Concerns have been expressed that persons with a pre‐existing mental disorder may represent a population at increased risk for COVID‐19 infection and with a higher likelihood of adverse outcomes of the infection, but there is no systematic research evidence in this respect. This study assessed the impact of a recent (within past year) diagnosis of a mental disorder – including attention‐deficit/hyperactivity disorder (ADHD), bipolar disorder, depression and schizophrenia – on the risk for COVID‐19 infection and related mortality and hospitalization rates. We analyzed a nation‐wide database of electronic health records of 61 million adult patients from 360 hospitals and 317,000 providers, across 50 states in the US, up to July 29, 2020. Patients with a recent diagnosis of a mental disorder had a significantly increased risk for COVID‐19 infection, an effect strongest for depression (adjusted odds ratio, AOR=7.64, 95% CI: 7.45‐7.83, p<0.001) and schizophrenia (AOR=7.34, 95% CI: 6.65‐8.10, p<0.001). Among patients with a recent diagnosis of a mental disorder, African Americans had higher odds of COVID‐19 infection than Caucasians, with the strongest ethnic disparity for depression (AOR=3.78, 95% CI: 3.58‐3.98, p<0.001). Women with mental disorders had higher odds of COVID‐19 infection than males, with the strongest gender disparity for ADHD (AOR=2.03, 95% CI: 1.73‐2.39, p<0.001). Patients with both a recent diagnosis of a mental disorder and COVID‐19 infection had a death rate of 8.5% (vs. 4.7% among COVID‐19 patients with no mental disorder, p<0.001) and a hospitalization rate of 27.4% (vs. 18.6% among COVID‐19 patients with no mental disorder, p<0.001). These findings identify individuals with a recent diagnosis of a mental disorder as being at increased risk for COVID‐19 infection, which is further exacerbated among African Americans and women, and as having a higher frequency of some adverse outcomes of the infection. This evidence highlights the need to identify and address modifiable vulnerability factors for COVID‐19 infection and to prevent delays in health care provision in this population.

The global pandemic of COVID-19 is colliding with the epidemic of opioid use disorders (OUD) and other substance use disorders (SUD) in the United States (US). Currently, there is limited data on risks, disparity, and outcomes for COVID-19 in individuals suffering from SUD. This is a retrospective case-control study of electronic health records (EHRs) data of 73,099,850 unique patients, of whom 12,030 had a diagnosis of COVID-19. Patients with a recent diagnosis of SUD (within past year) were at significantly increased risk for COVID-19 (adjusted odds ratio or AOR = 8.699 [8.411-8.997], P < 10 −30), an effect that was strongest for individuals with OUD (AOR = 10.244 [9.107-11.524], P < 10 −30), followed by individuals with tobacco use disorder (TUD) (AOR = 8.222 ([7.925-8.530], P < 10 −30). Compared to patients without SUD, patients with SUD had significantly higher prevalence of chronic kidney, liver, lung diseases, cardiovascular diseases, type 2 diabetes, obesity and cancer. Among patients with recent diagnosis of SUD, African Americans had significantly higher risk of COVID-19 than Caucasians (AOR = 2.173 [2.01-2.349],

