Retrospective Analysis of Clostridioides difficile Infection Rates in Hospitalized Patients during COVID-19 Pandemic. A Unicenter Study in Reus, Spain (preprint)

.Background: Clostridioides difficile infections (CDI) vary in severity from mild diarrhea to life-threatening conditions like pseudomembranous colitis or toxic megacolon, often leading to sepsis and death. The COVID-19 pandemic prompted changes in healthcare practices, potentially affecting CDI incidence, though reported data are inconclusive. We studied factors influencing CDI incidence and outcomes at a university hospital throughout the COVID-19 pandemic years. Methods: We conducted a retrospective study on all adult hospitalized CDI cases from January 1, 2020, to December 31, 2022. We collected demographic information, comorbid conditions, and concurrent infections. Results: While overall CDI and COVID-19 rates decreased in 2022, a nota-ble increase in CDI infections was observed among oncological patients and those undergoing some aggressive treatments, such as colon or gastroscopies. The prevalence of comorbidities remained unmodified, and there were declines in prior gastrointestinal surgeries and proton pump inhibitor prescriptions. Factors associated with patient fatality or prolonged hospitaliza-tion included older age, cancer, chronic kidney disease, higher Charlson and McCabe indices, elevated C-reactive protein, and low albumin concentrations. Conclusion: Our study shows the evolving landscape of CDI during the COVID-19 pandemic and emphasizes the impact of de-layed diagnoses and treatments exacerbated by telemedicine adoption. Identified risk factors for CDI-related mortality or prolonged hospital stays underscore the importance of targeted inter-ventions in high-risk populations.

Deaths averted by COVID-19 vaccination in select Latin American and Caribbean Countries: a modelling study (preprint)

BackgroundThe COVID-19 pandemic has had a significant impact on global health, with millions of lives lost worldwide. Vaccination has emerged as a crucial strategy in mitigating the impact of the disease. This study aims to estimate the number of deaths averted through vaccination in LAC during the first year and a half of vaccination rollout (January 2021 - May 2022). MethodsPublicly available data on COVID-19 deaths and vaccination rates were used to estimate the total number of deaths averted via vaccination in LAC. Using estimates for number of deaths, number of vaccinated, and vaccine effectiveness, a counterfactual estimated number of deaths observed without vaccination was calculated. Vaccine effectiveness estimates were obtained from published studies. The analysis focused on 17 countries in LAC and considered adults aged 18 years and above. FindingsAfter accounting for underreporting, the analysis estimated that over 1.49 million deaths were caused by COVID-19 in the selected countries during the study period. Without vaccination, the model estimated that between 2.10 and 4.11 million COVID-19 deaths would have occurred. Consequently, vaccination efforts resulted in approximately 610,000 to 2.61 million deaths averted. InterpretationThis study represents the first large-scale, multi-center estimate of population-level vaccine impact on COVID-19 mortality in LAC. The findings underscore the substantial impact of timely and widespread vaccination in averting COVID-19 deaths. These results provide crucial support for vaccination programs aimed at combating epidemic infectious diseases in the region and future pandemics. FundingThis study was funded by the Pan-American Health Organization (PAHO).

A statistical model to identify excess mortality in Italy in the period 2011-2022 (preprint)

Excess mortality is defined as an increase in the number of deaths above what is expected based on historical trends, hereafter called baseline. In a previous paper, we introduced a statistical method that allows an unbiased and robust determination of the baseline to be used for the computation of excesses. A good determination of the baseline allows us to efficiently evaluate the excess of casualties that occurred in Italy in the last 12 years and in particular in the last 3 years due to the Coronavirus Disease 2019 (COVID-19) epidemic. To this extent, we have analyzed the data on mortality in Italy in the period January 1st 2011 to December 31th 2022, provided by the Italian National Institute of Statistics (ISTAT). The dataset contains information on deaths for all possible causes, without specific reference to any particular one. The data exhibit strikingly evident periodicity in the number of deaths with pronounced maxima in the winter and minima in the summer, repeating itself in amplitude along the whole twelve-year sample. Superimposed on this wave-like structure are often present excesses of casualties, most likely due to occasional causes of death such as the flu epidemics (in winter) and heat waves (in summer). The very accurate periodicity along the seasons (the "baseline"), allows us to determine with great accuracy and confidence the number of expected deaths for each day of the year in the absence of occasional contributions. Each of the latter can be modeled with an additional function that parameterizes the deviation from the baseline.

