Coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines were authorized in the United States in December 2020. Although vaccine effectiveness (VE) against mild infection declines markedly ...after several months, limited understanding exists on the long-term durability of protection against COVID-19-associated hospitalization.
Case-control analysis of adults (≥18 years) hospitalized at 21 hospitals in 18 states 11 March-15 December 2021, including COVID-19 case patients and reverse transcriptase-polymerase chain reaction-negative controls. We included adults who were unvaccinated or vaccinated with 2 doses of a mRNA vaccine before the date of illness onset. VE over time was assessed using logistic regression comparing odds of vaccination in cases versus controls, adjusting for confounders. Models included dichotomous time (<180 vs ≥180 days since dose 2) and continuous time modeled using restricted cubic splines.
A total of 10 078 patients were included, 4906 cases (23% vaccinated) and 5172 controls (62% vaccinated). Median age was 60 years (interquartile range, 46-70), 56% were non-Hispanic White, and 81% had ≥1 medical condition. Among immunocompetent adults, VE <180 days was 90% (95% confidence interval CI, 88-91) versus 82% (95% CI, 79-85) at ≥180 days (P < .001). VE declined for Pfizer-BioNTech (88% to 79%, P < .001) and Moderna (93% to 87%, P < .001) products, for younger adults (18-64 years) (91% to 87%, P = .005), and for adults ≥65 years of age (87% to 78%, P < .001). In models using restricted cubic splines, similar changes were observed.
In a period largely predating Omicron variant circulation, effectiveness of 2 mRNA doses against COVID-19-associated hospitalization was largely sustained through 9 months.
Heat stress causes morbidity and mortality in humans and animals and threatens food security by limiting livestock productivity. Inflammatory signaling may contribute to heat stress-mediated skeletal ...muscle dysfunction. Previously, we discovered increased circulating endotoxin and intramuscular oxidative stress and TNF-α protein abundance, but not inflammatory signaling following 24 and 72 h of heat stress. Thus the purpose of this investigation was to clarify the role of inflammatory signaling in heat-stressed skeletal muscle. Crossbred gilts (n = 8/group) were assigned to either thermal neutral (24°C), heat stress (37°C), or pair-fed thermal neutral (24°C) conditions for 12 h. Following treatment, animals were euthanized, and the semitendinosus red (STR) and white (STW) were recovered. Heat stress did not alter inflammatory signaling in STW. In STR, relative heat shock protein abundance was similar between groups, as was nuclear content of heat shock factor 1. In whole homogenate, relative abundance of the NF-κB activator inhibitory κB kinase-α was increased by heat stress, although abundance of NF-κB was similar between groups. Relative abundance of phosphorylated NF-κB was increased by heat stress in nuclear fractions. Activator protein-1 (AP-1) signaling was similar between groups. While there were few differences in transcript expression between thermal neutral and heat stress, 80 and 56% of measured transcripts driven by NF-κB or AP-1, respectively, were increased by heat stress compared with pair-fed thermal neutral. Heat stress also caused a reduction in IL-6 transcript and relative protein abundance. These data demonstrate that short-term heat stress causes inflammatory signaling through NF-κB in oxidative, but not glycolytic, skeletal muscle.
Heat stress (HS) diminishes animal production, reducing muscle growth and increasing adiposity, especially in swine. Excess heat creates a metabolic phenotype with limited lipid oxidation that relies ...on aerobic and anaerobic glycolysis as a predominant means of energy production, potentially reducing metabolic rate. To evaluate the effects of HS on substrate utilization and energy expenditure, crossbred barrows (15.2 ± 2.4 kg) were acclimatized for 5 days (22 °C), then treated with 5 days of TN (thermal neutral, 22 °C,
= 8) or HS (35 °C,
= 8). Pigs were fed ad libitum and monitored for respiratory rate (RR) and rectal temperature. Daily energy expenditure (DEE) and respiratory exchange ratio (RER, CO2:O2) were evaluated fasted in an enclosed chamber through indirect calorimetry. Muscle biopsies were obtained from the longissimus dorsi pre/post. HS increased temperature (39.2 ± 0.1 vs. 39.6 ± 0.1 °C,
< 0.01) and RER (0.91 ± 0.02 vs. 1.02 ± 0.02 VCO2:VO2,
< 0.01), but decreased DEE/BW (68.8 ± 1.7 vs. 49.7 ± 4.8 kcal/day/kg,
< 0.01) relative to TN. Weight gain (
= 0.80) and feed intake (
= 0.84) did not differ between HS and TN groups. HS decreased muscle metabolic flexibility (~33%,
= 0.01), but increased leucine oxidation (~35%,
= 0.02) compared to baseline values. These data demonstrate that HS disrupts substrate regulation and energy expenditure in growing pigs.
