Current evidence for COVID-19 therapies: a systematic literature review

Abstract

Effective therapeutic interventions for the treatment and prevention of coronavirus disease 2019 (COVID-19) are urgently needed. A systematic review was conducted to identify clinical trials of pharmacological interventions for COVID-19 published between 1 December 2019 and 14 October 2020. Data regarding efficacy of interventions, in terms of mortality, hospitalisation and need for ventilation, were extracted from identified studies and synthesised qualitatively. In total, 42 clinical trials were included. Interventions assessed included antiviral, mucolytic, antimalarial, anti-inflammatory and immunomodulatory therapies. Some reductions in mortality, hospitalisation and need for ventilation were seen with interferons and remdesivir, particularly when administered early, and with the mucolytic drug, bromhexine. Most studies of lopinavir/ritonavir and hydroxychloroquine did not show significant efficacy over standard care/placebo. Dexamethasone significantly reduced mortality, hospitalisation and need for ventilation versus standard care, particularly in patients with severe disease. Evidence for other classes of interventions was limited. Many trials had a moderate-to-high risk of bias, particularly in terms of blinding; most were short-term and some included low patient numbers.This review highlights the need for well-designed clinical trials of therapeutic interventions for COVID-19 to increase the quality of available evidence. It also emphasises the importance of tailoring interventions to disease stage and severity for maximum efficacy.

Multidrug-resistant Acinetobacter baumannii infections in COVID-19 patients hospitalized in intensive care unit

“…A peculiar aspect of COVID-19 patients, especially during the “second wave”, was the widely use of steroids at high dosages. The use of dexamethasone resulted in lower 28-day mortality, especially in patients receiving invasive mechanical ventilation [ 27 , 28 ]. However, the prolonged use of high doses of steroids could be associated with the well-known immunomodulant effects of these drugs [ 29 ], but the association between steroid treatment and MDR infections deserves further comments.…”

Antivirals against SARS-CoV-2 by autumn?

“…They instead rely on host enzymes for replication and thus offer few viable drug targets. None of the currently available oral antiviral drugs are licensed for coronaviruses, and investigation into their use against SARS-CoV-2 in clinical trials has not been encouraging 4. Despite this, close to a hundred licensed antivirals are available for other pathogens and collectively save millions of lives every year 5.…”

“…Despite this, close to a hundred licensed antivirals are available for other pathogens and collectively save millions of lives every year 5. Most are highly specific for their target virus, and activity against different viruses is the exception rather than the rule 4. The European Union has shortlisted some intravenous medications for development, but these would not fit the UK government’s brief of oral drugs to be taken at home 6…”

“…Favipiravir and nitazoxanide have been shown to inhibit a large number of viruses in vitro, but phase III trials have been completed only for influenza 78. Medications against other pathogens might also have anti-SARS-CoV-2 activity,8 but several repurposing attempts have ended in disappointment, including ivermectin, azithromycin, and hydroxychloroquine 4…”

“…Vaccine efficacy against symptomatic disease is 67-95%, with unknown durability and effectiveness against new variants 2. Peak viral loads seem to determine the duration and severity of symptoms,3 but current covid-19 treatments are largely limited to anti-inflammatory drugs (dexamethasone, tocilizumab, and sarilumab) that save only around one in three patients who would otherwise have died 4. Remdesivir, the most commonly used antiviral for SARS-CoV-2 in the UK, requires intravenous administration and seems to offer little survival benefit 4…”