Search strategy used for MEDLINE.
Search strategy used for EMBASE.
Search strategy used for Cochrane Central.
Search strategy used for Web of Science Core Collection.
Search strategy used for medRxiv and bioRxiv.
Meta-regression of dispersion parameter (k) with the standard deviation (SD) of rVLs from contributing studies with low risk of bias (Pearson’s r = −0.73). Pooled estimates of k were determined from …
Meta-regression of dispersion parameter (k) with the standard deviation (SD) of rVLs from all contributing studies (Pearson’s r = −0.26). Pooled estimates of k were determined from the literature. …
Random-effects meta-analyses comparing the expected rVLs for COVID-19, SARS and A(H1N1)pdm09 cases during the infectious period. Quantitative specimen measurements were used to estimate rVLs, which …
Random-effects meta-analyses comparing the expected rVLs of adult (≥18 years old) COVID-19 cases with pediatric (<18 years old) ones (top) and symptomatic/presymptomatic infections with asymptomatic …
Random-effects meta-analyses, based on the risk of bias of contributing studies, of the expected rVLs of COVID-19 cases during the infectious period. Quantitative rVLs refer to virus concentrations …
Random-effects meta-analyses, based on the risk of bias of contributing studies, of the expected rVLs of SARS cases during the infectious period. Quantitative rVLs refer to virus concentrations in …
Random-effects meta-analyses, based on the risk of bias of contributing studies, of the expected rVLs of A(H1N1)pdm09 cases during the infectious period. Quantitative rVLs refer to virus …
Random-effects meta-analyses, based on the risk of bias of contributing studies, of the expected rVLs of adult (≥18 years old) COVID-19 cases during the infectious period. Quantitative rVLs refer to …
Random-effects meta-analyses, based on the risk of bias of contributing studies, of the expected rVLs of symptomatic/presymptomatic (≥18 years old) COVID-19 cases during the infectious period. …
(A) Estimated distribution of rVL for SARS-CoV-2 (N = 3834 samples from N = 26 studies) and A(H1N1)pdm09 (N = 512 samples from N = 10 studies) throughout the infectious periods. (B, C) Estimated …
(A–D) Normal (p≤0.01) (A), lognormal (p≤0.01) (B), gamma (p≤0.005) (C) and Weibull (p>0.10, not significant [NS]) (D) probability plots for individual sample data of SARS-CoV-2 respiratory viral …
(A–C) Estimated rVLs of SARS-CoV-2 (A), SARS-CoV-1 (B) and A(H1N1)pdm09 (C) across case percentile (cp) throughout the infectious periods. (D–G) Estimated SARS-CoV-2 rVLs for adult (D), pediatric (E)…
Editable version of Figure 4—figure supplement 3.
Editable version of Figure 4—figure supplement 4.
