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Abstract Background Respiratory Syncytial Virus (RSV) disease in young children ranges from mild cold symptoms to severe symptoms that require hospitalization and sometimes result in death. Studies have shown a statistical association between RSV subtype or phylogenic lineage and RSV disease severity, although these results have been inconsistent. Associations between variation within RSV gene coding regions or residues and RSV disease severity has been largely unexplored. Methods Nasal swabs from children (

Background: Respiratory Syncytial Virus (RSV) disease in young children ranges from mild cold symptoms to severe symptoms that require hospitalization and sometimes result in death. Studies have shown a statistical association between RSV subtype or phylogenic lineage and RSV disease severity, although these results have been inconsistent. Associations between variation within RSV gene coding regions or residues and RSV disease severity has been largely unexplored. Methods: Nasal swabs from children (< 8 months-old) infected with RSV in Rochester, NY between 1977–1998 clinically presenting with either mild or severe disease during their first cold-season were used. Whole-genome RSV sequences were obtained using overlapping PCR and next-generation sequencing. Both whole-genome phylogenetic and non-phylogenetic statistical approaches were performed to associate RSV genotype with disease severity. Results: The RSVB subtype was statistically associated with disease severity. A significant association between phylogenetic clustering of mild/severe traits and disease severity was also found. GA1 clade sequences were associated with severe disease while GB1 was significantly associated with mild disease. Both G and M2-2 gene variation was significantly associated with disease severity. We identified 16 residues in the G gene and 3 in the M2-2 RSV gene associated with disease severity. Conclusion: These results suggest that phylogenetic lineage and the genetic variability in G or M2-2 genes of RSV may contribute to disease severity in young children undergoing their first infection. [ABSTRACT FROM AUTHOR]

A healthcare provider unknowingly treated a patient with mpox and subsequently developed ocular mpox without rash. She breastfed during illness; her infant was not infected. This report addresses 3 challenges in mpox management and control: diagnosis in the absence of rash, exposures in healthcare settings, and management of lactating patients. [ABSTRACT FROM AUTHOR]

Aim: This population-based study investigated the occurrence of capillary leak syndrome (CLS) in children with multisystem inflammatory syndrome in children (MIS-C), associated with COVID-19. We also examined associations between CLS and MIS-C disease severity. Methods: All eligible individuals aged 0-18 years, who were diagnosed with MIS-C in Skåne, southern Sweden, from 1 April 2020 to 31 July 2021, were studied. They were all included in the Pediatric Rheumatology Quality Register and clinical and laboratory data were compared between patients with and without CLS. Results: We included 31 patients (61% male) with MIS-C in the study. The median age at diagnosis was 10.6 years (range 1.99-17.15) and 45% developed CLS. All six patients who required intensive care had CLS. Patients with CLS also had a higher incidence of reduced cardiac function, measured as low ejection fraction. The CLS group exhibited significantly higher C-reactive protein values (p < 0.001) and N-terminal pro-Btype natriuretic peptide levels (p < 0.001), as well as lower platelet counts (p = 0.03), during the first week of treatment. Individuals with CLS also received more intense immunosuppression. Conclusion: CLS was a common complication of MIS-C in our study and these patients had a more severe disease course that required more intensive treatment. [ABSTRACT FROM AUTHOR]

Abstract Introduction COVID-19 disease resulted in over six million deaths worldwide. Although vaccines against SARS-CoV-2 demonstrated efficacy, breakthrough infections became increasingly common. There is still a lack of data regarding the severity and outcomes of COVID-19 among vaccinated compared to unvaccinated individuals. Methods This was a historical cohort study of adult COVID-19 patients hospitalized in five Ascension hospitals in southeast Michigan. Electronic medical records were reviewed. Vaccine information was collected from the Michigan Care Improvement Registry. Data were analyzed using Student’s t-test, analysis of variance, the chi-squared test, the Mann-Whitney and Kruskal-Wallis tests, and multivariable logistic regression. Results Of 341 patients, the mean age was 57.9 ± 18.3 years, 54.8% (187/341) were female, and 48.7% (166/341) were black/African American. Most patients were unvaccinated, 65.7%, 8.5%, and 25.8% receiving one dose or at least two doses, respectively. Unvaccinated patients were younger than fully vaccinated (p = 0.001) and were more likely to be black/African American (p = 0.002). Fully vaccinated patients were 5.3 times less likely to have severe/critical disease (WHO classification) than unvaccinated patients (p

Background Coronavirus disease 2019 (COVID-19) has created the need to evaluate drugs such as favipiravir (FPV), an antiviral inhibitor of RNA-dependent RNA-polymerase (RdRp), and Maraviroc (MVC), an antiretroviral that antagonizes the chemokine receptor CCR5, which could affect the modulation of inflammation and viral replication in the treatment of COVID-19. We sought to evaluate the effect of MVC and/or FPV plus systemic steroid (SS) vs. SS alone on the viral load and progression to critical disease. Methods Sixteen patients with severe COVID-19 were evaluated in three treatment arms: 1) SS only (n=6), 2) SS plus one test drug MVC or FPV (n=5), and 3) SS plus both test drugs (MVC and FPV, n=5). The viral load was determined for N, E, and RdRp viral genes. Results A significant decrease in viral load was observed in the three treatment groups, with a larger effect size in the group that combined SS with both test drugs. The E, N, and RdRp genes with Cohen’s d were 120%, 123%, and 50%, respectively. Conclusions The largest effect on viral load reduction, as measured by effect size, was observed in the combination treatment group; however, no statistical significance was found, and it did not prevent progression to critical illness.

