Risk Factors For Severe COVID-19 Research Articles

#1567 Risk factors for COVID-19 hospitalization and death in kidney transplant recipients: a retrospective nationwide study in Sweden

Abstract Background and Aims Kidney transplant recipients (KTRs) are particularly susceptible to infections due to their continuous immunosuppressive treatment, the presence of other comorbidities, and, in some cases, impaired kidney function. While previous research has identified certain risk factors for severe COVID-19 in KTRs, comprehensive data at a national level—minimizing regional or center-specific influences—remains scarce. Our study aimed to fill this gap by examining risk factors for severe COVID-19 at a national level. Thus, we conducted a retrospective analysis of COVID-19 outcomes, alongside demographic, clinical, and medication-related risk factors associated with hospitalization and mortality due to COVID-19, within a comprehensive national cohort of Swedish KTRs over the initial two years of the pandemic. Method We assessed the outcomes and identified risk factors associated with hospitalization and mortality from COVID-19 among all kidney transplant recipients in Sweden who were alive as of January 1, 2020 during the first two years of the pandemic (2020-2021). We utilized data from the Swedish Renal Registry (SRR) and other interconnected healthcare registries. The SRR is a nationwide registry, with almost complete coverage (>97%) of patients with kidney replacement therapy in Sweden, including KTRs. Through multivariable adjusted logistic regression models, we systematically analyzed this data to pinpoint risk factors contributing to severe COVID-19 cases in this specific patient population. Results There were 5,824 KTRs in Sweden on January 1, 2020 with a mean age 58 years, 64% men. An increased risk of severe COVID-19 was observed for patients aged between 49 to 68 years, with the highest point estimate for patients aged 49-58 years (OR 2.26, 95% CI 1.50-3.45) and those who underwent a prolonged duration of dialysis before their transplantation (aOR 1.04, CI 95% 1.01-1.07 [per one year increase]). Conversely, KTRs with a longer elapsed time since the transplantation and those who had received a kidney from a living donor had a lower risk of severe COVID-19. Compared to KTRs who were transplanted less than a year ago, those who had received their transplant 6-10 years ago or >10 years ago had an about 50% lower risk of being hospitalized or die from COVID-19 (aOR 0.49, CI 95% 0.35-0.68 and aOR 0.55, CI 95% 0.40-0.74, respectively). While no significant correlation was observed directly between hypertension and severe COVID-19, a significant association was identified with the increasing number of antihypertensive medications prescribed to a patient (P-value <.0001). Furthermore, treatment with mycophenolate mofetil and the use of a higher number of immunosuppressive drugs were associated with a higher risk of severe COVID-19. The use of proton pump inhibitors was also linked to an increased risk of severe COVID-19 (aOR 1.66, 95% CI 1.33-2.07). Conclusion Our study reveals several critical insights into the risk factors associated with severe COVID-19 among KTRs in Sweden. A key finding is the increased risk observed in individuals of working age, potentially due to higher exposure to the virus. Additionally, our findings suggest that the severity of comorbidities, rather than the presence of comorbidities themselves, may play a more significant role in increasing the risk of severe COVID-19. Importantly, our research sheds light on the potential impact of proton pump inhibitor (PPI) therapy, as a modifiable risk factor in the management of COVID-19. In general, our findings are instrumental in developing more targeted prevention and treatment strategies for COVID-19 in KTRs, aiming to improve care for this particularly vulnerable group.

Whole blood transcriptome signature predicts severe forms of COVID-19: Results from the COVIDeF cohort study

COVID-19 is associated with heterogeneous outcome. Early identification of a severe progression of the disease is essential to properly manage the patients and improve their outcome. Biomarkers reflecting an increased inflammatory response, as well as individual features including advanced age, male gender, and pre-existing comorbidities, are risk factors of severe COVID-19. Yet, these features show limited accuracy for outcome prediction. The aim was to evaluate the prognostic value of whole blood transcriptome at an early stage of the disease. Blood transcriptome of patients with mild pneumonia was profiled. Patients with subsequent severe COVID-19 were compared to those with favourable outcome, and a molecular predictor based on gene expression was built. Unsupervised classification discriminated patients who would later develop a COVID-19-related severe pneumonia. The corresponding gene expression signature reflected the immune response to the viral infection dominated by a prominent type I interferon, with IFI27 among the most over-expressed genes. A 48-genes transcriptome signature predicting the risk of severe COVID-19 was built on a training cohort, then validated on an external independent cohort, showing an accuracy of 81% for predicting severe outcome. These results identify an early transcriptome signature of severe COVID-19 pneumonia, with a possible relevance to improve COVID-19 patient management.

