CoronaVac COVID-19 Vaccine Less Effective in Scleroderma in Brazil
People with systemic sclerosis (SSc) in Brazil had a weaker immune response to the CoronaVac COVID-19 vaccine than did healthy individuals, a study discovered.
The findings also showed that treatment with the immunosuppressant therapy CellCept (mycophenolate mofetil) — an oral medication that improves lung function in SSc patients — impaired the vaccine-generated immune response.
“This is the first study to specifically evaluate the deleterious effect of [CellCept] monotherapy in vaccine-induced antibody response in SSc patients,” the researchers wrote.
According to the team, the results “[reinforce] the need for additional strategies to up-modulate vaccine response in this subgroup of patients.”
The study, “SARS-CoV-2 vaccine in patients with systemic sclerosis: impact of disease subtype and therapy,” was published in the journal Rheumatology.
Several vaccines have been developed to prevent infection by SARS-CoV-2, the virus that causes COVID-19. Initial clinical trials supporting the use of these vaccines enrolled only healthy individuals.
But SARS-CoV-2 infection is of great concern for people with SSc, also known as scleroderma, because the lungs are the primary target for the virus. SSc is characterized by the buildup of scar tissue in the skin and several organs — including the lungs.
Early this year, Brazil began a large-scale vaccination of its adult population using Sinovac-CoronaVac — a vaccine containing an inactivated SARS-CoV-2 virus, designed to elicit an immune response without causing COVID-19.
In this study, the investigators assessed a subgroup of participants in a Phase 4 trial (NCT04754698), carried out at the University of Sao Paulo, in Brazil, to evaluate the safety and immune response — called immunogenicity — of the Sinovac-CoronaVac vaccine in people with SSc.
“Our aim was to specifically analyse the immunogenicity, safety and possible factors influencing CoronaVac response in SSc patients, focusing on disease subtype and drug treatment,” the team wrote.
Study participants, who were primarily female (94.1%), included 51 SSc patients and 153 age- and sex-matched healthy individuals, who served as a control group. More than half of the scleroderma patients (58.8%) were Caucasian. The median disease duration was 10 years, and 16 patients (31.4%) had the milder limited SSc. The other 35 (68.6%) had the more severe diffuse SSc.
Among the patient group, 80.4% had difficulties with their esophagus, 74.5% had lung disease, and 60.8% had anti-Scl-70 antibodies, a marker for the diffuse type of SSc. Most patients (72.5%) were treated with immunosuppressants, mainly CellCept, the treatment for 52.9%.
Participants visited the clinic on three occasions, defined as day 0 for the first vaccine dose, day 28 for the second vaccine dose, and day 69. Clinical staff assessed immunogenicity at all three visits by measuring the bloodstream levels of immunoglobulin G (IgG) antibodies that target SARS-CoV-2 as well as antibodies that actively neutralized the virus.
Of note, not all antibodies generated against the SARS-CoV-2 virus after vaccination will neutralize, or block viral infection.
Antibody levels, or titers, were reported in mean arbitrary units per milliliter (UA/mL), and seroconversion — the generation of anti-SARS-CoV-2 antibodies — was considered positive if UA/mL was 15.0 or higher.
Among the participants, 12 patients and 32 healthy controls were excluded from the final analysis due to the presence of anti-SARS-CoV-2 antibodies before vaccination or a diagnosis of COVID-19 after the first dose.
After full vaccination, 64.1% of patients were seropositive for anti-SARS-CoV-2 antibodies compared with 94.2% of controls. The mean overall antibody titers were significantly lower in patients than controls (26.4 vs. 66.9 UA/mL), as were the number of participants who were positive for neutralizing antibodies (53.8% vs. 76.9%).
In contrast, the activity of neutralizing antibodies among responders was significantly higher in the patient group than in the healthy controls (80.6% vs. 62.5%).
After the first dose, the seroconversion rates were low and comparable in both groups (35.9% vs. 36.4%), as were the overall antibodies titers (7.3 vs. 10.9 UA/mL). Similar results were seen for the levels of neutralizing antibodies (38.5 vs. 33.1 UA/mL), whereas neutralizing activity was moderate and comparable in both groups (46.5% vs. 44.4%).
Following an analysis of demographics, disease subtype and characteristics, and current treatments, the use of CellCept was the only variable associated with a significant reduction in the seroconversion rates — 20.0% in CellCept users versus 85.7% in those not treated with this medicine. Similar results were observed in the number of patients with neutralizing antibodies (14.3% vs. 77.8%).
Because only three (7.7%) were being treated with combined therapy with disease-modifying anti-rheumatic drugs (DMARDs), the team compared SSc patients treated with CellCept alone to no treatment or other therapies. After full vaccination, patients treated with CellCept had lower immunogenicity in both seroconversion rates (31.3% vs. 90%) and neutralizing antibody positivity (18.8% vs. 85%).
A statistical calculation showed that current CellCept use was significantly associated with impaired seroconversion and the production of neutralizing antibodies.
“[CellCept] dose was uniformly high, and we could not establish a threshold of interference on vaccine immunogenicity,” the researchers wrote.
All participants diagnosed with COVID-19 recovered completely — specifically, one patient after the first dose and two after the second dose.
The Sinovac-CoronaVac vaccine was well-tolerated by all participants, with only mild adverse events reported, including pain at the injection site in more than 10% of patients and controls. Body-wide reactions occurred in 40% of participants, with a sore throat the only symptom that was more frequent in patients than controls after the first dose (13.7% vs. 5.2%).
“In conclusion, SSc had an excellent safety profile and a suboptimal response to SARS-CoV-2 vaccine,” the researchers wrote. “We further identified that [CellCept], and not disease subtype, was [associated] with a major deleterious impact on vaccine response.”
“Novel strategies to improve the vaccine-induced antibody response, therefore, represent a relevant unmet need for the most vulnerable subgroups,” they added.