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The most fruitful prevention and treatment tools for the COVID-19 pandemic have proven to be vaccines and therapeutic antibodies, which have reduced the spread of the disease to manageable proportions. The search for the most effective antibodies against the widest set of COV-2 variants has required a long time and substantial resources. It would be desirable to have a tool that will enable us to understand the structural basis on which mutants escape at least some of the epitope-bound antibodies, a tool that may substantially reduce the time and resources invested in this effort. In this work, we applied a computational-based tool (employed previously by us to understand COV-2 spike binding to its cognate cell receptor) to the study of the effect of Delta and Omicron mutations on the escape tendencies. Our binding energy predictions agree extremely well with the experimentally observed escape tendencies. They have also allowed us to set forth a structural explanation for the results that could be used for the screening of antibodies. Lastly, our results explain the differences in molecular interactions that govern interaction of the spike variants with the receptor as opposed to those with antibodies. [ABSTRACT FROM AUTHOR]

Background/Objectives: Individuals with post-COVID-19 conditions risk developing short- and/or long-term neuromuscular impairments, including postural imbalance. However, there is limited evidence showing whether balance deficits are associated with declines in the functional status in post-COVID-19 individuals. This study examined postural balance in non-hospitalized post-COVID-19 individuals using different assessment tools and tested the most relevant balance tools in predicting functional status. Methods: This cross-sectional study enrolled 60 adults split into control (n = 30) and post-COVID-19 (n = 30) groups. Postural balance was assessed in both groups using the Functional Reach Test (FRT), Berg Balance Scale (BBS), Timed Up and Go (TUG), Tinetti Balance Test (Tinetti), and Mini-BESTest (MBT). Functional status in the post-COVID-19 group was assessed using post-COVID-19 functional status (PCFS). Results: Significant differences in postural stability between groups were found only for the FRT. All balance tests showed a statistically significant correlation with PCFS in the post-COVID-19 group, with better performance in all tests being associated with better functional status: Tinetti (r = −0.584), FRT (r = −0.542), MBT (r = −0.530), BBS (r = −0.415) and TUG (r = 0.368). Tinetti was the independent variable that significantly played an important role in determining PCFS (adjusted R2 = 0.318, p < 0.001). Conclusions: Post-COVID-19 functional status is best determined by the Tinetti Balance Test, making it an effective tool for assessing postural balance deficits in this population, with potential implications for postural control assessment and rehabilitation. [ABSTRACT FROM AUTHOR]

Background: Early risk stratification tools for COVID-19 patients have been indicated yet there are few data about their ability to effectively detect clinical deterioration among COVID-19 patients. Objectives: To evaluate the NEWS-2 to predict severe morbidity and mortality for COVID-19 patients admitted to hospitals. Methods: We conducted a prospective cohort study among adult COVID-19 patients with a confirmed diagnosis who were admitted to the inpatient units at COVID-19 Martyrs Medical Military Complex Hospital, from 1 March 2022, until 29 February 2023. NEWS-2 scores were measured at admission and 6, 12, 24, and 48 h after their admission to the hospital using receiver operating characteristic (ROC) curves. Results: Overall, 192 adult COVID-19 patients aged 25–94 years (mean = 62.1, SD = 13.9) were enrolled. Of those, 49.0% were males, 47.4% were vaccinated, and 53.6% had diabetes. The 192 enrolled patients were classified into NEWS-2 score categories, with almost 13% (12.5%) falling into the high-risk category already upon admission. The mean NEWS-2 scores were excellent predictors of mechanical ventilation, admission to the ICU, and mortality, as indicated by an AUROC of 0.94 (95% CI: 0.88–1.00, p < 0.001), 0.91 (95% CI: 0.87–0.96, p < 0.001), and 0.96 (95% CI: 0.92–1.00, p < 0.001), respectively. Significant differences in mean NEWS-2 scores were found between the participating patients, both with and without comorbidity in the course of the patient's stay in the ICU, and mortality (p = 0.004, p = 0.043, respectively). Positive correlations of the high NEWS-2 scores were revealed using a multiple linear regression model, indicating the necessity of administering non-invasive ventilatory assistance (p = 0.013), hospitalization for a minimum of six days (p = 0.013), and admission to the ICU (p = 0.006). Nonetheless, there was a negative association between mortality and the NEWS-2 score (p < 0.001). Conclusions: The NEWS-2 had moderate sensitivity and specificity in predicting the deterioration of patients with COVID-19 whereas there was high sensitivity and specificity in predicting the mortality for patients with COVID-19, both with and without comorbidity. Our findings support the utility of NEWS-2 monitoring as a sensitive approach for initially assessing COVID-19 patients. It could be helpful to enhance the accuracy of predictive performance by supplementing the score parameters by adding biological parameters in addition to clinical judgment. [ABSTRACT FROM AUTHOR]

