High Risk For Severe Disease Research Articles

Pharmacovigilance of Drug-Drug Interactions with Nirmatrelvir/Ritonavir.

Nirmatrelvir/ritonavir (NMV/r) is approved in the United States (US) and more than 70 other countries for the treatment of mild to moderate COVID-19 in nonhospitalized adults at high risk for severe disease. Because ritonavir inhibits several drug metabolizing enzymes, potential drug-drug interactions (DDIs) between ritonavir and concomitant medications are an important consideration for prescribers. Here, we conducted a real-world analysis of data from Pfizer's global safety database regarding adverse events (AEs) reported during use of NMV/r concomitantly with potentially interacting drugs. Data were extracted regarding DDI cases occurring from the start of NMV/r authorization through October 31, 2023. Results regarding concomitant treatment, specific AEs, and clinical outcomes are summarized. Overall NMV/r exposure was estimated based on packs of medication dispensed and was used to calculate reporting rates. Among 19,617,670 patients exposed globally to NMV/r, 966 cases of potential DDIs were reported. Of these, 594 occurred in the US against an estimated US exposure of 14,646,990 patients, representing a reporting rate of 0.004%. Globally and in the United States, 66.8% and 77.3% of cases, respectively, were nonserious. Simvastatin and tacrolimus were the most frequently reported drugs associated with potential DDIs, and the most frequently reported AE regarding a specific event or symptom was dysgeusia (altered sense of taste), an AE known to be associated with NMV/r. Low reporting rates of DDIs support the potential for NMV/r treatment to be safely managed with careful use of available drug interaction resources to aid in risk mitigation.

Respiratory Syncytial Virus among People Living with HIV: Is There a Case for Rolling Out Prophylaxis? A Viewpoint Based on a Systematic Review.

Respiratory Syncytial Virus (RSV) is responsible for a considerable burden of respiratory disease among children and older adults. Several prophylactic strategies have recently been introduced. We review the available evidence on the interplay between RSV infection and HIV, looking at the specific role of RSV prophylactic strategies in individuals affected by or exposed to HIV. We conducted a systematic review on the association between HIV infection and RSV incidence and severity. We searched in PubMed/MEDLINE for clinical epidemiological studies covering outcomes such as RSV-associated illness, severity, and mortality in individuals affected by or exposed to HIV. A total of 36 studies met the inclusion criteria and were included, the majority conducted in sub-Saharan Africa. There was no compelling evidence suggesting a higher incidence of RSV illness among HIV-infected people. A higher risk of severe disease was consistent among both HIV-positive and HIV-exposed but uninfected (HEU) children. Case fatality rates were also higher for these groups. Evidence on a differing risk among adults was scarce. HIV-positive pregnant women should be given priority for recently approved RSV vaccination, for protection of their newborns. HIV-infected and HEU infants should be considered risk groups for nirsevimab prophylaxis in their first year of life and possibly beyond.

Pertussis Epidemiology in Children: The Role of Maternal Immunization.

In the last twelve months, a significant global increase in pertussis cases has been observed, particularly among infants under three months of age. This age group is at the highest risk for severe disease, hospitalization, and death. Maternal immunization with the Tdap vaccine during pregnancy has been recommended to protect newborns by transferring maternal antibodies transplacentally. This review examines the current epidemiology of pertussis, the importance of preventing it in young children, and the effectiveness of maternal immunization. Despite the proven benefits of maternal vaccination, which has been found effective in pertussis prevention in up to 90% of cases, coverage remains suboptimal in many countries. Factors contributing to low vaccination rates include vaccine hesitancy due to low trust in health authority assessments, safety concerns, practical barriers to vaccine access, and the impact of the COVID-19 pandemic, which disrupted routine vaccination services. The recent increase in pertussis cases may also be influenced by the natural cyclic nature of the disease, increased Bordetella pertussis (Bp) activity in older children and adults, and the genetic divergence of circulating Bp strains from vaccine antigens. Given the high efficacy of maternal vaccination in preventing pertussis in infants, increasing coverage rates is crucial. Efforts to improve vaccine uptake should address barriers to access and vaccine hesitancy, ensuring consistent immune protection for the youngest and most vulnerable populations. Enhanced maternal vaccination could significantly reduce the incidence of whooping cough in infants, decreasing related hospitalizations and deaths.

