COVID-19 Research Articles

A koronavírus-járvány társadalmi és gazdasági hatásai a határ menti térségek fejlődésére a magyar–szlovák határrégiók esetében

The Social and Economic Impact of the Coronavirus Pandemic on the Development of Border Regions in the Case of the Hungarian–Slovak Border Regions Borders in a given social context seem to be eternal and unchangeable, but their exact location, their permeability, their functions and the regulations assigned to them are in fact constantly changing according to the ideals of the respective societal eras. The SARS-CoV-2 neo-coronavirus infection, identified in December 2019 as the cause of Covid-19 disease, has become a global pandemic, causing a major health, economic and social crisis. The pandemic had an impact on the single market mechanisms established by the European Union, affecting freedoms—the free movement of services, goods, capital and people—and on almost every aspect of everyday life as it had been until then. In border regions, these effects were magnified. The active socio-economic interactions of the Hungarian–Slovak border regions were interrupted overnight as a result of the border traffic measures, causing significant negative changes and restructuring the functioning of cross-border processes.

Study of the state of humoral immunity to COVID-19 in Arkhangelsk residents

The COVID-19 pandemic caused by SARS-CoV-2 has affected healthcare, society and the economy in all countries, including Russia. Several vaccines have been created as the method for COVID-19 prevention. One of the most widespread vaccines in Russia, which has received international recognition, is the Gam-COVID-Vac (Sputnik V) vaccine and its variant Sputnik Light, which represents its first component. This vaccine, like similar vaccines in many countries, was used during the pandemic. The purpose of this work is to study the humoral immunity status of Arkhangelsk city residents and the effect of vaccination on them. Adult residents of Arkhangelsk [N = 281] were enrolled in the randomized study. Samples from vaccinated people and the control group were collected for the study in October 2022.The median from the time of last vaccination/booster to sample collection was 10 months. The samples were tested for the level of IgG to the receptor-binding domain of the SARS-CoV-2 S protein. The work assessed the humoral immunity status among residents of Arkhangelsk. It was shown that in October 2022 high IgG values were recorded among the people in the studied groups, most likely caused by contact with the SARS-CoV-2 virus. The humoral immunity status of unvaccinated residents, for those who have had COVID-19 and those who have not, is described; a significant increase in the level of IgG among those vaccinated compared to unvaccinated people is shown, despite the fact that the average time after vaccination was more than 10 months. A comparative analysis of IgG levels among different age groups was carried out. The study found no difference in post-vaccination antibody levels among people over 65 years old compared to younger age groups. Also there were no statistically significant differences in antibody levels among unvaccinated people over 65 in respect to younger age groups.

From public health to political repression: COVID-19 lockdown measure in Hong Kong's opposition districts

Repression comes with costs, such as reducing regime legitimacy and citizen conformity. The COVID-19 pandemic was an opportunity and a pretext for authoritarian regimes to repress their populations at a low cost. This paper examines the case of Hong Kong, where restriction-testing declarations (RTDs) were used as a lockdown measure to facilitate mandatory testing for the virus from January 2021 to September 2022. Despite the government's claim that RTDs were implemented for public health reasons, statistical analyses showed that Hong Kong districts that opposed the regime or those with a mobilization legacy were more likely to be subject to RTDs, with the opposition district effect present only when COVID-19 infections were low. These RTDs highlight the authoritarian regime's tradeoff in using a nonpolitical measure to achieve its political aims and illustrates the enduring impact of past election and mobilization activities on the choice of selective repression sites in Hong Kong.

Micronutrients, Vitamin D, and Inflammatory Biomarkers in COVID-19: A Systematic Review and Meta-analysis of Causal Inference Studies.