A global shift to bivalent mRNA vaccines is ongoing to counterbalance the diminishing effectiveness of the original monovalent vaccines due to the evolution of SARS-CoV-2 variants, yet substantial variation in the bivalent vaccine effectiveness (VE) exists across studies and a complete picture is lacking. We searched papers evaluating absolute or relative effectiveness of SARS-CoV-2 BA.1 type or BA.4/5 type bivalent mRNA vaccines on eight publication databases published from September 1st, 2022, to November 8th, 2023. Pooled VE against Omicron-associated infection and severe events (hospitalization and/or death) was estimated in reference to unvaccinated, ≥2 original monovalent doses, and ≥ 3 original monovalent doses. From 630 citations identified, 28 studies were included, involving 55,393,303 individuals. Bivalent boosters demonstrated higher effectiveness against symptomatic or any infection for all ages combined, with an absolute VE of 53.5 % (95 % CI: –22.2–82.3 %) when compared to unvaccinated and relative VE of 30.8 % (95 % CI: 22.5–38.2 %) and 28.4 % (95 % CI: 10.2–42.9 %) when compared to ≥ 2 and ≥ 3 original monovalent doses, respectively. The corresponding VE estimates for adults ≥ 60 years old were 22.5 % (95 % CI: 16.8–39.8 %), 31.4 % (95 % CI: 27.7–35.0 %), and 30.6 % (95 % CI: −13.2–57.5 %). Pooled bivalent VE estimates against severe events were higher, 72.9 % (95 % CI: 60.5–82.4 %), 57.6 % (95 % CI: 42.4–68.8 %), and 62.1 % (95 % CI: 54.6–68.3 %) for all ages, and 72.0 % (95 % CI: 51.4–83.9 %), 63.4 % (95 % CI: 41.0–77.3 %), and 60.7 % (95 % CI: 52.4–67.6 %) for adults ≥ 60 years old, compared to unvaccinated, ≥2 original monovalent doses, and ≥ 3 original monovalent doses, respectively. The bivalent boosters demonstrated superior protection against severe outcomes than the original monovalent boosters across age groups, highlighting the critical need for improving vaccine coverage, especially among the vulnerable older subpopulation. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency and factors leading to the development of severe COVID-19 in patients presenting at civil hospital, Karachi. Study Design: Cross-sectional study. Setting: Department of Medicine, Dr. Ruth K.M Pfau Civil Hospital, Karachi. Period: July 16, 2021 to January 15, 2022. Methods: Patients of age 20 to 80 years of either gender and presented with fever (>38°C) for more than three days and diagnosed COVD-19 on PCR were included. Severity and factors of the disease were assessed and noted by researcher on pre-designed proforma. Results: The mean age was 48.5±11.07 years and most of the patients were males (56.7%) and urban residents (67%). Out of 97 COVID-19 patients, 12 had severe COVID-19 disease (12.4%), while 85 patients had mild to moderate COVID-19 disease (87.6%). In distribution of factors leading for development of severe covid-19, increasing age was noted in 8 (66.7%) patients, chronic kidney disease in 4 (33.3%), diabetes mellitus type II 3(25.0%), hypertension 6(50.0%), smoking 3 (25.0%), heart failure 2 (16.7%) while anemia was noted in 1 (8.3%) patient. Of 12 severe COVID-19 patients, 8 patients had positive family history of COVID-19. There was statistically significant association between COVID-19 severity and family history of COVID-19 (p=0.001). Conclusion: Severe covid-19 is common in patients presenting with fever while increasing age was noted as most common factor leading to development of severe covid-19 followed by hypertension and diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: As the global battle against the COVID-19 pandemic endures, the spread of the Delta variant has introduced nuanced challenges, prompting a nuanced examination. Materials and Methods: We performed a multilevel logistic regression analysis encompassing 197 patients, comprising 44 vaccinated individuals (V group) and 153 unvaccinated counterparts (UV). These patients, afflicted with the Delta variant of SARS-CoV-2, were hospitalized between October 2021 and February 2022 at the COVID-19 department of a University Centre in Cluj-Napoca, Romania. We compared patient characteristics, CT lung involvement, Padua score, oxygen saturation (O2 saturation), ventilation requirements, dynamics of arterial blood gas (ABG) parameters, ICU admission rates, and mortality rates between the two groups. Results: The UV group exhibited a statistically significant (p < 0.05) proclivity toward developing a more severe form of infection, marked by elevated rates of lung involvement, oxygen requirement, ICU admission, and mortality. Conclusion: Our findings underscore the substantial efficacy of the vaccine in diminishing the incidence of severe disease, lowering the rates of ICU admissions, and mitigating mortality among hospitalized patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effectiveness of SARS-CoV2 vaccination in preventing ordinary or intensive care unit (ICU) admissions and deaths among cases registered during a variant transitional pandemic phase in the geographically and culturally unique territory of the Province of Bolzano (South Tyrol), an Italian region with low vaccination coverage. Methods: We collected data from 93,643 patients registered as positive for SARS-CoV-2 by health authorities during the winter of 2021-22. The data were analyzed retrospectively using descriptive statistics and multiple logistic regression. Results: 925 patients were hospitalized (0.99%), 89 (0.10%) were in intensive care, and 194 (0.21%) died. Vaccinated patients had a significantly lower risk of being hospitalized: adjusted Odds Ratio (aOR): 0.39; 95% CI: 0.33-0.46, ICU admission: aOR: 0.16; 95% CI: 0.09-0.29 and death: aOR: 0.41; 95% CI: 0.29-0.58. Similar risk reductions were also observed in booster-vaccinated patients, independent of sex, age, and predominant variant. Furthermore, the median length of stay (LoS) in the ICU was significantly longer for unvaccinated individuals compared to vaccinated subjects (9 vs. 6 days; p < 0.003). Conclusion: Primary series vaccination and ongoing campaign booster doses were effective in preventing all severe disease-related outcomes and in reducing ICU Length of Stay, even during a transitional pandemic phase and in a unique territorial context. [ABSTRACT FROM AUTHOR]

Introduction: COVID-19 disease resulted in over six million deaths worldwide. Although vaccines against SARS-CoV-2 demonstrated efficacy, breakthrough infections became increasingly common. There is still a lack of data regarding the severity and outcomes of COVID-19 among vaccinated compared to unvaccinated individuals. Methods: This was a historical cohort study of adult COVID-19 patients hospitalized in five Ascension hospitals in southeast Michigan. Electronic medical records were reviewed. Vaccine information was collected from the Michigan Care Improvement Registry. Data were analyzed using Student's t-test, analysis of variance, the chi-squared test, the Mann-Whitney and Kruskal-Wallis tests, and multivariable logistic regression. Results: Of 341 patients, the mean age was 57.9 ± 18.3 years, 54.8% (187/341) were female, and 48.7% (166/341) were black/African American. Most patients were unvaccinated, 65.7%, 8.5%, and 25.8% receiving one dose or at least two doses, respectively. Unvaccinated patients were younger than fully vaccinated (p = 0.001) and were more likely to be black/African American (p = 0.002). Fully vaccinated patients were 5.3 times less likely to have severe/critical disease (WHO classification) than unvaccinated patients (p < 0.001) after controlling for age, BMI, race, home steroid use, and serum albumin levels on admission. The case fatality rate in fully vaccinated patients was 3.4% compared to 17.9% in unvaccinated patients (p = 0.003). Unvaccinated patients also had higher rates of complications. Conclusions: Patients who were unvaccinated or partially vaccinated had more in-hospital complications, severe disease, and death as compared to fully vaccinated patients. Factors associated with severe COVID-19 disease included advanced age, obesity, low serum albumin, and home steroid use. [ABSTRACT FROM AUTHOR]

Introduction and objective: Limited information is available on how neurologists make therapeutic decisions in neuromyelitis optica spectrum disorder (NMOSD), especially when new treatments with different mechanisms of action, administration, and safety profile are being approved. Decision-making can be complex under this uncertainty and may lead to therapeutic inertia (TI), which refers to lack of treatment initiation or intensification when therapeutic goals are not met. The study aim was to assess neurologists' TI in NMOSD. Methods: An online, cross-sectional study was conducted in collaboration with the Spanish Society of Neurology. Neurologists answered a survey composed of demographic characteristics, professional background, and behavioral traits. TI was defined as the lack of initiation or intensification with highefficacy treatments when there is evidence of disease activity and was assessed through five NMOSD aquaporin-4 positive (AQP4+) simulated case scenarios. A multivariate logistic regression analysis was used to determine the association between neurologists' characteristics and TI. Results: A total of 78 neurologists were included (median interquartile range [IQR] age: 36.0 [29.0--46.0] years, 55.1% male, median [IQR] experience managing demyelinating conditions was 5.2 [3.0--11.1] years). The majority of participants were general neurologists (59.0%) attending a median (IQR) of 5.0 NMOSD patients (3.0--12.0) annually. Thirty participants (38.5%) were classified as having TI. Working in a low complexity hospital and giving high importance to patient's tolerability/safety when choosing a treatment were predictors of TI. Conclusion: TI is a common phenomenon among neurologists managing NMOSD AQP4+. Identifying TI and implementing specific intervention strategies may be critical to improving therapeutic decisions and patient care. [ABSTRACT FROM AUTHOR]

The emergence of new virus variants, including the Omicron variant (B.1.1.529) of SARS-CoV-2, can lead to reduced vaccine effectiveness (VE) and the need for new vaccines or vaccine doses if the extent of immune evasion is severe. Neutralizing antibody titers have been shown to be a correlate of protection for SARS-CoV-2 and other pathogens, and could be used to quickly estimate vaccine effectiveness for new variants. However, no model currently exists to provide precise VE estimates for a new variant against severe disease for SARS-CoV-2 using robust datasets from several populations. We developed predictive models for VE against COVID-19 symptomatic disease and hospitalization across a 54-fold range of mean neutralizing antibody titers. For two mRNA vaccines (mRNA-1273, BNT162b2), models fit without Omicron data predicted that infection with the BA.1 Omicron variant increased the risk of hospitalization 2.8–4.4-fold and increased the risk of symptomatic disease 1.7–4.2-fold compared to the Delta variant. Out-of-sample validation showed that model predictions were accurate; all predictions were within 10% of observed VE estimates and fell within the model prediction intervals. Predictive models using neutralizing antibody titers can provide rapid VE estimates, which can inform vaccine booster timing, vaccine design, and vaccine selection for new virus variants. [ABSTRACT FROM AUTHOR]

Objective: To evaluate relationship between changes in the beneficial bacteria in intensive care unit (ICU) patients and nutritional therapy type. Methods: Ten patients aged ≥18 years admitted to the ICU between January and December 2020, were included. Good enteral nutrition was defined as early achievement of target calorie intake through enteral feeding. The ratio of beneficial bacteria at the first and second bowel movements after each patient's admission was calculated and the patients were classified into the increase or decrease group. Among all patients, five each were in the increase and decrease groups. We investigated patient background, changes in sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation (APACHE) II scores, nutritional doses or methods, and clinical outcomes. Results: No relationship was found between changes in the ratio of beneficial bacteria and changes in SOFA/APACHE II scores at the time of admission. The rate of good enteral nutrition was significantly higher in the increase group than in the decrease group (4/5 vs. 0/5, P=0.01). Conclusions: An increase in beneficial bacteria may be significantly related to the early establishment of enteral nutrition. In the future, accumulating cases may make it possible to establish a new nutritional strategy for critically ill patients from an intestinal microbiota perspective.

