicant competent virus isolation was 7.3 days (95%CI 5.7-8.8). The mean duration of SARS-CoV-2 shedding resulted equal to 26.5 days (95%CI 21.4-31.6) and 36.3 days (95%CI 21.9-50.6), and the mean duration of SARS-CoV-2 infectivity was 6.3 days (95%CI 4.9-7.8) and 29.5 days (95%CI 12.5-46.5), respectively considering immunocompetent and immunocompromised individuals. The maximum duration of infectivity among immunocompetent subjects was reported after 18 days from symptom onset, while in immunocompromised individuals it lasted up to 112 days. Conclusions: These findings suggest that the test-based strategy before return-to-work might not be warranted after 21 days among immunocompetent working age individuals, and could keep many workers out of occupation, reducing their livelihood and productivity.
Riferimenti bibliografici
WHO Director-General's opening remarks at the media briefing on COVID-19 - 11 March 2020. Available online: https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020 (accessed on 12 December 2021)
Joint ECDC-WHO Regional Office for Europe Weekly COVID-19 Surveillance Bulletin. Available online: https://worldhealthorg.shinyapps.io/euro-covid19/ (accessed on 29 November 2021)
Mossong J, Hens N, Jit M et al. Social contacts and mixing patterns relevant to the spread of infectious diseases. PLoS Med. 2008; 5(3), e74. Doi:10.1371/journal.pmed.0050074
Monod M, Blenkinsop A, Xi X et al. Age groups that sustain resurging COVID-19 epidemics in the United States. Science. 2021; 371(6536), eabe8372. Doi:10.1126/science.abe8372
European Centre for Disease Prevention and Control. COVID-19 clusters and outbreaks in occupational settings in the EU/EEA and the UK. Available online: https://www.ecdc.europa.eu/sites/default/files/documents/COVID-19-in-occupational-settings.pdf (accessed on 11 November 2021)
Mutti A. Occupational Medicine in the time of COVID-19. Med Lav. 2020; 111(2), 83-86. Doi:10.23749/mdl.v111i2.9546
European Centre for Disease Prevention and Control. Novel coronavirus (SARS-CoV-2) - Discharge criteria for confirmed COVID-19 cases – When is it safe to discharge COVID-19 cases from the hospital or end home isolation? – 28 February 2020. Available online: https://www.ecdc.europa.eu/sites/default/files/documents/COVID-19-Discharge-criteria.pdf (accessed on 5 Feb-ruary 2022)
Peiris JS, Chu CM, Cheng VC et al. Clinical progression and viral load in a community outbreak of corona-virus-associated SARS pneumonia: a prospective study. Lancet. 2003; 361(9371), 1767-1772. Doi: 10.1016/s0140-6736(03)13412-5
Chan KH, Poon LL, Cheng VC et al. Detection of SARS coronavirus in patients with suspected SARS. Emerg Infect Dis. 2004; 10(2), 294-299. Doi: 10.3201/eid1002.030610
Oh MD, Park WB, Choe PG et al. Viral Load Kinetics of MERS Coronavirus Infection. N Engl J Med. 2016; 375(13), 1303-1305. Doi: 10.1056/NEJMc1511695
Wang Y, Guo Q, Yan Z et al. Factors Associated With Prolonged Viral Shedding in Patients With Avian Influenza A(H7N9) Virus Infection. J Infect Dis. 2018; 217(11), 1708-1717. Doi: 10.1093/infdis/jiy115
