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APRIL 08, 2020 -- Dr Alberto Bassi, a 62-year-old Italian dermatologist, was still hospitalized in the town of Castel San Giovanni in Piacenza, Italy, and on oxygen when he decided to send a message to all his fellow physicians: "I'm now in the hospital with COVID-19 pneumonia. Tocilizumab changed everything."
He posted to Medscape Consult, a crowdsourced social media platform in which clinicians share and discuss real cases, and a frenzy of questions from healthcare providers tackling COVID-19 ensued.
Bassi's case is one of several confirmed and suspected cases of COVID-19 being discussed on Consult. One confirmed case showed classic respiratory symptoms that progressed rapidly in a 43-year-old Italian man. Anothershowed gastrointestinal symptoms — vomiting and diarrhea — that were resistant to therapy and no pulmonary symptoms. In more than 40 other threads, doctors from around the world are discussing epidemiology, comorbidities, and investigative treatments.
Initially, he took acetaminophen and rested, but 2 days later his oxygen saturation "had dropped from 98% to 88% with progressive respiratory failure," he told Medscape by email. On the recommendation of the chief of the local ICU, a close friend, Bassi was hospitalized, and clinicians took a nasal swab to confirm COVID-19. Over the following days he received a treatment regimen of Plaquenil (hydroxychloroquine), lansoprazole, antiretroviral therapy, enoxaparin, and methylprednisolone (intravenous).
Then, after one dose of tocilizumab, an immunosuppressant used to treat rheumatoid arthritis, Bassi's breathing improved almost immediately, he said in an email interview. Tocilizumab is an interleukin-6 receptor antagonist, blocking the proinflammatory IL-6 from its binding site and stopping the uncontrolled inflammatory response that may be a cause of mortality in some COVID-19 patients. A recent retrospective study of 150 patients in China suggested virally activated hyperinflammation may be a major cause of COVID-19 mortality.
As one physician commented on Bassi's Consult post, "The second phase of [COVID-19] appears to be immunological. The virus may not even be present anymore and people die from the cytokine storm."
Pranatharthi Chandrasekar, MD, division chief of infectious diseases at Wayne State University in Detroit, Michigan, says that it is still unclear if the virus or host inflammatory response are to blame. But if hydroxychloroquine isn't effective, anti-inflammatories are the next course of action. And when prescribing anti-inflammatory drugs, such as tocilizumab or corticosteroids, for COVID-19, "timing seems to be most critical," he told Medscape.
Cytokine storms, the uncontrollable pro-inflammatory reaction that can cause sepsis and organ failure, are also a key factor in cytokine release syndrome (CRS), which tocilizumab is FDA-approved to treat. Immunosuppressive therapies like tocilizumab may be an especially important treatment option, since corticosteroids can exacerbate lung injuries caused by COVID-19, according to a recent study published in The Lancet.
If caught in time, steroids may be enough to dampen the inflammatory reaction and prevent further deterioration, Chandrasekar said. "If conditions worsen further, tocilizumab as another, more potent anti-inflammatory drug may be useful."
Bassi was given both — tocilizumab and intravenous corticosteroids. Many physicians responded to his message asking if the two were synergistic. "Of course, methylprednisolone was stopped when [they started] tocilizumab and reintroduced again the day after," he said. But he has no way to be sure there was not a combined effect.
In Italy, current guidelines only allow tocilizumab after the high viral load phase of COVID-19 has passed. Patients must be without fever for 72 hours or have been showing symptoms for at least 7 days. China approved its own tocilizumab clinical trial in mid-February, but the trial is still recruiting. However, a preprint from ChinaXiv that followed 20 patients given tocilizumab in early February found that the drug could reduce fever, need for oxygen therapy, blood lymphocytes, C-reactive protein, and lung abnormalities on the CT scan.
The drug is not yet approved by the FDA for treating COVID-19. But Bassi's testimony on Consult came just days after the FDA green-lighted phase 3 trials of tocilizumab (Actemra, Genentech) for COVID-19 pneumonia treatment. Genentech, a subsidiary of Roche, will move forward with the double-blind, placebo-controlled trial evaluating intravenous tocilizumab combined with the standard of care in patients with COVID-19 pneumonia.
Bassi remains in the hospital on oxygen therapy, but is "getting better every day." He's no longer on Plaquenil or the retroviral. "This is a very dangerous illness," he wrote to Medscape, "It certainly requires admittance in special intensive critical care units, close follow up is essential, and — as usual — so is a lot of luck."
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