Association of alpha-1-antitrypsin deficiency with vitamin D status: who is most at risk of getting severe COVID-19?

Abstract

Introduction Coronavirus disease 2019 (COVID-19), a new disease that we do not know yet how to treat, is rapidly evolving and has forced us to stay indoors. Surprisingly, a broad range of symptoms has been reported since COVID-19 emergence. Individual variations in susceptibility to SARS-CoV-2 can be due to non-genetic and genetic factors. Alpha-1-antitrypsin deficiency (AATD) is an inherited condition that is associated with an increased risk of liver and lung diseases which may increase susceptibility to COVID-19 infection. At the same time, there could be a possibility of developing non-hereditary AATD. Discussion In addition to some evidence showing the role of vitamin D deficiency in COVID-19 pathology, it has been recognized that there is a biological link between AAT and vitamin D. Therefore, here we offer a new perspective that lower vitamin D levels in COVID-19 patients can cause acquired AATD that provide a condition with more disease severity and a higher risk of death. As a consequence, COVID-19 individuals with vitamin D deficiency may have a higher risk of morbidity and mortality. Conclusion Therefore, early vitamin D and AAT assessments and optimal interventions could be helpful to prevent severe COVID-19 outcomes. Keywords Coronavirus disease 2019(COVID-19) • Alpha-1-antitrypsin deficiency • Vitamin D Abbreviations COVID-19 Coronavirus disease 2019 SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 AATD Alpha-1-antitrypsin deficiency AAT Alpha-1-antitrypsin TMPRSS2 Transmembrane serine protease 2 ADAM17 A disintegrin and metalloproteinase-17 ACE2 Angiotensin-converting enzyme 2 RAS Renin-angiotensin-aldosterone system 1, 25(OH)2D3 1,25-Dihydroxy-vitamin D3 IL-10 Interleukin 10 ARDS Acute respiratory distress syndrome 25(OH)VD 25-Hydroxy-vitamin D COPD Chronic obstructive pulmonary disease Inflammation Research

Correlation between α1-Antitrypsin Deficiency and SARS-CoV-2 Infection: Epidemiological Data and Pathogenetic Hypotheses

“…Shimi et al hypothesized that low vitamin D levels in patients with COVID-19 could result in acquired AATD, leading to greater clinical severity and a higher risk of death [ 74 ].…”

Alpha-1-antitrypsin antagonizes COVID-19: a review of the epidemiology, molecular mechanisms, and clinical evidence

“…Interestingly, when AAT and glucocorticoid are combined in macrophages, lower glucocorticoid concentrations used allowed up-regulation of IL-1Ra, whereas higher glucocorticoid levels antagonized the effects of AAT [ 112 ]. Vitamin D deficiency may also lead to decreased release of AAT from T cells, causing decreased release of the anti-inflammatory cytokine IL-10 [ 115 , 116 ]. Tumpara et al [ 117 ] showed that recombinant AAT (made in Chinese hamster ovary cells) was more potent than plasma-derived AAT in inhibiting pro-inflammatory cytokine production from peripheral blood mononuclear cells stimulated with both lipopolysaccharide and spike proteins.…”

COVID-19 and Re-Commencement of Early Phase Clinical Trials in Respiratory Medicine

“…Thirdly, people with certain respiratory diseases, may be at a higher risk of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection and/or developing severe respiratory complications [3][4][5][6], which may discourage them from trial participation. Early stage trials investigate safety, tolerability and PK of new drug candidates, formulations and routes of administration and explore pharmacological effects and potential drug interactions.…”