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Research Article| Volume 129, P228-235, April 2023

Duration of viable virus shedding and polymerase chain reaction positivity of the SARS-CoV-2 Omicron variant in the upper respiratory tract: a systematic review and meta-analysis

Open AccessPublished:February 17, 2023DOI:https://doi.org/10.1016/j.ijid.2023.02.011

      Highlights

      • The duration of viable virus shedding of the Omicron variant was 5.16 days.
      • The average duration of polymerase chain reaction positivity of the Omicron variant was 10.82 days.
      • The duration in symptomatic patients was higher than that in asymptomatic patients.
      • Some studies found a difference between the Omicron and Delta variant infections.

      Abstract

      Objectives

      To assess the duration of viable virus shedding and polymerase chain reaction (PCR) positivity of the SARS-CoV-2 Omicron variant in the upper respiratory tract.

      Methods

      We systematically searched PubMed, Cochrane, and Web of Science for original articles reporting the duration of viable virus shedding and PCR positivity of the SARS-CoV-2 Omicron variant in the upper respiratory tract from November 11, 2021 to December 11, 2022. This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered with PROSPERO (CRD42022357349). We used the DerSimonian-Laird random-effects meta-analyses to obtain the pooled value and the 95% confidence intervals.

      Results

      We included 29 studies and 230,227 patients. The pooled duration of viable virus shedding of the SARS-CoV-2 Omicron variant in the upper respiratory tract was 5.16 days (95% CI: 4.18-6.14), and the average duration of PCR positivity was 10.82 days (95% CI: 10.23-11.42). The duration of viable virus shedding and PCR positivity of the SARS-CoV-2 Omicron variant in symptomatic patients was slightly higher than that in asymptomatic patients, but the difference was not significant (P >0.05).

      Conclusion

      The current study improves our understanding of the status of the literature on the duration of viable virus shedding and PCR positivity of Omicron in the upper respiratory tract. Our findings have implications for pandemic control strategies and infection control measures.

      Keywords

      Introduction

      SARS-CoV-2 is a new coronavirus responsible for the COVID-19 pandemic. Over 546 and 6.33 million confirmed COVID-19 cases and deaths, respectively, had been reported to the World Health Organization as of July 4, 2022 [

      World Health Organization. Coronavirus disease (COVID-19) pandemic, https://www.who.int/emergencies/diseases/novel-coronavirus-2019; 2022 [accessed 04 July 2022].

      ]. Since the beginning of the pandemic, SARS-CoV-2 has continually evolved and mutated, producing variants with different transmissibility and virulence levels. Currently, the Omicron variant is the dominant strain of SARS-CoV-2. The first case of Omicron infection was reported to the World Health Organization by South Africa on November 24, 2021. Since then, the variant has spread rapidly to many countries and regions worldwide [

      World Health Organization. Classification of Omicron (B.1.1.529): SARS-CoV-2 variant of concern, https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern); 2021 [accessed 26 November 2021].

      ]. Omicron appears to have a shorter incubation period and series interval but stronger infectivity and immune evasion than Delta and other strains [
      • Wu Y
      • Liu J
      • Liu M
      • Liang W.
      Epidemiologic features and containment of SARS-CoV-2 omicron variant.
      ,
      • Chen J
      • Wang R
      • Gilby NB
      • Wei GW.
      Omicron variant (B.1.1.529): infectivity, vaccine breakthrough, and antibody resistance.
      ], which complicates the prevention and control of Omicron.
      The duration of viral shedding is a key determinant of disease transmission. This indicates the duration of infectiousness, which is a crucial parameter essential for the effective control and modeling of diseases [
      • Cevik M
      • Tate M
      • Lloyd O
      • Maraolo AE
      • Schafers J
      • Ho A.
      SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis.
      ]. Reverse transcription-polymerase chain reaction (PCR) is the gold standard for the diagnosis and screening of COVID-19. However, reverse transcription PCR results may be persistently positive without necessarily indicating the presence of viable virus (e.g., infectious or replication-competent virus) and viral transmissibility [
      • Murata T
      • Sakurai A
      • Suzuki M
      • et al.
      Shedding of viable virus in asymptomatic SARS-CoV-2 carriers.
      ]. In their systematic review and meta-analysis, Cevik et al. [
      • Cevik M
      • Tate M
      • Lloyd O
      • Maraolo AE
      • Schafers J
      • Ho A.
      SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis.
      ] indicated that the mean duration of SARS-CoV-2 PCR positivity was 17.0 days (95% confidence interval [CI]: 15.5-18.6; studies, 43; individuals, 3229) in the upper respiratory tract; they further revealed that no study reported a live virus beyond day 9 of illness.
      The epidemiological characteristics of Omicron are different from those of the original strain and other variants of SARS-CoV-2. Few studies have focused on the duration of viable virus shedding and PCR positivity of the Omicron variant. Studies have reported inconsistent findings regarding the viral load dynamics and viral shedding duration. Therefore, we reviewed the literature available since the emergence of Omicron, assessed the duration of viable virus shedding and PCR positivity of this variant in the upper respiratory tract, and compared the duration of viable virus shedding and PCR positivity of the Omicron variant in different populations.

      Methods

      Search strategy

      This meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline and was registered with PROSPERO (CRD42022357349). The literature (November 11, 2021 to December 11, 2022) was searched for relevant studies. Articles published before November 11, 2021 were excluded because the first confirmed case of the SARS-CoV-2 Omicron variant was reported on November 11, 2021. PubMed, Cochrane, and Web of Science were searched using the following keywords: “SARS-CoV-2” OR “2019-nCoV” OR “COVID-19” AND “virus” OR “viral shedding” OR “rna” OR “ribonucleic” (Supplementary Table S1). No restriction on language or publication status was imposed provided that an English abstract was available. Furthermore, we manually screened the references of the included original studies to obtain additional studies. The initial searches were performed by six investigators (Yu Wu, Zirui Guo, Jie Yuan, Yaping Wang, Guiying Cao, and Peng Gao).

      Outcome measures and study selection

      The following outcome variables were assessed: conversion time to negative viral culture and conversion time to negative PCR results. For both outcomes, we regarded the earliest date of symptom onset or first positive PCR test as the index date of observation. The first day after the last positive PCR or positive culture was regarded as the end date. The duration of viable virus shedding and PCR positivity was estimated in terms of the conversion time to negative viral culture and conversion time to negative PCR, respectively.
      Studies on the Omicron infection that reported viral load kinetics, viral shedding duration, or viable virus shedding duration were included in the current study. We excluded review studies, animal studies, environmental sampling studies, studies lacking clear data on virus shedding and PCR positivity duration, and modeling studies with no original data.
      The search results were screened in two stages. First, the titles and abstracts of the entries were screened, and only relevant articles were retained. Next, the articles were read in detail. The studies were selected for meta-analysis if they reported relevant parameters and CIs or sufficient information to facilitate the calculation of these values.
      From the selected studies, the following data were extracted: the name of the first author, area of study, time period for data collection, characteristics of the study population, type of strain, duration of viable virus shedding or PCR positivity, and 95% CI values. Some studies reported only the median and interquartile range values; for such studies, we calculated the corresponding mean and SD values through an appropriate approximation to ensure consistency in synthesizing data for the meta-analysis [
      • 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.
      ].

      Quality assessment

      Two authors (Yu Wu, Zirui Guo) independently appraised the quality of the included studies. To assess the quality of observational studies, we used a scale modified from the Newcastle-Ottawa scale [
      • Wells G
      • Shea B
      • O’Connell D
      • et al.
      ] by McAloon et al. [
      • McAloon C
      • Collins Á
      • Hunt K
      • et al.
      Incubation period of COVID-19: a rapid systematic review and meta-analysis of observational research.
      ] (Supplementary Table S2). This scale comprises two parts, with a total score of 5 stars. The first part is “external validity”, with a maximum score of 1 star. The second part is “internal validity”, which includes the “exposure window”, with a maximum score of 2 stars, and the “outcomes”, with a maximum score of 2 stars. By combing the scores of the included studies on each part, we divided the studies into three categories (≤1 star: weak; 2-3 stars: moderate; ≥4 stars: strong). Two investigators independently evaluated the studies; the results were compared, and the differences in ratings were resolved through discussion until a consensus was achieved.

      Meta-analysis

      A meta-analysis of continuous outcomes was performed. We analyzed the data obtained during the incubation period. After extracting all essential data into Excel (Microsoft Corporation, Redmond, WA, USA), Stata (version 14.1) was used for the meta-analysis. A random-effects (DerSimonian and Laird method) meta-analysis was performed. The pooled average estimates with 95% CIs were presented using forest plots. To determine the extent of variation across studies, we performed a heterogeneity test using the Higgins method, which was quantified in terms of I2 statistics.