Although a fourth dose of SARS-CoV-2 vaccine was shown to be effective, the immunogenicity of a fifth dose in immunocompetent individuals had not been well described. This was a prospective observational cohort study of previously vaccinated healthcare workers at a single tertiary hospital in Israel. Individuals were administered up to three booster doses of the BNT162b2 mRNA vaccine (i.e., up to five overall doses), during the period between July 2021 and January 2023. Immunogenicity was assessed using the SARS-CoV-2 IgG (sCOVG) semi-quantitative assay, performed at several time points. The cohort consisted of 162 individuals (median age 69 years, 62% female). Of these, 104 (64%) received four doses and 58 (36%) received five doses. Anti-SARS-CoV-2 antibody levels increased in all cases, regardless of the baseline levels. The fold-change increase in the mean sCOVG index was 29.2 (SD 2.6) after the third vaccine, 3.8 (SD 2.4) after the fourth vaccine, and 3.6 (SD 3.0) after the fifth vaccine. A waning effect over time was seen in 78% and 43% of participants for the third and fourth doses, respectively. Adverse events following the fifth dose were limited and mild. Similar to previous booster vaccines, a fifth dose of BNT162b2 is immunogenic and safe in healthy individuals, although the clinical implications remain unclear. [ABSTRACT FROM AUTHOR]

Dual antiplatelet therapy (DAPT), which is essential in AMI management, combines aspirin with a P2Y12 receptor antagonist. This study compared the effectiveness of potent P2Y12 inhibitors versus clopidogrel in AMI patients treated with percutaneous coronary intervention (PCI). Methods: 65,986 AMI patients included in a nationwide prospective registry who underwent PCI and received DAPT were studied. In total, 9,014 patients received potent P2Y12 inhibitors, and 56,074 received clopidogrel. This study focused on mortality, recurrent myocardial infarction, stroke, repeat revascularization, and major adverse cardiovascular events (MACE) over seven years. The analysis utilized unadjusted models and inverse probability of treatment weighting (IPTW) to compare prognosis, and decision curve analyses were constructed to aid clinical decision making. Results: Potent P2Y12 inhibitors significantly reduced mortality risk (unadjusted hazard ratio (HR): 0.58; IPTW HR: 0.68) and MACE (unadjusted HR: 0.66; IPTW HR: 0.78). Diabetic patients showed greater benefits (HR:0.45). In patients at high bleeding risk, the mortality rate was 13% (HR: 0.87, p = 0.08). For patients aged 75–79, the HR for mortality was 0.82, whereas for those aged >80 years, it was 0.79, indicating significant mortality risk reduction. Similar trends were observed for MACE. Conclusion: This study demonstrated that potent P2Y12 inhibitors are more effective than clopidogrel in reducing mortality and MACE in patients with AMI and underscored their potential role in improving outcomes across diverse patient subgroups. The trend was consistent even during the COVID-19 pandemic. These findings highlight the need for personalized DAPT strategies, particularly for high-bleeding-risk patients, and challenge current guidelines favoring clopidogrel use in older patients. [ABSTRACT FROM AUTHOR]

