Current best evidence for clinical care (more info)
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: World Health Organization 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.
CONCLUSIONS: 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).
| Discipline / Specialty Area | Score |
|---|---|
| Infectious Disease | |
| Public Health | |
| Hospital Doctor/Hospitalists | |
| Internal Medicine | |
| Occupational and Environmental Health | |
Nil
Prophylaxis for preventing Covid-19 infection, the jury is in. Despite the short timeframe that we have been studying and treating Covid-19 infections, there is sufficient high quality research on hydrochloroquine and chloroquine to demonstrate is lack of utility as a prophylactic or active treatment alone or in combination. Other agents, such as Ivermectin have not been well studied sufficiently not be conclusive, but appear ineffective, as well.
This study uses a complex methodology to assess the potential benefits of different medication regimens to prevent SARS-CoV 2 infection. Th results indicate no significant benefit for hydroxy chloroquine and probably no benefit for ivermectin with or without iota-carageenan. As this is a living systematic study, we should expect additional updates in the near future.
This relevant article precisely provides all the uncertainty on the pharmacological prevention of Covid-19 infections. Although the yields are inconclusive, and need a programmed update, the study proves argument to avoids the prophylactic use of Hydroxychloroquine and ivermectin for SARS-2 infections.