COVID-19: Patients improve after immune-suppressant treatment
Anti-inflammatory medication is used to fight dangerous immune response
in coronavirus patients

Date:
July 15, 2020
Source:
Cedars-Sinai Medical Center
Summary:
Most patients hospitalized with COVID-19 (coronavirus) pneumonia
experienced improvement after receiving an FDA-approved drug
normally given for rheumatoid arthritis, according to an
observational study.

Outcomes for patients who received the drug, tocilizumab, included
reduced inflammation, oxygen requirements, blood pressure support
and risk of death, compared with published reports of illness and
death associated with severely ill COVID-19 patients.



FULL STORY ==========================================================================
Most patients hospitalized with COVID-19 (coronavirus)
pneumonia experienced improvement after receiving a Food and Drug Administration-approved drug normally given for rheumatoid arthritis,
according to an observational study at Cedars-Sinai. Outcomes for patients
who received the drug, tocilizumab, included reduced inflammation,
oxygen requirements, blood pressure support and risk of death, compared
with published reports of illness and death associated with severely
ill COVID-19 patients.


==========================================================================
The single-center, observational study of 27 patients was led by Stanley Jordan, MD, director of the Cedars-Sinai Nephrology and Transplant
Immunology Programs, and published June 23 in Clinical Infectious
Diseases.

While the patient outcomes were encouraging, investigators said they
were not sufficient to prove the drug was safe and effective for use in COVID-19 patients because they did not conduct a clinical trial with a
control group.

The team examined laboratory and clinical changes -- including oxygen
levels, the need for medication to increase blood pressure and patient
survival -- in 27 patients with COVID-19 pneumonia who received the immunosuppressive drug tocilizumab to slow an out of control immune
response. The researchers observed improved inflammatory markers and
patient survival, compared with reports of patients not treated with tocilizumab.

"Researchers have been studying tocilizumab for a decade, focusing
on its use for rheumatoid arthritis and cytokine storms with cancer,"
said Jordan, a Cedars-Sinai professor of Medicine. The medication was
approved in 2010 by the FDA as treatment for rheumatoid arthritis.

The Cedars-Sinai investigators found that interleukin 6 -- a protein
that fuels immune cell production and is the target for tocilizumab --
was the main cytokine elevated in COVID-19 patients.



========================================================================== "Since tocilizumab blocks interleukin 6, we reasoned that it made sense
to try it with COVID-19 pneumonia patients," Jordan explained.

Cytokines are molecules secreted by multiple cell types, including immune system cells that regulate the body's immune response. A cytokine storm is
a severe reaction in which immune cells flood and attack healthy organs
they are supposed to protect. In COVID-19 patients, the virus stimulates
immune cells that lead to collateral lung damage, which may cause blood
vessels to leak and blood to clot. The patient's blood pressure sinks,
and organs start to fail.

Early on in the COVID-19 pandemic, healthcare professionals discovered
that cytokine storms were causing rapid deterioration in some
patients. The key to patient survival, investigators are learning,
is to keep that storm from gathering strength.

Most of the patients who received tocilizumab were on ventilators to
support breathing. They each received one dose of tocilizumab, which
helps block the signaling of the cytokine, interleukin 6 -- the only
cytokine detected in damaging amounts in all of the study patients.

"The more interleukin 6 present in the body, the worse the patient
outcome," Jordan said.



========================================================================== Post-treatment results showed that 23 patients experienced significant
drops in body temperature and C-reactive protein (CRP) levels. CRP
levels increase when infection is present in the body. Four patients
did not have rapid declines in CRP levels, and three of them had poorer outcomes. Adverse events were minimal, but two deaths unrelated to
tocilizumab occurred, Jordan said.

"Our observational study suggests the medication may help reduce
inflammation, oxygen requirements, blood pressure support and the risk
of death," Jordan said.

Jordan's current research builds on his earlier work with
tocilizumab. That research focused on the drug's potential for blocking
the harmful effects of interleukin 6 on organ transplantation, including rejection of a donor organ.

The study found that tocilizumab helps regulate the immune response
and prevents organ rejection. Jordan and his colleagues currently are
carrying out a randomized, placebo-controlled trial of the investigational medication clazakizumab, another interleukin 6 blocker.

Based on his past and current research, Jordan is encouraged about
potential benefits of tocilizumab for patients with COVID-19 pneumonia.

"Based on our preliminary results, I am hopeful that this class of drugs
may help patients with COVID-19 pneumonia improve," Jordan said. "But
we won't know the outcome until we complete a randomized controlled
clinical trial." Disclosure: Stanley Jordan, MD, and Edmund Huang, MD,
have received research grant funding from Vitaeris. Jordan has patents
on anti-IL-6 for treatment of allograft rejection and desensitization, consulting contracts with Vitaeris for development of anti-IL-6 in kidney transplant rejection and grants evaluating anti-IL-6 (clazakizumab)
for treatment of COVID-19 pneumonia, outside the submitted work.

Read about COVID-19 terminology on the Cedars-Sinai
blog: "Understanding COVID- 19 Vocabulary" (www.cedars-sinai.org/blog/covid-19-vocabulary.html).


========================================================================== Story Source: Materials provided by Cedars-Sinai_Medical_Center. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Edmund Huang, Shili Ge, Mieko Toyoda, Sanjeev Kumar, Peter Chen,
Ashley
Vo, Noriko Ammerman, Rita Shane, Catherine Le, Benjamin Bluen,
Jillian Oft, Hayden Lowenstein, Rachel Zabner, Gregory Marks,
Cyril Gaultier, Ethan A Smith, Hai P Tran, Phillip Zakowski,
Stanley C Jordan.

Compassionate Use of Tocilizumab for Treatment of SARS-CoV-2
Pneumonia.

Clinical Infectious Diseases, 2020; DOI: 10.1093/cid/ciaa812 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200715111435.htm

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