Abstract
BackgroundSeverity and mortality of COVID-19 largely depends on the ability of the immune system to clear the virus. Among various comorbidities potentially impacting on this process, the weight and the consequences of an antibody deficiency have not yet been clarified.MethodsWe used serum protein electrophoresis to screen for hypogammaglobulinemia in a cohort of consecutive adult patients with COVID-19 pneumonia, hospitalized in non-intensive care setting between December 2020 and January 2021. The disease severity, measured by a validated score and by the need for semi intensive (sICU) or intensive care unit (ICU) admission, and the 30-day mortality was compared between patients presenting hypogammaglobulinemia (HYPO) and without hypogammaglobulinemia (no-HYPO). Demographics, comorbidities, COVID-19 specific treatment during the hospital stay, disease duration, complications and laboratory parameters were also evaluated in both groups.ResultsWe enrolled 374 patients, of which 39 represented the HYPO cohort (10.4%). In 10/39 the condition was previously neglected, while in the other 29/39 hematologic malignancies were common (61.5%); 2/39 were on regular immunoglobulin replacement therapy (IgRT). Patients belonging to the HYPO group more frequently developed a severe COVID-19 and more often required sICU/ICU admission than no-HYPO patients. IgRT were administered in 8/39 during hospitalization; none of them died or needed sICU/ICU. Among HYPO cohort, we observed a significantly higher prevalence of neoplastic affections, of active oncologic treatment and bronchiectasis, together with higher prevalence of viral and bacterial superinfections, mechanical ventilation, convalescent plasma and SARS-CoV-2 monoclonal antibodies administration during hospital stay, and longer disease duration. Multivariate logistic regression analysis and Cox proportional hazard regression confirmed the impact of hypogammaglobulinemia on the COVID-19 severity and the probability of sICU/ICU admission. The analysis of the mortality rate in the whole cohort showed no significant difference between HYPO and no-HYPO.ConclusionsHypogammaglobulinemia, regardless of its cause, in COVID-19 patients hospitalized in a non-intensive care setting was associated to a more severe disease course and more frequent admission to s-ICU/ICU, particularly in absence of IgRT. Our findings emphasize the add-value of routine serum protein electrophoresis evaluation in patients admitted with COVID-19 to support clinicians in patient care and to consider IgRT initiation during hospitalization.
Highlights
Since the beginning of the SARS-CoV2 pandemic in 2019, clinical and experimental evidence has tried to dissect mechanisms of disease and to identify the critical elements to improve the management of patients
In one of the first published reports of 7 Italian cases of COVID-19 in patients affected by primary antibody deficiency (PAD) described a more severe clinical course of COVID-19 in common variable immunodeficiency than in X-linked agammaglobulinemia patients, suggesting that a B cell dysfunction may be more dangerous than the complete lack of antibody production [8]
The observations derived from hematologic patients, when a severe hypogammaglobulinemia was detected without mention of immunoglobulin replacement therapy (IgRT), COVID-19 was associated with higher mortality and severe inflammatory response compared to the general population [12, 13]
Summary
Since the beginning of the SARS-CoV2 pandemic in 2019, clinical and experimental evidence has tried to dissect mechanisms of disease and to identify the critical elements to improve the management of patients. The consequences of SARS-CoV-2 infection in individuals with primary and secondary antibody deficiencies are still unclear [6, 7]. A multicenter retrospective study investigated the impact of SARS-CoV-2 infection on 94 patients with a spectrum of IEIs, mainly antibody deficiencies, reporting that disease severity and mortality were globally similar to those in the general population [11]. When evaluating these findings, it is important to consider that almost all patients with PAD enrolled in those studies were receiving immunoglobulin substitution as standard therapy, presenting adequate serum IgG trough levels at the time of SARS-CoV-2 infection. Among various comorbidities potentially impacting on this process, the weight and the consequences of an antibody deficiency have not yet been clarified
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