      Results

      Search results

      We identified 28,672 studies by searching the databases and the reference lists of relevant articles. Of these studies, 643 were subjected to full-text review. Finally, 29 studies (230,227 patients) containing information regarding the duration of viable virus shedding and PCR positivity of the Omicron variant were analyzed (Figure 1). Table 1 summarizes the characteristics of the studies included in the current systematic review and meta-analysis.
      Figure 1
      Figure 1Preferred Reporting Items for Systematic Reviews and Meta-Analyses study flow diagram for search up to May 28, 2022.
      Table 1Characteristics of the studies included in the systematic review and meta-analysis.
      StudyArea of studyTime period for dataType of studyDetection methodSample size
      Boucau et al.
      • Boucau J
      • Marino C
      • Regan J
      • et al.
      Duration of shedding of culturable virus in SARS-CoV-2 omicron (BA.1) infection.
      US2021.07-2022.01Cohort studyViral culture & RT-PCR19
      Bouton et al.
      • Bouton TC
      • Atarere J
      • Turcinovic J
      • et al.
      Viral dynamics of Omicron and Delta SARS-CoV-2 variants with implications for timing of release from isolation: a longitudinal cohort study.
      US2021.11-2022.04Cohort studyViral culture85
      Chen et al.
      • Chen X
      • Wang H
      • Ai J
      • et al.
      Identification of CKD, bedridden history and cancer as higher-risk comorbidities and their impact on prognosis of hospitalized Omicron patients: a multi-centre cohort study.
      US2022.03.20-2022.05.10Cohort studyRT-PCR847
      Hay et al.
      • Hay JA
      • Kissler SM
      • Fauver JR
      • et al.
      Viral dynamics and duration of PCR positivity of the SARS-CoV-2 Omicron variant.
      US2021.07.05-2022.01.10Case seriesRT-PCR97
      Hua et al.
      • Hua Q
      • Zheng D
      • Yu B
      • et al.
      Effectiveness of inactivated COVID-19 vaccines against COVID-19 caused by the SARS-CoV-2 Delta and omicron variants: a retrospective cohort study.
      China2022.07.11-2022.07.26Cohort studyRT-PCR225
      Jang et al.
      • Jang YR
      • Jeong-Min K
      • Rhee JE
      • et al.
      Clinical features and duration of viral shedding individuals with SARS-CoV-2 omicron variant infection.
      Korea2021.12Case seriesViral culture9
      Jung et al.
      • Jung J
      • Kang SW
      • Lee S
      • et al.
      Risk of transmission of COVID-19 from healthcare workers returning to work after a 5-day isolation, and kinetics of shedding of viable SARS-CoV-2 variant B.1.1.529 (Omicron).
      Korea2022.03.14-2022.04.03Cohort studyViral culture & RT-PCR32
      Kang et al.
      • Kang SW
      • Kim JY
      • Park H
      • et al.
      Comparison of secondary attack rate and viable virus shedding between patients with SARS-CoV-2 Delta and omicron variants: a prospective cohort study.
      Korea2021.11-2022.05Cohort studyViral culture & RT-PCR34
      Keske et al.
      • Keske Ş
      • Güney-Esken G
      • Vatansever C
      • et al.
      Duration of infectious shedding of SARS-CoV-2 Omicron variant and its relation with symptoms.
      Turkey2022.01.08-2022.02.17Case seriesViral culture & RT-PCR55
      Kim et al.
      • Kim H
      • Yang JS
      • Ko JH
      • et al.
      Can nirmatrelvir/ritonavir treatment shorten the duration of COVID-19 isolation?.
      Korea2022.01-2022.03Cohort studyViral culture37
      Kojima et al.
      • Kojima N
      • Roshani A
      • Klausner JD.
      Duration of COVID-19 PCR positivity for Omicron vs earlier variants.
      US2021.12Case seriesRT-PCR734
      Lin et al.
      • Lin J
      • Frediani JK
      • Damhorst GL
      • et al.
      Where is omicron? Comparison of SARS-CoV-2 RT-PCR and antigen test sensitivity at commonly sampled anatomic sites over the course of disease.
      US2022.01Cohort studyRT-PCR3
      Lu et al.
      • Lu G
      • Zhang Y
      • Zhang H
      • et al.
      Geriatric risk and protective factors for serious COVID-19 outcomes among older adults in Shanghai Omicron wave.
      China2022.04-2022.05Cohort studyRT-PCR1377
      Luna-Muschi et al.
      • Luna-Muschi A
      • Noguera SV
      • Borges IC
      • et al.
      Characterization of severe acute respiratory syndrome coronavirus 2 omicron variant shedding and predictors of viral culture positivity on vaccinated healthcare workers with mild coronavirus disease 2019.
      Brazil2022.01.11-2022.01.24Case seriesViral culture & RT-PCR30
      Ma et al.
      • Ma E
      • Ai J
      • Zhang Y
      • et al.
      Omicron infections profile and vaccination status among 1881 liver transplant recipients: a multi-centre retrospective cohort.
      ChinaBy 2022.06.16Cohort studyRT-PCR11
      Mack et al.
      • Mack CD
      • Wasserman EB
      • Killerby ME
      • et al.
      Results from a test-to-release from isolation strategy among fully vaccinated National Football League players and staff members with COVID-19 - United States, December 14–19, 2021.
      US2021.12.14-2021.12.19Case seriesRT-PCR173
      Okumura et al.
      • Okumura N
      • Tsuzuki S
      • Saito S
      • et al.
      The first eleven cases of SARS-CoV-2 Omicron variant infection in Japan: a focus on viral dynamics.
      Japan2021.11-2021.12Case seriesRT-PCR11
      Pei et al.
      • Ying-Hao P
      • Yuan-Yuan G
      • Hai-Dong Z
      • Qiu-Hua C
      • Xue-Ran G
      • Hai-Qi Z
      • Hua J
      Clinical characteristics and analysis of risk factors for disease progression of patients with SARS-CoV-2 Omicron variant infection: a retrospective study of 25207 cases in a Fangcang hospital.
      China2022.04.05-2022.05.08Cohort studyRT-PCR25168
      Saade et al.
      • Saade C
      • Brengel-Pesce K
      • Gaymard A
      • et al.
      Dynamics of viral shedding during ancestral or Omicron BA.1 SARS-CoV-2 infection and enhancement of pre-existing immunity during breakthrough infections.
      France2021.11-2022.02Case seriesViral culture44
      Shen et al.
      • Shen Y
      • Ai J
      • Lin N
      • et al.
      An open, prospective cohort study of VV116 in Chinese participants infected with SARS-CoV-2 omicron variants.
      China2022.03.08-2022.03.24Randomized controlled trialRT-PCR76
      Takahashi et al.
      • Takahashi K
      • Ishikane M
      • Ujiie M
      • et al.
      Duration of infectious virus shedding by SARS-CoV-2 omicron variant-infected vaccinees.
      Japan2021.11.29-2021.12.18Case seriesViral culture10
      Tassetto et al.
      • Tassetto M
      • Garcia-Knight M
      • Anglin K
      • et al.
      Detection of higher cycle threshold values in culturable SARS-CoV-2 omicron BA.1 sublineage compared with pre-Omicron variant specimens – San Francisco Bay Area, California, July 2021-March 2022.
      US2021.07-2022.03Cohort studyViral culture39
      Tillmann et al.
      • Tillmann FP
      • Figiel L
      • Ricken J
      • et al.
      Effect of third and fourth mRNA-based booster vaccinations on SARS-CoV-2 neutralizing antibody titer formation, risk factors for non-response, and outcome after SARS-CoV-2 omicron breakthrough infections in patients on chronic hemodialysis: a prospective multicenter cohort study.
      Germany-Cohort studyRT-PCR20
      Wang et al.
      • Wang X
      • Chang H
      • Tian H
      • et al.
      Epidemiological and clinical features of SARS-CoV-2 Infection in children during the outbreak of Omicron Variant in Shanghai, March 7-31, 2022.
      ChinaBy 2022.03.31Case seriesRT-PCR376
      Xu et al.
      • Xu N
      • Pan J
      • Sun L
      • et al.
      Interferon α-2b spray shortened viral shedding time of SARS-CoV-2 Omicron variant: an open prospective cohort study.
      China2022.04.16-2022.05.05Cohort studyRT-PCR458
      Yin et al.
      • Yin Y
      • Lin J
      • Yuan S
      • et al.
      The relationship between early isolation and the duration of viral shedding of mild and asymptomatic infection with SARS-CoV-2 Omicron BA.2 variant.
      China2022.03.26-2022.05.20Case seriesRT-PCR199590
      Yu et al.
      • Yu SY
      • Xie JR
      • Luo JJ
      • et al.
      Liver test abnormalities in asymptomatic and mild COVID-19 patients and their association with viral shedding time.
      China2022.04.05-2022.04.29Cohort studyRT-PCR331
      Zeng et al.
      • Zeng QL
      • Lv YJ
      • Liu XJ
      • et al.
      Clinical characteristics of omicron SARS-CoV-2 variant infection after Non-mRNA-Based vaccination in China.
      China2022.01.08-2022.01.29Cohort studyRT-PCR380