US Real-World Effectiveness Study of Nirmatrelvir/Ritonavir in Preventing Hospitalization of High-Risk COVID-19 Patients

PurposeWe describe nirmatrelvir/ritonavir (NMV/r) effectiveness in preventing hospitalization among COVID-19 patients at high risk of severe disease. MethodsAn ongoing US population-based observational cohort study with retrospective and prospective collection of national electronic healthcare data collected from the US Optum® deidentified COVID-19 Electronic Health Record dataset during December 22, 2021−July 20, 2022. Participants were ≥12 years old; had a positive SARS-CoV-2 test, COVID-19 diagnosis, or NMV/r prescription; and were at high risk of severe COVID-19 based on demographic/clinical characteristics. Potential confounders between groups were balanced using propensity score matching. Immortal time bias was addressed. Hospitalization rates within 30 days from COVID-19 diagnosis were evaluated. Sensitivity analyses included 15-day hospitalization, chart review to investigate incidental hospitalization effects, and exclusion of patients identified as having COVID-19 based on NMV/r prescription alone. Outcomes were also evaluated by race, age, and COVID-19 vaccine status. FindingsOverall, 12,440 and 234,123 patients were included in the NMV/r and non-NMV/r groups, respectively. After propensity score matching, baseline characteristics were well balanced across groups (NMV/r, n = 12,439; non-NMV/r, n = 36,490). Incidence of hospitalization (95% CI) within 30 days was 0.90% (0.74%−1.08%) for the NMV/r group and 5.91% (5.67%−6.16%) for the non-NMV/r group, with relative risk (95% CI) of 0.15 (0.13−0.18; 85% risk reduction). NMV/r was comparably effective in Black patients (relative risk, 0.19 [0.10−0.34]; 81% risk reduction). Sensitivity analyses supported the main outcomes. ImplicationsReal-world NMV/r effectiveness against hospitalization during Omicron predominance among COVID-19 patients at high risk of severe disease supports demonstrated clinical trial efficacy. Black patients underutilized NMV/r despite high effectiveness.

Long-standing COVID-19 Disease in Immunocompromised and Immunocompetent Patients; Case Reports and Literature Review.

Patients with immunodeficiency are at higher risk of severe disease and death following SARS-CoV-2 infection compared to the general population. Here, we describe humoral and cellular immune responses in 5 patients with immunodeficiency, 2 patients with multiple sclerosis, 1 patient with chronic lymphocytic leukemia (CLL), 1 patient with Good's syndrome, and 1Human Immunodeficiency Virus (HIV) positive with developed Acquired immunodeficiency syndrome (AIDS)- patient. T-cell responses were evaluated using the QuantiFERON SARS-CoV-2 assay following incubation with the SARS-CoV-2 Ag1, Ag2, and Ag3 viral antigens. Immunophenotyping of CD4+ and CD8+ T cells and CD19+ and CD20+ B cells was determined by flow cytometry. All studied immunocompromised patients or those with acquired immune dysregulation patients showed reduced cellular immune responses (release of interferon (IFN)-g) to SARS-CoV-2 antigens than healthy controls [patients; Ag1, Ag2 and Ag3 and Nil (Median 5-95% percentile) (12 (1-95), 12 (1.5-78), 13.5 (12-95) and 3 (1-98) U/mL)], controls; Ag1, Ag2 and Ag3 and Nil (Median 5-95% percentile) 24.5 (7-89), 65 (31-173), 53.5 (13-71.5) and 3 (1-14) U/mL)]. The frequency of peripheral blood B cells was also reduced in these patients compared to healthy control subjects. T-cell-dependent antibody responses require the activation of B cells by helper T cells. Reduced B cell numbers in immunocompromised patients infected with SARS-CoV-2 indicate the need for these patients to take additional precautions to prevent COVID-19 infection.

Disease severity in subsequent pregnancies with RhD immunization: A nationwide cohort.

