Feinberg Investigators Explore COVID-19 Treatments & Impact

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02/04/2021

news.feinberg.northwestern.edu

Despite rising case counts and record deaths from COVID-19, there is a light on the horizon: vaccines are being administered to frontline healthcare workers and the elderly, and Feinberg investigators continue to investigate new treatments and share insights on combating misinformation and innovative techniques for mitigating the spread of the virus.

Early Treatment Shows Promise

Prompt treatment with tocilizumab was associated with lower mortality among critically ill patients with COVID-19, according to a study published in JAMA Internal Medicine.

The study used patient data from a large multicenter cohort and emulated a hypothetical randomized trial. These findings show that tocilizumab may have promise, but a formal trial is necessary to establish efficacy, according to Anand Srivastava, MD, MPH, assistant professor of Medicine in the Division of Nephrology and Hypertension and a co-author of the study.

“In patients who are critically ill, early treatment with tocilizumab may reduce mortality,” Srivastava said. “However, large randomized controlled trials in critically ill patients are needed to determine if tocilizumab is an effective therapy to reduce mortality in this patient population.”

The results showed that treatment with tocilizumab was associated with a lower risk of mortality, likely a result of the drug’s anti-inflammatory properties, according to Srivastava.

“Since inflammation may play an important role in the progression from acute viral illness to organ failure and death, the use of medications that target dysregulation inflammation may be a promising therapeutic strategy for COVID-19,” Srivastava said.

Performing an emulated trial from a large multicenter cohort study provided useful information at a time when speed is a priority. However, these results are still subject to confounding factors that are less present in a full randomized trial, so further study of tocilizumab is required to ascertain its benefit.

Srivastava is supported by the National Institutes of Health grant K23DK120811 and core resources from the George M. O’Brien Kidney Research Center at Northwestern University (NU-GoKIDNEY) grant P30DK114857.

Antimicrobial Resistance & COVID-19: Stopping Misinformation

Well before the COVID-19 pandemic, the world already faced the threat of antimicrobial resistance. Lack of basic knowledge of infections and their treatment has resulted in overuse of general antibiotics against COVID-19, possibly exacerbating antimicrobial resistance.

According to Mehreen Arshad, MBBS, assistant professor of Pediatrics in the Division of Infectious Diseases, a concerted effort is required to ensure medical providers have rapid, timely access to evidence and strategies for management of COVID-19.

“Unfortunately, the instinct to do ‘something’ often leads to the prescription of readily available antimicrobials such as azithromycin despite multiple studies showing no effect of these regimens,” said Arshad, who was the lead author of an editorial published in The BMJ. “Organizations need to emphasize the lack of effectiveness of antimicrobials, especially anti-bacterial, in treatment of COVID in their online campaigns targeting the public, as well as medical professionals.”

The spread of misinformation during pandemics has been previously documented, but the rise of the internet and social media along with political polarization have resulted in a global deluge of misinformation about COVID-19, Arshad wrote.

Further, this misinformation can also affect clinicians and policymakers. Poorly reported and preliminary research findings, including non-peer-reviewed preprint research, has contributed to inaccurate media reporting and a muddle of information for healthcare professionals to sift through.

“Medical professionals need to have the ability to refer to updated research findings from credible sources quickly and easily for their own knowledge, and be prepared to effectively communicate that knowledge to patients to allay their anxiety about watchful waiting in the outpatient settings,” Arshad said.

Boosting Efficacy of Remdesivir

Combining remdesivir with a cytokine inhibitor called baricitinib was superior to remdesivir alone in reducing recovery time for some patients with severe COVID-19, according to a study published in The New England Journal of Medicine.

These findings broaden the landscape of treatments for COVID-19, which are still very valuable even as vaccine distribution begins, according to Babafemi Taiwo, MBBS, ’06 GME, the Gene Stollerman Professor of Medicine, chief of Infectious Diseases in the Department of Medicine, and a co-author of the study.

“Developing therapeutics remains very important because vaccines are expected to markedly reduce but not eradicate new infections,” Taiwo said. “Moreover, it is unclear how long vaccine-induced immunity will last, and there is room to significantly improve upon the current antiviral and immune-modulatory treatment options.”

Patients receiving the combination treatment had a median time to recovery of seven days, as compared to eight days for patients receiving just remdesivir. Much of the improvement was in patients on high-flow oxygen or non-invasive ventilation.

Further, the combination treatment was associated with fewer adverse events. This makes the combination treatment a good alternative for patients who are unable to receive dexamethasone, which is the preferred treatment.

“It should be noted that COVID-19 treatment guidelines currently express a preference for dexamethasone over baricitinib, though these drugs have not been compared to each other,” Taiwo said. “A new study is underway to compare dexamethasone plus remdesivir to baricitinib plus remdesivir — this will, hopefully, help sort out the best approach to patient care.”

The trial was sponsored and primarily funded by the National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID) grants UM1AI148684, UM1AI148576, UM1AI148573, UM1AI148575, UM1AI148452, UM1AI148685, UM1AI148450, and UM1AI148689, and the NIH Stimulating Access to Research in Residency grant 5R38AI140299-02. Other funding includes the National Cancer Institute, NIH, under contract HHSN261200800001E 75N910D00024, task order number 75N91019F00130/75N91020F00010, and by the Department of Defense, Defense Health Program.

Network Interventions for Managing the Pandemic

Interventions that divide or balance social groups could substantially reduce transmission of COVID-19 while sustaining economic activity, according to a study published in Proceedings of the National Academy of the Sciences (PNAS).

The investigators used agent-based simulation to estimate the network effects of dividing group strategies, for example, mandating that one group of customers can go to the grocery store in the morning while the other group can go in the evening.

“Our findings show that alternative strategies to the widely unpopular strict lockdowns that many areas experienced in the spring of 2020 could slow the spread while allowing the economy to remain open,” said Justin Smith, Ph.D., adjunct associate professor of Psychiatry and Behavioral Sciences and a co-author of the study. “For these to be effective as our modeling indicated they could be, the public must be willing to follow the guidelines put forth and governments must similarly have the will to enforce it.”

In their analysis, Smith and his collaborators tested two strategies: splitting groups into two distinct subgroups that no longer physically interact, and balancing groups, where individuals approaching a destination are redirected to a different location to equalize the number of people at each location.

The simulation involved 10,000 individuals with network ties approximating an actual social network: family ties had the highest probability of transmission, non-family ties with an intermediate probability, and weak ties having the lowest probability. These ties were nested into eight sectors, including homes, workplaces, grocery stores, and restaurants or cafés.

The investigators simulated transmission of COVID-19 with different network mitigation strategies, finding that combining both splitting and balancing achieved nearly as much transmission reduction as strict lockdowns. This brought the effective reproduction – or R-naught – down to below one, meaning that each infected person spreads COVID-19 to less than one person, on average.

However, Smith cautions that these interventions require tremendous buy-in from policymakers and the public alike, and willingness to adhere to masks, social distancing, and other mitigation measures would be key for a network strategy such as the ones tested to reach the level of effectiveness found in the simulations.

“Our models showed that non-adherence to the proposed strategies could negate all benefits to the public and necessitate stricter options,” Smith said. “As policymakers plan for and react to spiking infection rates, proposed mitigation strategies have to consider these key factors on both sides of the equation.”

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