Table 1.
Observational studies evaluating antimalarials ± azithromycin for the treatment of COVID-19.
| Study | Design | Country | Sample size, population | Antimalarial dosing | Comparator | Primary Outcome | Secondary Outcomes | Main Results |
|---|---|---|---|---|---|---|---|---|
| Huang et al. | Cohort | China | 373 hospitalized | CQ 500 mg for maximum of 10 days | No CQ | Conversion to negative PCR in two consecutive samples | - Proportion who had conversion to negative PCR by days 10 and 14 - Length of hospitalization - Duration of fever - Adverse events |
There was a significant difference in the time of conversion to negative PCR between the CQ group (3) and the control (9) (p < 0.0001) There was a significant difference in conversion to negative PCR at day 14 between The CQ group (96%) and the control (80%) (p < 0.0001) |
| Gautret. et al. | Case series | France | 36 hospitalized | HCQ 200 mg thrice daily for 10 days (6 patients received AZT [500 mg first day, then 250 mg daily for 4 days]) |
Supportive treatment | Conversion to negative PCR of respiratory tract specimens at day 6 | - Clinical status - Conversion to negative PCR period - Side effects |
There was a significant difference in conversion to negative PCR at 6 days between the HCQ group (70%) and the control (12.5%) (p < 0.001) |
| Gautret et al. | Case series | France | 80 hospitalized | HCQ 200 mg thrice daily for 10 days AND AZT 500 mg on day 1, then 250 mg for 4 days |
N/A | - At least 3 days of supplemental oxygen or ICU level of care | - PCR and culture - Length of stay in the infectious diseases unit |
Conversion to negative PCR at day 5: 83%; At day 7: 93%; At day 8: 98% |
| Million et al. | Case series | France | 1061 hospitalized | HCQ 200 mg thrice daily for 10 days AND AZT 500 mg on day 1, then 250 mg for 4 days |
N/A | - Death - Clinical worsening (ICU or >10-day hospitalization - Conversion to negative PCR at day 10 |
- Clinical worsening: 4.3% - Death: 0.75% - Conversion to negative PCR at day 10: 95.6% |
|
| Membrillo et al. | Cohort | Spain | 166 hospitalized | Loading dose of HCQ 1200 mg, Maintenance dose of HCQ 400 mg; Unknown duration |
No HCQ | - Death | There was a significant difference in mortality between the HCQ group (22%) and the control (48.8%) (p = 0.002) |
|
| Mallat et al. | Cohort | UAE | 34 hospitalized | HCQ 400 mg twice daily for 1 day, then 400 mg daily for 10 days | No HCQ | Conversion to negative PCR | - Hospital length of stay - Conversion to negative PCR at day 14 - Admission to ICU - Required high flow O2 and ventilation - Pneumonia |
There was a significant difference in conversion to negative PCR at day 14 between the HCQ group (47.8%) and the control (90.9%) (p = 0.016) |
| Mahévas et al. | Cohort | France | 181 hospitalized with pneumonia | HCQ 600 mg daily for 7 days | Supportive care | Transfer to the ICU within 21 days | - All cause mortality - ARDS |
There was not a significant difference in ICU transfers at 21 days between the HCQ group (76%) and the control (75%) (p > 0.05) |
| Molina et al. | Case series | France | 11 hospitalized | HCQ 600 mg for 10 days AND AZT 500 mg on day 1, then 250 mg for 4 days |
N/A | - Virological status - Clinical status |
Conversion to negative PCR at day 6: 20% Mortality: 9% |
|
| Chen et al. | Cohort | China | 284 hospitalized; 25 received CQ (8%) |
CQ duration and dose unknown | Supportive treatment No CQ (n = 121) |
Conversion to negative PCR at 7, 14, 21 days | There was not a significant difference in conversion to negative PCR at 14 days between the CQ group (64.7) and the control (71.7%); OR 0.98, 95% CI 0.58–1.67 |
|
| Yu et al. | Cohort | China | 568 hospitalized patients requiring the ICU (48 HCQ, 520 control) | HCQ 200 mg twice daily for 7–10 days | Supportive treatment+ antiviral/antibiotic | - Death | - Cytokine levels - Hospital stay duration |
There was a significant difference in mortality between the HCQ group (18.8%) and the control (47.4%) (p < 0.001) |
| Rosenberg et al. | Cohort | USA | 1438 hospitalized | HCQ + AZT/HCQ alone/AZT alone; Dose and duration unknown |
Supportive | - In-hospital mortality | - Cardiac arrest - QTc prolongation |
There was no significant association with in-hospital mortality for HCQ alone (HR 1.08, 95% CI 0.63–1.85), AZT alone (HR 1.35, 95% CI 0.76–2.40), or combination HCQ + AZT (HR 0.56, 95% CI 0.26–1.26) groups |
| Geleris et al. | Cohort | USA | 1376 hospitalized with respiratory distress | HCQ 600 mg twice daily on day 1, then 400 mg daily for 4 days AND AZT 500 mg on day 1, then 250 mg daily for 4 days |
Supportive treatment/No HCQ | Death or intubation | There was no significant association between HCQ use and the primary outcome of death or intubation (HR 1.04, 95% CI 0.82–1.32) | |
| Magagnoli et al. | Cohort | USA | 368 hospitalized | HCQ + AZT or HCQ alone; Dose and duration Unknown |
Supportive treatment +AZT |
- Mortality - Need for mechanical ventilation |
- Hospitalization among patients requiring mechanical ventilation | There was a significant difference in mortality between the HCQ group (19.2%), HCQ + AZT group (22.9%), and the control (9.4%) (p < 0.001). There was no significant difference in need for mechanical ventilation between the HCQ + AZT group (6.9%) and the control (14.11%) (p > 0.05) |
| Arshad et al. | Cohort | USA | 2541 patients | HCQ 400 mg twice daily on day 1, then 200 mg twice daily on days 2–5. 500 mg AZT daily on day 1 followed by 250 mg daily for 4 days. |
Supportive treatment | Mortality | Compared to those receiving neither treatment, those receiving either HCQ alone or in combination with azithromycin had a lower risk of in-hospital mortality in multivariable models (HR 0.34, 95% CI 02.5–0.46; HR 0.29, 95% CI 0.22–0.40). |
Abbreviations: HCQ: Hydroxychloroquine; CQ: Chloroquine; AZT: Azithromycin; RR: Relative Risk; OR: Odds Ratio; HR: Hazard Ratio; CI: Confidence Interval; ICU: intensive care unit; PCR: polymerase chain reaction; ARDS: acute respiratory distress syndrome.