Sissoko D, Duraffour S, Kerber R et al. Persistence and clearance of Ebola virus RNA from seminal fluid of Ebola virus disease survivors: a longitudinal analysis and modelling study. Lancet Glob Health. 2017; 5(1), e80-e88. Doi: 10.1016/S2214-109X(16)30243-1
Paz-Bailey G, Rosenberg ES, Doyle K et al. Persistence of Zika Virus in Body Fluids - Final Report. N Engl J Med. 2017; 379(13), 1234-1243. Doi: 10.1056/NEJMoa1613108
Atkinson B, Petersen E. SARS-CoV-2 shedding and infectivity. Lancet. 2020; 395(10233), 1339-1340. Doi:10.1016/S0140-6736(20)30868-0
Michalakis Y, Sofonea MT, Alizon S, Bravo IG. SARS-CoV-2 viral RNA levels are not 'viral load'. Trends Microbiol. 2021; 29(11), 970-972. Doi:10.1016/j.tim.2021.08.008
Jefferson T, Spencer EA, Brassey J, Heneghan C. Viral cultures for COVID-19 infectious potential assessment - a systematic review. Clin Infect Dis. 2020; ciaa1764. Doi:10.1093/cid/ciaa1764
European Centre for Disease Prevention and Control. Infection prevention and control and preparedness for COVID-19 in healthcare settings – Sixth update. 9 February 2021. Available online: https://www.ecdc.europa.eu/sites/default/files/documents/Infection-prevention-and-control-in-healthcare-settings-COVID-19_6th_update_9_Feb_2021.pdf (accessed on 11 November 2021)
Centers for Disease Control and Prevention. Interim Guidance for Managing Healthcare Personnel with SARS-CoV-2 Infection or Exposure to SARS-CoV-2. Available online: https://www.cdc.gov/coronavirus/2019-ncov/hcp/guidance-risk-assesment-hcp.html (accessed on 11 November 2021)
World Health Organization. Criteria for releasing COVID-19 patients from isolation. Scientific Brief. Available online: https://apps.who.int/iris/rest/bitstreams/1282284/retrieve (accessed on 11 November 2021)
Ministero della Salute. COVID-19: indicazioni per la durata ed il termine dell’isolamento e della quarantena. Circular n. 32850 on 12/10/2020. Available online: http://www.normativasanitaria.it/jsp/dettaglio.jsp?id=76613 (accessed on 11 November 2021)
Ministero della Salute. Indicazioni per la riammissione in servizio dei lavoratori dopo assenza per malattia Co-vid-19 correlata. Circular n. 15127 on 12/04/2021. Available online: http://www.normativasanitaria.it/jsp/dettaglio.jsp?id=79702 (accessed on 11 November 2021)
Hansson SO. How Extreme Is the Precautionary Principle?. Nanoethics. 2020; 14, 245–257. Doi: 10.1007/s11569-020-00373-5
Page MJ, McKenzie JE, Bossuyt PM et al. The PRISMA 2020 statement: an updated guideline for reporting sys-tematic reviews. BMJ. 2021; 372(71). Doi: 10.1136/bmj.n71
Università degli Studi di Genova. UNO per TUTTO (platform). Available online: https://unopertutto.unige.net/ (accessed on 5 February 2022)
Organisation for Economic Co-operation and Development. Working age population (indicator). Available online: https://doi.org/10.1787/d339918b-en (accessed on 11 November 2021)
COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Available online: https://www.covid19treatmentguidelines.nih.gov/ (accessed on 11 No-vember 2021)
Shi J, Luo D, Wan X et al. Detecting the skewness of data from the sample size and the five-number summary. arXiv preprint. 2020. arXiv:2010.05749.
