COVID-19 Research Articles

Clinical and immunological characteristics of COVID-19 in patients with disease dynamics

The aim is to study the clinical and immunological indicators of COVID-19 in the dynamics of the disease with the determination of predictors of the development of changes in the lungs. Materials and methods. The object of the study was 35 patients aged 22 to 75 years in the acute period and dynamics of COVID-19 disease, divided into two groups according to the identified clinical and immunological disorders. Markers of cellular (CD-3, CD-4, CD-8, CD-19) and humoral immunity, cytokines (IL-6,8, TGF-β, TNF-α), CEC were determined in all examined patients. Statistical processing of the obtained results was carried out using the computer program Statistica 10.0. Results. It was found that all the subjects retained clinical and immunological changes during the entire follow-up period, which indicates an ongoing disease. At the same time, significant differences in the severity of changes in individuals were revealed, taking into account age and the presence of chronic somatic pathology, expressed primarily in violation of the parameters of the T-system of immunity. In patients with the development of postcovoid changes in the lungs, characteristic immunological features were revealed, taking into account age. Conclusions. A violation of the detected indicators of the immune system may indicate the persistence of the virus, which means a prolongation of a specific inflammatory response with the risk of extensive tissue damage. Within three months after recovery, the tendency towards the formation of humoral immunity persists in both groups, which occurs by the end of 1 month after the disease in both groups and continues throughout the entire follow-up period. In the risk group for the development of pneumofibrosis in the outcome of a new coronavirus infection, the combination of IL-8 and TGF-β is the most optimal, despite their significant decrease in dynamics compared with the acute period.

HbA1c and leukocyte mtDNA levels as major factors associated with post-COVID-19 syndrome in type 2 diabetes patients

Post-COVID-19 syndrome (PCS) is an emerging health problem in people recovering from COVID-19 infection within the past 3–6 months. The current study aimed to define the predictive factors of PCS development by assessing the mitochondrial DNA (mtDNA) levels in blood leukocytes, inflammatory markers and HbA1c in type 2 diabetes patients (T2D) with regard to clinical phenotype, gender, and biological age. In this case-control study, 65 T2D patients were selected. Patients were divided into 2 groups depending on PCS presence: the PCS group (n = 44) and patients who did not develop PCS (n = 21) for up to 6 months after COVID-19 infection. HbA1c and mtDNA levels were the primary factors linked to PCS in different models. We observed significantly lower mtDNA content in T2D patients with PCS compared to those without PCS (1.26 ± 0.25 vs. 1.44 ± 0.24; p = 0.011). In gender-specific and age-related analyses, the mt-DNA amount did not differ significantly between the subgroups. According to the stepwise multivariate logistic regression analysis, low mtDNA content and HbA1c were independent variables associated with PCS development, regardless of oxygen, glucocorticoid therapy and COVID-19 severity. The top-performing model for PCS prediction was the gradient boosting machine (GBM). HbA1c and mtDNA had a notably greater influence than the other variables, indicating their potential as prognostic biomarkers.

Rural–Urban Divide of COVID-19 Fatalities in India—Investigating the Role of Lifestyle Disorder Diseases

AbstractUsing data on weekly COVID-19 infections and fatalities at the district level for 19 states and 4 union territories of India, we investigate the determinants of COVID-19 deaths focusing exclusively on the second wave of infections. We include several macroeconomic and structural indicators for districts namely, per capita district domestic product, the degree of urbanization, population density, percentage of aged population, share of agriculture, poverty, among several others. Our findings suggest that fatalities have a clear rural–urban divide. Rural agricultural districts with more poor people have experienced less cases and fatalities. Fatalities are more clustered in prosperous and dense industrial districts. Regions having higher COVID-19 fatalities also have a higher proportion of ageing population with urban life-style disorder related diseases such as obesity, diabetes, and hypertension. Prevalence of respiratory illnesses further aggravates the effects of some of these life-style disorder diseases on COVID-19 fatalities.

