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Infectious Diseases

Updated 29 September 2020

What experts have learned, and the questions that remain about severe Covid-19-infections

Authors of a recent editorial reviewed the latest evidence on the management of Covid-19, including drugs that have been proven to work, and those that still lack reliable evidence.

  • There are still many key questions about Covid-19 and its treatment that scientists are trying to answer
  • In a recently published editorial, researchers discuss available evidence on treatments and gaps in knowledge that still remain
  • They discuss drugs like dexamethasone, hydroxychloroquine, and remdesivir

For months, scientists have been trying to understand the new coronavirus, SARS-CoV-2, and Covid-19 disease caused by the virus.

Based on intensive research since the outbreak in central China late last year, we know that the virus behaves differently compared to similar pathogens. But although the understanding of Covid-19 disease has made great progress, many questions still remain.

In a recently published editorial, three researchers review current information about the management of patients with the acute respiratory distress syndrome (ARDS) that may be experienced by patients with severe Covid-19. They also explore what has been learned about the treatment of Covid-19 patients, and look at the gaps in knowledge that warrant further research.

Their paper was published in Jama Internal Medicine.

ARDS and Covid-19

ARDS is a rapidly progressive disease in critically ill patients, where the patient’s lungs cannot supply enough oxygen to their vital organs. Patients with ARDS are usually placed on ventilators.

The condition has been seen to develop in many patients with severe Covid-19. A systemic review and meta-analysis that was submitted to the Bulletin of the World Health Organization (WHO) earlier this year explained that the prevalence of mortality among patients with comorbidities and advanced age was very high, with ARDS, “the most likely independent predictor of in-hospital mortality”. 

While no particular pharmacologic therapies are currently available for ARDS, the authors wrote that decades of rigorous clinical trials have indicated that careful supportive care with the foundation of lung-protective ventilation can improve ARDS outcomes.

They also indicate that, at present, the majority of reports suggest that the respiratory physiology of ARDS – both associated and not associated with Covid-19 – are similar, and that this evidence reinforces the importance of adhering to evidence-based management principles that have proven effective for ARDS management.

“Whereas studies published early in the pandemic, largely from hospitals overwhelmed by critically ill patients, reported hospital mortality rates approaching 90%, more recent studies have reported outcomes more typical for patients with ARDS, with hospital mortality of 30% to 40% and in some cases remarkably lower,” the researchers wrote.

Covid-19 and treatment: remdesivir

Late in June, doctors received the go-ahead to use remdesivir – an antiviral drug that failed to successfully treat Ebola, but showed successful preclinical results against SARS and MERS – as a targeted treatment for Covid-19, Health24 reported.

In the editorial, the authors stressed that treatment of the underlying cause of ARDS is essential to improving Covid-19 outcomes. They add that in hospitalised patients, treatment of SARS-CoV-2 with remdesivir shortens the time to recovery.

However, what still remains uncertain is the use of the drug in patients requiring mechanical ventilation, and additional evidence is needed, they wrote.

Covid-19 and dexamethasone

Dexamethasone, which researchers praised as a "breakthrough" Covid-19 treatment in June, was found to have saved the lives of a third of the most serious Covid-19 cases (patients requiring oxygen or mechanical ventilation) in the RECOVERY trial, led by the University of Oxford researchers.

Subsequently, three additional randomised clinical trials and a meta-analysis have been published, note the researchers in their editorial, all showing consistent results with a beneficial effect of the use of corticosteroids in severe or critical Covid-19 cases.

According to their paper, WHO has issued guidelines recommending the use of corticosteroids in such patients.

In the case of Covid-19, ARDS, and dexamethasone, they note that greater clarity in the results for patients with Covid-19 has been established, compared to prior corticosteroid trials in ARDS that have led to conflicting results and, unfortunately, no consensus.

Unproven therapies and the need to exercise caution

Hydroxychloroquine, a drug primarily used to treat malaria, made global headlines earlier this year after US President Donald Trump touted it as a cure for Covid-19. This was despite scientists not having concluded their research on the drug at the time.

The same goes for lopinavir/ritonavir, the researchers wrote, adding that, despite the hype around the use of these two drugs early in the pandemic, they have proven ineffective for treating Covid-19.

“The lessons are that unproven therapies for Covid-19 may provide more harm than benefit and that there are no substitutes or shortcuts for well-conducted randomised clinical trials,” they wrote.

Further questions that still remain

Although there have been hopeful developments in the area of Covid-19, and these developments can be seen as a testament to the value of careful critical care provided by hospitals with adequate resources, one cannot ignore the disproportionate effects of the pandemic on vulnerable populations, including minority communities, those with low socioeconomic status, and the elderly, the authors note.

This, they say, demonstrates the vital need to bridge the gaps in healthcare systems, and to address systemic biases, eventually lessening these disparities.

“Finally, many patients, gratefully, recover from severe Covid-19," they mention, adding: “The long-term sequelae of the disease need to be further studied, including how recovery from Covid-19 does or does not differ from recovery from other forms of severe critical illness.

“Critical care has been revolutionised by the realisation that many patients survive their acute illness only to suffer serious long-term functional and psychological consequences of their stay in intensive care units.

“A better understanding of the most common post-recovery sequelae of severe Covid-19 can help clinicians best care for the increasing number of patients who do survive,” they concluded.