Clinical and Laboratory Profile, Management and Outcome of Pediatric SARS-CoV-2 Infection Admitted at the Philippine General Hospital

Background. The Philippines has recorded over 470,000 COVID-19 cases in children, with over 1,500 deathsduring the same period. Although a Philippine online pediatric COVID-19 registry exists, this only relies on passive surveillance. Objectives. This study determined the clinical and laboratory profile, risk factors for severe COVID-19, and mortality, management, and outcome of pediatric SARS-CoV-2 patients admitted at the Philippine General Hospital (PGH) from April 2020 to June 2022 to fill in knowledge gaps on the epidemiology of COVID-19 infection in children. Methods. This was a retrospective cohort study of pediatric COVID-19 cases admitted at the PGH, a designatedCOVID referral center during the study period. Demographic and clinical profile, risk factors, comorbidities, laboratory and radiologic findings, management, and outcomes across different disease severity states were gathered by chart review and the data were analyzed using STATA 17. Results. There were 448 pediatric patients admitted and diagnosed with COVID-19 during the study period. Most patients belonged to the 1-5-year age group (25.9%), had no known exposure to a COVID-19 case (65.4%), were mild cases (37.3%%), and did not receive any dose of the COVID-19 vaccine (96.7%). The most common presenting symptoms across all disease categories were fever (44.4%), cough (28.6%), and shortness of breath (26.6%). Multisystem inflammatory syndrome in children (MIS-C) presented with fever (100%) and rash (53.9%). The risk factors for severe disease were the presence of a congenital anomaly lung disease, and elevated procalcitonin. Most patients with MIS-C were previously well with no comorbidities. Laboratory findings which were markedly elevated among severe and critical cases were ESR, CRP, D-dimer, LDH, and IL-6. Ferritin, procalcitonin (PCT) and IL-6 were elevated only in severe to critical COVID-19 cases and remained within normal for the other disease categories. As to treatment, asymptomatic, mild, and moderate cases were given supportive medications (zinc, vitamin D, and vitamin C), while investigational drugs particularly corticosteroids, IVIG, and remdesivir, were used in severe cases. Antibiotics were given to 71.7% of patients at the outset.As to the outcomes, 89% recovered, while 8.9% died. The case fatality rate from COVID-19 infection was at2.2%. Conclusion. Admitted pediatric COVID-19 cases are generally mild but admission is due to underlying illnessor comorbidities. Those with severe to critical cases have underlying comorbidities and had either progression or complications due to COVID disease. D-dimer, LDH, IL-6, ferritin and procalcitonin were elevated among severe and critical cases which can be utilized as inflammatory markers.

Dysphagia Is an Underrecognized Risk Factor for Viral Pneumonia Severity.

The aim of this study was to examine the role of pre-existing dysphagia as a risk factor for COVID-19 severity among adults ≥50years of age presenting to the emergency department (ED). This was a retrospective cohort study that used electronic health record data from two Midwestern EDs in the same health care system. The sample included patients ≥50years of age who tested positive for SARS-COV-2 during an ED visit between March 15, 2020 and November 19, 2020. Patients were dichotomized based on documented history of dysphagia. The primary outcome was the highest World Health Organization COVID-19 clinical severity score within 30-days of ED arrival. Patients with a score of <4 were classified as non-severe whereas a score ≥4 was considered severe. Chi-square tests were used to assess differences in clinical severity scores between patients with and without dysphagia. A logistic regression model was created to estimate the odds of a severe COVID-19 clinical score. The sample included 126 patients without dysphagia and 40 patients with dysphagia. Patients with a history of dysphagia were more likely to develop severe COVID-19 disease compared to patients without (65.0% vs. 41.3%, p = 0.015). In multivariable analysis, patients with preexisting dysphagia (OR 2.38, 95% CI: 1.05-5.42; p = 0.038) and diabetes (OR 2.42 95% CI: 1.15-5.30; p = 0.021) had significantly increased odds of developing severe COVID-19. This study showed that a pre-existing diagnosis of dysphagia was independently associated with COVID-19 severity in adults ≥50years of age.

Risk Factors for Severe COVID-19 Among Children and Adolescents Enrolled in Acute Respiratory Infection Sentinel Surveillance in South Africa, 2020-2022.

