Possible synergistic effects of hydroxychloroquine and steroids in COVID-19, time for a nuanced approach. Comment on Arshad et al.

Wiseman, David M.

doi:10.1016/j.ijid.2020.07.064

Cited by 1 publication

(2 citation statements)

References 12 publications

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“…Further confounding within a number of observational studies is related to the possibly synergistic use of steroids. 32 At earlier stages, any effect associated with HCQ appears independent of zinc, evinced by the lack of synergy we observed between HCQ and zinc. Further, using zinc may be futile in otherwise healthy, especially younger subjects with no zinc deficiency or dysregulation.…”

Section: Discussionmentioning

confidence: 70%

“…[29] In hospitalized patients, factors confounding HCQ's effectiveness are beginning to be better understood [30], with clear reports of significant HCQ-associated reductions in mortality with the use of zinc. [3], [31] The possibly synergistic use of steroids [32] may further confound some studies. At earlier stages, any HCQ-associated effect appears independent of zinc, evinced (weakly) by the lack of synergy we observed.…”

Section: Findings In the Context Of Other Covid-19 Studiesmentioning

confidence: 99%

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Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine: Prospective re-analysis of a public dataset incorporating novel data

Wiseman

Kory

Saidi

et al. 2020

Preprint

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BACKGROUND: A recent trial (NCT04308668) found that post-exposure prophylaxis with hydroxychloroquine (HCQ) was associated with a reduced incidence of Covid-19 by 17% overall; 36% in younger subjects, 31% in household contacts and 49% given within one day. To understand these trends, we prospectively re-analyzed the released dataset. METHODS: Our protocol conformed to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT). We compared the incidence of Covid-19 after HCQ or placebo, stratifying primarily by time to drug receipt, age and gender. RESULTS: Requesting additional data, we found that 52% of subjects received medication 1-2 days after the intended overnight delivery; 19% of them outside the intended four-day window from exposure. After re-analysis, there was a reduced incidence of Covid-19 associated with HCQ compared with placebo (9.6% vs. 16.5%) when received up to 3 days (Early) after exposure (RR 0.58, 95%CI 0.35 - 0.97; p=0.044; NNT 14.5) but not later (Late) (RR 1.22, 95%CI 0.72 - 2.04). We found a significant HCQ-associated reduction in subjects 18 to 45 years old associated with Early (RR 0.53, 95%CI 0.29-0.97; p=0.0448, NNT 11.5) but not Late (RR 1.02, 95%CI 0.55-1.89) prophylaxis, attenuated in older subjects (RR 0.75, 95%CI 0-27-2.05) and by co-morbidities. There were reductions associated with Early prophylaxis in household contacts (RR 0.35, 95%CI 0.13-0.89; p=0.025, NNT 5.7) and Health Care Workers (RR 0.74, 95%CI 0.4-1.38). We did not detect effects of gender, folate, zinc, or ascorbic acid. CONCLUSIONS: Using novel data with a prospective post hoc re-analysis, hydroxychloroquine, in an age-dependent manner, was associated with reduced illness compatible with Covid-19 or confirmed infection when supplied for post-exposure prophylaxis between 1 and 3 days after high-risk or moderate-risk exposure. This finding warrants prospective confirmation. Registered with the Open Science Framework (last revised September 27, 2020, osf.io/fqtnw).

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Section: Discussionmentioning

confidence: 70%