This study aims to assess the cost-effectiveness of the fall 2023 COVID-19 mRNA XBB.1.5 vaccination campaign in the Netherlands, comparing the XBB1.5 updated mRNA-1273.222 with the XBB1.5 updated BNT162b2 vaccine.

A 1-year decision tree-based cost-effectiveness model was developed, considering three scenarios: no fall 2023 vaccination, BNT162b2 vaccination, and mRNA-1273 vaccination in the COVID-19 high-risk population in the Netherlands. The high-risk population includes everyone of 60 and older, and younger adults at high risk as identified by the Dutch Health Council. Costs were included from a societal perspective and the modelled period started in October 2023 and ended in September 2024, including life years lost with a lifetime horizon. Sensitivity and scenario analyses were conducted to evaluate model robustness.

In the base case, mRNA-1273 demonstrated substantial benefits over BNT162b2, potentially averting 20,629 symptomatic cases, 924 hospitalizations (including 32 intensive care unit admissions), 207 deaths, and 2124 post-COVID cases. Societal cost savings were €12.9 million (excluding vaccination costs), with 1506 quality-adjusted life years (QALYs) gained. The break-even incremental price of mRNA-1273 compared to BNT162b2 was €16.72 or €34.32 considering a willingness to pay threshold (WTP) of 20,000 or 50,000 euro per QALY gained.

This study provides a comprehensive cost-effectiveness analysis supporting the adoption of the mRNA-1273 vaccine in the national immunization program in the Netherlands, provided that the Dutch government negotiates a vaccine price that is at most €34.32 per dose higher than BNT162b2. Despite limitations, the findings emphasize the substantial health and economic benefits of mRNA-1273 over BNT162b2 in the high-risk population.

The real-world effectiveness of the oral antivirals nirmatrelvir-ritonavir and molnupiravir against the SARS-CoV-2 Omicron variant remains uncertain. We aimed to estimate their effectiveness in non-hospitalized adults with COVID-19.

This retrospective cohort study used data from the Municipal Department for Public Health Services of Vienna, Austria, to identify non-hospitalized adults with confirmed SARS-CoV-2 infection between January 2022 and May 2023. Nirmatrelvir-ritonavir users were compared with untreated controls and molnupiravir users with untreated controls by calculating adjusted risk differences (aRDs) using a covariate-adjusted logistic regression model with inverse probability weighting. Outcomes were hospitalization and all-cause death within 28 days.

We identified 113 399 eligible cases (90 481 untreated controls, 12 166 nirmatrelvir-ritonavir users, and 10 752 molnupiravir users). Over 96% of the patients were immunized by previous infection or vaccination. In the nirmatrelvir-ritonavir analysis, the estimated risk of hospitalization was 0.57% (95% CI, 0.35-0.78) in nirmatrelvir-ritonavir users and 1.09% (95% CI, 0.86-1.32) in untreated controls (aRD, -0.53%; 95% CI, -0.77 to -0.28). The estimated risk of death was 0.0% (95% CI, 0.0-0.0) in nirmatrelvir-ritonavir users and 0.13% (95% CI, 0.08-0.18) in untreated controls (aRD, -0.13%, 95% CI, -0.18 to -0.08). The number needed to treat to prevent hospitalization and death was 190 (95% CI, 130-356) and 792 (95% CI, 571-1289), respectively. These statistically significant aRDs were restricted to the subgroup of patients ≥60 years. In the molnupiravir analysis, the estimated risk of hospitalization was 1.36% (95% CI, 0.95-1.77) in molnupiravir users and 1.16% (95% CI, 0.93-1.39) in untreated controls (aRD, 0.2%; 95% CI, -0.08 to 0.49). The estimated risk of death was 0.12% (95% CI, 0.01-0.23) in molnupiravir users and 0.14% (95% CI, 0.06-0.21) in untreated controls (aRD, -0.01%; 95% CI, -0.08 to -0.06).

Among outpatients aged ≥60 years with COVID-19 in an Omicron-dominated era, treatment with nirmatrelvir-ritonavir was associated with a lower risk of hospitalization and all-cause death within 28 days, albeit with wide CIs and high numbers needed to treat. This finding was not observed in molnupiravir users and younger nirmatrelvir-ritonavir users.

Post-COVID Syndrome (PCS), occurs several weeks after Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2 infection), has a frequency of 10 %‒35 % of cases, presents a wide range of symptoms that can persist for months or years and markedly reduces the quality of life of patients.

To describe clinical, epidemiological and evolutionary aspects of a cohort of patients diagnosed with PCS followed on an outpatient basis.

Individuals of both sexes, > 18-years old who presented symptoms suggestive of PCS and had previously confirmed SARS-CoV-2 infection were included. Clinical evaluation was carried out monthly by a multidisciplinary team, and if necessary laboratorial exams were performed.

From June 2021 to June 2022, 92 cases of PCS were diagnosed, of which 60 (65.2 %) were female and the average age was 49.1 years. In 61 (66.3 %) of the cases, SARS-CoV-2 infection occurred between January and November 2021. In 55 (59.7 %) of the cases the symptoms were mild, while 31 (36.0 %) were moderate or severe cases. Most cases of PCS occurred in individuals with the mild form of COVID-19. The predominant symptoms were chronic fatigue in 59 (68.6 %) cases, brain fog in 68 (73.4 %), myalgias and arthralgias in 44 (47.8 %), cramps and paresthesia's in 40 (46.5 %). The main comorbidities observed were high blood pressure, obesity and diabetes mellitus. The persistence of symptoms was greater in those cases who presented severe forms of COVID-19. Most patients experienced gradual and progressive improvement over the months.

The profile of patients with PCS in this cohort is similar to other reports. A great number of symptoms is remarkable with variable presentation and evolution and their frequency exceeds that previously described in a large meta-analysis. Inflammatory phenomena mediated by the virus, autoimmunity and direct organic damage have been implicated in the genesis of this syndrome.

