COVID-19: Could remdesivir be the game-changer? A physician at an epicenter looks at the need, and the hope

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Dr. Kwan Kew Lai, photo credit: Charles FitzGibbon

The following is a guest post by Kwan Kew Lai, MD, DMD

It was my last day of volunteering as a medical doctor at Elmhurst Hospital Center, Queens, New York, heeding the call of Gov. Cuomo to help my colleagues in desperate need of relief from their burden of caring for COVID-19 patients. I usually volunteer in disasters and epidemics occurring in far-flung places but the epicenter of this coronavirus pandemic is right next door.

At the end of my last day, after rounding in three intensive care units, I returned to the office I shared with a fellow to find him listening intently to the breaking news in which Dr. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases announced that remdesivir has been shown to shorten the duration of illness of seriously ill COVID-19 patients.

The interim analysis from a randomized, placebo-controlled trial of intravenous remdesivir in nearly 1,100 patients hospitalized with COVID-19 with lung involvement, including those requiring supplemental oxygen or mechanical ventilation found that compared to placebo, remdesivir-treated patients recovered faster. It took them a median time of 11 days versus 15 days to ditch their oxygen requirement or being discharged from the hospital. The mortality rate was 8.0% with remdesivir and 11.6% with placebo.

Because of ethical considerations, the Food and Drug Administration temporarily approved the emergency use of remdesivir for the treatment of COVID-19.

This announcement brought back the memory of so many years ago when zidovudine or AZT was found to slow the progression of HIV infection in interim data analysis of the AIDS Clinical Trials Group or ACTG 019, a double-blind trial where AZT was compared to placebo in the treatment of HIV-infected patients. I was a young freshly minted infectious disease attending physician involved in several clinical trials for HIV/AIDS treatments. I remembered that day when it was announced that AZT indeed was found to be effective in slowing down the progression of HIV infection. The 019 study would stop enrolling patients as it would be unethical to continue when an effective medication for HIV-infected patients was found. It came too late for many of my patients seeking help and cure, beset by wasting syndrome, dying from respiratory failure from Pneumocystis jerovechi infection, then Pneumocystis carinii pneumonia, and many other opportunistic infections. At that time Drs. Margaret Fishl and Paul Voldberding declared that the availability of AZT was a game-changer in the fight against HIV/AIDS and it was.

Will remdesivir be a game-changer in the fight against the coronavirus pandemic?

When I started to volunteer in this COVID-19 pandemic, my assignment was in the ICUs, so I saw the sickest patients. It was a baptism and a trial by fire. These patients had been in the ICUs from 1 to almost 4 weeks, over 90% of them intubated; some in the field, some on arrival in the emergency room as their oxygen saturation was so low that it was incompatible with life. A few were supported with high flow oxygen and non-rebreather masks for as long as possible until finally it was impossible to keep their oxygenation high enough and mechanical ventilation was used. There is no question that those who are intubated seem to fare less well, so clinicians tend to delay intubation using whatever means to improve the oxygen saturation of the patients. Some of these patients have been intubated for such a long period now they are being considered for tracheostomy. There are also teams to help to prone and un-prone patients every 12 hours as this position seems to improve their oxygen saturation levels.

As with the early days of HIV/AIDS epidemic, doctors are learning how to treat COVID-19 infection. These patients present with fever, cough, and shortness of breath with low oxygenation requiring assistance with a respiratory device with oxygen supplementation. With the stay-at-home mandate, many seem to heed it and present during the second or more weeks of symptoms. By then many of them are in a very dire state and when they arrive at the emergency room, they rapidly decompensate. All of them have a chest x-ray with bilateral diffuse infiltrates. Many patients proceed to respiratory failure and acute respiratory distress syndrome and over half of them require dialysis for renal failure.

During the course of severe coronavirus infection, inflammatory markers are released, a phenomenon called a cytokine storm. Many patients have high D-Dimer, a marker for significant blood clots or thrombus in the body. In some cases, the level is in the 60-80,000 range (normal is less than 0.5), a likely indication of a hypercoagulable state, prompting clinicians to start anticoagulation. Indeed there are now reports of COVID-19 patients with strokes, heart attacks, pulmonary embolism, and deep venous thrombosis.

The initial protocol for the treatment of the COVID-19 infection started with azithromycin, hydroxychloroquine, and ceftriaxone, the last to treat for the possibility of community-acquired pneumonia. As the weeks proceeded, because of the complication of prolongation of QT interval and possible cardiac arrhythmia and its lack of efficacy, azithromycin had been dropped from the protocol with hydroxychloroquine still being used for some patients.

Recently, Tocilizumab, a monoclonal antibody against interleukin-6 (IL-6), has emerged as an alternative treatment for COVID-19 patients with a risk of cytokine storms and here it has been used in a few critically ill patients.

Initially convalescent plasma was in short supply even as the hospital began to be involved in a clinical trial. Then all of a sudden it became more readily available and with such liberal inclusion criteria, convalescent plasma was given to many COVID-19 patients, those who just presented as well as those already been in the hospital, fighting to survive. It was as though we were all desperate, racing to save lives. It would be a while before we know its efficacy.

COVID-19 hit us hard and fast and clinicians have learned to confront the onslaught with resourcefulness, not only in their daily communication with family members to update the conditions of their loved ones and to ease their pain in not able to see them in time of their deep distress, in the use and conservation of personal protective equipment, to ensure the safety of their coworkers but to also banded together in giving the best treatment for the patients, even as this is a thing in progress.  The learning curve in understanding COVID-19 infection and its treatment remains very steep.

Several decades after AZT was pronounced to be a game-changer, great strides have been achieved in the treatment of HIV/AIDS. AZT is a drug of the past but still remains iconic for the first sign of hope in the conquest of HIV/AIDS, although a vaccine for HIV still remains elusive.

As the COVID-19 pandemic unfolds, our hope is that there would come a time when a vaccine for SARS-CoV-2 would be available, that there may be a point-of-care diagnostic test just like that for influenza and that we as clinicians could prescribe a medication to prevent the progression of COVID-19 infection. Whether remdesivir is the game-changing drug remains to be seen.

Kwan Kew Lai, MD, DMD, FACP is a Harvard Medical School faculty physician at Beth Israel Lahey Health, an infectious disease specialist, disaster relief volunteer in various parts of the world, including the Ebola outbreak, the Syrian, Rohingya refugee crises and the war in Yemen, and the author of Lest We Forget; A Doctor’s Experience with Life and Death during the Ebola Outbreak and the upcoming Into the African Bush out of Academia: A Doctor’s Memoir.

Photo credit: Charles FitzGibbon

2 thoughts on “COVID-19: Could remdesivir be the game-changer? A physician at an epicenter looks at the need, and the hope

  1. Stuart Burstin

    Thank you for the eloquent comments . I 1979, while a fellow at the Brigham, Weinstein had a patient who has AIDS, before we knew about it and reported him in Gastroenterology. I have been working in HIV since, and share your concerns about the efficacy of remdesivir, having been at Gilead for the launch of TDF. However, I believe, this being a more acute process for which most infected people develop sterilizing immunity, a disease modification that allows immunity to develop, as long as we can learn to manage that immunity, may be enough. Combination therapy directed at the RNA metabolism as well as cell based TMPRSS or another point in viral growth may be needed, and a collaborative group conducting studies should be formed.. With what we have learned in the last 30 + years, and the need the world has, I am optimistic. All we need is appropriate leadership, and popular support of rational activities.

    Reply

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