Objectives: The influence of comorbidity on long-term hospitalization and mortality after COVID-19 in adults (40–59 years) and older adults (≥60 years) is yet to be explored. Methods: This is a Danish population-based cohort study of patients with a first-time positive PCR test for COVID-19 from 1 March 2020, to 28 February 2022 (N = 1,034,103). Exposed cohorts were patients with 1) a Charlson Comorbidity Index (CCI) score of 1–2 and 2) a CCI score ≥3, who were compared to patients without comorbidity (CCI of zero) within the groups of adults (67.9%) and older adults (32.1%) for the risk of hospitalization and mortality. Next, within the age groups, each disease category of the CCI was considered as an exposed cohort and compared to patients who did not have the specific disease of interest. Adjusted hazard ratios (HR) for hospitalization and mortality were estimated by Cox regression models adjusted for confounders. Results: The highest HRs were in adult patients with a CCI score of ≥3. The adjusted HR was 4.54 (95%CI: 4.38–4.70) for hospitalization, and among older adults it was 3.05 (95%CI: 2.99–3.11). The adjusted HR for mortality among adults with a CCI score ≥3 was 21.04 (95%CI: 18.86–23.47), and the adjusted HR for mortality among older adults was 4.61 (95%CI: 4.44–4.78). The underlying disease influenced the risk estimates among adults and older adults, and "dementia" had the highest impact on mortality. Conclusion: A CCI score of 1 or above increases the risk of hospitalization and mortality up to 2 years after a positive PCR test of COVID-19 for adults and older adults. Further, the type of underlying disease in older adults highly influences the risk of hospitalization and mortality. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has brought significant attention to the respiratory system, with much focus on lung-related disorders. However, the diaphragm, a crucial component of respiratory physiology, has not been adequately studied, especially in the context of long COVID. This review explores the multipotential role of the diaphragm in both respiratory health and disease, emphasizing its involvement in long-term complications following SARS-CoV-2 infection. The diaphragm's fundamental role in respiratory physiology and its impact on balance and posture control, breathing patterns, and autonomic nervous system regulation are discussed. This review examines complications arising from COVID-19, highlighting the diaphragm's involvement in neurological, musculoskeletal, and inflammatory responses. Particular attention is given to the neuroinvasive impact of SARS-CoV-2, the inflammatory response, and the direct viral effects on the diaphragm. The diaphragm's role in long COVID is explored, with a focus on specific symptoms such as voice disorders, pelvic floor dysfunction, and sleep disturbances. Diagnostic challenges, current methods for assessing diaphragmatic dysfunction, and the complexities of differentiating it from other conditions are also explored. This article is the first to comprehensively address diaphragmatic dysfunction resulting from COVID-19 and long COVID across various physiological and pathological aspects, offering a new perspective on its diagnosis and treatment within a multisystem context. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has profoundly affected young adults' lives globally, including those in Germany. This study investigated mental health and quality of life during the pandemic, with a particular focus on mood. Immune fitness, the body's capacity to respond to health challenges (such as infections) by activating an appropriate immune response, was assessed as a physical health indicator. Methods: Data were collected from 317 participants, aged 18 to 35, via an online survey conducted between November 2021 and March 2022. Participants included 103 men (32.5%) and 214 women (67.5%), with a mean age of 25.5 years (SD = 4.1). Results: Compared to pre-pandemic levels, significant declines in mood, quality of life, immune fitness, and sleep quality were observed during the lockdown periods of the COVID-19 pandemic (p < 0.0125). The most pronounced effects were observed during the second lockdown, with declines extending into the second no-lockdown period for fatigue, depression, happiness, optimism, and immune fitness (p < 0.0125). Significant sex differences were found for the magnitude of mood effects (anxiety, depression, stress). No significant differences were found according to age or occupational status (student vs. work). Conclusions: The COVID-19 pandemic and associated lockdown periods had a significant negative effect on the mood, immune fitness, and well-being of young adults living in Germany. [ABSTRACT FROM AUTHOR]

