Vaccination prevents severe COVID-19 outcome in patients with neutralizing type 1 interferon autoantibodies

Abstract

A hallmark of patients with autoimmune polyendocrine syndrome type 1 (APS-1) is serological neutralizing autoantibodies against type 1 interferons (IFN-I). The presence of these antibodies has been associated with severe course of COVID-19. The aims of this study were to investigate SARS-CoV-2 vaccine tolerability and immune responses in a large cohort of patients with APS-1 (N = 33) and how these vaccinated patients coped with subsequent infections. We report that adult patients with APS-1 were able to mount adequate SARS-CoV-2 spike-specific antibody responses after vaccination and observed no signs of decreased tolerability. Compared with age- and gender-matched healthy controls, patients with APS-1 had considerably lower peak antibody responses resembling elderly persons, but antibody decline was more rapid in the elderly. We demonstrate that vaccination protected patients with APS-1 from severe illness when infected with SARS-CoV-2 virus, overriding the systemic danger of IFN-I autoantibodies observed in previous studies.

Keywords: Biological sciences; Health sciences; Immune response; Immunology.

Graphical abstract

Figure 1

APS-1 SARS-CoV-2 vaccine study (A) Vaccine and sampling design for patients with APS-1 and age- and gender-matched and elderly healthy control groups. For patients, it is not always the same individuals that are included in the «time after second dose » response groups. (B) SARS-CoV-2 vaccines used for patients with APS-1. Pfizer-BioNTech BNT162b2 mRNA vaccine (Pfizer), Oxford/AstraZeneca ChAdOx1-S vaccine (Astra Zeneca), Moderna mRNA-1273 vaccine (Moderna). (C) Number of vaccine doses for patients with APS-1 from Feb-2021 to Nov-2022. (D) Vaccine adverse events in patients with APS-1. Mild transient symptoms included low-grade fever, headache, and tiredness. A moderate symptom is here described as abnormal vaginal bleedings for several months after vaccination. (E) Patients with APS-1 (N = 32, black) and representative healthy controls (N = 2, red) spike IgG endpoint binding titers after SARS-CoV-2 vaccination. Threshold (dotted line) = 450. (F) IgG neutralization titers toward live human COVID-19/Norway/Bergen-01/2020 (Wuhan virus, GISAID accession ID EPI_ISL_541970) in patients with APS-1 (N = 29, black) after SARS-CoV-2 vaccination. Threshold (dotted red line) = 10. (E and F) Black arrow shows the first vaccine dose. Responses after vaccine doses 1, 2, and 3 are shown but time points for vaccine dose 2 and 3 vary and time points are therefore not shown in these figures.

Figure 2

COVID-19 vaccine response in patients with APS-1 (A) Antibody responses in patients with APS-1, age- and gender-matched controls, and an older adult cohort after 1 and 2 vaccine doses, respectively. Only samples taken before the third vaccination have been included. Statistical differences between the three groups have been calculated when the time point for controls and patients with APS-1 matches (One-way ANOVA). (B and C) Model-based estimated IgG binding spike-specific vaccine responses for patients with APS-1, control cohort 1 (age- and gender-matched controls), and the older adult cohort. The figure shows the expected/median (log) response for a “typical” patient/control (i.e., a subject with the value zero for both random effects). The bands indicate 95% confidence intervals, calculated using bootstrapping (1,000 replications). The decay over time shows a linear slope for patients with APS-1 and matched controls, but follows a non-exponential pattern for elderly persons. Time 0 corresponds to 14 days after the second vaccine dose. (B) Linear axis for antibody titer. (C) Log-transformed axis, with the threshold for positivity indicated.

Figure 3

COVID-19 clinical study in Norwegian patients with APS-1 (A) Patients with APS-1 reporting SARS-CoV-2 infection. (B) Confirmation test that was used to determine SARS-CoV-2 infection. (C) Time point for SARS-CoV-2 infection in relation to publicly available numbers of infected persons in the Norwegian population from Dec-2021 to Nov-2022 [31, 32]. (D) Number of SARS-CoV-2 vaccine doses before infection. (E) Time from last COVID vaccine dose to infection. (F) Number of symptoms after SARS-CoV-2 infection. (G) Nature of the COVID-19 symptoms in patients with APS-1 and a published control cohort [25]. Only symptoms that were reported in both studies and only for patients with APS-1 (∗) are shown. Note that we did not ask our patients regarding taste/smell disturbances, appetite, headache, and sneezing and the reference paper did not describe concentration issues nor had data on hospitalization. Extra use of medications when infected is indicated by ∗∗. (H) Time to full reconstitution after SARS-CoV-2 infection.