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      A single-center experience of COVID-19 infection in patients with primary immunodeficiency

      brief-report
      Author(s): , BMed, MD a , ∗ , , BMedSci, MBBS(Hons), DPhil, FRACP, FRCPA b , c , , MBBS a , , MBBS, BSc(Hons), FRACP a , d , , MBBS(Hons), BMedSc(Hons), FRACP a , e , , MNSc a , f , , BMedSc(Hons), MBBS (Hons), MD, FRACP a , d , , MBBS, FRACP, MPH, PhD g , h , i , , MBBS, FRACP, MD, FAAHMS, FECMM g , h , i , , Bsc(Hons), Bsc, PhD a , f , j , , MBBS, BA, BSc, FRACP, FRCPA, PhD a , f , j , , MBBS, BMedSci, FRACP, MPH a , d , f
      Publication date (Electronic):
      Journal: The Journal of Allergy and Clinical Immunology: Global
      Publisher: Elsevier
      Keywords: Primary immunodeficiency, COVID-19 infection

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          Abstract

          Background

          Reported outcomes in patients with primary immunodeficiency (PID) infected by coronavirus disease 2019 (COVID-19) have been variable owing to a combination of viral strain heterogeneity, differences in patient populations and health systems, and local availability of vaccination and specific COVID-19 therapies. There are few reports on the experience of Australian patients with PID during the pandemic.

          Objectives

          In this retrospective study, we describe the baseline characteristics and short-term outcomes of patients with PID who were infected by COVID-19 and known to the Royal Melbourne Hospital, a major tertiary center in Victoria, Australia.

          Methods

          Between April 2021 and April 2022, a total of 31 of 138 patients with PID were affected by COVID-19. More than half of them had 3 vaccine doses at the time of infection (which at the time was considered being fully vaccinated) and received COVID-19–targeted treatment.

          Results

          All of the infected patients had ambulatory disease, with no cases of morbidity or mortality. In line with the current literature, the PID subtypes described did not appear to independently predict worse outcomes.

          Conclusions

          Some protective factors include this cohort's relatively younger average age and its high uptake of vaccination and COVID-19 therapies.

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          Coronavirus disease 2019 in patients with inborn errors of immunity: An international study

          Isabelle Meyts, Giorgia Bucciol, Isabella Quinti … (2020)
          Background There is uncertainty about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in individuals with rare inborn errors of immunity (IEI), a population at risk of developing severe coronavirus disease 2019. This is relevant not only for these patients but also for the general population, because studies of IEIs can unveil key requirements for host defense. Objective We sought to describe the presentation, manifestations, and outcome of SARS-CoV-2 infection in IEI to inform physicians and enhance understanding of host defense against SARS-CoV-2. Methods An invitation to participate in a retrospective study was distributed globally to scientific, medical, and patient societies involved in the care and advocacy for patients with IEI. Results We gathered information on 94 patients with IEI with SARS-CoV-2 infection. Their median age was 25 to 34 years. Fifty-three patients (56%) suffered from primary antibody deficiency, 9 (9.6%) had immune dysregulation syndrome, 6 (6.4%) a phagocyte defect, 7 (7.4%) an autoinflammatory disorder, 14 (15%) a combined immunodeficiency, 3 (3%) an innate immune defect, and 2 (2%) bone marrow failure. Ten were asymptomatic, 25 were treated as outpatients, 28 required admission without intensive care or ventilation, 13 required noninvasive ventilation or oxygen administration, 18 were admitted to intensive care units, 12 required invasive ventilation, and 3 required extracorporeal membrane oxygenation. Nine patients (7 adults and 2 children) died. Conclusions This study demonstrates that (1) more than 30% of patients with IEI had mild coronavirus disease 2019 (COVID-19) and (2) risk factors predisposing to severe disease/mortality in the general population also seemed to affect patients with IEI, including more younger patients. Further studies will identify pathways that are associated with increased risk of severe disease and are nonredundant or redundant for protection against SARS-CoV-2.
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            Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1

            Paul Bastard, Elizaveta M Orlova, Leila S Sozaeva … (2021)
            Patients with autoimmune polyendocrine syndrome type-1 (APS-1) have circulating auto-Abs neutralizing most type I interferons. These auto-Abs can underlie life-threatening COVID-19 pneumonia in the general population. The authors report 22 APS-1 patients infected with SARS-CoV-2, including 15 (68%) who developed life-threatening disease. Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti–IFN-β and another anti–IFN-ε, but none had anti–IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.
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              Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial

              Peter Bergman, Ola Blennow, Lotta Hansson … (2021)
              Background Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls. Methods 539 study subjects (449 patients and 90 controls) were included. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/CAR T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection. Findings Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72.2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43.4%) and CLL (63.3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively. Interpretation The results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. Rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups to improve immunity. Funding Knut and Alice Wallenberg Foundation, the Swedish Research Council, Nordstjernan AB, Region Stockholm, Karolinska Institutet, and organizations for PID/CLL-patients in Sweden.
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                Author and article information

                Contributors
                Jessie J. Zhou
                Journal
                Journal ID (nlm-ta): J Allergy Clin Immunol Glob
                Journal ID (iso-abbrev): J Allergy Clin Immunol Glob
                Title: The Journal of Allergy and Clinical Immunology: Global
                Publisher: Elsevier
                ISSN (Electronic): 2772-8293
                Publication date PMC-release: 07 March 2024
                Publication date Collection: May 2024
                Publication date (Electronic): 07 March 2024
                Volume: 3
                Issue: 2
                Electronic Location Identifier: 100241
                Affiliations
                [a ]Department of Clinical Immunology and Allergy, Melbourne, Australia
                [c ]Department of Pathology, Royal Melbourne Hospital, Melbourne, Australia
                [g ]Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne, Australia
                [b ]Infectious Diseases and Immune Defence Division, Walter and Eliza Hall Institute, Melbourne, Australia
                [f ]Immunology Division, Walter and Eliza Hall Institute, Melbourne, Australia
                [h ]Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia
                [d ]Department of Medicine, University of Melbourne, Melbourne, Australia
                [j ]Department of Medical Biology, University of Melbourne, Melbourne, Australia
                [i ]National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Australia
                [e ]Department of Infectious Diseases and Immunology, Austin Health, Melbourne, Australia
                Author notes
                [∗ ]Corresponding author: Jessie Zhou, BMed, MD, Department of Clinical Immunology and Allergy, Royal Melbourne Hospital, Melbourne, Australia. jessie.zhou@ 123456mh.org.au
                Article
                Publisher Item ID: S2772-8293(24)00037-7 Publisher ID: 100241
                DOI: 10.1016/j.jacig.2024.100241
                PMC ID: 10997894
                PubMed ID: 38585448
                SO-VID: 2d964b50-2c0e-479a-a832-83b2fa7811e1
                Copyright © © 2024 The Authors
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 13 July 2023
                Date revision received : 22 October 2023
                Date accepted : 8 January 2024
                Categories
                Subject: Brief Report

                Keywords: primary immunodeficiency,covid-19 infection
                Data availability:
                Keywords: primary immunodeficiency, covid-19 infection

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