Current Coronavirus Disease Research Articles

Possible rapid reduction of anti-RBD antibody titre after SARS-CoV-2 mRNA vaccination in pregnant women: Multicentre prospective study.

Pregnant women are at increased risk for severe illness associated with coronavirus disease 2019 (COVID-19) compared to nonpregnant women. The aim of this multicenter prospective study was to assess the current COVID-19 vaccination status of pregnant women in the southern Osaka district and to compare their antibody titers with those of nonpregnant women. Serum antibody titers of anti-NCP antibodies (antibodies against the SARS-CoV-2 nucleocapsid) and anti-RBD antibodies (the receptor binding domain of the S1 subunit of the spike protein) were evaluated in 753 pregnant women at 34-35 weeks of gestation from October 2021 to March 2022. Anti-RBD antibody titre was also investigated in 1003 health care workers at Kindai University hospital 3 and 6 months after a second dose of the vaccine from March 2021 to April 2021. 519 (68.9%) pregnant women were vaccinated during pregnancy, of whom 497 (95.8%) received two doses. The COVID-19 infection rate calculated from the number of pregnant women with a positive anti-NCP antibody titre or with confirmed diagnosis was 5.1% (12/234) in the unvaccinated and 3.5% (18/519) in the vaccinated. The estimated half-life calculated from anti-RBD antibody titers and the number of days between vaccination and antibody testing was 39.9 days. The antibody titre and half-life in pregnant women were significantly lower and shorter than in nonpregnant women aged 20-39 years (109.4 days). Our study showed that pregnant women may have lower vaccine-acquired COVID-19 immunity than nonpregnant women.

Improving Patient Wait Times on the First Day of Radiotherapy Treatment

Long wait times on starting day of radiotherapy (day 1) can cause dissatisfaction among both patients and healthcare providers. Reducing these wait times will decrease stress and decongest hospital facilities especially in current coronavirus disease 2019 times. A multidisciplinary core team was formed during the Stanford-India Collaborative Quality Improvement training to reduce the median wait times on day 1 of treatment from 6 to 4.5 hours (a 25% reduction). Several factors were identified on the fishbone diagram, and key causes were identified using a Pareto chart and action prioritization matrix. The Plan-Do-Study-Act Cycle strategy was undertaken for the identified interventions. The outcome measure was time from arrival at the hospital to entry into a treatment room. Data were obtained from time charts at various stations and electronic records. The secondary measures were visual analog scale (VAS) scores, 80th percentile wait times, and the day-2 delay percentage. The balancing measure was “new errors” due to interventions. The interventions included the completion of all administrative tasks not needing patients' presence on the day before day 1. Baseline data from 198 patients and postintervention data from 160 patients were compared and analyzed. The median wait time at baseline, which was 6 hours, was reduced to 4.2 hours. The VAS score showed 70.4, 67.7, and 71.9% satisfaction for the resident physician, therapists, and patients, respectively. The 80th percentile wait times reduced from 8 to 5.7 hours; and the day 2 starting rate decreased from 22.5 to 2.04%, with no new errors reported. Radiotherapy day 1 wait times can be safely decreased, leading to improved satisfaction among patients and healthcare providers, by utilizing classic quality improvement methods and tools.

Possible mechanisms of SARS-CoV-2-associated myocardial fibrosis: reflections in the post-pandemic era.

Since December 2019, coronavirus disease 2019 (COVID-19) has been spreading worldwide with devastating immediate or long-term effects on people's health. Although the lungs are the primary organ affected by COVID-19, individuals infected with SARS-CoV-2 also develop systemic lesions involving multiple organs throughout the body, such as the cardiovascular system. Emerging evidence reveals that COVID-19 could generate myocardial fibrosis, termed "COVID-19-associated myocardial fibrosis." It can result from the activation of fibroblasts via the renin-angiotensin-aldosterone system (RAAS), transforming growth factor-β1 (TGF-β1), microRNAs, and other pathways, and can also occur in other cellular interactions with SARS-CoV-2, such as immunocytes, endothelial cells. Nonetheless, to gain a more profound insight into the natural progression of COVID-19-related myocardial fibrosis, additional investigations are necessary. This review delves into the underlying mechanisms contributing to COVID-19-associated myocardial fibrosis while also examining the antifibrotic potential of current COVID-19 treatments, thereby offering guidance for future clinical trials of these medications. Ultimately, we propose future research directions for COVID-19-associated myocardial fibrosis in the post-COVID-19 era, such as artificial intelligence (AI) telemedicine. We also recommend that relevant tests be added to the follow-up of COVID-19 patients to detect myocardial fibrosis promptly.

