Table 3.
Selected clinical studies in respiratory viral infections
| Study Population | Study design | Treatments | Key results | Conclusion | References |
|---|---|---|---|---|---|
| COVID‐19, >12 years (N = 36) | Observational, nonrandomized, external control, open‐label |
Nonrandomized Control HCQ (200 mg q.8h. × 10 days) HCQ + AZ (500 mg D1 and 250 mg D2‐5) |
At D6 post‐inclusion, negative nasopharyngeal PCR in: 100% (6/6) pts. HCQ + AZ 57.1% (8/14) HCQ 12.5% controls (P < 0.001). |
The authors concluded that HCQ is significantly associated with viral load reduction and its effect is reinforced by AZ. Additional studies are needed in more severe patient population (NEWS score) with a robust control group. | 2 |
| COVID‐19, >18 years (N = 80) | Observational, single arm | HCQ (200 mg q.8h. × 10 days) + AZ (500 mg D1 and 250 mg D2‐5) |
Decrease in nasopharyngeal viral load (qPCR): 83% negative at D7, and 93% at D8. Patients presumably contagious (PCR Ct < 34) decreased and reached zero on D12. |
The authors concluded that these results corroborated the efficacy of HCQ with AZ and its potential effectiveness in the early impairment of contagiousness. This finding provides further evidence in uncontrolled case series, deserving replication. | 3 |
| COVID‐19, 20–77 years, (N = 11) | Observational, single arm | HCQ + AZ (unspecified doses) |
Within 5 days, one patient died, two were transferred to the ICU. One patient discontinued after 4 days due to QT interval of 460 msec to 470 msec (baseline 405 msec). At D6, 8/10 patients were positive for SARS‐CoV‐2 RNA in nasopharyngeal swabs. |
No evidence of strong antiviral activity with the combination of HCQ and AZ. | 27 |
| Healthy children < 5 years (N not specified) | Ad hoc analysis of an interventional, randomized, cluster‐controlled, blinded study. |
Placebo AZ suspension every 6 months for 2 years |
At 24 months, an 8x reduction (via RNA‐seq) in alpha‐coronavirus and a 14x reduction in beta‐coronavirus in AZ group vs. placebo. At 36 months, number of children with coronavirus was not different between groups. |
AZ may decrease viral load but not prevalence of colonization. | MORDOR II Studyb |
| MERS (N = 349) | Retrospective, multicenter cohort database |
Macrolide, n = 136 (39%), (71.3% with AZ) No macrolide |
90‐day mortality (adjusted OR: 0.84; 95% CI 0.47–1.51) or MERS‐CoV RNA clearance (adjusted HR: 0.88; 95% CI: 0.47–1.64) | Macrolide therapy was not associated with a reduction in 90‐day mortality or improvement in MERS‐CoV RNA clearance. | 28 |
|
Confirmed SARS (2003) 16–84 years (N = 190) |
Retrospective review |
Ribavirin + C/S (N = 40) FQ + AZ+IFN‐α (+steroid) (n = 30) Q + AZ (+IFN‐α + steroid) (n = 60) Levo + AZ (+IFN‐ α + steroid) (n = 60) |
Early use of high‐dose steroids with a quinolone plus AZ showed improvement of clinical symptoms and signs and a decreased incidence of ARDS, mechanical ventilation, and mortality. Respiratory improvement and mean time to discharge was shorter in Q + AZ and Levo + AZ groups. |
The early use of high‐dose steroids with a quinolone plus AZ gave the best clinical outcome. | 29 |
| Influenza A infection, >20 years (N = 107) | Prospective, randomized, controlled, open‐label, multicenter |
Oseltamivir (75 mg q.12h. × 5 days) (n = 56) Oseltamivir (75 mg q.12h. × 5 days) + AZ (2,000 mg single dose extended release) (n = 51) |
No significant treatment differences in inflammatory markers. Trends in favor of combination therapy for reduction in max temp on D3–5 (P = 0.048); improvement in sore throat on D2. |
Combination therapy showed an early resolution of some symptoms. | 30 |
| Diagnosed for Influenza‐A (H1N1) pdm09 strain (N = 329) | Retrospective chart review |
Oseltamivir Oseltamivir + AZ (500 q.d.) |
Monotherapy vs. combination: secondary bacterial infections (23.4% vs. 10.4%), length of hospitalization (6.58 vs. 5.09 days), incidences of respiratory support (38.3% vs. 17.6%), influenza symptom severity score D5 (12.7 vs. 10.7). |
Combination therapy was more efficacious compared with oseltamivir alone in rapid recovery of influenza‐associated complications in high‐risk patients. | 31 |
|
RSV Otherwise healthy infants (N = 40) |
Randomized, double‐masked, placebo‐controlled, proof‐of‐concept |
AZ Placebo (14 days) |
Azithromycin did not reduce serum IL‐8 levels at D8 (P = 0.6) but reduced nasal lavage IL‐8 by D15 (P = 0.03). ≥3 wheezing episodes (22% in AZ vs. 50% in placebo) (P = 0.07). |
Azithromycin treatment during RSV bronchiolitis reduced upper airway IL‐8 levels, prolonged the time to the third wheezing episode and reduced overall respiratory morbidity. | 32 |
ARDS, acute respiratory distress syndrome; AZ, azithromycin; CI, confidence interval; CoV, coronavirus; COVID‐19, coronavirus infectious disease‐2019; C/S, cefoperazone/sulbactam; Ct, cycle threshold; D, day; FQ, fluoroquinolone; HCQ, hydroxychloroquine; HR, hazard ratio; ICU, intensive care unit; IFN, interferon; IL, interleukin; Levo, levofloxacin; MERS, Middle East respiratory syndrome; N, number of patients; n, subgroup or subpopulation; NEWS, National Early Warning Score; OR, odds ratio; PCR, polymerase chain reaction; Q, quinolone; q.8h., every 8 hours; q.12h., every 12 hours; q.d., once daily; qPCR, quantitative PCR; RSV, respiratory syncytial virus; RNA‐seq, RNA sequencing; SARS, severe acute respiratory syndrome.
In press: Doan T, Hinterworth A, Arzika A, et al. "Reduction of coronavirus burden with mass azithromycin distribution."