Patients with hematological malignancies (HMs) are at higher risk of severe COVID-19 and secondary infections, which further complicate their outcomes. This study evaluated the impact of secondary infections (SIs) on mortality in hospitalized HM patients with SARS-CoV-2 infection and identified risk factors associated with SIs. We included 217 patients with HMs and COVID-19 admitted to a tertiary hospital in Rome, from April 2020 to September 2022. SIs occurred in 44.2% of patients, with bloodstream infections (42.7%) and respiratory infections (30.5%) being most frequent; among the latter, COVID-19-associated pulmonary aspergillosis (CAPA) was observed in 41.4% of cases. Viral reactivations, predominantly CMV, occurred in 9.2% of patients. The overall mortality rate was 29%, with higher mortality observed in patients with SIs (47.4% vs. 14.7%, p < 0.01). Risk factors for SIs included severe COVID-19 (OR = 2.957, p < 0.05) and prolonged hospitalization (OR = 1.095, p < 0.001). Severe COVID-19 (OR = 8.229, p < 0.001), intensive care unit (ICU) admission (OR = 15.232, p < 0.001), chronic steroid therapy (OR = 2.803, p < 0.05), SIs (OR = 2.892, p < 0.05), and viral reactivation (OR = 6.269, p < 0.01) were independent predictors of mortality. SIs and viral reactivations are common in patients with HMs and SARS-CoV-2 infection and significantly increase mortality, highlighting the need for timely management and preventive strategies in this vulnerable population.

Background/Objectives: Vaccination against SARS-CoV-2 remains a key measure to control COVID-19. Nuvaxovid, a recombinant Matrix-M-adjuvanted protein-based vaccine, showed similar efficacy to mRNA vaccines in clinical trials and real-world studies, with lower rates of reactogenicity. Methods: To support decision making on UK vaccine selection, a population-based compartmental dynamic transmission model with a cost-utility component was developed to evaluate the cost-effectiveness of Nuvaxovid compared with mRNA vaccines from a UK National Health Service perspective. The model was calibrated to official epidemiology statistics for mortality, incidence, and hospitalisation. Scenario and sensitivity analyses were conducted. Results: In the probabilistic base case, a Nuvaxovid-only strategy provided total incremental cost savings of GBP 1,338,323 and 1558 additional quality-adjusted life years (QALYs) compared with an mRNA-only vaccination strategy. Cost savings were driven by reduced cold chain-related operational costs and vaccine wastage, while QALY gains were driven by potential differences in vaccine tolerability. Probabilistic sensitivity analysis indicated an approximately 70% probability of cost-effectiveness with Nuvaxovid-only versus mRNA-only vaccination across most cost-effectiveness thresholds (up to GBP 300,000/QALY gained). Conclusions: Nuvaxovid remained dominant over mRNA vaccines in scenario analyses assessing vaccine efficacy waning, Nuvaxovid market shares, and the vaccinated population.

At the time of Omicron BA.2 outbreak, it was shown that mild to moderate COVID-19 was associated with worsening of asthma control after recovery. Whether the same phenomenon was also observed at a later phase of COVID-19 pandemic by other variants have not been reported.

We conducted a follow-up study on patients with asthma who received clinical care in Queen Mary Hospital. The patients were first recruited in the study entitled "Worsening of asthma control after recovery from mild to moderate COVID-19 in patients from Hong Kong". The primary outcome was the asthma control test (ACT) score difference among the patients who never had COVID-19 (no COVID-19 group), patients who had COVID-19 diagnosed in the initial study (past COVID-19 group) and patients who had COVID-19 diagnosed in the follow-up period (new COVID-19 group) of the current study.

189 patients were included. The change of ACT score from the last visit in the previous study to the last follow-up visit in current study was - 0.34 ± 3.7 in the no COVID-19 group, -0.0 ± 5.0 in the past COVID-19 group and - 0.17 ± 4.5 in the new COVID-19 group (p = 0.94). There were 10 (24.4%), 24 (25.5%) and 12 (22.2%) patients in the no COVID-19, past COVID-19 and new COVID-19 group who had worsening of asthma control by an increase in ACT score ≥ 3 from the last visit in the previous study to the last follow-up visit in current study (p = 0.90).

Patients who had COVID-19 in 2023 with Omicron XBB as the dominant strain did not have worsening of asthma control seen in previous study done in 2022 with Omicron BA.2 as the circulating strain. Patients who had worsening of asthma control after COVID-19 in 2022 had subsequent improvement of asthma control with longer follow-up interval.

Studies on COVID-19 mortality during the Omicron-predominant wave have focused primarily on the inpatient/emergency room setting, and real-world data including both inpatients and outpatients are lacking.

Patients diagnosed with COVID-19 (n = 27,440,148) or influenza (n = 8,179,641) from January 2020 to April 2023 were identified using nationwide claims data in Japan. Patients with COVID-19 in the Omicron-predominant wave were compared with their counterparts in earlier waves, and a subset of the former group (May 2022-April 2023) was compared with patients with influenza as controls.

The mortality rates (average number of deaths/cases per week) of COVID-19 decreased over time, being 2.7% (169/6312), 2.1% (397/18,754), 0.7% (195/28,273), and 0.4% (1613/378,848) in the wild-type-, Alpha-, Delta-, and Omicron-predominant waves, respectively. However, the number of deaths increased substantially in the Omicron-predominant wave, especially among the elderly (e.g., in the Delta- and Omicron-predominant waves, the average numbers of deaths/cases per week were < 1/5527 (< 0.01%) and 4/105,763 (< 0.01%) respectively, in patients aged 0-19, versus 101/925 (10.9%) and 1212/20,771 (5.8%), respectively, in patients aged ≥ 80). The mortality rate was lower for patients with COVID-19 than in those with influenza among those aged ≤ 39 years but higher among those aged ≥ 40 years.