Experimental and observational studies suggest that circulating micronutrients, including vitamin D (VD), may increase COVID-19 risk and its associated outcomes. Mendelian randomization (MR) studies provide valuable insight into the causal relationship between an exposure and disease outcomes. The aim was to conduct a systematic review and meta-analysis of causal inference studies that apply MR approaches to assess the role of these micronutrients, particularly VD, in COVID-19 risk, infection severity, and related inflammatory markers. Searches (up to July 2023) were conducted in 4 databases. The quality of the studies was evaluated based on the MR-STROBE guidelines. Random-effects meta-analyses were conducted where possible. There were 28 studies (2 overlapped) including 12 on micronutrients (8 on VD) and COVID-19, 4 on micronutrients (all on VD) and inflammation, and 12 on inflammatory markers and COVID-19. Some of these studies reported significant causal associations between VD or other micronutrients (vitamin C, vitamin B6, iron, zinc, copper, selenium, and magnesium) and COVID-19 outcomes. Associations in terms of causality were also nonsignificant with regard to inflammation-related markers, except for VD levels below 25 nmol/L and C-reactive protein (CRP). Some studies reported causal associations between cytokines, angiotensin-converting enzyme 2 (ACE2), and other inflammatory markers and COVID-19. Pooled MR estimates showed that VD was not significantly associated with COVID-19 outcomes, whereas ACE2 increased COVID-19 risk (MR odds ratio = 1.10; 95% CI: 1.01-1.19) but did not affect hospitalization or severity of the disease. The methodological quality of the studies was high in 13 studies, despite the majority (n = 24) utilizing 2-sample MR and evaluated pleiotropy. MR studies exhibited diversity in their approaches but do not support a causal link between VD/micronutrients and COVID-19 outcomes. Whether inflammation mediates the VD-COVID-19 relationship remains uncertain, and highlights the need to address this aspect in future MR studies exploring micronutrient associations with COVID-19 outcomes. PROSPERO registration no. CRD42022328224.

Immunogenicity and Efficacy of Combined mRNA Vaccine Against Influenza and SARS-CoV-2 in Mice Animal Models

Background. The combined or multivalent vaccines are actively used in pediatric practice and offer a series of advantages, including a reduced number of injections and visits to the doctor, simplicity of the vaccination schedule and minimization of side effects, easier vaccine monitoring and storage, and lower vaccination costs. The practice of widespread use of the combined vaccines has shown the potential to increase vaccination coverage against single infections. The mRNA platform has been shown to be effective against the COVID-19 pandemic and enables the development of combined vaccines. There are currently no mRNA-based combined vaccines approved for use in humans. Some studies have shown that different mRNA components in a vaccine can interact to increase or decrease the immunogenicity and efficacy of the combined vaccine. Objectives. In the present study, we investigated the possibility of combining the mRNA vaccines, encoding seasonal influenza and SARS-CoV-2 antigens. In our previous works, both vaccine candidates have shown excellent immunogenicity and efficacy profiles in mice. Methods. The mRNA-LNPs were prepared by microfluidic mixing, immunogenicity in mice was assessed by hemagglutination inhibition assay, enzyme-linked immunoassay and virus neutralization assay. Immunological efficacy was assessed in a mouse viral challenge model. Results. In this work, we demonstrated that the individual mRNA components of the combined vaccine did not affect the immunogenicity level of each other. The combined vaccine demonstrated excellent protective efficacy, providing a 100% survival rate when mice were infected with the H1N1 influenza virus and reducing the viral load in the lungs. Four days after the challenge with SARS-CoV-2 EG.5.1.1., no viable virus and low levels of detectable viral RNA were observed in the lungs of vaccinated mice. Conclusions. The combination does not lead to mutual interference between the individual vaccines. We believe that such a combined mRNA-based vaccine could be a good alternative to separated human vaccinations for the prevention of COVID-19 and influenza.

Antiviral combination treatment strategies for SARS-CoV-2 infection in immunocompromised patients.

The purpose of this review is to report the available evidence regarding the use of combination regimens of antivirals and/or antibody-based therapy in the treatment of SARS-CoV-2 in immunocompromised patients. Literature search identified 24 articles, excluding single case reports, which included mainly patients with hematological malignancies and/or B-cell depletion. Data were divided based on the timing and reason for administration of combination treatment, that is, early treatment to prevent progression to severe COVID-19 and treatment of prolonged or relapsed infection. We described the treated populations, treatment duration and composition of combination treatment. We briefly addressed new treatment options and we proposed an algorithm for the management of COVID-19 infection in patients affected by hematological malignancies. Combination treatment seems an effective (73-100%) and well tolerated (<5% reported bradycardia, hepatotoxicity, neutropenia) strategy for treating prolonged/relapsed SARS-CoV-2 infections in the immunocompromised host, although its optimal composition and duration cannot be defined based on the currently available evidence. The role of combination treatment as an early treatment strategy for immunocompromised patients at a high risk of progression to severe disease/persistent shedding requires further evidence from comparison with monotherapy, even though high efficacy was reported for combinations of antivirals plus mAbs in case of previous viral variants.

