Clinical Characteristics and Comparative Proteomics Analysis of COVID-19-Related Atrioventricular Block.

Background: Atrioventricular block (AVB) is thought to be a rare cardiovascular complication of the coronavirus disease 2019 (COVID-19), though limited data are available beyond case reports. We aim to describe the baseline characteristics, proteomics profile, and outcomes for patients with COVID-19-related AVB.

Methods: We prospectively recruited patients diagnosed with COVID-19-related AVB between November 2022 and March, 2023. Inclusion criteria were hospitalization for COVID-19 with the diagnosis of AVB. A total of 24 patients diagnosed with COVID-19 without AVB were recruited for control. We analyzed patient characteristics and outcomes and performed a comparative proteomics analysis on plasma samples of those patients and controls.

Results: A total of 17 patients diagnosed with COVID-19-related AVB and 24 individuals diagnosed with COVID-19 infection without AVB were included. Among patients with COVID-19-related AVB, the proportion of concurrent pneumonia was significantly higher than controls (7/17 versus 2/24, p $<$ 0.05). All 17 AVB patients (9 of permanent AVB, 8 of paroxysmal AVB) received permanent pacemaker implantation. No procedural-related complication occurred. In laboratory tests, the level of biomarkers indicating myocardial damage were substantially higher than controls, including high-sensitivity cardiac troponin-I (median 0.005 versus 0.002 ng/mL, p $<$ 0.05), myoglobulin (median 39.0 versus 27.6 ng/mL, p $<$ 0.05), and MB isoenzyme of creatine kinase (median 1.2 versus 0.8 U/L, p $<$ 0.05). The level of N-terminal pro-b-type natriuretic peptide (median 241.0 versus 33.5 pg/mL, p $<$ 0.05), C-reactive protein (median 4.8 versus 2.0 mg/L, p $<$ 0.05), D-dimer (median 1.2 versus 0.2 µg/mL, p $<$ 0.05), left ventricular end-diastolic diameter (median 49.3 versus 45.7 mm, p $<$ 0.05) in patients with COVID-19-related AVB were significantly higher than controls. The level of albumin (median 41.9 versus 44.5 g/L, p $<$ 0.05) was significantly lower than controls. In comparative proteomics analysis, we identified 397 human proteins. Several significantly altered plasma proteins related to inflammatory response (Serum amyloid A protein, C-reactive protein, Protein Adenosine 5'-monophosphate-activated protein kinase (AMPK), Alpha-2-macroglobulin), complement and coagulation cascades (Tetranectin, haptoglobin), and immune response (Neutrophil defensin 3, Fibrinogen beta chain) may contribute to the pathogenesis of COVID-19-related AVB.

Conclusions: Patients with COVID-19-related AVB are more prone to have myocardial damage and concurrent pneumonia. Through laboratory tests and comparative proteomics analysis, we identified several differential expressed proteins (Serum amyloid A protein, Tetranectin, Neutrophil defensin 3) releated to the inflammatory response, complement and coagulation cascades, and immune response, which provides evidence of potential biomarkers and sheds light on the pathogenesis of COVID-19-related AVB.