Evolving impact of the COVID-19 pandemic in chronic dialysis recipients over the course of pandemic waves and COVID-19 vaccination rollout: a French national study. (preprint)

BackgroundThis observational study aims to assess the impact of the pandemic on the evolving of kidney transplantations, survival, and vaccination in chronic dialysis recipients (CDR) over the COVID-19 pandemic subperiods. MethodsUsing the French national health claims database, incident persons with end stage kidney disease in years 2015 to 2021 treated with dialysis were followed-up until December 31, 2022. Kidney transplantion and survival over pandemic subperiods versus the prepandemic period were investigated using longitudinal models with time-dependent covariates. Moreover, the impact of cumulative doses of COVID-19 vaccine on hospitalization and survival were compared between CDR and matched-control individuals. FindingsFollow-up of the 71,583 CDR and 143,166 controls totalized 639,341 person-years (CDR: 184,909; controls: 454,432). The likelihood of receiving a kidney transplant decreased during all pandemic subperiods except one. Mortality in CDR increased during the 3 wave subperiods (hazard ratio (HR [95% confidence interval]): 1{middle dot}19 [1{middle dot}13-1{middle dot}27], 1{middle dot}19 [1{middle dot}15-1{middle dot}23], and 1{middle dot}12 [1{middle dot}07-1{middle dot}17], respectively). While vaccine coverage declined with each booster dose, receiving such doses was associated with lower risks of COVID-19-related hospitalization (0{middle dot}66 [0{middle dot}56-0{middle dot}77], 0{middle dot}83 [0{middle dot}72-0{middle dot}94] for 1st booster versus 2nd dose and 2nd booster versus 1st booster, respectively) and death (corresponding HR: 0{middle dot}55 [0{middle dot}51-0{middle dot}59], 0{middle dot}88 [0{middle dot}83-0{middle dot}95]). Evolving patterns in mortality and vaccination outcomes were similar in CDR and controls. InterpretationThe impact of the pandemic in CDR was not specific of the kidney disease per se. Study results also suggest future research aimed at increasing adherence to vaccine booster doses.

Trust and transfer during the covid-19 pandemic: did digital cash transfer save lives? (preprint)

BACKGROUNDIn the first semester of 2020 one in six people in the world (1.36 billion) received cash transfers to tide them over the spreading pandemic that originated in Wuhan. By December 2021 it had claimed up to 18.2 million excess deaths. Compared to no (digital) transfer, did digital cash transfer reduce excess deaths? Serendipitously, two years earlier the world reported levels of trust in science. Did such trust inoculate societies from the pandemic? MATERIALS & METHODSThe growing excess deaths literature distinguishes causal factors (e.g. digital transfer) from risk factors (e.g. trust). During the pandemic period, no randomised trials of digital transfer with excess deaths as primary outcome were registered. This study used reports from 170 countries and applied endogenous treatment models to overcome the endogeneity of digital transfer. RESULTS & DISCUSSIONI found that serendipity matters: countries with high trust in science suffered fewer excess deaths. But creativity matters more. Digital transfers -some creatively scrambled from scratch- reduced excess deaths by many more. Equally marked, North-South inequity in excess deaths persists, consistent with the concentration of vaccine distributions in the North early on. All three are statistically significant. A series of robustness analyses points to the results being reliable to change in outcome estimates, change in trust sources, and change in treatment of omitted countries. Mechanistic analyses show evidence that digital transfer created leg room for governments to expand stringent restrictions to control the spread of SARS-CoV-2, while in the South it weakened the correlation between informal economy and excess deaths. This study of the causal effect of digital cash transfer on a hard outcome (excess deaths) revealed ample global digital dividends across the largest number of countries. This new evidence also suggests that improving and monitoring trust in science can offer considerable benefits for humanity.

