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2.
Circulation ; 144(SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1632416

ABSTRACT

Cardiac microthrombi are postulated to underlie cardiac injury in critical COVID-19. To determine pathogenic mechanism(s) of cardiac injury in fatal COVID-19, we conducted a single-center prospective cohort study of 69 consecutive COVID-19 decedents. Microthrombi was the most commonly detected acute cardiac histopathologic feature (n=48, 70%). We tested associations of cardiac microthrombi with biomarkers of inflammation, cardiac injury, and fibrinolysis and with inhospital antiplatelet therapy, therapeutic anticoagulation, and corticosteroid treatment, while adjusting for multiple clinical factors, including COVID-19 therapies. Higher peak ESR and CRP during hospitalization were independently associated with higher odds of microthrombi (ESR, Pnonlinearity 0.015, Passociation=0.008;CRP per 20mg/L increase, OR 1.17, 95%CI 1.00-1.36). Using single nuclei RNA-sequence analysis, we discovered an enrichment of prothrombotic, anti-fibrinolytic, and extracellular matrix signaling amongst cardiac fibroblasts in microthrombi-positive COVID-19 hearts, compared with microthrombi-negative COVID-19 hearts and non-COVID-19 donor hearts. Our cumulative findings identify these specific transcriptomic changes in cardiac fibroblasts as salient features of COVID-19-associated cardiac microthrombi.

4.
American Journal of Respiratory and Critical Care Medicine ; 203(9), 2021.
Article in English | EMBASE | ID: covidwho-1277613

ABSTRACT

Rationale: Over 60 million people have had coronavirus disease 2019 (COVID-19), but consequences of severe infection are unknown. We sought to characterize interstitial lung abnormalities (ILA) after COVID-19, and to identify risk factors for the development of lung fibrosis.Methods: We performed a prospective single-center cohort study with 4-month follow-up after COVID-19 hospitalization. We sequentially enrolled 76 community-dwelling adults who were hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and required supplemental oxygen between March and May 2020. Participants had no prior history of interstitial lung disease and were discharged to acute rehabilitation or home, with sampling weighted to include half who were mechanically ventilated. We used a radiologic scoring system to quantify non-fibrotic ILA (ground glass opacities alone) and fibrotic ILA (defined as presence of reticulations, traction bronchiectasis, or honeycombing) on chest high-resolution computed tomography scans four months after hospital admission. We assessed measures of severity of illness during hospitalization, as well as pulmonary function and leukocyte telomere length at followup. Results: Participants had a mean age of 54 (SD14) years;most were male (61%) and Hispanic (57%). Thirty-two (43%) required mechanical ventilation. After a median (IQR) of 4.4 (4.0-4.8) months following hospital admission, the most common ILAs were ground glass opacities, reticulations, and traction bronchiectasis, which correlated with lower diffusion capacity (ρ -0.34, - 0.64, and -0.49, respectively, all p<0.01). A total of 31 participants (41%) had no ILA, 13 (17%) had only non-fibrotic ILA, and 32 (42%) had fibrotic ILA. Fibrotic ILA was more common in mechanically ventilated patients (72%) than non-mechanically ventilated patients (20%), (p=0.001). In adjusted analyses, each 1 point increase in admission SOFA score, additional day of ventilator support, and 10% decrease in blood leukocyte telomere length were associated with fibrotic ILA [OR 1.49 (95%CI 1.17 - 1.89), 1.07 (95%CI 1.03-1.12), and 1.35 (95%CI 1.06 - 1.72), respectively].Conclusions: Radiographic evidence of lung fibrosis four months after severe COVID-19 infection is associated with initial severity of illness, duration of mechanical ventilation, and telomere length.

5.
Thorax ; 29:29, 2021.
Article in English | MEDLINE | ID: covidwho-1209856

ABSTRACT

The risk factors for development of fibrotic-like radiographic abnormalities after severe COVID-19 are incompletely described and the extent to which CT findings correlate with symptoms and physical function after hospitalisation remains unclear. At 4 months after hospitalisation, fibrotic-like patterns were more common in those who underwent mechanical ventilation (72%) than in those who did not (20%). We demonstrate that severity of initial illness, duration of mechanical ventilation, lactate dehydrogenase on admission and leucocyte telomere length are independent risk factors for fibrotic-like radiographic abnormalities. These fibrotic-like changes correlate with lung function, cough and measures of frailty, but not with dyspnoea.

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