Background: We have previously demonstrated that high-risk obstructive sleep apnea (HR-OSA), based on a modified Berlin Questionnaire (mBQ), is linked to worse clinical outcomes. Chest computed tomography (CT) imaging with the implementation of an artificial intelligence (AI) analysis program has been a valuable tool for the speedy assessment of huge numbers of patients during the COVID-19 epidemic. In the current study, we addressed how the severity of AI-guided, CT-based total opacity ratio (TOR) scores are associated with high-risk OSA and short-term outcomes in the same cohort. Methods: The ratio of the volume of high opacity areas to that of the total lung volume constituted the TOR. We arbitrarily applied thresholds of <5 (no or mild TOR), ≥5 and <15 (moderate TOR), and ≥15 (severe TOR). Results: In total, 221 patients were included. HR-OSA was observed among 11.0% of the no or mild TOR group, 22.2% of the moderate TOR group, and 38.7% of the severe TOR group (p < 0.001). In a logistic regression analysis, HR-OSA was associated with a severe TOR with an adjusted odds ratio of 3.06 (95% confidence interval [CI] 1.27–7.44; p = 0.01). A moderate TOR predicted clinical worsening with an adjusted hazard ratio (HR) of 1.93 (95% CI 1.00–3.72; p = 0.05) and a severe TOR predicted worsening with an HR of 3.06 (95% CI 1.56–5.99; p = 0.001). Conclusions: Our results offer additional radiological proof of the relationship between HR-OSA and worse outcomes in patients with COVID-19 pneumonia. A TOR may also potentially indicate the individuals that are at higher risk of HR-OSA, enabling early intervention and management strategies. The clinical significance of TOR thresholds needs further evaluation in larger samples. [ABSTRACT FROM AUTHOR]

Background/Objectives: Severe clinical course and mortality from COVID-19 are mostly associated with increased concentrations of IL-6 and IL-10. Findings from clinical trials suggest that both statins and renin–angiotensin–aldosterone system inhibitors (RAASI) might have the potential to reduce unfavorable outcomes in patients with COVID-19. The aim of this study was to evaluate the effect of statins and RAASI on the cytokine concentrations in COVID-19 patients. Methods: SARS-CoV-2 infected patients were enrolled in this study, and demographic, clinical, and routine laboratory data were evaluated. Plasma cytokine levels were measured by multiplex assay. Results: COVID-19 patients with chronic cardiovascular diseases (CVD) had significantly lower median plasma IL-6 levels than COVID-19 patients with no co-morbidities (26 vs. 53 pg/mL, p = 0.021). COVID-19 patients with CVD who were taking statins had significantly lower median concentrations of IL-6 (21 vs. 44 pg/mL, p = 0.027), TNFα (21 vs. 39.5 pg/mL, p = 0.036), and IL-10 (19 vs. 25.5 pg/mL, p = 0.025) compared to COVID-19 patients with no CVD. In a binary logistic regression model, IL-6 was a significant variable, with an odds ratio value of 0.961 (95% CI 0.929–0.995). Regarding RAASI, only plasma IL-6 (22 vs. 44 pg/mL, p = 0.012) levels were found to be significantly lower in COVID-19 patients with CVD consuming these medications compared to patients who did not have any CVD. Conclusions: COVID-19 patients who had chronic cardiovascular co-morbidities and who were administered statins or RAASI had significantly lower concentrations of IL-6 than COVID-19 patients who did not have any co-morbidities. These findings suggest that the use of statins or RAASI may be of value in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background/Objectives: This retrospective study analyzed soluble urokinase plasminogen activator receptor (suPAR) plasma levels alongside routine inflammatory markers, including the neutrophil-to-lymphocyte count ratio, C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), and D-dimers in COVID-19 patients hospitalized during the Omicron wave of the pandemic. Methods: We measured plasma suPAR levels using a suPARnostic® Quick Triage kit. We divided COVID-19 patients into two groups based on the severity of SARS-CoV-2 infection according to the National Institutes of Health (NIH) criteria. The logistic regression analysis tested the predictive value of the biomarkers. Results: We evaluated 160 consecutive COVID-19 patients hospitalized between January and August 2022. The cohort exhibited a high incidence of comorbidities, with an in-hospital mortality rate of 5.6%. Upon admission, the median suPAR plasma levels were not significantly different between patients with mild COVID-19 (n = 110) and those with moderate/severe disease (n = 50), with 7.25 ng/mL and 7.55 ng/mL, respectively. We observed significant differences (p < 0.01) between the groups for CRP and IL-6 levels that were higher in moderate/severe disease than in mild infection. Additionally, suPAR plasma levels were above the normal range (0–2.00 ng/mL) in all patients, with a significant positive correlation identified between suPAR levels and serum IL-6, PCT, and creatinine levels. Conclusions: These findings indicate that COVID-19 during the Omicron wave is strongly associated with elevated suPAR levels; however, these levels do not directly correlate with the severity of SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

