Influenza vaccine effectiveness among outpatients in the US Influenza Vaccine Effectiveness Network by study site 2011‐2016

BackgroundInfluenza vaccination is recommended for all US residents aged ≥6 months. Vaccine effectiveness (VE) varies by age, circulating influenza strains, and the presence of high‐risk medical conditions. We examined site‐specific VE in the US Influenza VE Network, which evaluates annual influenza VE at ambulatory clinics in geographically diverse sites.MethodsAnalyses were conducted on 27 180 outpatients ≥6 months old presenting with an acute respiratory infection (ARI) with cough of ≤7‐day duration during the 2011‐2016 influenza seasons. A test‐negative design was used with vaccination status defined as receipt of ≥1 dose of any influenza vaccine according to medical records, registries, and/or self‐report. Influenza infection was determined by reverse‐transcription polymerase chain reaction. VE estimates were calculated using odds ratios from multivariable logistic regression models adjusted for age, sex, race/ethnicity, time from illness onset to enrollment, high‐risk conditions, calendar time, and vaccination status‐site interaction.ResultsFor all sites combined, VE was statistically significant every season against all influenza and against the predominant circulating strains (VE = 19%‐50%) Few differences among four sites in the US Flu VE Network were evident in five seasons. However, in 2015‐16, overall VE in one site was 24% (95% CI = −4%‐44%), while VE in two other sites was significantly higher (61%, 95% CI = 49%‐71%; P = .002, and 53%, 95% CI = 33,67; P = .034).ConclusionWith few exceptions, site‐specific VE estimates aligned with each other and overall VE estimates. Observed VE may reflect inherent differences in community characteristics of the sites and highlights the importance of diverse settings for studying influenza vaccine effectiveness.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155981/1/irv12741_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155981/2/irv12741.pd

Immune complex-mediated co-ligation of the BCR with FcγRIIB results in homeostatic apoptosis of B cells involving Fas signalling that is defective in the MRL/Lpr model of systemic lupus erythematosus

Negative regulation of B cell activation by cognate immune complexes plays an important homeostatic role in suppressing B cell hyperactivity and preventing consequent autoimmunity. Immune complexes co-ligate the BCR and FcγRIIB resulting in both growth arrest and apoptosis. We now show that such apoptotic signalling involves induction and activation of p53 and its target genes, the pro-apoptotic Bcl-2 family members, Bad and Bid, as well as nuclear export of p53. Collectively, these events result in destabilisation of the mitochondrial and lysosomal compartments with consequent activation and interplay of executioner caspases and endosomal-derived proteases. In addition, the upregulation of Fas and FasL with consequent activation of caspase 8-dependent death receptor signalling is required to facilitate efficient apoptosis of B cells. Consistent with this role for Fas death receptor signalling, apoptosis resulting from co-ligation of the BCR and FcγRIIB is defective in B cells from Fas-deficient MRL/MpJ-Faslpr mice. As these mice develop spontaneous, immune complex-driven lupus-like glomerulonephritis, targeting this FcγRIIB-mediated apoptotic pathway may therefore have novel therapeutic implications for systemic autoimmune disease

Physical health and mental health functional status during and following hospitalization for an acute respiratory illness

Background: Influenza is a serious respiratory illness causing thousands of hospitalizations annually. This study used the Short Form 12 (SF-12) to evaluate physical and mental health status during and post hospitalization for an acute respiratory illness (ARI). Methods: Adults ≥18 years of age enrolled in the Hospitalized Adult Influenza Vaccine Effectiveness Network study – Pittsburgh site in the 2017–2018 and 2018–2019 influenza seasons with an ARI with cough of ≤10 days’ duration were eligible. Enrollees were included regardless of respiratory pathogen identified by respiratory viral panel testing of nasopharyngeal specimens. Respondents completed the SF-12 at enrollment and 3–14 weeks later. Respondents were grouped using discriminant cluster analysis based on SF-12 individual scores and age. Linear regression was used to predict convalescent physical and mental health composite scores. Results: Of 72 enrollees who completed both surveys, 35 were grouped as the high functioning group (HFG), 12 as the low functioning group (LFG) and 25 as the medium functioning group (MFG). At enrollment, the LFG more frequently reported body aches and confusion, lower pre-illness physical activity levels and other measures of physical function than the HFG (P < 0.016). At approximately 5 weeks post enrollment, the HFG reported significant decrements in most SF-12 individual scores and overall physical health (−4.26 ± 8.1; P = 0.017) and mental health (−5.98 ± 10.5; P = 0.011) composite scores. Changes in mental but not physical composite scores from enrollment to convalescence differed significantly (P = 0.016) between HFG and LFG. Conclusions: Although their enrollment and convalescent SF-12 scores were higher, HFG reported larger losses in mental function during an ARI hospitalization than groups with lower enrollment SF-12 scores

