The DOI matches its Crossref record; 91 of the 91 references it cites were found in a registry or an index.
Prophylaxis against covid-19: living systematic review and network meta-analysis
Open accessPublished version of a preprint
Abstract
Updates: This is the second version (first update) of the living systematic review, replacing the previous version (available as a data supplement). When citing this paper please consider adding the version number and date of access for clarity. Objective: To determine and compare the effects of drug prophylaxis on severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (covid-19). Design: Living systematic review and network meta-analysis (NMA). Data sources: WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature to 4 March 2022. Study selection: Randomised trials in which people at risk of covid-19 were allocated to prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles. Methods: After duplicate data abstraction, we conducted random-effects bayesian network meta-analysis. We assessed risk of bias of the included studies using a modification of the Cochrane risk of bias 2.0 tool and assessed the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. Results: The second iteration of this living NMA includes 32 randomised trials which enrolled 25 147 participants and addressed 21 different prophylactic drugs; adding 21 trials (66%), 18 162 participants (75%) and 16 (76%) prophylactic drugs. Of the 16 prophylactic drugs analysed, none provided convincing evidence of a reduction in the risk of laboratory confirmed SARS-CoV-2 infection. For admission to hospital and mortality outcomes, no prophylactic drug proved different than standard care or placebo. Hydroxychloroquine and vitamin C combined with zinc probably increase the risk of adverse effects leading to drug discontinuation—risk difference for hydroxychloroquine (RD) 6 more per 1000 (95% credible interval (CrI) 2 more to 10 more); for vitamin C combined with zinc, RD 69 more per 1000 (47 more to 90 more), moderate certainty evidence. Conclusion: Much of the evidence remains very low certainty and we therefore anticipate future studies evaluating drugs for prophylaxis may change the results for SARS-CoV-2 infection, admission to hospital and mortality outcomes. Both hydroxychloroquine and vitamin C combined with zinc probably increase adverse effects. Systematic review registration: This review was not registered. The protocol established a priori is included as a supplement. Funding: This study was supported by the Canadian Institutes of Health Research (grant CIHR-IRSC:0579001321).
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Our thresholds for beneficial and harmful effects were informed by surveys of the coauthors in the parallel living SRNMAs.17–19”
From Consistency of covid-19 trial preprints with published reports and impact for decision making: retrospective review (2022) · cites this paper as [19]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
3 retracted
WITHDRAWN: Efficacy and Safety of Ivermectin for Treatment and prophylaxis of COVID-19 PandemicPreprint
Elgazzar, A. G., Hani, B. M., Youssef, S. A., Hafez, M., Moussa, H. H., & El-Taweel, A. I. (2020) · Research Square · doi:10.21203/rs.3.rs-100956/v2 · Cited by 24
RetractedWITHDRAWN: Efficacy and Safety of Ivermectin for Treatment and prophylaxis of COVID-19 Pandemic
Elgazzar, A., Eltaweel, A., Youssef, S. A., Hany, B., Hafez, M., & Moussa, H. (2020) · doi:10.21203/rs.3.rs-100956/v3 · Cited by 17