      Zhong et al.
      • Zhong W
      • Jiang X
      • Yang X
      • et al.
      The efficacy of Paxlovid in elderly patients infected with SARS-CoV-2 omicron variants: results of a non-randomized clinical trial.
      China2022.04.24-2022.05.28Non-randomized clinical trialRT-PCR36
      RT-PCR, reverse transcription-polymerase chain reaction; US, United States.
      Among the 29 studies, 12, 11, and six exhibited strong, moderate, and weak power, respectively (Supplementary Table S3). A total of 27 were published articles [
      • Boucau J
      • Marino C
      • Regan J
      • et al.
      Duration of shedding of culturable virus in SARS-CoV-2 omicron (BA.1) infection.
      ,
      • Bouton TC
      • Atarere J
      • Turcinovic J
      • et al.
      Viral dynamics of Omicron and Delta SARS-CoV-2 variants with implications for timing of release from isolation: a longitudinal cohort study.
      ,
      • Chen X
      • Wang H
      • Ai J
      • et al.
      Identification of CKD, bedridden history and cancer as higher-risk comorbidities and their impact on prognosis of hospitalized Omicron patients: a multi-centre cohort study.
      ,
      • Hua Q
      • Zheng D
      • Yu B
      • et al.
      Effectiveness of inactivated COVID-19 vaccines against COVID-19 caused by the SARS-CoV-2 Delta and omicron variants: a retrospective cohort study.
      ,
      • Jang YR
      • Jeong-Min K
      • Rhee JE
      • et al.
      Clinical features and duration of viral shedding individuals with SARS-CoV-2 omicron variant infection.
      ,
      • Jung J
      • Kang SW
      • Lee S
      • et al.
      Risk of transmission of COVID-19 from healthcare workers returning to work after a 5-day isolation, and kinetics of shedding of viable SARS-CoV-2 variant B.1.1.529 (Omicron).
      ,
      • Kang SW
      • Kim JY
      • Park H
      • et al.
      Comparison of secondary attack rate and viable virus shedding between patients with SARS-CoV-2 Delta and omicron variants: a prospective cohort study.
      ,
      • Keske Ş
      • Güney-Esken G
      • Vatansever C
      • et al.
      Duration of infectious shedding of SARS-CoV-2 Omicron variant and its relation with symptoms.
      ,
      • Kim H
      • Yang JS
      • Ko JH
      • et al.
      Can nirmatrelvir/ritonavir treatment shorten the duration of COVID-19 isolation?.
      ,
      • Kojima N
      • Roshani A
      • Klausner JD.
      Duration of COVID-19 PCR positivity for Omicron vs earlier variants.
      ,
      • Lu G
      • Zhang Y
      • Zhang H
      • et al.
      Geriatric risk and protective factors for serious COVID-19 outcomes among older adults in Shanghai Omicron wave.
      ,
      • Luna-Muschi A
      • Noguera SV
      • Borges IC
      • et al.
      Characterization of severe acute respiratory syndrome coronavirus 2 omicron variant shedding and predictors of viral culture positivity on vaccinated healthcare workers with mild coronavirus disease 2019.
      ,
      • Ma E
      • Ai J
      • Zhang Y
      • et al.
      Omicron infections profile and vaccination status among 1881 liver transplant recipients: a multi-centre retrospective cohort.
      ,
      • Mack CD
      • Wasserman EB
      • Killerby ME
      • et al.
      Results from a test-to-release from isolation strategy among fully vaccinated National Football League players and staff members with COVID-19 - United States, December 14–19, 2021.
      ,
      • Okumura N
      • Tsuzuki S
      • Saito S
      • et al.
      The first eleven cases of SARS-CoV-2 Omicron variant infection in Japan: a focus on viral dynamics.
      ,
      • Ying-Hao P
      • Yuan-Yuan G
      • Hai-Dong Z
      • Qiu-Hua C
      • Xue-Ran G
      • Hai-Qi Z
      • Hua J
      Clinical characteristics and analysis of risk factors for disease progression of patients with SARS-CoV-2 Omicron variant infection: a retrospective study of 25207 cases in a Fangcang hospital.
      ,
      • Saade C
      • Brengel-Pesce K
      • Gaymard A
      • et al.
      Dynamics of viral shedding during ancestral or Omicron BA.1 SARS-CoV-2 infection and enhancement of pre-existing immunity during breakthrough infections.
      ,
      • Shen Y
      • Ai J
      • Lin N
      • et al.
      An open, prospective cohort study of VV116 in Chinese participants infected with SARS-CoV-2 omicron variants.
      ,
      • Takahashi K
      • Ishikane M
      • Ujiie M
      • et al.
      Duration of infectious virus shedding by SARS-CoV-2 omicron variant-infected vaccinees.
      ,
      • Tassetto M
      • Garcia-Knight M
      • Anglin K
      • et al.
      Detection of higher cycle threshold values in culturable SARS-CoV-2 omicron BA.1 sublineage compared with pre-Omicron variant specimens – San Francisco Bay Area, California, July 2021-March 2022.
      ,
      • Tillmann FP
      • Figiel L
      • Ricken J
      • et al.
      Effect of third and fourth mRNA-based booster vaccinations on SARS-CoV-2 neutralizing antibody titer formation, risk factors for non-response, and outcome after SARS-CoV-2 omicron breakthrough infections in patients on chronic hemodialysis: a prospective multicenter cohort study.
      ,
      • Wang X
      • Chang H
      • Tian H
      • et al.
      Epidemiological and clinical features of SARS-CoV-2 Infection in children during the outbreak of Omicron Variant in Shanghai, March 7-31, 2022.
      ,
      • Xu N
      • Pan J
      • Sun L
      • et al.
      Interferon α-2b spray shortened viral shedding time of SARS-CoV-2 Omicron variant: an open prospective cohort study.
      ,
      • Yin Y
      • Lin J
      • Yuan S
      • et al.
      The relationship between early isolation and the duration of viral shedding of mild and asymptomatic infection with SARS-CoV-2 Omicron BA.2 variant.
      ,
      • Yu SY
      • Xie JR
      • Luo JJ
      • et al.
      Liver test abnormalities in asymptomatic and mild COVID-19 patients and their association with viral shedding time.
      ,
      • Zeng QL
      • Lv YJ
      • Liu XJ
      • et al.
      Clinical characteristics of omicron SARS-CoV-2 variant infection after Non-mRNA-Based vaccination in China.
      ,
      • Zhong W
      • Jiang X
      • Yang X
      • et al.
      The efficacy of Paxlovid in elderly patients infected with SARS-CoV-2 omicron variants: results of a non-randomized clinical trial.
      ], and two were preprints [
      • Hay JA
      • Kissler SM
      • Fauver JR
      • et al.
      Viral dynamics and duration of PCR positivity of the SARS-CoV-2 Omicron variant.
      ,
      • Lin J
      • Frediani JK
      • Damhorst GL
      • et al.
      Where is omicron? Comparison of SARS-CoV-2 RT-PCR and antigen test sensitivity at commonly sampled anatomic sites over the course of disease.
      ]. All 29 studies reported the duration of either viable virus shedding (11 studies [
      • Boucau J
      • Marino C
      • Regan J
      • et al.
      Duration of shedding of culturable virus in SARS-CoV-2 omicron (BA.1) infection.
      ,
      • Bouton TC
      • Atarere J
      • Turcinovic J
      • et al.
      Viral dynamics of Omicron and Delta SARS-CoV-2 variants with implications for timing of release from isolation: a longitudinal cohort study.
      ,
      • Jang YR
      • Jeong-Min K
      • Rhee JE
      • et al.
      Clinical features and duration of viral shedding individuals with SARS-CoV-2 omicron variant infection.
      ,
      • Jung J
      • Kang SW
      • Lee S
      • et al.
      Risk of transmission of COVID-19 from healthcare workers returning to work after a 5-day isolation, and kinetics of shedding of viable SARS-CoV-2 variant B.1.1.529 (Omicron).
      ,
      • Kang SW
      • Kim JY
      • Park H
      • et al.
      Comparison of secondary attack rate and viable virus shedding between patients with SARS-CoV-2 Delta and omicron variants: a prospective cohort study.
      ,
      • Keske Ş
      • Güney-Esken G
      • Vatansever C
      • et al.
      Duration of infectious shedding of SARS-CoV-2 Omicron variant and its relation with symptoms.
      ,
      • Kim H
      • Yang JS
      • Ko JH
      • et al.
      Can nirmatrelvir/ritonavir treatment shorten the duration of COVID-19 isolation?.
      ,
      • Luna-Muschi A
      • Noguera SV
      • Borges IC
      • et al.
      Characterization of severe acute respiratory syndrome coronavirus 2 omicron variant shedding and predictors of viral culture positivity on vaccinated healthcare workers with mild coronavirus disease 2019.
      ,
      • Saade C