In the Omicron-predominant wave, the mortality rate of COVID-19 decreased, but the number of patients increased, leading to a substantial increase in the number of deaths, especially among the elderly. The mortality rate of COVID-19 was higher than that of influenza in the elderly but not in the young, highlighting the need for age-specific interventions.

Early remdesivir administration in high-risk patients with coronavirus disease 2019 (COVID-19) is known to be effective in preventing the progression to severe disease. However, the effect of early remdesivir administration on Omicron variants, which are known to have decreased severity, remains unclear.

This study aimed to analyze the effects of early remdesivir administration during the Omicron wave in hospitalized patients. Electronic medical records of hospitalized patients with confirmed COVID-19 between February 2022 and February 2023 were reviewed. We included patients aged ≥ 18 years who had symptom onset within 7 days and had at least one risk factor for disease progression at the time of diagnosis. We compared the clinical outcomes between the early remdesivir administration group and the group not administered early remdesivir. The primary outcome was all-cause mortality within 28 days and the secondary outcome was the need for oxygen supplementation within 28 days. Multivariable analysis was conducted to assess risk factors for all-cause mortality and the need for oxygen supplementation.

A total of 286 patients were enrolled, including 88 in the early remdesivir administration group and 198 in the control group. Clinical outcomes, including all-cause mortality (3.4% vs. 6.1%, P = 0.556) and need for oxygen supplementation (15.9% vs. 14.6%, P = 0.783) within 28 days, were not significantly different between the two groups. Age (HR, 1.061; 95% CI: 1.002, 1.124; P = 0.043), BMI (HR, 0.849; 95% CI: 0.725, 0.994; P = 0.041), and malignancy (HR, 4.619; 95% CI: 1.618, 13.189; P = 0.004) were identified as independent factors associated with all-cause mortality. Additionally, BMI (OR, 0.908; 95% CI, 0.824, 1.000; P = 0.049) and vaccination with more than three doses (OR, 0.412; 95% CI, 0.202, 0.839; P = 0.015) were independent factors associated with the need for oxygen supply. Early remdesivir administration was not significantly associated with all-cause mortality (HR, 0.393; 95% CI: 0.109, 1.417; P = 0.154) or the need for oxygen supplementation (OR, 0.823; 95% CI: 0.389, 1.740; P = 0.610).

In our study, early remdesivir administration was not associated with preventing progression to severe disease when used as previously indicated during the Omicron wave. Considering the decline in the severity of the Omicron variant and the increased vaccination rate reported in previous studies, further studies are needed to establish new indications for the use of early remdesivir in the Omicron variant.

The study aimed to analyze in-hospital mortality (IHM) among all COVID-19 patients hospitalized in Spain between March 1, 2020, and December 31, 2021, and to compare two distinct periods: the prevaccination period (March 1, 2020, to January 31, 2021) and the vaccination period (February 1, 2021, to December 31, 2021). The objective was to assess the impact of vaccination on IHM and identify associated risk factors, using data from Spain's national hospitalization registry.

This retrospective analysis used data from the Spanish National Surveillance System for Hospital Data. The primary outcome was in-hospital mortality (IHM). Multivariate logistic regression identified risk factors across the overall study period, as well as during the prevaccination and vaccination periods. Risk factors included age (in 20-year intervals), sex, comorbidities (e.g., hypertension, diabetes, chronic kidney failure, obesity, neurodegenerative disorders, and others), and admission to the intensive care unit.

A total of 524,314 COVID-19 hospitalizations were recorded in Spain, with 329,690 during the prevaccination period and 194,624 during the vaccination period. Hospitalization rates dropped from 697/100,000 people to 411/100,000, and in-hospital mortality (IHM) decreased from 16.2 to 11.5% (adjusted odds ratio [AOR]: 0.71, 95% CI: 0.70-0.73, p < 0.001). IHM rose with age, from 0.8% in patients aged 18-39 to 31.7% in those ≥80 years (p < 0.001), but significant decreases were observed across all age groups after vaccination, especially in those ≥80 years (AOR: 0.76, 95% CI: 0.75-0.79, p < 0.001). Risk factors for IHM remained consistent, with leukemia, neoplasm, and lymphoma posing the highest risks, while female sex (AOR: 0.75, 95% CI: 0.74-0.77, p < 0.001) and dyslipidemia (AOR: 0.85, 95% CI: 0.32-0.86, p < 0.001) were protective factors.

During the vaccination period, the risk of in-hospital mortality (IHM) was 29% lower than in the prevaccination period, after adjusting for sex, age, and comorbidities. This reduced risk was observed across sexes, age groups, and comorbidities. The risk factors for IHM remained consistent between the two periods, with age as the main risk factor, while female sex and dyslipidemia were identified as protective factors.

It is thought that patients with inborn errors of immunity (IEI) are more susceptible to severe coronavirus disease 2019 (COVID-19) than the general population, but a quantification of this potential risk is largely missing.

We assessed the impact of COVID-19 on patients with IEI.

A nationwide cohort study was performed to estimate the relative risk (RR) for hospitalization, intensive care, and death within 30 days after a positive severe acute respiratory syndrome coronavirus 2 test result in an IEI population (n = 2392) compared to the general population (n = 8,270,705) using data from Swedish national registries. Three time periods were studied: the prevaccination period, and the Alpha/Delta and Omicron periods. Adjustment was made for demographics, income, comorbidities, and vaccination status.

During the prevaccination period, 25.2% of the IEI population was hospitalized, compared to 17.5% and 5.2% during the Alpha/Delta and Omicron periods, respectively. For the 3 time periods, the adjusted RR [95% confidence interval] for hospitalization in the IEI population compared to the general population was 3.1 [2.1-4.2], 3.5 [2.4-4.8], and 4.3 [2.5-6.7], respectively. The respective values for intensive care after COVID-19 were 5.6 [2.6-10.8], 4.7 [1.7-10.1], and 4.7 [1.7-10.1] for the 3 periods. Five patients (0.6%) in the IEI population died within 30 days of a positive PCR test result compared to 18,773 (0.2%) in the general population during the 3 study periods.