(A, B) Estimated kinetics of uninfected (blue) and productively infected (red) airway epithelial cells (left axis) and SARS-CoV-2 (right axis) in the respiratory tract, as shown in linear (A) and …
(A, B) Estimated likelihood of respiratory particles containing viable SARS-CoV-2 when expelled by the mean (top) or 98th case percentile (cp) (bottom) COVID-19 cases at −1 (A) or 1 (B) days from …
(A–E) Estimated likelihood that droplets and aerosols contain viable SARS-CoV-2 when expelled by the 25th case percentile (cp) (A), mean (B), 65th cp (C), 80th cp (D) or 90th cp (E) for COVID-19 …
(A–D) Rate profiles of particles expelled while talking (A), singing (B), breathing (C) and coughing (D). (E) Comparison of the rate profiles of aerosol emission from singing and different …
(A–C) Case heterogeneity in the total SARS-CoV-2 shedding rate (over all particle sizes) by talking at a moderate amplitude (A), breathing (B) or coughing (C) for COVID-19 cases across the …
(A, B) Estimated time for a A(H1N1)pdm09 case to expel one virion via only aerosols (A) or either droplets or aerosols (B) by talking, singing, breathing or coughing. (C, D) Estimated time for a …
Study* | Country | No. of cases included (no. of specimens) | No. of pediatric cases (no. of specimens) | No. of asymptomatic cases (no. of specimens) | Disease caused by virus (WHO case definition) | Treatments given (type)† | Individual data extracted (diluent volume reported)‡ | Adjusted viral load§ (type of specimen) | Weight, % (meta-analysis category)|| | Weight, % (meta-regression) | Risk of bias¶ |
---|---|---|---|---|---|---|---|---|---|---|---|
Argyropoulos et al., 2020 | USA | 205 (205) | 0 | 0 | COVID-19 (confirmed) | N/A | No (no) | Yes (NPS) | 3.80 (V), 5.09 (A), 3.98 (S/Ps) | 2.13 | ******** |
Baggio et al., 2020 | Switzerland | 405 (405) | 58 (58) | 0 | COVID-19 (confirmed) | N/A | Yes (no) | Yes (NPS) | 3.84 (V), 5.14 (A), 13.9 (P), 3.88 (S/Ps) | 4.20 | ******* |
Fajnzylber et al., 2020 | USA | - (31) | 0 | 0 | COVID-19 (confirmed) | Yes (remdesivir) | Yes (yes) | Yes (NPS, OPS) No (Spu) | 3.45 (V), 4.62 (A), 3.76 (S/Ps) | 0.32 | ******** |
Hung et al., 2020 | South Korea | 2 (8) | 1 (6) | 0 | COVID-19 (confirmed) | N/A | Yes (no) | Yes (NPS, OPS) | 2.53 (V), 4.06 (S/Ps) | 0.08 | ****** |
Hung et al., 2020 | South Korea | 12 (27) | 12 (27) | 3 (7) | COVID-19 (confirmed) | N/A | Yes (no) | Yes (NPS) | 3.43 (V), 17.5 (P), 4.10 (S/Ps), 14.3 (As) | 0.28 | ******** |
Hung et al., 2020 | China | 41 (310) | 0 | 0 | COVID-19 (confirmed) | Yes (control group: lopinavir ritonavir, antimicrobial treatment for secondary bacterial infection as indicated clinically, hydrocortisone for those requiring oxygen support) | No (no) | Yes (NPS, OPS, POS) | 3.81 (V), 5.10 (A), 3.81 (S/Ps) | 3.22 | ********* |