To evaluate the severity of haemolytic disease of the foetus and newborn (HDFN) in subsequent pregnancies with RhD immunization and to identify predictive factors for severe disease. Nationwide prospective cohort study, including all pregnant women with RhD antibodies. All women with at least two pregnancies with RhD antibodies and RhD-positive foetuses were selected. The main outcome measure was the severity of HDFN in the first and subsequent pregnancy at risk. A subgroup analysis was performed for the group of women where RhD antibodies developed after giving birth to an RhD-positive child and thus after receiving anti-D at least twice (group A) or during the first pregnancy at risk for immunization (group B). Sixty-two RhD immunized women with a total of 150 RhD-positive children were included. The severity of HDFN increased for the whole group significantly in the subsequent pregnancy (p < 0.001), although it remained equal or even decreased in 44% of women. When antibodies were already detected at first trimester screening in the first immunized pregnancy, after giving birth to an RhD-positive child (group A), severe HDFN in the next pregnancy was uncommon (22%). Especially when no therapy or only non-intensive phototherapy was indicated during the first immunized pregnancy (6%) or if the antibody-dependent cell-mediated cytotoxicity result remained <10%. Contrarily, women with a negative first trimester screening and RhD antibodies detected later during the first pregnancy of an RhD-positive child (group B), often before they had ever received anti-D prophylaxis, were most prone for severe disease in a subsequent pregnancy (48%). RhD-mediated HDFN in a subsequent pregnancy is generally more severe than in the first pregnancy at risk and can be estimated using moment of antibody detection and severity in the first immunized pregnancy. Women developing antibodies in their first pregnancy of an RhD-positive child are at highest risk of severe disease in the next pregnancy.

Antivirals for post-exposure prophylaxis of influenza: a systematic review and network meta-analysis

Antiviral post-exposure prophylaxis with neuraminidase inhibitors can reduce the incidence of influenza and the risk of symptomatic influenza, but the efficacy of the other classes of antiviral remains unclear. To support an update of WHO influenza guidelines, this systematic review and network meta-analysis evaluated antiviral drugs for post-exposure prophylaxis of influenza. We systematically searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Global Health, Epistemonikos, and ClinicalTrials.gov for randomised controlled trials published up to Sept 20, 2023 that evaluated the efficacy and safety of antivirals compared with another antiviral or placebo or standard care for prevention of influenza. Pairs of reviewers independently screened studies, extracted data, and assessed the risk of bias. We performed network meta-analyses with frequentist random effects model and assessed the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. The outcomes of interest were symptomatic or asymptomatic infection, admission to hospital, all-cause mortality, adverse events related to antivirals, and serious adverse events. This study is registered with PROSPERO, CRD42023466450. Of 11 845 records identified by our search, 33 trials of six antivirals (zanamivir, oseltamivir, laninamivir, baloxavir, amantadine, and rimantadine) that enrolled 19 096 individuals (mean age 6·75-81·15 years) were included in this systematic review and network meta-analysis. Most of the studies were rated as having a low risk of bias. Zanamivir, oseltamivir, laninamivir, and baloxavir probably achieve important reductions in symptomatic influenza in individuals at high risk of severe disease (zanamivir: risk ratio 0·35, 95% CI 0·25-0·50; oseltamivir: 0·40, 0·26-0·62; laninamivir: 0·43, 0·30-0·63; baloxavir: 0·43, 0·23-0·79; moderate certainty) when given promptly (eg, within 48 h) after exposure to seasonal influenza. These antivirals probably do not achieve important reductions in symptomatic influenza in individuals at low risk of severe disease when given promptly after exposure to seasonal influenza (moderate certainty). Zanamivir, oseltamivir, laninamivir, and baloxavir might achieve important reductions in symptomatic zoonotic influenza in individuals exposed to novel influenza A viruses associated with severe disease in infected humans when given promptly after exposure (low certainty). Oseltamivir, laninamivir, baloxavir, and amantadine probably decrease the risk of all influenza (symptomatic and asymptomatic infection; moderate certainty). Zanamivir, oseltamivir, laninamivir, and baloxavir probably have little or no effect on prevention of asymptomatic influenza virus infection or all-cause mortality (high or moderate certainty). Oseltamivir probably has little or no effect on admission to hospital (moderate certainty). All six antivirals do not significantly increase the incidence of drug-related adverse events or serious adverse events, although the certainty of evidence varies. Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir probably decreases the risk of symptomatic seasonal influenza in individuals at high risk for severe disease after exposure to seasonal influenza viruses. Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir might reduce the risk of symptomatic zoonotic influenza after exposure to novel influenza A viruses associated with severe disease in infected humans. World Health Organization.