Identifying children at risk for severe COVID-19 disease from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may guide future mitigation interventions. Using sentinel surveillance data, we aimed to identify risk factors for SARS-CoV-2-associated hospitalisation among patients aged ≤ 18 years with respiratory illness. From April 2020 to March 2022, patients meeting study case definitions were enrolled at four outpatient influenza-like illness (ILI) and five inpatient severe respiratory infection (SRI) surveillance sites and tested for SARS-CoV-2 infection using polymerase chain reaction (PCR). Each ILI clinic shared a catchment area with its corresponding SRI hospital. Potential risk factors for SARS-CoV-2-associated hospitalisation were analysed using multivariable logistic regression by comparing inpatient versus outpatient SARS-CoV-2 cases. Of 4688 participants aged ≤ 18 years, 4556 (97%) with complete PCR and HIV data were included in the analysis. Among patients with ILI and SRI, 92/1145 (8%) and 154/3411 (5%) tested SARS-CoV-2 positive, respectively. Compared to outpatients, hospitalised SARS-CoV-2 cases were associated with age < 6 months ([adjusted odds ratio (aOR) 8.0, 95% confidence interval (CI) 2.7-24.0] versus 1-4 years); underlying medical condition other than HIV [aOR 5.8, 95% CI 2.3-14.6]; laboratory-confirmed Omicron BA.1/BA.2 or Delta variant ([aOR 4.9, 95% CI 1.7-14.2] or [aOR 2.8, 95% CI 1.1-7.3] compared to ancestral SARS-CoV-2); and respiratory syncytial virus coinfection [aOR 6.2, 95% CI 1.0-38.5]. Aligning with previous research, we identified age < 6 months or having an underlying condition as risk factors for SARS-CoV-2-associated SRI hospitalisation and demonstrated the potential of sentinel surveillance to monitor COVID-19 in children.

Potential Risk Factors to COVID-19 Severity: Comparison of SARS-CoV-2 Delta- and Omicron-Dominant Periods.

Continued study of risk factors can inform future pandemic preparedness and response. We aimed to determine the potential risk factors of COVID-19 severity among patients admitted to the hospital during the Delta- and Omicron-dominant periods. We utilized the J-SPEED-style COVID-19 Hospital version, a pre-administered questionnaire, to collect data from hospitals in Hiroshima Prefecture between 8 August 2021 and 19 April 2022. During the Delta-dominant period, patients aged over 65 (OR = 2.59, 95% CI = 1.75-3.84), males (OR = 1.42, 95% CI = 1.12-1.81) and with BMI exceeding 25 (OR = 1.99, 95% CI = 1.57-2.52), diabetes (OR = 2.03, 95% CI = 1.40-2.95), and those with fewer than two doses of vaccine (OR = 2.39, 95% CI = 1.46-3.91) were at a greater risk of severe COVID-19 compared to those without these risk factors. During the Omicron-dominant period, significantly greater severity was observed among patients over 65 years old (OR = 3.89, 95% CI = 2.95-5.12), males (OR = 1.76, 95% CI = 1.40-2.21), those with high blood pressure (OR = 1.30, 95% CI = 1.02-1.65), and mental disorder (OR = 2.22, 95% CI = 1.69-2.92) compared to patients without these risks. Our findings indicate that risk factors vary across different SARS-CoV-2 variants. Examining variant-specific risk factors for COVID-19 severity can aid policymakers, public health specialists, and clinicians in prioritizing screening, treatment, and vaccination efforts, especially during potential healthcare resource shortages.

Risk factors for severe COVID-19 in patients with rheumatic diseases

The aim – to study risk factors for severe COVID-19 in patients with rheumatic diseases (RD).Patients and methods. The study included medical histories of 464 patients with RD who were admitted at the V.A. Nasonova Research Institute of Rheumatology from September 27, 2021 to April 26, 2023Results. Age over 60 years, hypertension, obesity, lung disease, chronic kidney disease, coronary heart disease, diabetes mellitus, acute cerebrovascular accident or a history of pulmonary tuberculosis increase the risk of hospitalization in patients with RD with COVID-19 by 3–5 times. In addition, with an increase in the number of concomitant diseases, an increase in the risk of hospitalization was noted by 2–6 times. Taking glucocorticoids, including at a dose of ≥10 mg per day for prednisolone, mycophenolate mofetil and rituximab, leads to an increase risk of hospitalization by 1.5–4.5 times, while patients taking hydroxychloroquine or tumor necrosis factor α inhibitors was more often required outpatient treatment.Conclusions. It has been established that older age, the presence of comorbid pathology and the use of glucocorticoids, including at a dose of ≥10 mg per day for prednisolone, mycophenolate mofetil and rituximab, are risk factors for severe COVID-19.