Causes of death in people living with HIV in the post 95 -95 -95 era: Lessons from five AIDS Healthcare Foundation clinics in Eswatini (preprint)

Background Eswatini has a high HIV prevalence in adults (24.8%), and despite achieving HIV epidemic control, AIDS-related deaths are still high at 200 per 100,000 population. This study, therefore, describes the causes of death among people living with HIV (PLHIV) receiving care at five clinics in Eswatini. Methods Data of clients receiving antiretroviral therapy (ART) from five AIDS Healthcare Foundation (AHF) Clinics in Eswatini who died was analysed to describe the causes of death. Clients' records were included if they received treatment from any of the five clinics from January 1, 2021, to June 30, 2022. Clients' sociodemographic, clinical, and specific cause of death data were extracted from their clinical records into an Excel spreadsheet for mortality reporting and audits. The different causes of death were categorised and descriptive, and comparative analysis was done using Stata 15 and R. Odds ratio significant at p<0.05 (with 95% confidence interval) to estimate the different associations between the client's characteristics and the four leading causes of death. Results Of 257 clients, 52.5% (n=135) were males, and the median age was 47 years (IQR: 38, 59). The leading causes of death were non-communicable diseases (NCDs) (n=59, 23.0%), malignancies (n=37, 14.4%), Covid-19 (n=36, 14.0%) and advanced HIV disease (AHD) (n=24, 9.3%). Patients aged ≥60 years (OR 0.08; 95% CI: 0.004, 0.44) had lower odds of death from AHD than ≥40 years, and those who had been on ART for 12 – 60 months (OR 0.01; 95% CI: 0.0006, 0.06) and >60 months (OR 0.006; 95% CI: 0.0003, 0.029) had lower odds of death from AHD compared to those on ART for <12 months. Patients aged ≥40 years had higher odds of dying from COVID-19, while females (OR 2.64; 95% CI: 1.29, 5.70) had higher odds of death from malignancy. Conclusion Most patients who died were aged 40 years and above and died from an NCD, malignancy, COVID-19 and AHD-related cause. This indicates a need to expandprevention, screening, and integration of treatment for NCDs and cancers into HIV services. Specific interventions targeting younger PLHIV will limit their risks for AHD.

Orphanhood and caregiver death among children in the United States due to all-cause mortality 2000-2021: A Modeling Study (preprint)

Importance: Deaths of parents and grandparent caregivers linked to social and health crises threaten child wellbeing due to losses of nurturance, financial support, physical safety, family stability, and care. Little is known about the full burden of all-causes and leading cause-specific orphanhood and caregiver death beyond estimates from select causes. Objective: To estimate 2000-2021 prevalence and incidence trends of all-cause orphanhood and caregiver death among children <18, by cause, age, race/ethnicity, and state. Data Sources: National Center for Health Statistics (NCHS) birth, death, race/ethnicity, and population data to estimate fertility rates and identify causes of death; 1983-1998 ICD-9 causes-of-death harmonized to ICD-10 classifications; 1999-2021 ICD-10 causes-of-death; CDC WONDER for state-specific estimates; and American Community Survey for grandparent population estimates. Data extraction and synthesis: We extracted U.S. population-level death, birth, population size, race, and ethnicity data from NCHS and attributed to each deceased individual the average number of children left behind according to subgroup-specific fertility rates in the previous 0-17 years. We examined prevalence and incidence of orphanhood by leading causes-of-death, including COVID-19, the leading 5 causes-of-death for 1983-2021, and additional leading causes for ages 15-44. We extended these to obtain state-level outcome estimates. Main outcome measures: National incidence and prevalence of orphanhood and caregiver death from 2000-2021, with orphanhood by year, parental cause-of-death and sex, child age, race/ethnicity, and state. Results: From 2000-2021, orphanhood and custodial/co-residing grandparent caregiver loss annual incidence and prevalence trends increased 49.2% and 8.3%, respectively. By 2021, 2.9 million children (4% of all children) had experienced prevalent orphanhood and caregiver death. Populations disproportionately affected by orphanhood included 5.0% of all adolescents; 6.5%, 4.8%, and 3.9% respectively of non-Hispanic American Indian/Alaska Native, non-Hispanic Black, and non-Hispanic White children; and children in New Mexico and Southern and Eastern States. Parental death due to drug overdose during 2020-2021 surpassed COVID-19 as the leading cause of incident and prevalent orphanhood during the COVID-19 pandemic. Conclusions and Relevance: Policies, programs, and practices aimed at orphanhood prevention, identification, and linkage to services and support of nearly 3 million bereaved children are needed, foremost prioritizing rapidly increasing overdose-linked orphanhood.