Shi J, Luo D, Weng H, et al. Optimally estimating the sample standard deviation from the five-number summary. Res Synth Methods. 2020; 11(5), 641-654. Doi:10.1002/jrsm.1429
Luo D, Wan X, Liu J, Tong T. Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods Med Res. 2018; 27(6), 1785-1805. Doi:10.1177/0962280216669183
Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014; 14, 135. Doi:10.1186/1471-2288-14-135
Deeks JJ, Higgins JPT, Altman DG (editors). Chapter 10: Analysing data and undertaking meta-analyses. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Sys-tematic Reviews of Interventions version 6.2 (updated February 2021). Cochrane, 2021. Available online: www.training.cochrane.org/handbook (accessed on 11 November 2021)
Duval S, Tweedie R. Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics. 2000; 56(2), 455–463. Doi: 10.1111/j.0006-341X.2000.00455.x
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997; 315, 629–634. Doi: 10.1136/bmj.315.7109.629
Alshukairi AN, Tolah AM, Dada A et al. Test-based de-isolation in COVID-19 immunocompromised patients: Cycle threshold value versus SARS-CoV-2 viral culture. Int J Infect Dis. 2021; 108, 112-115. Doi:10.1016/j.ijid.2021.05.027
Aydillo T, Gonzalez-Reiche AS, Aslam S et al. Shedding of Viable SARS-CoV-2 after Immunosuppressive Therapy for Cancer. N Engl J Med. 2020; 383(26), 2586-2588. Doi:10.1056/NEJMc2031670
Basile K, McPhie K, Carter I et al. Cell-based Culture Informs Infectivity and Safe De-Isolation Assessments in Patients with Coronavirus Disease 2019. Clin Infect Dis. 2021; 73(9), e2952-e2959. Doi:10.1093/cid/ciaa1579
Benotmane I, Risch S, Doderer-Lang C et al. Long-term shedding of viable SARS-CoV-2 in kidney transplant re-cipients with COVID-19. Am J Transplant. 2021; 21(8), 2871-2875. Doi:10.1111/ajt.16636
Bullard J, Dust K, Funk D, et al. Predicting Infectious Severe Acute Respiratory Syndrome Coronavirus 2 From Diagnostic Samples. Clin Infect Dis. 2020; 71(10), 2663-2666. Doi:10.1093/cid/ciaa638
Gniazdowski V, Paul Morris C, Wohl S et al. Repeated Coronavirus Disease 2019 Molecular Testing: Correlation of Severe Acute Respiratory Syndrome Coronavirus 2 Culture With Molecular Assays and Cycle Thresholds. Clin Infect Dis. 2021; 73(4), e860-e869. Doi:10.1093/cid/ciaa1616
Jeong HW, Kim SM, Kim HS et al. Viable SARS-CoV-2 in various specimens from COVID-19 patients. Clin Mi-crobiol Infect. 2020; 26(11), 1520-1524. Doi:10.1016/j.cmi.2020.07.020
Kim JY, Bae JY, Bae S et al. Diagnostic usefulness of subgenomic RNA detection of viable SARS-CoV-2 in patients with COVID-19. Clin Microbiol Infect. 2021; S1198-743X(21), 00466-3. Doi:10.1016/j.cmi.2021.08.009
Kujawski SA, Wong KK, Collins JP et al. COVID-19 Investigation Team. Clinical and virologic characteristics of the first 12 patients with coronavirus disease 2019 (COVID-19) in the United States. Nat Med. 2020; 26(6), 861-868. Doi:10.1038/s41591-020-0877-5
Laferl H, Kelani H, Seitz T et al. An approach to lifting self-isolation for health care workers with prolonged shedding of SARS-CoV-2 RNA. Infection. 2021; 49(1), 95-101. Doi:10.1007/s15010-020-01530-4
Li Q, Zheng XS, Shen XR et al. Prolonged shedding of severe acute respiratory syndrome coronavirus 2 in patients with COVID-19. Emerg Microbes Infect. 2020; 9(1), 2571-2577. Doi:10.1080/22221751.2020.1852058
Lu J, Peng J, Xiong Q et al. Clinical, immunological and virological characterization of COVID-19 patients that test re-positive for SARS-CoV-2 by RT-PCR. EBioMedicine. 2020; 59, 102960. Doi:10.1016/j.ebiom.2020.102960
Owusu D, Pomeroy MA, Lewis NM et al. Persistent SARS-CoV-2 RNA Shedding Without Evidence of Infec-tiousness: A Cohort Study of Individuals With COVID-19. J Infect Dis. 2021; 224(8), 1362-1371. Doi:10.1093/infdis/jiab107
