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

Karakoc Aydiner, Elif; Bilgic Eltan, Sevgi; Babayeva, Royale; Aydiner, Omer; Kepenekli, Eda; Kolukisa, Burcu; Sefer, Asena Pinar; Yalcin Gungoren, Ezgi; Karabiber, Esra; Yucel, Esra Ozek; Ozdemir, Oner; Kiykim, Ayca; Artac, Hasibe; Yakici, Nalan; Yalcin, Koray; Cokugras, Haluk; Celkan, Tulin Tiraje; Orhan, Fazil; Yesilipek, Mehmet Akif; Baris, Safa; Ozen, Ahmet

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.