Introduction Multiple COVID-19 vaccines have been approved and employed in the fight against the pandemic. However, these vaccines have limited long-term effectiveness against severe cases and a decreased ability to prevent mild disease. Areas covered This review discusses the relevant factors influencing the efficacy of the vaccines against mild and severe infection, analyzes the possible underlying mechanisms contributing to the different outcomes in terms of vaccine function and disease progression, and proposes improvements for the next generation of vaccines. Expert Opinion The reduced efficacy of the COVID-19 vaccine in the prevention of viral infection is closely related to the emergence of novel SARS-CoV-2 variants and their rapid transmission ability. Fundamentally, the immune responses induced by COVID-19 vaccines cannot effectively halt virus replication in the upper respiratory tract because only a limited number of specific antibodies reach these areas and decrease in concentration over time. However, the established immune response can provide sufficient protection against severe diseases by blocking viral infection of the lower respiratory tract or lung owing to sufficient antibody repertoires and memory responses. Considering this situation, future COVID-19 vaccines should have the potential to replenish the mucosal immune response in the respiratory tract to prevent viral infection.

Background Coronavirus disease 2019 (COVID-19) has created the need to evaluate drugs such as favipiravir (FPV), an antiviral inhibitor of RNA-dependent RNA-polymerase (RdRp), and Maraviroc (MVC), an antiretroviral that antagonizes the chemokine receptor CCR5, which could affect the modulation of inflammation and viral replication in the treatment of COVID-19. We sought to evaluate the effect of MVC and/or FPV plus systemic steroid (SS) vs. SS alone on the viral load and progression to critical disease. Methods Sixteen patients with severe COVID-19 were evaluated in three treatment arms: 1) SS only (n=6), 2) SS plus one test drug MVC or FPV (n=5), and 3) SS plus both test drugs (MVC and FPV, n=5). The viral load was determined for N, E, and RdRp viral genes. Results A significant decrease in viral load was observed in the three treatment groups, with a larger effect size in the group that combined SS with both test drugs. The E, N, and RdRp genes with Cohen’s d were 120%, 123%, and 50%, respectively. Conclusions The largest effect on viral load reduction, as measured by effect size, was observed in the combination treatment group; however, no statistical significance was found, and it did not prevent progression to critical illness.

Severe outcomes were common among adults hospitalized for COVID-19 or influenza, while the percentage of COVID-19 hospitalizations involving critical care decreased from October 2021 to September 2022. During the Omicron BA.5 period, intensive care unit admission frequency was similar for COVID-19 and influenza, although patients with COVID-19 had a higher frequency of in-hospital death. [ABSTRACT FROM AUTHOR]

Background: Some data have recognized an association between shorter prodromal phase and severe episode of Shiga toxin-producing Escherichia coli-related hemolytic uremic syndrome (STEC-HUS). Our aims were to confirm such association and analyze characteristics of STEC-HUS patients according to duration of the prodromal phase. Methods: Patients treated from 2000 to 2022 were compared according to the presence of severe (> 10 days of dialysis and/or extra-renal complications) or non-severe disease. Association between prodromal phase duration and disease severity was assessed by ROC curve and by classifying the cohort in 3 groups according to time to diagnosis. Results: Non-severe (n = 145) and severe (n = 71) cases were compared. The latter had shorter prodromal phase, higher leukocyte count, hemoglobin, lactic dehydrogenase, liver enzymes, C-reactive protein, urea and creatinine, and lower albumin and sodium; only prodromal phase duration (p = 0.02) and leukocyte count (p = 0.02) remained significant in multivariate analysis. By ROC curve analysis, time to diagnosis resulted in a poor predictor of outcomes (AUC = 0.27). Since prodromal phase duration was 5 days (IQR 3–7), we divided the cohort into Groups A (1–2 days), B (3–7 days), and C (≥ 8 days). Rates of severe disease were 75.8%, 29.6%, and 11.4%, respectively. Taking Group B as reference, Group A patients had higher risk of complications (p = 0.00001; OR 7.4, 95% CI: 2.98–18.7) while Group C ones had significantly less risk (p = 0.02; OR 0.3, 95% CI: 0.1–0.91). Conclusions: This study found that duration of prodromal phase is an independent predictor of complicated STEC-HUS and confirms that shorter prodromal phase is associated with worse prognosis. [ABSTRACT FROM AUTHOR]

Objective: Decrease in free thyroid hormone T3 (FT3) can be used as an independent prognostic indicator for the risk of death in ICUs. However, FT3 as a predictive marker is hindered by its accuracy. The study introduces the concept of dynamic FT3 data as a means to bolster the value of FT3 as a prognostic tool. Therefore, the aim of this study is to investigate the prognostic value of dynamic FT3 evolution in a comprehensive ICU setting, analyze the consistency between dynamic FT3 changes and variations in disease severity, and explore the feasibility of FT3 as an objective indicator for real-time clinical treatment feedback. Methods: Employing a single-center prospective observational study, FT3 measurements were taken on multiple days following enrollment, corresponding clinical data were collected. To investigated the pattern of dynamic changes of FT3, its prognostic significance in forecasting the risk of 28-day mortality, the alignment between dynamic FT3 changes and variations in the Sequential Organ Failure Assessment (SOFA) score. Results: The survival group exhibited higher last FT3 levels compared to the lowest point (p<0.05), while the death group did not show statistically significant differences (p>0.05). The study also identifies the optimal correlation between FT3 and SOFA score at day 5 (optimal correlation coefficient -0.546). The ROC curve for FT3 at day 5 yielded an optimal AUC of 0.88, outperforming the SOFA score. The study categorizes FT3 curve patterns, Kaplan-Meier survival analysis of these patterns highlighted that the descending-type curve was significantly associated with increased risk of death (P<0.001). Additionally, the research explores the consistency between changes in FT3 and SOFA scores. While overall consistency rates were modest, subgroup analyses unveiled that greater disease severity led to higher consistency rates. Conclusions: This study introduces the concept of dynamic FT3 changes to augment its prognostic utility in comprehensive ICU settings. The research identifies day 5 as the optimal time point for predictive efficacy, the descending FT3 curve as indicative of poor prognosis. While overall consistency with SOFA scores is modest, the correlation strengthens with greater disease severity. [ABSTRACT FROM AUTHOR]

