PURPOSE: There is still scarce data on SARS-CoV-2 infection in patients with Inborn Errors of Immunity (IEI) and many unresolved questions. We aimed to describe the clinical outcome of SARS-CoV-2 infection in Brazilian IEI patients and identify factors influencing the infection.
METHODS: We did a cross-sectional, multicenter study that included patients of any age affected by IEI and SARS-CoV-2 infection. The variables studied were sex, age, type of IEI, comorbidities (number and type), treatment in use for IEI, clinical manifestations and severity of SARS-CoV-2 infection.
RESULTS: 121 patients were included: 55.4% female, ages from six months to 74 yo (median age = 25.1 yo). Most patients had predominantly antibody deficiency (n = 53). The infection was mostly asymptomatic (n = 21) and mild (n = 66), and one child had multisystem inflammatory syndrome (MIS-C). We could not observe sex-related susceptibility, and there was a weak correlation between age and severity of infection. The number of comorbidities was higher in severe cases, particularly bronchiectasis and cardiopathy. There were no severe cases in hereditary angioedema patients. Six patients aged 2 to 74 years died, three of them with antibody deficiency.
CONCLUSION: The outcome was mild in most patients, but the Case Fatality Ratio was higher than in the general population. However, the type of IEI was not a determining factor for severity, except for complement deficiencies linked to milder COVID-19. The severity of SARS-CoV-2 infection seems to be more related to older age, a higher number of comorbidities and type of comorbidities (bronchiectasis and cardiopathy).
The outcome was mild in most patients, but the Case Fatality Ratio was higher than in the general population.
the observed 5% rate lacks an ascertainment- and demography-adjusted general-population comparison
the type of IEI was not a determining factor for severity, except for complement deficiencies linked to milder COVID-19.
small heterogeneous IEI strata and unadjusted comparisons cannot establish absence of subtype effects
The severity of SARS-CoV-2 infection seems to be more related to older age, a higher number of comorbidities and type of comorbidities (bronchiectasis and cardiopathy).
cross-sectional bivariate analyses cannot identify independent severity predictors
We could not observe sex-related susceptibility, and there was a weak correlation between age and severity of infection.
reported cohort analyses directly support the cautious, sample-specific wording
Derived from the full evaluation — not a separate score.
Strengths
The 121-patient multicentre series extends the early evidence base beyond the European and UK cohorts discussed in the paper and includes a broad age range and multiple IEI groups.
↳ Methods; Results, Fig. 1A; Discussion, paragraphs 1–3
The paper reports infection-confirmation routes, acute severity counts, hospitalization, mortality, and detailed rare subgroups such as post-HSCT patients.
↳ Results, opening paragraph, Fig. 1B, Table 1, and mortality paragraphs
The Discussion compares age, sex, IEI composition, comorbidities, and fatality outcomes with the Meyts, Shields, Marcus, and Ho reports rather than treating the cohort in isolation.
↳ Discussion, paragraphs 1–4 and CFR comparison paragraphs
Limitations
Age, comorbidity burden, bronchiectasis, immunoglobulin use, and immunosuppression are assessed through separate bivariate tests. The analysis cannot identify independent prognostic relationships or resolve confounding by indication.
↳ Methods, statistical analysis; Results, treatment and comorbidity analyses
Testing was not systematic, asymptomatic cases were found mainly through contact or unrelated hospitalization, and 11 patients lacked laboratory confirmation. The resulting case mix may not represent all infected IEI patients.
↳ Methods, inclusion criteria; Results, opening and acute-infection paragraphs; Discussion, testing paragraph
Numerous uncorrected bivariate tests include several borderline p-values, while the symptom section prints anosmia as n=380 among 99 symptomatic patients. A nominal sex variable is also analysed using Kendall's tau-b despite the stated methods framework.
↳ Methods, statistical analysis; Results, sex, treatment, comorbidity, and symptom-severity paragraphs
The 121-patient multicentre cohort provides useful early descriptive evidence from Brazil and is reported with clear severity counts, diagnostic pathways, and comparisons with international series. The principal limitation is analytical: treatment, age, comorbidity, and IEI-type associations are tested bivariately without adjustment for their evident interrelationships. The Discussion acknowledges incomplete testing and sparse disease strata, which supports a reasonably contextualized interpretation, but several mechanistic or determinant-style phrases exceed what the design establishes. The resulting evidence is most useful for cohort description and hypothesis generation rather than independent risk prediction.
Nabu’s assessment, alongside the field’s view.
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Confidence highThe 121-patient Brazilian cohort meaningfully expands the early geographic evidence base and includes a comparatively prominent complement-deficiency subgroup. Its advance remains incremental because it mainly extends contemporaneous descriptive case-series findings.
“there are little data reported on SARS-CoV-2 in IEI patients and many unanswered questions”
The multicentre descriptive design reports eligibility, ascertainment, severity criteria, and statistical procedures, but all severity associations are bivariate and lack confounding control. Mixed infection ascertainment also receives no analysis of likely misclassification.
“We performed correlations between variables”
The progression from cohort description through severity analyses to interpretation is readily traceable, and the abstract and conclusion generally use associational wording. Stronger phrases such as “determinant factor” in the Discussion reduce precision but do not redefine the paper's overall argument as causal.
“seems to be related to older age”
The Discussion compares the cohort directly with the Meyts, Shields, Marcus, and Ho series and explains demographic and IEI-distribution differences. It also identifies under-ascertainment, sparse strata, and descriptive methods as limits on precise inference.
“preventing, therefore, precise statements about the relationship”
Lower confidence on Contribution, Positioning — domain match limited.
Caveats4 of 4 checks
The principal cohort and outcome totals reconcile, but the paper contains a clear symptom-count typo, a statistical-method inconsistency, and extensive uncorrected bivariate testing. These issues warrant caution without making the central descriptive results unusable.
Ethics approval and participant consent are declared in Methods, and the supplied text presents no specific conduct concern. The linked supplement was outside the supplied material and is treated as an assessability gap rather than a reliability defect.
Flags: 2 declared / 5 total
47 of 47 checkable references verified
52 references in manuscript 5 are books, websites or datasets — counted, but not index-checkable
References not verified automatically are resolved manually within 24 hours.
No retraction or expression of concern found in Crossref (includes Retraction Watch).
Sources: Crossref (incl. Retraction Watch) ✓
Where this paper’s evidence sits on the path from initial observation to real-world use.
The findings arise from real-world patients and can inform cautious risk discussions, but no intervention or prognostic tool is tested. Unadjusted associations remain short of deployment-ready clinical guidance.
“cross-sectional, multicenter study”
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