SARS-CoV-2 infection risk is higher in vaccinated patients with inflammatory autoimmune diseases or liver transplantation treated with mycophenolate due to an impaired antiviral immune response: results of the extended follow up of the RIVALSA prospective cohort

Abstract

Background: A relevant proportion of immunocompromised patients did not reach a detectable seroconversion after a full primary vaccination cycle against SARS-CoV-2. The effect of different immunosuppressants and the potential risks for SARS-CoV-2 infection in these subjects is largely unknown.

Methods: Patients from the Rivalsa prospective, observational cohort study with planned anti SARS-CoV-2 third dose mRNA vaccination between October and December 2021 were asked to participate to this follow-up study. Patients were asked about eventual confirmed positivity to SARS-CoV-2 infection within 6 months from the third dose and to undergo a blood draw to evaluate seroconversion status after the additional vaccine shot.

Results: 19 out of 114 patients taking part in the survey developed a confirmed SARS-CoV-2 infection; we identified mycophenolate treatment as an independent predictor of an increased risk of infection even after the third vaccine dose (OR: 5.20, 95% CI: 1.70-20.00, p=0.0053). This result is in agreement with the in vitro evidence that MMF impairs both B and T lymphocytes driven immune responses (reduction both in memory B cells producing anti-spike antibodies and in proliferating CD4+ and CD8+ T cells).

Conclusions: Immunocompromised patients need an additional vaccine administration to reach a detectable seroconversion, thus fostering a more personalized approach to their clinical management. Moreover, patients undergoing mycophenolate treatment show a specific increased infection risk, with respect to other immunosuppressants thus supporting a closer monitoring of their health status.

Keywords: SARS-CoV-2; anti-COVID-19 mRNA vaccination; inflammatory autoimmune diseases; liver transplantation; mycophenolate.

Figure 1

Study design. Flow chart of patient enrollment. *Ten patients have overlapping diseases.

Figure 2

Spike-specific (A) and total (B) IgG memory B-cell response in immunocompetent and immunocompromised vaccinated subjects. Grey circles represent samples treated with MMF, while white circles represent untreated samples. The horizontal dotted line indicates the cutoff value for a positive response. **p<0.01, ***p<0.001, ns, not significant.

Figure 3

Spike-specific IFN-γ T cell response in immunocompetent and immunocompromised vaccinated subjects. Grey circles represent samples treated with MMF, while white circles represent untreated samples. The horizontal dotted line indicates the cutoff value for a positive response. ns, non-significant.

Figure 4

Spike-specific CD4⁺ (A) and CD8⁺ (B) T cell proliferative response in immunocompetent and immunocompromised vaccinated subjects. Grey circles represent MMF treated samples, while white circles represent untreated samples. The horizontal dotted line indicates the cutoff value for a positive response. **p<0.01, ***p<0.001, ns, non-significant.

Figure 5

Perforin expression by total CD4+ (A) and CD8+ (B) T cells, and by spike-specific CD4⁺ (C) and CD8⁺ (D) proliferating T cells in immunocompetent and immunocompromised vaccinated subjects. Grey circles represent MMF treated samples, while white circles represent untreated samples. Perforin expression was not determined in MMF treated proliferating T cells, since proliferating T cells were not detectable after MMF treatment. The horizontal dotted line indicates the cutoff value for a positive response. ns, non-significant.