Co-Administration of Remdesivir and Azithromycin May Protect against Intensive Care Unit Admission in COVID-19 Pneumonia Requiring Hospitalization: A Real-Life Observational Study

Abstract

The benefits of remdesivir treatment, with or without co-administration of antibiotics such as azithromycin, are uncertain in COVID-19 pneumonia. The aim of this retrospective single-center study was to assess the effects of remdesivir, with or without azithromycin, on hospital mortality, intensive care unit (ICU) admission, and need of non-invasive ventilation. The clinical records of the COVID-19 patients hospitalized in an Italian ward in March 2021 were analyzed, and data on comorbidities and clinical, radiological, and laboratory presentation of the disease were collected. Among 394 participants (234 M), 173 received remdesivir (43.9%), including 81 with azithromycin (20.5%). Remdesivir recipients were younger, with less comorbidities, and had better PaO2/FiO2 and clinical outcomes, including reduced mortality, but the differences were not independent of covariates. Rates of ICU transferal were 17%, 9%, and 1% in the no remdesivir, remdesivir without azithromycin, and remdesivir/azithromycin groups, respectively. In a stepwise multivariate logistic regression model, remdesivir/azithromycin co-treatment was independently associated with reduced ICU admission (vs remdesivir alone, OR 0.081, 95% CI 0.008–0.789, p = 0.031; vs no remdesivir, OR 0.060, 95% CI 0.007–0.508, p = 0.010). These data suggest that the therapeutical effect of remdesivir in COVID-19 pneumonia may be potentiated by azithromycin. The association between the two drugs should be further investigated.

Synergistic drug combinations designed to fully suppress SARS-CoV-2 in the lung of COVID-19 patients

“…Similarly, combining antivirals might lead to synergy and complete inhibition of SARS-CoV-2, the causative agent of the COVID-19 pandemic, especially when attacking the virus at multiple steps of its life cycle by broad-spectrum antivirals acting with different mechanisms of action such as RDV, AZI and IVM. In line with our hypothesis and proposed mechanism of action, a recent clinical study at the hospital of Parma, Italy, one of the first provinces hit by COVID-19 outside China in early 2020, showed that intensive care unit admission was significantly delayed by the combination of AZI and RDV, but not by RDV alone, in a stepwise multivariate logistic regression model [17].…”

“…Our results would suggest the possibility of once-a-day (QD) administration may be effective for any of these combinations. A clinical study submitted after our study had been submitted and published while our manuscript was under review found that the coadministration of RDV and AZI was associated with reduced risk of ICU admission, independently of covariates [ 17 ].…”

Insights from comparison of the clinical presentation and outcomes of patients hospitalized with COVID-19 in an Italian internal medicine ward during first and third wave

“…Intravenous dexamethasone treatment has rapidly gained the role of cornerstone treatment of COVID-19 related interstitial pneumonia, for its capacity of reducing mortality, oxygen supplementation and ventilatory support need ( 32 ). Intravenous remdesivir was also commonly used during the third wave, but not in the first one ( 33 ). Interestingly, the higher frequencies of NIV support and ICU treatment detected in the third wave ( Table 1 ) could reflect improved management protocols and better understanding of indications and timing of ventilatory escalation in patients with severe respiratory failure.…”

Comparison of Clinical Characteristics and Outcomes of Hospitalized Patients Infected with the D614G Strain or Alpha Variant of COVID-19 in Taiwan: A Multi-Center Cohort Study

“…A study by Du et al reported azithromycin demonstrated in vitro anti-viral effect against SARS-COV-2 and blocks the entry of SARS-CoV-2 in HEK293T-ACE2 and Caco2 cells [26]. Another observational study also reported the clinical benefits of antibiotics: the combination of remdesivir-azithromycin treatment significantly decreased the ICU admission rate [27]. However, the exact mechanism of antibiotics in SARS-COV-2 viral clearance remains to be investigated.…”