Introduction: The efficacy and safety of ixekizumab, an anti-interleukin-17A antibody, in patients with severe symptoms of psoriatic arthritis are largely unexplored. We report the efficacy and safety of ixekizumab in a post hoc analysis of the SPIRIT-P1 trial. Methods: Patients were treated with placebo, ixekizumab 80 mg every 2 weeks (Q2W) or 4 weeks (Q4W), or adalimumab 40 mg Q2W for 24 weeks. In this subgroup analysis of SPIRIT-P1, the population with severe psoriatic arthritis was defined using the modified composite psoriatic activity index total score > 7 and peripheral arthritis score = 3 (> 4 tender or swollen joint count and ≥ 0.5 Health Assessment Questionnaire-Disability Index). Efficacy was measured by joint and skin endpoints including disease progression. Results: In the severe population, significantly more patients (p ≤ 0.001) treated with ixekizumab than placebo achieved 20% improvement according to the American College of Rheumatology criteria (ACR 20): 63.3% for ixekizumab Q4W, 60.4% for ixekizumab Q2W, and 24.5% for placebo. Statistically greater responses compared with placebo were observed in the severe population for ACR 50, ACR 70, ACR core set, disease activity index for psoriatic arthritis (DAPSA) low disease activity and DAPSA remission, and 28-joint disease activity score using C-reactive protein, as well as Psoriasis Area and Severity Index (PASI) 75, PASI 90, and PASI 100 (p ≤ 0.001). Efficacy findings and the safety profile of ixekizumab in the severe population were consistent with those of the overall population, with no new safety concerns identified. Conclusions: In patients with severe psoriatic arthritis, 24 weeks of treatment with ixekizumab resulted in improvements in both joint and skin symptoms. The safety profile in the severe population was consistent with the established safety profile of ixekizumab. Trial Registration: ClinicalTrials.gov identifier, NCT01695239. [ABSTRACT FROM AUTHOR]

To examine the change in racial disparity in severe maternal morbidity (SMM) during the COVID-19 pandemic and the associations between SARS-CoV-2 infection and SMM. This retrospective cohort study used linked databases of all livebirths delivered between 2018 and 2021 in South Carolina (n = 162,576). Exposures were 1) pre-pandemic and pandemic periods (before vs. March 2020 onwards); 2) SARS-CoV-2 infection, severity, and timing of first infection. Log-binomial regression models were used. SMM rate was higher among pandemic childbirths than pre-pandemic period (p = 0.06). The risk of SMM among Hispanics was doubled from pre-pandemic to pandemic periods (adjusted relative risk (aRR)= 2.50, 95% CI: 1.27, 4.94). During pre-pandemic, compared to White women, Black women (aRR=1.37, 95% CI: 1.14–1.64), while Hispanics had lower risk of SMM (aRR=0.42, 95% CI: 0.24–0.73). During the pandemic, the Black-White difference in the risk of SMM persisted (aRR=1.24, 95% CI: 1.00–1.54) and Hispanic-White difference in SMM risk became insignificant (aRR=0.85, 95% CI: 0.54–1.34). SARS-CoV-2 infection, its severity, and the late diagnosis were associated with 1.78–5.06 times higher risk of SMM. During pandemic, Black-White racial disparity in SMM persisted but the relative pre-pandemic advantage in SMM among Hispanic women over White women disappeared during the pandemic. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effectiveness of SARS-CoV2 vaccination in preventing ordinary or intensive care unit (ICU) admissions and deaths among cases registered during a variant transitional pandemic phase in the geographically and culturally unique territory of the Province of Bolzano (South Tyrol), an Italian region with low vaccination coverage.Methods: We collected data from 93,643 patients registered as positive for SARS-CoV-2 by health authorities during the winter of 2021–22. The data were analyzed retrospectively using descriptive statistics and multiple logistic regression.Results: 925 patients were hospitalized (0.99%), 89 (0.10%) were in intensive care, and 194 (0.21%) died. Vaccinated patients had a significantly lower risk of being hospitalized: adjusted Odds Ratio (aOR): 0.39; 95% CI: 0.33–0.46, ICU admission: aOR: 0.16; 95% CI: 0.09–0.29 and death: aOR: 0.41; 95% CI: 0.29–0.58. Similar risk reductions were also observed in booster-vaccinated patients, independent of sex, age, and predominant variant. Furthermore, the median length of stay (LoS) in the ICU was significantly longer for unvaccinated individuals compared to vaccinated subjects (9 vs. 6 days; p < 0.003).Conclusion: Primary series vaccination and ongoing campaign booster doses were effective in preventing all severe disease-related outcomes and in reducing ICU Length of Stay, even during a transitional pandemic phase and in a unique territorial context.

ObjectivesTo 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.Methods4310 (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.ResultsRegarding 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.ConclusionInflammatory 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.

Abstract Background This case series of 5 patients with severely necrotic mpox highlights the predominantly necrotic nature of lesions seen in cases of severe mpox as shown by skin and lung biopsy, as well as the extensive dissemination of the infection, as shown by polymerase chain reaction (PCR) assessment in different body sites. Case presentations Patients were male, the median age was 37, all lived with HIV (2 previously undiagnosed), the median CD4+ cell count was 106 cells/mm3, and 2/5 were not receiving antiretroviral treatment. The most common complication was soft tissue infection. Skin and lung biopsies showed extensive areas of necrosis. Mpox PCR was positive in various sites, including skin, urine, serum, and cerebrospinal fluid. The initiation of antiretroviral treatment, worsened the disease, like that seen in immune reconstitution syndrome. Three patients died due to multiple organ failure, presumably associated with mpox since coinfections and opportunistic pathogens were ruled out. Conclusions Severely necrotic manifestations of mpox in people living with advanced and untreated HIV are related to adverse outcomes.

Abstract Introduction The efficacy and safety of ixekizumab, an anti-interleukin-17A antibody, in patients with severe symptoms of psoriatic arthritis are largely unexplored. We report the efficacy and safety of ixekizumab in a post hoc analysis of the SPIRIT-P1 trial. Methods Patients were treated with placebo, ixekizumab 80 mg every 2 weeks (Q2W) or 4 weeks (Q4W), or adalimumab 40 mg Q2W for 24 weeks. In this subgroup analysis of SPIRIT-P1, the population with severe psoriatic arthritis was defined using the modified composite psoriatic activity index total score > 7 and peripheral arthritis score = 3 (> 4 tender or swollen joint count and ≥ 0.5 Health Assessment Questionnaire-Disability Index). Efficacy was measured by joint and skin endpoints including disease progression. Results In the severe population, significantly more patients (p ≤ 0.001) treated with ixekizumab than placebo achieved 20% improvement according to the American College of Rheumatology criteria (ACR 20): 63.3% for ixekizumab Q4W, 60.4% for ixekizumab Q2W, and 24.5% for placebo. Statistically greater responses compared with placebo were observed in the severe population for ACR 50, ACR 70, ACR core set, disease activity index for psoriatic arthritis (DAPSA) low disease activity and DAPSA remission, and 28-joint disease activity score using C-reactive protein, as well as Psoriasis Area and Severity Index (PASI) 75, PASI 90, and PASI 100 (p ≤ 0.001). Efficacy findings and the safety profile of ixekizumab in the severe population were consistent with those of the overall population, with no new safety concerns identified. Conclusions In patients with severe psoriatic arthritis, 24 weeks of treatment with ixekizumab resulted in improvements in both joint and skin symptoms. The safety profile in the severe population was consistent with the established safety profile of ixekizumab. Trial Registration ClinicalTrials.gov identifier, NCT01695239.

Background: Several types of vaccines are available across the world. Efficacy in preventing disease or reducing severity in terms of hospitalization, morbidity, and mortality needs to be studied in vaccinated patients, as most of them fail to prevent COVID-19 infections. Aims and Objectives: We aimed to correlate the disease severity and impact of a single dose of vaccine in COVID-19 breakthrough infections. Materials and Methods: The present study included 348 COVID-19 patients admitted to a tertiary hospital in Telangana, India, from March to August 2021 (and divided into an elderly group as Group 1 and a middle-aged group as Group 2 according to the vaccination protocol). Data were taken from the medical records of patients retrospectively regarding demographic and clinical details, as well as vaccination status during their hospital stay. Results: Diabetes mellitus and hypertension were found to be prevalent together as comorbidities (40%) in patients with prolonged hospitalization and 36% in those with severe disease (assisted ventilation). In vaccinated groups, irrespective of age, prolonged hospitalization was drastically halved (PR=0.418 for Group 1 and PR=0.416 for Group 2). Overall mortality in Group 1 is 2 times more frequent than in the Group 2 (odds ratio=2.12). Overall, prolonged hospital stays need for ventilatory support and deaths were also 2 times more common in men than in women. Conclusion: Older age, male gender, and more than one comorbidity are the most important factors determining poor clinical outcomes in persons with breakthrough severe acute respiratory syndrome coronavirus 2 infection, whereas vaccination is associated with a strong protective effect.