Evaluation of Antibody Response and Reinfection in Improved Hypertensive, Cardiac, and Diabetic Patients with COVID-19 for Six Months in Unvaccinated Outpatients

Background: This study presents a unique investigation into the relationship between the persistence of IgG antibody levels and reinfection in recovered coronavirus disease 2019 (COVID-19) patients. By shedding light on this aspect, we aim to address concerns about the risk of reinfection in unvaccinated patients, offering a fresh perspective in the current COVID-19 research landscape. Objectives: This study takes a novel approach by focusing on the antibody response and reinfection in COVID-19 patients who were treated in outpatient settings for six months. This approach distinguishes our research within the broader context of COVID-19 studies. Methods: Our comprehensive and rigorous prospective cohort study included 149 COVID-19 outpatients referred to Imam Ali Clinic in Dezfoul City, Khuzestan province, Iran. Data was meticulously collected from September 2021 to February 2022. All unvaccinated patients underwent RT-PCR testing, and their anti-SARS-CoV-2 IgM/IgG levels were measured at the onset of illness. Serum IgG levels were then measured again after three and six months using ELISA. Results: All COVID-19 patients had their IgG antibody levels tested three times (on days two to four of the illness, at three months, and at six months). Significant differences in IgG antibody levels were observed between the vaccinated and unvaccinated groups during each period (P < 0.05). Additionally, there were substantial differences between the hypertension and non-hypertension groups (P = 0.032). Importantly, our findings reaffirm the impartiality of our research, as no significant differences were found between reinfection rates and various demographic or disease-related factors. Conclusions: The findings of this study suggest that high levels of IgG antibodies in unvaccinated patients could potentially reduce the risk of reinfection. This insight could have important implications for public health strategies and the management of COVID-19 in unvaccinated populations, providing valuable information for decision-makers in the field.

Performance of the 4C and SEIMC scoring systems in predicting mortality from onset to current COVID-19 pandemic in emergency departments

The evolution of the COVID-19 pandemic has been associated with variations in clinical presentation and severity. Similarly, prediction scores may suffer changes in their diagnostic accuracy. The aim of this study was to test the 30-day mortality predictive validity of the 4C and SEIMC scores during the sixth wave of the pandemic and to compare them with those of validation studies. This was a longitudinal retrospective observational study. COVID-19 patients who were admitted to the Emergency Department of a Spanish hospital from December 15, 2021, to January 31, 2022, were selected. A side-by-side comparison with the pivotal validation studies was subsequently performed. The main measures were 30-day mortality and the 4C and SEIMC scores. A total of 27,614 patients were considered in the study, including 22,361 from the 4C, 4,627 from the SEIMC and 626 from our hospital. The 30-day mortality rate was significantly lower than that reported in the validation studies. The AUCs were 0.931 (95% CI: 0.90–0.95) for 4C and 0.903 (95% CI: 086–0.93) for SEIMC, which were significantly greater than those obtained in the first wave. Despite the changes that have occurred during the coronavirus disease 2019 (COVID-19) pandemic, with a reduction in lethality, scorecard systems are currently still useful tools for detecting patients with poor disease risk, with better prognostic capacity.

Coronavirus Disease-19-associated Mucormycosis: A Single-center Observational Study of 69 Patients.

