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Background There are limited data on the effectiveness of the vaccines against symptomatic coronavirus disease 2019 (Covid-19) currently authorized in the United States with respect to hospitalization, admission to an intensive care unit (ICU), or ambulatory care in an emergency department or urgent care clinic. Methods We conducted a study involving adults (≥50 years of age) with Covid-19–like illness who underwent molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed 41,552 admissions to 187 hospitals and 21,522 visits to 221 emergency departments or urgent care clinics during the period from January 1 through June 22, 2021, in multiple states. The patients’ vaccination status was documented in electronic health records and immunization registries. We used a test-negative design to estimate vaccine effectiveness by comparing the odds of a positive test for SARS-CoV-2 infection among vaccinated patients with those among unvaccinated patients. Vaccine effectiveness was adjusted with weights based on propensity-for-vaccination scores and according to age, geographic region, calendar time (days from January 1, 2021, to the index date for each medical visit), and local virus circulation. Results The effectiveness of full messenger RNA (mRNA) vaccination (≥14 days after the second dose) was 89% (95% confidence interval [CI], 87 to 91) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization, 90% (95% CI, 86 to 93) against infection leading to an ICU admission, and 91% (95% CI, 89 to 93) against infection leading to an emergency department or urgent care clinic visit. The effectiveness of full vaccination with respect to a Covid-19–associated hospitalization or emergency department or urgent care clinic visit was similar with the BNT162b2 and mRNA-1273 vaccines and ranged from 81% to 95% among adults 85 years of age or older, persons with chronic medical conditions, and Black or Hispanic adults. The effectiveness of the Ad26.COV2.S vaccine was 68% (95% CI, 50 to 79) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization and 73% (95% CI, 59 to 82) against infection leading to an emergency department or urgent care clinic visit. Conclusions Covid-19 vaccines in the United States were highly effective against SARS-CoV-2 infection requiring hospitalization, ICU admission, or an emergency department or urgent care clinic visit. This vaccine effectiveness extended to populations that are disproportionately affected by SARS-CoV-2 infection. (Funded by the Centers for Disease Control and Prevention.)

Objective:To determine the prevalence and associated mortality of well-defined neurologic diagnoses among COVID-19 patients, we prospectively followed hospitalized SARS-Cov-2 positive patients and recorded new neurologic disorders and hospital outcomes.Methods:We conducted a prospective, multi-center, observational study of consecutive hospitalized adults in the NYC metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between COVID-19 patients with and without neurologic disorders.Results:Of 4,491 COVID-19 patients hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were: toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis, or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were RT-PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all P<0.05). After adjusting for age, sex, SOFA-scores, intubation, past history, medical complications, medications and comfort-care-status, COVID-19 patients with neurologic disorders had increased risk of in-hospital mortality (Hazard Ratio[HR] 1.38, 95% CI 1.17-1.62, P<0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63-0.85, P<0.001).Conclusions:Neurologic disorders were detected in 13.5% of COVID-19 patients and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness.

Metabolic syndrome comprises a cluster of related disorders that includes obesity, glucose intolerance, insulin resistance, dyslipidemia, and fatty liver. Recently, gut-derived chronic endotoxemia has been identified as a primary mediator for triggering the low-grade inflammation responsible for the development of metabolic syndrome. In the present study we examined the role of the small intestinal brush-border enzyme, intestinal alkaline phosphatase (IAP), in preventing a high-fat-diet-induced metabolic syndrome in mice. We found that both endogenous and orally supplemented IAP inhibits absorption of endotoxin (lipopolysaccharides) that occurs with dietary fat, and oral IAP supplementation prevents as well as reverses metabolic syndrome. Furthermore, IAP supplementation improves the lipid profile in mice fed a standard, low-fat chow diet. These results point to a potentially unique therapy against metabolic syndrome in at-risk humans.etabolic syndrome is a complex syndrome composed of a cluster of disorders that includes obesity, glucose intolerance, insulin resistance, abnormal lipid profile (dyslipidemia), fatty liver, and hypertension (1, 2). Metabolic syndrome leads to type 2 diabetes, atherosclerosis, and nonalcoholic fatty liver disease (1, 2). Approximately 35-39% of the US population suffers from the syndrome (3). This epidemic of metabolic syndrome has devastating consequences in terms of mortality, morbidity, and total healthcare expenditures (4).Recently, "metabolic endotoxemia" has been proposed to be central to the pathogenesis of metabolic syndrome. The Gramnegative bacterial cell wall component lipopolysaccharide (LPS) is known as endotoxin, and metabolic endotoxemia is defined as a two-to threefold persistent increase in circulating endotoxin concentrations above the normal levels (5). Metabolic endotoxemia leads to low-grade systemic inflammation as evidenced by increased serum levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1, and IL-6 (5). It is well recognized that chronic inflammation causes damage to pancreatic beta cells (6), hepatocytes (7), and vascular endothelial cells (8), and dysfunction of these cells is thought to contribute to metabolic syndrome.A high-fat diet (HFD) has been shown to cause metabolic endotoxemia in animals and humans (5, 9), but the underlying molecular mechanisms remain incompletely understood. Ghoshal et al. (10) demonstrated that intestinal epithelial cells (enterocytes) internalize LPS from the apical surface, which is then transported to the Golgi apparatus where it complexes with chylomicrons, the lipoproteins that transport the absorbed longchain fatty acids in enterocytes. The chylomicron-LPS complex is then secreted into mesenteric lymph and makes its way into the systemic circulation. Excess chylomicron formation during highfat feeding leads to prolonged chylomicronemia (complexed with LPS) that ultimately induces systemic inflammation. Also, it has been shown that an HFD causes local intestinal inflammation (11). Systemic and local inf...

Local area community cumulative incidence (per 1,000 population) Health care personnel with positive test results for SARS-CoV-2 antibodies (%) Abbreviation: COVID-19 = coronavirus disease 2019. * Calculated as the total number of reported community COVID-19 cases within a hospital-area county or counties between the beginning of the pandemic and 7 days after the first day of health care personnel enrollment at the hospital divided by population of the county or counties x 1,000.

† The data in these analyses come from 306 ED and UC clinics and 164 hospitals. § The study period at Baylor Scott and White Health began on September 11, 2021. *** With a test-negative design, vaccine performance is assessed by comparing the odds of antecedent vaccination among case-patients with acute laboratory-confirmed COVID-19 and control-patients without acute COVID-19. This odds ratio was adjusted for age, geographic region, calendar time (days from January 1), and local virus circulation in the community and weighted for inverse propensity to be vaccinated or unvaccinated.

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