Hurst et al., 2020 | USA | 133 (133) | 54 (54) | 52 (52) | COVID-19 (confirmed) | Yes (remdesivir) | Yes (no) | Yes (NPS) | 3.77 (V), 15.3 (P), 3.88 (S/Ps), 21.6 (As) | 1.38 | ******** |
Iwasaki et al., 2020 | Japan | 5 (5) | 0 | 0 | COVID-19 (confirmed) | N/A | Yes (no) | Yes (NPS) | 2.53 (V), 3.37 (A), 4.12 (S/Ps) | 0.05 | **** |
Kawasuji et al., 2020 | Japan | 16 (16) | - | - | COVID-19 (confirmed) | Yes (antivirals, antibiotics – specifics not reported) | Yes (no) | Yes (NPS) | 3.15 (V) | 0.18 | ***** |
L'Huillier et al., 2020 | Switzerland | 23 (23) | 23 (23) | 0 | COVID-19 (confirmed) | N/A | Yes (no) | Yes (NPS) | 2.91 (V), 14.7 (P), 3.73 (S/Ps) | 0.24 | ******** |
Lavezzo et al., 2020 | Italy | 103 (110) | 2 (3) | 49 (49) | COVID-19 (confirmed) | N/A | Yes (yes) | Yes (NPS, OPS) | 3.77 (V), 5.03 (A), 11.57 (P), 3.57 (S/Ps), 21.8 (As) | 1.14 | ******* |
Lennon et al., 2020 | USA | 2200 (2,200) | 18 (18) | 2200 (2200#) | COVID-19 (confirmed) | N/A | No (yes) | Yes (NPS) | 3.88 (V), 5.20 (A), 24.0 (As) | 22.84 | ********* |
Lucas et al., 2020 | USA | 24 (33) | 0 | 0 | COVID-19 (confirmed) | Yes (tocilizumab for moderate and severe patients, glucocorticoid and vasopressor for severe patients) | Yes (yes) | Yes (NPS) | 3.51 (V), 4.69 (A), 4.08 (S/Ps) | 0.34 | ******* |
Mitjà et al., 2020 | Spain | 148 (296) | 0 | 0 | COVID-19 (confirmed) | N/A | No (no) | Yes (NPS) | 3.81 (V), 5.10 (A), 3.93 (S/Ps) | 3.07 | ********* |
Pan et al., 2020 | China | 75 (104) | - | 0 | COVID-19 (confirmed) | N/A | Yes (no) | Yes (OPS) No (Spu) | 3.45 (V), 2.50 (S/Ps) | 1.24 | **** |
Peng et al., 2020 | China | 6 (6) | 0 | 0 | COVID-19 (confirmed) | Yes (arbidol, lopinavir, ritonavir, interferon alfa-2b inhalation) | Yes (no) | Yes (OPS) | 3.03 (V), 4.05 (A), 4.02 (S/Ps) | 0.06 | ******** |
Perera et al., 2020 | China | - (36) | 0 | - | COVID-19 (confirmed) | Yes lopinavir-ritonavir alone, combination lopinavir-ritonavir and ribavirin, ribavirin and β interferon, β interferon alone, combination ribavirin, β interferon, and tocilizumab, and corticosteroid | Yes (no) | Yes (NPA, NPS, OPS, Spu) | 3.23 (V), 4.32 (A) | 0.39 | **** |
Shi et al., 2020 | China | 103 (103) | 0 | 0 | COVID-19 (confirmed) | No (samples drawn before antivirals given) | Yes (no) | Yes (NPS, OPS) | 3.87 (V), 5.18 (A), 4.34 (S/Ps) | 1.07 | ***** |
Shrestha et al., 2020 | USA | 171 (171) | 0 | 0 | COVID-19 (confirmed) | Yes (indicated no hydroxychloroquine or other COVID-19-related treatments were used) | Yes (no) | Yes (NPS) | 3.79 (V), 5.07 (A), 3.86 (S/Ps) | 1.78 | ******* |
To et al., 2020 | China | 23 (51) | 0 | 0 | COVID-19 (confirmed) | N/A | Yes (yes) | Yes (ETA, POS) | 3.37 (V), 4.51 (A), 3.25 (S/Ps) | 0.53 | ********* |
van Kampen et al., 2021 | The Netherlands | - (154) | 0 | 0 | COVID-19 (confirmed) | Yes (lopinavir-ritonavir with or without ribavirin and/or interferon beta 1b) | Yes (yes) | Yes (NPS, Spu) | 3.80 (V), 5.09 (A), 4.10 (S/Ps) | 1.60 | ******** |