EGFR-TKI therapy does not increase risk of COVID-19 infection

EGFR-TKI therapy does not increase risk of COVID-19 infection

Bibliometric and Content Analysis of Articles on Artificial Intelligence in Healthcare

The use of artificial intelligence in the healthcare sector is becoming widespread for reasons such as analyzing digital patient data, including it in decision-making processes, improving the quality of healthcare services, and providing cost, time, and access advantages. This study aims to evaluate published articles on bibliometric indicators and the use of artificial intelligence in the healthcare sector and examine the content of the most cited articles. Articles about artificial intelligence in the health sector in the Web of Science database were included in the study using the criteria of “keyword, publication year, and publication language”. The research covers 2,680 articles published in English by 14,195 authors from 106 countries in 1084 journals between 2020-2024. 4,671 different keywords were used in the published articles. The country that published the most was “USA”, the journal was “Journal of Medical Internet Research”, the author was “Meng Ji”, and the most cited author was “Weihua Li”. The 55 most cited (≥50) articles focused on themes related to “diagnosis of COVID-19 disease”, “diagnosis of diseases”, “detection and classification of cancerous cells”, “identification of disease risk factors and disease prediction”, “prediction of treatment outcomes”, “prediction of disease course”, “personalized treatment recommendations”, “decision-making processes”, “ethical considerations, risks, and responsibilities”. With the COVID-19 pandemic, it is seen that the number of articles on artificial intelligence in the healthcare sector has increased exponentially. In the research, articles related to artificial intelligence in the health sector were examined, and a framework was created for researchers by revealing the most publishing countries, journals, authors, most cited authors, and keywords that were used the most.

Potential Beneficial Role of Nitric Oxide in SARS-CoV-2 Infection: Beyond Spike-Binding Inhibition

SARS-CoV-2, the causative virus for the COVID-19 disease, uses its spike glycoprotein to bind to human ACE2 as a first step for viral entry into the cell. For this reason, great efforts have been made to find mechanisms that disrupt this interaction, avoiding the infection. Nitric oxide (NO) is a soluble endogenous gas with known antiviral and immunomodulatory properties. In this study, we aimed to test whether NO could inhibit the binding of the viral spike to ACE2 in human cells and its effects on ACE2 enzymatic activity. Our results show that ACE2 activity was decreased by the NO donors DETA-NONOate and GSNO and by the NO byproduct peroxynitrite. Furthermore, we found that DETA-NONOate could break the spike–ACE2 interaction using the spike from two different variants (Alpha and Gamma) and in two different human cell types. Moreover, the same result was obtained when using NO-producing murine macrophages, while no significant changes were observed in ACE2 expression or distribution within the cell. These results support that it is worth considering NO as a therapeutic agent for COVID-19, as previous reports have suggested.

New insights into the increased risk of migraines from COVID-19 infection and vaccination: a Mendelian randomization study

IntroductionMigraine is a prevalent neurological disorder characterized by recurrent attacks, leading to a substantial global disease burden. Recent observational studies have reported the onset and worsening of migraine following COVID-19 infection and vaccination. However, traditional observational study designs have limitations in controlling for confounding factors, potentially resulting in biased and inconsistent conclusions. To address this, we applied Mendelian randomization (MR) to investigate the causal relationship between COVID-19 infection and vaccination with migraine.MethodsThis study utilized summary-level genome-wide association study (GWAS) data from the GWAS catalog and FinnGen database to evaluate the effects of varying degrees of COVID-19 infection and vaccination on migraine. We employed inverse variance weighted (IVW) fixed-effect and random-effect models as the primary methods for MR analysis, with MR-Egger and other approaches as complementary methods. Sensitivity analyses, including Cochran's Q test, MR-Egger intercept regression, and MR-PRESSO, were conducted to ensure robustness of the results.ResultsOur MR analysis revealed no significant causal association between COVID-19 infection and migraine. However, a significant causal association was found between COVID-19 vaccination and migraine (beta = 0.071, P = 0.034). The results were confirmed through a series of sensitivity tests, demonstrating the robustness of the findings.DiscussionThis study provides novel evidence of a significant causal link between COVID-19 vaccination and migraine, while no such association was observed with COVID-19 infection. These findings may have important implications for clinical practice, particularly in planning treatment adjustments and optimizing patient care for individuals with migraines in the context of COVID-19 vaccination.

