Lower serum alpha 1 antitrypsin levels in patients with severe COVID-19 compared with patients hospitalized due to non-COVID-19 pneumonia

Introduction

Coronavirus disease 2019 (COVID-19), caused by severeacute respiratory syndrome coronavirus 2 (SARS-Cov-2)is an ongoing global pandemic [1]. SARS-CoV-2 cellentry is facilitated by host proteases that activate thevirus spike protein and enable its engagement with theangiotensin-converting enzyme 2 (ACE2) receptor [2,3].The transmembrane serine protease 2 (TMPRSS2) is cru-cial for SARS-CoV-2 cell entry and is inhibited by alpha 1antitrypsin (A1AT), which is the primary human bloodserine protease inhibitor [4–6]. Recently, two studiesfrom Italy and Portugal reported that patients withknown A1AT deficiency (A1ATD) have a higher risk ofcontracting COVID-19 and suffering from a severe dis-ease [7,8]. The prevalence of homozygous patients withA1AT deficiency in Europe is estimated at 0.01%–0.02%,and the most frequent clinically relevant alleles are PiZ(Glu342Lys) and PiS (Glu264Val). However, the exactA1ATD prevalence is unknown due to the lack of large-scale A1AT genotyping studies. Moreover, there is con-siderable  heterogeneity  in  the  clinical  presentationamong A1ATD carriers, and some may exhibit severedisease with childhood onset while others may beasymptomatic. These patients may still have mild A1ATdeficiency and thus be more susceptible to pulmonaryinfections [6,9]. Hence, genetic variations may be amongfactors that contribute to differences in COVID-19 infec-tion rates and severity [10]. To further assess thishypothesis, we evaluated the serum levels of A1AT inpatients with severe COVID-19 infection and comparedit with patients with non-COVID-19 pulmonary infection.

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