We studied the clinical presentation, risk factors, complications, and in-hospital outcomes of patients with coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM). A retrospective study was done on 69 COVID-19 patients with microbiologically proven mucormycosis admitted over a period of seven months from March 2021 to September 2021. All 69 mucormycosis patients (46 males, 23 females) had reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed COVID-19 infection. Their mean age was 52.8 years, with mucormycosis developing in 51 patients (73.9%) within 30 days of COVID-19 infection; 7 (10.1%) were positive on admission. Rhino-orbital-cerebral mucormycosis (ROCM) was the most common (40.3%), followed by rhino-orbital (37.3%) and sinonasal (22.4%). Diabetes mellitus was present in 98.6% of patients. Common symptoms of mucormycosis were facial pain, headache, facial swelling, and vision loss. During COVID-19, 88.4 and 52.5% received immunosuppressive treatment and zinc sulfate, respectively; 34.7% needed intensive care unit (ICU) admission. The mortality rate was 26.1%. On multivariate logistic regression analysis, the presence of chronic kidney disease, leukocytosis, ophthalmoplegia, oral/palate ulceration, current need for invasive ventilation, and past duration of oxygen therapy and zinc supplementation were significantly associated with mortality. Patients with current COVID-19 infection had severe disease with increased need for intensive care (57.1 vs 14.5%) and higher mortality (57.1 vs 22.6%) compared to mucormycosis patients with previous COVID-19 infection. Rhino-orbital-cerebral, rhino-orbital, and sinonasal were the most common presentations in cases of mucormycosis, with a mortality rate of 26.1%. COVID-19 coinfection predisposes patients with mucormycosis to severe disease with higher mortality.

Abstract We119: Treatment of Viral Myocarditis by Targeting the TRIM29-PERK Axis-Mediated ER Stress Immune Response

Viral myocarditis, an inflammatory disease of the myocardium, is a significant cause of sudden death in children and young adults. The current coronavirus disease 19 pandemic emphasizes the need to understand the pathogenesis mechanisms and potential treatment strategies for viral myocarditis. Here, we found that TRIM29 was highly induced by cardiotropic viruses and promoted protein kinase RNA-like endoplasmic reticulum kinase (PERK)-mediated endoplasmic reticulum (ER) stress, apoptosis, and reactive oxygen species (ROS) responses that promote viral replication in cardiomyocytes in vitro . TRIM29 deficiency protected mice from viral myocarditis by promoting cardiac antiviral functions and reducing PERK-mediated inflammation and immunosuppressive monocytic myeloid-derived suppressor cells (mMDSC) in vivo . Mechanistically, TRIM29 interacted with PERK to promote SUMOylation of PERK to maintain its stability, thereby promoting PERK-mediated signaling pathways. Finally, we demonstrated that the PERK inhibitor GSK2656157 mitigated viral myocarditis by disrupting the TRIM29-PERK connection, thereby bolstering cardiac function, enhancing cardiac antiviral responses, and curbing inflammation and immunosuppressive mMDSC in vivo . Our findings offer insight into how cardiotropic viruses exploit TRIM29-regulated PERK signaling pathways to instigate viral myocarditis, suggesting that targeting the TRIM29-PERK axis could mitigate disease severity.

The status and influencing factors of COVID-19 vaccination in patients with COPD

In this study, we investigated the status and influencing factors of coronavirus disease 2019 (COVID-19) vaccination in patients with chronic obstructive pulmonary disease (COPD). A questionnaire on COVID-19 vaccination in patients with COPD was developed. The clinical characteristics, COVID-19 vaccination status, other relevant vaccinations, and vaccination status of the patients with COPD were collected anonymously. Logistic regression analysis was used to analyze the factors influencing COVID-19 vaccination in patients with COPD. There were 1898 returned questionnaires, of which 1874 were valid. The proportion of patients who completed the COVID-19 vaccination program was 78.60%. Factors influencing the COVID-19 vaccination rate were: the age of individuals who were 75–85 years old and > 85 years old, acute exacerbation 3–4 times in the previous year, comorbid cardiovascular and endocrine system diseases, failure to take regular medication for COPD, application of non-invasive ventilation machines, believing that their current health condition has deteriorated, believing that the current COVID-19 vaccine is not safe, medical staff not specifying whether they would recommend vaccination against COVID-19, medical staff not recommending the COVID-19 vaccine, and fear of adverse reactions and aggravation of COPD. Patients with COPD had a high COVID-19 vaccination rate in China, whereas patients with pneumonia, influenza, and herpes zoster had a low vaccination rate. Improving the patients’ understanding of the safety and effectiveness of the vaccine and promoting effective communication between medical staff and patients would help increase the vaccination rate of patients with COPD.

