Guest Post Dr Kister reports on the advantages of COVID infection

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At this point in the pandemic (Summer, 2022) most people in countries such as US and the UK, have had COVID-19 infection at least once and were also vaccinated against COVID-19. Combination of prior infection and vaccination is referred to as ‘hybrid immunity’. Several large-scale population studies have shown that hybrid immunity is superior to infection or vaccination alone in protecting people against reinfection and hospitalization. This is likely due to the fact that antibody and T-cell responses to SARS CoV-2 antigens in people who had both infection and vaccination are stronger and broader (i.e. more diverse) than in people who had either infection or vaccination alone.  

An interesting question, which has not received much attention to date, is whether hybrid immunity to COVID-19 is also stronger than vaccine-only immunity in MS patients who receive disease modifying-therapies, such as B-cell depleting agents (e.g. ocrelizumab) and S1P receptor modulators (e.g. fingolimod, siponimod) that are known to suppress immune responses to both infection and vaccination. To answer this question, we recruited 370 MS patients from NYU Comprehensive Care MS Center in New York and assessed their immune responses to SARS CoV-2 with two antibody assays and two assays of cellular (T-cell) immunity. All patients were fully vaccinated, nearly all with mRNA Pfizer and Moderna vaccines, and 22% of patients have had laboratory-document prior COVID-19 infection.  As expected, patients on ocrelizumab and S1P class agents had markedly depressed antibody responses, and patients on S1P, depressed cellular responses as well, as compared to patients on no therapy. Importantly, we found that patients with prior infection and vaccination consistently had higher antibody and (to a lesser extent) T-cell responses as compared to patients with vaccination only. These differences were evident even in patients on ocrelizumab and S1P class agents.

We also carried out additional analyses comparing immune responses by vaccine (Pfizer v Moderna) and by race/ethnicity (as our patient population was mostly non-white). We have shown that patients who received Moderna vaccine tended to have somewhat higher antibody and cellular responses than patients on Pfizer. Race/ethnicity, on the other hand, did not make any difference for immune responses to SARS CoV-2 in our study.

Finally, we put our data in a statistical model (multivariate analyses) to identify predictors of immune responses. We found that prior infection was a very significant predictor of higher post-vaccine antibody responses in both antibody assays: 8-fold higher in one assay and 3-fold higher on the other assay among patients with prior infection compared to patients with vaccination only. Prior infection also predicted higher cellular responses, though the increases were not as impressive as for antibodies, 2.5-fold on IFNγ assay and 1.6-fold higher on IL-2 assay. Vaccine type and DMT class also predicted both antibody and cellular responses.

In summary, our study demonstrated that the immunologic benefits of hybrid immunity extend to MS patients, including those on B-cell depleting and S1P therapies. This suggests that it may be possible to improve humoral and cellular immune response defenses following repeated exposure to virus-specific antigens even in patients whose immune system has been partially compromised by MS medications.

More information about our study is available at https://www.medrxiv.org/content/10.1101/2022.06.28.22276989v1.full-text.

Hybrid and vaccine-induced immunity against SARS-CoV-2 in MS patients on different disease-modifying therapies

Ilya Kister, Ryan Curtin, Jinglan Pei, Katherine Perdomo, Tamar E. Bacon, Iryna Voloshyna, Joseph Kim, Ethan Tardio, Yogambigai Velmurugu, Samantha Nyovanie, Andrea Valeria Calderon, Fatoumatta Dibba, Stanzin Idga, Marie I. Samanovic, Pranil Raut, Catarina Raposo, Jessica Priest, Mark Cabatingan, Ryan C. Winger, Mark J. Mulligan, Yury Patskovsky, Gregg J. Silverman, Michelle Krogsgaard

doi: https://doi.org/10.1101/2022.06.28.22276989

Objective To compare ‘hybrid immunity’ (prior COVID-19 infection plus vaccination) and post-vaccination immunity to SARS CoV-2 in MS patients on different disease-modifying therapies (DMTs) and to assess the impact of vaccine product and race/ethnicity on post-vaccination immune responses.

Methods Consecutive MS patients from NYU MS Care Center (New York, NY), aged 18-60, who completed COVID-19 vaccination series ≥6 weeks previously were evaluated for SARS CoV-2-specific antibody responses with electro-chemiluminescence and multiepitope bead-based immunoassays and, in a subset, live virus immunofluorescence-based microneutralization assay. SARS CoV-2-specific cellular responses were assessed with cellular stimulation TruCulture IFNγ and IL-2 assay and, in a subset, with IFNγ and IL-2 ELISpot assays. Multivariate analyses examined associations between immunologic responses and prior COVID-19 infection while controlling for age, sex, DMT at vaccination, time-to-vaccine, and vaccine product.

Results Between 6/01/2021-11/11/2021, 370 MS patients were recruited (mean age 40.6 years; 76% female; 53% non-White; 22% with prior infection; common DMT classes: ocrelizumab 40%; natalizumab 15%, sphingosine-1-phosphate receptor modulators 13%; and no DMT 8%). Vaccine-to-collection time was 18.7 (±7.7) weeks and 95% of patients received mRNA vaccines. In multivariate analyses, patients with laboratory-confirmed prior COVID-19 infection had significantly increased antibody and cellular post-vaccination responses compared to those without prior infection. Vaccine product and DMT class were independent predictors of antibody and cellular responses, while race/ethnicity was not.

Interpretation Prior COVID-19 infection is associated with enhanced antibody and cellular post-vaccine responses independent of DMT class and vaccine type. There were no differences in immune responses across race/ethnic groups.

COI: Nothing relevant

Disclaimer> These are the views of the author

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MouseDoctor

4 comments

  • I’m sure I haven’t yet had Covid. I have had 3 Pfizer and one Moderna vaccination/s. I have RRMS and have never been on any DMTs. I do not take any other meds, no over the counter ones, or supplements. Did the Kister study assay any participants that fit that profile and if so, what did they find?

  • Rituximab, quadruple vaccinated and currently covid day 12. Has hit me hard. On the plus side lateral flow negative and not under attack by Russians. Grateful for prompt Paxlovid and any additional antibodies produced!

    • BA.4/BA.5 are largely immune escape variants meaning that the vaccines are unlikely to stop you getting COVID…however once infected the immune response will kick in.

      • https://www.nature.com/articles/s41591-022-01705-6

        Although not done in MS patients this heterozygous vaccine strategy of sinovac (attenuated virus) followed by Moderna booster showed elevated ab levels compared to other groups. Unfortunately the sub variant BA.5 is as mentioned is not neutralized by this strategy. The RNA sequence will have to tweaked in the RNA based vaccines or the attenuated virus will have to include the circulating sub variant analogous to seasonal influenza a vaccines.

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