Immunoglobulin Deficiency as an Indicator of Disease Severity in Patients with COVID-19

Am J Physiol Lung Cell Mol Physiol. 2020 Nov 25. doi: 10.1152/ajplung.00359.2020. Online ahead of print.


Despite the pandemic status of COVID-19, there is limited information about host risk factors and treatment beyond supportive care. Immunoglobulin G (IgG) could be a potential treatment target. Our aim was to determine the incidence of IgG deficiency and associated risk factors in a cohort of 62 critical ill COVID-19 patients admitted to two German ICUs (72.6% male, median age: 61 years). 13 (21.0%) of the patients displayed IgG deficiency (IgG <7 g/L) at baseline (predominant for the IgG1, IgG2, and IgG4 subclasses). IgG-deficient patients had worse measures of clinical disease severity than those with normal IgG levels (shorter duration from disease onset to ICU admission, lower ratio of PaO2 to FiO2, higher Sequential Organ Failure Assessment score, and higher levels of ferritin, neutrophil-to-lymphocyte ratio and serum creatinine). IgG-deficient patients were also more likely to have sustained lower levels of lymphocyte counts and higher levels of ferritin throughout the hospital stay. Furthermore, IgG-deficient patients compared to those with normal IgG levels displayed higher rates of acute kidney injury (76.9% vs. 26.5%; p=0.005) and death (46.2% vs. 14.3%; p=0.012), longer ICU (28 [6-48] vs. 12 [3-18] days; p=0.012) and hospital length of stay (30 [22-50] vs. 18 [9-24] days; p=0.004). Multivariable logistic regression showed increasing odds of 90-day overall mortality associated with IgG-deficiency (OR 12.8, 95% CI 1.5-108.4; p=0.019). IgG deficiency might be common in critically ill COVID-19 patients, and warrants investigation as both a marker of disease severity as well as a potential therapeutic target.

Keywords: Cytokine release syndrome; Immunodysregulation; Respiratory failure; Severe acute respiratory syndrome coronavirus 2.