Patients with IEI had a 3 to 4 times higher risk for hospitalization and a 5 times higher risk for intensive care during COVID-19 compared to the general population.

With limited access to mRNA COVID-19 vaccines in lower income countries, and people living with HIV (PLWH) largely excluded from clinical trials, Part A of the multicentre CoVPN 3008 (Ubuntu) study aimed to assess the safety of mRNA-1273, the relative effectiveness of hybrid versus vaccine immunity, and SARS-CoV-2 viral persistence among PLWH in East and Southern Africa during the omicron outbreak.

Previously unvaccinated adults with HIV and/or other comorbidities associated with severe COVID-19 received either one (hybrid immunity) or two (vaccine immunity) 100-mcg doses of ancestral strain mRNA-1273 in the first month, depending on baseline evidence of prior SARS-CoV-2 infection. In a prospective cohort study design, we used covariate-adjusted Cox regression and counterfactual cumulative incidence methods to determine the hazard ratio and relative risk of COVID-19 and severe COVID-19 with hybrid versus vaccine immunity within six months. The ongoing Ubuntu study is registered on ClinicalTrials.gov (NCT05168813) and this work was conducted from December 2021 to March 2023.

Between December 2021 and September 2022, 14,237 participants enrolled, and 14,002 (83% PLWH, 69% SARS-CoV-2 seropositive) were included in the analyses. Vaccinations were safe and well tolerated. Common adverse events were pain or tenderness at the injection site (26.7%), headache (20.4%), and malaise (20.3%). Severe adverse events were rare (0.8% of participants after the first and 1.1% after the second vaccination), and none were life-threatening or fatal. Among PLWH, the median CD4 count was 635 cells/μl and 18.5% had HIV viraemia. The six-month cumulative incidences in the hybrid immunity and vaccine immunity groups were 2.02% (95% confidence interval [CI] 1.61-2.44) and 3.40% (95% CI 2.30-4.49) for COVID-19, and 0.048% (95% CI 0.00-0.10) and 0.32% (95% CI 0.59-0.63) for severe COVID-19. Among all PLWH the hybrid immunity group had a 42% lower hazard rate of COVID-19 (hazard ratio [HR] 0.58; 95% CI 0.44-0.77; p < 0.001) and a 73% lower hazard rate of severe COVID-19 (HR 0.27; 95% CI 0.07-1.04; p = 0.056) than the vaccine immunity group, but this effect was not seen among PLWH with CD4 counts <350 cells/μl or HIV viraemia. Twenty PLWH had persistent SARS-CoV-2 virus at least 50 days.

Hybrid immunity was associated with superior protection from COVID-19 compared to vaccine immunity with the ancestral mRNA-1273 vaccine. Persistent infections among immunocompromised PLWH may provide reservoirs for emerging variants.

National Institute of Allergy and Infectious Diseases.

The emergence of SARS-CoV-2 variants has significantly impacted the global response to the COVID-19 pandemic. This review examines the genetic diversity of SARS-CoV-2 variants, their roles in epidemiological tracking, and their influence on viral fitness. Variants of concern (VOCs) such as Alpha, Beta, Gamma, Delta, and Omicron have demonstrated increased transmissibility, altered pathogenicity, and potential resistance to neutralizing antibodies. Epidemiological tracking of these variants is crucial for understanding their spread, informing public health interventions, and guiding vaccine development. The review also explores how specific mutations in the spike protein and other genomic regions contribute to viral fitness, affecting replication efficiency, immune escape, and transmission dynamics. By integrating genomic surveillance data with epidemiological and clinical findings, this review provides a comprehensive overview of the ongoing evolution of SARS-CoV-2 and its implications for public health strategies and new vaccine development.

Severe COVID-19 typically results in pulmonary sequelae. However, current research lacks clarity on the differences in these sequelae among various clinical subtypes. This study aimed to evaluate the changing lung imaging features and predictive factors in patients with COVID-19 pneumonia in northern China over a 12-month follow-up period after the relaxation of COVID-19 restrictions in 2022.

Imaging and clinically relevant data from three groups (moderate, severe, and critical) of patients with varying severity were prospectively analyzed. Low-dose CT scans were conducted at 3, 6, and 12 months after discharge, with chest CT images evaluated at baseline and each follow-up using qualitative and quantitative analyses. Clinical symptoms and pulmonary function recovery at 12 months were documented. The correlation between lung function and CT results was analyzed. Univariate and multivariable logistic regression analyses were employed to examine factors influencing prognosis, while a post-hoc analysis model was utilized to investigate the relationships among different groups, time points, and chest CT findings.

Among the 103 hospitalized patients with COVID-19 pneumonia, 64 completed the 12-month evaluation. The median age was 63.70 ± 12.15%, and 62.5% (40/64) were men. During the follow-up period, while 67.19% (43/64) showed abnormalities, including fibrotic changes in 9.38% (6/64). Multivariable logistic regression identified age ≥ 65 (OR: 8.66; 95% CI: 1.86, 40.34; P = 0.006), length of hospital stays (OR: 1.23; 95% CI: 1.03, 1.47; P = 0.022), and baseline consolidation volume as a percentage of the whole lung (OR: 56.95; 95% CI: 1.198, 2706.782; P = 0.04) as independent risk factors for persistent CT lung abnormalities at 1 year. After 1 year, 34.38% (22/64) of patients still had abnormal lung function, and 9.38% (6/64) had pulmonary fibrosis and restrictive ventilatory dysfunction. The relationship between lung function and CT findings is weak correlation. The mixed model analysis revealed significant differences between groups, particularly between the moderate and severe groups, and significant changes in CT values over time.

One year after infection, more than one third of even moderate patients with mild symptoms had persistent pulmonary abnormalities. In our study, fibrotic changes were seen in severe and critically ill patients and remained stable 6 months after discharge from hospital. Imaging parameters can predict the prognosis. The larger the extent of baseline consolidation, the worse the prognosis of elderly patients.