      • Brengel-Pesce K
      • Gaymard A
      • et al.
      Dynamics of viral shedding during ancestral or Omicron BA.1 SARS-CoV-2 infection and enhancement of pre-existing immunity during breakthrough infections.
      ,
      • Takahashi K
      • Ishikane M
      • Ujiie M
      • et al.
      Duration of infectious virus shedding by SARS-CoV-2 omicron variant-infected vaccinees.
      ,
      • Tassetto M
      • Garcia-Knight M
      • Anglin K
      • et al.
      Detection of higher cycle threshold values in culturable SARS-CoV-2 omicron BA.1 sublineage compared with pre-Omicron variant specimens – San Francisco Bay Area, California, July 2021-March 2022.
      ]) or PCR positivity (23 studies [
      • Boucau J
      • Marino C
      • Regan J
      • et al.
      Duration of shedding of culturable virus in SARS-CoV-2 omicron (BA.1) infection.
      ,
      • Chen X
      • Wang H
      • Ai J
      • et al.
      Identification of CKD, bedridden history and cancer as higher-risk comorbidities and their impact on prognosis of hospitalized Omicron patients: a multi-centre cohort study.
      ,
      • Hua Q
      • Zheng D
      • Yu B
      • et al.
      Effectiveness of inactivated COVID-19 vaccines against COVID-19 caused by the SARS-CoV-2 Delta and omicron variants: a retrospective cohort study.
      ,
      • Jung J
      • Kang SW
      • Lee S
      • et al.
      Risk of transmission of COVID-19 from healthcare workers returning to work after a 5-day isolation, and kinetics of shedding of viable SARS-CoV-2 variant B.1.1.529 (Omicron).
      ,
      • Kang SW
      • Kim JY
      • Park H
      • et al.
      Comparison of secondary attack rate and viable virus shedding between patients with SARS-CoV-2 Delta and omicron variants: a prospective cohort study.
      ,
      • Keske Ş
      • Güney-Esken G
      • Vatansever C
      • et al.
      Duration of infectious shedding of SARS-CoV-2 Omicron variant and its relation with symptoms.
      ,
      • Kojima N
      • Roshani A
      • Klausner JD.
      Duration of COVID-19 PCR positivity for Omicron vs earlier variants.
      ,
      • Lu G
      • Zhang Y
      • Zhang H
      • et al.
      Geriatric risk and protective factors for serious COVID-19 outcomes among older adults in Shanghai Omicron wave.
      ,
      • Luna-Muschi A
      • Noguera SV
      • Borges IC
      • et al.
      Characterization of severe acute respiratory syndrome coronavirus 2 omicron variant shedding and predictors of viral culture positivity on vaccinated healthcare workers with mild coronavirus disease 2019.
      ,
      • Ma E
      • Ai J
      • Zhang Y
      • et al.
      Omicron infections profile and vaccination status among 1881 liver transplant recipients: a multi-centre retrospective cohort.
      ,
      • Mack CD
      • Wasserman EB
      • Killerby ME
      • et al.
      Results from a test-to-release from isolation strategy among fully vaccinated National Football League players and staff members with COVID-19 - United States, December 14–19, 2021.
      ,
      • Okumura N
      • Tsuzuki S
      • Saito S
      • et al.
      The first eleven cases of SARS-CoV-2 Omicron variant infection in Japan: a focus on viral dynamics.
      ,
      • Ying-Hao P
      • Yuan-Yuan G
      • Hai-Dong Z
      • Qiu-Hua C
      • Xue-Ran G
      • Hai-Qi Z
      • Hua J
      Clinical characteristics and analysis of risk factors for disease progression of patients with SARS-CoV-2 Omicron variant infection: a retrospective study of 25207 cases in a Fangcang hospital.
      ,
      • Shen Y
      • Ai J
      • Lin N
      • et al.
      An open, prospective cohort study of VV116 in Chinese participants infected with SARS-CoV-2 omicron variants.
      ,
      • Tillmann FP
      • Figiel L
      • Ricken J
      • et al.
      Effect of third and fourth mRNA-based booster vaccinations on SARS-CoV-2 neutralizing antibody titer formation, risk factors for non-response, and outcome after SARS-CoV-2 omicron breakthrough infections in patients on chronic hemodialysis: a prospective multicenter cohort study.
      ,
      • Wang X
      • Chang H
      • Tian H
      • et al.
      Epidemiological and clinical features of SARS-CoV-2 Infection in children during the outbreak of Omicron Variant in Shanghai, March 7-31, 2022.
      ,
      • Xu N
      • Pan J
      • Sun L
      • et al.
      Interferon α-2b spray shortened viral shedding time of SARS-CoV-2 Omicron variant: an open prospective cohort study.
      ,
      • Yin Y
      • Lin J
      • Yuan S
      • et al.
      The relationship between early isolation and the duration of viral shedding of mild and asymptomatic infection with SARS-CoV-2 Omicron BA.2 variant.
      ,
      • Yu SY
      • Xie JR
      • Luo JJ
      • et al.
      Liver test abnormalities in asymptomatic and mild COVID-19 patients and their association with viral shedding time.
      ,
      • Zeng QL
      • Lv YJ
      • Liu XJ
      • et al.
      Clinical characteristics of omicron SARS-CoV-2 variant infection after Non-mRNA-Based vaccination in China.
      ,
      • Zhong W
      • Jiang X
      • Yang X
      • et al.
      The efficacy of Paxlovid in elderly patients infected with SARS-CoV-2 omicron variants: results of a non-randomized clinical trial.
      ,
      • Hay JA
      • Kissler SM
      • Fauver JR
      • et al.
      Viral dynamics and duration of PCR positivity of the SARS-CoV-2 Omicron variant.
      ,
      • Lin J
      • Frediani JK
      • Damhorst GL
      • et al.
      Where is omicron? Comparison of SARS-CoV-2 RT-PCR and antigen test sensitivity at commonly sampled anatomic sites over the course of disease.
      ]) of the Omicron variant in the upper respiratory tract. Of the included studies, seven were conducted in the United States, [
      • Boucau J
      • Marino C
      • Regan J
      • et al.
      Duration of shedding of culturable virus in SARS-CoV-2 omicron (BA.1) infection.
      ,
      • Bouton TC
      • Atarere J
      • Turcinovic J
      • et al.
      Viral dynamics of Omicron and Delta SARS-CoV-2 variants with implications for timing of release from isolation: a longitudinal cohort study.
      ,
      • Kojima N
      • Roshani A
      • Klausner JD.
      Duration of COVID-19 PCR positivity for Omicron vs earlier variants.
      ,
      • Mack CD
      • Wasserman EB
      • Killerby ME
      • et al.
      Results from a test-to-release from isolation strategy among fully vaccinated National Football League players and staff members with COVID-19 - United States, December 14–19, 2021.
      ,
      • Tassetto M
      • Garcia-Knight M
      • Anglin K
      • et al.
      Detection of higher cycle threshold values in culturable SARS-CoV-2 omicron BA.1 sublineage compared with pre-Omicron variant specimens – San Francisco Bay Area, California, July 2021-March 2022.
      ,
      • Hay JA
      • Kissler SM
      • Fauver JR
      • et al.
      Viral dynamics and duration of PCR positivity of the SARS-CoV-2 Omicron variant.
      ,
      • Lin J
      • Frediani JK
      • Damhorst GL
      • et al.
      Where is omicron? Comparison of SARS-CoV-2 RT-PCR and antigen test sensitivity at commonly sampled anatomic sites over the course of disease.
      ], 12 in China [
      • Chen X
      • Wang H
      • Ai J
      • et al.
      Identification of CKD, bedridden history and cancer as higher-risk comorbidities and their impact on prognosis of hospitalized Omicron patients: a multi-centre cohort study.
      ,
      • Hua Q
      • Zheng D
      • Yu B
      • et al.
      Effectiveness of inactivated COVID-19 vaccines against COVID-19 caused by the SARS-CoV-2 Delta and omicron variants: a retrospective cohort study.
      ,
      • Lu G
      • Zhang Y
      • Zhang H
      • et al.
      Geriatric risk and protective factors for serious COVID-19 outcomes among older adults in Shanghai Omicron wave.
      ,
      • Ma E
      • Ai J
      • Zhang Y
      • et al.
      Omicron infections profile and vaccination status among 1881 liver transplant recipients: a multi-centre retrospective cohort.
      ,
      • Ying-Hao P
      • Yuan-Yuan G
      • Hai-Dong Z
      • Qiu-Hua C
      • Xue-Ran G
      • Hai-Qi Z
      • Hua J
      Clinical characteristics and analysis of risk factors for disease progression of patients with SARS-CoV-2 Omicron variant infection: a retrospective study of 25207 cases in a Fangcang hospital.
      ,
      • Shen Y
      • Ai J
      • Lin N
      • et al.
      An open, prospective cohort study of VV116 in Chinese participants infected with SARS-CoV-2 omicron variants.
