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Page 2 of 10 Ramadori. Hepatoma Res 2020;6:28 I http://dx.doi.org/10.20517/2394-5079.2020.43

cornonavirus-1 and Middle East respiratory syndrome coronavirus caused primarily pulmonary diseases.
HuCoV 229E, 0C43, NL63 and HKU1 are mainly responsible for the common cold, but can also cause lethal
[1]
nonspecific pneumonias . However, SARS-CoV-2 has a wide range of clinical presentations, with acute
[2-4]
respiratory distress syndrome being the often fatal pulmonary complication .
Most of the publications reporting clinical characteristics for patients with SARS-CoV-2-infection originate
from China, many from the city of Wuhan. These publications are descriptive retrospective case series about
[5,6]
patients hospitalized with the virus or who died in intensive care units (ICU) . The symptoms reported
mainly concern the reason for hospitalisation. The spectrum of all symptoms, and key timings from when
[7,8]
patients first felt unwell is less well reported . In fact, far less is known about the symptomatology at the
time of first appearance of the disease in hospitalized patients and in infected persons who remained at
home, and who may had even died there.

Parameters indicating liver damage include prothrombin time, serum transaminase and bilirubin levels,
acute-phase response markers such as leukocyte count. C-reactive protein, procalcitonin, and several
serum cytokine levels have been reported in patients with SARS-CoV-2, together with changes in serum
albumin levels [2-5,9,10] . Previous experiences in patients with SARS or MERS suggested that hypoalbuminemia,
lymphopenia, a serum CRP level greater than 4 mg/dL, plus elevated lactate dehydrogenase on hospital
admission were predictive for pneumonia progressing to respiratory failure [11-14] . Low serum albumin levels
have now been found to be an important predictor of progression to severe disease and increased mortality
in hospitalised SARS-CoV-2 positive patients of older age [15,16] .

PATHOPHYSIOLOGICAL ASPECTS OF HYPOALBUMINEMIA AND CLINICAL RELEVANCE OF
ALBUMIN INFUSION
Albumin is a single chain protein with a molecular weight of 66 kDa made of 585 amino acids which
represents more than 50% of the serum proteins and represents an important component of interstitial
fluid. The albumin fraction was first separated from the other components of the plasma in 1944 by
[17]
Edwin Cohn , who also appreciated its strong oncotic properties. This characteristic of albumin was
[18]
also confirmed by Scatchard et al. in 1944. Serum albumin levels are used as useful surrogates of liver
[19]
function . Soon after the fractionation studies, intravenous albumin administration was performed in
patients with advanced liver disease. This was done in the United States during the 1940’s [21,22] and also in the
[22]
United Kingdom at the beginning of the 1960’s by Wilkinson and Sherlock et al. .
The beneficial effect of prolonged administration was first demonstrated in a clinical trial by the group of
[23]
[24]
Paolo Gentilini in Florence , and more recently by Caraceni et al. in Bologna.
The positive diuretic effect of albumin infusion in three patients with liver cirrhosis was published by
[25]
Patek et al. . This finding was subsequently corroborated in a group of ten patients [26,27] , showing that
albumin infusion in patients with liver cirrhosis and ascites (without spontaneous bacterial peritonitis)
increased sodium excretion in the urine, and led to weight reduction and a reduction in diuretics required.

It was shown that repeated daily intravenous administration of albumin was able to avoid the requirement
[28]
for transjugular stent placement into the portal tract trough the hepatic vein (TIPS) . A similar experience,
[29]
in a larger patient numbers, was published by Trotter et al. .

The positive effects of albumin infusion in cirrhotic patients with low levels of serum albumin was shown by
[30]
Bajaj et al. who observed a normalisation in serum sodium concentration in patients with liver cirrhosis
and hyponatriemia. Infusion of intravenous albumin solution in decompensated cirrhotic patients was also
[31]
able to reduce encephalopathic episodes and associated mortality .