Drugs used to treat autoimmune rheumatic disease may weaken the immune response induced by COVID-19

A study published in Nature Medicine evaluated individuals before and after taking CoronaVac. Based on the results, researchers at the University of São Paulo’s Medical School are testing novel strategies such as suspending treatment one or two weeks before vaccination.

By Elton Alisson | Agência FAPESP – Researchers at the University of São Paulo’s Medical School (FM-USP) in Brazil have found that some types of medication used to treat patients with autoimmune rheumatic diseases such as rheumatoid arthritis can weaken the immune response to COVID-19 induced by vaccines.

The study is reported in an article in the journal Nature Medicine, and was supported by FAPESP and B3 S.A., Brazil’s stock exchange. 

The researchers set out appraise the safety and efficacy of CoronaVac in patients with nine types of autoimmune rheumatic disease. CoronaVac is produced in Brazil by Butantan Institute. Further tests are required to find out whether the same effect occurs in patients inoculated with other vaccines.

Based on the results, the researchers are working on novel vaccination strategies for these patients, including suspension of treatment one or two weeks before CoronaVac is administered and resumption of treatment after vaccination with the aim of improving the immune response.

“We observed that some drugs, such as glucocorticoids, as well as immunosuppressants such as methotrexate and mycophenolate mofetyl, and some biologics weaken the immune response in these patients,” Eloísa Bonfá, Clinical Director of FM-USP’s hospital and principal investigator for the study, told Agência FAPESP. “Based on this observation, we began studying different vaccination strategies, including the suspension of medication with mofetyl one week before administering the vaccine and with methotrexate two weeks before.”

According to Bonfá, the risk of a weakened immune response to vaccines is high in immunosuppressed patients, who include cancer patients, transplanted patients and patients with HIV, as well as those with autoimmune diseases. In addition, rheumatic autoimmune disease can increase the probability of thrombosis. 

To find out whether COVID-19 vaccines were safe and efficacious for these people, the researchers monitored 910 adult patients enrolled at the hospital’s rheumatology laboratory for 40 days after they were given the second dose of CoronaVac.

“The patients are followed up at a tertiary center, with severe rheumatoid arthritis and psoriatic arthritis, as well as axial spondyloarthritis and other systemic autoimmune rheumatic diseases, such as lupus, vasculitis, Sjögren’s syndrome, systemic sclerosis, idiopathic inflammatory myopathy and anti-phospholipid syndrome,” Bonfá explained.

Blood samples taken to detect antibodies against SARS-CoV-2 were analyzed before vaccination, and 28 days and six weeks after administration of both doses of CoronaVac. The results were compared with those of a control group comprising 182 people who did not have autoimmune disease and were not taking immunosuppressants.

The results of the analyses showed that vaccination induced seroconversion to IgG antibodies in 70.4% of the patients with autoimmune rheumatic disease, compared to 95.5% of the control group.

“We saw a reduction of the immune response in these patients compared to the control group, but we considered the reduction moderate and in line with the standards set by the WHO [World Health Organization],” Bonfá said. “A serological response at 70.4% is very important for immunosuppressed patients or patients who take medications that reduce their immunity.”

Ten days after taking the first dose, when the response to the vaccine was not complete, 33 participants in the study had COVID-19. After 40 days, when the second dose had been administered and the response was complete, only six patients had the disease. Four required hospitalization. There were no deaths.

The reduction in cases of infection among the participants, from 33 to only six, contrasted with the trajectory of new cases in São Paulo, which rose 45% in the period. “The sharp fall in the number of cases ten days after the second dose shows that the vaccine is apparently efficacious even in this population of immunosuppressed patients, who are more likely to be infected. This reinforces the recommendation that these patients should be vaccinated,” Bonfá said.

Priority group

Besides the high risk of contracting infectious disease and falling severely ill, immunosuppressed patients are also more likely to suffer from comorbidities such as high blood pressure and obesity, which are risk factors for COVID-19. They should therefore be prioritized at the start of a coronavirus vaccination campaign.

In addition, it is more difficult for immunosuppressed patients to clear the virus from their organism than for healthy people, and this favors the emergence of variants with mutations. “Prioritizing this group for vaccination purposes is important not just for them but also for the entire population, as a strategy to reduce the emergence of viral variants,” Bonfá said.

The article “Immunogenicity and safety of the CoronaVac inactivated vaccine in patients with autoimmune rheumatic diseases: A phase 4 trial” by Ana C. Medeiros-Ribeiro, Nadia E. Aikawa, Carla G. S. Saad, Emily F. N. Yuki, Tatiana Pedrosa, Solange R. G. Fusco, Priscila T. Rojo, Rosa M. R. Pereira, Samuel K. Shinjo, Danieli C. O. Andrade, Percival D. Sampaio-Barros, Carolina T. Ribeiro, Giordano B. H. Deveza, Victor A. O. Martins, Clovis A. Silva, Marta H. Lopes, Alberto J. S. Duarte, Leila Antonangelo, Ester C. Sabino, Esper G. Kallas, Sandra G. Pasoto and Eloisa Bonfa is at: www.nature.com/articles/s41591-021-01469-5.