      ,
      • Wang X
      • Chang H
      • Tian H
      • et al.
      Epidemiological and clinical features of SARS-CoV-2 Infection in children during the outbreak of Omicron Variant in Shanghai, March 7-31, 2022.
      ,
      • Xu N
      • Pan J
      • Sun L
      • et al.
      Interferon α-2b spray shortened viral shedding time of SARS-CoV-2 Omicron variant: an open prospective cohort study.
      ,
      • Yin Y
      • Lin J
      • Yuan S
      • et al.
      The relationship between early isolation and the duration of viral shedding of mild and asymptomatic infection with SARS-CoV-2 Omicron BA.2 variant.
      ,
      • Yu SY
      • Xie JR
      • Luo JJ
      • et al.
      Liver test abnormalities in asymptomatic and mild COVID-19 patients and their association with viral shedding time.
      ,
      • Zeng QL
      • Lv YJ
      • Liu XJ
      • et al.
      Clinical characteristics of omicron SARS-CoV-2 variant infection after Non-mRNA-Based vaccination in China.
      ,
      • Zhong W
      • Jiang X
      • Yang X
      • et al.
      The efficacy of Paxlovid in elderly patients infected with SARS-CoV-2 omicron variants: results of a non-randomized clinical trial.
      ], two in Japan [
      • Okumura N
      • Tsuzuki S
      • Saito S
      • et al.
      The first eleven cases of SARS-CoV-2 Omicron variant infection in Japan: a focus on viral dynamics.
      ,
      • Takahashi K
      • Ishikane M
      • Ujiie M
      • et al.
      Duration of infectious virus shedding by SARS-CoV-2 omicron variant-infected vaccinees.
      ], and three in Korea [
      • Jang YR
      • Jeong-Min K
      • Rhee JE
      • et al.
      Clinical features and duration of viral shedding individuals with SARS-CoV-2 omicron variant infection.
      ,
      • Kang SW
      • Kim JY
      • Park H
      • et al.
      Comparison of secondary attack rate and viable virus shedding between patients with SARS-CoV-2 Delta and omicron variants: a prospective cohort study.
      ,
      • Kim H
      • Yang JS
      • Ko JH
      • et al.
      Can nirmatrelvir/ritonavir treatment shorten the duration of COVID-19 isolation?.
      ]. A total of 11 studies were case series [
      • Jang YR
      • Jeong-Min K
      • Rhee JE
      • et al.
      Clinical features and duration of viral shedding individuals with SARS-CoV-2 omicron variant infection.
      ,
      • Keske Ş
      • Güney-Esken G
      • Vatansever C
      • et al.
      Duration of infectious shedding of SARS-CoV-2 Omicron variant and its relation with symptoms.
      ,
      • Kojima N
      • Roshani A
      • Klausner JD.
      Duration of COVID-19 PCR positivity for Omicron vs earlier variants.
      ,
      • Luna-Muschi A
      • Noguera SV
      • Borges IC
      • et al.
      Characterization of severe acute respiratory syndrome coronavirus 2 omicron variant shedding and predictors of viral culture positivity on vaccinated healthcare workers with mild coronavirus disease 2019.
      ,
      • Mack CD
      • Wasserman EB
      • Killerby ME
      • et al.
      Results from a test-to-release from isolation strategy among fully vaccinated National Football League players and staff members with COVID-19 - United States, December 14–19, 2021.
      ,
      • Okumura N
      • Tsuzuki S
      • Saito S
      • et al.
      The first eleven cases of SARS-CoV-2 Omicron variant infection in Japan: a focus on viral dynamics.
      ,
      • Saade C
      • Brengel-Pesce K
      • Gaymard A
      • et al.
      Dynamics of viral shedding during ancestral or Omicron BA.1 SARS-CoV-2 infection and enhancement of pre-existing immunity during breakthrough infections.
      ,
      • Takahashi K
      • Ishikane M
      • Ujiie M
      • et al.
      Duration of infectious virus shedding by SARS-CoV-2 omicron variant-infected vaccinees.
      ,
      • Wang X
      • Chang H
      • Tian H
      • et al.
      Epidemiological and clinical features of SARS-CoV-2 Infection in children during the outbreak of Omicron Variant in Shanghai, March 7-31, 2022.
      ,
      • Yin Y
      • Lin J
      • Yuan S
      • et al.
      The relationship between early isolation and the duration of viral shedding of mild and asymptomatic infection with SARS-CoV-2 Omicron BA.2 variant.
      ,
      • Hay JA
      • Kissler SM
      • Fauver JR
      • et al.
      Viral dynamics and duration of PCR positivity of the SARS-CoV-2 Omicron variant.
      ], 16 were cohort studies [
      • Boucau J
      • Marino C
      • Regan J
      • et al.
      Duration of shedding of culturable virus in SARS-CoV-2 omicron (BA.1) infection.
      ,
      • Bouton TC
      • Atarere J
      • Turcinovic J
      • et al.
      Viral dynamics of Omicron and Delta SARS-CoV-2 variants with implications for timing of release from isolation: a longitudinal cohort study.
      ,
      • Chen X
      • Wang H
      • Ai J
      • et al.
      Identification of CKD, bedridden history and cancer as higher-risk comorbidities and their impact on prognosis of hospitalized Omicron patients: a multi-centre cohort study.
      ,
      • Hua Q
      • Zheng D
      • Yu B
      • et al.
      Effectiveness of inactivated COVID-19 vaccines against COVID-19 caused by the SARS-CoV-2 Delta and omicron variants: a retrospective cohort study.
      ,
      • Jung J
      • Kang SW
      • Lee S
      • et al.
      Risk of transmission of COVID-19 from healthcare workers returning to work after a 5-day isolation, and kinetics of shedding of viable SARS-CoV-2 variant B.1.1.529 (Omicron).
      ,
      • Kang SW
      • Kim JY
      • Park H
      • et al.
      Comparison of secondary attack rate and viable virus shedding between patients with SARS-CoV-2 Delta and omicron variants: a prospective cohort study.
      ,
      • Kim H
      • Yang JS
      • Ko JH
      • et al.
      Can nirmatrelvir/ritonavir treatment shorten the duration of COVID-19 isolation?.
      ,
      • Lu G
      • Zhang Y
      • Zhang H
      • et al.
      Geriatric risk and protective factors for serious COVID-19 outcomes among older adults in Shanghai Omicron wave.
      ,
      • Ma E
      • Ai J
      • Zhang Y
      • et al.
      Omicron infections profile and vaccination status among 1881 liver transplant recipients: a multi-centre retrospective cohort.
      ,
      • Ying-Hao P
      • Yuan-Yuan G
      • Hai-Dong Z
      • Qiu-Hua C
      • Xue-Ran G
      • Hai-Qi Z
      • Hua J
      Clinical characteristics and analysis of risk factors for disease progression of patients with SARS-CoV-2 Omicron variant infection: a retrospective study of 25207 cases in a Fangcang hospital.
      ,
      • Tassetto M
      • Garcia-Knight M
      • Anglin K
      • et al.
      Detection of higher cycle threshold values in culturable SARS-CoV-2 omicron BA.1 sublineage compared with pre-Omicron variant specimens – San Francisco Bay Area, California, July 2021-March 2022.
      ,
      • Tillmann FP
      • Figiel L
      • Ricken J
      • et al.
      Effect of third and fourth mRNA-based booster vaccinations on SARS-CoV-2 neutralizing antibody titer formation, risk factors for non-response, and outcome after SARS-CoV-2 omicron breakthrough infections in patients on chronic hemodialysis: a prospective multicenter cohort study.
      ,
      • Xu N
      • Pan J
      • Sun L
      • et al.
      Interferon α-2b spray shortened viral shedding time of SARS-CoV-2 Omicron variant: an open prospective cohort study.
      ,
      • Yu SY
      • Xie JR
      • Luo JJ
      • et al.
      Liver test abnormalities in asymptomatic and mild COVID-19 patients and their association with viral shedding time.
      ,
      • Zeng QL
      • Lv YJ
      • Liu XJ
      • et al.
      Clinical characteristics of omicron SARS-CoV-2 variant infection after Non-mRNA-Based vaccination in China.
      ,
      • Lin J
      • Frediani JK
      • Damhorst GL
      • et al.
      Where is omicron? Comparison of SARS-CoV-2 RT-PCR and antigen test sensitivity at commonly sampled anatomic sites over the course of disease.
      ], one was a randomized controlled trial [
      • Shen Y
      • Ai J
      • Lin N
      • et al.
      An open, prospective cohort study of VV116 in Chinese participants infected with SARS-CoV-2 omicron variants.
      ], and one was a nonrandomized clinical trial [
      • Zhong W
      • Jiang X
      • Yang X
      • et al.
      The efficacy of Paxlovid in elderly patients infected with SARS-CoV-2 omicron variants: results of a non-randomized clinical trial.
      ].