Epidemiological and Clinical Characteristics Associated with COVID-19 Severity Among Hospitalized Patients in the United Arab Emirates: A Retrospective Multicentre Study.

To investigate the clinical and epidemiological factors associated with severe COVID-19 cases in hospitalized patients across two emirates within the United Arab Emirates (UAE). A retrospective observational analytical study analysed data from 738medical records and conducted 573 in-depth interviews with patients hospitalized across multiple healthcare centers in the UAE, between 29 January 2020 and 14 October 2021. Regression analysis predicted risk factors for COVID-19 severity. Main risk factors identified were crowding (aOR 1.919; 95%CI 1.144, 3.221), obesity (aOR 2.383; 95%CI 1.332, 4.263), diabetes (aOR 11.14; 95%CI 2.653-46.797), severe dehydration (aOR 3.219; 95%CI 2.161, 4.795), cough or sore throat (aOR 1.607; 95%CI 1.032, 2.502), shortness of breath (aOR 1.921; 95%CI 1.294, 2.853), increased days from symptom onset to admission (aOR 1.055; 95%CI 1.006, 1.105), elevated ANC (aOR 1.263, 95%CI 1.121, 1.424), and AST/SGOT (aOR 1.055, 95% CI 1.016, 1.095). Protective factors included smoking (aOR 0.367; 95%CI 0.182, 0.740), first dose of COVID-19 vaccination (aOR 0.595; 95%CI 0.377, 0.93), higher oxygen saturation (aOR 0.853; 95%CI: 0.801, 0.907) and elevated ALC (aOR 0.540; 95%CI 0.323, 0.905). Identifying risk factors is crucial for high-risk individuals who may require closer monitoring to improve their outcomes. This can provide guidance for surveillance systems and early detection strategies to mitigate the impact of future outbreaks.

Health Status Associated with SARS-CoV-2 Risk Perceptions in Sierra Leone and Zimbabwe

Background &amp; Aims. The COVID-19 pandemic had a significant impact on health in countries of every income level. While much is known about risk factors for COVID-19 severity, less is known about the relationship between COVID related risk perceptions and behaviors, particularly in low-income settings. The purpose of this study is to investigate the relationship between existing health status and COVID-19 risk perceptions and behaviors in Sierra Leone and Zimbabwe.&#x0D; Methods. Data for this study came from a cross-sectional survey conducted simultaneously among 1158 adults in Sierra Leone and 1154 in Zimbabwe during July and August of 2022. Respondents were recruited from among communities served by the Christian Health Association of Sierra Leone (CHASL) and Zimbabwe Association of Church-Related Hospitals (ZACH), both members of the Africa Christian Health Associations Network (ACHAP).&#x0D; Results. The relationship between health status and COVID-19 risk perceptions and behaviors varied significantly by health condition. Cardiovascular disease was significantly associated with heightened perceptions of COVID-19 risk, heightened perceived safety of COVID vaccines, and subsequent greater vaccine acceptance while cancer was likewise statistically significant in each of lower perceived susceptibility, perceived safety, and vaccination uptake. Similarly, obesity was associated with both lower perceived susceptibility of COVID-19 and decreased perceived safety of COVID vaccines.&#x0D; Conclusion. Results suggest that the association between health conditions and COVID perceptions and behaviors is neither clear nor consistent across a variety of NCDs. Hence, findings from this study may inform public health interventions aimed at reducing COVID-19 morbidity and mortality, including increasing vaccine acceptance and uptake in Sierra Leone and Zimbabwe. Further, findings potentially have broader implications for understanding how health status is associated with COVID-19 risk perceptions in other LMICs.

The Intersections of COVID-19, HIV, and Race/Ethnicity: Machine Learning Methods to Identify and Model Risk Factors for Severe COVID-19 in a Large U.S. National Dataset.

We investigate risk factors for severe COVID-19 in persons living with HIV (PWH), including among racialized PWH, using the U.S. population-sampled National COVID Cohort Collaborative (N3C) data released from January 1, 2020 to October 10, 2022. We defined severe COVID-19 as hospitalized with invasive mechanical ventilation, extracorporeal membrane oxygenation, discharge to hospice or death. We used machine learning methods to identify highly ranked, uncorrelated factors predicting severe COVID-19, and used multivariable logistic regression models to assess the associations of these variables with severe COVID-19 in several models, including race-stratified models. There were 3 241 627 individuals with incident COVID-19 cases and 81 549 (2.5%) with severe COVID-19, of which 17 445 incident COVID-19 and 1 020 (5.8%) severe cases were among PWH. The top highly ranked factors of severe COVID-19 were age, congestive heart failure (CHF), dementia, renal disease, sodium concentration, smoking status, and sex. Among PWH, age and sodium concentration were important predictors of COVID-19 severity, and the effect of sodium concentration was more pronounced in Hispanics (aOR 4.11 compared to aOR range: 1.47-1.88 for Black, White, and Other non-Hispanics). Dementia, CHF, and renal disease was associated with higher odds of severe COVID-19 among Black, Hispanic, and Other non-Hispanics PWH, respectively. Our findings suggest that the impact of factors, especially clinical comorbidities, predictive of severe COVID-19 among PWH varies by racialized groups, highlighting a need to account for race and comorbidity burden when assessing the risk of PWH developing severe COVID-19.