The effects of mass media messages, perceived susceptibility and self-rated health on public attitude towards COVID-19 in South Africa

ObjectivesSouth Africa was the worst affected country in Africa by the COVID-19 pandemic and it is important to interrogate the attitude of the populace towards the pandemic for future interventions. Therefore, this study examined effects of mass media messages, susceptibility to COVID-19 and self-rated health on the attitudes of South Africans towards the COVID-19 pandemic.MethodsData was from the National Income Dynamics Study – Coronavirus Rapid Mobile Survey (NIDS-CRAM) of 2021 which is a nationally representative panel survey of about 7,000 South African individuals in all the nine provinces. Analyses of data were through descriptive statistics, chi square test and logistic regression models.ResultsThe results showed that 61.28% of the resondents did not take COVID-19 test while 91.09% of them engaged in behavioral changes such as social distancing and wearing of face masks. In addition, 74.27% of the respondents had access to mass media information, 70.44% believed they have good physical health while 32.43% felt they were not susceptible to COVID-19. The chi-square results of attitude towards COVID-19 showed significant differences in access to mass media messages on COVID-19, race, and province of residence. Furthermore, respondents who had access to mass media information on COVID-19 (OR = 1.469; p = 0.001) and respondents who believed that they were susceptible to COVID-19 infection (OR = 1.443; p = 0.001) were significantly associated with increased likelihood of engagement in behavioral changes to avoid the COVID-19.ConclusionThese findings therefore emphasize the need for increased awareness and sensitization of the people about the susceptibility and adverse effects of diseases to ensure that they adopt the appropriate attitudes that will safeguard them from such diseases outbreak.

Excess Cardiopulmonary Arrest and Mortality after COVID-19 Vaccination in King County, Washington

Introduction: Since the onset of widespread COVID-19 vaccination campaigns, there have been concerns about serious cardiovascular adverse events as a result of mass vaccination. This study aimed to estimate excess cardiopulmonary arrest mortality in King County, WA, and investigate any association with COVID-19 vaccination rates. Methods: An exploratory data analysis was performed. Comparative analyses were performed to evaluate the changes in total EMS attendances over time. Excess deaths were calculated using the 2015-2020 cardiopulmonary arrest mortality trend line. The relationship between excess cardiopulmonary arrest mortality and vaccination rates was analyzed using polynomial regression analysis. Results: Approximately 98% of the King County population received at least one dose of a COVID-19 vaccine by 2023. As of August 2nd, 2024, there have been approximately 589,247 confirmed COVID-19 cases in King County. In 2021- 2022, Total EMS attendances in King County sharply increased by 35.34% from 2020 and by 11% from pre-pandemic years. Cases of 'obvious death' upon EMS arrival increased by 19.89% in 2020, 36.57% in 2021, and 53.80% in 2022 compared to the 2017-2019 average. We found a 25.7% increase in total cardiopulmonary arrests and a 25.4% increase in cardiopulmonary arrest mortality from 2020 to 2023 in King County, WA. Excess fatal cardiopulmonary arrests were estimated to have increased by 1,236% from 2020 to 2023, rising from 11 excess deaths (95% CI: -12, 34) in 2020 to 147 excess deaths (95% CI: 123, 170) in 2023. A quadratic increase in excess cardiopulmonary arrest mortality was observed with higher COVID-19 vaccination rates. The general population of King County sharply declined by 0.94% (21,300) in 2021, deviating from the expected population size. Applying our model from these data to the entire United States yielded 49,240 excess fatal cardiopulmonary arrests from 2021-2023. Conclusions: We identified a significant ecological and temporal association between excess fatal cardiopulmonary arrests and the COVID-19 vaccination campaign. The increase in excess cardiopulmonary arrest deaths may also be attributed to COVID-19 infection and disruptions in emergency care during the pandemic. Urgent further research is needed to confirm our observations with attention to risk mitigation for incident events and improved survival with resuscitation.

P70S6K as a Potential Anti-COVID-19 Target: Insights from Wet Bench and In Silico Studies.