      Duration of viable virus shedding

      A total of 11 studies (n = 384) reported the duration of viable virus shedding of Omicron; the pooled viable virus shedding duration was 5.16 days (95% CI: 4.18-6.14; Figure 2). The maximum duration of viable virus shedding was 15 days in the upper respiratory tract [
      • Bouton TC
      • Atarere J
      • Turcinovic J
      • et al.
      Viral dynamics of Omicron and Delta SARS-CoV-2 variants with implications for timing of release from isolation: a longitudinal cohort study.
      ].
      Figure 2
      Figure 2Forest plot for the meta-analysis of viable virus shedding duration of the SARS-CoV-2 Omicron variant in upper respiratory tract. CI, confidence interval; DL, DerSimonian and Laird method.
      Boucau et al. [
      • Boucau J
      • Marino C
      • Regan J
      • et al.
      Duration of shedding of culturable virus in SARS-CoV-2 omicron (BA.1) infection.
      ] revealed that >50% of all patients carried replication-competent, culturable virus on day 5 and 25% of all patients had culturable virus on day 8. Takahashi et al. [
      • Takahashi K
      • Ishikane M
      • Ujiie M
      • et al.
      Duration of infectious virus shedding by SARS-CoV-2 omicron variant-infected vaccinees.
      ] detected an infectious virus in 10 patients with Omicron infection, and the highest proportion (41.7%) of virus isolates was detected in samples collected 2-5 days after diagnosis. Jang et al. [
      • Jang YR
      • Jeong-Min K
      • Rhee JE
      • et al.
      Clinical features and duration of viral shedding individuals with SARS-CoV-2 omicron variant infection.
      ] reported that the rate of Omicron culture positivity was 22-100% in unvaccinated patients within 0-8 days after symptom onset and the rate of viral culture positivity on day 5 was the highest (100%). The preliminary data obtained from the National Institute of Infectious Diseases [

      National Institute of Infectious Diseases disease control and prevention center. Active epidemiological investigation on SARS-CoV-2 infection caused by Omicron variant (Pango lineage B.1.1.529) in Japan: preliminary report on infectious period, https://www.niid.go.jp/niid/en/2019-ncov-e/10884-covid19-66-en.html; 2022 [accessed 05 January 2022].

      ], which conducts disease surveillance in Japan, indicated that 41.2% of all patients with Omicron infection had a culturable virus 3-6 days after diagnosis, and no infectious virus was detected in the respiratory samples collected 10 days after diagnosis or symptom onset. Keske et al. [
      • Keske Ş
      • Güney-Esken G
      • Vatansever C
      • et al.
      Duration of infectious shedding of SARS-CoV-2 Omicron variant and its relation with symptoms.
      ] revealed that in 19% of all patients, the duration of shedding was longer than that of symptoms. On day 5, four patients reported the absence of symptoms; although, the viral culture was positive.

      Duration of PCR positivity

      A total of 23 studies (n = 230,013) reported the duration of PCR positivity of Omicron; the pooled PCR positivity duration was 10.82 days (95% CI: 10.23-11.42; Figure 3). The maximum duration of PCR positivity was 23 days in the upper respiratory tract [
      • Boucau J
      • Marino C
      • Regan J
      • et al.
      Duration of shedding of culturable virus in SARS-CoV-2 omicron (BA.1) infection.
      ].
      Figure 3
      Figure 3Forest plot for the meta-analysis of PCR positivity duration of the SARS-CoV-2 Omicron variant in upper respiratory tract. CI, confidence interval; DL, DerSimonian and Laird method.
      Boucau et al. [
      • Boucau J
      • Marino C
      • Regan J
      • et al.
      Duration of shedding of culturable virus in SARS-CoV-2 omicron (BA.1) infection.
      ] simultaneously reported the duration of viable virus shedding and PCR positivity of Omicron in the upper respiratory tract. The mean duration of PCR positivity was 14.40 days (95% CI: 12.02-16.78), which was higher than that of viable virus shedding (6.00 days; 95% CI: 4.56-7.44).
      Takahashi et al. [
      • Takahashi K
      • Ishikane M
      • Ujiie M
      • et al.
      Duration of infectious virus shedding by SARS-CoV-2 omicron variant-infected vaccinees.
      ] reported that the highest amount of Omicron RNA was detected 2-5 days after diagnosis or symptom onset and then decreased gradually until it was markedly reduced 10 days after diagnosis or symptom onset. The lowest quantitation cycle (Cq) value (i.e., viral RNA levels) was 18.7-30. The period with the lowest Cq value was that from 1 day before symptoms onset to 5 days after it. At least three patients were infectious during the incubation period.

      Subgroup analysis

      Duration of viable virus shedding and PCR positivity of Omicron in symptomatic and asymptomatic patients

      Two studies reported the duration of PCR positivity in symptomatic and asymptomatic patients [
      • Shen Y
      • Ai J
      • Lin N
      • et al.
      An open, prospective cohort study of VV116 in Chinese participants infected with SARS-CoV-2 omicron variants.
      ,
      • Wang X
      • Chang H
      • Tian H
      • et al.
      Epidemiological and clinical features of SARS-CoV-2 Infection in children during the outbreak of Omicron Variant in Shanghai, March 7-31, 2022.
      ]. Shen et al. [
      • Shen Y
      • Ai J
      • Lin N
      • et al.
      An open, prospective cohort study of VV116 in Chinese participants infected with SARS-CoV-2 omicron variants.
      ] indicated that the mean duration of PCR positivity was slightly higher in symptomatic patients than in asymptomatic patients; however, the difference was nonsignificant (P >0.05). By contrast, Wang et al. [
      • Wang X
      • Chang H
      • Tian H
      • et al.
      Epidemiological and clinical features of SARS-CoV-2 Infection in children during the outbreak of Omicron Variant in Shanghai, March 7-31, 2022.
      ] revealed no difference between symptomatic and asymptomatic patients; both were 11.70 days (P = 0.064, Table 2).
      Table 2Duration of viable virus shedding and PCR positivity of the SARS-CoV-2 Omicron variant in patients with different characteristics.
      StudyOutcome variableCharacteristics of patientsSample SizeMean duration (95% confidence interval)
      Shen et al
      • Shen Y
      • Ai J
      • Lin N
      • et al.
      An open, prospective cohort study of VV116 in Chinese participants infected with SARS-CoV-2 omicron variants.
      Duration of PCR positivitySymptomatic3912.25 (10.99-13.51)
      Asymptomatic379.95 (8.69-11.20)
      Wang et al
      • Wang X
      • Chang H
      • Tian H
      • et al.
      Epidemiological and clinical features of SARS-CoV-2 Infection in children during the outbreak of Omicron Variant in Shanghai, March 7-31, 2022.
      Duration of PCR positivitySymptomatic25711.70 (11.26-12.14)
      Asymptomatic11911.70(11.00-12.40)
      Takahashi et al
      • Takahashi K
      • Ishikane M
      • Ujiie M
      • et al.
      Duration of infectious virus shedding by SARS-CoV-2 omicron variant-infected vaccinees.
      Duration of viable virus sheddingSymptomatic86.25(4.98-7.52)
      Asymptomatic25.00(5.00-5.00)
      Bouton et al
      • Bouton TC
      • Atarere J
      • Turcinovic J
      • et al.
      Viral dynamics of Omicron and Delta SARS-CoV-2 variants with implications for timing of release from isolation: a longitudinal cohort study.
      Duration of viable virus sheddingFully vaccinated by two doses443.00(2.09-3.91)
      Vaccinated with a third booster dose412.67(1.96-3.37)
      Shen et al
      • Shen Y
      • Ai J
      • Lin N
      • et al.
      An open, prospective cohort study of VV116 in Chinese participants infected with SARS-CoV-2 omicron variants.
      Duration of PCR positivityUnvaccinated1213.05 (11.34-14.76)
      Fully vaccinated by two doses3610.46 (9.07-11.85)
      Vaccinated with a third booster dose2711.13 (9.48-12.79)
      Zeng et al.
      • Zeng QL
      • Lv YJ
      • Liu XJ
      • et al.
      Clinical characteristics of omicron SARS-CoV-2 variant infection after Non-mRNA-Based vaccination in China.
      Duration of PCR positivityFull inactivated vaccination35517.00 (16.23-17.77)
      Full recombinant vaccination1421.53 (17.87-25.20)
      Partial vaccination1116.67 (8.65-24.69)
      Ma et al.
      • Ma E
      • Ai J
      • Zhang Y
      • et al.
      Omicron infections profile and vaccination status among 1881 liver transplant recipients: a multi-centre retrospective cohort.
      Duration of PCR positivityUnvaccinated311.05 (5.19-16.90)
      Vaccinated1111.67 (7.16-16.18)
      Hua et al.
      • Hua Q
      • Zheng D
      • Yu B
      • et al.
      Effectiveness of inactivated COVID-19 vaccines against COVID-19 caused by the SARS-CoV-2 Delta and omicron variants: a retrospective cohort study.
      Duration of PCR positivityUnvaccinated2210.67 (9.01-12.32)
      Fully vaccinated6410.33 (9.78-10.89)
      Booster vaccination13911.00 (10.50-11.50)
      Chen et al.
      • Chen X
      • Wang H
      • Ai J
      • et al.
      Identification of CKD, bedridden history and cancer as higher-risk comorbidities and their impact on prognosis of hospitalized Omicron patients: a multi-centre cohort study.
      Duration of PCR positivityFully vaccinated or booster33910.00 (9.52-10.48)
      Not fully vaccinated26814.33 (13.71-14.96)
      PCR, polymerase chain reaction.
      Only Takahashi et al. [
      • Takahashi K
      • Ishikane M
      • Ujiie M
      • et al.
      Duration of infectious virus shedding by SARS-CoV-2 omicron variant-infected vaccinees.
      ] reported the duration of viable virus shedding in symptomatic and asymptomatic patients. They detected the infectious virus in 10 patients (symptomatic, eight; asymptomatic, two) and found that the duration of viable virus shedding was similar between symptomatic and asymptomatic patients (6.25 vs 5.00 days, respectively; P >0.05). Two symptomatic patients shed the live virus before symptom onset (i.e., incubation period).