We assessed case fatality rates (CFRs) in adults aged ≥70 years in 10 prefectures in Japan (14.8 million residents) diagnosed between January 2022 and March 2023, when the Omicron variant was dominant in Japan. We selected incident reports on 283,052 cases from participating public health centers reported according to the Infectious Diseases Control Law. Patients were passively followed up until the end of their isolation, date of death, or 28 days after COVID-19 diagnosis, whichever occurred first. We calculated age-standardized CFRs with 95% confidence intervals (CIs) using the Japanese population aged 70-79, 80-89 and ≥90 years in 2022, divided into 16 subgroups according to the period of COVID-19 diagnosis. The overall CFR was 1.59% (95% CI: 1.55-1.64%); ranging between 0.67% (95% CI: 0.38-0.96%, from May 23 to June 19, 2022) and 2.58% (95% CI: 2.36-2.80%, from January 31 to February 27, 2022). The age-standardized CFRs had three peaks, (2.2% from January 31 to February 27, 2022; 1.0% from July 18 to August 14, 2022; and 1.6% from December 26, 2022 to January 22, 2023) coinciding with the 6th, 7th, and 8th COVID-19 waves in Japan caused by the Omicron variant. Population-based CFRs for Omicron variant COVID-19 in adults aged ≥70 years remained <3% throughout the period January 2022 to March 2023, including during three large waves in Japan.

A new model is proposed to explore interactions between diabetes and novel coronavirus. The model accounted for both the omicron variant and variants varying from omicron. The model investigated compartments such as hospitalization, diabetes, co-infection, omicron variant, and quarantine. Additionally, the impact of different vaccination doses is assessed. Sensitivity analysis is carried out to determine disease prevalence and control options, emphasizing the significance of knowing epidemics and their characteristics. The model is validated using actual data from Japan. The parameters are fitted with the help of "Least Square Curve Fitting" method to describe the dynamic behavior of the proposed model. Simulation results and theoretical findings demonstrate the dynamic behavior of novel coronavirus and diabetes mellitus (DM). Biological illustrations that illustrate impact of model parameters are evaluated. Furthermore, effect of vaccine efficacy and vaccination rates for the vaccine's first, second, and booster doses is conducted. The impact of various preventive measures, such as hospitalization rate, quarantine or self-isolation rate, vaccine dose-1, dose-2, and booster dose, is considered for diabetic individuals in contact with symptomatic or asymptomatic COVID-19 infectious people in the proposed model. The findings demonstrate the significance of vaccine doses on people with diabetes and individuals infectious with omicron variant. The proposed work helps with subsequent prevention efforts and the design of a vaccination policy to mitigate the effect of the novel coronavirus.

In December 2022, China classified COVID-19 as a category B infectious disease. This ended 2 years of close epidemiological surveillance of COVID-19. The objective of this questionnaire was to assess the infection status in the COVID-19 pandemic since December in Henan Province, China, and the prevalence of infection in people who were taking ursodeoxycholic acid (UDCA) during this period. We distributed questionnaires to patients attending the gastroenterology clinic at the First Affiliated Hospital of Henan University of Chinese Medicine. The questionnaire lasted for 3 weeks and a total of 660 were collected, of which the number of people taking UDCA was 70. This is the first investigation into the rate of infection among those taking UDCA during the time of the COVID-19 pandemic. Our results showed that the overall infection rate among those taking UDCA was 71.43% (n = 50), with a 10% (n = 7) rate of asymptomatic infections, which was significantly lower than the 85.42% (n = 504) and 6.27% (n = 37) rates among respondents who did not take. The administration of UDCA showed a trend toward reducing the rate of COVID-19 infection, but the difference was not statistically significant when compared to patients with shorter durations of medication use. While less than 30% of participants remained uninfected during the study period, indicating a potential protective effect, it is important to note that complete prevention of SARS-CoV-2 infection by UDCA was not observed.

Early reports have indicated that the Omicron variant of coronavirus disease 2019 (COVID-19) may be associated with low mortality. However, the mortality rate of critical patients in Taiwan with COVID-19 caused by different variants has not been well described.

This retrospective cohort study was conducted at the Linkou Branch of Chang Gung Memorial Hospital, Taiwan, from April 2020 to September 2022. Critically ill patients who had confirmed SARS-CoV-2 infection and were on mechanical ventilation (MV) were enrolled. Demographic data, laboratory results, and treatment information were collected and analyzed. In addition, clinical outcomes for different SARS-CoV-2 variants were analyzed.

This study included 110 critical patients with COVID-19 who required intubation and intensive care unit (ICU) admission. Among these patients, 46 (41.8%) required intensive care during Alpha predominance period and 64 (58.2%) during the Omicron predominance period. The Alpha group had a higher body mass index, had a longer ICU stay, and included more patients with acute respiratory distress syndrome, and the Omicron group included more active smokers, had more comorbidities, had worse initial laboratory data (including higher white blood cell counts, prothrombin time [PT], activated partial prothrombin time, blood urine nitrogen levels, and creatine levels), and had higher in-hospital mortality rates (40.6% vs 15.2%, p = 0.004). The independent risk factors for in-hospital mortality, were Charlson Comorbidity Index (CCI) ≥ 3 and higher PT and creatine levels.

Our study discovered that CCI ≥ 3, elevated serum creatine levels, and prolonged PT were independently associated with a high mortality rate in patients with critical COVID-19. Patients with those risk factors may require intensive monitoring during their treatment course.

Variant-adapted COVID-19 vaccines are recommended for patients with inflammatory bowel disease (IBD). However, many patients rely on pre-existing immunity by original vaccines or prior infections.

To assess whether such immunity sufficiently combats the highly immune-evasive SARS-CoV-2 JN.1 variant.