Excess mortality in low-and lower-middle-income countries: A systematic review and meta-analysis (preprint)

Background: The COVID-19 pandemic caused a massive death toll, but its effect on mortality remains uncertain in low- and lower-middle-income countries (LLMICs). This review summarized the available literature on excess mortality in LLMICs, including methods, data sources, and factors that might have influenced excess mortality. Methods: The protocol was registered in PROSPERO (ID: CRD42022378267). We searched PubMed, Embase, Web of Science, Cochrane Library, Google Scholar, and Scopus for studies conducted in LLMICs on excess mortality. These included studies with at least a one-year non-COVID-19 period as the comparator in estimating excess mortality and with publication dates from 2019 to date. The meta-analysis included studies with extractable data on excess mortality, methods, population size, and observed and expected deaths. We used the Mantel-Haenszel method to estimate the pooled risk ratio of excess mortality with 95% confidence intervals. Results: The review included studies from 29 countries, of which 10 were included in the meta-analysis. Of 1,405,128,717 individuals, 2,152,474 deaths were expected, and 3,555,880 deaths were reported. The pooled excess mortality was 100.3 deaths per 100,000 population per pandemic period. The excess risk of death was 1.65 (95% CI: 1.649, 1.655 p<0.001). Data sources included civil registration systems, obituary notifications, surveys, public cemeteries, funeral counts, burial site imaging, and demographic surveillance systems. Techniques used to estimate excess mortality were mainly statistical forecast modelling and geospatial analysis. Of the 24 studies, only one found higher excess mortality in urban settings. Conclusion: Our results show that excess mortality in LLMICs during the pandemic was substantial. There is uncertainty around excess mortality estimates given comparatively weak data. Further studies are needed to identify the drivers of excess mortality by exploring different methods and data sources.

Female Legislators Decrease Epidemic Deaths (preprint)

Recent discourse has lauded the efficacy of female leadership in national governments, particularly during the COVID-19 pandemic. This study employs two-way fixed effect (TWFE) and instrumental variable (IV) regression methodologies to reveal a more pronounced association between the proportion of female legislators and reduced epidemic-related mortality, rather than a direct correlation with female executive leadership. Further analysis elucidates that the effectiveness of female legislative representation is amplified through its interaction with the deliberative processes in governance. This suggests that policy diversity and inclusive decision-making mechanisms are instrumental in enhancing epidemic response efficacy.

Dynamic Vaccine Allocation for Control of Human Transmissible Disease (preprint)

During pandemics, such as COVID-19, supplies of vaccines can be insufficient to meet all needs, particularly when vaccines first become available. Our study develops a dynamic methodology for vaccine allo- cation, segmented by region, age, and timeframe, using a time-sensitive, age-structured compartmental model. Based on the objective of mini- mizing a weighted sum of deaths and cases, we used the Sequential Least Squares Quadratic Programming method to search for a locally opti- mal COVID-19 vaccine allocation for the United States, for the period from December 16, 2020, to June 30, 2021, where regions corresponded to the 50 states in the United States (US). We also compared our solu- tion to actual allocations of vaccines. From our model, we estimate that approximately 1.8 million cases and 9 thousand deaths could have been averted in the US with an improved allocation. When case reduction is prioritized over death reduction, we found that young people (17 and younger) should receive priority over old people due to their potential to expose others. However, if death reduction is prioritized over case reduc- tion, we found that more vaccines should be allocated to older people, due to their propensity for severe disease. While we have applied our methodology to COVID-19, our approach generalizes to other human- transmissible diseases, with potential application to future epidemics.