The Possible Impact of COVID-19 on Glycated Hemoglobin and Systolic Blood Pressure in Type 2 Diabetes and Obesity

Background: There are still discrepancies in the literature as to whether COVID-19 infection could impact biochemical, anthropometric, and cardiovascular markers. The purpose of this study was firstly to observe the effects of COVID-19 infection over 12 months on Type 2 diabetes (T2D) and obesity. Secondarily, we analyzed the individual influence of COVID-19 infection on changes in biochemical, anthropometric, and cardiovascular markers. Methods: This study is part of a secondary analysis of a recently published article. The research involved 84 participants with T2D, divided into two groups: the control group (40 participants) received only medical care, while the intervention group (44 participants) received both medical care and nutritional assessment. Consultations were held quarterly over 12 months, with a follow-up after 3 months. Data Analysis: For influence analysis, non-normal variables were compared using the Mann–Whitney test, and normal variables were compared using unpaired t-tests. For all cases, α = 0.05 and p < 0.05 were considered significant. Results: The analysis revealed a high percentage of patients in both groups who had a COVID-19 infection (70% control and 72.7% intervention) over 12 months. Regarding the influence analysis, participants in the intervention group who were infected with COVID-19 showed smaller reductions in glycated hemoglobin (HbA1c) (p = 0.0120) and systolic blood pressure (SBP) (p = 0.0460). For the other biochemical, anthropometric, and cardiovascular markers, in both groups, no significant differences were found (p > 0.05). Conclusion: COVID-19 possibly influenced SBP and HbA1c levels over 12 months in people with T2D and obesity. However, caution should be exercised in generalizing these results due to the limitations of this study. Additionally, influence analysis does not establish a causal relationship, and more clinical trials in different populations are needed to fully analyze this topic.

Cutaneous Manifestations of Pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children (MIS-C)

Background: Characteristics of dermatological manifestations are frequently encountered in pediatric COVID-19, similar to the presentation in multisystem inflammatory syndrome in children (MIS-C), which typically emerges following COVID-19 infection. The rash exhibits considerable diversity and lacks specificity. However, investigations into the dermatological features of COVID-19 in children and MIS-C remain limited. Objective: To investigate cutaneous manifestations in both COVID-19 and MIS-C in children. Materials and Methods: Cross-sectional study between February and August 2022 in hospitalized children with COVID-19 who had cutaneous lesions and all hospitalized children with MIS-C. Results: Forty-six cases of COVID-19 patients with dermatological manifestations were identified among 1,602 COVID-19 patients, constituting 2.9%. Additionally, 35 cases of MIS-C were diagnosed. The majority of COVID-19 patients in the present study exhibited mild symptoms, accounting for 42 cases (91.3%). The median age of COVID-19 patients was 1.8 years, which was significantly lower than that of the MIS-C group, which was 4.3 years, with a statistically significant difference (p=0.024). The most common rash types observed in both groups were urticaria, maculopapular rash, and macular erythema. Other rash types noted in COVID-19 included erythema nodosum, Stevens-Johnson syndrome, erythema multiformelike, vesicles, and livedo reticularis. Among MIS-C patients, 31 cases (88.6%) presented with mucocutaneous manifestations, with 26 cases (74.3%) exhibiting concurrent mucocutaneous involvement. There was no significant difference in the occurrence of cardiac symptoms between the group with mucocutaneous manifestations and/or dermatological symptoms, which was 81.8%, compared to the group without mucocutaneous or dermatological symptoms, which was 100% (p=0.102). Conclusion: The cutaneous manifestations in pediatric COVID-19 and those with MIS-C vary widely and are non-specific. In patients presenting with fever and rash during a COVID-19 outbreak, recognizing these cutaneous symptoms is crucial for prompt diagnosis and treatment especially those who are asymptomatic. Further studies involving COVID-19 patients, both with and without rash, may provide correlation between disease progression and skin manifestation.