Effects of gonadectomy on the incidence rate of babesiosis and the risk of severe babesiosis in dogs aged 6 months and older at a veterinary academic hospital in South Africa: A case-control and retrospective cohort study

Gonadectomy in dogs is associated with changes in risks of a variety of non-infectious health conditions, but few studies have examined its effects on infectious disease outcomes. The objectives of our study were to estimate the causal effect of gonadectomy on the incidence rate of babesiosis diagnosis, and on the risk of severe babesiosis in diagnosed cases, in dogs 6 months and older seen at a veterinary academic hospital in South Africa from 2013 through 2020. To estimate the effect of gonadectomy on the incidence rate of babesiosis diagnosis in dogs, we conducted a case-control study with incidence density sampling of dogs seen through the hospital’s primary care service, adjusting for sex, age, breed category and weight. We identified 811 cases and selected 3244 time-matched controls. To estimate the effect of gonadectomy on disease severity in dogs with babesiosis, we conducted a retrospective cohort study among all dogs with a diagnosis of babesiosis (n=923), including these 811 cases and a further 112 referred to the hospital, also adjusting for sex, age, breed category and weight. Gonadectomy substantially reduced the incidence rate of babesiosis (total effect incidence rate ratio [IRR] 0.5; 95 % confidence interval [CI] 0.41–0.60) and the risk of severe babesiosis among diagnosed dogs (total effect risk ratio [RR] 0.72; 95 % CI 0.60–0.86). Tipping point sensitivity analysis shows that these effect estimates are robust to unmeasured confounding bias. There was no evidence for modification of the effect of gonadectomy by sex, with effect estimates qualitatively similar for males and females for both outcomes. Compared to females, males had a higher incidence rate of babesiosis (IRR 1.74; 95 % CI 1.49–2.04) and a higher risk of severe disease (RR 1.12; 95 % CI 0.98–1.28). In conclusion, our study shows a robust protective effect of gonadectomy on the incidence and severity of babesiosis in both male and female dogs 6 months of age and older, and contributes important evidence to the debate on the overall risks and benefits of gonadectomy to dogs in this population.

Evaluation of Oxidative Stress and Endothelial Dysfunction in COVID-19 Patients.

Background and Objectives: Heat shock proteins (HSPs) are stress proteins. The endogenous nitric oxide (NO) synthase inhibitor asymmetric dimethyl arginine (ADMA) is a mediator of endothelial dysfunction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causes endothelial dysfunction and coagulopathy through severe inflammation and oxidative stress. Using these markers, we analyzed the prognostic value of serum ADMA and HSP-90 levels for early prediction of severe coronavirus disease (COVID-19) patients. Materials and Methods: A total of 76 COVID-19 patients and 35 healthy control subjects were included in this case-control study. COVID-19 patients were divided into two groups: mild and severe. Results: Serum ADMA and HSP-90 levels were significantly higher in the COVID-19 patients compared to the control subjects (p < 0.001). Additionally, serum ADMA and HSP-90 levels were determined to be higher in a statistically significant way in severe COVID-19 compared to mild COVID-19 (p < 0.001). Univariable logistic regression analysis revealed that ADMA and HSP-90, respectively, were independent predictors of severe disease in COVID-19 patients (ADMA (OR = 1.099, 95% CI = 1.048-1.152, p < 0.001) and HSP-90 (OR = 5.296, 95% CI = 1.719-16.316, p = 0.004)). When the cut-off value for ADMA was determined as 208.94 for the prediction of the severity of COVID-19 patients, the sensitivity was 72.9% and the specificity was 100% (AUC = 0.938, 95%CI = 0.858-0.981, p < 0.001). When the cut-off value for HSP-90 was determined as 12.68 for the prediction of the severity of COVID-19 patients, the sensitivity was 88.1% and the specificity was 100% (AUC = 0.975, 95% CI= 0.910-0.997, p < 0.001). Conclusions: Increased levels of Heat shock proteins-90 (HSP-90) and ADMA were positively correlated with increased endothelial damage in COVID-19 patients, suggesting that treatments focused on preventing and improving endothelial dysfunction could significantly improve the outcomes and reduce the mortality rate of COVID-19. ADMA and HSP-90 might be simple, useful, and prognostic biomarkers that can be utilized to predict patients who are at high risk of severe disease due to COVID-19.

Effectiveness of mRNA COVID-19 Vaccines as First Booster Doses in England: An Observational Study in OpenSAFELY-TPP.

