| Comparative observational study18 |
3737 |
1. HCQ+AZ
2. Others sub divided to:
-
HCQ-AZ <3 days
-
HCQ
-
AZ
-
SOC
|
HCQ+AZ treatment compared to control:
-
↓ Risk of death or transfer to ICU (HR 0.18; 95% CI 0.11–0.27)*
-
↓ Hospitalization ≥10 days (OR 0.38; 95% CI 0.27–0.54)
-
Shorter viral shedding duration in HCQ+AZ compared with all other subdivided groups, compared with SOC (HR 1.29; 95% CI 1.17–1.42)
|
-
Unequal group sizes (Tx Pts n=3,119 vs “Other” Pts n=618; with many Txs and no pre-specified protocol
|
| Comparative observational study15 |
2541 |
1. HCQ
2. HCQ+AZ
3. AZ
4. SOC |
Overall in-hospital mortality lower in all treatment groups:
HCQ+AZ: 20.1% (95% CI 17.3%–23.0%)
HCQ: 13.5% (95% CI 11.6%–15.5%)
AZ: 22.4% (95% CI 16.0%–30.1%)
SOC: 26.4% (95% CI 22.2%–31.0%) |
-
Tx group Pts mean age 5 y older than in controls
-
↑ steroid Tx rates in HCQ groups
-
Missing data due to reliance only on electronic health records
|
| Comparative observational study10 |
1438 |
1. HCQ
2. HCQ+AZ
3. AZ
4. SOC |
No Sig.Dif. in mortality rates for HCQ+AZ (HR 1.35; 95% CI 0.76–2.40), HCQ alone (HR 1.08; 95% CI 0.63–1.85), or AZ alone (HR 0.56; 95% CI 0.26–1.21) compared with control* |
-
No follow-up of discharged Pts
-
Missing group characteristics data
-
Major difference between size of SOC vs Tx groups
|
| Comparative observational study12 |
1376 |
1. HCQ
2. SOC |
No significant association between HCQ and intubation or death vs SOC (HR 1.04; 95% CI 0.82–1.32) |
HCQ Pts more severely ill than SOC at baseline |
| Comparative observational study of critically ill ventilated patients with ARDS14 |
568 |
1. HCQ
2. SOC |
Primary Outcome
-
Significant mortality rate differences between HCQ (18.8%) and SOC (45.8%) groups; P<0.001
Secondary Outcomes
-
Longer HCQ hospitalization time before death compared to SOC (P<0.05)
-
IL-6 levels significantly lower during Tx period for HCQ group; SOC group unchanged
|
-
Such dramatic ↓ in mortality rate not described in any other study
-
Different rates of antibiotics use and interferon imply inherent selection bias for HCQ vs SOC (HCQ 0% interferon vs 10.8% in SOC (P=0.01)
|
| Comparative observational study16 |
72 |
1. HCQ-asymptomatic
2. SOC-asymptomatic |
-
No Sig.Dif. in recovery rates (HCQ 97.5% vs SOC 96.85%)
-
Earlier Tx group recovery (5.4 days) vs SOC (7.6 days)
|
-
HCQ efficiency only assessed in asymptomatic Pts
-
Inclusion to SOC due to HCQ contraindications that probably imply underlying medical conditions
|
| Comparative observational study of only electronic health records13 |
368 |
1. HCQ
2. HCQ+AZ
3. SOC |
Primary Outcomes
-
↑ mortality rates for HCQ (AHR 2.61; 95% CI 1.10–6.17; P=0.03) vs SOC, but not in HCQ+AZ (AHR 1.14; 95% CI 0.56–2.32; P=0.72)
-
No Sig.Dif. in ventilation rates among HCQ, HCQ+AZ, and SOC (13.3%, 6.9%, 14.1%, respectively)
Secondary Outcomes
-
No difference in risk of death after ventilation in HCQ (AHR 4.08; 95% CI 0.77–21.70; P=0.10), HCQ+AZ (AHR 1.20; 95% CI 0.25–5.77; P=0.82), compared with the no HCQ group
|
-
Missing data due to reliance on electronic health record codes
-
~95% males in all groups
|
| Comparative observational study of pneumonia patients requiring O2 without ICU admission11 |
181 |
1. HCQ
2. SOC |
Primary Outcome
-
No Sig.Dif. in survival rates at day 21 for Pts not transferred to the ICU; HCQ 76% vs SOC 75% (WHR 0.9; 95% CI 0.4–2.1)
Secondary Outcomes
-
No Sig.Dif. in overall survival at day 21: HCQ (89%) vs SOC (91%) (WHR 1.2; 95% CI 0.4–3.3)
-
No SC for O2 weaning at day 21: HCQ 82% vs SOC 76% (WRR 1.1; 95% CI 0.9–1.3)
|
-
HCQ Pts with fewer comorbidities
-
No Tx allocation protocols
|
| Comparative observational study17 |
84 |
1. HCQ
2. SOC |
No Sig.Dif. for:
-
Reducing unfavorable outcome risk (defined as death, ICU admission, or decision to withdraw or withhold life-sustaining treatments) (HR 0.90; 95% CI 0.38–2.1; P=0.81)
-
Overall survival (HR 0.89; 95% CI 0.23–3.47; P=1)
|
Small-scale study |
| Comparative observational study19 |
65 |
1. HCQ
2. Lopinavir-ritonavir |
Primary Outcome
-
Significantly shorter time to virological cure in lopinavir-ritonavir group (median 21 days vs 28 days; P=0.029)
Secondary Outcome
-
No Sig.Dif. in time to clinical improvement between groups (median 18 days vs 21 days; P=0.216)
|
More pneumonia Pts in lopinavir-ritonavir group |
| Comparative observational study20 |
60 |
1. Azithromycin, prednisolone, naproxen, and lopinavir/ritonavir
2. Meropenem, levofloxacin, vancomycin, HCQ, and oseltamivir |
Primary Outcome
-
SpO2 saturation, body temperature, and CRP values more favorable in Group 1 Pts (P=0.013, P=0.012, P<0.001, respectively).
Secondary Outcome
-
Significantly ↓ length of hospitalization for Group 1 vs Group 2 (P=0.001)
|
-
Due to multiple drug regimens, unclear relative contribution of each drug to the results
-
Adding broad-spectrum antibiotic to COVID-19 is probably unnecessary21
|
| Uncontrolled observational study9 |
1061 |
1. HCQ+AZ |
-
Poor clinical outcome for 46 Pts (4.3%), 8 died (0.75%), 6 transferred to ICU (0.56%); 30 hospital stays >10 days (2.8%)
-
Prolonged viral carriage in 47 Pts (4.4%)
|
-
Uncontrolled study
-
Relatively young Pts: mean age 43.6 y
|
| Uncontrolled observational study8 |
80 |
1. HCQ+AZ |
-
Clinical improvement: 97.5% Pts
-
Mean length of hospital stay: 5 days
-
Negative virus cultures in 97.5% Pts at day 5
|
-
Uncontrolled study
-
Inadequate length of post-treatment follow-up
-
Relatively young Pts: median age 52.5 y
|