Vetter et al., 2020 | Switzerland | 5 (63) | 0 | 0 | COVID-19 (confirmed) | Yes (paracetamol, alfuzosin, ibuprofen, enoxaparin, amoxicillin clarithromycin, piperacillin, tazobactam, lopinavir, ritonavir, folic acid) | Yes (yes) | Yes (NPS, OPS) | 3.68 (V), 4.93 (A), 4.14 (S/Ps) | 0.65 | ********* |
Wölfel et al., 2020 | Germany | 9 (136) | 0 | 1 (4) | COVID-19 (confirmed) | N/A | Yes (yes) | Yes (NPS, OPS) No (Spu) | 3.76 (V), 5.03 (A), 3.93 (S/Ps) | 1.38 | ******* |
Wyllie et al., 2020 | USA | 40 (42) | - | 9 (9) | COVID-19 (confirmed) | N/A | Yes (yes) | Yes (NPS) | 3.55 (V), 4.75 (A), 4.00 (S/Ps), 18.3 (As) | 0.44 | ******* |
Xu et al., 2020 | China | 7 (14) | 7 (14) | 1 (1) | COVID-19 (confirmed) | Yes (α-interferon oral spray, azithromycin) | Yes (no) | Yes (NPS) | 3.40 (V). 17.3 (P), 4.1 (S/Ps) | 0.15 | ******** |
Yonker et al., 2020 | USA | 17 (17) | 14 (14) | 0 | COVID-19 (confirmed) | N/A | Yes (no) | Yes (NPS) | 2.58 (V), 9.79 (P), 3.28 (S/Ps) | 0.18 | ****** |
Zhang et al., 2020b | China | 9 (9) | 0 | 0 | COVID-19 (confirmed) | N/A | Yes (no) | Yes (NPS, OPS) | 2.97 (V), 3.97 (A), 3.68 (S/Ps) | 0.09 | ******** |
Zheng et al., 2020 | China | - (19) | 0 | 0 | COVID-19 (confirmed) | Yes (gamma globulin, glucocorticoids, antibiotics, antiviral combination of interferon α inhalation, lopinavir-ritonavir combination, arbidol, favipiravir, and darunavir-cobicistat) | Yes (no) | Yes (POS, Spu) | 3.66 (V), 4.90 (A), 4.23 (S/Ps) | 0.20 | ******* |
Zou et al., 2020 | China | 14 (55) | 0 | 1 (4) | COVID-19 (confirmed) | N/A | Yes (no) | Yes (NPS, OPS) | 3.64 (V), 4.87 (A), 3.65 (S/Ps) | 0.57 | ******* |
Chen et al., 2006 | China | 154 (154#) | 0 | 0 | SARS (confirmed) | N/A | Yes (no) | Yes (NPS) | 14.0 (V) | 1.59 | ******** |
Chu et al., 2004** | China | 11 (11) | 0 | 0 | SARS (confirmed) | Yes (control group: ribavirin, hydrocortisone, methylprednisolone) | Yes (yes) | Yes (NPS) | 8.6 (V) | 0.11 | ********* |
Chu et al., 2005 | China | 57 (57) | 0 | 0 | SARS (confirmed) | N/A | Yes (yes) | Yes (NPA) | 13.3 (V) | 0.59 | ********* |
Cheng et al., 2004 | China | 59 (59) | 0 | 0 | SARS (confirmed) | Yes (amoxicillin-clavulanate, azithromycin, levofloxacin, ribavirin, hydrocortisone, prednisolone, methylprednisolone) | Yes (yes) | Yes (NPA) | 13.4 (V) | 0.61 | ********* |
Hung et al., 2004 | China | 60 (60) | 0 | 0 | SARS (confirmed) | N/A | No (yes) | Yes (NPA) | 13.5 (V) | 0.62 | ******* |
Peiris et al., 2003** | China | 14 (42) | 0 | 0 | SARS (confirmed) | Yes (ribavirin, hydrocortisone, prednisolone, methylprednisolone) | Yes (no) | Yes (NPA) | 13.4 (V) | 0.44 | ******** |
Poon et al., 2003 | China | 40 (40) | 0 | 0 | SARS (confirmed) | N/A | No (yes) | Yes (NPA) | 11.3 (V) | 0.42 | ***** |
Poon et al., 2004 | China | - (43) | 0 | 0 | SARS (confirmed) | N/A | No (yes) | Yes (NPA) | 12.5 (V) | 0.45 | ******* |