IMPORTANCE Patients with specific cancers may be at higher risk than those without cancer for coronavirus disease 2019 and its severe outcomes. At present, limited data are available on the risk, racial disparity, and outcomes for COVID-19 illness in patients with cancer.OBJECTIVES To investigate how patients with specific types of cancer are at risk for COVID-19 infection and its adverse outcomes and whether there are cancer-specific race disparities for COVID-19 infection. DESIGN, SETTING, AND PARTICIPANTSThis retrospective case-control analysis of patient electronic health records included 73.4 million patients from 360 hospitals and 317 000 clinicians across 50 US states to August 14, 2020. The odds of COVID-19 infections for 13 common cancer types and adverse outcomes were assessed.EXPOSURES The exposure groups were patients diagnosed with a specific cancer, whereas the unexposed groups were patients without the specific cancer. MAIN OUTCOMES AND MEASURESThe adjusted odds ratio (aOR) and 95% CI were estimated using the Cochran-Mantel-Haenszel test for the risk of COVID-19 infection. RESULTS Among the 73.4 million patients included in the analysis (53.6% female), 2 523 920 had at least 1 of the 13 common cancers diagnosed (all cancer diagnosed within or before the last year), and 273 140 had recent cancer (cancer diagnosed within the last year). Among 16 570 patients diagnosed with COVID-19, 1200 had a cancer diagnosis and 690 had a recent cancer diagnosis of at least 1 of the 13 common cancers. Those with recent cancer diagnosis were at significantly increased risk for COVID-19 infection (aOR, 7.14 [95% CI, 6.91-7.39]; P < .001), with the strongest association for recently diagnosed leukemia (aOR, 12.16 [95% CI, 11.03-13.40]; P < .001), non-Hodgkin lymphoma (aOR, 8.54 [95% CI,; P < .001), and lung cancer (aOR, 7.66 [95% CI,]; P < .001) and weakest for thyroid cancer (aOR, 3.10 [95% CI,; P < .001). Among patients with recent cancer diagnosis, African Americans had a significantly higher risk for COVID-19 infection than White patients; this racial disparity was largest for breast cancer (aOR, 5.44 [95% CI,]; P < .001), followed by prostate cancer (aOR, 5.10 [95% CI,]; P < .001), colorectal cancer (aOR, 3.30 [95% CI,; P < .001), and lung cancer (aOR, 2.53 [95% CI,; P < .001). Patients with cancer and COVID-19 had significantly worse outcomes (hospitalization, 47.46%; death, 14.93%) than patients with COVID-19 without cancer (hospitalization, 24.26%; death, 5.26%) (P < .001) and patients with cancer without COVID-19 (hospitalization, 12.39%; death, 4.03%) (P < .001). CONCLUSIONS AND RELEVANCEIn this case-control study, patients with cancer were at significantly increased risk for COVID-19 infection and worse outcomes, which was further exacerbated among African Americans. These findings highlight the need to protect and monitor patients with cancer as part of the strategy to control the pandemic.

Despite the widespread use of vaccinia virus (VV) as a vector for other Ags and as the smallpox vaccine, there is little information available about the protective components of the immune response following VV infection. In this study, protection against wild-type VV was evaluated in mice with respect to the relative contributions of CD8+ T cells vs that of CD4+ T cells and Ab. C57BL/6 mice primed with the Western Reserve strain of VV mount significant IgM and IgG Ab responses, specific cytotoxic T cell responses, IFN-γ responses in CD4+ and CD8+ T cells, and effectively clear the virus. This protection was abrogated by in vivo depletion of CD4+ T cells or B cells in IgH−/− mice, but was not sensitive to CD8+ T cell depletion alone. However, a role for CD8+ T cells in primary protection was demonstrated in MHC class II−/− mice, where depleting CD8+ T cells lead to increase severity of disease. Unlike control MHC class II−/− mice, the group depleted of CD8+ T cells developed skin lesions on the tail and feet and had adrenal necrosis. Adoptive transfer experiments also show CD8+ T cells can mediate protective memory. These results collectively show that both CD4+ and CD8+ T cell-mediated immunity can contribute to protection against VV infection. However, CD4+ T cell-dependent anti-virus Ab production plays a more important role in clearing virus following acute infection, while in the absence of Ab, CD8+ T cells can contribute to protection against disease.

Introduction At present, there is limited data on the risks, disparity, and outcomes for COVID‐19 in patients with dementia in the United States. Methods This is a retrospective case‐control analysis of patient electronic health records (EHRs) of 61.9 million adult and senior patients (age ≥ 18 years) in the United States up to August 21, 2020. Results Patients with dementia were at increased risk for COVID‐19 compared to patients without dementia (adjusted odds ratio [AOR]: 2.00 [95% confidence interval (CI), 1.94–2.06], P < .001), with the strongest effect for vascular dementia (AOR: 3.17 [95% CI, 2.97–3.37], P < .001), followed by presenile dementia (AOR: 2.62 [95% CI, 2.28–3.00], P < .001), Alzheimer's disease (AOR: 1.86 [95% CI, 1.77–1.96], P < .001), senile dementia (AOR: 1.99 [95% CI, 1.86–2.13], P < .001) and post‐traumatic dementia (AOR: 1.67 [95% CI, 1.51–1.86] P < .001). Blacks with dementia had higher risk of COVID‐19 than Whites (AOR: 2.86 [95% CI, 2.67–3.06], P < .001). The 6‐month mortality and hospitalization risks in patients with dementia and COVID‐19 were 20.99% and 59.26%, respectively. Discussion These findings highlight the need to protect patients with dementia as part of the strategy to control the COVID‐19 pandemic.