The UK delivered its first "booster" COVID-19 vaccine doses in September 2021, initially to individuals at high risk of severe disease, then to all adults. The BNT162b2 Pfizer-BioNTech vaccine was used initially, then also Moderna mRNA-1273. With the approval of the National Health Service England, we used routine clinical data to estimate the effectiveness of boosting with BNT162b2 or mRNA-1273 compared with no boosting in eligible adults who had received two primary course vaccine doses. We matched each booster recipient with an unboosted control on factors relating to booster priority status and prior COVID-19 immunization. We adjusted for additional factors in Cox models, estimating hazard ratios up to 182 days (6 months) following booster dose. We estimated hazard ratios overall and within the following periods: 1-14, 15-42, 43-69, 70-97, 98-126, 127-152, and 155-182 days. Outcomes included a positive SARS-CoV-2 test, COVID-19 hospitalization, COVID-19 death, non-COVID-19 death, and fracture. We matched 8,198,643 booster recipients with unboosted controls. Adjusted hazard ratios over 6-month follow-up were: positive SARS-CoV-2 test 0.75 (0.74, 0.75); COVID-19 hospitalization 0.30 (0.29, 0.31); COVID-19 death 0.11 (0.10, 0.14); non-COVID-19 death 0.22 (0.21, 0.23); and fracture 0.77 (0.75, 0.78). Estimated effectiveness of booster vaccines against severe COVID-19-related outcomes peaked during the first 3 months following the booster dose. By 6 months, the cumulative incidence of positive SARS-CoV-2 test was higher in boosted than unboosted individuals. We estimate that COVID-19 booster vaccination, compared with no booster vaccination, provided substantial protection against COVID-19 hospitalization and COVID-19 death but only limited protection against positive SARS-CoV-2 test. Lower rates of fracture in boosted than unboosted individuals may suggest unmeasured confounding. Observational studies should report estimated vaccine effectiveness against nontarget and negative control outcomes.

Pharmacokinetics and Safety of Remdesivir in Pregnant and Nonpregnant Women With COVID-19: Results From IMPAACT 2032.

Pregnant people with coronavirus disease 2019 (COVID-19) experience higher risk for severe disease and adverse pregnancy outcomes, but no pharmacokinetic (PK) data exist to support dosing of COVID-19 therapeutics during pregnancy. We report PK and safety data for intravenous remdesivir in pregnancy. IMPAACT 2032 was a phase 4 prospective, open-label, nonrandomized opportunistic study of hospitalized pregnant and nonpregnant women receiving intravenous remdesivir as part of clinical care. Intensive PK sampling was performed on infusion days 3, 4, or 5 with collection of plasma and peripheral blood mononuclear cells (PBMCs). Safety data were recorded from first infusion through 4 weeks after last infusion and at delivery. Geometric mean ratios (GMR) (90% confidence intervals [CI]) of PK parameters between pregnant and nonpregnant women were calculated. Fifty-three participants initiated remdesivir (25 pregnant; median gestational age, 27.6 weeks; interquartile range, 24.9-31.0 weeks). Plasma exposures of remdesivir, its 2 major metabolites (GS-704277 and GS-441524), and the free remdesivir fraction were similar between pregnant and nonpregnant participants. Concentrations of the active triphosphate (GS-443902) in PBMCs increased 2.04-fold (90% CI, 1.35-3.03) with each additional infusion in nonpregnant versus pregnant participants. Three adverse events in nonpregnant participants were related to treatment (1 grade 3; 2 grade 2 resulting in treatment discontinuation). There were no treatment-related adverse pregnancy outcomes or congenital anomalies detected. Plasma remdesivir PK parameters were comparable between pregnant and nonpregnant women, and no safety concerns were identified based on our limited data. These findings suggest no dose adjustments are indicated for intravenous remdesivir during pregnancy. NCT04582266.

Molnupiravir's real-world effectiveness in COVID-19 outpatients at high risk of severe disease: a single-center study.

The coronavirus disease 2019 (COVID-19) pandemic started in March 2020. Since then, there has been an urgent need for effective therapeutic methods to manage the disease. We aimed to assess the effectiveness of molnupiravir in reducing the need for hospitalization in at-risk, non-hospitalized COVID-19 patients. This was a single-center, non-randomized, observational retrospective study of non-hospitalized patients with confirmed COVID-19, treated at the Clinic for Infectious and Tropical Diseases, University Clinical Center in Belgrade, Serbia. The study was conducted between 15 December 2021 and 15 February 2022 and included 320 patients. Of these, 165 (51.6%) received treatment with molnupiravir. The study and control groups were similar in gender and age distribution. The study group had a higher proportion of vaccination (75.2% vs. 51%, p < 0.001). There was no statistically significant difference in presence of comorbidity within the groups. Majority of the patients who received molnupiravir did not require hospitalization; and this was statistically significant in comparison to control group (92.7 vs. 24.5%, p < 0.001). Oxygen supplementation was less frequently required in the study group compared to the control group (0.6% vs. 31%, p < 0.001). During the follow-up period of 12.12 ± 3.5 days, significantly less patients from the study group were admitted to the intensive care unit (p < 0.001). Molnupiravir significantly reduced the risk of hospitalization by 97.9% (HR 0.021; 95% CI 0.005-0.089; p < 0.001). Molnupiravir is an effective therapy in preventing the development of severe forms of COVID-19 and hospitalization.