Utilising two longitudinal cohorts, we evaluated immunity against JN.1 induced by original vaccines (IBD: n = 98; healthy: n = 48), omicron breakthrough infection (IBD: n = 55; healthy: n = 57) or XBB.1.5-adapted vaccines (IBD: n = 18). Neutralisation and anti-receptor-binding domain (RBD) IgG levels against wild-type SARS-CoV-2 and JN.1 were assessed using multiplex immunoassays. Study outcomes were wild-type and JN.1 neutralisation following three doses of original mRNA vaccines, stratified by immunosuppressive therapy (primary outcome), and JN.1 neutralisation following third-dose breakthrough infection or a fourth dose of XBB.1.5-adapted mRNA vaccines (secondary outcomes).

Following original vaccines, JN.1 neutralisation was lower than wild-type neutralisation in all study groups (healthy, anti-TNF and non-anti-TNF; each p < 0.001); most individuals lacked JN.1 neutralisation (healthy: 97.9%; anti-TNF: 98.3% and non-anti-TNF: 92.3%). Confounder-adjusted multivariable modelling strongly associated anti-TNF therapy with low levels of anti-JN.1-RBD IgG (fold-change 0.48 [95% CI 0.39-0.59]). JN.1 neutralisation was similar in patients with or without breakthrough infection (anti-TNF, non-anti-TNF; each p > 0.05); neutralisation failure was 100% despite breakthrough infection. XBB.1.5-adapted vaccines enhanced JN.1 neutralisation (p < 0.001) and reduced neutralisation failure rates in patients with IBD (94.4% pre-vaccination vs. 44.4% post-vaccination; p = 0.003).

Only variant-adapted vaccines protect against emerging SARS-CoV-2 variants. Patients with IBD and healthy individuals without recent vaccination may lack protection against the JN.1 subvariant KP.3 which causes current COVID-19 surges.

We evaluated the impact of preoperative SARS-CoV-2 infections on postoperative outcomes among patients undergoing elective cancer surgery.

This ambidirectional (retrospective and prospective) study was conducted among patients undergoing elective cancer surgery between December 2022 and March 2023. Patients with different time intervals between SARS-CoV-2 infection and surgery (0-6 weeks and ≥7 weeks) were compared with those without SARS-CoV-2 infection. The primary outcome was 30-day postoperative pulmonary complications (PPCs). Secondary outcomes included 30-day postoperative mortality, major adverse cardiovascular events (MACE), and other postoperative adverse outcomes.

Of the 830 patients analyzed, 239 (28.8%) had SARS-CoV-2 infection 0-6 weeks before cancer surgery, and they had a higher incidence of PPCs (4.6% in no SARS-CoV-2 infection, 12.1% in 0-6 weeks, and 5.1% in ≥7 weeks, p = 0.001). The logistic regression model revealed that, compared with patients without SARS-CoV-2 infection, surgery performed 0-6 weeks after SARSCoV-2 infection was associated with a higher risk of PPCs (adjusted odds ratio [aOR] 2.83; 95% confidence interval [CI] 1.34-5.98), and surgery performed ≥7 weeks after SARSCoV-2 infection was associated with a similar risk of PPCs (aOR 1.19; 95% CI 0.54-2.64). However, preoperative SARS-CoV-2 infection was not associated with a risk of 30-day postoperative mortality, MACE, or other adverse postoperative outcomes.

In patients with preoperative Omicron variant infection, nonemergency cancer surgery can be scheduled ≥7 weeks after the infection to decrease the risk of PPCs, but it can be advanced if the risk of delay exceeds the risk of proceeding with the surgery.

Human cytomegalovirus (HCMV) infection occurs in immunosuppressed individuals and is known to increase mortality. Patients with coronavirus disease 2019 (COVID-19) are often treated with steroids, require intensive care unit (ICU) treatment, and may therefore be at risk for HCMV infection. However, which factors predispose severely ill patients with COVID-19 to HCMV infection and the prognostic value of such infections remain largely unexplored. This study aimed to examine the incidence and potential risk factors of HCMV infection in patients with severe or critical COVID-19 and evaluate the relationship between HCMV infection and mortality.

We used administrative claims data from advanced treatment hospitals in Japan to identify and analyze patients with severe or critical COVID-19. We explored potential risk factors for HCMV infection using multivariable regression models and its contribution to mortality in patients with COVID-19. Overall, 33,151 patients who progressed to severe or critical COVID-19 illness were identified. The incidence of HCMV infection was 0.3-1.7 % depending on the definition of HCMV infection. Steroids, immunosuppressants, ICU admission, and blood transfusion were strongly associated with HCMV infection. Furthermore, HCMV infection was associated with patient mortality independent of the observed risk factors for death.

HCMV infection is a notable complication in patients with severe or critical COVID-19 who are admitted to the ICU or receive steroids, immunosuppressants, and blood transfusion and can significantly increase mortality risk.

The Omicron variant of SARS-CoV-2 emerged as a new variant of concern, characterized by high transmissibility and lower severity compared with previous variants, and became the majority variant in the sixth wave in Spain. This study aims to assess the impact of SARS-CoV-2 infection on liver transplant recipients (LTRs) during 2023 in the population of Cantabria.

The study included 295 LTRs undergoing follow-up at the Liver Transplant Unit of the Marqués de Valdecilla University Hospital. Data on patient characteristics, comorbidities, and vaccination schedules were collected. Humoral response to mRNA vaccines was evaluated using IgG antibodies against the S protein and an adequate response was defined as antibody titers of >260 BAU/mL 1 month after the third vaccine dose.

In Cantabria, 0.75% of the general population and 7.10% of LTRs were infected with SARS-CoV-2. Most LTRs were men with comorbidities, mainly cardiovascular disease and hypertension. Of the LTRs, 95.2% were fully vaccinated and received 3 doses of the Moderna mRNA vaccine, and all had an adequate response after 4 to 5 doses. Most infections in LTRs were asymptomatic or mild, with lower hospitalization rates. No LTRs required intensive care admission or died owing to SARS-CoV-2 infection.