Genetic association of ACE2 and TMPRSS2 polymorphisms with COVID-19 severity; a single centre study from Egypt

BackgroundSince the emergence of the COVID-19 infection in China, it has caused considerable morbidity, mortality, and economic burden. It causes the vast majority of clinical manifestations, ranging from mild or even no symptoms to severe respiratory failure. There are many risk factors for severe COVID-19, such as old age, male gender, and associated comorbidities. A major role for genetic factors may exist. The SARS-CoV-2 virus enters the cell primarily through ACE2 receptors. rs2285666 is one of many polymorphisms found in the ACE2 receptor gene. To enable endosome-independent entry into target cells, the transmembrane protease serine-type 2 (TMPRSS2) is necessary to cleave the virus’ spike (S) glycoprotein. TMPRSS2 is characterized by an androgen receptor element. The rs12329760 polymorphism in TMPRSS2 may explain different genetic susceptibilities to COVID-19.MethodThis cross-sectional study was held in Mansoura University Hospitals during the period from June 2020 to April 2022 on patients who had mild and severe COVID-19. Demographic, clinical, and laboratory data were collected, and the TaqMan real-time polymerase chain was used for allelic discrimination in the genotyping of rs2285666 and rs12329760.ResultsThis study included 317 Egyptian patients, aged from 0.2 to 87 years. Males were 146, while females were 171. They were divided into mild and severe groups (91 and 226 patients, respectively) based on their clinical symptoms. There was a significant association between COVID-19 severity and male gender, hypertension, diabetes mellitus, and high CRP. The genotype and allele frequency distributions of the ACE2 rs2285666 polymorphism showed no significant association with the severity of COVID-19 in both. In contrast, in TMPRSS2 rs12329760 minor T allele and CT, TT genotypes were significantly associated with a reduced likelihood of developing severe COVID-19.ConclusionOur study indicates that the ACE2 rs2285666 polymorphism is not related to the severity of COVID-19, whether genotypes or alleles. In TMPRSS2 rs12329760, the dominant model and T allele showed significantly lower frequencies in severe cases, with a protective effect against severity. The discrepancies with previous results may be due to variations in other ACE2 receptor-related genes, inflammatory mediators, and coagulation indicators. Haplotype blocks and differences in racial makeup must be taken into consideration. Future research should be done to clarify how ethnicity affects these polymorphisms and how other comorbidities combine to have an additive effect.

Evaluation of Genetic or Cellular Impairments in Type I IFN Immunity in a Cohort of Young Adults with Critical COVID-19

Several genetic and immunological risk factors for severe COVID-19 have been identified, with monogenic conditions relating to 13 genes of type I interferon (IFN) immunity proposed to explain 4.8% of critical cases. However, previous cohorts have been clinically heterogeneous and were not subjected to thorough genetic and immunological analyses. We therefore aimed to systematically investigate the prevalence of rare genetic variants causing inborn errors of immunity (IEI) and functionally interrogate the type I IFN pathway in young adults that suffered from critical COVID-19 yet lacked comorbidities. We selected and clinically characterized a cohort of 38 previously healthy individuals under 50 years of age who were treated in intensive care units due to critical COVID-19. Blood samples were collected after convalescence. Two patients had IFN-α autoantibodies. Genome sequencing revealed very rare variants in the type I IFN pathway in 31.6% of the patients, which was similar to controls. Analyses of cryopreserved leukocytes did not indicate any defect in plasmacytoid dendritic cell sensing of TLR7 and TLR9 agonists in patients carrying variants in these pathways. However, lymphocyte STAT phosphorylation and protein upregulation upon IFN-α stimulation revealed three possible cases of impaired type I IFN signaling in carriers of rare variants. Together, our results suggest a strategy of functional screening followed by genome analyses and biochemical validation to uncover undiagnosed causes of critical COVID-19.