Safety and Efficacy of Tocilizumab in critically ill patients with COVID-19: An Observational study

Abstract Background The current coronavirus disease 2019 (COVID-19) outbreak is a worldwide emergency, as its rapid spread and high mortality rate has caused severe disruptions. The number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2), the causative agent of COVID-19, is rapidly increasing worldwide. Patients with COVID- 19 can develop pneumonia. Severe symptoms of acute respiratory distress syndrome (ARDS), and multiple organ failure. Aim of the Work to compare Compare between clinical symptoms (MMRC Dyspnea score), oxygen therapy, TlC & Lymphocytic count and inflammatory markers (CRP, serum ferritin, D.dimer) before and after the administration of 2 doses of tocilizumab noting that the second dose is given within 24-48 hours from first dose on 50 patients admitted to Ain-Shams isolation university hospital at Al-Obour, Ain-shams Geriatrics isolation hospital and Ain- shams isolation field hospital from 1st of May 2020 to 1st of January 2022. Patients and Methods Baseline cbc with differential, liver function tests, kidney functions tests, D dimer, serum ferritin and CRP. 2 doses of tocilizumab given on two days, first dose is 8mg/kg diltuted in 100 cc saline 0.9% given along 1 hour while the second dose (4mg/kg diltuted in 100 cc saline 0.9%) is given after 24 hours. Follow up inflammatory markers (cbc with differential, crp, d dimer, serum ferritin) were withdrawn after 3 days from second dose of tocilizumab. Assestment of clinical symptoms after 48 hours of second dose of tocilizumab. Assestment of oxygen thearpy on day 2 and day 30 after administration of tocilizumab. Results the administration of tocilizumab highly significantly improves some clinical symptoms (bony aches, fatigue, fever) while worsens expectoration, but highly significantly improves oxygen therapy and po2/fio2 ratio, with no significant effect on inflammatory marker other than CRP which showed marked increase. Tocilizumab shows neither effect on patients’ fate and mortality nor on hospital stay although mean age of 63 was statistically highly significant on increased patients’ mortality and renal impairment significantly affected length of hospital stay. the effect of timing of tocilizumab administration on patients’ fate and mortality showed non statistically significant improvement when given from day 6 to day 10 since onset of symptoms Conclusion The administration of tocilizumab highly significantly improves clinical symptoms, oxygen therapy and po2/fio2 ratio, with no siginifcant effect on inflammatory marker other than CRP which showed marked increase, which may be attributed to early withdrawal of inflammatory markers. Tocilizumab shows neither effect on patients’ fate and mortality nor on hospital stay although mean age of 63 was statistically highly significant on increased patients’ mortality and renal impairment significantly affected length of hospital stay. We studied the effect of timing of tocilizumab administration on patients’ fate and mortality which showed non statistically significant improvement when given from day 6 to day 10 since onset of symptoms which may be due to small sample size.

Integrated CNN and Federated Learning for COVID-19 Detection on Chest X-Ray Images.

Currently, Coronavirus Disease 2019 (COVID-19) is still endangering world health and safety and deep learning (DL) is expected to be the most powerful method for efficient detection of COVID-19. However, patients' privacy concerns prohibit data sharing between medical institutions, leading to unexpected performance of deep neural network (DNN) models. Fortunately, federated learning (FL), as a novel paradigm, allows participating clients to collaboratively train models without exposing source data outside original location. Nevertheless, the current FL-based COVID-19 detection methods prefer optimizing secondary objectives including delay, energy consumption and privacy, while few works focus on improving the model accuracy and stability. In this paper, we propose a federated learning framework with dynamic focus for COVID-19 detection on CXR images, named FedFocus. Specifically, to improve the training efficiency and accuracy, the training loss of each model is taken as the basis for parameter aggregation weights. As training layer deepens, a constantly updated dynamic factor is designed to stabilize the aggregation process. In addition, to highly restore the real dataset, the training sets in our experiments are divided based on the population and the infection of three real cities. Extensive experiments conducted on the real-world CXR images dataset demonstrate that FedFocus outperforms the baselines in model training efficiency, accuracy and stability.

Cost-effectiveness of COVID rapid diagnostic tests for patients with severe/critical illness in low- and middle-income countries: A modeling study.

