COVID-19 vulnerabilities are intensified by declining human serum albumin levels

Abstract

What is the topic of this review? Human serum albumin (HSA) a common factor in COVID-19 vulnerabilities. What advances does it highlight? Understanding of HSA capacity, and systemic vulnerabilities to COVID-19. Raising HSA in COVID-19 patients may alleviate systemic injury caused by diminished native HSA binding. A change in fluid therapy administration into the portal system of the liver is proposed to safely raise HSA levels. ABSTRACT: The specific nature of the vulnerabilities to COVID-19 are an intrinsic part of COVID-19 infection in many patients. This paper proposes that vulnerabilities to COVID-19 may be intensified by a decrease in human serum albumin (HSA) as a ligand carrier for nutrients. A mechanism for COVID-19 vulnerabilities is evident from consideration of ligand carriers such as HSA as intermediaries. We hypothesise that low levels of pool HSA binding, caused for whatever reason, affect the performance of albumin as a carrier protein reducing the availability of nutrients. Hypoalbuminaemia (low HSA) has been implicated as an indicator of COVID-19 and long-COVID-19. The levels of HSA directly affect the immune system and vulnerabilities to age, diabetes and obesity in COVID-19. Any slight reduction in available HSA has profound effects on ligand concentrations in the small capillaries where damage occurs in COVID-19. The clinical implication is that attempts should be made to return HSA to clinical levels to compensate for the additional ligands caused by infection (SARS-CoV-2 virions, antibodies and cellular breakdown products). Therapeutic albumin is usually given peripherally, and usual preparations are unbound to ligands, but we suggest that a clinical trial of HSA therapy via the hepatic portal vein should be considered.

Keywords: COVID-19; SARS-CoV-2; albumin therapy; human serum albumin; hypoalbuminemia; long-COVID; nutrient distribution; portal system; virion vulnerabilities.

FIGURE 1

Illustrative profile match of albumin decrease with age and risk of COVID‐19. Levels of albumin binding changes during ageing making older males more vulnerable after 50 years and females after 65. Serum albumin levels of males (a) decrease with age earlier than those of females (b) (derived from Weaving et al., 2016). SARS‐CoV2 virions, antibodies, excess waste and factors from other illnesses reduce the tolerance of unbound albumin further (c). When the number of ligands caused by COVID‐19 (c) exceeds that of either the male HSA binding tolerance (a) or the female HSA binding tolerance (b), the ability of HSA to transport nutrients is exhausted. The implication is that as SARS‐CoV2 virions enter the system they, and the consequential antibodies and other created ligands, block the natural ability of HSA to bind the correct nutrients causing cellular stress and crisis in the systemic system affecting all organs, leading to excess death rates in both males and females as illustrated (curves derived from data of Islam et al., 2021). Human figures designed by Tartila/Freepik

FIGURE 2

Illustration of direction of flow of nutrients from the gut and ligand exchange in the capillaries. (a) Circulatory system showing direction and flow of nutrients from the intestine through the heart and lungs. Fluid therapy to the periphery of unbound HSA will flow to the heart and then is concentrated in the lungs and may make many circulations before re‐entering the liver . HSA entering the liver is charged with ligands before circulating. Thus fresh, unbound HSA could be introduced into the hepatic portal vein using standard techniques as described in the discussion. (b) At the capillary level, concentrations, and therefore delivery of ligands (FFA – free fatty acids), are determined by relative concentrations across cells. Competition exists to maintain equilibrium and any outside element such as SARS‐CoV2 will interfere with this balance. (From Johnson et al., – reproduced under the Creative Commons Licence.) (a) modified from pikissuperstar freepik