The onset of SARS-CoV-2 infection in 2019 sparked a global COVID-19 pandemic. This infection is marked by a significant rise in both viral and host kinase activity. Our primary objective was to identify a pivotal host kinase essential for COVID-19 infection and the associated phenomenon of the cytokine storm, which may lead to long-term COVID-19 complications irrespective of viral genetic variations. To achieve this, our study tracked kinase phosphorylation dynamics in RAW264.7 macrophages following SPIKE transfection over time. Among the kinases surveyed, p70S6K (RPS6KB1) exhibited a 3.5-fold increase in phosphorylation at S418. This significant change prompted the selection of p70S6K for in silico investigation, utilizing its structure bound to M2698 (PDB: 7N93). M2698, an oral dual Akt/p70S6K inhibitor with an IC50 of 1.1 nM, exhibited psychosis side effects in phase I clinical trials, potentially linked to its interaction with Akt2. Our secondary objective was to discover a small-molecule analogue of M2698 that exhibits a distinct binding preference for p70S6K over Akt2 through computational modeling and analysis. The in silico part of our project began with validating the prediction accuracy of the docking algorithm, followed by an OCA analysis pinpointing specific atoms on M2698 that could be modified to enhance selectivity. Subsequently, our investigation led to the identification of an analog of M2698, designated as S34, that showed a superior docking score towards p70S6K compared to Akt2. To further assess the stability of S34 in its protein-ligand (PL) complexes with p70S6K and Akt2, MD simulations were conducted. These simulations suggest that S34, on average, forms two hydrogen bond interactions with p70S6K, whereas it only forms one hydrogen bond interaction with Akt2. This difference in hydrogen bond interactions likely contributed to the observed larger root mean square deviation (RMSD) of 0.3 nm in the S34-Akt2 complex, compared to 0.1 nm in the S34-p70S6K complex. Additionally, we calculated free binding energy to predict the strength of the binding interactions of S34 to p70S6K and Akt2, which showed ~2-fold favorable binding affinity of S34 in the p70S6K binding pocket compared to that in the Akt2 binding pocket. These observations may suggest that the S34-p70S6K complex is more stable than the S34-Akt2 complex. Our work focused on identifying a host kinase target and predicting the binding affinity of a novel small molecule to accelerate the development of effective treatments. The wet bench results specifically highlight p70S6K as a compelling anti-COVID-19 target. Meanwhile, our in silico investigations address the known off-target effects associated with M2698 by identifying a close analog called S34. In conclusion, this study presents novel and intriguing findings that could potentially lead to clinical applications with further investigations.

MONITORING OF A SEVERE COVID-19 PATIENT WITH PNEUMOTHORAX COMPLICATIONS THROUGH RADIOLOGICAL AND LABORATORY DIAGNOSIS

Introduction: Monitoring and treatment of severely ill patients with the coronavirus disease who are on mechanical ventilation due to the severity of the disease with the development of many complications remains a challenge. The increased incidence of pneumothorax in Covid-19 patients on mechanical ventilation may be due to a combination of infection-induced parenchymal injury and infl ammatory response with additional positive pressure ventilation. Materials and methods: In our study, we report a case of a severe Covid-19 patient with a pneumothorax complication through radiological and laboratory diagnostics. The performed radiogram of the lungs was taken each time in the AP projection in a semi-sitting position. A digital mobile X-ray device was used for imaging. All laboratory parameters that were monitored in the patient are performed in the panel of standard routine controls for patients with Covid-19. Results: The radiogram was better as the administration of therapy and chest drain were eff ective. Biochemical and hematological parameters are performed, which indicate a decrease in the number in blood count and biochemistry. The patient spent a total of 80 days in the hospital. Conclusion: Survival of a severe form of Covid-19 infection with the complication of pneumothorax is very rare, but still possible, as shown in our case. A chest radiograph with laboratory monitoring of the condition is of great importance in establishing the diagnosis of Covid-19 infection, and in the fi nal assessment of the patient's condition upon discharge from the hospital. Keywords: Covid-19, mechanical ventilation, pneumothorax, radiological diagnostics, laboratory diagnostics.

Construction and Evaluation of a Model for the Prediction of Risk Factors Associated with Severe Pneumonia in Patients with Positive Hepatitis B Core Antibody and COVID-19 Infection in China

