Adverse COVID‐19 outcomes in immune deficiencies: Inequality exists between subclasses

Abstract

Background Genetic deficiencies of immune system, referred to as inborn errors of immunity (IEI), serve as a valuable model to study human immune responses. In a multicenter prospective cohort, we evaluated the outcome of SARS‐CoV‐2 infection among IEI subjects and analyzed genetic and immune characteristics that determine adverse COVID‐19 outcomes. Methods We studied 34 IEI patients (19M/15F, 12 [min: 0.6‐max: 43] years) from six centers. We diagnosed COVID‐19 infection by finding a positive SARS‐CoV‐2 PCR test ( n = 25) and/or a lung tomography scoring (CORADS) ≥4 ( n = 9). We recorded clinical and laboratory findings prospectively, fitted survival curves, and calculated fatality rates for the entire group and each IEI subclass. Results Nineteen patients had combined immune deficiency (CID), six with predominantly antibody deficiency (PAD), six immune dysregulation (ID), two innate immune defects, and one in the autoinflammatory class. Overall, 23.5% of cases died, with disproportionate fatality rates among different IEI categories. PAD group had a relatively favorable outcome at any age, but CIDs and IDs were particularly vulnerable. At admission, presence of dyspnea was an independent risk for COVID‐related death (OR: 2.630, 95% CI; 1.198–5.776, p < .001). Concerning predictive roles of laboratory markers at admission, deceased subjects compared to survived had significantly higher CRP, procalcitonin, Troponin‐T, ferritin, and total‐lung‐score ( p = .020, p = .003, p = .014, p = .013, p = .020; respectively), and lower absolute lymphocyte count, albumin, and trough IgG ( p = .012, p = .022, p = .011; respectively). Conclusion Our data disclose a highly vulnerable IEI subgroup particularly disadvantaged for COVID‐19 despite their youth. Future studies should address this vulnerability and consider giving priority to these subjects in SARS‐Cov‐2 therapy trials.

COVID-19-related health outcomes in people with primary immunodeficiency: A systematic review

“…Of the 68 included articles, 47 were case reports or case series, and 21 were cohort or cross-sectional studies. The cohort and cross-sectional studies covered a variety of COVID-19-related health outcomes including mortality, hospitalization, and oxygen requirement [ [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] ] ( Table 1 ). Cohort and cross-sectional studies also had COVID-19-related health outcomes for people, and all of these studies had small numbers (n of 11 to 169) of people with PI and COVID-19.…”

“…A total of 459 people with PI and COVID-19 are described from 54 of the 68 studies [ 12 , 13 , 16 , [18] , [19] , [20] , [21] , 24 , 26 , 27 , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] ] (Table 2). These cases came from case reports as well as cohort studies with information available for individual patients.…”

“… CD19 + IgD + CD27- naïve B Cells as predictors of humoral response to COVID-19 mRNA vaccination in immunocompromised patients [ 15 ] Schulz E. Austria 25 After mRNA COVID-19 vaccination, patients with primary immunodeficiency had lower antibody production compared to healthy patients. The clinical course and outcome of SARS-COVID 19 in patients with inborn errors of immunity, does it relate to the type of immune defects [ 16 ] Sherkat R. Iran 14 Not all patients with inborn errors of immunity are predisposed to severe COVID-19. Out of the 14 patients, 3 (21.4%) were hospitalized and 1 (7.1%) was admitted to the ICU.…”

SARS-CoV-2 T Cell Response in Severe and Fatal COVID-19 in Primary Antibody Deficiency Patients Without Specific Humoral Immunity

“…Severity of COVID-19 is associated with increased age, male sex, and comorbidities, such as diabetes, arterial hypertension or pulmonary disease ( 1 ). In patients with inborn errors of immunity (IEI), morbidity and mortality of COVID-19 is increased ( 2 – 9 ). However, IEI form a very heterogeneous group of patients ( 10 ).…”

Outstanding Features of COVID-19 Overlapping Primary Immunodeficiency in Children

“…A total of 7 eligible studies ( 1 2 3 4 5 6 7 ) encompassing 166 children with COVID-19 overlapping PID were incorporated in this correspondence, through searches of PubMed, Web of Science and Medline from inception to January 2022 ( Table 1 ), after exclusion of studies with fewer than 10 PID children.…”