Rapid diagnostic tests (RDTs) for coronavirus disease (COVID) are used in low- and middle-income countries (LMICs) to inform treatment decisions. However, to date, it is unclear when this use is cost-effective. Existing analyses are limited to a narrow set of countries and uses. The aim of this study is to assess the cost-effectiveness of COVID RDTs to inform the treatment of patients with severe illness in LMICs, considering real world practice. We assessed the cost-effectiveness of COVID testing across LMICs using a decision tree model, differentiating results by country income level, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) prevalence, and testing scenario (none, RDTs, polymerase chain reaction tests-PCRs and combinations). LMIC experts defined realistic care pathways and treatment options. Using a healthcare provider perspective and net monetary benefit approach, we assessed both intended (COVID symptom alleviation) and unintended (treatment side effects) health and economic impacts for each testing scenario. We included the side effects of corticosteroids, which are often the only available treatment for COVID. Because side effects depend both on the treatment and the patient's underlying illness (COVID or COVID-like illnesses, such as influenza), we considered the prevalence of COVID-like illnesses in our analyses. We found that SARS-CoV-2 testing of patients with severe COVID-like illness can be cost-effective in all LMICs, though only in some circumstances. High influenza prevalence among suspected COVID cases improves cost-effectiveness, since incorrectly provided corticosteroids may worsen influenza outcomes. In low- and some lower-middle-income countries, only patients with a high index of suspicion for COVID should be tested with RDTs, while other patients should be presumed to not have COVID. In some lower-middle-income and upper-middle-income countries, suspected severe COVID cases should almost always be tested. Further, in these settings, negative test results in patients with a high initial index of suspicion should be confirmed through PCR and, during influenza outbreaks, positive results in patients with a low initial index of suspicion should also be confirmed with a PCR. The use of interleukin-6 receptor blockers, when supported by testing, may also be cost-effective in higher-income LMICs. The cost at which they would be cost-effective in low-income countries ($162 to $406 per treatment course) is below current prices. The primary limitation of our analysis is substantial uncertainty around some of the parameters in our model due to limited data, most notably on current COVID mortality with standard of care, and insufficient evidence on the impact of corticosteroids on patients with severe influenza. COVID testing can be cost-effective to inform treatment of LMIC patients with severe COVID-like disease. The optimal algorithm is driven by country income level and health budgets, the level of suspicion that the patient may have COVID, and influenza prevalence. Further research to better characterize the unintended effects of corticosteroids, particularly on influenza cases, could improve decision making around the treatment of those with COVID-like symptoms in LMICs.

Discovery of Novel Spike Inhibitors against SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current coronavirus disease pandemic. With the rapid evolution of variant strains, finding effective spike protein inhibitors is a logical and critical priority. Angiotensin-converting enzyme 2 (ACE2) has been identified as the functional receptor for SARS-CoV-2 viral entry, and thus related therapeutic approaches associated with the spike protein-ACE2 interaction show a high degree of feasibility for inhibiting viral infection. Our computer-aided drug design (CADD) method meticulously analyzed more than 260,000 compound records from the United States National Cancer Institute (NCI) database, to identify potential spike inhibitors. The spike protein receptor-binding domain (RBD) was chosen as the target protein for our virtual screening process. In cell-based validation, SARS-CoV-2 pseudovirus carrying a reporter gene was utilized to screen for effective compounds. Ultimately, compounds C2, C8, and C10 demonstrated significant antiviral activity against SARS-CoV-2, with estimated EC50 values of 8.8 μM, 6.7 μM, and 7.6 μM, respectively. Using the above compounds as templates, ten derivatives were generated and robust bioassay results revealed that C8.2 (EC50 = 5.9 μM) exhibited the strongest antiviral efficacy. Compounds C8.2 also displayed inhibitory activity against the Omicron variant, with an EC50 of 9.3 μM. Thus, the CADD method successfully discovered lead compounds binding to the spike protein RBD that are capable of inhibiting viral infection.

Adherence to COVID-19 preventive measures among residents in selected townships, Yangon Region, Myanmar: a community-based cross-sectional study

BackgroundTo fight the current coronavirus disease (COVID-19) pandemic, many countries have implemented various mitigation measures to contain the spread of the disease. By engaging with health service providers, the community’s participation in adherence to preventive measures is certainly required in the implementation of COVID-19 mitigation strategies. Therefore, this study aimed to assess the level of adherence to COVID-19 preventive measures and its associated factors among the residents, Yangon Region, Myanmar.MethodsA community-based cross-sectional study was carried out among 636 residents in Yangon Region, Myanmar, from October to December 2021. A multistage non-probability sampling method, purposively selected for three townships in Yangon Region and convenience sampling for 212 participants from each township, was applied and the data were collected by face-to-face interviews using structured and pretested questionnaires. Data were entered, coded, and analyzed using IBM SPSS version 25.0. Simple and multiple logistic regression analysis were performed to identify the significant variables of adherence to COVID-19 preventive measures.ResultsAs a level of adherence to COVID-19 preventive measures, the proportion of residents who had good adherence was 39.3% (95% CI 35.5–43.2%), moderate adherence was 37.6% (95% CI 33.8–41.5%), and poor adherence was 23.1% (95% CI 19.9–26.6%). The age group of 31–40 years (AOR: 3.13, 95% CI 1.62–6.05), 30 years and younger (AOR: 3.22, 95% CI 1.75–5.92), Burmese ethnicity (AOR: 2.52, 95% CI 1.44–4.39), own business (AOR: 3.19, 95% CI 1.15–8.87), high school education level and below (AOR: 1.64, 95% CI 1.02–2.69), less than 280.90 USD of monthly family income (AOR: 1.51, 95% CI 1.01–2.29), low knowledge about COVID-19 (AOR: 1.90, 95% CI 1.26–2.88) were significantly associated with poor adherence to COVID-19 preventive measures.ConclusionsIn this study, nearly one-fourth of the residents were experiencing poor adherence to COVID-19 preventive measures. Therefore, building up the risk communication through the community using widely used mainstream media, the continuation of disease surveillance and announcement of updated information or advice for the public to increase awareness towards COVID-19, and enforcement to follow the recommended directions and regulations of health institutions are vital to consider for improving the adherence to preventive measures against COVID-19 among the residents.

Specific Immune Marker Associated With Coronavirus Disease 2019

Background: The infection that caused the pneumonia, the virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the source of coronavirus disease 2019 (COVID-19) is the source of the global pandemic. The pneumonia cases began in Wuhan, China in December 2019 and had no apparent reason. Essential inflammatory mediators Chemokines are necessary for an immune response to eliminate pathogens. However, the fundamental cause of hyperinflammation is their excessive release. Chemokines may be directly responsible for the acute respiratory illness syndrome in the current COVID-19 outbreak. Objective: The current study aimed to estimate hematological changes with immunogenic markers CD177, GNLY, and CXCR4 gene expression in COVID-19 patients, and compare these parameters among patients and healthy individuals. Materials and Methods: The study was conducted at Al-Yarmouk Teaching Hospital and Medical Teaching Laboratories. Finally, to detect the immune markers level in samples of patients, by RT-PCR. Results: The results revealed the gene expression results in patients with COVID-19 means Ct difference of CD177 (24.70) fold more than (10.5) elevated when compared with the mean of Ct control healthy group is (28.21) fold of gene expression is 1.00 of CD177 when our study showed increased gene expression the mean of GNLY Ct receptor was reached to (28.70 ng/L) with fold more than 15.0 in COVID-19 patients, while mean Ct in healthy control was (32.61 ng/L) with fold 1.00, the current study found mean CT of CXCR4 gene expression ( 31.2) with fold (1.1) compared with healthy control CT(31.3) fold of gene expression was (1.0). Conclusion: It was concluded that COVID-19 caused significant changes in many immunological parameters and found the titer of immune markers was higher in infection compared with control.