COVID-19 is an enveloped virus with a single-stranded R N A genome. The surface of the virus contains spike proteins, which enable the virus to attach to host cells and enter the interior of the cells. After entering the cell, the virus exploits the host cell's mechanisms for replication and dissemination. Since the end of 2019, COVID-19 has spread rapidly around the world, leading to a large-scale epidemic. In response to the COVID-19 pandemic, the global scientific community quickly launched vaccine research and development. Vaccination is regarded as a crucial strategy for controlling viral transmission and mitigating severe cases. In this paper, we propose a novel mathematical model for COVID-19 infection incorporating vaccine-induced immunization failure. As a cornerstone of infectious disease prevention measures, vaccination stands as the most effective and efficient strategy for curtailing disease transmission. Nevertheless, even with vaccination, the occurrence of vaccine immunization failure is not uncommon. This necessitates a comprehensive understanding and consideration of vaccine effectiveness in epidemiological models and public health strategies. In this paper, the basic regeneration number is calculated by the next generation matrix method, and the local and global asymptotic stability of disease-free equilibrium point and endemic equilibrium point are proven by methods such as the Routh–Hurwitz criterion and Lyapunov functions. Additionally, we conduct fractional-order numerical simulations to verify that order 0.86 provides the best fit with COVID-19 data. This study sheds light on the roles of immunization failure and fractional-order control. [ABSTRACT FROM AUTHOR]

Despite numerous studies conducted by various research teams, predicting long-term outcomes (known as Post-COVID-19 Syndrome, PCS) that may result from Coronavirus Disease 2019 (COVID-19) remains challenging. PCS affects over a million people, primarily those with comorbid conditions. Therefore, it is crucial to undertake research aimed at developing a predictive model for early diagnosis of PCS, which in turn would enable faster preventive actions. The aim of this study was to assess the value of measuring and attempt a quantitative evaluation using Enzyme-Linked Immunosorbent Assay (ELISA) tests of three non-serum proteins, whose presence in the blood during COVID-19 was associated with severe disease progression: neutrophil elastase (NE), calcium-binding protein S100B, and neuron-specific enolase (NSE). The concentrations of these proteins were measured in blood serum samples collected before the COVID-19 pandemic from (1) patients with type 2 diabetes (T2DM); (2) advanced stage diabetic nephropathy (NfT2DM); (3) a healthy group; and in blood serum samples collected two years after recovering from COVID-19 from patients with (4) T2DM and (5) NfT2DM. It was found that elevated levels of NE and NSE were significantly more common (p < 0.05) in patients with NfT2DM after recovering from COVID-19 compared to the other groups, while elevated levels of S100B were significantly more frequently observed in patients with T2DM after recovering from COVID-19 (p < 0.05). Demonstrating differences in the prevalence of NE, NSE, and S100B in individuals who recovered from COVID-19 with T2DM and NfT2DM makes these proteins important components of the developing predictive model for early detection of PCS. To our knowledge, this is the first study showing the significance of NE, NSE, and S100B in PCS in the context of T2DM and NfT2DM. [ABSTRACT FROM AUTHOR]

COVID-19, caused by SARS-CoV-2, triggers a complex immune response, with T regulatory cells (Tregs) playing a crucial role in maintaining immune homeostasis and preventing excessive inflammation. The current study investigates the function of T regulatory cells during COVID-19 infection and the subsequent recovery period, emphasizing their impact on immune regulation and inflammation control. We conducted a comprehensive analysis of Treg subpopulations in peripheral blood samples from COVID-19 patients at different stages: acute infection, early convalescence, and long-term recovery. Flow cytometry was employed to quantify Tregs including "naïve", central memory (CM), effector memory (EM), and terminally differentiated CD45RA+ effector cells (TEMRA). Additionally, the functional state of the Tregs was assessed by the expression of purinergic signaling molecules (CD39, CD73). Cytokine profiles were assessed through multiplex analysis. Our findings indicate a significant decrease in the number of Tregs during the acute phase of COVID-19, which correlates with heightened inflammatory markers and increased disease severity. Specifically, we found a decrease in the relative numbers of "naïve" and an increase in EM Tregs, as well as a decrease in the absolute numbers of "naïve" and CM Tregs. During the early convalescent period, the absolute counts of all Treg populations tended to increase, accompanied by a reduction in pro-inflammatory cytokines. Despite this, one year after recovery, the decreased subpopulations of regulatory T cells had not yet reached the levels observed in healthy donors. Finally, we observed the re-establishment of CD39 expression in all Treg subsets; however, there was no change in CD73 expression among Tregs. Understanding these immunological changes across different T regulatory subsets and adenosine signaling pathways offers important insights into the disease's pathogenesis and provides a broader view of immune system dynamics during recovery. [ABSTRACT FROM AUTHOR]