Rodrigues Guimarães Alves et al., 2020 | Brazil | 86 (86) | - | 15 (15) | A(H1N1)pdm09 (confirmed) | Yes (oseltamivir) | No (yes) | Yes (NPA, NPS, OPS) | 3.7 (V) | 0.89 | ***** |
Chan et al., 2011 | China | 58 (58) | 0 | 0 | A(H1N1)pdm09 (confirmed) | Yes (oseltamivir, zanamivir, peramivir) | Yes (no) | Yes (NPA, NPS, OPS) | 3.7 (V) | 0.60 | ****** |
Cheng et al., 2010 | China | 60 (60) | - | 0 | A(H1N1)pdm09 (confirmed) | No (pretreatment samples) | No (no) | Yes (NPA) | 3.7 (V) | 0.62 | ****** |
Cowling et al., 2010 | China | 45 (54) | 22 (31) | 0 | A(H1N1)pdm09 (confirmed) | Yes (oseltamivir) | Yes (yes) | Yes (NPS, OPS) | 3.7 (V) | 0.56 | ********* |
Duchamp et al., 2010 | France | 209 (209) | 209 (209) | 0 | A(H1N1)pdm09 (confirmed) | Yes (oseltamivir, zanamivir) | No (yes) | Yes (NPS) | 3.8 (V) | 2.17 | ***** |
Esposito et al., 2011 | Italy | 74 (282) | 74 (282) | 0 | A(H1N1)pdm09 (confirmed) | No | Yes (yes) | Yes (NPS) | 3.8 (V) | 2.93 | ******* |
Hung et al., 2010 | China | 87 (87) | - | 0 | A(H1N1)pdm09 (confirmed) | Yes (oseltamivir) | Yes (no) | Yes (NPA, NPS) | 3.8 (V) | 0.90 | ****** |
Ip et al., 2016 | China | 17 (20) | 7 (-) | 0 | A(H1N1)pdm09 (confirmed) | N/A | Yes (no) | Yes (NPS, OPS) | 3.6 (V) | 0.21 | ******* |
Ito et al., 2012 | Japan | 34 (34) | - | 0 | A(H1N1)pdm09 (confirmed) | No (pretreatment samples) | Yes (yes) | Yes (NPS) | 3.7 (V) | 0.35 | ***** |
Killingley et al., 2010 | United Kingdom | 12 (21) | - | 0 | A(H1N1)pdm09 (confirmed) | Yes (oseltamivir) | Yes (yes) | Yes (NPS) | 3.5 (V) | 0.22 | ******** |
Launes et al., 2012 | Spain | 47 (47) | 47 (47) | 0 | A(H1N1)pdm09 (confirmed) | No (pretreatment samples) | No (no) | Yes (NPA) | 3.7 (V) | 0.49 | ******* |
Lee et al., 2011a | China | 48 (48) | 0 | 0 | A(H1N1)pdm09 (confirmed) | No (pretreatment samples) | No (no) | Yes (NPA) | 3.7 (V) | 0.50 | ******** |
Lee et al., 2011a | Singapore | 578 (578) | 231 (231) | 0 | A(H1N1)pdm09 (confirmed) | No (pretreatment samples) | No (no) | Yes (NPS) | 3.8 (V) | 6.00 | ********* |
Li et al., 2010a | China | 581 (581) | 522 (522) | 0 | A(H1N1)pdm09 (confirmed) | Yes (oseltamivir) | No (no) | Yes (OPS) | 3.8 (V) | 6.03 | ******** |
Li et al., 2010b | China | 27 (59) | - | 0 | A(H1N1)pdm09 (confirmed) | No (control group no treatment) | No (no) | Yes (NPA, NPS, OPS) | 3.7 (V) | 0.61 | ******* |
Loeb et al., 2012 | Canada | 97 (218) | - | - (17) | A(H1N1)pdm09 (confirmed) | No | No (no) | Yes (NPS) | 3.8 (V) | 2.26 | ******* |
Lu et al., 2012 | China | 13 (25) | - | 0 | A(H1N1)pdm09 (confirmed) | Yes (oseltamivir, zanamivir) | Yes (no) | Yes (NPS) | 3.5 (V) | 0.26 | ******* |
Meschi et al., 2011 | Italy | 533 (533) | 0 | 0 | A(H1N1)pdm09 (confirmed) | No (pretreatment samples) | No (no) | Yes (NPS) | 3.8 (V) | 0.92 | ********* |
Ngaosuwankul et al., 2010 | China | 12 (33) | - | 0 | A(H1N1)pdm09 (confirmed) | No (pretreatment samples) | No (yes) | Yes (NPA, NPS, OPS) | 3.6 (V) | 0.34 | ****** |