Proposed clinical indicators for efficient screening and testing for COVID-19 infection using Classification and Regression Trees (CART) analysis

The introduction and rapid transmission of SARS-CoV-2 in the United States resulted in methods to assess, mitigate, and contain the resulting COVID-19 disease derived from limited knowledge. Screening for testing has been based on symptoms typically observed in inpatients, yet outpatient symptoms may differ. Classification and regression trees recursive partitioning created a decision tree classifying participants into laboratory-confirmed cases and non-cases. Demographic and symptom data from patients ages 18–87 years enrolled from March 29–June 8, 2020 were included. Presence or absence of SARS-CoV-2 was the target variable. Of 832 tested, 77 (9.3%) tested positive. Cases significantly more often reported diarrhea (12 percentage points (PP)), fever (15 PP), nausea/vomiting (9 PP), loss of taste/smell (52 PP), and contact with a COVID-19 case (54 PP), but less frequently reported sore throat (−27 PP). The 4-terminal node optimal tree had sensitivity of 69%, specificity of 78%, positive predictive value of 20%, negative predictive value of 97%, and AUC of 76%. Among those referred for testing, negative responses to two questions could classify about half (49%) of tested persons with low risk for SARS-CoV-2 and would save limited testing resources. Outpatient symptoms of COVID-19 appear to be broader than the inpatient syndrome. Initial supplies of anticipated COVID-19 vaccines may be limited and administration of first such available vaccines may need to be prioritized for essential workers, the most vulnerable, or those likely to have a robust response to vaccine. Another priority group could be those not previously infected. Those who screen out of testing may be less likely to have been infected by SARS-CoV-2 virus thus may be prioritized for vaccination when supplies are limited

Effect of mild COVID-19 on health-related quality of life

Background: Little is known about the effects of a mild SARS-CoV-2 infection on health-related quality of life. Methods: This prospective observational study of symptomatic adults (18–87 years) who sought outpatient care for an acute respiratory illness, was conducted from 3/30/2020 to 4/30/2021. Participants completed the Short Form Health Survey (SF-12) at enrollment and 6–8 weeks later, to report their physical and mental health function levels as measured by the physical health and mental health composite scores (PHC and MHC, respectively). PHC and MHC scores for COVID-19 cases and non-COVID cases were compared using t-tests. Multivariable regression modeling was used to determine predictors of physical and mental health function at follow-up. Results: Of 2301 enrollees, 426 COVID-19 cases and 547 non-COVID cases completed both surveys. PHC improved significantly from enrollment to follow-up for both COVID-19 cases (5.4 ± 0.41; P < 0.001) and non-COVID cases (3.3 ± 0.32; P < 0.001); whereas MHC improved significantly for COVID-19 cases (1.4 ± 0.51; P < 0.001) and decreased significantly for non-COVID cases (−0.8 ± 0.37; P < 0.05). Adjusting for enrollment PHC, the most important predictors of PHC at follow-up included male sex (β = 1.17; SE = 0.5; P = 0.021), having COVID-19 (β = 1.99; SE = 0.54; P < 0.001); and non-white race (β = −2.01; SE = 0.70; P = 0.004). Adjusting for enrollment MHC, the most important predictors of MHC at follow-up included male sex (β = 1.92; SE = 0.63; P = 0.002) and having COVID-19 (β = 2.42; SE = 0.67; P < 0.001). Conclusion: Both COVID-19 cases and non-COVID cases reported improved physical health function at 6–8 weeks’ convalescence; whereas mental health function improved among COVID-19 cases but declined among non-COVID cases. Both physical and mental health functioning were significantly better among males with COVID-19 than females

International Society of Cardiovascular Infectious Diseases Guidelines for the Diagnosis, Treatment and Prevention of Disseminated Mycobacterium chimaera Infection Following Cardiac Surgery with Cardiopulmonary Bypass.

Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and and there is a growing need for a consensus-based expert opinion to provide international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectious Diseases (ISCVID) covers aspects of prevention (field of hospital epidemiology), clinical management (infectious disease specialists, cardiac surgeons, ophthalmologists, others), laboratory diagnostics (microbiologists, molecular diagnostics), device management (perfusionists, cardiac surgeons) and public health aspects

The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified &gt;300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection