Viruses spread between hosts through particles, but within hosts, viral genomes can spread from cell to cell through fusion, evading antiviral defenses and obviating costly infectious virion production1-3. Billions of electromechanically coupled cardiomyocytes (CMs) make myocardium inherently vulnerable to pathological electromechanical short circuits caused by intercellular viral spread 4-6. Beyond respiratory illness, COVID-19 affects the heart7 and cardiac injury and arrhythmias are serious public health concerns8-12. By studying myocardium of a young woman who died suddenly, diagnosed postmortem with COVID-19, we discovered highly focal myocardial SARS-CoV-2 infection spreading from one CM to another through intercellular junctions identified by highly concentrated sarcolemmal t-tubule viral spike glycoprotein. SARS-CoV-2 permissively infected beating human induced pluripotent stem cell (hiPSC)-CMs building multinucleated cardiomyotubes (CMTs) through cell type-specific fusion driven by proteolytically-activated spike glycoprotein. Recombinant spike glycoprotein, co-localizing to sarcolemma and sarcoplasmic reticulum, produced multinucleated CMTs with pathological structure, electrophysiology and Ca2+ excitation-contraction coupling. Blocking cleavage, a peptide-based protease inhibitor neutralized SARS-CoV-2 spike glycoprotein pathogenicity. We conclude that SARS-CoV-2 spike glycoprotein, efficiently primed, activated and strategically poised during biosynthesis, can exploit the CM’s inherent membranous connectivities to drive heart damage directly, uncoupling clinically common myocardial injury from lymphocytic myocarditis, often suspected but rarely confirmed in COVID-19.

Importance: Contracting COVID-19 peri-operatively has been associated with a mortality rate as high as 23%. Using hot and cold sites has led to a low rate of post-operative diagnosis of COVID-19 infection and allowed safe continuation of important emergency and cancer operations in our centre. Objective: The primary objective was to determine the safety of the continuation of surgical admissions and procedures during the height of the COVID-19 pandemic using hot and cold surgical sites. The secondary objective is to determine risk factors of contracting COVID-19 to help guide further prevention. Setting: A single surgical department at a tertiary care referral centre in London, United Kingdom. Participants: All consecutive patients admitted under the care of the urology team over a 3-month period from 1st March to 31st May 2020 over both hot acute admission sites and cold elective sites were included. Exposures: COVID-19 was prevalent in the community over the three months of the study at the height of the pandemic. The majority of elective surgery was carried out in a cold site requiring patients to have a negative COVID-19 swab 72 hours prior to admission and to self-isolate for 14 days pre-operatively, whilst all acute admissions were admitted to the hot site. Main outcomes and measures: COVID-19 was detected in 1.6% of post-operative patients. There was 1 (0.2%) post-operative mortality due to COVID-19. Results: A total of 611 patients, 451 (73.8%) male and 160 (26.2%) female, with a median age of 57 (interquartile range 44-70) were admitted under the surgical team. Of these, 101 (16.5%) were admitted on the cold site and 510 (83.5%) on the hot site. Surgical procedures were performed in 495 patients of which 8 (1.6%) contracted COVID-19 post-operatively with 1 (0.2%) post-operative mortality due to COVID-19. Overall, COVID-19 was detected in 20 (3.3%) patients with 2 (0.3%) deaths. On multivariate analysis, length of stay was associated with contracting COVID-19 in our cohort (OR 1.25, 95% CI 1.13-1.39). Conclusions and Relevance: Continuation of surgical procedures using hot and cold sites throughout the COVID-19 pandemic was safe practice, although the risk of COVID-19 remained and is underlined by a post-operative mortality. Reducing length of stay may be able to reduce contraction of COVID-19.

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