Some patients’ immune systems have responded to SARS-CoV-2 infections by going into a form of overdrive, leading to the overzealous response known as a cytokine storm—a very dangerous situation. When this occurs, the death rate associated with COVID-19 is extremely high. In association with this condition, the Feinstein Institutes for Medical Research and Northwell COVID-19 Research Consortium completed a retrospective study of 6,000 patients and the findings lead to somewhat of a potential breakthrough: results point to the most effective immunomodulatory therapies to treat patients with evidence of this cytokine storm and importantly, improve patient survival. Led by Negin Hajizadeh, MD, a pulmonary and critical care physician, and associate professor at the Feinstein Institutes, a multidisciplinary team of investigators analyzed the electronic health records of hospitalized COVID-19 patients across 12 of Northwell Health hospitals – New York State’s largest health system – between March 1 and April 24, 2020. The results were published today in CHEST, by Sonali Narain, MD, assistant professor at the Feinstein Institutes, corresponding author, and team.
The Retrospective Study
Patients were divided into one of six groups; no immunomodulatory treatment (standard of care), patients who received intravenous corticosteroids, anti-interleukin 6 antibody therapy (tocilizumab) or anti-interleukin-1 therapy (anakinra) alone or in combination with corticosteroids.
Results Point to Combination of Dexamethasone & Tocilizumab
The results show that the most effective treatment was the combination of corticosteroids – such as dexamethasone – with tocilizumab when compared to standard of care. Additionally, there was an improvement if corticosteroids were used alone, or in combination with tocilizumab or anakinra when compared with standard of care.
“Cytokine storms are a hallmark for many COVID-19 patients and are associated with the most severe form of this illness,” said Dr. Hajizadeh, associate professor at the Zucker School of Medicine at Hofstra/Northwell and co-senior author on the paper. “Our findings suggest that with the intervention of certain drugs like corticosteroids, we can battle the cytokine storm and improve outcomes to the point that we believe we have found a new standard of care for seriously ill patients.”
Overall, there were twice as many males as females in the cohorts, and more than 65 percent had never smoked. Contradictory to previous reports, the Black population was associated with better survival compared to white patients. Additionally, the most common comorbidities across the groups of patients that experienced a cytokine storm include:
- Hypertension (44-59 percent);
- Diabetes (32-46 percent);
- Cardiovascular disease (5-14 percent);
- Chronic kidney disease (5-12 percent);
- Cancer (5-11 percent);
- Asthma (3-12 percent).
“Dr. Hajizadeh’s major COVID-19 research study gives timely and crucial new knowledge about using currently available anti-inflammatory drugs,” said Kevin J. Tracey, MD, president and CEO of the Feinstein Institutes. “This information will help others save lives.”
The researchers hope that the findings are useful for frontline providers to care for severely ill COVID-19 patients and to aid in the future design of large randomized controlled clinical trials, the gold standard of medical research.
Not a Randomized Controlled Trial
Note that when establishing medical evidence randomized controlled, blinded studies represent the strongest form of evidence. Hence the medical establishment will place the highest weight on well-designed randomized controlled studies. The randomized controlled trial produces the highest level of evidence for causality, however there are issues that can impact the findings of both randomized controlled studies and retrospective studies. A retrospective study, a form of observational study, such as this, while not a randomized controlled trial, does introduce important real world data and cannot be ignored. They are often the next best approach to address the limitations of randomized controlled trials (especially during a pandemic). For more on the importance of well designed observational studies, see the link.
Previous Tocilizumab Alone Studies Don’t Work Out Targeting COVID
Investigators and pharmaceutical companies reported challenges with use of Tocilizumab as a COVID-19 therapy. On July 30, TrialSite reported that recent studies produced results leaning researchers’ opinions away from tocilizumab. Roche was on the record that Actemra® failed to meet an endpoint against COVID-19 while an Italian study revealed a negative signal as well. As a consequence of these trial findings, the National Institutes of Health (NIH) doesn’t recommend the use of anti IL-6 receptor monoclonal antibodies (e.g. sarilumab, tocilizumab) or anti-IL-6 monoclonal antibody (siltuximab) for the treatment of COVID-19, except in a clinical trial. Note the most recent Feinstein Institutes study, however, looks at a combination including Dexamethasone (corticosteroid), which has been shown in the RECOVERY study to help critical and severe COVID-19 patients who either A) mechanically ventilated or B) require supplemental oxygen but not mechanically ventilated–see the NIH guidelines.
About the Feinstein Institutes
The Feinstein Institutes for Medical Research is the research arm of Northwell Health, the largest healthcare provider and private employer in New York State. Home to 50 research labs, 3,000 clinical research studies and 5,000 researchers and staff, the Feinstein Institutes raises the standard of medical innovation through its five institutes of behavioral science, bioelectronic medicine, cancer, health innovations and outcomes, and molecular medicine. We make breakthroughs in genetics, oncology, brain research, mental health, autoimmunity, and are the global scientific leader in bioelectronic medicine – a new field of science that has the potential to revolutionize medicine. For more information about how we produce knowledge to cure disease.
Negin Hajizadeh, MD Assistant Professor, Institute of Health Innovations & Outcomes Research, Feinstein Institutes for Medical Research; Associate Professor, Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
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