Extensive research has been conducted on the SARS-CoV-2 virus in association with various infectious diseases to understand the pathophysiology of the infection and potential co-infections. In tropical countries, exposure to local viruses may alter the course of SARS-CoV-2 infection and coinfection. Notably, only a portion of the antibodies produced against SARS-CoV-2 proteins demonstrate neutralizing properties, and the immune response following natural infection tends to be temporary. In contrast, long-lasting IgG antibodies are common after dengue virus infections. In cases where preexisting antibodies from an initial dengue virus infection bind to a different dengue serotype during a subsequent infection, there is a potential for antibody-dependent enhancement (ADE) and the formation of immune complexes associated with disease severity. Both SARS-CoV-2 and dengue infections can result in immunodeficiency. Viral proteins of both viruses interfere with the host's IFN-I signaling. Additionally, a cytokine storm can occur after viral infection, impairing a proper response, and autoantibodies against a wide array of proteins can appear during convalescence. Most of the reported autoantibodies are typically short-lived. Vaccines against both viruses alter the immune response, affecting the course of viral infection and enhancing clearance. A comprehensive analysis of both viral infections and pathogenicity is revisited to prevent infection, severity, and mortality. [ABSTRACT FROM AUTHOR]

The high variability observed in the clinical symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has been attributed to the presence, in a proportion of infection-naive subjects, of pre-existing cross-reactive immune responses. Here, we demonstrate that the bovine coronavirus spike protein (BoS) may represent a source of protective immunity to SARS-CoV-2. Indeed, vaccination of BALB/c mice with a Bovine herpesvirus 4 (BoHV-4)-based vector expressing BoS induced both cell-mediated and humoral immune responses that cross-react with SARS-CoV-2 spike protein. Although the spike-specific antibodies induced by BoS did not neutralize SARS-CoV-2, the T lymphocytes activated by BoS were able to induce cytotoxicity of cells expressing spike proteins derived from several SARS-CoV-2 variants. These results demonstrate that immunization with BoS may represent a source of cross-reactive immunity to SARS-CoV-2, and that these cross-reactive immune responses may exert protective functions. These results contribute to deciphering the mechanisms responsible for lack or mildness of symptoms observed in many individuals upon SARS-CoV-2 infection and may open new ways for the development of new vaccines for coronaviruses. [ABSTRACT FROM AUTHOR]

IL-6 remains a key molecule of the cytokine storms characterizing COVID-19, exerting both proinflammatory and anti-inflammatory effects. Emerging research underscores the significance of IL-6 trans-signaling over classical signaling pathways, which has shifted the focus of therapeutic strategies. Additionally, the synergistic action of TNF-α and IFN-γ has been found to induce inflammatory cell death through PANoptosis, further amplifying the severity of cytokine storms. Long COVID-19 patients, as well as those with cytokine storms triggered by other conditions, exhibit distinct laboratory profiles, indicating the need for targeted approaches to diagnosis and management. Growing evidence also highlights the gut microbiota's crucial role in modulating the immune response during COVID-19 by affecting cytokine production, adding further complexity to the disease's immunological landscape. Targeted intervention strategies should focus on specific cytokine cutoffs, though accurate cytokine quantification remains a clinical challenge. Current treatment strategies are increasingly focused on inhibiting IL-6 trans-signaling, which offers promise for more precise therapeutic approaches to manage hyperinflammatory responses in COVID-19. In light of recent discoveries, this review summarizes key research findings on cytokine storms, particularly their role in COVID-19 and other inflammatory conditions. It explores emerging therapeutic strategies targeting cytokines like IL-6, TNF-α, and IFN-γ, while also addressing open questions, such as the need for better biomarkers to detect and manage cytokine storms. Additionally, the review highlights ongoing challenges in developing targeted treatments that mitigate hyperinflammation without compromising immune function, emphasizing the importance of continued research in this field. [ABSTRACT FROM AUTHOR]