Racial/ethnic disparities in COVID-19 clinical outcomes: A comparison between Asian ethnic subgroups (preprint)

Background Since the outbreak of COVID-19, general studies about relationship between COVID-19 clinical outcome and ethnicity have been performed on the overall ethnic groups, but studies on ethnic subgroups is limited.Methods We conducted a population-based retrospective cohort study on hospitalized patients with suspected/confirmed COVID-19 to evaluate whether ethnic background influences disease severity and clinical outcomes. Patients were categorized into three groups: mild, moderate, and severe to critical. Analyses were adjusted for socio-demographic and comorbidities.Results Among all hospitalized patients, in the unadjusted model, Afghans had a lower risk of severe to critical illness than Iranians (OR, 0.52; 95%CI, 0.41–0.64; P < 0.000). After adjusting for age, sex and comorbidities the risk remained lower in Afghans (OR, 0.69; 95%CI, 0.56–0.88; P < 0.003). But among positive cases was comparable even after full adjustment (OR, 0.86; 95%CI, 0.54–1.3; P < 0.547). Among all hospitalized patients, in the unadjusted model, the risk of death was comparable between Afghans and Iranians (OR, 1.037; 95%CI, 0.70–1.5; P < 0.003). After adjusting for age, sex and comorbidities, Afghans had a higher risk of death than Iranians (OR, 1.66; 95%CI, 1.08–2.55; P = 0.020). Similar results were observed in positive cases (OR, 2.34; 95%CI, 1.47–3.72; P = 0.000).Conclusions In this cohort study, Iranians represented more COVID-19-related symptoms and disease severity than Afghans; but mortality was higher in Afghans. The impact of COVID-19 may be different in various Asian ethnic groups

Impact of Comorbidity on Mortality in COVID-19 Patients: A Single- Center Retrospective Study (preprint)

The global spread of COVID-19 has had a profound impact on human health, with millions of people infected and a significant death. Comorbidities play a pivotal role in the prognosis of COVID-19 patients. The aim of this study was to assess the impact of the comorbidity on mortality in COVID-19 patients in a Single-Centre Retrospective Study. The characteristics and results of patients with COVID-19 admitted to KLE's Hospital in Belgaum, Karnataka, India, were examined through retrospective research. 642 participants having COVID-19 diagnoses between October 1, 2020, and September 30, 2021 were enrolled in the research. Data such as, patients' clinical features, vital signs, demographic information and patients' outcomes (survived or deceased) were collected. The findings of this study showed that out of 642 patients, 256 patients had co morbidities, 62.8% of them had poly morbidity and most prevalent underlying medical conditions were hypertension, diabetes, and heart disease which affected 30.7%, 29.1, and 7.9%, respectively. Only diabetes and renal disease reported strong associations (P.value: 0.011, aOR: 1.852 95% CI: 1.148–2.988), (p.value: 0.000, aOR: 6.491 (95% CI: 2.613–16.124), respectively. Furthermore, Comorbidities such kidney disease, and diabetes mellitus can lead to more serious complications and death in COVID-19 patients. Understanding the impact of these comorbidities on COVID-19 mortality is essential for more effective patient care and resource allocation.

High transferability of neutralizing antibodies against SARS-CoV-2 to umbilical cord blood in pregnant women with BNT162b2 XBB.1.5 vaccine - a retrospective cohort study (preprint)

Coronavirus disease 2019 (COVID-19), when contracted by pregnant women, can lead to severe respiratory illness, rapid disease progression, and higher rates of intensive care unit admission. COVID-19 infection during pregnancy is associated with an increased risk of preterm delivery, cesarean section, fetal dysfunction, preeclampsia, and perinatal death. Additionally, vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from pregnant women to their fetuses has been observed. While severe infections in neonates and infants are rare, newborns can experience serious consequences from COVID-19, despite their suboptimal humoral immune system protection. The amino acids in the structural proteins of SARS-CoV-2 are subjected to constant mutation. Since around January 2023, COVID-19, caused by infection with omicron-type SARS-CoV-2 variants, has been prevalent globally. Omicron-type SARS-CoV-2 variants can evade the immune response triggered by traditional mRNA-based COVID-19 vaccines, such as BNT162b2. Therefore, vaccination with a vaccine (BNT162b2 XBB.1.5) that can provide protection against omicron-type SARS-CoV-2 variants is recommended. Therefore, we examined the titers of anti-spike glycoprotein of SARS-CoV-2 IgG and IgA in the blood and umbilical cord blood obtained from pregnant women vaccinated with BNT162b2 XBB.1.5. The results showed that anti-spike glycoprotein of SARS-CoV-2 IgG and IgA titers were highest in the blood and cord blood obtained from pregnant women vaccinated with BNT162b2 XBB.1.5 at late gestational age (28-34 weeks). No serious side effects or adverse events caused by vaccination of pregnant women with BNT162b2 XBB.1.5 were observed in either pregnant women or newborns. In the future, to validate our findings, large cohort clinical studies involving numerous pregnant women must be conducted.