Introduction and objectiveLimited information is available on how neurologists make therapeutic decisions in neuromyelitis optica spectrum disorder (NMOSD), especially when new treatments with different mechanisms of action, administration, and safety profile are being approved. Decision-making can be complex under this uncertainty and may lead to therapeutic inertia (TI), which refers to lack of treatment initiation or intensification when therapeutic goals are not met. The study aim was to assess neurologists’ TI in NMOSD.MethodsAn online, cross-sectional study was conducted in collaboration with the Spanish Society of Neurology. Neurologists answered a survey composed of demographic characteristics, professional background, and behavioral traits. TI was defined as the lack of initiation or intensification with high-efficacy treatments when there is evidence of disease activity and was assessed through five NMOSD aquaporin-4 positive (AQP4+) simulated case scenarios. A multivariate logistic regression analysis was used to determine the association between neurologists’ characteristics and TI.ResultsA total of 78 neurologists were included (median interquartile range [IQR] age: 36.0 [29.0–46.0] years, 55.1% male, median [IQR] experience managing demyelinating conditions was 5.2 [3.0–11.1] years). The majority of participants were general neurologists (59.0%) attending a median (IQR) of 5.0 NMOSD patients (3.0–12.0) annually. Thirty participants (38.5%) were classified as having TI. Working in a low complexity hospital and giving high importance to patient’s tolerability/safety when choosing a treatment were predictors of TI.ConclusionTI is a common phenomenon among neurologists managing NMOSD AQP4+. Identifying TI and implementing specific intervention strategies may be critical to improving therapeutic decisions and patient care.

ObjectiveThe Omicron variant has a weaker pathogenicity compared to the Delta variant but is highly transmissible and elderly critically ill patients account for the majority. This study has significant implications for guiding clinical personalized treatment and effectively utilizing healthcare resources.MethodsThe study focuses on 157 patients infected with the novel coronavirus Omicron variant, from December, 2022, to February, 2023. The objective is to analyze the baseline data, test results, imaging findings and identify risk factors associated with severe illness.ResultsAmong the 157 included patients, there were 55 cases in the non-severe group (all were moderate cases) and 102 cases in the severe group (including severe and critical cases). Infection with the Omicron variant exhibits significant differences between non-severe and severe cases (baseline data, blood routine, coagulation, inflammatory markers, cardiac, liver, kidney functions, Chest CT, VTE score, etc.). A multifactorial logistic regression analysis showed that neutrophil percentage >75%, eosinophil percentage 0.55 mg/L, PCT >0.25 ng/mL, LDH >250 U/L, albumin 357 mole/L and blood calcium

Background: This case series of 5 patients with severely necrotic mpox highlights the predominantly necrotic nature of lesions seen in cases of severe mpox as shown by skin and lung biopsy, as well as the extensive dissemination of the infection, as shown by polymerase chain reaction (PCR) assessment in different body sites. Case presentations: Patients were male, the median age was 37, all lived with HIV (2 previously undiagnosed), the median CD4+ cell count was 106 cells/mm3, and 2/5 were not receiving antiretroviral treatment. The most common complication was soft tissue infection. Skin and lung biopsies showed extensive areas of necrosis. Mpox PCR was positive in various sites, including skin, urine, serum, and cerebrospinal fluid. The initiation of antiretroviral treatment, worsened the disease, like that seen in immune reconstitution syndrome. Three patients died due to multiple organ failure, presumably associated with mpox since coinfections and opportunistic pathogens were ruled out. Conclusions: Severely necrotic manifestations of mpox in people living with advanced and untreated HIV are related to adverse outcomes. [ABSTRACT FROM AUTHOR]

A total of 110 dogs presented to Teaching Veterinary Clinical Complex, CSKHPKV, Palampur (H.P.), India with the history of enteritis/gastroenteritis were screened for Canine Parvovirus (CPV). Out of these 110 dogs, 48 dogs were found positive for CPV by using Scanvet - a rapid antigen detection kit. All the 110 samples were subjected to Polymerase Chain Reaction (PCR) to check whether there were some cases that were false positive or false negative by Scanvet. Positive cases were, then, divided into 4 groups of 12 dogs each, with 4 different treatment regimens followed for each group. In addition to standard treatment protocol, our study tested effect of immunomodulators (Vitamin E & Selenium) and antiviral “Oseltamivir” on recovery of dogs. This type of study (using Oseltamivir and immunomodulators) was not done previously in the state and hence, our aim was to test whether this treatment increases survivability and recovery rate for dogs with Parvoviral enteritis in Himachal Pradesh. Groups containing immunomodulators were more efficacious than their counterparts without immunomodulators. Addition of Oseltamivir and immunomodulators to standard therapy resulted in reduced mortality, cessation of diarrhoea and vomiting earlier than routine therapy. Scanvet diagnostic kit was found to be a quick alternate method for diagnosis of Parvo Viral Enteritis. Overall, the group treated with antibiotic+ supportive+ symptomatic+ antiviral treatment along with immunomodulator displayed promising results.

The emergence of new virus variants, including the Omicron variant (B.1.1.529) of SARS-CoV-2, can lead to reduced vaccine effectiveness (VE) and the need for new vaccines or vaccine doses if the extent of immune evasion is severe. Neutralizing antibody titers have been shown to be a correlate of protection for SARS-CoV-2 and other pathogens, and could be used to quickly estimate vaccine effectiveness for new variants. However, no model currently exists to provide precise VE estimates for a new variant against severe disease for SARS-CoV-2 using robust datasets from several populations. We developed predictive models for VE against COVID-19 symptomatic disease and hospitalization across a 54-fold range of mean neutralizing antibody titers. For two mRNA vaccines (mRNA-1273, BNT162b2), models fit without Omicron data predicted that infection with the BA.1 Omicron variant increased the risk of hospitalization 2.8–4.4-fold and increased the risk of symptomatic disease 1.7–4.2-fold compared to the Delta variant. Out-of-sample validation showed that model predictions were accurate; all predictions were within 10% of observed VE estimates and fell within the model prediction intervals. Predictive models using neutralizing antibody titers can provide rapid VE estimates, which can inform vaccine booster timing, vaccine design, and vaccine selection for new virus variants.

Introduction Understanding the changing epidemiology of adults hospitalized with coronavirus disease 2019 (COVID-19) informs research priorities and public health policies. Methods Among adults (≥18 years) hospitalized with laboratory-confirmed, acute COVID-19 between 11 March 2021, and 31 August 2022 at 21 hospitals in 18 states, those hospitalized during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-predominant period (BA.1, BA.2, BA.4/BA.5) were compared to those from earlier Alpha- and Delta-predominant periods. Demographic characteristics, biomarkers within 24 hours of admission, and outcomes, including oxygen support and death, were assessed. Results Among 9825 patients, median (interquartile range [IQR]) age was 60 years (47–72), 47% were women, and 21% non-Hispanic Black. From the Alpha-predominant period (Mar–Jul 2021; N = 1312) to the Omicron BA.4/BA.5 sublineage-predominant period (Jun–Aug 2022; N = 1307): the percentage of patients who had ≥4 categories of underlying medical conditions increased from 11% to 21%; those vaccinated with at least a primary COVID-19 vaccine series increased from 7% to 67%; those ≥75 years old increased from 11% to 33%; those who did not receive any supplemental oxygen increased from 18% to 42%. Median (IQR) highest C-reactive protein and D-dimer concentration decreased from 42.0 mg/L (9.9–122.0) to 11.5 mg/L (2.7–42.8) and 3.1 mcg/mL (0.8–640.0) to 1.0 mcg/mL (0.5–2.2), respectively. In-hospital death peaked at 12% in the Delta-predominant period and declined to 4% during the BA.4/BA.5-predominant period. Conclusions Compared to adults hospitalized during early COVID-19 variant periods, those hospitalized during Omicron-variant COVID-19 were older, had multiple co-morbidities, were more likely to be vaccinated, and less likely to experience severe respiratory disease, systemic inflammation, coagulopathy, and death. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Coronavirus disease 2019 (COVID-19) was first discovered in December 2019, and since then rapidly spread worldwide. Our study aimed to investigate the early indicators of death in patients suffering from severe and critical COVID-19. PATIENTS AND METHODS: A retrospective cohort study was conducted on patients with severe and critical COVID-19, admitted to the Seventh Hospital of Wuhan. Clinical information was collected from electronic medical records according to standardized data collection tables. Patients were divided into non-survival and survival groups based on the disease outcome. Using univariate and multivariate logistic regression analysis, and calculating odds ratios (OR) and 95% confidence intervals (CI), independent risk factors for death in severe and critically ill COVID-19 patients were identified. RESULTS: The median age of 162 patients (57.4% males) was 67.5 years old. Patients in the non-survival group had significantly higher white blood cell count, decreased lymphocyte count, anemia and thrombocytopenia compared to patients in the survival group (p < 0.05). A 28-day mortality rate of the study cohort was 31.5%. Multivariate logistic regression analysis showed that underlying heart disease, lymphocyte count < 1.0 × 109/L, glomerular filtration rate < 66, lactate > 2.2 mmol/L, higher Sequential Organ Failure Assessment (SOFA) score, lower oxygenation index (OR 1.748; 95% CI 1.024-2.984; p=0.041) and higher "multi-lobar infiltration, hypo lymphocytosis, bacterial co-infection, smoking history, hypertension and age" (MuLBSTA) score (OR 1.601; 95% CI 1.062-2.415; p=0.025) were risk factors associated with death in patients with severe and critical COVID-19. CONCLUSIONS: Underlying heart disease, lymphocyte count, glomerular filtration rate, lactate, oxygenation index, SOFA score, and MuLBSTA score were associated with the risk of death in severe and critical COVID-19 patients. [ABSTRACT FROM AUTHOR]