COVID-19 in patients with acute leukemia: 3 years' experience of pandemic

Patients with acute leukemia are one of the most vulnerable risk groups for infection with SARS-CoV-2 and severe course of coronavirus infection. During the first 2 years of the pandemic, the mortality rate of patients with acute leukemia was 11-48 %, depending on leukemia type, and only reached population levels in 2022. Risk factors for severe COVID-19 in patients with acute leukemia are old age, concomitant cardiac pathology, metabolic syndrome, and the absence of acute leukemia remission. Chemotherapy administered one month before hospitalization with COVID-19 diagnosis showed statistical significance in influencing hospital mortality only in the group of patients with acute myeloid leukemia. Despite this, the international medical community has recommended delaying the start of chemotherapy until clinical symptoms of coronavirus infection have completely resolved and a negative test result for SARS-CoV-2 has been obtained for all types of leukemia. Currently, the most optimal tactic is to prevent SARS-CoV-2 infection by vaccinating patients with acute leukemia receiving antitumor treatment. If the immunological response to vaccination is insufficient, it is possible to use virus-neutralizing monoclonal antibodies as a safe and effective method of primary prevention of COVID-19.

Educational Intervention to Increase COVID-19 Vaccine Uptake in Rural Patients with Chronic Diseases: Lessons Learned from An Innovative Academic-Community Partnership.

The pandemic has disproportionately impacted rural communities with a higher burden of chronic disease and COVID-19 infection. West Virginia is a rural state with a high rate of diabetes, hypertension, and COPD, which are known risk factors for severe COVID-19 and long COVID. Yet, there is a significant hesitancy regarding COVID-19 vaccination uptake in the state. The purpose of this study was to use an educational intervention to increase vaccine knowledge and vaccine acceptance in rural patients with chronic disease(s) in West Virginia. This project used an academic-community partnership comprised of researchers, practitioners, community organizations, community-engaged partners, and patient stakeholders to increase COVID-19 health literacy and increase vaccine acceptance among rural West Virginians with chronic conditions. A quasi-experimental study design was used to deliver an educational intervention by trained Health Navigators using short videos to increase COVID-19 health literacy and address participants' vaccine concerns. Eligibility included adults (18 years and older) who have at least one chronic condition. A statewide community advisory board (CAB) guided the development of the educational training curriculum and implementation strategies. An adapted version of the Exploration, Preparation, Implementation, Sustainment (EPIS) framework guided the development of the intervention. Health Navigators (n = 45) delivered the educational intervention in their local communities between November 2022 and October 2023 (project implementation is still ongoing). Intervention fidelity checks, an adaptable script, and a flow chart allowed tailoring of brief videos to address participants' specific COVID-19 questions and vaccine concerns. A validated online survey, monitored by an online Research Electronic Data Capture (REDCap) database, assessed participants' knowledge, perceived susceptibility, and vaccine intention. Health Navigators delivered the intervention to 1368 West Virginians in 52 counties (59.2% women; 61.8% without a college degree). Participants reported living with an average of 2.1 ± 1.4 chronic conditions. The mean age was 43.5 ± 18.8 years. The majority of participants (81.2%) had received the primary vaccination series, and 63.1% had at least one booster. However, 18% were unvaccinated or did not complete the primary COVID-19 vaccine series. Discussions to improve vaccine literacy focused on how the vaccine was so quickly developed and protects against variants, addressing concerns related to the safety, short- and long-term side effects, and importance of vaccine uptake for immunocompromised individuals. Participants with higher concerns were more likely to be unvaccinated and to have not completed their primary series or boosters (p < 0.001). However, the educational intervention improved the willingness of individuals who were either unvaccinated or did not complete their primary vaccine series to get vaccinated (11.4%). Our findings highlight the importance of vaccine literacy in increasing vaccination rates among rural patients with chronic diseases. Using the EPIS framework allowed us to reflect upon the challenges, ensure resilience during changing local contexts, and plan and implement a promising, cost-effective intervention in rural areas. This study provides insights into the need for tailored educational interventions based on disease status, which has implications for public health and patient care in rural and underserved communities. Academic-community partnerships can be useful for successful knowledge transfer for vaccine acceptance to reduce rural health disparities.

Association of ACE1 I/D polymorphism and susceptibility to COVID-19 in Egyptian children and adolescents.