'I am more stressed if my infection affects others': development of a COVID-19-related stress scale in older people and examination of its validity and associations with mental health risks.

COVID-19 was a collective traumatic event; however, different individuals may have perceived it differently. This study investigated what older people in a collective culture perceived as stressful during COVID-19 and examined how different stressors related to COVID-19 infection and mental health risks. Thirty-six participants from diverse backgrounds engaged in a three-round Delphi study to generate items for a COVID-19-related stress scale for older adults (CSS-OA). Subsequently, 4674 people (aged ≥60 years) participated in a cross-sectional telephone survey; interviewers collected their responses to CSS-OA and information about COVID-19 infection, depressive symptoms, anxiety, loneliness and demographics. Exploratory factor analysis and confirmatory factor analysis were conducted on CSS-OA. A multiple indicator multiple cause (MIMIC) model was used to examine associations between CSS-OA and other measures. The Delphi process generated eight items, all secondary or tertiary stressors related to infection. Exploratory factor analysis revealed a three-factor model, and confirmatory factor analysis confirmed an excellent fit (comparative fit index = 0.99, root mean square error of approximation = 0.06). Pre-existing mental health conditions, having family members/friends infected with COVID-19, loneliness, anxiety and depressive symptoms were associated with higher stress. Conversely, self-infection with COVID-19, older age, being female and living alone were negatively associated with some domains of CSS-OA (all P < 0.05). The Delphi process enhanced our understanding of what older people perceived as stressful, much of which resulted from certain healthcare strategies and reflected cultural influences. These and the MIMIC results highlight the need to balance public health policies with respect to infectious diseases and older people's mental health and quality of life.

Безопасность применения двухкомпонентного препарата моноклональных антител к SARS-CoV-2 (тиксагевимаб + цилгавимаб) для доконтактной профилактики новой коронавирусной инфекции у детей с ревматическими заболеваниями

New coronavirus infection (COVID-19) is an acute respiratory disease caused by the SARS-CoV-2 coronavirus. Tixagevimab+cilgavimab has been developed for the prevention and treatment of COVID-19. The purpose of this research was to evaluate the safety of the use of the two-component drug of monoclonal antibodies to SARS-CoV-2 (tixagevimab+cilgavimab) for pre-exposure prophylaxis of the new coronavirus infection in children with rheumatic diseases (RDs). Materials and methods used: a single-center retrospective study with prospective stage had been carried out that included 300 pediatric patients aged 12 to 18 y/o with RDs. The safety of pre-exposure prophylaxis of COVID-19 was assessed based on the dynamics of clinical and laboratory parameters as well as the total indices of RD activity. The effectiveness of pre-exposure prophylaxis was assessed based on recording the incidence of the new coronavirus infection. Safety and effectiveness were assessed after 3, 6, and 9 months after the administration of tixagevimab+cilgavimab drug. Results: no statistically significant increase in RDs activity was registered during 9 months of observation after pre-exposure prophylaxis of COVID-19. On the contrary, in patients with various types of juvenile arthritis, systemic lupus erythematosus and juvenile ankylosing spondylitis during the observation period against the background of antirheumatic therapy, a statistically significant decrease in the activity indices was registered - JADAS71 (p&lt;0.001, p=0.002, p=0.030), SELENA-SLEDAI (p&lt;0.001, p=0.027, p=0.570) and JSpADA (p=0.009, p=0.205, p=1.000), respectively; in patients with juvenile dermapolymyositis, systemic sclerosis and systemic vasculitis - a tendency to decrease in activity indices - DAS (p=0.002, p=0.050, p=0.193), J4S (p=0.840, p=0.720, p=1.000), PVAS (p=0.120, p=0.230, p=1.000 for the new and p=0.360, p=1.000, p=0.860 for the constant attributes), respectively. The new coronavirus infection was suffered by 6/300 (2%) patients within 9 months after pre-exposure prophylaxis. Conclusion: pre-exposure prophylaxis of COVID-19 with the two-component drug of monoclonal antibodies to SARS-CoV-2 (tixagevimab+cilgavimab) may be considered as both effective and safe and can therefore be suggested to pediatric patients with RDs.