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease. Recurrent fever, serositis, and arthritis are common findings of the disease. In addition, musculoskeletal complaints such as exertional leg pain can be overlooked, although they are common and affect patients' quality of life. The aim of this study was to evaluate the frequency of exertional leg pain in pediatric FMF patients and to analyze the association of this finding with other characteristics of FMF The files of FMF patients were retrospectively evaluated. The clinical characteristics and disease severity of the patients with exertional leg pain were compared with the patients without exertional leg pain. International severity scoring system for FMF (ISSF) and Mor severity score were used for assessment. The study included 541 FMF patients (287 females), 149 (27.5%) with exertional leg pain. The median colchicine dosage was significantly higher in patients with exertional leg pain (p = 0.02), arthritis (p = 0.001) and arthralgia (p˂0.001) were encountered more frequently in the attacks of these patients. The median disease severity scores calculated by both Mor severity scale and ISSF were significantly higher in patients with exertional leg pain compared to those without (p˂0.001). In the group of patients with exertional leg pain, the M694V mutation, either in one allele or in two alleles, was found to be significantly more common (p = 0.006 and p˂0.001, respectively). Exertional leg pain in pediatric FMF patients is the component of moderate-to-severe disease course, and this may be considerably associated with the presence of M694V mutation. [ABSTRACT FROM AUTHOR]

Background: Several types of vaccines are available across the world. Efficacy in preventing disease or reducing severity in terms of hospitalization, morbidity, and mortality needs to be studied in vaccinated patients, as most of them fail to prevent COVID-19 infections. Aims and Objectives: We aimed to correlate the disease severity and impact of a single dose of vaccine in COVID-19 breakthrough infections. Materials and Methods: The present study included 348 COVID-19 patients admitted to a tertiary hospital in Telangana, India, from March to August 2021 (and divided into an elderly group as Group 1 and a middle-aged group as Group 2 according to the vaccination protocol). Data were taken from the medical records of patients retrospectively regarding demographic and clinical details, as well as vaccination status during their hospital stay. Results: Diabetes mellitus and hypertension were found to be prevalent together as comorbidities (40%) in patients with prolonged hospitalization and 36% in those with severe disease (assisted ventilation). In vaccinated groups, irrespective of age, prolonged hospitalization was drastically halved (PR=0.418 for Group 1 and PR=0.416 for Group 2). Overall mortality in Group 1 is 2 times more frequent than in the Group 2 (odds ratio=2.12). Overall, prolonged hospital stays need for ventilatory support and deaths were also 2 times more common in men than in women. Conclusion: Older age, male gender, and more than one comorbidity are the most important factors determining poor clinical outcomes in persons with breakthrough severe acute respiratory syndrome coronavirus 2 infection, whereas vaccination is associated with a strong protective effect. [ABSTRACT FROM AUTHOR]

Background: The world witnessed the emergence of a global pandemic. Individuals with chronic illnesses like chronic kidney disease (CKD), already known to be immunologically compromised, have the potential to develop a scenario of an acute-on-chronic condition on coronavirus disease 2019 (COVID-19) contraction. Measurement of serum inflammatory biomarkers like interleukin (IL-6), high-sensitivity C-reactive protein (hsCRP) and ferritin may foresee the prognosis despite the pre-existing low-grade inflammation in these patients. Aims: To determine the utility of serum IL-6, hsCRP and Ferritin levels to determine COVID-19 severity and probable prognosis in CKD patients with COVID-19. Materials and Methods: A cross-sectional study was performed on 100 adult known cases of stage 5 of CKD, recently diagnosed as COVID-19 positive by real-time reverse transcription-polymerase chain reaction. The study population was divided into two groups according to COVID-19 severity: A non-severe and a severe group based on guidelines given in the Clinical Management Protocol: COVID-19. Their clinical and laboratory data obtained on the day of admission were analysed. Results: The severe group (n = 17) had 65% of males and 35% of females. A significant difference was found with respect to the age, body mass index and serum IL-6, hsCRP and ferritin levels between the two groups (P < 0.05). Among the three inflammatory biomarkers, hsCRP was found to have the maximum potential to categorise COVID-19 as severe or non-severe disease. Conclusion: Similar to patients with uncomplicated COVID-19 disease, higher serum levels of inflammatory biomarkers – IL-6, hsCRP and ferritin are seen in patients of CKD with severe COVID-19 illness in comparison to those with non-severe COVID-19, despite having a pre-existing background of low-grade chronic inflammation. The serum levels of IL-6, hsCRP and ferritin can be utilised to determine COVID-19 severity and probable prognosis in CKD patients with COVID-19.

Background. Pathogenetic factors that cause the deve­lopment of inflammatory bowel diseases (IBD) remain poorly understood, namely, the peculiarities of saturated fatty acids (SFAs) in the blood serum at different degrees of disease severity, which is quite an important task. Objective: to evaluate serum level of SFAs depending on IBD severity. Materials and methods. Thirty-seven patients with IBD were examined, their average age was (38.5 ± 2.1) years. Depending on the severity of the disease, the patients were divided into 2 groups: group I — with IBD of moderate severity (n = 24) and group II — with severe IBD (n = 13). The control group consisted of 16 healthy people. The quantitative content of SFAs in the blood serum of the examined patients was determined by gas chromatography. Median (Me), lower (25%) and upper (75%) quartiles were used to describe the data. Results. Biochemical analysis revealed a tendency to decrease in the level of short-chain SFA (butyric acid; p > 0.05) and a significant increase in the total content of medium- and long-chain SFAs (MCSFAs and LCSFAs; p 0.05) in group I against group II of patients. The content of LCSFAs, namely: tridecylic acid (p ≤ 0.012), myristic acid (p

Abstract Background The risk of developing severe and even fatal coronavirus disease 2019 (COVID-19) increases with various factors such as advanced age and chronic diseases, especially those treated with immunosuppressive drugs. Viral ribonucleic acid (RNA) and viral load detection in extra-pulmonary specimens have been proposed to indicate disease severity. Case presentation Here we describe a fatal COVID-19 case of an 83-year-old Caucasian male patient with various underlying comorbidities, including cardiovascular and autoimmune disorders, as well as immunosuppression due to lymphoma treatment. Upon admission, the patient was radiologically diagnosed with severe COVID-19. The patient was febrile and presented with diarrhea, continued dyspnea, tachypnea, and low blood oxygen saturation, treated with high-concentration oxygen supplementation and antibacterial therapy. Overall the patient was treated for COVID-19 for 19 days. Blood tests were performed upon admission, on the fifth, 10th, 13th, and 19th day. In addition, nasopharyngeal swab, blood, urine, and fecal samples were collected from the patient on the 14th day for virological and immunological investigations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detectable in all samples collected from this patient, including blood plasma and peripheral blood mononuclear cells (PBMC), with very high viral loads. However, neither virus-specific IgA, IgM, nor IgG antibodies were detectable. Conclusions The various cardiovascular, autoimmune, and oncological disorders, advanced age, and the high levels of inflammatory markers predisposed the patient to severe COVID-19 and determined the fatal outcome of the disease. We believe that the multiple specimen SARS-CoV-2 positivity and extremely high viral loads in nasopharyngeal swab and fecal samples to be the result of COVID-19 severity, the inability of viral clearance and weakened immune response due to advanced age, comorbidities, and the presence of non-Hodgkin's lymphoma and the immunosuppressive treatment for it, highlighting the risks of COVID-19 in such patients.