Dietary calcium and phosphorus are required for bone and muscle development. Deficiencies of these macrominerals reduce bone mineral and muscle accretion potentially via alterations of mesenchymal ...stem cell (MSC) and satellite cell (SC) activities.
With increasing interest in the role of early-life events on lifetime health outcomes, we aimed to elucidate the impact of dietary calcium and phosphorus, from deficiency through excess, on MSC and SC characteristics during neonatal development.
Neonatal pigs 30 females, 1-d-old, 1.46 ± 0.04 kg body weight (BW) were fed milk replacers for 16 d that were isonitrogenous and isocaloric with a consistent ratio of calcium to phosphorus, but either 25% deficient (calcium: 0.78%; phosphorus: 0.60%; CaPD), adequate (calcium: 1.08%; phosphorus: 0.84%; CaPA), or 25% in excess (calcium: 1.38%; phosphorus: 1.08%; CaPE) of calcium and phosphorus requirements based on sow-milk composition and extrapolation from NRC requirements for older pigs. BW and feed intake were recorded daily. Blood was collected for serum phosphorus, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23) determination. Humeri were collected for MSC isolation and radii/ulnae bone were collected for analysis. Longissimus dorsi muscle was collected for SC isolation and analysis.
Therewas 4.6% increase in bone ash percentage in CaPE- versus CaPD-fed pigs (P < 0.05). In vivo proliferationindicated a 41.3%increase in MSCs in CaPA compared with CaPD and a 19%increase in SCs in CaPA comparedwith bothCaPE and CaPD. MSCs from CaPD had 2- to 5-fold greater expression of peroxisome proliferator-activated receptor γ(PPARγ ), fatty acidbinding protein 4 (FABP4), and lipoprotein lipase (LPL) but lower osteocalcin (BGLAP) and fibronectin(FN1) expression than CaPA (P < 0.05). SCs from CaPD-fed pigs had 19% lower in vivo proliferation than in CaPA-fedpigs.
IThese findings demonstrated that feeding a diet marginally deficient in calcium and phosphorus to neonatal pigs had a great impact on bone development, MSC, and SC characteristics. These dietary deficiencies may program future bone health and muscle development by altering MSC and SC activities.
Basic principles governing skeletal muscle growth and development, from a cellular point of view, have been realized for several decades. Skeletal muscle is marked by the capacity for rapid ...hypertrophy and increases in protein content. Ultimately, skeletal muscle growth is controlled by 2 basic means: 1) myonuclear accumulation stemming from satellite cell (myoblast) proliferation and 2) the balance of protein synthesis and degradation. Each process underlies the rapid changes in lean tissue accretion evident during fetal and neonatal growth and is particularly sensitive to nutritional manipulation. Although multiple signals converge to alter skeletal muscle mass, postprandial changes in the anabolic hormone insulin link feed intake with enhanced rates of protein synthesis in the neonate. Indeed, a consequence of insulin-deficient states such as malnutrition is reduced myoblast activity and a net loss of body protein. A well-characterized mechanism mediating the anabolic effect of insulin involves the phosphatidylinositol 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) signaling pathway. Activation of mTOR leads to translation initiation control via the phosphorylation of downstream targets. Modulation of this pathway by insulin, as well as by other hormones and nutrients, accounts for enhanced protein synthesis leading to efficient lean tissue accretion and rapid skeletal muscle gain in the growing animal. Dysfunctional insulin activity during fetal and neonatal stages likely alters growth through cellular and protein synthetic capacities.
