Treating severe COVID patients with many drugs has no impact on survival - study

"Treatment with more drugs does not necessarily achieve more health-wise for patients,” Shaare Zedek Surgical Intensive Care director Sharon Einav said.

 Scanning electron microscope image shows SARS-CoV-2, also known as novel coronavirus (photo credit: U.S. NIAID-RML/Handout via REUTERS)
Scanning electron microscope image shows SARS-CoV-2, also known as novel coronavirus
(photo credit: U.S. NIAID-RML/Handout via REUTERS)

Administering multiple experimental or compassionate drugs to patients with severe cases of COVID-19 has nothing to do with the patients’ survival of the disease and could impact the accuracy of research being done on these treatments, according to a new Israeli study.

The research, conducted by a team from the Hebrew University of Jerusalem and Shaare Zedek Medical Center, was recently published in the peer-reviewed journal Advances in Therapy. It aimed to evaluate the question of how experimental drugs are used in the hospital, with an emphasis on the number of such drugs that an average patient received during the first wave of coronavirus in Israel.

The authors were at the forefront of patient care during the first wave. As such, the report was written based on a combination of observational data seen firsthand in the field and retrospective data analysis.

The data collected included patient demographics, co-morbidities, admission vital signs, laboratory values, the most extreme respiratory intervention during hospitalization and data regarding treatment with compassionate/experimental drugs during their hospital stay. This is the first study to examine the association between patient severity and multiple drug administration.

The findings indicated that “patients who were in worse condition upon arrival received more respiratory support and drugs during admission, and also had a longer length of stay [in the hospital], but still survived less well despite these efforts.”

 Empty beds in the intensive care unit at the Coronavirus ward of Shaare Zedek hospital in Jerusalem on October 14, 2021. (credit: OLIVIER FITOUSSI/FLASH90) Empty beds in the intensive care unit at the Coronavirus ward of Shaare Zedek hospital in Jerusalem on October 14, 2021. (credit: OLIVIER FITOUSSI/FLASH90)

Sharon Einav, director of Surgical Intensive Care at Shaare Zedek, who helped lead the study, explained that more than half of the serious patients as defined in the study also died.

"Treatment with more drugs does not necessarily achieve more health-wise for patients,” she said. “Therefore, it may be better to give less medicine to coronavirus patients, but to document much more, so that we can accumulate more knowledge for the following patients.

“This is how we learned in the past about cancer and AIDS, which have turned from incurable diseases into diseases that can be lived with for years,” she continued. “Thinking about the coronavirus should also be long-term.”

Specifically, the study collected data from 292 coronavirus patients over the age of 18 who were hospitalized between March 1 and April 17, 2020. The researchers collected information with an emphasis on the number of experimental or “compassionate” medications given to patients during their period of hospitalization.

In this experiment, medications included azithromycin, hydroxychloroquine, corticosteroids, remdesivir, convalescent plasma, lopinavir, opaganib and/or tocilizumab. However, a large number of drugs have been proposed as potential cures for COVID-19 and many of these drugs are being tested in medical centers.

“This unique collaboration between medical centers and researchers stems from the desperate hope that at least one of the many drugs tested will mitigate disease severity among the patients being treated,” the report said.

The results showed that 21% of the patients hospitalized during the first wave received two or more of these medications. They were routinely given to patients in life-threatening situations from the virus when it appeared that no other treatment options might be available or that other treatments were not working – despite the lack of clear proof of the benefit of those drugs for the patients.

The more severe a patient’s condition, the higher the chances of the patient receiving more than one experimental drug, according to the study.

A patient who did not need respiratory support at all had a 3% chance and a patient who was in a condition that needed mechanical respiration or a heart-lung ECMO machine had a 77.3% chance of receiving two or more experimental drugs. The average number of drugs received by critical patients was 1.92, compared to 0.55 for non-critical patients.

Nearly a third of coronavirus patients (31.5%) received one experimental drug during hospitalization. The maximum number of medications given at once to a single patient was four.

“When you see a patient deteriorating in front of your eyes, what you want to try to do is help him,” according to Hebrew University researcher Or Assouline, who led the study. “But what we saw was that most of our interventions were not helping – at least based on our clinical experience in the wards.”

A further challenge arose from the situation: The issue of mixed treatments may also be a major research setback, Assouline explained. That is because when multiple treatments are administered at the same time, it becomes nearly impossible to isolate the effect of any of them.

Although the research was done based on the situation during the first wave, he said that it is still applicable today. “We see today, during the fourth wave, the importance of the studies done during the first wave in terms of the treatment options available to us.”