Developing Correlates of Protection for Vaccines Is Needed More than Ever—Influenza, COVID-19 and RSV Infection

One of the greatest success stories of modern medicine is the prevention of infectious diseases by vaccination, most notably against smallpox and poliomyelitis. However, recent events, such as the 2009–2010 swine flu and the 2020 COVID-19 pandemics, as well as the continued emergence of highly pathogenic avian influenza viruses highlighted the fact that we still need to develop new vaccines, and perhaps we should be proactive, rather than reacting to epidemics and pandemics. However, the development of tools for evaluating novel vaccines has not been able to keep up with the rate of vaccine production. Humoral and cellular immune responses to vaccination have both been suggested to be important in preventing infections or ameliorating their consequences, although there is uncertainty regarding their exact roles and importance. This, together with the rapid development of new vaccines, means that the need for developing immunogenicity parameters, and even more importantly, reliable correlates of protection, is more important than ever.

Ectopic Mediastinal Thyroid: A Crossroad Between a Multi-Layered Endocrine Perspective and a Contemporary Approach in Thoracic Surgery

An ectopic thyroid (ET) involves numerous scenarios of detection and outcomes, while its current management is not standardised. A mediastinal ET (MET) represents a low index of suspicion. In this paper, we introduce a 47-year-old female who was accidentally identified with an MET, and a modern surgical approach was provided. An anterior mediastinal mass of 3.2 cm was found at CT upon a prior COVID-19 infection. Previous to the infection, she experienced non-specific complaints for a few months (intermittent night sweats, facial erythema, chest pressure, and dyspnoea). Also, CT identified a thymus-like mass and a left adrenal incidentaloma of 3 cm. The endocrine panel was normal, and the subject declined further investigations. She was re-admitted 12 months later: the MET had increased +1 cm (+45% volume) and was confirmed at a 99mTc pertechnetate scintigraphy. Noting the symptoms, mediastinal anatomy, and size change, the MET was removed via a minimally invasive trans-cervical approach (eutopic gland preservation) with the help of a Cooper thymectomy retractor (which also allowed for a synchronous thymus mass resection). No post-operatory complications were registered, the thyroid function remained normal, and the mentioned symptoms were remitted. A histological exam confirmed a benign MET and thymus hyperplasia, respectively. To conclude, this case pinpoints important aspects, such as the clinical picture became clear only upon thoracic surgery due to the complete remission of the complaints that initially seemed widely non-specific. The incidental MET finding was associated with a second (adrenal) incidentaloma, a scenario that might not be so rare, following multiple imaging scans amid the COVID-19 era (no common pathogenic traits have been identified so far). The co-presence of a thymus mass represented one more argument for surgery. Minimally invasive cervicotomy associated with eutopic gland conservation and the use of a Cooper thymectomy retractor highlight modern aspects in video-assisted thoracic surgery, which provided an excellent outcome, involving one of the lowest mediastinal thyroids to be removed by this specific procedure. Awareness of such unusual entities helps inform individualised, multidisciplinary decisions for optimum prognoses.