LTRs are targets for SARS-CoV-2 vaccination. The Omicron variant has shown greater transmissibility but causes milder disease in vaccinated LTRs. All vaccinated LTRs showed an adequate response after 4 to 5 doses. Therefore, vaccination protects against severe disease and mortality in LTRs, and booster vaccinations with variant-adapted vaccines are recommended.

The prognosis of patients with coronavirus disease 2019 (COVID-19) was poor although its survival rate has been improved after the occurrence of the Omicron strain. Autoimmune pulmonary alveolar proteinosis (APAP), a lung disease caused by macrophage dysfunction induced by anti-granulocyte-macrophage colony-stimulating factor (GM-CSF)-neutralizing autoantibodies, is characterized by the deposition of proteinaceous material in the alveolar spaces. The clinical course of COVID-19 in patients with APAP remains unclear and this study aimed to clarify it.

The data of 23 patients with APAP, who were diagnosed with COVID-19 between January 2020 and May 2023 and collected through a nationwide questionnaire surveillance system, were retrospectively reviewed.

Based on the epidemiological frequency at disease onset, suspected strains of severe acute respiratory syndrome coronavirus 2 were Omicron (n = 18) and non-Omicron (n = 5). Fifteen patients were vaccinated. Six and three patients received anti-viral drugs and corticosteroids, respectively. One patient in the third trimester of pregnancy died despite treatment in the intensive care unit. Six patients were complicated by pneumonia and/or required supplemental oxygen. These patients were suspected to have non-Omicron strains (p = 0.087). Vaccination status showed a significant association with suspected Omicron strains. The radiological findings in four patients and shortness of breath improved in two of the four patients after COVID-19.

The severity and prognosis of the patients were not worse than those predicted based on the results of a previous study. The transition from a non-Omicron strain to an Omicron strain and the vaccination status may have affected these results.

Myocarditis is a potentially fatal complication of coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. COVID-19 myocarditis appears to have distinct inflammatory characteristics that distinguish it from other viral etiologies. COVID-19 myocarditis can present with symptoms ranging from dyspnea and chest pain to acute heart failure and death. It is critical to detect any cases of myocarditis, especially fulminant myocarditis, which can be characterized by signs of heart failure and arrhythmias. Serial troponins, echocardiography, and electrocardiograms should be performed as part of the initial workup for suspected myocarditis. The second step in detecting myocarditis is cardiac magnetic resonance imaging and endomyocardial biopsy. Treatment for COVID-19 myocarditis is still debatable; however, combining intravenous immunoglobulins and corticosteroids may be effective, especially in cases of fulminant myocarditis. Overall, more research is needed to determine the incidence of COVID-19 myocarditis, and the use of intravenous immunoglobulins and corticosteroids in combination requires large randomized controlled trials to determine efficacy. The purpose of this review is to summarize current evidence on the subject.

Acute disseminated encephalomyelitis (ADEM) has been identified as an Adverse Event of Special Interest in the COVID-19 vaccine programme due to its long-standing temporal association with a wide range of other vaccines. Case reports of ADEM shortly following COVID-19 vaccination have now been documented.    There were 217 ADEM admissions in 215 individuals in the period 8th December 2020 to 31st March 2023. An increased risk of ADEM following the first dose of ChAdOx1 vaccine was observed (relative incidence (RI) = 3.13, 95% Confidence Interval (CI) [1.56-6.25]) with a vaccine attributable risk of 0.39 per million doses. When doses 1 and 2 were combined this increased risk remained just significant (1.96 [95%CI 1.01-3.82]). No significant increased risk was observed with any other vaccine or dose. This small, elevated risk after the first dose of ChAdOx1-S vaccine demonstrates how large national electronic datasets can be used to identify very rare risks and provides reassurance that any risk of ADEM following the ChAdOx1-S COVID-19 vaccination is extremely small. Given the rarity of this risk, further studies in settings with access to data on large populations should be carried out to verify these findings.

Modeling and predicting mutations are critical for COVID-19 and similar pandemic preparedness. However, existing predictive models have yet to integrate the regularity and randomness of viral mutations with minimal data requirements. Here, we develop a non-demanding language model utilizing both regularity and randomness to predict candidate SARS-CoV-2 variants and mutations that might prevail. We constructed the "grammatical frameworks" of the available S1 sequences for dimension reduction and semantic representation to grasp the model's latent regularity. The mutational profile, defined as the frequency of mutations, was introduced into the model to incorporate randomness. With this model, we successfully identified and validated several variants with significantly enhanced viral infectivity and immune evasion by wet-lab experiments. By inputting the sequence data from three different time points, we detected circulating strains or vital mutations for XBB.1.16, EG.5, JN.1, and BA.2.86 strains before their emergence. In addition, our results also predicted the previously unknown variants that may cause future epidemics. With both the data validation and experiment evidence, our study represents a fast-responding, concise, and promising language model, potentially generalizable to other viral pathogens, to forecast viral evolution and detect crucial hot mutation spots, thus warning the emerging variants that might raise public health concern.

The emergence of the Omicron variant of severe acute respiratory syndrome coronavirus-2 has significantly altered the clinical features and severity of coronavirus disease 2019 (COVID-19).

This study aims to evaluate whether the clinical factors that previously predicted COVID-19 remain valid following the emergence of the Omicron variant.

This cross-sectional study was conducted at Showa University Fujigaoka Hospital from April 2022 to March 2023. A total of 576 patients with suspected COVID-19 were included, of which 258 (44.8%) were diagnosed with COVID-19 based on real-time reverse-transcription polymerase chain reaction tests. Clinical data were collected retrospectively, and multivariate logistic regression was used to analyze factors associated with a COVID-19 diagnosis.