Predictions for charged hadron, identified light hadron, quarkonium, photon, jet and gauge bosons in p+ Pb collisions at [Formula: see text] are compiled and compared. When test run data are available, they are compared to the model predictions.

T cell activation and function are critically regulated by positive and negative costimulatory molecules. Aberrant expression and function of costimulatory molecules have been associated with persistent activation of self-reactive T cells in autoimmune diseases such as rheumatoid arthritis (RA). In this study, initial analysis of costimulatory molecules led to the unexpected observation that, in addition to CD80, several negative regulators (e.g., CTLA-4, programmed death-1 (PD-1), and PD ligand-1) were overexpressed in synovial T cells and macrophages derived from RA patients as opposed to controls. The expression of CD80 and PD ligand-1 on monocytes could be induced in vitro by IFN-γ and TNF-α that were produced abundantly in RA-derived synovial fluid (SF). Furthermore, the soluble form of negative costimulatory molecules occurred at high concentrations in sera and SF of RA patients and correlated with titers of rheumatoid factor in RA patients. In particular, the levels of soluble PD-1 were found to correlate significantly with those of TNF-α in SF derived from RA patients. Detailed characterization of soluble PD-1 revealed that it corresponded to an alternative splice variant (PD-1Δex3) and could functionally block the regulatory effect of membrane-bound PD-1 on T cell activation. Our data indicate a novel pathogenic pathway in which overexpression of negative costimulatory molecules to restrict synovial inflammation in RA is overruled by the excessive production of soluble costimulatory molecules.

Background The Omicron SARS-CoV-2 variant is rapidly spreading in the US since December 2021 and is more contagious than earlier variants. Currently, data on the severity of the disease caused by the Omicron variant compared with the Delta variant is limited. Here we compared 3-day risks of emergency department (ED) visit, hospitalization, intensive care unit (ICU) admission, and mechanical ventilation in patients who were first infected during a time period when the Omicron variant was emerging to those in patients who were first infected when the Delta variant was predominant. Method This is a retrospective cohort study of electronic health record (EHR) data of 577,938 first-time SARS-CoV-2 infected patients from a multicenter, nationwide database in the US during 9/1/2021-12/24/2021, including 14,054 who had their first infection during the 12/15/2021-12/24/2021 period when the Omicron variant emerged (Emergent Omicron cohort) and 563,884 who had their first infection during the 9/1/2021-12/15/2021 period when the Delta variant was predominant (Delta cohort). After propensity-score matching the cohorts, the 3-day risks of four outcomes (ED visit, hospitalization, ICU admission, and mechanical ventilation) were compared. Risk ratios, and 95% confidence intervals (CI) were calculated. Results Of 14,054 patients in the Emergent Omicron cohort (average age, 36.4), 27.7% were pediatric patients (<18 years old), 55.4% female, 1.8% Asian, 17.1% Black, 4.8% Hispanic, and 57.3% White. The Emergent Omicron cohort differed significantly from the Delta cohort in demographics, comorbidities, and socio-economic determinants of health. After propensity-score matching for demographics, socio-economic determinants of health, comorbidities, medications and vaccination status, the 3-day risks in the Emergent Omicron cohort outcomes were consistently less than half those in the Delta cohort: ED visit: 4.55% vs. 15.22% (risk ratio or RR: 0.30, 95% CI: 0.28-0.33); hospitalization: 1.75% vs. 3.95% (RR: 0.44, 95% CI: 0.38-0.52]); ICU admission: 0.26% vs. 0.78% (RR: 0.33, 95% CI:0.23-0.48); mechanical ventilation: 0.07% vs. 0.43% (RR: 0.16, 95% CI: 0.08-0.32). In children under 5 years old, the overall risks of ED visits and hospitalization in the Emergent Omicron cohort were 3.89% and 0.96% respectively, significantly lower than 21.01% and 2.65% in the matched Delta cohort (RR for ED visit: 0.19, 95% CI: 0.14-0.25; RR for hospitalization: 0.36, 95% CI: 0.19-0.68). Similar trends were observed for other pediatric age groups (5-11, 12-17 years), adults (18-64 years) and older adults (>= 65 years). Conclusions First time SARS-CoV-2 infections occurring at a time when the Omicron variant was rapidly spreading were associated with significantly less severe outcomes than first-time infections when the Delta variant predominated.