Background: Hepatitis B virus (HBV) infection is a high-risk factor for severe COVID-19 cases, leading clinicians to enhance the monitoring of patients with concurrent HBV and COVID-19 infections. However, this focus is typically on patients with active HBV infection. Patients who are HBV surface antigen (HBsAg) negative and HBV core antibody (anti-HBc) positive are often considered to have either a past infection that has naturally cleared or to be in a low-replication state, and thus receive less clinical attention. However, in immunosuppressed states, such as during immunosuppressive treatment following COVID-19 infection, the virus in these patients may reactivate. In such cases, this reactivation can increase the risk of COVID-19 progressing to a severe illness. Therefore, being HBsAg negative and anti-HBc positive could be a potential risk factor for severe COVID-19. Studying the combination of anti-HBc positivity and COVID-19 infection can help identify high-risk populations, allowing for the implementation of targeted prevention and management measures, thereby reducing the occurrence of severe COVID-19 cases. Objectives: To establish and evaluate a model for predicting severe pneumonia in patients with positive anti-HBc combined with COVID-19 infection. Methods: We retrospectively enrolled 380 patients who tested positive for anti-HBc, negative for HBsAg, and HBV e-antigen (HBeAg), combined with COVID-19 infection, in our hospital from December 2022 to May 2023. Based on the inclusion criteria, 163 patients were included in the study. We applied the Lasso binary logistic regression model to optimize feature selection, identifying eight non-zero coefficients using a minimum of one standard error. Using the multiple logistic regression method with backward selection, we screened six factors from the eight selected by the Lasso binary logistic regression model. These six factors were used to construct the predictive model and a nomogram. The validity of our nomogram was assessed using the area under the receiver operating characteristic curve (AUC), calibration curve, Hosmer-Lemeshow (HL) test, and decision-curve analysis (DCA). Results: Hypertension, diabetes, decreased absolute lymphocyte count, prolonged prothrombin time, elevated aspartate aminotransferase, and decreased albumin are high-risk factors for severe pneumonia in patients with positive anti-HBc combined with COVID-19 infection. The AUC of the predictive model constructed using these six factors is 0.785, with a 95% confidence interval of (0.709-0.862). The HL test, performed using the calibration curve, yielded a p-value of 0.868. The application of this diagnostic curve will increase the net benefit when the threshold probability is between 5% and 75%. Conclusions: The constructed nomogram can be used to predict the risk of patients with positive anti-HBc combined with COVID-19 infection progressing to severe pneumonia, based on routine blood parameters, liver function, coagulation, lactate dehydrogenase levels, and the patient's underlying disease. The predictive model demonstrates good discrimination, calibration, and clinical utility.

Comparison οf Immune Responses Through Multiparametric T-Cell Cytokine Expression Profile Between Children with Convalescent COVID-19 or Multisystem Inflammatory Syndrome

Background/objectives: The immunological pathways that cause Multisystem Inflammatory Syndrome after SARS-CoV-2 infection in children (MIS-C) remain under investigation. Methods: The aim of this study was to prospectively compare the T-cell cytokine expression profile in unvaccinated children with acute MIS-C (MISC_A) before immunosuppression, convalescent MIS-C (one month after syndrome onset, MISC_C), convalescent COVID-19 (one month after hospitalization), and in healthy, unvaccinated controls. The intracellular expression of IL-4, IL-2, IL-17, IFNγ, TNF-α and Granzyme B, and the post SARS-CoV-2-Spike antigenic mix stimulation of T-cell subsets was analyzed by 13-color flow cytometry. Results: Twenty children with a median age (IQR) of 11.5 (7.25–14) years were included in the study. From the comparison of the flow cytometry analysis of the 14 markers of MISC_A with the other three groups (MISC_C, post-COVID-19 and controls), significant differences were identified as follows: 1. CD4+IL-17+/million CD3+: 293.0(256.4–870.9) vs. 50.7(8.4–140.5); p-value: 0.03, vs. 96.7(89.2–135.4); p-value: 0.03 and vs. 8.7(0.0–82.4); p-value: 0.03, respectively; 2. CD8+IL-17+/million CD3+: 335.2(225.8–429.9) vs. 78.0(31.9–128.9) vs. 84.1(0.0–204.6) vs. 33.2(0.0–114.6); p-value: 0.05, respectively; 3. CD8+IFNγ+/million CD3+: 162.2(91.6–273.4) vs. 41.5(0.0–77.4); p-value: 0.03 vs. 30.3(0.0–92.8); p-value: 0.08, respectively. Conclusions: In children presenting with MIS-C one month after COVID-19 infection, T cells were found to be polarized towards IL-17 and IFNγ production compared to those with uncomplicated convalescent COVID-19, a finding that could provide possible immunological biomarkers for MIS-C detection.

COVID-19 Vaccination Response in Patients with Multiple Sclerosis Treated with Ofatumumab in the United States: A Medical Record Review.

