key: cord-0777560-ad3wyl8v
authors: Pérez, José María Hernández; Gonçálves, Juan Marco Figueira; Fariña, Yolanda Ramallo
title: Alpha-1 antitrypsin as a risk marker in SARS-CoV-2 infection
date: 2021-05-22
journal: Arch Med Sci
DOI: 10.5114/aoms/136562
sha: ac2a67c29c1c558dd94c33228c4f39568602b2bb
doc_id: 777560
cord_uid: ad3wyl8v

nan

The SARS-CoV-2 virus has infected millions of people worldwide. Given its unpredictability, much research is being focused on potential indicators of a poor course of the resulting disease, COVID-19. Various serum biomarkers, e.g., total leukocyte and lymphocyte counts, lactate dehydrogenase (LDH), D-dimer, procalcitonin, troponin I and ferritin levels, seem to provide support for decision making on process severity and the need of intensive care unit (ICU) transfer, and even predict mortality [1, 2].

Alpha-1 antitrypsin (AAT) is a water-soluble glycoprotein, mainly synthesised by hepatocytes, and provides the largest part of anti-protease activity to the human body. Being an acute phase reactant, its plasma levels increase in response to inflammatory or infectious stimuli and persist for 7 to 15 days [3] . In addition to its anti-inflammatory activity, AAT has anti-microbial properties, as its carboxy-terminal 20 amino-acid residues can interfere with virus replication and infectivity, e.g., of the human immunodeficiency virus [4] . A similar response could be expected in SARS-CoV2-infected patients, although only a few studies have focused on this aspect so far.

Accordingly, we wanted to explore AAT levels as a potential risk marker for severe SARS-CoV-2 infections with a poor course. To this end, a prospective, observational, descriptive study was performed on patients admitted consecutively to our hospital with SARS-CoV-2 pneumonia. The study was conducted in accordance with the Declaration of Helsinki and approved by the hospital's ethics committee. Diagnosis was established through real-time, reverse polymerase chain reaction (RT-PCR) for SARS-CoV-2 in samples from nasopharyngeal smears, paralleled by lung consolidation on current chest radiography. The criteria inclusion comprised AAT, LDH, ferritin, D-dimer, total lymphocyte count, C-reactive protein and interleukin 6 (IL-6) determination in all patients within 48 h after admission, an RT-PCR confirmed diagnosis and radiological diagnoses pneumonia. Patients in whom some of the established measurement parameters were missing, or performed later than 48 h after admission, as well as patients who did not present radiological infiltrates on admission were discarded. Emerging adult respiratory distress syndrome (ARDS), determined by pulse oximetric saturation/fraction of inspired oxygen ratio (SpO 2 /FiO 2 ) < 300 [5] , was considered the reference parameter for a poor disease course.

The study sample consisted of 45 patients; 37.8% were women and 62.2% men. Their median age was 59 ±11.49 years. The mean time from onset of symptom to hospital admission was 5.12 ±3.48 days; 37.8% of the patients developed ARDS, 11.11% eventually needed transfer to the ICU. The overall mortality was 2.22%. Patients who developed ARDS had significantly higher levels of AAT, LDH, ferritin and D-dimer than the rest (Table I) . AAT levels > 200 mg/dl, i.e. above the upper reference level, correlated with emerging ARDS with an odds ratio (OR) of 30.9 (95% confidence interval (95% CI): 3.17-301.55). Applying multivariate analysis, only AAT correlated significantly (in 82.2% of the cases) with ARDS (OR = 1.026, 95% CI: 1.004-1.047) .

Only a few studies have assessed AAT in SARS-CoV-2 infection so far. McElvaney et al. [6] reported a higher IL-6/AAT ratio in patients who needed ICU transfer than in subjects with a more favourable disease course.

Other authors, such as Wettstein et al. [7] , have demonstrated in vitro that AAT is capable of inhibiting SARS-CoV-2 replication in infected cells. These cells increase serine transmembrane protease 2 (STP2) expression, which in turn has an anti-inflammatory effect that facilitates virus entry into the cells. AAT appears to act by inhibiting STP2, thus hampering viral uptake. Our study indicated that AAT levels > 200 mg/dl constitute an important predictor of ARDS and thus a potential means for patient monitoring.

To date, only a few studies have evaluated AAT as a prognostic marker. Age, comorbidities, lymphopenia, increased inflammatory biomarkers (e.g., C-reactive protein, serum ferritin and erythrocyte sedimentation rate) and elevated aspartate aminotransferase, creatinine and LDH levels have been correlated with ARDS in patients with COVID-19 [8] .

In conclusion, the results of our study indicate that AAT may be a reliable marker in predicting the occurrence of ARDS and therefore the disease course in patients affected by SARS-CoV-2, although further studies with a larger sample size are needed to confirm these findings.

The C-terminal 26-residue peptide of serpin A1 is an inhibitor of HIV-1

The use of the pulse oximetric saturation to fraction of inspired oxygen ratio in an automated acute respiratory distress syndrome screening tool

Characterization of the inflammatory response to severe COVID-19 illness

Alpha-1 antitrypsin inhibits SARS-CoV-2 infection

Lactate dehydrogenase and C-reactive protein as predictors of respiratory failure in COVID-19 patients

The authors declare no conflict of interest.R e f e r e n c e s