Heat stress (HS) causes morbidities and mortalities, in part by inducing organ-specific injury and dysfunction. Further, HS markedly reduces farm animal productivity, and this is especially true for ...lean tissue accretion. The purpose of this investigation was to determine the extent to which short-term HS caused muscle dysfunction in skeletal muscle. We have previously found increased free radical injury in skeletal muscle following 24 h of HS. Thus, we hypothesized that HS would lead to apoptosis, autophagy, and decreased mitochondrial content in skeletal muscle. To test this hypothesis, crossbred gilts were divided into 3 groups ( = 8/group): thermal neutral (TN: 21°C), HS (37°C), and pair-fed thermal neutral (PFTN: feed intake matched with heat-stressed animals). Following 12 h of treatment, animals were euthanized and red (STR) and white (STW) portions of the semitendinosus were recovered. Heat stress did not alter intracellular signaling in STW. In STR, the oxidative stress marker malondialdehyde protein and concentration were increased in HS ( = 0.007) compared to TN and PFTN, which was matched by an inadequate antioxidant response, including an increase in superoxide dismutase (SOD) I ( = 0.03) and II relative protein abundance ( = 0.008) and total SOD activity ( = 0.02) but a reduction ( = 0.006) in catalase activity in HS compared to TN. Further, B-cell lymphoma 2-associated X protein ( = 0.02) and apoptotic protease activating factor 1 ( = 0.01) proteins were increased by HS compared to TN and PFTN. However, caspase 3 activity was similar between groups, indicating a lack of apoptotic execution. Despite increased initiation, autophagy appeared to be inhibited by HS as the microtubule-associated protein A/B light chain 3 II/I ratio and mitofusin-2 proteins were decreased ( < 0.03) and sequestosome 1(p62) protein abundance was increased ( = 0.001) in HS compared to TN and PFTN. Markers of mitochondrial content cytochrome c, cytochrome c oxidase IV, voltage-dependent anion channel, pyruvate dehydrogenase, and prohibitins 1 were increased ( < 0.05) in HS compared to TN, whereas mitochondrial biogenesis and mitophagy markers were similar between groups. These data demonstrate that HS caused aberrant intracellular signaling, which may contribute to HS-mediated muscle dysfunction.
Abstract
Study objectives were to determine the effects of rapamycin (Rapa) on biomarkers of metabolism and inflammation during acute heat stress (HS) in growing pigs. Crossbred barrows (n = 32; 63.5 ...± 7.2 kg body weight BW) were blocked by initial BW and randomly assigned to 1 of 4 environmental-therapeutic treatments: 1) thermoneutral (TN) control (n = 8; TNCon), 2) TN and Rapa (n = 8; TNRapa), 3) HS control (n = 8; HSCon), or 4) HS and Rapa (n = 8; HSRapa). Following 6 d of acclimation to individual pens, pigs were enrolled in two experimental periods (P). During P1 (10 d), pigs were fed ad libitum and housed in TN conditions (21.3 ± 0.2°C). During P2 (24 h), HSCon and HSRapa pigs were exposed to constant HS (35.5 ± 0.4°C), while TNCon and TNRapa pigs remained in TN conditions. Rapamycin (0.15 mg/kg BW) was orally administered twice daily (0700 and 1800 hours) during both P1 and P2. HS increased rectal temperature and respiration rate compared to TN treatments (1.3°C and 87 breaths/min, respectively; P < 0.01). Feed intake (FI) markedly decreased in HS relative to TN treatments (64%; P < 0.01). Additionally, pigs exposed to HS lost BW (4 kg; P < 0.01), while TN pigs gained BW (0.7 kg; P < 0.01). Despite marked changes in phenotypic parameters caused by HS, circulating glucose and blood urea nitrogen did not differ among treatments (P > 0.10). However, the insulin:FI increased in HS relative to TN treatments (P = 0.04). Plasma nonesterified fatty acids (NEFA) increased in HS relative to TN treatments; although this difference was driven by increased NEFA in HSCon compared to TN and HSRapa pigs (P < 0.01). Overall, circulating white blood cells, lymphocytes, and monocytes decreased in HS compared to TN pigs (19%, 23%, and 33%, respectively; P ≤ 0.05). However, circulating neutrophils were similar across treatments (P > 0.31). The neutrophil-to-lymphocyte ratio (NLR) was increased in HS relative to TN pigs (P = 0.02); however, a tendency for reduced NLR was observed in HSRapa compared to HSCon pigs (21%; P = 0.06). Plasma C-reactive protein tended to differ across treatments (P = 0.06) and was increased in HSRapa relative to HSCon pigs (46%; P = 0.03). Circulating haptoglobin was similar between groups. In summary, pigs exposed to HS had altered phenotypic, metabolic, and leukocyte responses; however, Rapa administration had limited impact on outcomes measured herein.
Abstract
Background
. Adults in the United States (US) began receiving the adenovirus vector coronavirus disease 2019 (COVID-19) vaccine, Ad26.COV2.S (Johnson & Johnson Janssen), in February 2021. We ...evaluated Ad26.COV2.S vaccine effectiveness (VE) against COVID-19 hospitalization and high disease severity during the first 10 months of its use.