The effect of COVID-19 vaccination on symptomatic infection and related symptoms among preterm-born children aged 3–7 years in China

Vaccination plays a crucial role in preventing and controlling SARS-CoV-2 infections as well as their associated adverse outcomes. But there is a notable lack of research on the effectiveness of COVID-19 vaccination in children, particularly those young preterm-born children, who are more vulnerable to severe outcomes from SARS-CoV-2 infection. We aimed to determine the effect of vaccination with inactivated vaccines BBIBP-CorV and CoronaVac on symptomatic COVID-19 infection and related symptoms in preterm-born children aged 3–7 years after relaxation of the COVID-19 prevention and control measures in December 2022 in China. We performed a retrospective cohort study involving 242 preterm-born children aged 3–7 years and the data were collected in March 2023. Logistic regression models and modified Poisson regression models combined with entropy balancing were used to explore the associations of vaccination against SARS-CoV-2 with symptomatic COVID-19, specific symptoms, and persistent symptoms one month after recovery from COVID-19. Of the 242 recruited preterm-born children, 156 (64.5%) were vaccinated with inactivated vaccines BBIBP‐CorV and CoronaVac. After entropy balancing, the covariates were balanced between the vaccinated and the unvaccinated groups, with standardized mean difference < 0.001. Vaccination with the said SARS-CoV-2 vaccines lowered the risk of developing symptomatic COVID-19 in preterm-born children (risk ratio [RR] = 0.783; 95% confidence interval [CI]: (0.711, 0.861). Likewise, COVID-19 vaccination was associated with a decline in the risk of pneumonia (odds ratio [OR] = 0.318; 95% CI 0.110, 0.913), fever (RR = 0.710; 95% CI 0.635, 0.794), high fever (RR = 0.542; 95% CI 0.297, 0.988), sore throat (OR = 0.304; 95% CI 0.139, 0.664), and persistent symptoms (RR = 0.425; 95% CI 0.182, 0.993). Immunization with inactivated vaccines BBIBP‐CorV and CoronaVac provides protection against symptomatic COVID-19 for preterm-born children 3–7 years.

Cross-cultural adaptation and validation of an Urdu version of the Vaccine Attitudes Examination (VAX-U) scale.

Martin and Petrie developed the Vaccine Attitudes Examination (VAX) scale with an aim to document general vaccination attitudes. Vaccine acceptance plays an important role in curbing COVID-19 infections. Thus, it was important to assess vaccination attitudes of Pakistani people towards novel COVID-19 vaccines. The VAX scale was not available in Urdu language for Pakistani population. The study aimed to carry out cross-cultural adaptation and validation of an Urdu version of the Vaccine Attitude Examination (VAX) scale in a selected population sample from Pakistan. A cross sectional study was conducted in September 2021 in an outpatient department of a healthcare facility in Karachi, Pakistan. Adult visitors, eligible for COVID-19 vaccine and spoke Urdu as first language were invited. Convenient sampling was used, and sample size was based on an item response ratio of 1:20. An Urdu version of the VAX scale was developed. The reliability was assessed using Cronbach's alpha (α) and intraclass correlation coefficient (ICC). The model fitness was evaluated using confirmatory factor analysis (CFA) and fit indices namely goodness of fit index (GFI), adjusted goodness of fit index (AGFI), Tucker Lewis index (TLI), comparative fit index (CFI), and root mean square error of approximation (RMSEA). A structural equation model (SEM) was also developed. IBM SPSS and AMOS were used to analyse the data. The study had ethical clearance. A total of 211 responses were analysed. The reliability (Cronbach's α) was 0.821. The ICC was 0.831 (95% CI: 0.795-0.863). CFA using a 4-factor model revealed the following values for fit indices; GFI = 0.944, AGFI = 0.909, TLI = 0.953, CFI = 0.966, and RMSEA = 0.051. All values reported were in the acceptable range. The VAX Urdu version is a reliable and valid instrument for use in an Urdu speaking population and will enable clinicians to assess the public's attitude towards general vaccination including COVID-19 vaccination. Clinicians can use the VAX-U to document a person's vaccine hesitancy and tailor their counselling to address the issues in vaccine uptake.

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.

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.