Elevated plasma levels of epithelial and endothelial cell markers in COVID-19 survivors with reduced lung diffusing capacity six months after hospital discharge

Abstract

Background Some COVID-19 survivors present lung function abnormalities during follow-up, particularly reduced carbon monoxide lung diffusing capacity (DLCO). To investigate risk factors and underlying pathophysiology, we compared the clinical characteristics and levels of circulating pulmonary epithelial and endothelial markers in COVID-19 survivors with normal or reduced DLCO 6 months after discharge. Methods Prospective, observational study. Clinical characteristics during hospitalization, and spirometry, DLCO and plasma levels of epithelial (surfactant protein (SP) A (SP-A), SP-D, Club cell secretory protein-16 (CC16) and secretory leukocyte protease inhibitor (SLPI)), and endothelial (soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin and Angiopoietin-2) 6 months after hospital discharge were determined in 215 COVID-19 survivors. Results DLCO was < 80% ref. in 125 (58%) of patients, who were older, more frequently smokers, had hypertension, suffered more severe COVID-19 during hospitalization and refer persistent dyspnoea 6 months after discharge. Multivariate regression analysis showed that age ≥ 60 years and severity score of the acute episode ≥ 6 were independent risk factors of reduced DLCO 6 months after discharge. Levels of epithelial (SP-A, SP-D and SLPI) and endothelial (sICAM-1 and angiopoietin-2) markers were higher in patients with reduced DLCO, particularly in those with DLCO ≤ 50% ref. Circulating SP-A levels were associated with the occurrence of acute respiratory distress syndrome (ARDS), organizing pneumonia and pulmonary embolisms during hospitalization. Conclusions Reduced DLCO is common in COVID-19 survivors 6 months after hospital discharge, especially in those older than 60 years with very severe acute disease. In these individuals, elevated levels of epithelial and endothelial markers suggest persistent lung damage.

Mediators of Obesity Do Not Influence SARS-CoV-2 Infection or Activation of Primary Human Lung Microvascular Endothelial Cells In Vitro

“…Analysis of longitudinal plasma samples have shown that soluble endothelial markers increase during the course of COVID-19 and sVCAM-1 specifically is associated with non-survival ( 51 ). This study and others illustrate the importance of endothelial responses in driving severe disease ( 43 , 52 , 53 ) as well as post-COVID-19 persistent lung damage ( 54 ).…”

Sequelae of COVID-19 among previously hospitalized patients up to 1 year after discharge: a systematic review and meta-analysis

“…Second, some sequelae had a small sample size so that the pooled estimate may not be generalized. Third, clinical symptoms may have various diagnostic standards and symptoms such as cough and chest pain were mainly self-reported [ 20 , 25 , 29 – 31 , 36 , 38 , 40 – 43 , 46 , 47 , 51 – 58 , 60 , 62 , 74 , 80 , 81 , 86 , 88 , 89 , 91 ], as healthcare resources were already stretched coping with the evolving pandemic. Finally, the excess burden of each sequela compared to the general population was not quantified which were available from a limited number of controlled cohort studies only.…”

Brief Research Report: Serum clara cell 16 kDa protein levels are increased in patients hospitalized for severe SARS-CoV-2 or sepsis infection

“…who assessed CC16 serum levels in relation to the lung diffusion capacity in Covid-19 survivors six months after hospital discharge did not show any significant differences between participants with normal or low “diffusing capacity of the lung for carbon monoxide” (DLCO) test. Still, the median CC16 levels of the assessed groups both exceed the median level seen in our healthy control subjects ( 21 ) which might suggest dysregulated CC16 passage from the lungs into the circulation even 6 months after the infection independent of DLCO.…”