Given the sparse data on the renin-angiotensin system (RAS) and its biological effector molecules ACE1 and ACE2 in pediatric COVID-19 cases, we investigated whether the ACE1 insertion/deletion (I/D) polymorphism could be a genetic marker for susceptibility to COVID-19 in Egyptian children and adolescents. This was a case-control study included four hundred sixty patients diagnosed with COVID-19, and 460 well-matched healthy control children and adolescents. The I/D polymorphism (rs1799752) in the ACE1 gene was genotyped by polymerase chain reaction (PCR), meanwhile the ACE serum concentrations were assessed by ELISA. The ACE1 D/D genotype and Deletion allele were significantly more represented in patients with COVID-19 compared to the control group (55% vs. 28%; OR = 2.4; [95% CI: 1.46-3.95]; for the DD genotype; P = 0.002) and (68% vs. 52.5%; OR: 1.93; [95% CI: 1.49-2.5] for the D allele; P = 0.032). The presence of ACE1 D/D genotype was an independent risk factor for severe COVID-19 among studied patients (adjusted OR: 2.6; [95% CI: 1.6-9.7]; P < 0.001. The ACE1 insertion/deletion polymorphism may confer susceptibility to SARS-CoV-2 infection in Egyptian children and adolescents. Recent studies suggested a crucial role of renin-angiotensin system and its biological effector molecules ACE1 and ACE2 in the pathogenesis and progression of COVID-19. To our knowledge, ours is the first study to investigate the association of ACE1 I/D polymorphism and susceptibility to COVID-19 in Caucasian children and adolescents. The presence of the ACE1 D/D genotype or ACE1 Deletion allele may confer susceptibility to SARS-CoV-2 infection and being associated with higher ACE serum levels; may constitute independent risk factors for severe COVID-19. The ACE1 I/D genotyping help design further clinical trials reconsidering RAS-pathway antagonists to achieve more efficient targeted therapies.

SARS-CoV-2 Antiviral Prescribing Gaps Among Non-Hospitalized High-Risk Adults.

Within a multi-state clinical cohort, SARS-CoV-2 antiviral prescribing patterns were evaluated from April 2022-June 2023 among non-hospitalized SARS-CoV-2-infected patients with risk factors for severe COVID-19. Among 3,247 adults, only 31.9% were prescribed an antiviral agent (87.6% nirmatrelvir/ritonavir, 11.9% molnupiravir, 0.5% remdesivir), highlighting the need to identify and address treatment barriers.

The protective effect of tumor necrosis factor-alpha inhibitors in COVID-19 in patients with inflammatory rheumatic diseases compared to the general population-A comparison of two German registries.

To investigate, whether inflammatory rheumatic diseases (IRD) inpatients are at higher risk to develop a severe course of SARS-CoV-2 infections compared to the general population, data from the German COVID-19 registry for IRD patients and data from the Lean European Survey on SARS-CoV-2 (LEOSS) infected patients covering inpatients from the general population with SARS-CoV-2 infections were compared. 4310 (LEOSS registry) and 1139 cases (IRD registry) were collected in general. Data were matched for age and gender. From both registries, 732 matched inpatients (LEOSS registry: n = 366 and IRD registry: n = 366) were included for analyses in total. Regarding the COVID-19 associated lethality, no significant difference between both registries was observed. Age > 65°years, chronic obstructive pulmonary disease, diabetes mellitus, rheumatoid arthritis, spondyloarthritis and the use of rituximab were associated with more severe courses of COVID-19. Female gender and the use of tumor necrosis factor-alpha inhibitors (TNF-I) were associated with a better outcome of COVID-19. Inflammatory rheumatic diseases (IRD) patients have the same risk factors for severe COVID-19 regarding comorbidities compared to the general population without any immune-mediated disease or immunomodulation. The use of rituximab was associated with an increased risk for severe COVID-19. On the other hand, the use of TNF-I was associated with less severe COVID-19 compared to the general population, which might indicate a protective effect of TNF-I against severe COVID-19 disease.

Predictive Role of Platelet and Inflammation Markers for Severe COVID-19 by Propensity Score Matching.