RetractedBalmforth, D., Swales, J. A., Silpa, L., Dunton, A. W., Davies, K. E., Davies, S. G., Kamath, A., Gupta, J., Gupta, S., Masood, M. A., et al. (2022) · Journal of Clinical Virology · doi:10.1016/j.jcv.2022.105248 · Cited by 14
RetractedRoB 2: a revised tool for assessing risk of bias in randomised trials
Sterne, J. A. C., Savović, J., Page, M. J., Elbers, R. G., Blencowe, N. S., Boutron, I., Cates, C. J., Cheng, H.-Y., Corbett, M. S., Eldridge, S. M., et al. (2019) · BMJ · doi:10.1136/bmj.l4898 · Cited by 34,787
Hutton, B., Salanti, G., Caldwell, D. M., Chaimani, A., Schmid, C. H., Cameron, C., Ioannidis, J. P. A., Straus, S., Thorlund, K., Jansen, J. P., et al. (2015) · Annals of Internal Medicine · doi:10.7326/m14-2385 · Cited by 8,269
GRADE guidelines: 4. Rating the quality of evidence—study limitations (risk of bias)
Guyatt, G. H., Oxman, A. D., Vist, G., Kunz, R., Brozek, J., Alonso-Coello, P., Montori, V., Akl, E. A., Djulbegovic, B., & Falck-Ytter, Y. (2011) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2010.07.017 · Cited by 2,798
Self-citationGraphical tools for network meta-analysis in STATA
Chaimani, A., Higgins, J. P. T., Mavridis, D., Spyridonos, P., & Salanti, G. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076654 · Cited by 2,473
Puhan, M. A., Schunemann, H. J., Murad, M. H., Li, T., Brignardello-Petersen, R., Singh, J. A., Kessels, A. G., Guyatt, G. H., & for the GRADE Working Group (2014) · BMJ · doi:10.1136/bmj.g5630 · Cited by 1,812
Self-citationA Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19
Boulware, D. R., Pullen, M. F., Bangdiwala, A. S., Pastick, K. A., Lofgren, S. M., Okafor, E. C., Skipper, C. P., Nascene, A. A., Nicol, M. R., Abassi, M., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2016638 · Cited by 1,349
A living WHO guideline on drugs for covid-19 (2020-2023)
Agarwal, A., Hunt, B. J., Stegemann, M., Rochwerg, B., Lamontagne, F., Siemieniuk, R. A., Agoritsas, T., Askie, L., Lytvyn, L., Leo, Y.-S., et al. (2020) · BMJ · doi:10.1136/bmj.m3379 · Cited by 1,041
Self-citation
Flagged first, then by citations
Research works printed but not linked: 10
- 10.1016/j.jclinepi.2017.08.010 · DOI · Paper page
- Veritas Health Innovation. Covidence systematic review software. Melbourne, Australia.
- 10.1371/journal.pone.0076654 · DOI · Paper page
- 10.1056/NEJMoa2016638 · DOI
- 10.1056/NEJMoa2021801 · DOI
- 10.7860/JCDR/2020/46795.0000 · DOI
- 10.1016/j.jacc.2020.05.040 · DOI
- 10.1371/journal.pone.0244778 · DOI
- 10.18433/jpps31457 · DOI
- 10.1016/j.jclinepi.2010.07.017 · DOI · Paper page
Cited by
Sorted by citations
Items 101–113 of 113
Epigenetic features, methods, and implementations associated with COVID-19
Sen, R., Sarkar, S., Chlamydas, S., Garbati, M. R., & Barnes, C. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-91794-0.00008-1
Yin, J., Li, Y., Wang, C., Qin, C., & Miao, M. (2023) · doi:10.2196/preprints.46323
Zhou, G., de Vos, S., Schuiling‐Veninga, C. C. M., Bos, J., Rengerink, K. O., Pasmooij, A. M. G., Mol, P. G. M., de Bock, G. H., & Hak, E. (2023) · Clinical Epidemiology · doi:10.2147/clep.s418069
Nair, R. K., & Nimimole, K. L. (2023) · International Journal of Homoeopathic Sciences · doi:10.33545/26164485.2023.v7.i3g.940
Zahedi, R., Chegeni, M., & Rahmanian, V. (2023) · Taḥqīq va tusi̒ah-i salāmata · doi:10.61186/jhrd.1.1.1
Velpandian, T., Das, U. S., Moksha, L., Srivastava, S., Singh, N., Nath, M., Mahalingam, K., Gupta, R., Mohan, A., & Halder, N. (2025) · Indian Journal of Physiology and Pharmacology · doi:10.25259/ijpp_440_2024