Loss of TRIM29 mitigates viral myocarditis by attenuating PERK-driven ER stress response in male mice

Viral myocarditis, an inflammatory disease of the myocardium, is a significant cause of sudden death in children and young adults. The current coronavirus disease 19 pandemic emphasizes the need to understand the pathogenesis mechanisms and potential treatment strategies for viral myocarditis. Here, we found that TRIM29 was highly induced by cardiotropic viruses and promoted protein kinase RNA-like endoplasmic reticulum kinase (PERK)-mediated endoplasmic reticulum (ER) stress, apoptosis, and reactive oxygen species (ROS) responses that promote viral replication in cardiomyocytes in vitro. TRIM29 deficiency protected mice from viral myocarditis by promoting cardiac antiviral functions and reducing PERK-mediated inflammation and immunosuppressive monocytic myeloid-derived suppressor cells (mMDSC) in vivo. Mechanistically, TRIM29 interacted with PERK to promote SUMOylation of PERK to maintain its stability, thereby promoting PERK-mediated signaling pathways. Finally, we demonstrated that the PERK inhibitor GSK2656157 mitigated viral myocarditis by disrupting the TRIM29-PERK connection, thereby bolstering cardiac function, enhancing cardiac antiviral responses, and curbing inflammation and immunosuppressive mMDSC in vivo. Our findings offer insight into how cardiotropic viruses exploit TRIM29-regulated PERK signaling pathways to instigate viral myocarditis, suggesting that targeting the TRIM29-PERK axis could mitigate disease severity.

Heterogeneity of the effect of the COVID-19 pandemic on the incidence of Metabolic Syndrome onset at a Japanese campus.

The coronavirus disease 2019 (COVID-19) outbreak began in China in December 2019, with the World Health Organization declaring a state of emergency in January 2020. Worldwide implementation of lockdown measures to slow the spread of the virus led to reduced physical activity, disrupted eating habits, mental health issues, and sleep disturbances, which increased the risk of lifestyle-related diseases such as metabolic syndrome (MetS). During the COVID-19 pandemic, healthcare workers, especially intensive care workers, experienced longer working hours and burnout, which further increased the risk of lifestyle-related diseases. Accordingly, it is important to identify individuals at a risk of new-onset MetS during a pandemic, which could direct preventive interventions. This study aimed to assess the heterogeneous impact of the COVID-19 pandemic on the incidence of new-onset MetS based on the conditional average treatment effect (CATE) and to identify at-risk populations. This study analyzed health checkup data obtained from Okayama University Shikata Campus workers using paired baseline and follow-up years. Baseline data encompassed 2017 to 2019, with respective follow-up data from 2018 to 2020. Furthermore, as the COVID-19 pandemic in Japan began in January 2020, workers who underwent follow-up health checkups in 2018 to 2019 and 2020 were considered as "unexposed" and "exposed," respectively. As the Shikata campus has several departments, comparisons among departments were made. The primary outcome was new-onset MetS at follow-up. Predictor variables included baseline health checkup results, sex, age, and department (administrative, research, medical, or intensive care department). X-learner was used to calculate the CATE. This study included 3,572 eligible individuals (unexposed, n=2,181; exposed, n=1,391). Among them, 1,544 (70.8%) and 866 (62.3%) participants in the unexposed and exposed groups, respectively, were females. The mean age (±standard deviation) of the unexposed and exposed groups was 48.2 ± 8.2 and 47.8 ± 8.3 years, respectively. The COVID-19 pandemic increased the average probability of new-onset MetS by 4.4% in the overall population. According to the department, the intensive care department showed the highest CATE, with a 15.4% increase. Moreover, there was large heterogeneity according to the department. The high-CATE group was characterized by older age, urinary protein, elevated liver enzymes, higher triglyceride levels, and a history of hyperlipidemia treatment. This study demonstrated that the COVID-19 pandemic increased the incidence of new-onset MetS, with this effect showing heterogeneity at a single Japanese campus. Regarding specific populations, workers in the intensive care department showed an increased risk of new-onset MetS. At-risk populations require specific preventive interventions in case the current COVID-19 pandemic persists or a new pandemic occurs.