Identification of CXCL9 chemokine as a potential biomarker for assessing clinical severity in COVID-19 patients.

The severity and clinical outcome of COVID-19 depend on virus-specific factors and the host's inflammatory response. Identifying biomarkers of severe COVID-19 is a crucial condition and predicts disease severity. This study enrolled a total of 167 patients with COVID-19. These patients were categorized into three groups based on the severity of the disease: moderate course - 78 individuals, severe course - 52 individuals, and extremely severe course - 37 individuals. We analyzed chemokines (IP-10, CXCL9, CCL17) and cytokine IL28B levels using the enzyme immunoassay (EIA) method. CXCL9 levels were increased in severe and extremely severe cases compared to moderate ones. The CCL17 chemokine demonstrated significant elevation in severe cases. However, there was no significant difference in the level of IP-10, and IL28B in the compared groups. Our findings suggest that CXCL9 and CCL17 chemokines could be used as biomarkers to assess the clinical status of patients with COVID-19 and can relate to disease severity. These biomarkers could aid in identifying patients at high risk for severe disease and help guide clinical decision-making for the effective management of COVID-19.

Follow-up of immune response in patients with common variable immunodeficiency following SARS-CoV-2 vaccination.

The COVID-19 pandemic highlighted the importance of effective vaccination strategies in controlling the spread of infectious diseases. SARS-CoV-2 vaccine has demonstrated high efficacy in preventing COVID-19 infection in the general population. However, the efficacy of this vaccine in patients with predominantly antibody deficiencies, such as common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA), should be closely monitored. CVID and XLA are rare genetic disorders that impair the immune system's ability to produce antibodies, which are crucial for fighting infections. Patients with these disorders have a higher risk of severe disease and mortality from COVID-19 due to their compromised immune systems. In this study, we evaluated the humoral and cellular immune responses after four doses of mRNA-1273 and one BNT162b2 bivalent vaccine in a cohort of patients with CVID and XLA. The response in this population was lower than in the control group. However, the administration of the third dose improved the number of patients with seroconversion and the intensity of the humoral response, as well as the number of patients with a positive cellular response. Finally, the administration of the fourth and fifth doses improves the antibody titer and neutralization against wild type variant, but not against the prevalent XBB1.5 variant.

Effectiveness of patient reminders on influenza vaccination coverage among adults with chronic conditions: A feasibility study in Australian general practices

BackgroundInfluenza vaccination is recommended for Australians 18+ years old with medical risk factors, but coverage is suboptimal. We aimed to examine whether automatic, opportunistic patient reminders (SMS and/or printed) before appointments with a general practitioner increased influenza vaccination uptake. MethodsThis clustered non-randomised feasibility study in Australian general practice included patients aged 18–64 years with at least one medical risk factor attending participating practices between May and September 2021. Software installed at intervention practices identified unvaccinated eligible patients when they booked an appointment, sent vaccination reminders (SMS on booking and 1 h before appointments), and printed automatic reminders on arrival. Control practices provided usual care. Clustered analyses adjusted for sociodemographic differences among practices were performed using logistic regression. ResultsA total of 12,786 at-risk adults attended 16 intervention practices (received reminders = 4066; ‘internal control’ receiving usual care = 8720), and 5082 individuals attended eight control practices. Baseline influenza vaccination uptake (2020) was similar in intervention and control practices (∼34%). After the intervention, uptake was similar in all groups (control practices = 29.3%; internal control = 30.0%; intervention = 31.6% (p-value = 0.203). However, SMS 1 h before appointments increased vaccination coverage (39.3%, adjusted OR = 1.65; 95%CI 1.20;2.27; number necessary to treat = 13), especially when combined with other reminder forms. That effect was more evident among adults with chronic respiratory, rheumatologic, or inflammatory bowel disease. ConclusionThese findings indicate that automated SMS reminders delivered at proximate times to appointments are a low-cost strategy to increase influenza vaccination among adults at higher risk of severe disease attending Australian general practices.

Hereditary Connective Tissue Diseases and Risk of Post-Acute SARS-CoV-2.