Background/Objectives: The relationship between BMI, inflammation, and mental health is complex. A high BMI, especially obesity, is associated with chronic inflammation, which can lead to mental disorders such as depression. Inflammatory cytokines affect neurotransmitters and the stress axis, worsening mental health. Obesity and mental disorders can mutually reinforce each other. New findings show that inflammation can lead to neurobiological changes, and the gut microbiota may play a key role. Obesity has been implicated as a factor in the high mortality and duration of influenza-like illnesses, even in people who do not have other chronic diseases that may increase the risk of complications. The aim of this study was to determine the associations between BMI and chronic inflammation, metabolic disorders, depression, and anxiety in patients hospitalized with COVID-19 up to 12 months after hospitalization. Methods: The study included 248 participants previously hospitalized for SARS-CoV-2 infection up to 12 months after hospitalization. The study was conducted in a multistage design using a diagnostic survey, anthropometric measurements, and laboratory methods. Results: A statistically significantly higher BDI-II score was observed among women. Statistical analysis showed a statistically significant higher GAD-7 score among women and those over 75 years of age. Conclusions: Higher BMI among subjects is often associated with elevated values of inflammatory markers and immune cells, such as WBC, neutrophils, monocytes, and CRP, as well as higher blood glucose levels. These associations may be related to the chronic inflammation and metabolic disorders that often accompany obesity. Lymphocytes and eosinophils may show more varied relationships depending on individual factors and specific health conditions. It is therefore important to continue research in this area. [ABSTRACT FROM AUTHOR]

Since the onset of the COVID-19 pandemic, a variety of diagnostic approaches, including RT-qPCR, RAPID, and LFA, have been adopted, with RT-qPCR emerging as the gold standard. However, a significant challenge in COVID-19 diagnostics is the wide range of symptoms presented by patients, necessitating early and accurate diagnosis for effective management. Although RT-qPCR is a precise molecular technique, it is not immune to false-negative results. In contrast, CRISPR-based detection methods for SARS-CoV-2 offer several advantages: they are cost-effective, time-efficient, highly sensitive, and specific, and they do not require sophisticated instruments. These methods also show promise for scalability, enabling diagnostic tests. CRISPR technology can be customized to target any genomic region of interest, making it a versatile tool with applications beyond diagnostics, including therapeutic development. The CRISPR/Cas systems provide precise gene targeting with immense potential for creating next-generation diagnostics and therapeutics. One of the key advantages of CRISPR/Cas-based therapeutics is the ability to perform multiplexing, where different sgRNAs or crRNAs can target multiple sites within the same gene, reducing the likelihood of viral escape mutants. Among the various CRISPR systems, CRISPR/Cas13 and CARVER (Cas13-assisted restriction of viral expression and readout) are particularly promising. These systems can target a broad range of single-stranded RNA viruses, making them suitable for the diagnosis and treatment of various viral diseases, including SARS-CoV-2. However, the efficacy and safety of CRISPR-based therapeutics must be thoroughly evaluated in pre-clinical and clinical settings. While CRISPR biotechnologies have not yet been fully harnessed to control the current COVID-19 pandemic, there is an optimism that the limitations of the CRISPR/Cas system can be overcome soon. This review discusses how CRISPR-based strategies can revolutionize disease diagnosis and therapeutic development, better preparing us for future viral threats. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The global coronavirus disease 2019 (COVID-19) pandemic has affected multiple aspects of people's lives, which may also influence the results of studies conducted during this period across diverse research domains. This particularly includes the field of nutritional science, investigating the gut microbiota as a potential mediator in the association between dietary intake and health-related outcomes. This article identifies the challenges currently facing this area of research, points out potential solutions, and highlights the necessity to consider a range of issues when interpreting trials conducted during this period. Some of these issues have arisen specifically because of the measures implemented to interrupt the spread of small acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while others remain relevant beyond the pandemic. [ABSTRACT FROM AUTHOR]