This study aims to ascertain the predictive value of platelet and inflammation markers in severe cases of COVID-19. A retrospective real-world cohort study was conducted using propensity score matching (PSM). Patients were classified into severe and non-severe COVID-19 groups based on the severity of the disease, and the correlation between severe COVID-19 and laboratory parameters at admission was analyzed. The study included 397 adult patients, comprising 212 (53%) males and 185 (47%) females. Among these, 309 were non-severe and 88 were severe cases. The severe group had a higher median age than the non-severe group (60 vs. 42 years, p < 0.001). Independent risk factors for severe COVID-19 included age, diabetes comorbidity, fever, respiratory symptoms, platelet count, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and the ratio of arterial oxygen partial pressure (PaO2) to the fraction of inspired oxygen (FiO2) (P/F ratio). After one-to-one PSM, adjusted for age, diabetes comorbidities, fever, and respiratory symptoms, significant differences in laboratory parameters at admission were observed. Compared to the non-severe group (n = 71), in the severe group (n = 71), elevated levels of hsCRP (median: 27.1 mg/L vs. 14.6 mg/L, p = 0.005) and IL-6 (median: 16.2 pg/mL vs. 15.3 pg/mL, p = 0.005) were observed, while platelet count (164 ± 36 × 109 vs. 180 ± 50 × 109, p = 0.02) and P/F ratio (median: 351 vs. 397, p = 0.001) were reduced. Elevated levels of hsCRP and IL-6, along with reduced platelet count and P/F ratio at admission, were significantly associated with severe COVID-19 and may serve as predictive indicators.

Estimating spatially disaggregated probability of severe COVID-19 and the impact of handwashing interventions: The case of Zimbabwe.

The severity of COVID-19 disease varies substantially between individuals, with some infections being asymptomatic while others are fatal. Several risk factors have been identified that affect the progression of SARS-CoV-2 to severe COVID-19. They include age, smoking and presence of underlying comorbidities such as respiratory illness, HIV, anemia and obesity. Given that respiratory illness is one such comorbidity and is affected by hand hygiene, it is plausible that improving access to handwashing could lower the risk of severe COVID-19 among a population. In this paper, we estimate the potential impact of improved access to handwashing on the risk of respiratory illness and its knock-on impact on the risk of developing severe COVID-19 disease across Zimbabwe. Spatial generalized additive models were applied to cluster level data from the 2015 Demographic and Health Survey. These models were used to generate continuous (1km resolution) estimates of risk factors for severe COVID-19, including prevalence of major comorbidities (respiratory illness, HIV without viral load suppression, anemia and obesity) and prevalence of smoking, which were aggregated to district level alongside estimates of the proportion of the population under 50 from Worldpop data. The risk of severe COVID-19 was then calculated for each district using published estimates of the relationship between comorbidities, smoking and age (under 50) and severe COVID-19. Two scenarios were then simulated to see how changing access to handwashing facilities could have knock on implications for the prevalence of severe COVID-19 in the population. This modeling conducted in this study shows that (1) current risk of severe disease is heterogeneous across the country, due to differences in individual characteristics and household conditions and (2) that if the quantifiable estimates on the importance of handwashing for transmission are sound, then improvements in handwashing access could lead to reductions in the risk of severe COVID-19 of up to 16% from the estimated current levels across all districts. Taken alongside the likely impact on transmission of SARS-CoV-2 itself, as well as countless other pathogens, this result adds further support for the expansion of access to handwashing across the country. It also highlights the spatial differences in risk of severe COVID-19, and thus the opportunity for better planning to focus limited resources in high-risk areas in order to potentially reduce the number of severe cases.

COVID-19 in pediatric palliative care patients: Multicenter, retrospective cohort study

Background: Studies have shown the risk factors for COVID-19 severity in children, including comorbidities, but information on the infection course in children with life-limiting conditions is sparse. Aim: To describe the effect of COVID-19 on pediatric patients receiving palliative care due to life-limiting conditions. Design: We conducted retrospective cohort study. The WHO Clinical Progression Scale was used to measure COVID-19 severity. Setting/participants: Seven of the 24 invited pediatric palliative care centers participated in this study. We analyzed the medical records of children under palliative care with confirmed COVID-19 (January 2020–April 2022) Results: Records of 60 patients with COVID-19 aged 0.24 to 21.6 years (mean (SD); 9.8 (6.6)) were collected. The largest group of patients with COVID-19 was children with congenital malformations and chromosomal abnormalities (42%); the most common manifestation was fever (85%). Bacterial coinfection was confirmed in 17 (28%) children. Fifteen (25%) children required hospitalization, including four admitted to the Intensive Care Unit. Mild COVID-19 was identified in 44 (73%) children, moderate in 11 (18%), severe in 3 (5%), and death in 2 (3%). Six of the 20 eligible children were vaccinated against SARS-CoV-2, followed by 16 mothers and fathers. Conclusion: In the study population initial presentation of COVID-19 was predominantly a mild; however, the small sample size precluded definitive conclusions. For children under palliative care, we should identify if they have an advance care plan for COVID-19, such as desires for intensive care support. Further studies are needed to define the short and long-term effects of COVID-19 in children with life-limiting conditions.