Perera RAPM, Tso E, Tsang OTY et al. SARS-CoV-2 Virus Culture and Subgenomic RNA for Respiratory Speci-mens from Patients with Mild Coronavirus Disease. Emerg Infect Dis. 2020; 26(11), 2701-2704. Doi:10.3201/eid2611.203219
Pérez-Lago L, Aldámiz-Echevarría T, García-Martínez R et al. Different Within-Host Viral Evolution Dynamics in Severely Immunosuppressed Cases with Persistent SARS-CoV-2. Biomedicines. 2021; 9(7), 808. Doi:10.3390/biomedicines9070808
Sohn Y, Jeong SJ, Chung WS et al. Assessing Viral Shedding and Infectivity of Asymptomatic or Mildly Symp-tomatic Patients with COVID-19 in a Later Phase. J Clin Med. 2020; 9(9), 2924. Doi:10.3390/jcm9092924
Vetter P, Eberhardt CS, Meyer B et al. Daily Viral Kinetics and Innate and Adaptive Immune Response Assess-ment in COVID-19: a Case Series. mSphere. 2020; 5(6), e00827-20. Doi:10.1128/mSphere.00827-20
Wang X, Huang K, Jiang H et al. Long-Term Existence of SARS-CoV-2 in COVID-19 Patients: Host Immunity, Viral Virulence, and Transmissibility. Virol Sin. 2020; 35(6), 793-802. Doi:10.1007/s12250-020-00308-0
Wölfel R, Corman VM, Guggemos W et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020; 581(7809), 465-469. Doi:10.1038/s41586-020-2196-x
Young BE, Ong SWX, Ng LFP et al. Viral Dynamics and Immune Correlates of Coronavirus Disease 2019 (COVID-19) Severity. Clin Infect Dis. 2021; 73(9), e2932-e2942. Doi:10.1093/cid/ciaa1280
Wan XF, Tang CY, Ritter D et al. SARS-CoV-2 show no infectivity at later stages in a prolonged COVID-19 patient despite positivity in RNA testing. J Med Virol. 2021; 93(7), 4570-4575. Doi:10.1002/jmv.27001
Ashcroft P, Lehtinen S, Angst DC et al. Quantifying the impact of quarantine duration on COVID-19 transmission. Elife. 2021; 10, e63704. Doi:10.7554/eLife.63704
Bays D, Whiteley T, Pindar M et al. Mitigating isolation: The use of rapid antigen testing to reduce the impact of self-isolation periods. medRxiv. 2021; 21268326. Doi:10.1101/2021.12.23.21268326
Thieme CJ, Anft M, Paniskaki K et al. The Magnitude and Functionality of SARS-CoV-2 Reactive Cellular and Humoral Immunity in Transplant Population Is Similar to the General Population Despite Immunosuppression. Transplantation. 2021; 105(10), 2156-2164. Doi:10.1097/TP.0000000000003755
Kamińska D, Augustyniak-Bartosik H, Kościelska-Kasprzak K et al. Comparing Humoral and Cellular Adaptive Immunity during Convalescent Phase of COVID-19 in Hemodialysis Patients and Kidney Transplant Recipients. J Clin Med. 2021;10(21), 4833. Doi: 10.3390/jcm10214833
Jordan SC. Innate and adaptive immune responses to SARS-CoV-2 in humans: relevance to acquired immunity and vaccine responses. Clin Exp Immunol. 2021; 204(3), 310-320. Doi: 10.1111/cei.13582
Corey L, Beyrer C, Cohen MS et al. SARS-CoV-2 Variants in Patients with Immunosuppression. N Engl J Med. 2021; 385(6), 562-566. Doi: 10.1056/NEJMsb2104756
Weigang S, Fuchs J, Zimmer G et al. Within-host evolution of SARS-CoV-2 in an immunosuppressed COVID-19 patient as a source of immune escape variants. Nat Commun. 2021; 12(1), 6405. Doi: 10.1038/s41467-021-26602-3
Binnicker MJ. Can testing predict SARS-CoV-2 infectivity? The potential for certain methods to be surrogates for replication-competent virus. J Clin Microbiol. 2021; 59(11), e0046921. Doi: 10.1128/JCM .00469-21
Pubblicato
Fascicolo
Sezione
Licenza
All Journal's articles are Open Access papers distributed under the terms of the Creative Commons Attribution License CC BY-NC 4.0 Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Reproductions with commercial intent will require written permission and payment of royalties.