Real-world data are required to provide a greater understanding of the impact of ofatumumab on the ability to mount an effective immune response following the receipt of approved COVID-19 vaccinations. This retrospective real-world analysis aimed to describe the humoral immune response to COVID-19 vaccination during ofatumumab treatment in patients with multiple sclerosis (MS). Data from patients with MS treated with ofatumumab who were fully vaccinated against COVID-19 infection were abstracted from medical charts at four clinical sites in the USA. Patient characteristics and humoral response were summarized descriptively. Differences in humoral response were documented on the basis of vaccination status during ofatumumab treatment (i.e., after full vaccination and after booster vaccination) and prior disease-modifying treatment (DMT) exposure (i.e., DMT naïve, prior anti-CD20/sphingosine 1-phosphate [S1P] therapy, prior non-anti-CD20/S1P therapy). The sample size precluded formal statistical analysis. Thirty-eight patients were included. The mean (standard deviation) duration of ofatumumab treatment upon data collection was 20.4 (4.6) months (treatment ongoing for 35 [92%] patients). Definitive humoral response after full vaccination was documented for 34 patients, of whom 20 (60%) were seropositive. Definitive humoral response after booster vaccination was documented among five patients, of whom three (60%) were seropositive. Among patients who were DMT naïve prior to ofatumumab (n = 15), 73% were seropositive; among patients exposed to prior anti-CD20/S1P therapy (n = 14), 33% were seropositive; and among patients exposed to prior non-anti-CD20/S1P therapy (n = 9), 56% were seropositive. Patients naïve to DMT had been living with an MS diagnosis for a shorter duration than those experienced with DMTs. Patients with MS receiving ongoing treatment with ofatumumab can mount a positive humoral response to a COVID-19 vaccination. Prior treatment with anti-CD20 or S1P DMTs may be a risk factor for lower humoral response.

In silico assessment of CAR macrophages activity against SARS-CoV-2 infection

Macrophage engineering with chimeric antigen receptor is a promising technique first applied to the treatment of tumours and recently suggested as a possible immunotherapeutic route against the COVID-19 disease. Four immunotherapies based on engineered macrophages have been tested in vitro revealing promising, with one of them acting without increasing the cytokines level. We present a mathematical model aimed at the evaluation of both the SARS-CoV-2 virions dynamics and the cytokines production induced, while such newly developed constructs interact with the immune system once administered. The importance of the study lies both in monitoring the dynamics of the infection and in evaluating the cytokine production, since clinical studies show that in critical COVID-19 patients an abnormal cytokines production occurs, a concern to be accounted for in designing appropriate therapeutic strategies. The mathematical model was built in the context of the continuum approach of the mass conservation, while the numerical simulations have been performed introducing parameters deduced from the experiments, using the finite element method. The model simulations allow to analyse and to compare the immune mechanisms underlying the virus dynamics, deepening the investigation for two selected immunotherapies, suggesting that a synergistic work of involved cytokines with phagocytic activity of macrophages occurs. The best SARS-CoV-2 clearance relies not only on the phagocytic capacity of the engineered macrophages, but also on the production of T-lymphocytes, pro- and anti-inflammatory cytokines which in the two cases examined in depth can decrease by 99.7 %, 99.6 % and 69 % respectively, passing from the most effective immunotherapy to the least effective one. This study is the first mathematical model that analyses the dynamics of macrophages engineered to fight the COVID-19, and paves the way for their possible exploitation against such a challenging disease, going beyond existing models involving other immune cells.

Epidemiological profile of patients hospitalized with Crohn's disease due to severe acute respiratory infection during the COVID-19 pandemic: a 2-year report from Brazil.

