COVID-19 treatment update: Which medications improve survival?

Nearly 2 years into the pandemic, researchers worldwide scramble to find a cure for COVID-19 but are disappointed over and over, as trials churn out unsatisfactory results for various repurposed drugs examined. However, one or two agents have shown promising results in terms of patient survival.

Robert Fowler, chair of the Canadian Critical Care Trials Group, recently presented up-to-date findings on medications being used for the treatment of COVID-19 at the Asia Pacific Intensive Care Symposium (APICS) 2021 virtual conference.

In a clinical update, Fowler and his colleagues stated that management of COVID-19 is “not different from management of most viral pneumonia causing respiratory failure.” The main feature of severe disease is the development of acute respiratory distress syndrome (ARDS), a syndrome characterized by acute onset of hypoxaemic respiratory failure with bilateral infiltrates. [JAMA 2020;323:1499-1500]

He then stressed adherence to evidence-based treatment guidelines for ARDS, such as conservative fluid strategies for patients without shock following resuscitation, early antibiotics for suspected bacterial co-infection until a diagnosis is made, lung-protective ventilation, prone positioning, and extracorporeal membrane oxygenation for refractory hypoxaemia. [Am J Respir Crit Care Med 2017;195:1253-1263]

Solidarity Trial

One of the biggest studies ever conducted to find a treatment for COVID-19 was the World Health Organization (WHO) Solidarity Trial, which had recruited close to 15,000 patients in 600 hospitals across 52 countries. WHO expert groups recommended tests of four repurposed antiviral drugs (ie, remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a) in patients hospitalized with COVID-19.

Unfortunately, these regimens exhibited little or no effect on hospitalized COVID-19 patients, as indicated by overall mortality, initiation of ventilation, and length of hospital stay. [N Engl J Med 2021;384:497-511]

“The main outcomes of mortality, initiation of ventilation, and hospitalization duration were not definitely reduced by any trial drug, either overall or in any particular subgroup,” the researchers said. “For each of these four repurposed nonspecific antivirals, several thousand patients have now undergone randomization in various trials.”

Solidarity is currently awaiting results for the following treatments: imatinib, infliximab, artesunate, and dexamethasone.

RECOVERY Trial

Another international critical trial sought to identify treatments that could be beneficial for hospitalized patients with suspected or confirmed COVID-19. The Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial included nearly 42,000 participants in 185 active sites across the globe.

RECOVERY had analysed nine regimens (ie, aspirin, azithromycin, colchicine, convalescent plasma, dexamethasone, hydroxychloroquine, lopinavir-ritonavir, casirivimab-imdevimab, and tocilizumab) so far and is currently testing three suggested treatments (ie, baricitinib, dimethyl fumarate, and high-dose vs standard corticosteroids). [https://www.recoverytrial.net/results]

Of the nine agents examined, only dexamethasone, tocilizumab, and the casirivimab-imdevimab combination therapy were associated with improved survival. [N Engl J Med 2021;384:693-704; medRxiv 2021;doi:10.1101/2021.06.15.21258542; Lancet 2021;397:1637-1645]

Aspirin, azithromycin, colchicine, convalescent plasma, hydroxychloroquine, and the combination of lopinavir-ritonavir all failed to reduce 28-day mortality or improve other clinical outcomes. Aspirin, however, correlated with a slight increase in the rate of being discharged alive within 28 days. [medRxiv 2021;doi:10.1101/2021.06.08.21258132; medRxiv 2020;doi:10.1101/2020.12.10.20245944; medRxiv 2021;doi:10.1101/2021.05.18.21257267; Lancet 2021;397:2049-2059; N Engl J Med 2020;383:2030-2040; Lancet 2020:396:1345-1352]

Overall, Fowler suggested best-patient and family-centred clinical care, dexamethasone, and tocilizumab for hospitalized patients with COVID-19. He also recommended using augmented dose prophylaxis or anticoagulation for nonintensive care unit patients and casirivimab-imdevimab therapy for outpatients and sero-negative inpatients.