We completed a retrospective review of data collected by the JH-CROWN consortium based on ICD10 codes for a hospitalized cohort. The severity and prevalence of COVID-19 and development of PASC within heritable connective tissue diseases were unknown; however, clinical observation suggested a thorough examination was necessary. We compared rates of disease severity, death, and PASC in connective tissue diseases versus the entire cohort as well as in diabetes and hypertension to determine if connective tissue disease was a risk factor. Of the 15,676 patients in the database, 63 (0.40%) had a connective tissue disease, which is elevated relative to the distribution in the population, suggesting a higher risk of severe disease. Within these 63 patients, 9.52% developed PASC compared to 2.54% in the entire cohort (p < 0.005). Elucidation of populations at high risk for severe disease and development of PASC is integral to improving treatment approaches. Further, no other study to date has examined the risk in those with connective tissue diseases and these data support a need for enhanced awareness among physicians, patients, and the community.

The effect of HIV and mpox co-infection on clinical outcomes: Systematic review and meta-analysis.

Co-infection with HIV and mpox is a significant issue for public health because of the potential combined impact on clinical outcomes. However, the existing literature lacks a comprehensive synthesis of the available evidence. The purpose of this meta-analysis is to provide insight into the impact of HIV and mpox co-infection on clinical outcomes. We systematically searched major electronic databases (PubMed, Embase, Cochrane Central, and Web of Science) for pertinent studies published up to June 2023. Included were studies that described the clinical outcomes of people who had both mpox and HIV. We performed the analysis using OpenMeta and STATA 17 software. With an overall number of participants of 35 207, 21 studies that met the inclusion criteria were considered. The greatest number of the studies (n = 10) were cohort designs, with three being cross-sectional and eight being case series studies. The meta-analysis found that people who had both HIV and mpox had a higher hospitalization rate than those who only had mpox (odds ratio [OR] 1.848; 95% confidence interval [CI] 0.918-3.719, p = 0.085, I2 = 60.19%, p = 0.020). Furthermore, co-infected patients had higher mortality rates than those who did not have HIV co-infection (OR 3.887; 95% CI 2.272-6.650, p < 0.001). Meta-regression analysis showed that CD4 levels can significantly predict the risk of hospitalization (p = 0.016) and death (p = 0.031). HIV causes immunosuppression, making it difficult for the body to mount an effective immune response against pathogens such as mpox. Individuals who are co-infected are at a higher risk of severe disease and death, according to our findings. Although hospitalization rates did not differ significantly between the two groups, it is critical to prioritize interventions and improve management strategies tailored specifically for people living with HIV. This meta-analysis provides substantial evidence that HIV and mpox co-infection has a negative impact on clinical outcomes. Co-infected individuals had higher hospitalization and significantly higher mortality rates. These findings highlight the significance of early diagnosis, prompt treatment initiation, and effective management strategies for people living with HIV and mpox.

Seroprevalence of SARS-CoV-2 IgG in people with cystic fibrosis

BackgroundWhen the first known US case of COVID-19 (Coronavirus Disease 2019) was reported in early 2020, little was known about the impact of this novel virus on the cystic fibrosis community. As the majority of individuals with CF have chronic lung disease, this population was initially considered to be at high risk for severe disease as infection with a multitude of viruses has proven to cause pulmonary exacerbation. SARS-CoV-2 virus has proven challenging to study given the multiple disease manifestations, range of severity, and wave-like phenomenon that varies geographically. People with CF who become infected with COVID-19 can be asymptomatic or have symptoms ranging from mild cough and congestion to full respiratory failure, similar to the manifestations seen in non-CF individuals. By studying the seroprevalence, clinical course, and antibody durability due to COVID-19 and vaccinations, we will be better equipped to provide appropriate and informed care to people with CF. MethodsBetween July 2020 and April 2021 we enrolled 123 people with CF (pwCF) who receive care at the MN CF Center. We monitored their serology every 6 months for SARS-CoV-2 immunoglobulins (nucleocapsid and spike IgG) for evidence of natural and induced immunity. Medication use, pulmonary function, exacerbation history, and hospitalizations were extracted via electronic medical record (EMR). Results84% (101/120) of enrolled participants were vaccinated against SARS-CoV-2 during the study. Eighty three percent of the cohort showed evidence of either natural or induced “immunity.” The average duration of antibody from induced immunity in participants was 6.1 months and from natural immunity was 7.4 months with an overall average duration of antibody of 6.8 months. Earliest antibody detected was 12 days after a single dose of the BNT162b2 vaccine and antibody was detectable across a span of 13 months. Eleven percent of vaccinated individuals did not have measurable IgG. 36% of non-responders (NRs) were solid organ transplant patients on chronic immunosuppressive therapy. Only 3 people within this cohort were hospitalized due to COVID pneumonia and all three survived. ConclusionTo our knowledge, this is the first report on the seroprevalence and longevity of SARS-CoV-2 IgG to 1 year in adults with CF after the widespread availability of SARS-CoV-2 vaccinations. These data show that pwCF respond to the COVID vaccination and produce long-lasting antibodies similar to the general population.

