Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new human disease with few effective treatments 1. Convalescent plasma, donated by persons who have recovered from COVID-19, is the acellular component of blood that contains antibodies, including those that specifically recognize SARS-CoV-2. These antibodies, when transfused into patients infected with SARS-CoV-2, are thought to exert an antiviral effect, suppressing virus replication before patients have mounted their own humoral immune responses 2,3. Virus-specific antibodies from recovered persons are often the first available therapy for an emerging infectious disease, a stopgap treatment while new antivirals and vaccines are being developed 1,2. This retrospective, propensity score-matched case-control study assessed the effectiveness of convalescent plasma therapy in 39 patients with severe or life-threatening COVID-19 at The Mount Sinai Hospital in New York City. Oxygen requirements on day 14 after transfusion worsened in 17.9% of plasma recipients versus 28.2% of propensity score-matched controls who were hospitalized with COVID-19 (adjusted odds ratio (OR), 0.86; 95% confidence interval (CI), 0.75-0.98; chi-square test P value = 0.025). Survival also improved in plasma recipients (adjusted hazard ratio (HR), 0.34; 95% CI, 0.13-0.89; chi-square test P = 0.027). Convalescent plasma is potentially effective against COVID-19, but adequately powered, randomized controlled trials are needed.

SARS-CoV2 host cell infection is mediated by the binding to angiotensin-converting enzyme 2 (ACE2). Systemic dysregulation observed in SARS-CoV was previously postulated to be due to ACE2/Ang1-7/Mas axis downregulation, increased ACE2 activity was shown to mediate disease protection. Since angiotensin II receptor blockers (ARBs), ACE inhibitors, and mineralocorticoid receptor antagonists (MRAs) increase ACE2 receptor expression, it has been tacitly believed that the use of these agents may facilitate viral disease, thus they should not be used in high-risk patients with cardiovascular disease. Based on the anti-inflammatory benefits of the upregulation of the ACE2/Ang1-7/Mas axis and previously demonstrated benefits of lung function improvement in SARS-CoV infections, we hypothesize that the benefits of treatment with reninangiotensin system inhibitors in SARS-COV2 may outweigh the risks and at the very least should not be withheld. Condensed abstract:SARS-CoV2 infection is mediated by binding to angiotensin-converting enzyme 2 (ACE2). Given the receptors upregulation with angiotensin II receptor blockers (ARBs), ACE inhibitors, and mineralocorticoid receptor antagonists (MRAs), it is unclear if clinical management of cardiovascular patients with COVID-19 should be reconsidered. Given the anti-inflammatory benefits of upregulation of the ACE2/Ang1-7/Mas axis in cardiovascular disease and previously demonstrated benefits in improving lung function in SARS-CoV infections, we propose that upregulation of ACE2 expression/activity via these cardiac agents should be beneficial in counteracting the systemic dysregulation inflicted by SARS-CoV2 due to ACE2 dysregulation.

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Transforming growth factor-β1 (TGF-β1) has been used as a biomarker in disorders associated with pathologic fibrosis. However, plasma TGF-β1 assessment is confounded by the significant variation in reported normal values, likely reflecting variable release of the large pool of platelet TGF-β1 after blood drawing. Moreover, current assays measure only total TGF-β1, which is dominated by the latent form of TGF-β1 rather than the biologically active form. To address these challenges, we developed methodologies to prevent ex vivo release of TGF-β1 and to quantify active TGF-β1. We then used these techniques to measure TGF-β1 in healthy controls and patients with heart failure (HF) before and after insertion of left ventricular assist devices (LVAD). Total plasma TGF-β1 was 1.0 ± 0.60 ng/mL in controls and 3.76 ± 1.55 ng/mL in subjects with HF (P < 0.001), rising to 5.2 ± 2.3 ng/mL following LVAD placement (P = 0.006). These results were paralleled by the active TGF-β1 values; controls had 3-16 pg/mL active TGF-β1, whereas levels were 2.7-fold higher in patients with HF before, and 4.2-fold higher after, LVAD implantation. Total TGF-β1 correlated with levels of the platelet-derived protein thrombospondin-1 (r = 0.87; P < 0.001), suggesting that plasma TGF-β1 may serve as a surrogate indicator of in vivo platelet activation. von Willebrand factor high molecular weight multimers correlated inversely with TGF-β1 levels (r = -0.63; P = 0.023), suggesting a role for shear forces in loss of these multimers and platelet activation. In conclusion, accurate assessment of circulating TGF-β1 may provide a valuable biomarker for in vivo platelet activation and thrombotic disorders.

Patients with both chronic kidney disease (CKD) and diabetes mellitus (DM) are at increased risk for thrombotic events compared to those with one abnormality alone. Whether this can be attributed to changes in platelet reactivity among those with both CKD and DM is unknown. We prospectively studied 438 clopidogrel-naïve patients undergoing percutaneous coronary intervention (PCI). Platelet function tests were performed 4-6 hours after loading with 600 mg of clopidogrel. Platelet reactivity was assessed using the VerifyNow system and expressed as P2Y12 reaction units (PRU). High residual platelet reactivity (HRPR) was defined as PRU > 230. Patients were categorised into four groups by the presence or absence of CKD and DM. Among those without CKD or DM (n=166), DM alone (n=150), CKD alone (n=60) and both CKD and DM (n=62) the mean PRU levels were 201.6 ± 96.3, 220.5 ± 101.1, 254.9 ± 106.7 and 275.0 ± 94.5, respectively (p<0.001). Analogously, the prevalence of HRPR was 42.3%, 50.7%, 63.3% and 75.8%, respectively (p< 0.001). Associations between either CKD or DM alone and HRPR were attenuated after multivariable adjustment while the odds for HRPR associated with both CKD and DM remained significant (OR [95% CI]: 2.61 [1.16 - 5.86]). In conclusion, the presence of both CKD and DM confers a synergistic impact on residual platelet reactivity when compared to either condition alone. Whether more potent platelet inhibitors may improve outcomes among patients with both abnormalities warrants investigation.