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0 0.5 1 1.5 2+ Mortality 13% Improvement Relative Risk Hospitalization 3% Case 9% Mortality (b) -8% Hospitalization (b) -6% Case (b) 5% HCQ for COVID-19  Fung et al.  Prophylaxis Is pre-exposure prophylaxis with HCQ beneficial for COVID-19? Retrospective study in the USA Fewer cases with HCQ (p=0.016) Fung et al., PLoS ONE, October 2021 Favors HCQ Favors control

Effect of common maintenance drugs on the risk and severity of COVID-19 in elderly patients

Fung et al., PLoS ONE, doi:10.1371/journal.pone.0266922 (date from preprint)
Oct 2021  
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HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
*, now known with p < 0.00000000001 from 422 studies, recognized in 42 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,000+ studies for 60+ treatments.
Retrospective database analysis of 374,229 patients in the USA, showing no significant difference with HCQ use, however authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 Ferri.
Authors compare with patients that never used HCQ and with patients that previously used HCQ. The comparison with patients previously using HCQ is more relevant because the matching of patients with systemic autoimmune disease is likely to be better.
This study is excluded in the after exclusion results of meta analysis: not fully adjusting for the different baseline risk of systemic autoimmune patients.
Study covers HCQ and famotidine.
risk of death, 13.0% lower, HR 0.87, p = 0.15, vs. past use (better match for systemic autoimmune diseases).
risk of hospitalization, 3.0% lower, HR 0.97, p = 0.63, vs. past use (better match for systemic autoimmune diseases).
risk of case, 9.0% lower, HR 0.91, p = 0.02, vs. past use (better match for systemic autoimmune diseases).
risk of death, 8.0% higher, HR 1.08, p = 0.26, vs. never used.
risk of hospitalization, 6.0% higher, HR 1.06, p = 0.13, vs. never used.
risk of case, 5.0% lower, HR 0.95, p = 0.03, vs. never used.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Fung et al., 1 Oct 2021, retrospective, population-based cohort, USA, peer-reviewed, 6 authors.
This PaperHCQAll
Effect of common maintenance drugs on the risk and severity of COVID-19 in elderly patients
Kin Wah Fung, Seo H Baik, Fitsum Baye, Zhaonian Zheng, Vojtech Huser, Clement J Mcdonald
PLOS ONE, doi:10.1371/journal.pone.0266922
Background Maintenance drugs are used to treat chronic conditions. Several classes of maintenance drugs have attracted attention because of their potential to affect susceptibility to and severity of COVID-19. Methods Using claims data on 20% random sample of Part D Medicare enrollees from April to December 2020, we identified patients diagnosed with COVID-19. Using a nested case-control design, non-COVID-19 controls were identified by 1:5 matching on age, race, sex, dualeligibility status, and geographical region. We identified usage of angiotensin-converting enzyme inhibitors (ACEI), angiotensin-receptor blockers (ARB), statins, warfarin, direct factor Xa inhibitors, P2Y12 inhibitors, famotidine and hydroxychloroquine based on Medicare prescription claims data. Using extended Cox regression models with time-varying propensity score adjustment we examined the independent effect of each study drug on contracting COVID-19. For severity of COVID-19, we performed extended Cox regressions on all COVID-19 patients, using COVID-19-related hospitalization and all-cause mortality as outcomes. Covariates included gender, age, race, geographic region, low-income indicator, and co-morbidities. To compensate for indication bias related to the use of hydroxychloroquine for the prophylaxis or treatment of COVID-19, we censored patients who only started on hydroxychloroquine in 2020. Results Up to December 2020, our sample contained 374,229 Medicare patients over 65 who were diagnosed with COVID-19. Among the COVID-19 patients, 278,912 (74.6%) were on at least one study drug. The three most common study drugs among COVID-19 patients were statins 187,374 (50.1%), ACEI 97,843 (26.2%) and ARB 83,290 (22.3%). For all three outcomes (diagnosis, hospitalization and death), current users of ACEI, ARB,
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