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Effectiveness of Hydroxychloroquine in COVID-19 disease: A done and dusted situation?

D'Arminio Monforte et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.07.056
Jul 2020  
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Mortality 34% Improvement Relative Risk HCQ+AZ 56% HCQ  D'Arminio Monforte et al.  LATE TREATMENT Is late treatment with HCQ beneficial for COVID-19? Retrospective 539 patients in Italy Lower mortality with HCQ (not stat. sig., p=0.12) c19hcq.org D'Arminio Monforte et al., Int. J. Inf.., Jul 2020 FavorsHCQ Favorscontrol 0 0.5 1 1.5 2+
HCQ for COVID-19
1st treatment shown to reduce risk in March 2020, now with p < 0.00000000001 from 419 studies, recognized in 46 countries.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 112 treatments. c19hcq.org
Retrospective 539 COVID-19 hospitalized patients in Milan, with treatment a median of 1 day after admission, showing lower mortality with HCQ and with HCQ+AZ, with statistical significance only for HCQ+AZ.
risk of death, 34.0% lower, HR 0.66, p = 0.12, treatment 53 of 197 (26.9%), control 47 of 92 (51.1%), NNT 4.1, adjusted per study.
HCQ+AZ, 56.0% lower, HR 0.44, p = 0.009, treatment 22 of 94 (23.4%), control 47 of 92 (51.1%), NNT 3.6, adjusted per study.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
D'Arminio Monforte et al., 29 Jul 2020, retrospective, Italy, peer-reviewed, 5 authors.
This PaperHCQAll
Effectiveness of hydroxychloroquine in COVID-19 disease: A done and dusted deal?
Antonella D’arminio Monforte, Alessandro Tavelli, Francesca Bai, Giulia Marchetti, Alessandro Cozzi-Lepri
International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.07.056
A total of 539 COVID-19 hospitalized patients were included in our cohort in Milan, from February 24 to May 17, 2020, of whom 174 died in hospital (day 14 probability of death: 29.5% -95%CI: 25.5-34.0). We divided a subset of our cohort into three groups who started treatment a median of 1 day after admission: those receiving hydroxychloroquine alone (N = 197), those receiving hydroxycholoroquine + azithromycin (N = 94), and those receiving neither (controls) (N = 92). Of the latter group, ten started HIV antivirals (boosted-lopinavir or -darunavir), one teicoplanin, twelve immunomodulatory drugs, or corticosteroids, 23 heparin and 46 remained untreated. The percent of death in the three groups was 27%, 23%, and 51%. Mechanical ventilation was used in 4.3% of hydroxychloroquine, 14.2% of hydroxychloroquine + azithromycin, and 26.1% of controls. Unweighted and weighted relative hazards of mortality are shown in Table 1 . After adjusting * Adjusted for age, gender, number of comorbidities, CVD (yes/no), duration of symptoms, date of admission, CRP and censoring using IPW. £ The overall estimate was also adjusted for baseline COVID-19 disease severity. # Heparin, immuno-modulatory drugs, HIV antivirals, combinations of these or no drugs at all. & 45 patients missing baseline PO2/FiO2 not included in the stratified analysis.
Declarations of interest None declared. Ethical approval This analysis is part of the study approved by Ethic Committee Area 1, Milan Italy (2020/ST/049 and 2020/ST/049_BIS, 11/03/ 2020).
References
Arshad, Kigore, Chaudhry, Jacobsen, Wang et al., Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalised with COVID-19, Int J Infect Dis, doi:10.1016/j.ijid.2020.06.09
Devaux, Rolain, Colson, Raoult, New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?, Int J Antimicrob Agents, doi:10.1016/j.antimicag.2020.105938
Gautret, Lagier, Parola, Hoang, Meddeb et al., Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomised clinical trial, Int J Antimicrob Agents, doi:10.1016/j.antimicag.2020.105949
Geleris, Sun, Platt, Zucker, Baldwin et al., Observational study on hydroxychloroquine in hospitalized patients with COVID-19, N Engl J Med, doi:10.1056/NEJMoa2012410
Horby, Lim, Emberson, Mafham, Bell et al., Effect of desamethasone in hospitalized patients with CVID-19: preliminary report
Lee, Mackenzie, Mcdonald, Tong, An observational cohort study of hydroxychloroquine and azithromycin for COVID-19: (Can't get no) satisfaction, Int J Infect Dis, doi:10.1016/j.ijid.2020.06.095
Liu, Cao, Xu, Wang, Zhang et al., Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro, Cell Discov
Tang, Cao, Han, Wang, Chen et al., Hydroxychloroquine in patients mainly with mild to moderate COVID-19: an open-label, randomised, controlled trial, BMJ, doi:10.1136/bmj.m1849
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Late treatment
is less effective
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