Background Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, previously named 2019-nCov), a novel coronavirus that emerged in China in December 2019 and was declared a global pandemic by World Health Organization by March 11th, 2020. Severe manifestations of COVID-19 are caused by a combination of direct tissue injury by viral replication and associated cytokine storm resulting in progressive organ damage. Discussion We reviewed published literature between January 1st, 2000 and June 30th, 2020, excluding articles focusing on pediatric or obstetric population, with a focus on virus-host interactions and immunological mechanisms responsible for virus associated cytokine release syndrome (CRS). COVID-19 illness encompasses three main phases. In phase 1, SARS-CoV-2 binds with angiotensin converting enzyme (ACE)2 receptor on alveolar macrophages and epithelial cells, triggering toll like receptor (TLR) mediated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ƙB) signaling. It effectively blunts an early (IFN) response allowing unchecked viral replication. Phase 2 is characterized by hypoxia and innate immunity mediated pneumocyte damage as well as capillary leak. Some patients further progress to phase 3 characterized by cytokine storm with worsening respiratory symptoms, persistent fever, and hemodynamic instability. Important cytokines involved in this phase are interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. This is typically followed by a recovery phase with production of antibodies against the virus. We summarize published data regarding virus-host interactions, key immunological mechanisms responsible for virus-associated CRS, and potential opportunities for therapeutic interventions. Conclusion Evidence regarding SARS-CoV-2 epidemiology and pathogenesis is rapidly evolving. A better understanding of the pathophysiology and immune system dysregulation associated with CRS and acute respiratory distress syndrome in severe COVID-19 is imperative to identify novel drug targets and other therapeutic interventions.

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Background Though the incidence of atrial fibrillation (AF) is increased in patients with cancer, the effectiveness of catheter ablation (CA) for AF in patients with cancer is not well studied. Methods We conducted a retrospective cohort study of patients who underwent CA for AF. Patients with a history of cancer within 5-years prior to, or those with an exposure to anthracyclines and/or thoracic radiation at any time prior to the index ablation were compared to patients without a history of cancer who underwent AF ablation. The primary outcome was freedom from AF [with or without anti-arrhythmic drugs (AADs), or need for repeat CA at 12-months post-ablation]. Secondary endpoints included freedom from AF at 12 months post-ablation with AADs and without AADs. Safety endpoints included bleeding, pulmonary vein stenosis, stroke, and cardiac tamponade. Multivariable regression analysis was performed to identify independent risk predictors of the primary outcome. Results Among 502 patients included in the study, 251 (50%) had a history of cancer. Freedom from AF at 12 months did not differ between patients with and without cancer (83.3% vs 72.5%, p 0.28). The need for repeat ablation was also similar between groups (20.7% vs 27.5%, p 0.29). Multivariable regression analysis did not identify a history of cancer or cancer-related therapy as independent predictors of recurrent AF after ablation. There was no difference in safety endpoints between groups. Conclusion CA is a safe and effective treatment for AF in patients with a history of cancer and those with exposure to potentially cardiotoxic therapy.

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Background The effects of Nirmatrelvir/Ritonavir (NMV-r or Paxlovid) on Covid-19 outcomes in younger vaccinated adults are unclear. Objective To assess if NMV-r use in vaccinated adults aged ≤50 is associated with improved outcomes and identify beneficial and non-beneficial subgroups. Design/Setting Cohort study, TriNetX database. Participants We generated two propensity-matched cohorts of 2,547 patients from an 86,119-person cohort assembled from the TriNetX database. Patients in one cohort received NMV-r, and patients in the matched control cohort did not. Measurements Main outcome: composite of all-cause emergency department visits, hospitalization, and mortality. Results The composite outcome was detected in 4.9% of the NMV-r cohort and 7.0% of the non-NMV-r cohort (OR 0.683, CI 0.540-0.864; p=0.001), indicating a 30% relative risk reduction. The number needed to treat (NNT) for the primary outcome was 47. Subgroup analyses found significant associations for patients with cancer (NNT=45), cardiovascular disease (NNT=30), and both conditions (NNT=16). No benefit was found for patients with only chronic lower respiratory disorders (asthma/COPD) or without serious comorbidities. 32% of NMV-r prescriptions in the overall database were for 18-50-year-olds. Conclusion NMV-r use in vaccinated adults aged 18-50, especially with serious comorbidities, was associated with reduced all-cause hospital visits, hospitalization, and mortality in the first 30 days of Covid-19 illness. However, NMR-r in patients without significant comorbidities or with only asthma/COPD had no association of benefit. Therefore, identifying high-risk patients should be a priority and avoid over-prescription should be avoided.