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Mass General Launching Randomized, Controlled Trial of Tocilizumab for COVID-19

In This Article

  • The clinical manifestations of COVID-19 seem to be related to dysregulated immune response, and dampening that response may prevent severe disease but needs to be carefully studied through controlled clinical trials
  • Several small studies have correlated the inflammatory cytokine interleukin-6 (IL-6) with clinical outcomes in COVID-19
  • According to a small case series from China (n=21), tocilizumab, an IL-6 blocker, is effective in slowing the progression of COVID-19
  • Massachusetts General Hospital is launching a randomized, controlled trial to investigate whether administering tocilizumab in early-stage COVID-19 can prevent progression to the need for ICU care and mechanical ventilation

The pathogenesis of COVID-19 and early small studies suggest that intervention with immunomodulatory agent (e.g., a monoclonal antibody)—including several already approved in the U.S. for other indications—may be an effective treatment. A multidisciplinary COVID-19 Immunomodulation Group at Massachusetts General Hospital, formed to study this therapeutic strategy, has designed a randomized, controlled trial of tocilizumab, a monoclonal antibody that blocks the interleukin-6 (IL-6) receptor.

Group member Michael K. Mansour, MD, PhD, physician and researcher in the Division of Infectious Diseases at Mass General, described the rationale during Massachusetts General Hospital's virtual medical grand rounds held on April 9, 2020.

Why Use an Immunomodulator?

Several groups have measured respiratory SARS-CoV-2 RNA throughout the course of COVID-19. The viral load seems to peak during the asymptomatic phase or the phase of nonspecific symptoms, then decrease in the proinflammatory phase when acute respiratory distress syndrome (ARDS) can develop. There appears to be a correlation with higher peaks and worse clinical outcomes.

These observations have led to the hypotheses that the clinical manifestations of SARS-CoV-2 infection, in later stages, are related to dysregulated immune response, and dampening that response may prevent severe disease.

Why Use Tocilizumab?

Scientists are examining many factors in the "cytokine storm" that occurs in severe COVID-19. IL-6 is top of mind right now because of several small studies (most are still in preprint form to date). For example, in a German study of 40 patients, outcomes of mechanical ventilation correlated with admission IL-6 concentration. In a Chinese hospital cohort, IL-6 was elevated in non-survivors compared with survivors throughout the clinical course, and it increased with illness deterioration.

Tocilizumab is a monoclonal antibody that blocks the IL-6 receptor. The study that spurred excitement about using it for COVID-19 was a nonrandomized case series of 21 patients in China. One 400-mg dose was given to patients who had bilateral pulmonary infiltrates and were in severe or critical condition (three patients who still had fever 12 hours later received another dose).

There was rapid improvement in C-reactive protein (an indirect measure of inflammatory status), need for oxygen and multiple other metrics. Since then, several anecdotal reports around the world have described positive results of using an IL-6 blocker or IL-6 receptor blocker.

The Mass General Trial

Mass General plans to administer a single 400-mg dose of tocilizumab (n=195) or placebo (n=97) to hospitalized patients with early-stage COVID-19. The primary outcomes will be the need for ICU-level care and the need for invasive ventilation.

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Learn more about infectious disease research at Mass General

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Mass General has launched a COVID-19 clinical trials platform that pairs its infectious disease and immunology experts with organ-specific physiology and clinical care leaders to rapidly implement and conduct new investigator- and industry-initiated clinical trials.


On April 9, 2020, the Department of Medicine held its fifth virtual Grand Rounds presentation related to COVID-19. Keith Flaherty, MD, at Massachusetts General Hospital, and Scott Gottlieb, MD, former FDA commissioner, along with other members of the Greater Boston medical community, presented on advancing experimental therapies to treat COVID-19.