Seeking the Common Thread in Severe COVID-19 – Precision Vaccinations

(Precision Vaccinations)

Severe COVID-19 patients tend to have one thing in common: insufficient or defective proteins that help regulate the immune system, known as type I interferons (IFNs), stated researchers with Rockefeller University.

Jean-Laurent Casanova, M.D., Ph.D., previously demonstrated that at least 10% of severe cases could be chalked up to either a genetic condition that cripples IFN production or misguided antibodies that attack those crucial proteins.

Two new studies published in Science Immunology on August 19, 2021, explain how another 10% of severe cases are linked to IFN.

These autoantibodies are found even in uninfected individuals, which suggests that they are a cause, rather than an effect, of severe COVID-19.

We can neatly explain much of severe COVID-19 as a net defect in type I IFN, Casanova stated in a press release.

To an extent never seen for any other acute infectious disease, these four studies collectively provide a molecular and immunological explanation for about 20 percent of critical cases.

The new papers highlight additional IFN-related defects unique to severe and fatal COVID-19 cases.

In the first study, Casanova and colleagues found that 1 to 2% of men under the age of 60 who experience severe COVID-19 have deleterious mutations in TLR7, a gene within the X chromosome involved in the production of type I IFN.

In the second study, the scientists demonstrated that confused antibodies were attacking type I IFNs instead of the virus account for a more significant number of severe cases than previously thought 20% of people who died from COVID-19 had high levels of autoantibodies that specifically target and destroy IFNs.

While they are in only about 0.5% of people under age 60, that number rises to 4% at age 70 and up to 7% by age 85.

These findings, resulting from the collaboration of the COVID Human Genetic Effort, a global international consortium co-led by Casanova, have immediate clinical implications.

First, it is quick and easy to test for auto-Abs against type I IFNs in patients infected with SARS-CoV-2. Screening for these antibodies is even possible in the general population before infection.

Second, patients with auto-Abs against type I IFN should be vaccinated against COVID-19 as a priority.

Third, live attenuated vaccines, including YFV-17D and vaccines using the YFV-17D backbone against SARS-CoV-2, should not be given to patients with auto-Abs.

Fourth, these patients appeared healthy before SARS-CoV-2 infection, but they should also be carefully followed for other viral illnesses, as exemplified by adverse reactions to YFV-17D.

Fifth, in cases of SARS-CoV-2 infection in unvaccinated individuals with auto-Abs against type I IFNs, the patients should be hospitalized for prompt management.

Early treatment with monoclonal antibodies can be administered in patients without symptoms of severe COVID-19 pneumonia, and IFN- can be administered in the absence of both pneumonia and auto-Abs against IFN-. Rescue treatment by plasma exchange is another therapeutic option in patients who already have pneumonia.

Sixth, blood products, especially plasma, should be screened for anti-IFN auto-Abs, and any products containing such antibodies should be excluded from donation. And plasma from donors convalescing from COVID-19 should be tested for such auto-Abs.

Seventh, given the documented innocuity and potential efficacy of a single injection, early therapy with IFN- may be considered for the contacts of contagious subjects or during the first week after infection, even in the absence of, or before the documentation of auto-Abs against type I IFNs, in elderly patients, who have a higher risk of critical pneumonia and auto-Abs against IFN-2 and IFN-, but not IFN-.

Another possibility would be the administration of monoclonal antibodies that can neutralize SARS-CoV-2.

Finally, it will be essential to decipher the mechanism underlying the development of these auto-Abs, which may differ in patients over and under 65 years of age.

Overall, our findings show that auto-Abs neutralizing concentrations of type I IFN lower than previously reported but still higher than physiological concentrations typical in the elderly population.

Notes: The COVID Human Genetic Effort is an international consortium aiming to discover the human genetic and immunological bases of the various clinical forms of SARS-CoV-2 infection.

The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the US NIH, and others. These researchers did not disclose relevant industry conflicts of interest.

PrecisionVaccinations publishes fact-checked research-based vaccine news.

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Seeking the Common Thread in Severe COVID-19 - Precision Vaccinations