Effect of apigetrin in pseudo-SARS-CoV-2-induced inflammatory and pulmonary fibrosis in vitro model (preprint)

SARS-CoV-2 has become a global public health problem. Acute respiratory distress syndrome (ARDS) is the leading cause of death due to the SARS-CoV-2 infection. Pulmonary fibrosis (PF) is a severe and frequently reported COVID-19 sequela. In this study, an in vitro model of ARDS and PF caused by SARS-CoV-2 was established in MH-S, THP-1, and MRC-5 cells using pseudo-SARS-CoV-2 (PSCV). Expression of proinflammatory cytokines (IL-6, IL-1β, and TNF-α) and HIF-1α was increased in PSCV-infected MH-S and THP-1 cells, ARDS model, consistent with other profiling data in SARS-CoV-2-infected patients have been reported. Hypoxia-inducible factor-1 alpha (HIF-1α) siRNA and cobalt chloride were tested using this in vitro model. Furthermore, apigetrin, a glycoside bioactive dietary flavonoid derived from several plants, including Crataegus pinnatifida, which is reported to be a HIF-1α inhibitor, was tested in this in vitro model [1]. Apigetrin significantly reduced the increased inflammatory cytokine (IL-6, IL-1β, and TNF-α) expression and secretion by PSCV in MH-S and THP-1 cells. Apigetrin inhibited the binding of the SARS-CoV-2 spike protein RBD to the ACE2 protein. An in vitro model of PF induced by SARS-CoV-2 was produced using a conditioned medium of THP-1 and MH-S cells that were PSCV-infected (CMPSCV) into MRC-5 cells. In a PF model, CMPSCV treatment of THP-1 and MH-S cells increased cell growth, migration, and collagen synthesis in MRC-5 cells. In contrast, apigetrin suppressed the increase in cell growth, migration, and collagen synthesis induced by CMPSCV in THP-1 and MH-S MRC-5 cells. Also, compared to control, fibrosis-related proteins (CTGF, COLA1, α-SMA, and HIF-1α) levels were over two-fold higher in CMPSV-treated MRC-5 cells. Apigetrin decreased protein levels in CMPSCV-treated MRC-5 cells. Thus, our data suggest that hypoxia-inducible factor-1 alpha (HIF-1α) might be a novel target for SARS-CoV-2 sequela therapies and apigetrin, representative of HIF-1alpha inhibitor, exerts anti-inflammatory and PF effects in PSCV-treated MH-S, THP-1, and CMPVSC-treated MRC-5 cells. These findings indicate that HIF-1α inhibition and apigetrin would have a potential value in controlling SARS-CoV-2-related diseases.

Postpartum suicidal ideation in Austria and Germany during the COVID-19 pandemic (preprint)

Introduction: Postpartum suicidal ideation is a significant concern, as it poses a risk for future suicide attempts, particularly in high income countries, where suicide ranks among the leading causes of death for postpartum mothers. The literature indicates a global average prevalence of postpartum suicidal ideation of approximately 7%, but for Austria and Germany there are few studies on this subject. Methods: In a web-based survey for Austrian and German mothers of children born during the COVID-19 pandemic, several measures of mental health (depression, stress), social support and other parenting and pandemic-related questions were assessed in 1964 mothers. Based on the answers for the last item of the Edinburgh Postpartum Depression Scale, the suicidality risk and the presence or absence of suicidal ideation were computed. Furthermore, possible risk or protective factors for suicidality were investigated. Results: The prevalence of suicidal ideation was 7.3%, which is in the range of the global prevalence reported in the literature, but two times higher than previous reports on German mothers. The three strongest risk factors for suicidal ideation were (i) high levels of stress (increased risk by 350%), (ii) a lack of perceived social support (increased risk by 265%), and (iii) a perceived negative effect of the pandemic on the relationship with the partner (increased risk by 223%). Not receiving help from family and friends, having a lower income, and feeling negatively impacted by the pandemic also significantly increased the risk of suicidal ideation. Discussion and conclusion: The results indicate a higher prevalence of suicidality than previously reported in German mothers, and confirm the risk factors previously associated with depression and suicidality. These risk and protective factors could be targets of social and public health policies, while the first step should be a general screening program for suicidality in this population group.

