Response to COVID-19 boosters in seronegative multiple sclerosis patients
Response to COVID-19 boosters in seronegative multiple sclerosis patients

Response to COVID-19 boosters in seronegative multiple sclerosis patients

Pr. March 21, 2022, coronavirus 2019 (COVID-19) has cost nearly 6.1 million lives globally. Vaccines have played a significant role in reducing overall COVID-19-related morbidity and mortality; however, their impact on patients with primary and secondary immunocompromising conditions is still unknown. For example, many people with multiple sclerosis (MS) treated with anti-CD20 and Sphingosine-1-phosphate (S1P) modulators show a weakened immune response to the first two doses of COVID-19 immunization.

Examination: Response to COVID-19 booster vaccinations in seronegative individuals with MS. Image credit: Teeradej /

To date, the majority of COVID-19 research has concentrated on humoral immune responses. Nevertheless, the effect of booster vaccination in those with MS who do not respond well to the initial COVID-19 vaccine regimen is unknown.

In a recent study published on the preprint server medRxiv *, researchers report humoral T-cell response in MS patients after receiving a third dose of COVID-19 booster vaccine in those who were seronegative after their second vaccine.

Study methodology

A subgroup of people with MS who actively participated in a seroprevalence study were selected to participate. The selection criteria for the current study included a negative immunoglobulin G (IgG) anti-spike SARS-CoV-2 antibody response between four and eight weeks after receiving the second vaccine dose, as well as a willingness to give a second blood sample two to 12 weeks after the third COVID-19 vaccine.

Between November 2021 and January 2022, dried blood stain samples were taken. Medical notes from January 2022 to February 2022 were used to extract information on demographics, MS type and treatment as well as COVID-19 infection / vaccine dates.

Following a third COVID-19 immunization, humoral responses to the S1 subunit of SARS-CoV-2 peak protein was assessed for dried blood stains using the US Food and Drug Administration (FDA) -approved EuroImmun enzyme-linked immunosorbent assay (ELISA). The optical density (OD) of the participants’ samples was compared with the OD of the calibrator to calculate the results.

Survey results

A total of 79 people gave a dried blood stain sample, of which 38 also gave a full blood sample; two people gave exclusively whole blood. Fifty-eight women with a mean age of 45.8 years were prescribed ocrelizumab and 15 fingolimod, while nine others were given various immunosuppressants and two did not take any disease-modifying therapies (DMT). The mean time between the third vaccine and blood sampling was 5.9 weeks.

Anti-spike IgG results from dried bloodstains revealed that 26 of the 79 individuals seroconverted after receiving the third COVID-19 vaccine. More specifically, eight of the 52 people who received ocrelizumab and seven of the fifteen people who took fingolimod seroconverted.

Three people on ocrelizumab and three on fingolimod showed cross-border results. Those who had received the CHAdOx1 nCoV-19 vaccine for their first and second immunizations were more likely to seroconvert than those who received the BNT162b2 vaccine.

COVID-19 was reported in 14 of the 40 individuals tested, two of whom had previously tested positive for COVID-19. According to Fishers’ exact test, no association was reported between the presence or absence of laboratory evidence of previous COVID-19 infection and either T cell response or anti-spike seroconversion after the third COVID-19 vaccine. Relatively, previous SARS-CoV-2 infection appeared to be associated with a stronger T cell response.

There was no significant difference in quantitative IgG responses among individuals with and without evidence of previous infection after excluding two outliers with very low IgG responses. Following the third vaccination and blood sampling, six of the 81 individuals had polymerase chain reaction (PCR) -confirmed COVID-19.

When evaluated prior to the development of COVID-19, four of these six subjects showed either a T cell or antibody response to the SARS-CoV-2 peak protein. But all of these individuals recovered without requiring antiviral drugs or hospitalization.


MS patients who have not responded to the first two doses of COVID-19 vaccine appear to benefit from a third dose of the vaccine. Therefore, all patients with MS should be encouraged to adhere to vaccination regimens in order to obtain the best possible protection.

T-cell and antibody testing of MS patients on specific DMTs may allow for more tailored infection risk counseling. However, further longitudinal research is needed to determine the clinical correlations and the lifespan of these immunological responses.

*Important message

medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered essential, guide clinical practice / health-related behavior or be treated as established information.

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