County-Level Factors Associated With Influenza and COVID-19 Vaccination in Indiana, 2020‒2022.

Objectives. To assess COVID-19 and influenza vaccination rates across Indiana's 92 counties and identify county-level factors associated with vaccination. Methods. We analyzed county-level data on adult COVID-19 vaccination from the Indiana vaccine registry and 2021 adult influenza vaccination from the Centers for Disease Control and Prevention. We used multiple linear regression (MLR) to determine county-level predictors of vaccinations. Results. COVID-19 vaccination ranged from 31.2% to 87.6% (mean = 58.0%); influenza vaccination ranged from 33.7% to 53.1% (mean = 42.9%). In MLR, COVID-19 vaccination was significantly associated with primary care providers per capita (b = 0.04; 95% confidence interval [CI] = 0.02, 0.05), median household income (b = 0.23; 95% CI = 0.12, 0.34), percentage Medicare enrollees with a mammogram (b = 0.29; 95% CI = 0.08, 0.51), percentage uninsured (b = -1.22; 95% CI = -1.57, -0.87), percentage African American (b = 0.31; 95% CI = 0.19, 0.42), percentage female (b = -0.97; 95% CI = -1.79, ‒0.15), and percentage who smoke (b = -0.75; 95% CI = -1.26, -0.23). Influenza vaccination was significantly associated with percentage uninsured (b = 0.71; 95% CI = 0.22, 1.21), percentage African American (b = -0.07; 95% CI = -0.13, -0.01), percentage Hispanic (b = -0.28; 95% CI = -0.40, -0.17), percentage who smoke (b = -0.85; 95% CI = -1.06, -0.64), and percentage who completed high school (b = 0.54; 95% CI = 0.21, 0.87). The MLR models explained 86.7% (COVID-19) and 70.2% (influenza) of the variance. Conclusions. Factors associated with COVID-19 and influenza vaccinations varied. Variables reflecting access to care (e.g., insurance) and higher risk of severe disease (e.g., smoking) are notable. Programs to improve access and target high-risk populations may improve vaccination rates. (Am J Public Health. 2024;114(4):415-423. https://doi.org/10.2105/AJPH.2023.307553).

Adverse effects of remdesivir for the treatment of acute COVID-19 in the pediatric population: a retrospective observational study

BackgroundAlthough the severity of coronavirus disease 2019 (COVID-19) tends to be lower in children, it can still lead to severe illness, particularly among those with chronic medical conditions. While remdesivir (RDV) is one of the few approved antiviral treatments for COVID-19 in children in many countries, the available data on the safety of RDV in this population is limited.MethodsTo address this knowledge gap, a multicenter study involving 65 patients retrospectively analyzed the clinical data from individuals aged <18 who were hospitalized due to severe COVID-19 (defined as SpO2 < 94% or requiring supplemental oxygen) and received at least one dose of RDV. Additionally, the study encompassed 22 patients with mild-moderate COVID-19 who were considered at high risk of developing severe disease.ResultsNineteen children (29%) experienced mild-to-moderate adverse events (AEs) attributed to RDV, including transaminitis in 20% of children, bradycardia in 8%, and hypotension in 5%. AEs did not require discontinuation of RDV, except in one patient who developed premature ventricular contractions. The rate of AEs did not differ between patients with severe COVID-19 and those with mild-moderate COVID-19 but at high risk for severe disease. All but one patient were discharged within 23 days of admission, and no fatalities were recorded. Among high-risk patients with mild-moderate disease, only 2 (9%) progressed to the point of needing supplemental oxygen.ConclusionsOur data suggests that RDV is safe in children, with no reported serious AEs. However, the absence of a control group limits the extent to which conclusions can be drawn. RDV may contribute to clinical improvement, particularly in high-risk patients.