      Duration of viable virus shedding and PCR positivity of the Omicron in patients with different vaccination statuses

      Six studies compared the duration of viable virus shedding and PCR positivity of Omicron across patients with different vaccination statuses [
      • Bouton TC
      • Atarere J
      • Turcinovic J
      • et al.
      Viral dynamics of Omicron and Delta SARS-CoV-2 variants with implications for timing of release from isolation: a longitudinal cohort study.
      ,
      • Chen X
      • Wang H
      • Ai J
      • et al.
      Identification of CKD, bedridden history and cancer as higher-risk comorbidities and their impact on prognosis of hospitalized Omicron patients: a multi-centre cohort study.
      ,
      • Hua Q
      • Zheng D
      • Yu B
      • et al.
      Effectiveness of inactivated COVID-19 vaccines against COVID-19 caused by the SARS-CoV-2 Delta and omicron variants: a retrospective cohort study.
      ,
      • Ma E
      • Ai J
      • Zhang Y
      • et al.
      Omicron infections profile and vaccination status among 1881 liver transplant recipients: a multi-centre retrospective cohort.
      ,
      • Shen Y
      • Ai J
      • Lin N
      • et al.
      An open, prospective cohort study of VV116 in Chinese participants infected with SARS-CoV-2 omicron variants.
      ,
      • Zeng QL
      • Lv YJ
      • Liu XJ
      • et al.
      Clinical characteristics of omicron SARS-CoV-2 variant infection after Non-mRNA-Based vaccination in China.
      ]. Bouton et al. [
      • Bouton TC
      • Atarere J
      • Turcinovic J
      • et al.
      Viral dynamics of Omicron and Delta SARS-CoV-2 variants with implications for timing of release from isolation: a longitudinal cohort study.
      ] revealed that the mean duration of viable virus shedding was 3.00 days (95% CI: 2.09-3.91) for fully vaccinated (two doses) patients and 2.67 days (95% CI: 1.96-3.37) for booster-vaccinated (third dose) patients.
      Chen et al. [
      • Chen X
      • Wang H
      • Ai J
      • et al.
      Identification of CKD, bedridden history and cancer as higher-risk comorbidities and their impact on prognosis of hospitalized Omicron patients: a multi-centre cohort study.
      ] indicated that the full or booster vaccination shortened the duration of PCR positivity (adjusted hazard ratio = 1.40, P = 0.001). Shen et al. [
      • Shen Y
      • Ai J
      • Lin N
      • et al.
      An open, prospective cohort study of VV116 in Chinese participants infected with SARS-CoV-2 omicron variants.
      ] reported that the mean duration of PCR positivity in unvaccinated, fully vaccinated, and booster-vaccinated patients were 13.05, 10.46, and 11.13 days, respectively; however, the difference was nonsignificant (P >0.05). As shown in Table 2, the findings reported by Hua et al. [
      • Hua Q
      • Zheng D
      • Yu B
      • et al.
      Effectiveness of inactivated COVID-19 vaccines against COVID-19 caused by the SARS-CoV-2 Delta and omicron variants: a retrospective cohort study.
      ] were similar to those reported by Shen et al. [
      • Shen Y
      • Ai J
      • Lin N
      • et al.
      An open, prospective cohort study of VV116 in Chinese participants infected with SARS-CoV-2 omicron variants.
      ].

      Duration of viable virus shedding and PCR positivity of SARS-CoV-2 in patients with Omicron infection and Delta infection

      Boucau et al. [
      • Boucau J
      • Marino C
      • Regan J
      • et al.
      Duration of shedding of culturable virus in SARS-CoV-2 omicron (BA.1) infection.
      ] compared the duration of viable virus shedding and PCR positivity between patients with the Omicron infection and those with the Delta infection. They found no difference between the two groups in the duration of viable virus shedding (both 6.00 days) or PCR positivity (Omicron: 12.00; Delta: 12.67 days; P >0.05).
      Kang et al. [
      • Kang SW
      • Kim JY
      • Park H
      • et al.
      Comparison of secondary attack rate and viable virus shedding between patients with SARS-CoV-2 Delta and omicron variants: a prospective cohort study.
      ] revealed that Omicron exhibited a shorter duration of PCR positivity (genomic and subgenomic RNA) and viable virus shedding than Delta (P <0.01, Table 3). Hay et al. [
      • Hay JA
      • Kissler SM
      • Fauver JR
      • et al.
      Viral dynamics and duration of PCR positivity of the SARS-CoV-2 Omicron variant.
      ] reported that the mean duration of PCR positivity was 9.87 days for Omicron (95% CI: 8.83-10.9) compared with 10.9 days (95% CI: 9.41-12.4) for Delta (Table 3). The peak viral RNA load (cycle threshold [Ct] value) was lower for Omicron than for Delta (Omicron: Ct, 23.3; 95% CI: 22.4-24.3; Delta: Ct, 20.5; 95% CI: 19.2-21.8).
      Table 3Duration of viable virus shedding and PCR positivity of the SARS-CoV-2 Omicron variant in patients with Omicron variant and Delta variant.
      StudyOutcome variableVariantSample sizeMean duration (95%CI)
      Boucau et al.
      • Boucau J
      • Marino C
      • Regan J
      • et al.
      Duration of shedding of culturable virus in SARS-CoV-2 omicron (BA.1) infection.
      Duration of viable virus sheddingOmicron196.00 (5.10-6.90)
      Delta376.00 (5.68-6.32)
      Duration of PCR positivityOmicron1912.00 (10.20-13.80)
      Delta3712.67 (11.70-13.63)
      Bouton et al.
      • Bouton TC
      • Atarere J
      • Turcinovic J
      • et al.
      Viral dynamics of Omicron and Delta SARS-CoV-2 variants with implications for timing of release from isolation: a longitudinal cohort study.
      Duration of viable virus sheddingOmicron753.00 (2.32-3.68)
      Delta163.67 (1.28-6.06)
      Hay et al.
      • Hay JA
      • Kissler SM
      • Fauver JR
      • et al.
      Viral dynamics and duration of PCR positivity of the SARS-CoV-2 Omicron variant.
      Duration of PCR positivityOmicron1079.87 (8.83-10.90)
      Delta9710.90 (9.41-12.40)
      Kang et al.
      • Kang SW
      • Kim JY
      • Park H
      • et al.
      Comparison of secondary attack rate and viable virus shedding between patients with SARS-CoV-2 Delta and omicron variants: a prospective cohort study.
      Duration of viable virus sheddingOmicron344.00 (2.44-5.56)
      Delta488.17 (6.44-9.90)
      Duration of PCR positivityOmicron349.00 (8.04-9.96)
      Delta4820.33 (18.39-22.28)
      Hua et al.
      • Hua Q
      • Zheng D
      • Yu B
      • et al.
      Effectiveness of inactivated COVID-19 vaccines against COVID-19 caused by the SARS-CoV-2 Delta and omicron variants: a retrospective cohort study.
      Duration of PCR positivityOmicron22511.00 (10.61-11.39)
      Delta32616.50 (15.61-17.39)
      PCR, polymerase chain reaction.

      Discussion

      We reviewed the viral dynamics of Omicron, including the duration of viable virus shedding and PCR positivity. The mean duration of viable virus shedding and PCR positivity were 5.16 (95% CI: 4.18-6.14) and 10.82 (95% CI: 10.23-11.42) days, respectively.
      Few studies have been conducted on the viable virus shedding of the Omicron variant. Because of the difficulty in obtaining information on the duration of viable virus shedding, most studies have assessed the duration of PCR positivity (i.e., the time of viral RNA shedding). Cevik et al. [
      • Cevik M
      • Tate M
      • Lloyd O
      • Maraolo AE
      • Schafers J
      • Ho A.
      SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis.
      ] reviewed and meta-analyzed 43 studies (3229 individuals) published until June 2020. They stated that the mean duration of SARS-CoV-2 RNA shedding was 17.0 days (95% CI: 15.5-18.6) in the upper respiratory tract. Fontana et al. [
      • Fontana LM
      • Villamagna AH
      • Sikka MK
      • McGregor JC.
      Understanding viral shedding of severe acute respiratory coronavirus virus 2 (SARS-CoV-2): review of current literature.
      ] reviewed 28 studies published through September 8, 2020; 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 <0.01). Viable virus was isolated (culture) between -6 and 20 days from symptom onset. The aforementioned studies focused mainly on the original strain of SARS-CoV-2, and the duration of PCR positivity was higher in these studies than in the current study. Omicron has a shorter incubation period [
      • Wu Y
      • Kang L
      • Guo Z
      • Liu J
      • Liu M
      • Liang W.
      Incubation period of COVID-19 caused by unique SARS-CoV-2 strains: a systematic review and meta-analysis.
      ] and a higher transmission rate [
      • Liu Y
      • Rocklöv J.
      The effective reproductive number of the Omicron variant of SARS-CoV-2 is several times relative to Delta.
      ] than the previously prevalent SARS-CoV-2 variants. Because of the shortened duration of viable virus shedding of Omicron, recent public health guidelines in several countries have recommended withdrawing isolation-related restrictions for asymptomatic patients who test positive for COVID-19 and shortening the quarantine time for the patients’ close contacts.
      In this study, the duration of PCR positivity of Omicron in the upper respiratory tract was considerably longer than that of viable virus shedding. Although Omicron may exhibit a long duration of PCR positivity (approximately 23 days), most studies reported no live virus isolation beyond day 10 after symptom onset. Cevik et al. [
      • Cevik M
      • Tate M
      • Lloyd O
      • Maraolo AE
      • Schafers J
      • Ho A.
      SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis.
      ], however, indicated that patients with SARS-CoV-2 infection have prolonged RNA shedding for approximately 83 days; yet, no live virus was isolated beyond day 9 after symptom onset, despite the persistently high loads of viral RNA. Fontana et al. [
      • Fontana LM
      • Villamagna AH
      • Sikka MK
      • McGregor JC.
      Understanding viral shedding of severe acute respiratory coronavirus virus 2 (SARS-CoV-2): review of current literature.
      ] found that the duration of RNA shedding of SARS-CoV-2 exceeded that of viable virus shedding (45 vs 13 days, respectively). These findings indicated that, in clinical practice, repeat testing might not be indicated to deem patients no longer infectious. Prevention and control strategies should be adjusted according to the duration of viable virus shedding.
      Patients with SARS-CoV-2 infection are infectious during the incubation period. In their study (February 24, 2020 to April 2, 2021), Jones et al. [
      • Jones TC
      • Biele G
      • Mühlemann B
      • et al.
      Estimating infectiousness throughout SARS-CoV-2 infection course.
      ] examined 415,935 patients with COVID-19 in and around Berlin, Germany to evaluate the viral load over the disease course. The viral load peaked 1-3 days before symptom onset, indicating that the virus shedding in patients with high infectivity could begin a few days before the onset of symptoms. Takahashi et al. [
      • Takahashi K
      • Ishikane M
      • Ujiie M
      • et al.
      Duration of infectious virus shedding by SARS-CoV-2 omicron variant-infected vaccinees.
      ] demonstrated that at least three of 18 patients were infectious during the incubation period. Studies on viable virus shedding and viral dynamics in asymptomatic and symptomatic patients with Omicron infection are scarce, thus necessitating further studies.
      In the current study, the duration of viable virus shedding and PCR positivity was slightly higher in symptomatic patients than in asymptomatic patients; although, the difference was nonsignificant (P >0.05). Studies have indicated that viral loads are similar between asymptomatic and symptomatic patients with SARS-CoV-2 infection, and viral load is the predominant predictive factor for virus viability in asymptomatic carriers [
      • Cevik M
      • Tate M
      • Lloyd O
      • Maraolo AE
      • Schafers J
      • Ho A.
      SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis.
      ,
      • Murata T
      • Sakurai A
      • Suzuki M
      • et al.
      Shedding of viable virus in asymptomatic SARS-CoV-2 carriers.
      ]. Nevertheless, most studies have reported faster viral clearance in asymptomatic patients than in symptomatic patients [
      • Yan D
      • Zhang X
      • Chen C
      • et al.
      Characteristics of viral shedding time in SARS-CoV-2 infections: a systematic review and meta-analysis.
      ]. This finding is consistent with the viral kinetics observed for other respiratory viruses, such as influenza and Middle East respiratory syndrome-related coronavirus, in which patients with asymptomatic infection have a shorter duration of viral shedding than those with symptomatic infection [
      • Cevik M
      • Tate M
      • Lloyd O
      • Maraolo AE
      • Schafers J
      • Ho A.
      SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis.
      ]. In the study conducted by Yan et al. [
      • Yan D
      • Zhang X
      • Chen C
      • et al.
      Characteristics of viral shedding time in SARS-CoV-2 infections: a systematic review and meta-analysis.
      ], the mean duration of viral shedding in symptomatic patients was 19.7 days (95% CI: 17.2-22.7), which was significantly longer than that in asymptomatic infections (10.9 days; 95% CI: 8.3-14.3; P <0.05). One reason for this is that viral clearance is faster in asymptomatic patients than in symptomatic patients [
      • Lu Y
      • Li Y
      • Deng W
      • et al.
      Symptomatic infection is associated with prolonged duration of viral shedding in mild coronavirus disease 2019: a retrospective study of 110 children in wuhan.
      ,
      • Xiao T
      • Wang Y
      • Yuan J
      • et al.
      Early viral clearance and antibody kinetics of COVID-19 among asymptomatic carriers.
      ]. Another reason may be that the duration of viral shedding in asymptomatic patients was calculated from the first positive PCR result and was dependent primarily on close contact tracking. Viral shedding in these individuals might have begun before the first positive PCR result and may have been missed because of the absence of clinical symptoms.
      Although we found no difference among unvaccinated, fully vaccinated, and booster-vaccinated patients in terms of the duration of viable virus shedding, complete vaccination with inactivated vaccines has been reported to promote early viral clearance. The magnitude of protection against prolonged viral shedding may be correlated with vaccine-induced antiviral immunity [
      • Hu Z
      • Yin Y
      • Wang K
      • et al.
      Impact of inactivated COVID-19 vaccines on viral shedding in B.1.617.2 (Delta) variant-infected patients.
      ].
      To the best of our knowledge, this study, a meta-analysis of the duration of viable virus shedding and PCR positivity of Omicron in the upper respiratory tract, is the first to compare the aforementioned parameters among symptomatic and asymptomatic patients, vaccinated and unvaccinated patients, and patients with Omicron infection and those with Delta infection. Our findings may facilitate public health-related policy making for the prevention and control of COVID-19.
      Our study has some limitations. First, almost all patients assessed in the included studies received various treatments, which might have modified the shedding dynamics. Second, many studies provided no information on the daily virus culture and PCR test results of the patients, which may have affected the measurement accuracy of the duration of viable virus shedding and PCR positivity. Finally, few studies have evaluated the duration of viable virus shedding of Omicron. The duration of viable virus shedding was estimated in a limited number of patients within a short period, which limits the generalizability of our findings. Furthermore, most studies reported the shedding duration in terms of median and interquartile range values, but the meta-analysis necessitated their conversion to mean and SD values. The validity of this conversion was based on the assumption that the data corresponding to the duration of viral shedding exhibited a normal distribution, which might not have been true for some studies.

      Conclusion

      The current study improves our understanding of the status of the literature on the duration of viable virus shedding and PCR positivity of Omicron in the upper respiratory tract. Our findings have implications for pandemic control strategies and infection control measures. The mean durations of viable virus shedding and PCR positivity were 5.16 and 10.82 days, respectively. Although Omicron RNA shedding from respiratory samples can be prolonged, the duration of viable virus is relatively short. The current study may provide important insights for the policy makers engaged in making public health-related policies.

      Funding

      This study was supported by the grant from the National Key Research and Development Project of China (2021ZD0114104, 2021ZD0114105, 2021ZD0114101) and the National Natural Science Foundation of China (71934002, 72122001).

      Ethical approval

      This study did not involve individual patient information; so, there was no requirement for written informed consent.

      Data sharing

      No additional data are available.

      Access to Data statement

      Min Liu and Yu Wu had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

      CRediT authorship contribution statement

      Yu Wu: Conceptualization, Writing – original draft, Data curation, Formal analysis. Zirui Guo: Data curation, Formal analysis. Jie Yuan: Data curation, Formal analysis. Guiying Cao: Data curation, Formal analysis. Yaping Wang: Data curation, Formal analysis. Peng Gao: Data curation, Formal analysis. Jue Liu: Conceptualization, Writing – original draft, Formal analysis. Min Liu: Conceptualization, Writing – original draft, Formal analysis.

      Declaration of competing interest

      The authors have no competing interests to declare.

      Acknowledgments

      This manuscript was edited by Wallace Academic Editing.

      Appendix. Supplementary materials

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