Vasculopathy and Increased Vascular Congestion in Fatal COVID-19 and Acute Respiratory Distress Syndrome.

Rationale: The leading cause of death in coronavirus disease 2019 (COVID-19) is severe pneumonia, with many patients developing acute respiratory distress syndrome (ARDS) and diffuse alveolar damage (DAD). Whether DAD in fatal COVID-19 is distinct from other causes of DAD remains unknown. Objective: To compare lung parenchymal and vascular alterations between patients with fatal COVID-19 pneumonia and other DAD-causing etiologies using a multidimensional approach. Methods: This autopsy cohort consisted of consecutive patients with COVID-19 pneumonia (n = 20) and with respiratory failure and histologic DAD (n = 21; non-COVID-19 viral and nonviral etiologies). Premortem chest computed tomography (CT) scans were evaluated for vascular changes. Postmortem lung tissues were compared using histopathological and computational analyses. Machine-learning-derived morphometric analysis of the microvasculature was performed, with a random forest classifier quantifying vascular congestion (CVasc) in different microscopic compartments. Respiratory mechanics and gas-exchange parameters were evaluated longitudinally in patients with ARDS. Measurements and Main Results: In premortem CT, patients with COVID-19 showed more dilated vasculature when all lung segments were evaluated (P = 0.001) compared with controls with DAD. Histopathology revealed vasculopathic changes, including hemangiomatosis-like changes (P = 0.043), thromboemboli (P = 0.0038), pulmonary infarcts (P = 0.047), and perivascular inflammation (P < 0.001). Generalized estimating equations revealed significant regional differences in the lung microarchitecture among all DAD-causing entities. COVID-19 showed a larger overall CVasc range (P = 0.002). Alveolar-septal congestion was associated with a significantly shorter time to death from symptom onset (P = 0.03), length of hospital stay (P = 0.02), and increased ventilatory ratio [an estimate for pulmonary dead space fraction (Vd); p = 0.043] in all cases of ARDS. Conclusions: Severe COVID-19 pneumonia is characterized by significant vasculopathy and aberrant alveolar-septal congestion. Our findings also highlight the role that vascular alterations may play in Vd and clinical outcomes in ARDS in general.

A CONFOUNDING CASE OF NON-ISCHEMIC CARDIOMYOPATHY: ACQUIRED MYOCARDITIS FROM COVID-19 AND SYSTEMIC LUPUS ERYTHEMATOSUS LEADING TO CLINICAL HEART FAILURE

CASE: We report a 50-year-old Caucasian female with a history of systemic lupus erythematosus (SLE) in remission and chronic kidney disease (CKD) stage 5. The patient presented with dyspnea on exertion and orthopnea for two weeks. Six weeks ago, she was diagnosed with COVID-19 after presenting to the ED for substernal chest pain, myalgias, and fatigue. During this admission, she denied any current joint pain, chest pain, or rashes. She denies a history of alcohol or illicit drug use. EKG in the ED showed T-wave inversions in lead I and aVL, stable from prior EKG. The brain natriuretic peptide level was elevated at 3,500 pg/ml. There was no transaminitis, and kidney function was at baseline. Chest x-ray showed pulmonary vascular congestion and cardiomegaly. A transthoracic echocardiogram showed a left ventricular ejection fraction of 15-20% with severe global hypokinesis. The patient had a full cardiomyopathy workup. We ruled out ischemic cardiomyopathy with a negative coronary angiogram. Non-ischemic cardiomyopathy (NICMO) workup was initiated, with a focus on viral or autoimmune myocarditis. While a cardiac MRI would have been the gold standard to assess for myocardial scarring, the patient's CKD status prohibited this possibility. Similarly, an endomyocardial biopsy was not performed due to its low sensitivity for diagnosing viral or autoimmune myocarditis. Without evidence of infiltrative disease, or other exposures, it was deemed that the patient's recent history of COVID-19 infection, in conjunction with underlying SLE, were the causes of her new-onset NICMO. The patient's dyspnea responded to intravenous bumetanide. We initiated guideline-directed medical therapy with carvedilol and isosorbide-dinitrate. She continues regular follow-up in the outpatient heart failure clinic. IMPACT/DISCUSSION: Classification and evaluation of NICMO can be broad, and thus the clinical picture plays an essential role in the workup. Acquired cardiomyopathy from prior myocarditis was the most likely etiology of our patient's new-onset NICMO. Our patient had no clinical symptoms of myocarditis prior to her exposure to COVID-19, making it unlikely that SLE was the sole driving factor. There is a known association between COVID-19 and myocarditis. A few proposed mechanisms for COVID-19 induced myocarditis include upregulation of cytokines, particularly interleukin-6, and downregulation of ACE2, leading to microvascular and cardiac pericyte dysfunction. Cytokine release from COVID-19 coupled with subclinical SLE could have acted synergistically to cause this patient's condition. Given the increasing incidence of COVID-19 infections, internists must consider COVID-19 exposures during the workup of new-onset heart failure. CONCLUSION: The workup for NICMO in the COVID-19 era must include detailed history taking for sick contacts and prior history of COVID-19 diagnosis. More research is needed to determine if COVID-19 infection can increase the risk of NICMO in patients with a known history of SLE.

Vascular Abnormalities Detected with Chest CT in COVID-19: Spectrum, Association with Parenchymal Lesions, Cardiac Changes, and Correlation with Clinical Severity (COVID-CAVA Study).

Although vascular abnormalities are thought to affect coronavirus disease 2019 (COVID-19) patients' outcomes, they have not been thoroughly characterized in large series of unselected patients. The Swiss national registry coronavirus-associated vascular abnormalities (CAVA) is a multicentric cohort of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who underwent a clinically indicated chest computed tomography (CT) aiming to assess the prevalence, severity, distribution, and prognostic value of vascular and non-vascular-related CT findings. Clinical outcomes, stratified as outpatient treatment, inpatient without mechanical ventilation, inpatient with mechanical ventilation, or death, will be correlated with CT and biological markers. The main objective is to assess the prevalence of cardiovascular abnormalities-including pulmonary embolism (PE), cardiac morphology, and vascular congestion. Secondary objectives include the predictive value of cardiovascular abnormalities in terms of disease severity and fatal outcome and the association of lung inflammation with vascular abnormalities at the segmental level. New quantitative approaches derived from CT imaging are developed and evaluated in this study. Patients with and without vascular abnormalities will be compared, which is supposed to provide insights into the prognostic role and potential impact of such signs on treatment strategy. Results are expected to enable the development of an integrative score combining both clinical data and imaging findings to predict outcomes.