Background & Aims: Budd‐Chiari syndrome (BCS) is a rare and potentially life‐threatening disorder characterized by obstruction of the hepatic outflow tract. It is unknown whether patients with BCS represent a high risk for severe disease and mortality from coronavirus disease 2019 (COVID‐19). Thus, we aimed to assess hospitalization rates, severe disease, all‐cause mortality, intensive care unit (ICU) requirement and acute kidney injury (AKI) from COVID‐19 diagnoses. Methods & Results: We identified 467 patients with BCS with COVID‐19, 96 427 non‐chronic liver disease (CLD) and 9652 non‐BCS CLD. The BCS and non‐CLD cohorts (n = 467 each) and BCS and non‐BCS CLD (n = 440 each) were well balanced after propensity matching. When compared to the non‐CLD cohort, the BCS group had a higher risk of all‐cause mortality (5.1% vs. 2.4%, HR 2.18; 95% CI, 1.08–4.40), severe disease (6.0% vs. 2.4%, HR 2.20; 95% CI, 1.09–4.43), hospitalization (24.6% vs. 13.1%, HR 1.77; 95% CI, 1.30–2.42) and AKI (7.9% vs. 2.8%, HR 2.57; 95% CI, 1.37–4.85), but no significant differences in ICU requirements (2.4% vs. 2.1%, HR 0.75; 95% CI, 0.27–2.08) at 60‐days time points. When compared to the non‐BCS CLD cohort, the BCS group had a higher risk of all‐cause mortality (3.6% vs. 2.5%, HR 3.94; 95% CI, 1.31–11.79), hospitalization (29.8% vs. 21.6%, HR 1.43; 95% CI, 1.09–1.86), but differences in ICU requirements (HR 0.90 (0.38–2.12)), AKI (HR 1.41 (0.86–2.30)) or severe disease (HR 1.92 (0.99–3.71)) did not reach statistical significance at 60‐day follow up. Conclusion: In conclusion, COVID‐19 infection in patients with BCS is associated with poor outcomes. Patients with BCS infected with COVID‐19 carry a significantly higher risk of hospitalization and all‐cause mortality and a possible effect on severe disease and AKI compared with COVID‐19 patients without CLD or with non‐BCS‐CLD. [ABSTRACT FROM AUTHOR]

Purpose: The relationship between the TIR and mortality may be influenced by the presence of diabetes and other glycemic indicators. The purpose of this study was to investigate the relationship between TIR and in-hospital mortality in diabetic and non-diabetic patients in ICU. Methods: A total of 998 patients with severe diseases in the ICU were selected for this retrospective analysis. The TIR is defined as the percentage of time spent in the target blood glucose range of 3.9–10.0 mmol/L within 24 h. The relationship between TIR and in-hospital mortality in diabetic and non-diabetic patients was analyzed. The effect of glycemic variability was also analyzed. Results: The binary logistic regression model showed that there was a significant association between the TIR and the in-hospital death of severely ill non-diabetic patients. Furthermore, TIR≥70% was significantly associated with in-hospital death (OR = 0.581, P = 0.003). The study found that the coefficient of variation (CV) was significantly associated with the mortality of severely ill diabetic patients (OR = 1.042, P = 0.027). Conclusions: Both diabetic and non-diabetic critically ill patients should control blood glucose fluctuations and maintain blood glucose levels within the target range, it may be beneficial in reducing mortality.

Background Clostridioides difficile infection (CDI) is a leading cause of health care–associated infection and may result in organ dysfunction, colectomy, and death. Published risk scores to predict severe complications from CDI demonstrate poor performance upon external validation. We hypothesized that building and validating a model using geographically and temporally distinct cohorts would more accurately predict risk for complications from CDI. Methods We conducted a multicenter retrospective cohort study of adults diagnosed with CDI. After randomly partitioning the data into training and validation sets, we developed and compared 3 machine learning algorithms (lasso regression, random forest, stacked ensemble) with 10-fold cross-validation to predict disease-related complications (intensive care unit admission, colectomy, or death attributable to CDI) within 30 days of diagnosis. Model performance was assessed using the area under the receiver operating curve (AUC). Results A total of 3646 patients with CDI were included, of whom 217 (6%) had complications. All 3 models performed well (AUC, 0.88–0.89). Variables of importance were similar across models, including albumin, bicarbonate, change in creatinine, non-CDI-related intensive care unit admission, and concomitant non-CDI antibiotics. Sensitivity analyses indicated that model performance was robust even when varying derivation cohort inclusion and CDI testing approach. However, race was an important modifier, with models showing worse performance in non-White patients. Conclusions Using a large heterogeneous population of patients, we developed and validated a prediction model that estimates risk for complications from CDI with good accuracy. Future studies should aim to reduce the disparity in model accuracy between White and non-White patients and to improve performance overall. [ABSTRACT FROM AUTHOR]

Background We compare the risk of coronavirus disease 2019 (COVID-19) outcomes among co-circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants between January 2021 and May 2022 in Navarra, Spain. Methods We compared the frequency of hospitalization and severe disease (intensive care unit admission or death) due to COVID-19 among the co-circulating variants. Variants analyzed were nonvariants of concern (non-VOCs), Alpha, Delta, Omicron BA.1, and Omicron BA.2. Logistic regression models were used to estimate adjusted odds ratio (aOR). Results The Alpha variant had a higher risk of hospitalization (aOR, 1.86 [95 confidence interval {CI}, 1.282.71]) and severe disease (aOR, 2.40 [95 CI, 1.314.40]) than non-VOCs. The Delta variant did not show a significantly different risk of hospitalization (aOR, 0.73 [95 CI,.401.30]) and severe disease (aOR, 3.04 [95 CI,.5716.22]) compared to the Alpha variant. The Omicron BA.1 significantly reduced both risks relative to the Delta variant (aORs, 0.28 [95 CI,.16.47] and 0.23 [95 CI,.12.46], respectively). The Omicron BA.2 reduced the risk of hospitalization compared to BA.1 (aOR, 0.52 [95 CI,.29.95]). Conclusions The Alpha and Delta variants showed an increased risk of hospitalization and severe disease, which decreased considerably with the Omicron BA.1 and BA.2. Surveillance of variants can lead to important differences in severity. [ABSTRACT FROM AUTHOR]

A total of 110 dogs presented to Teaching Veterinary Clinical Complex, CSKHPKV, Palampur (H.P.), India with the history of enteritis/gastroenteritis were screened for Canine Parvovirus (CPV). Out of these 110 dogs, 48 dogs were found positive for CPV by using Scanvet - a rapid antigen detection kit. All the 110 samples were subjected to Polymerase Chain Reaction (PCR) to check whether there were some cases that were false positive or false negative by Scanvet. Positive cases were, then, divided into 4 groups of 12 dogs each, with 4 different treatment regimens followed for each group. In addition to standard treatment protocol, our study tested effect of immunomodulators (Vitamin E & Selenium) and antiviral "Oseltamivir" on recovery of dogs. This type of study (using Oseltamivir and immunomodulators) was not done previously in the state and hence, our aim was to test whether this treatment increases survivability and recovery rate for dogs with Parvoviral enteritis in Himachal Pradesh. Groups containing immunomodulators were more efficacious than their counterparts without immunomodulators. Addition of Oseltamivir and immunomodulators to standard therapy resulted in reduced mortality, cessation of diarrhoea and vomiting earlier than routine therapy. Scanvet diagnostic kit was found to be a quick alternate method for diagnosis of Parvo Viral Enteritis. Overall, the group treated with antibiotic+ supportive+ symptomatic+ antiviral treatment along with immunomodulator displayed promising results. [ABSTRACT FROM AUTHOR]

