The effect of sex on cardiovascular dynamics in normal and diabetic rates

CHAPTER II In this study, we evaluated the effect of L-NAME, a NOS antagonist, on MAP, HR, and selective vascular flows in male and female normal and diabetic rats. Rats were made diabetic using streptozotocin (50 mg/kg, IV) and maintained for 5-6 weeks. Following anesthesia with urethane/α-chloralose, the femoral artery and vein were cannulated for recording and sampling and flow probes were placed on the iliac, renal and superior mesenteric arteries. A bolus infusion of L-NAME resulted in a rapid increase in MAP in normal females and males. However, in diabetic females and males this response was significantly lower and especially so in diabetic females. L-NAME decreased the conductance in all three vascular beds in normal rats. In diabetic animals, the response to L-NAME was decreased to a greater extent in the iliac bed of diabetic males while the renal conductance was actually increased in females. We concluded that diabetics decreased pressor response to NOS inhibition and the lack of response of the renal vessels in female diabetics may play a role in the increased renal pathology in diabetic females. CHAPTER III SNP (1-20 µg/kg) infusions resulted in a dose-dependent decrease in MAP m normal and diabetic rats. Reflex tachycardia was more prominent in diabetic males. The vascular conductance was increased in normal and diabetic rats in a dose-dependent fashion, however, the responsiveness was less in the iliac and superior mesenteric and increased in the renal arteries in diabetics when compared to normals. We concluded that diabetes is associated with an increased response to NO in the renal vessels and a decreased response in the iliac and superior mesenteric vessels in both females and males. CHAPTER IV Prazosin (4 mg/kg) administration decreased the MAP in normal and diabetic rats to a comparable degree. It increased the vascular conductance in all three vascular beds in normal and diabetic rats with the greater increase occurring in the iliac and superior mesenteric arteries. α-adrenergic tone was greatest in diabetic female and male rats. We concluded that decreased vascular flow in diabetes is associated with an increased adrenergic tone in the splachnic and skeletal muscle bed in both diabetic female and male rats

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