Comparative safety and effectiveness of Pfizer BA.4-5 versus Sanofi during the spring 2023 COVID-19 booster vaccination programme in England: a matched cohort study in OpenSAFELY-TPP (preprint)

Introduction: The spring 2023 COVID-19 booster vaccination programme in England used both Pfizer BA.4-5 and Sanofi vaccines. All people aged 75 years or over and the clinically vulnerable were eligible to receive a booster dose. Direct comparisons of the effectiveness of these two vaccines in boosting protection against severe COVID-19 events have not been made in trials or observational data. Methods With the approval of NHS England, we used the OpenSAFELY-TPP database to compare effectiveness of the Pfizer BA.4-5 and Sanofi vaccines during the spring 2023 booster programme, between 1 April and 30 June 2023. We investigated two cohorts separately: those aged 75 or over (75+); and those aged 50 or over and clinically vulnerable (CV). In each cohort, vaccine recipients were matched on date of vaccination, COVID-19 vaccine history, age, and other characteristics. Effectiveness outcomes were COVID-19 hospital admission, COVID-19 critical care admission, and COVID-19 death up to 16 weeks after vaccination. Safety outcomes were pericarditis and myocarditis up to 4 weeks after vaccination. We report the cumulative incidence of each outcome, and compare safety and effectiveness using risk differences (RD), relative risks (RR), and incidence rate ratios (IRRs). Results 492,642 people were 1-1 matched in the CV cohort, and 673,926 in the 75+ cohort, contributing a total of 7,423,251 and 10,173,230 person-weeks of follow-up, respectively. The incidence of COVID-19 hospital admission was higher for Sanofi than for Pfizer BA.4-5. In the CV cohort, 16-week risks per 10,000 people were 22.3 (95%CI 20.4 to 24.3) for Pfizer BA.4-5 and 26.4 (24.4 to 28.7) for Sanofi, with an IRR of 1.19 (95%CI 1.06 to 1.34). In the 75+ cohort, these were 17.5 (16.1 to 19.1) for Pfizer BA.4-5 and 20.4 (18.9 to 22.1) for Sanofi, with an IRR of 1.18 (1.05-1.32). These findings were similar across all pre-specified subgroups. More severe COVID-19 related outcomes (critical care admission and death), and safety outcomes at 4 weeks, were rare in both vaccines so we could not reliably compare effectiveness of the two vaccines. Conclusion This observational study comparing effectiveness of Pfizer BA.4-5 and Sanofi vaccine during the spring 2023 programme in England in the two main eligible cohorts - people aged 75 and over and in clinically vulnerable people - found some evidence of superior effectiveness against COVID-19 hospital admission for Pfizer BA.4-5 compared with Sanofi within 16 weeks after vaccination.

Characterization of Maternal Mortality and Severe Maternal Morbidity before and during Covid-19: an analysis for the Dominican Republic (preprint)

The Covid-19 pandemic disturbed the delivery of health services, which included obstetric care, in many parts of the word. In countries where maternal mortality was already elevated before the pandemic, this disruption brought about catastrophic events. Using data from the Sistema Nacional de Vigilancia Epidemiológica (SINAVE) of the maternal morbidity and mortality of the Dominican Republic, this paper estimated the severe maternal morbidity rate and the maternal mortality rate by causes of death (direct, indirect, and specific causes). Mixed effects models were used to identify individual and contextual factors that contribute to a higher risk of dying. Results indicate that the severe maternal morbidity rate decrease from 12.1 to 10.4 per 1,000 live births in 2020 compared to 2019; however, the maternal mortality rate went from 91.4 to 124.2 per 100,000 live births in the same period. In 2021, a significant increase in morbidity and mortality was observed, registering a rate of 16.5 cases of severe maternal morbidity per 1,000 live births and a rate of 153.7 maternal deaths per 100,000 live births. Additionally, maternal mortality in the Dominican Republic is associated with the sociodemographic and economic conditions of women, revealing inequalities related to national origin, area of residence and access to health services which were worsening during the pandemic.