Rath et al., 2012 | Germany | 27 (41) | 27 (41) | 0 | A(H1N1)pdm09 (confirmed) | Yes (oseltamivir) | Yes (yes) | Yes (NPS) | 3.7 (V) | 0.43 | ********* |
Suess et al., 2010 | Germany | 51 (129) | 12 (-) | 1 (1) | A(H1N1)pdm09 (confirmed) | Yes (oseltamivir) | No (no) | Yes (NPA, NPS, OPS) | 3.8 (V) | 1.34 | ******** |
Thai et al., 2014 | Vietnam | 33 (123) | 16 (-) | 5 (28) | A(H1N1)pdm09 (confirmed) | Yes (oseltamivir) | Yes (yes) | Yes (NPS) | 3.8 (V) | 1.28 | ********* |
To et al., 2010a | China | 50 (50) | 0 | 0 | A(H1N1)pdm09 (confirmed) | Yes (oseltamivir, zanamivir, inotropes) | No (no) | Yes (NPA, NPS) | 3.6 (V) | 0.52 | ****** |
To et al., 2010b | China | 22 (22) | - | 0 | A(H1N1)pdm09 (confirmed) | No (pretreatment samples) | No (no) | Yes (NPA, NPS, OPS) | 3.4 (V) | 0.23 | ***** |
Watanabe et al., 2011 | Japan | 251 (251) | 251 (251) | 0 | A(H1N1)pdm09 (confirmed) | No (pretreatment samples) | No (yes) | Yes (NPA) | 3.8 (V) | 2.61 | ********** |
Wu et al., 2012 | China | 64 (89) | - | 0 | A(H1N1)pdm09 (confirmed) | Yes (oseltamivir) | No (yes) | Yes (NPS) | 3.7 (V) | 5.53 | ******* |
Yang et al., 2011 | China | 251 (251) | - | 0 | A(H1N1)pdm09 (confirmed) | N/A | No (yes) | Yes (OPS) | 3.8 (V) | 6.57 | ***** |
*Data shown as ‘-' were not obtained from the paper or authors.
†Responses of ‘N/A’ indicate that no details were reported on treatment for COVID-19 in the study.
‡For studies reporting specimen measurements as individual sample data (either in numerical or graphical formats), the sample data was extracted for analysis.
§Specimen measurements were converted to rVLs based on the dilution factor for specimens in transport media.
||Abbreviations for random-effects meta-analyses: virus meta-analysis (V), adult subgroup (A), pediatric subgroup (P), symptomatic/presymptomatic subgroup (S/Ps) and asymptomatic subgroup (As).
¶The hybrid JBI critical appraisal checklist was used, with more stars indicating lower risk of bias. Studies were considered to have low risk of bias if they met the majority of the items (≥6/10 items). Results from each study are shown in Appendix 1—table 2.
#For these studies, 2147 (Lennon et al., 2020) and 134 (Chen et al., 2006) individual specimen measurements were obtained for the individual sample datasets.
**For Chu et al., 2004, only specimen measurements at 20 DFSO were collected as 5–15 DFSO were specimens reported in Peiris et al., 2003.
NPS: nasopharyngeal swab; OPS, oropharyngeal swab; Spu: sputum; POS, posterior oropharyngeal saliva; NPA: nasopharyngeal aspirate; ETA: endotracheal aspirate; DFSO: days from symptom onset; rVL: respiratory viral load.
*Descriptions of each item are included in the hybrid JBI critical appraisal checklist (Appendix). Y (green), U (yellow) and N (red) represent yes, unclear and no, respectively.