Fetal programming of COVID-19: May the barker hypothesis explain the susceptibility of a subset of young adults to develop severe disease?

Gerosa C.;Faa G.;Fanni D.;Manchia M.;Suri J. S.;Ravarino A.;Barcellona D.;Pichiri G.;Coni P.;Congiu T.;Piras M.;Cerrone G.;Cau F.;Ledda F.;Aimola V.;Coghe F.;Porcu M.;Cau R.;Orru' G.;Van Eyken P.;La Nasa G.;Castagnola M.;Marongiu F.;Saba L.

2021-01-01

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Abstract

The risk stratification of young adults between subjects who will develop a mild form COVID-19 and subjects who will undergo a severe disease remains inaccurate. In this review, we propose that the Barker hypothesis might explain the increased susceptibility to severe forms of COVID-19 in subjects who underwent intrauterine growth restriction (IUGR). In this paper evidence indicating an association between a low birth weight and an adult phenotype which might favor a severe outcome of SARS-CoV-2 infection are presented: lower lung functional capacity; increased respiratory morbidity; changes in fibrinogen and Factor VII serum levels and dysregulation of the hemostasis and thrombosis system; acquisition of a pro-thrombotic phenotype; low nephron number, with decreased ability to sustain renal function and increased renal morbidity; heart remodeling, with a less efficient cardiac function; endothelial dysfunction, a risk factor for the insurgence of the multiple organ failure; remodeling of arteries, with changes in the elastic properties of the arterial wall, predisposing to the insurgence and progression of atherosclerosis; dysfunction of the innate immune system, a risk factor for immune diseases in adulthood. These data suggest that young and adult subjects born too small (IUGR) or too early (pre-terms) might represent a subgroup of "at risk subjects", more susceptible toward severe forms of COVID-19. Given that LBW may be considered a surrogate of IUGR, this phenotypic marker should be included among the indispensable clinical data collected in every patient presenting with SARSCOV- 2 infection, irrespectively of his/her age.