Substantial reduction in the clinical and economic burden of disease following variant-adapted mRNA COVID-19 vaccines in immunocompromised patients in France (preprint)

An economic evaluation was conducted to predict the economic and clinical burden of vaccinating immunocompromised (IC) individuals aged ≥30 years with mRNA-1273 variant-adapted COVID-19 vaccines in Fall 2023 and Spring 2024 versus BNT162b2 variant-adapted vaccines in France. The number of symptomatic COVID-19 infections, hospitalizations, deaths, and long COVID cases, costs and quality-adjusted life years (QALYs) was estimated using a static decision-analytic model. Predicted vaccine effectiveness (VE) were based on real-world data from prior versions, suggesting higher protection against infection and hospitalization with mRNA-1273 vaccines. VE estimates were combined with COVID-19 incidence and probability of COVID-19 severe outcomes. Uncertainty surrounding VE, vaccine coverage, infection incidence, hospitalization and mortality rates, costs and QALYs were tested in sensitivity analyses. The mRNA-1273 variant-adapted vaccine is predicted to prevent an additional 3,882 infections, 357 hospitalizations, 81 deaths, and 326 long COVID cases when compared to BNT162b2 variant-adapted vaccines in 230,000 IC individuals. This translates to €10.1 million cost-savings from a societal perspective and 645 QALYs saved. Results were consistent across all analyses and most sensitive to variations surrounding VE and coverage. These findings highlight the importance of increasing vaccine coverage, and ability to induce higher levels of protection with mRNA-1273 formulations in this vulnerable population.

Real-word immunogenicity of a recombinant subunit COVID-19 vaccine and effectiveness against omicron infection: a prospective, multi-centre, longitudinal cohort study in Alzheimer's disease patients (preprint)

Introduction Vaccination is an essential strategy against COVID-19 in the current era of emerging variants. This study evaluates the real-world immunogenicity and effectiveness of the recombinant subunit COVID-19 vaccine (Zifivax) in Alzheimer's disease (AD) patients.Methods 249 AD patients were enrolled in a multicentre, longitudinal cohort study. Levels of RBD-IgG, neutralization antibody activity, and cytokines were identified to evaluate the immune responses. Clinical outcomes were assessed within one month following Omicron infection..Results Following three doses, the vaccine induced a robust immune response, elevating neutralizing antibodies and activating T-cells. AD patients exhibited significantly higher humoral immune responses compared to unvaccinated counterparts. Following Omicron infection, unvaccinated patients experienced higher levels of Th1/Th2-type cytokines than vaccinated individuals. Vaccination correlated with increased survival rates and extended survival times after infection..Discussion The findings highlight the vaccine's efficacy in reducing severe illness, and preventing death in AD patients facing Omicron infection.

Impact of the COVID-19 Epidemic on Death Among Critically Ill Patients (preprint)

Backgrounds: The coronavirus disease 2019 (COVID-19) epidemic is a major public health problem worldwide. This study estimated the impact of SARS-CoV-2 in terms of the excess mortality from any cause during the COVID-19 epidemic in the Republic of Korea. Methods: The excess mortality, ICU admissions and hospital admissions during the COVID-19 epidemic was analyzed using the number of deaths over the past 5 years (2015–2019) in Korea. The numbers of total deaths and COVID-19–related deaths were counted from January 2020 through May 2022, using public data from the Korean Statistical Information Service (KOSIS) of Statistics Korea. Data of hospital admissions were obtained from Health Insurance Review and Assessment (HIRA) service and KOSIS of Statistics Korea. Results: These numbers were compared with nationwide mortality data from January 1, 2015, through December 2019. There were more than 24,000 reported deaths officially across Korea from January 2020 through May 2022. Excess mortality was observed nationwide in March, August, October, November, and December 2020; January, March, July, and August 2021; and October 2021 through May 2022, which was consistent with the epidemic waves in the country. There was a decline in ICU admissions, especially soon after the declaration of the COVID-19 epidemic. Conclusions: After 2021, significant excess mortality occurred at the national level despite decreasing COVID-19 case fatality rates and decreased admissions to intensive care units, which means there might be an another relevant factors on all-cause mortality aside from the direct effect of deaths from COVID-19.