Methods
. In a multicenter case-control analysis of US adults (≥18 years) hospitalized 11 March to 15 December 2021, we estimated VE against susceptibility to COVID-19 hospitalization (VEs), comparing odds of prior vaccination with a single dose Ad26.COV2.S vaccine between hospitalized cases with COVID-19 and controls without COVID-19. Among hospitalized patients with COVID-19, we estimated VE against disease progression (VEp) to death or invasive mechanical ventilation (IMV), comparing odds of prior vaccination between patients with and without progression.
Results
. After excluding patients receiving mRNA vaccines, among 3979 COVID-19 case-patients (5% vaccinated with Ad26.COV2.S) and 2229 controls (13% vaccinated with Ad26.COV2.S), VEs of Ad26.COV2.S against COVID-19 hospitalization was 70% (95% confidence interval CI: 63–75%) overall, including 55% (29–72%) among immunocompromised patients, and 72% (64–77%) among immunocompetent patients, for whom VEs was similar at 14–90 days (73% 59–82%), 91–180 days (71% 60–80%), and 181–274 days (70% 54–81%) postvaccination. Among hospitalized COVID-19 case-patients, VEp was 46% (18–65%) among immunocompetent patients.
Conclusions
. The Ad26.COV2.S COVID-19 vaccine reduced the risk of COVID-19 hospitalization by 72% among immunocompetent adults without waning through 6 months postvaccination. After hospitalization for COVID-19, vaccinated immunocompetent patients were less likely to require IMV or die compared to unvaccinated immunocompetent patients.
In a multicenter case-control analysis of hospitalized US adults (≥18 years), the viral vector coronavirus disease 2019 (COVID-19) vaccine, Ad26.COV2.S, reduced risk of hospitalization with COVID-19 by 70%, consistent up to >180 days postvaccination and across periods of different variant predominance.
Study objectives were to determine the effects of zinc (Zn) amino acid complex (Availa Zn, Zinpro Corporation, Eden Prairie, MN) on metabolism, biomarkers of leaky gut, and inflammation during and ...following heat stress (HS) and nutrient restriction. Crossbred gilts (n = 50; 50 ± 2 kg BW) were blocked by initial BW and randomly assigned to one of five treatments: 1) thermoneutral (TN) and ad libitum fed a control diet (TNCtl), 2) TN and pair-fed a control diet (PFCtl), 3) TN and pair-fed a Zn-supplemented diet (PFZn), 4) HS and ad libitum fed a control diet (HSCtl), and 5) HS and ad libitum fed a Zn-supplemented diet (HSZn). The study consisted of 3 experimental periods (P): during P1 (7 d), all pigs were fed their respective diets ad libitum and housed in TN conditions (20.84 ± 0.03 °C, 47.11 ± 0.42% relative humidity). During P2 (7 d), HSCtl and HSZn pigs were exposed to progressive cyclical HS conditions (27 to 30 °C, 41.9 ± 0.5% relative humidity), while TNCtl, PFCtl, and PFZn pigs remained in TN conditions and were fed ad libitum or pair-fed to their respective HSCtl and HSZn counterparts. During P3 (5 d; "recovery phase"), all pigs were housed in TN conditions and fed ad libitum. Pigs exposed to HS had overall increased rectal temperature, skin temperature, and respiration rate (0.33 °C, 3.76 °C, and 27 bpm, respectively; P < 0.01). Relative to TN controls, HS decreased ADFI and ADG (28 and 35%, respectively; P < 0.05), but these variables were unaffected by dietary treatment. Additionally, circulating insulin did not differ between HS and TN pigs (P = 0.41), but was decreased in PF relative to TN pigs (P < 0.01). During recovery, no differences were observed in rectal temperature or respiration rate across treatments, but HSZn pigs had decreased skin temperature relative to TN, PF, and HSCtl pigs (P < 0.01). During P3, no Zn effects were observed in production parameters; however, PF pigs had increased ADFI and ADG relative to TN and HS treatments (P < 0.01). During P3, circulating insulin was increased in pigs that were HS relative to TN and PF pigs (75%, P < 0.05). Interestingly, tumor necrosis factor alpha (TNFα) levels were decreased during P3 (P = 0.04) in Zn relative to Ctl-fed pigs. Circulating lipopolysaccharide-binding protein was not different among periods (P > 0.10). In summary, Zn reduced TNFα (regardless of HS), and the stimulatory effect of HS on insulin secretion is amplified during HS recovery.
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