COVID-19 Vaccine Researchers Mindful of Patients Producing Antibodies that Make the Disease Worse

COVID-19 Vaccine Researchers Mindful of Patients Producing Antibodies that Make the Disease Worse

More than 10% of people with severe COVID-19 produce a type of antibodies that, instead of protecting them from the virus, worsen the infection by boycotting their immune system. It is the result of an international study that may explain why some people go through COVID-19 without realizing it or with very mild symptoms, while others develop a serious or fatal disease.

Until now, three major risk factors were known: being a man, being elderly and having previous illnesses. The work adds a fourth: birth defects that can prevent the immune system from fighting and eliminating the virus. This type of problem seems to be much more common in men than in women.

“This discovery will change the treatment of some patients,” explains Carlos Rodríguez-Gallego, an immunologist at Gran Canaria University Hospital Doctor Negrín and co-author of the study, published on Thursday in the journal Science. “Our team is already studying how to establish clinical tests to identify patients who produce these types of autoantibodies and perhaps treat them with other types of antibodies to neutralize the problem,” he says.

The study looked at the blood of nearly 1,000 patients with very severe coronavirus pneumonia and compared it with that of 600 asymptomatic or mildly infected people and a third group of 1,200 healthy volunteers. Antibodies that neutralize interferon type 1, a molecule essential to trigger a general alarm when a virus enters our body, were found in 10.2% of critically ill patients.

Minutes after SARS-CoV-2 infects a cell, our immune system’s first line of defense comes into play. Upon detecting the presence of the virus, dendritic cells begin to produce a protein that sends an alarm signal to the entire body: interferon 1. These interferons can bind to cells in almost every tissue in the body and modify their metabolism so that activate their antiviral defense mechanisms.

The work noted that a percentage of patients have genetic defects that cause them to produce antibodies that, instead of finding and neutralizing the virus, were made to block interferon 1. The study found several types of antibodies against interferons in that 10.2 % of patients and points out that they are the cause of these patients getting worse until they see their life in danger.

“Interferon is called that because it interferes with the multiplication of the virus and stops it”, explains Javier Martínez-Picado, ICREA researcher at IrsiCaixa and co-author of the study. “The autoantibodies that these patients produce sequester interferon and cancel it,” he says.

In another work also published in Science, the same international consortium shows that certain genetic alterations that affect interferon production would explain 3.5% of severe cases of COVID-19. Both works help explain why 14% of infected people end up developing a serious illness that can kill them.

The immune system is a highly complex set of molecules with specialized functions: antibodies that neutralize viral particles, lymphocytes that identify infected cells and kill them, B cells capable of producing tens of thousands of antibodies, natural killer cells … Among them all there are three major types of interferons and, within type one, there are 17 different classes. “If we find patients that produce antibodies against alpha interferon, which is a type of interferon 1, we could treat them with interferon beta, which is already used as a drug in other contexts,” explains the immunologist. The second option is to make a plasmapheresis: a filtering of the patient’s blood to eliminate the malignant antibodies and also other inflammatory molecules that may be aggravating the disease.

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