COVID-19 and progress in therapeutic approaches: a narrative review

Coronavirus disease 2019 (COVID-19), scientifically known as severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has adversely affect the respiratory system of humans and badly crushed the economies of most developed countries. This study aims to investigate the current COVID-19 situation and therapeutic approaches including non-viral vaccines, efficacy, safety, their trials, dosage protocols and mass vaccination established for COVID-19. A comprehensive literature search was conducted using PubMed, Scopus, Google Scholar, and MEDLINE databases. The title of the research articles were reviewed first, followed by the abstracts and finally the complete studies. This review critically focuses on the damaging effects of COVID-19 and its mutations, multiple variants, pharmacological approaches, and mRNA vaccines. COVID-19 is an emerging new variant with a different mutation and altered genomic structure. Different pharmacological and therapeutic approaches (interferon, oligonucleotides, anti-viral drug molecules, antibody peptides) have been made so far to combat COVID-19. Interferons are employed in COVID-19 treatment approaches owing to the role of Type I interferons in COVID-19 pathogenesis. Along with these therapeutic methodologies, companies from all over the world participated in the run to develop a vaccine for COVID-19. Vaccines were developed in less than a year for vaccinating humans on a mass level for the first time in world history. These vaccines target structural components of the virus, such as membrane proteins with a spike protein. This article provides valuable information for researchers regarding COVID-19 and progress in therapeutic approaches. This article will serve as a hallmark for understanding the COVID-19 mutation mechanism and strategies to combat these mutation points.

Frequency of Covid-19 Infection and The Disease Profile in Patients Followed with Multiple Sclerosis

Objective: For a long time immunomodulatory / immunosuppressive drugs have been used to slow the progression of multiple sclerosis (MS). These treatments are known to suppress the immune system and create susceptibility to infections. In our study, it was aimed to review the severity and frequency of COVID-19 disease in MS patients who received immunomodulatory/immunosuppressive treatments during the current coronavirus disease 2019 (COVID-19) pandemic, and also to evaluate whether they were adversely affected in terms of psychological outcomes. Material and Methods: Participants consisted of MS patients who acquired COVID-19 (group 1) aged 18-65, using disease-modifying treatments (DMT) with follow-up in a neurology outpatient the clinic and the other two control groups consisted of similar ages and genders. One of the other two groups is MS patients who have not had COVID-19 (group 2), the other group consisted of patients who had COVID-19 and did not have MS (group 3). MS profile, coronavirus anxiety scale (CAS), and Beck depression inventory (BDI) scales between groups 1 and 2; COVID-19 profile between groups 1 and 3 compared. Results: As a result of comparing the MS disease profile of the 1st and 2nd groups and in terms of the COVID-19 disease profile of the 1st and 3rd groups, there was no statistically a significant difference in these paired comparison groups (p> 0.05). Conclusions: It was concluded that DMT use does not increase the severity of COVID-19 and having COVID-19 does not cause any additional changes in the psychiatric status of MS patients, since no a statistically significant difference was observed in the 2 MS group and 2 COVID-19 group comparison.

A multi‐objective transportation model for COVID‐19 patients: lesson learned from France

AbstractThe current COronaVIrus Disease 2019 (COVID‐19) pandemic has revealed many challenges to the world. The pandemic obliged public authorities to impose lockdowns and stop several activities. Limited hospital capacity was considered one of the main reasons behind lockdown decisions. To partially face hospital congestion, the healthcare authorities suggested transferring patients to hospitals in regions with available beds to relieve overloaded hospitals. Such transfer operations required exceptional modes of transportation such as trains and airplanes. This paper aims to demonstrate that efficient health logistics might help face the pandemic health effects and save lives. In this paper, we propose a multi‐objective mathematical program to schedule the transfer of patients using trains and airplanes. The proposed sustainable logistics model was tested using French real‐life data for the period March–April 2020 using CPLEX software. We also illustrate the health benefits of our solution.

Immune rebalancing at the maternal-fetal interface of maternal SARS-CoV-2 infection during early pregnancy.

The current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) remains a threat to pregnant women. However, the impact of early pregnancy SARS-CoV-2 infection on the maternal-fetal interface remains poorly understood. Here, we present a comprehensive analysis of single-cell transcriptomics and metabolomics in placental samples infected with SARS-CoV-2 during early pregnancy. Compared to control placentas, SARS-CoV-2 infection elicited immune responses at the maternal-fetal interface and induced metabolic alterations in amino acid and phospholipid profiles during the initial weeks post-infection. However, subsequent immune cell activation and heightened immune tolerance in trophoblast cells established a novel dynamic equilibrium that mitigated the impact on the maternal-fetal interface. Notably, the immune response and metabolic alterations at the maternal-fetal interface exhibited a gradual decline during the second trimester. Our study underscores the adaptive immune tolerance mechanisms and establishment of immunological balance during the first two trimesters following maternal SARS-CoV-2 infection.