Of the 258 patients diagnosed with COVID-19, 60% had mild disease, and the overall severity was lower than in previous reports prior to the emergence of the Omicron variant. In the multivariate analysis, only C-reactive protein (CRP) levels were significantly associated with COVID-19 (odds ratio, 0.3164; 95% confidence interval, 0.2077-0.4819), while factors such as age, sex, body mass index, lactate dehydrogenase, and comorbidities were not significantly associated. Non-COVID-19 cases were primarily bacterial infections, accounting for 57.2% of the non-COVID-19 diagnoses. Mortality rates did not differ significantly between the COVID-19 and non-COVID-19 groups.

The clinical characteristics of COVID-19 have become less distinct since the emergence of the Omicron variant, with CRP being the primary marker associated with a COVID-19 diagnosis. As COVID-19 continues to transition towards a more common infectious disease, distinguishing it will become increasingly challenging.

The emergence of SARS-CoV-2 variants of concern (VOCs) during the COVID-19 pandemic necessitates investigation into their clinical differentiation and outcomes. This study aimed to examine these differences among VOCs, considering multiple related factors. An observational cohort study was conducted on patients diagnosed with SARS-CoV-2 infection via nasopharyngeal/oropharyngeal swab who visited the emergency department of a public Greek hospital between October 2020 and July 2022 during different VOC circulation in the region. Data on clinical manifestations, outcomes, and medical history (comorbidities, prior SARS-CoV-2 infection, vaccination status against COVID-19) were collected through a questionnaire and medical records for those hospitalized. A total of 913 patients were included in this study (813 adults ≥18 years old, 100 children <18 years old). Significant differences were observed across VOCs for both adults and children. A lower proportion of children developed symptoms during the non-Omicron variants, 73.5%, compared to Omicron variants, 86.4%. Fever, dyspnea, and taste and smell disorders were observed more frequently among non-Omicron adult cases, in contrast to upper respiratory symptoms, which were more common symptoms among Omicron infections. The non-Omicron variants were associated with higher rates of hospitalization at 30.6%, pneumonia at 23.0%, and death at 6.1% compared to Omicron variants at 8.0%, 5.0%, and 1.8%, respectively. Vaccination against COVID-19 was shown to be a protective factor for severe outcomes. Our findings suggest distinct clinical presentations and outcomes associated with different VOCs. Despite the fact that current VOCs circulating are less severe, the COVID-19 vaccine continues to play a protective role for severe cases.

A few years into the COVID-19 pandemic, the SARS-CoV-2 Omicron strain rapidly becomes and has remained the predominant strain. To date, Omicron and its subvariants, while more transmittable, appear to cause less severe disease than prior strains. To study the cause of this reduced pathogenicity we compare SARS-CoV-2 ancestral Nsp6 with Nsp6-Omicron, which we have previously identified as one of the most pathogenic viral proteins. Here, through ubiquitous expression in Drosophila, we show that ancestral Nsp6 causes both structural and functional damage to cardiac, muscular, and tracheal (lung) tissue, whereas Nsp6-Omicron has minimal effects. Moreover, we show that ancestral Nsp6 dysregulates the glycolysis pathway and disrupts mitochondrial function, whereas Nsp6-Omicron does not. Through validation in mouse primary cardiomyocytes, we find that Nsp6-induced dysregulated glycolysis underlies the cardiac dysfunction. Together, the results indicate that the amino acid changes in Omicron might hinder its interaction with host proteins thereby minimizing its pathogenicity.

In the realm of infectious disease control, accurate modeling of the transmission dynamics is pivotal. As human mobility and commuting patterns are key components of communicable disease spread, we introduce a novel travel time aware metapopulation model. Our model aims to enhance estimations of disease transmission. By providing more reliable assessments on the efficacy of interventions, curtailing personal rights or human mobility behavior through interventions can be minimized. The proposed model is an advancement over traditional compartmental models, integrating explicit transmission on travel and commute, a factor available in agent-based models but often neglected with metapopulation models. Our approach employs a multi-edge graph ODE-based (Graph-ODE) model, which represents the intricate interplay between mobility and disease spread. This granular modeling is particularly important when assessing the dynamics in densely connected urban areas or when heterogeneous structures across entire countries have to be assessed. The given approach can be coupled with any kind of ODE-based model. In addition, we propose a novel multi-layer waning immunity model that integrates waning of different paces for protection against mild and severe courses of the disease. As this is of particular interest for late-phase epidemic or endemic scenarios, we consider the late-phase of SARS-CoV-2 in Germany. The results of this work show that accounting for resolved mobility significantly influences the pattern of outbreaks. The improved model provides a refined tool for predicting outbreak trajectories and evaluating intervention strategies in relation to mobility by allowing us to assess the transmission that result on traveling. The insights derived from this model can serve as a basis for decisions on the implementation or suspension of interventions, such as mandatory masks on public transportation. Eventually, our model contributes to maintaining mobility as a social good while reducing exuberant disease dynamics potentially driven by travel activities.

Despite the widespread administration of coronavirus disease 2019 (COVID-19) vaccines, the impact on patients with asymptomatic to mild illness remains unclear. Here, we aimed to assess the efficacy of various vaccine doses and types on the duration of isolation duration and discharge rates, the viral shedding duration, and negative rates in asymptomatic to mild COVID-19 patients.

We included adult patients at the Fangcang isolation centres in Pazhou or Yongning between November and December 2022. We analysed data on basic demographics, admission details, laboratory indicators and vaccination information.

A total of 6560 infected patients were included (3584 from Pazhou and 2976 from Yongning). Of these, 90.6% received inactivated vaccines, 3.66% received recombinant SARS-CoV-2 spike protein subunit vaccines and 0.91% received adenovirus vaccines. Among the 6173 vaccinated individuals, 71.9% received a booster dose. By day 9, the isolation rate reached 50% among vaccinated patients. On day 7.5, the positive rate among vaccinated individuals reached 50%.

Full vaccination was effective, with heterologous vaccines showing greater efficacy than inactivated vaccines alone. However, there was no significant difference in the vaccine protective effect 12 months after vaccination.