Metabolic characteristics of human hearts preserved for 12 hours by static storage, antegrade perfusion, or retrograde coronary sinus perfusion

ObjectiveMachine perfusion of donor hearts is a promising strategy to increase the donor pool. Antegrade perfusion is effective but can lead to aortic valve incompetence and nonnutrient flow. Experience with retrograde coronary sinus perfusion of donor hearts has been limited. We tested the hypothesis that retrograde perfusion could support myocardial metabolism over an extended donor ischemic interval.MethodsHuman hearts from donors that were rejected or not offered for transplantation were preserved for 12 hours in University of Wisconsin Machine Perfusion Solution by: (1) static hypothermic storage; (2) hypothermic antegrade machine perfusion; or (3) hypothermic retrograde machine perfusion. Myocardial oxygen consumption (MVO2), and lactate accumulation were measured. Ventricular tissue was collected for proton and phosphorus 31 magnetic resonance spectroscopy (MRS) to evaluate the metabolic state of the myocardium. Myocardial water content was determined at the end of the experiment.ResultsStable perfusion parameters were maintained throughout the perfusion period with both perfusion techniques. Lactate/alanine ratios were lower in perfused hearts compared with static hearts (P < .001). Lactate accumulation (antegrade 2.0 ± 0.7 mM, retrograde 1.7 ± 0.1 mM) and MVO2 (antegrade 0.25 ± 0.2 mL, retrograde 0.26 ± 0.3 mL O2/min/100 g) were similar in machine-perfused groups. High-energy phosphates were better preserved in both perfused groups (P < .05). Left ventricular myocardial water content was increased in retrograde perfused hearts (80.2 ± 0.8%) compared with both antegrade perfused hearts (76.6 ± 0.8%, P = .02) and static storage hearts (76.7 ± 1%, P = .02).ConclusionsMachine perfusion by either the antegrade or the retrograde technique can support myocardial metabolism over long intervals. Machine perfusion seems promising for long-term preservation of human donor hearts

Risk of COVID-19 after natural infection or vaccinationResearch in context

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health

Risk of COVID-19 after natural infection or vaccinationResearch in context

Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health