Therapeutics Overview for Agents of Bioterrorism and Viral Outbreaks
Golnabi, E. Y., Sanders, J. M., Hodge, C. K., & Cutrell, J. B. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-54841-0.00018-4
Davidson, M., Evrenoglou, T., Graña, C., Chaimani, A., & Boutron, I. (2024) · Figshare · doi:10.6084/m9.figshare.24987783
Luo, J., Chen, Z., Liu, D., Li, H., He, S., Zeng, L., Yang, M., Liu, Z., Xiao, X., & Zhang, L. (2023) · Figshare · doi:10.6084/m9.figshare.23812451
What can we learn from network meta-analyses published in top medical journals
Tian, C., Li, M., Jiang, J., Hou, L., Pan, B., Wang, Y. C., Ge, L., & Yue, X. (2026) · Systematic Reviews · doi:10.1186/s13643-025-03066-w
Self-citationZINC: FROM DEFICIENCY PREVENTION TO THERAPEUTIC POTENTIAL. PART 2
Русланович, К. М., Prakoshyna, N. R., & Sabalenka, T. M. (2025) · Vestnik Farmacii · doi:10.52540/2074-9457.2025.2.65
Integration of various types of information in living systematic reviews
Davidson, M. (2024) · theses.fr (ABES) · doi:10.70675/a60f5802z1fb9z4866z9e22z7be74c96be25
Golob, M. M., Leinberger‐Jabari, A., Loufek, B. T., Livingstone‐Banks, J., Roberts, N. W., & Nunan, D. (2026) · Systematic Reviews · doi:10.1186/s13643-026-03209-7
Metadata
- Authors
- Bartoszko, J. J., Siemieniuk, R. A., Kum, E., Qasim, A., Zeraatkar, D., Martinez, J. P. D., Azab, M., Ibrahim, S., Izcovich, A., Soto, G. B., Roldan, Y., Agarwal, A., Agoritsas, T., Chu, D. K., Couban, R., Devji, T., Foroutan, F., Ghadimi, M., Honarmand, K., Khamis, A., Lamontagne, F., Loeb, M., McLeod, S. L., Motaghi, S., Murthy, S., Mustafa, R. A., Rochwerg, B., Switzer, C., Thabane, L., Vandvik, P. O., Vernooij, R. W., Wang, Y., Yao, L., Guyatt, G. H., & Brignardello-Petersen, R.
- Affiliations
- McMaster University (CA)
- Hospital Alemán (AR)
- University of Toronto (CA)
- University Hospital of Geneva (CH)
- Western University (CA)
- Hull York Medical School (GB)
- University of British Columbia (CA)
- University of Oslo (NO)
- Utrecht University (NL)
- ORCID
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2021-04-26
- Volume
- 373
- Pages
- n949
- ISSN
- 1756-1833 (ISSN-L)
- PMC
- PMC8073806
- OpenAlex
- W3158131439
- Cited by
- 113
- References
- 84
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 10 · 2023: 25 · 2022: 40 · 2021: 28
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.bmj.com/company/legal-information/terms-conditions/legal-information/tdm-licencepolicy (tdm)
- Locations
- BMJ (publishedVersion)
- medRxiv (acceptedVersion, cc-by-nc)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- cIRcle (University of British Columbia) (submittedVersion, cc-by-nc)
- Lanzhou University Institutional Repository (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- MacSphere (McMaster University) (submittedVersion, cc-by-nc)
- Funders
- Canadian Allergy, Asthma and Immunology Foundation
- American Academy of Allergy, Asthma and Immunology Foundation
- Canadian Institutes of Health Research (174897_1, 174897)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
- Keywords
- COVID-19 prevention, COVID-19 pandemic, preventive medication, hydroxychloroquine, adverse drug reactions, hospitalization, mortality, drug discontinuation, quality of evidence, risk of bias assessment, GRADE, antiviral agents, antimalarial drugs
- MeSH terms
- COVID-19, SARS-CoV-2, Anti-Infective Agents, Carrageenan, Humans, Hydroxychloroquine, Ivermectin, Global Health, Treatment Outcome, Chemoprevention, Uncertainty
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