Multiple COVID-19 vaccines have been approved and employed in the fight against the pandemic. However, these vaccines have limited long-term effectiveness against severe cases and a decreased ability to prevent mild disease. This review discusses the relevant factors influencing the efficacy of the vaccines against mild and severe infection, analyzes the possible underlying mechanisms contributing to the different outcomes in terms of vaccine function and disease progression, and proposes improvements for the next generation of vaccines. The reduced efficacy of the COVID-19 vaccine in the prevention of viral infection is closely related to the emergence of novel SARS-CoV-2 variants and their rapid transmission ability. Fundamentally, the immune responses induced by COVID-19 vaccines cannot effectively halt virus replication in the upper respiratory tract because only a limited number of specific antibodies reach these areas and decrease in concentration over time. However, the established immune response can provide sufficient protection against severe diseases by blocking viral infection of the lower respiratory tract or lung owing to sufficient antibody repertoires and memory responses. Considering this situation, future COVID-19 vaccines should have the potential to replenish the mucosal immune response in the respiratory tract to prevent viral infection. [ABSTRACT FROM AUTHOR]

Background/Objective SARS-CoV-2 continues to spread widely in the US and worldwide. Pregnant women are more likely to develop severe or critical illness than their non-pregnant counterparts. Known risk factors for severe and critical disease outside of pregnancy, such as asthma, diabetes, and obesity have not been well-studied in pregnancy. We aimed to determine which clinical and pregnancy-related factors were associated with severe and critical COVID illness in pregnancy. Study design This was a retrospective cohort study of women with confirmed intrauterine pregnancy and positive nasopharyngeal swab for SARS-CoV-2 who presented to an academic medical center in New York City from 1 March 2020 to 1 July 2020. Severe and critical COVID-19 disease was defined by World Health Organization criteria. Women with severe/critical disease were compared to women with asymptomatic/mild disease. Continuous variables were compared with Mann–Whitney or t-test and categorical variables were compared using chi-square and Fisher’s exact. Statistical significance was set at p < .05. Multivariable logistic regression was performed including variables that were significantly different between groups. Results Two hundred and thirty-three patients were included, 186 (79.8%) with asymptomatic/mild disease and 47 (20.2%) with severe/critical disease. Women with asymptomatic/mild disease were compared to those with severe/critical disease. Women with severe/critical disease were more likely to have a history of current or former smoking (19.6 vs. 5.4%, p = .004), COVID-19 diagnosis in the 2nd trimester (42.6 vs. 11.8%, p = .001), and asthma or other respiratory condition (21.3 vs. 7.0%, p = .01). Women with severe/critical disease were more likely to have cesarean delivery (35.5 vs. 15.6%, p < .01) and preterm delivery <37 weeks (25.8 vs. 3.8%, p < .01). After adjustment, history of smoking remained significantly predictive of severe/critical disease [aOR 3.84 (95% CI, 1.25–11.82)]. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinical value of serum intestinal fatty acid binding protein (I-FABP) and D-lactic acid (D-LA) in the evaluation of intestinal injury in severe neurosurgical patients. Methods The clinical data of 80 severe patients admitted to Department of Neurosurgery, The First People's Hospital of Yulin from January 2018 to January 2020 were analyzed retrospectively. According to whether the patients were complicated with intestinal injury, 38 patients with intestinal injury were set as intestinal injury group, and 42 patients with simple severe neurosurgery were set as no intestinal injury group. The levels of albumin (PA), ceruloplasmin (CP), transferrin (TF), I-FABP, D-LA, total protein (TP), D-Dimer (D-D), C-reactive protein (CRP) and acute physiology and chronic health score II (APACHE-II) on the first day and the third day after admission were compared between the two groups, and the correlation between I-FABP, D-LA and PA, CP, TF, TP, D-D, CRP was analyzed. Results There were no statistically significant differences in the PA, CP, TF, TP, DD, CRP, I-FABP, D-LA levels and APACHE-II scores between the two groups on the first day after admission, and the levels of DD and CRP on the third day after admission (P>0.05). PA, CP, TF, TP of the intestinal injury group on the 3rd day of admission were lower than those of the non-intestinal injury group(t = 7.630,2.712,5. 701,5. 574, P<0.05). I- FABP, D-LA, APACHE-II were higher than the group without intestinal injury (t = 18. 481,26. 924,5. 037, P < 0.05). The results of correlation analysis showed that there was no significant correlation between the levels of I- FABP, D-LA and DD, CRP(r=0. 143,0. 182, P > 0.05), and positively correlated with APACHE-II (r = 0.386, P<0.05), and negatively correlated with PA, CP, TF, TP(r = −0.531, -0.742, -0.673, -0.802, P <0.05). Conclusion The expression levels of I-FABP and D-LA in serum of severe neurosurgical patients with intestinal injury are significantly increased, and the levels of I-FABP and D-LA are associated with the severity of patients. [ABSTRACT FROM AUTHOR]

Background: The future of the SARS-CoV-2 pandemic hinges on virus evolution and duration of immune protection of natural infection against reinfection. We investigated duration of protection afforded by natural infection, the effect of viral immune evasion on duration of protection, and protection against severe reinfection, in Qatar, between February 28, 2020 and June 5, 2022.Methods: Three national, matched, retrospective cohort studies were conducted to compare incidence of SARS-CoV-2 infection and COVID-19 severity among unvaccinated persons with a documented SARS-CoV-2 primary infection, to incidence among those infection-naïve and unvaccinated. Associations were estimated using Cox proportional-hazard regression models.Results: Effectiveness of pre-Omicron primary infection against pre-Omicron reinfection was 85.5% (95% CI: 84.8-86.2%). Effectiveness peaked at 90.5% (95% CI: 88.4-92.3%) in the 7th month after the primary infection, but waned to ~ 70% by the 16th month. Extrapolating this waning trend using a Gompertz curve suggested an effectiveness of 50% in the 22nd month and < 10% by the 32nd month. Effectiveness of pre-Omicron primary infection against Omicron reinfection was 38.1% (95% CI: 36.3-39.8%) and declined with time since primary infection. A Gompertz curve suggested an effectiveness of < 10% by the 15th month. Effectiveness of primary infection against severe, critical, or fatal COVID-19 reinfection was 97.3% (95% CI: 94.9-98.6%), irrespective of the variant of primary infection or reinfection, and with no evidence for waning. Similar results were found in sub-group analyses for those ≥50 years of age.Conclusions: Protection of natural infection against reinfection wanes and may diminish within a few years. Viral immune evasion accelerates this waning. Protection against severe reinfection remains very strong, with no evidence for waning, irrespective of variant, for over 14 months after primary infection. [ABSTRACT FROM AUTHOR]

Objective: To examine the clinical severity and magnitude of COVID-19 patients after the second dose of the COVID-19 vaccine. Study Design: Cross-sectional study. Place and Duration of Study: Tertiary Care Hospital, Islamabad Pakistan, from Feb to Jun 2021. Methodology: The individuals who had two doses of the vaccine (dead inactivated-Vero Cell) and got COVID-19 at least two weeks after vaccination were included in the study. These patients were divided into Mild, Moderate and Severe categories based on their symptoms and Investigations. Results: Out of 5000 individuals vaccinated, 225(4.5%) got infected with COVID-19 later. Among these 225, 172(76.4%) had mild symptoms and recovered, with only 1(0.4%) death was reported. Conclusion: COVID-19 vaccination does not infer 100% immunity, but if someone gets infected with COVID after vaccination, there are remarkable chances of recovery. [ABSTRACT FROM AUTHOR]