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. Another
showed 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.
Bassi’s symptoms started on March 8: fever, cough, and muscle aches.
He suspects he was exposed at a hospital in Correggio, Italy where he
underwent retinal surgery 2 weeks before.
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.”
https://www.medscape.com/viewarticle/928152#vp_1