The novel coronavirus-induced severe acute respiratory syndrome (COVID-19) led to one of the most significant global pandemics of the 21st century, causing substantial challenges for healthcare systems worldwide, including those in Brazil. This study aimed to investigate the demographic and clinical profiles of hospitalized patients in Brazil who had both COVID-19 and Crohn's disease (CD) over a 2-year period. An epidemiological analysis was conducted using data from Open-Data-SUS. The study focused on describing the demographic characteristics, clinical manifestations, comorbidities, and hospitalization details of patients afflicted with severe acute respiratory syndrome due to COVID-19 and CD, with the aim of predicting mortality risk. The states of São Paulo, Paraná, and Minas Gerais accounted for 50% of the reported COVID-19 cases. The most affected racial group consisted of individuals who self-declared as mixed race. Common comorbidities included heart disease, diabetes mellitus, and obesity. The age group most affected was 25 to 60 years old, particularly among hospitalized patients with both CD and COVID-19 who ultimately succumbed to the illness. A multivariable analysis was conducted to identify the following significant risk factors for death: (a) the presence of neurological disorder (OR = 6.716; 95% CI = 1.954-23.078), (b) the need for intensive care (OR = 3.348; 95% CI = 1.770-6.335), and (c) the need for invasive mechanical ventilation (OR = 59.017; 95% CI = 19.796-175.944). There was no discernible gender-based prevalence among hospitalized patients with CD and COVID-19; however, individuals of mixed race were disproportionately affected. The 25 to 60 age group emerged as the most vulnerable demographic group, with high risks of hospitalization and mortality. Moreover, the study highlights the potential for COVID-19 to induce systemic pathologies that may result in long-term degenerative effects and sequelae.

Atorvastatin and telmisartan do not reduce nasopharyngeal carriage of SARS-CoV-2 in mild or moderate COVID-19 in a phase IIb randomized controlled trial

Observational studies suggest a reduction in fatal or severe COVID-19 disease with the use of ACE2 inhibitors and statins. We implemented a randomized controlled tree-arm open label trial evaluating the benefits of adding telmisartan (TLM) or atorvastatin (ATV) to lopinavir boosted ritonavir (LPVr) on the SARS-CoV-2 nasopharyngeal viral load in patients with mild / moderate COVID-19 infection in Côte d’Ivoire. RT-PCR positive COVID-19 patients ≥ 18 years, with general or respiratory symptoms for less than 7 days were randomized (1:1:1) to receive LPVr (400 mg/100 mg twice daily), LPVr + TLM (10 mg once daily) or LPVr + ATV (20 mg once daily) for 10 days. The primary endpoint was viro-inflammatory success defined as a composite variable at day 11: Ct ≥ 40 and C-reactive protein < 27 mg/L. We randomized 294 patients: 96 to LPVr, 100 to LPVr + TLM, 98 to LPVr + ATV arms. Baseline characteristics were well balanced between arms. In the primary analysis (missing = failure), 46% patients in the LPVr arm reached viro-inflammatory success at day 11 vs 43% in the LPVr + TLM arm (p = 0.69) and 43% in the LPVr + ATV arm (p = 0.68). The median time from baseline to resolution of COVID-19 related symptoms was not different between arms. Nine patients were hospitalized: 2 in the LPVr arm, 5 in the LPVr + TLM arm and 2 in the LPVr + ATV arm and 4 patients died. Among adults with mild to moderate COVID-19 infection, the addition of telmisartan or atorvastatin, to the standard LPVr treatment is not associated with a better virological or clinical outcome.Trial registration: NCT04466241, registered on 10/07/2020

Outcomes of COVID-19 in Pregnant Women: A Retrospective Analysis of 300 Cases in Jordan.

The impact of COVID-19 on pregnancy remains a critical area of research, with growing evidence suggesting that maternal infection, particularly in the third trimester, may lead to significant complications Aims: The primary aim was to investigate the maternal and neonatal outcome of pregnant Jordanian women with COVID-19. The secondary aim included exploring demographics, obstetrics characteristics, and comorbidities among these women. A retrospective comprehensive review of the records of 300 cases of pregnant women with COVID-19, who were treated between November 2020 and April 2021 at Queen Alia Military Hospital (a main referral center for patients with COVID-19) in Jordan. All cases were confirmed by the rapid antigen test (RAT) + long polymerase chain reaction (PCR) test used to detect SARS-CoV-2 by amplifying viral RNA from patient samples. Women infected with COVID-19 were categorized into four groups according to the RCOG guidelines for COVID-19 infection in pregnancy: asymptomatic, mild, moderate, and severe cases. All cases were managed following the Royal College of Obstetricians and Gynecologists protocol for COVID-19 in pregnancy. Data extracted from patient's records included demographic information, COVID-19 clinical manifestations, obstetric history, diagnostic findings, treatment plans, comorbidities, gestational age at diagnosis, treatment protocols, and maternal and neonatal outcomes. The mean age was 29.7 years; 98.3% were nonsmokers; 8% had previous miscarriages, and 67.3% had the infection in the third trimester. Iron deficiency anemia affected 30.3%, while 18.3% had comorbidities, mainly hypothyroidism. Most women were asymptomatic 61.7%, but 33% had respiratory symptoms, 4.7% needed intensive care unit (ICU) admission, and 2.7% resulted in maternal deaths. First-trimester and second-trimester miscarriages were recorded in 2.67% and 3.67% of cases, respectively, while preterm labor occurred in 3.0% of pregnancies. Additionally, age and hospitalization duration had a positive correlation with the neonatal outcomes (r = 0.349, p < 0.01), (r = 0.376, p < 0.01), respectively. Furthermore, COVID-19 presentation and treatment options demonstrated a strong positive correlation (p-value <0.01). On the other hand, maternal death had a strong negative correlation with poor neonatal outcomes (r = -0.776, p < 0.01). The study showed that COVID-19 in pregnant women, particularly in the third trimester, is associated with significant neonatal complications, with age, hospitalization duration, and COVID-19 severity strongly impacting outcomes.

Lipschütz ulcer following first dose of COVID-19 tozinameran vaccine: Report of a case and review of a World Health Organization pharmacovigilance database.

Lipschütz ulcer (LU) is a condition known for painful vulvar ulcers, typically affecting young women and often linked to infectious agents. Recent reports have indicated a potential connection between LU and COVID-19 vaccination, particularly after the second or booster doses. This study presents a case of LU following the first dose of tozinameran in a young woman who had a previous SARS-CoV-2 infection and investigates similar cases globally. An 18-year-old woman experienced vulvar pain and ulcers 2-days after her initial COVID-19 vaccine dose. After ruling out infections through serological tests, a diagnosis of LU was made, and her symptoms resolved after 10 days. A literature search and VigiBase® analysis revealed 11 cases of LU following COVID-19 vaccination, and 519 vulvovaginal ulcer cases associated with these vaccines were identified in Vigibase®, with a median onset of 2 days. Most LU cases occurred after the second dose or booster shots. The primary hypothesis for this association is a type 3 hypersensitivity reaction mediated by immune complexes, possibly triggered by prior exposure, as many cases occurred after the second dose. Interestingly, the presented case suggests that prior COVID-19 infection could serve as sensitization. In conclusion, this study highlights the potential occurrence of LU after the initial COVID-19 vaccine dose in young patients with prior COVID-19 infection. While the risk of recurrence after subsequent vaccinations or infections remains uncertain, the benefits of vaccination outweigh the risks. Clinicians and patients should be aware of this potential issue to make informed decisions regarding vaccination.

Gegenbauer Wavelet Solutions of the SIR and the SITR Systems of the COVID-19 Disease

Gegenbauer Wavelet Solutions of the SIR and the SITR Systems of the COVID-19 Disease

Enhancing COVID-19 disease severity classification through advanced transfer learning techniques and optimal weight initialization schemes

ObjectiveMedical imaging plays a central role in medicine today by supporting diagnosis and treatment. For small medical image datasets, training from scratch is a time-consuming process and transfer learning emerges as a solution. In these cases, ImageNet weights are usually used as initial weights, after which fine-tuning is performed. We propose a methodology for COVID-19 severity classification (mild, moderate, severe, critical) in chest X-ray images based on transfer learning using DenseNet121 architecture as a base model. MethodsThe novelty of the approach mainly lies in the investigation of three different weight initialization schemes (i) ImageNet (ii) CheXNeXt (iii) DeepCOVID-XR, which are similar in a graded manner in terms of image nature, with ImageNet being the least similar, CheXNeXt similar as they were trained on different lung diseases not including COVID-19 and DeepCOVID-XR the most similar as they were obtained by training specifically on COVID-19 X-ray images. ResultsThe results show that the worst results are achieved using ImageNet as initial weights (average AUC = 0.700), followed by the better results with DeepCOVID-XR (average AUC = 0.774) while CheXNeXt performed significantly better (average AUC = 0.917). The results of weaker performing classification models were improved when the severe and critical classes were merged, to account for the similarity between these classes in the dataset (average AUC for initialization schemes were ImageNet AUC = 0.867, CheXNeXt AUC = 0.900 and DeepCOVID-XR AUC = 0.794). ConclusionThis leads to a conclusion that, in the medical domain, where image datasets are usually small and highly imbalanced, if initial weights are chosen to be in nature similar to the new dataset, achieved results are better. However, there is no need to start from weights obtained during training on the same disease, as this may cause overfitting. There are significant discrepancies between ImageNet and medical imaging datasets and the results from this paper could help in guiding future implementations of transfer learning in medical applications.