Background: In the COVID-19 pandemic, novel regional services and communication channels emerged across all sectors of the German healthcare system. To contribute to pandemic preparedness, this study aims to describe newly established services in response to the COVID-19 pandemic from a stakeholder perspective and to examine the interprofessional communication channels, applying a nationwide cross-sectional approach. Methods: A nationwide sample of German healthcare stakeholders comprising general practitioners, associations of statutory health insurance physicians, hospital medical directors, local health departments, rescue coordination centres, medical directors of emergency services, outpatient nursing services, nursing homes, community care access centres, and hospital nursing managers was surveyed. A web-based questionnaire asked for their level of participation in newly implemented regional COVID-19 services and communication channels. Stakeholders' level of recommendation was measured using the Net Promotor Score (NPS), a metric that assesses their satisfaction towards the services surveyed. Results: In total, 1312 healthcare stakeholders participated in the survey. Diagnostic centres (23.0–90.9%), COVID-19 wards in hospitals (40.5–92.1%), emergency medical vehicles designated solely for COVID-19 patients (16.5–68.4%), and crisis intervention teams (11.6–30.6%) exhibited the highest rates of engagement. The services receiving the highest recommendation for future use were COVID-19 focus practices (NPS: 33.4–43.7), COVID-19 wards in hospitals (NPS: 47.6–84.4), transportation of COVID-19 patients exclusively by predefined professional groups (NPS: 12.5–36.4), and newly implemented digitally supported nursing services (NPS: 58.3–100.0). Telephones emerged as the most frequently used communication channel (58.0–96.7%), while email was the primary digital channel (23.7–81.5%). Conclusions: During the COVID-19 pandemic, Germany experienced significant variation in the implementation of pandemic-related services across healthcare sectors, with stakeholders prioritising services built on existing healthcare structures. Developing a proactive digital infrastructure to connect healthcare professionals from different sectors is crucial for better future pandemic management. [ABSTRACT FROM AUTHOR]

Background/Objectives: The COVID-19 pandemic has led to a global health crisis, impacting physical, and mental well-being, particularly among those who have recovered from the illness. This study aimed to assess the mental health status of patients recovered from COVID-19 in Macau, focusing on the impact of sequelae of COVID-19, and identifying demographic factors associated with poor mental health. Methods: A cross-sectional online survey was conducted involving 494 adults who had recovered from COVID-19, with 426 participants included in the final analysis. Mental health was evaluated using the 12-item General Health Questionnaire (GHQ-12), with scores ≥3 indicating poor mental health. Results: This study revealed a high prevalence of poor mental health, affecting 71.8% of the respondents. Binary logistic regression identified experiencing COVID-19 sequelae (OR = 5.727, 95% CI: 2.973–11.031), being in the age groups of 26–45 (OR = 4.227, 95% CI: 1.754–10.185), or 61, and above (OR = 18.072, 95% CI: 3.590–90.962), being male (OR = 0.501, 95% CI: 0.257–0.979), being married (OR = 5.714, 95% CI: 1.919–17.016), and dissatisfaction with family relationships (OR = 2.957, 95% CI: 1.228–7.119) as significant risk factors for poor mental health. Conclusions: This study underscores the critical need for targeted psychological support for patients recovered from COVID-19 in Macau, particularly for those with sequelae, and those in vulnerable demographic groups. The findings suggest that specific age groups and individuals with sequelae may face higher mental health risks, indicating the necessity for prioritized interventions. [ABSTRACT FROM AUTHOR]

Background: The Heart Failure Post-Acute Care [HF-PAC] program is a specialized healthcare program aimed at providing comprehensive care and support for patients with heart failure [HF] as they transition from acute hospital settings to home. But the impact of the coronavirus disease 2019 [COVID-19] pandemic on the HF-PAC program remains unknown. Furthermore, the effects of the comprehensive COVID-19 vaccination program on these patients with HF-PAC warrants further investigation. Methods: A total of 265 patients with acute decompensated HF were admitted to the hospital between May 2020 and October 2022. Of these, 159 patients underwent planned HF-PAC follow-up for 6 months, followed by scheduled follow-up visits every 3 months and unscheduled telephone randomized visits for at least another 6 months. Results: The program completion rate was nearly 92%. COVID-19 significantly impacted patients with HF-PAC, leading to an increased mortality [13.3%] compared to before the pandemic [6.5%]. In our patient cohort, 83% had received at least 1 dose of vaccine and 61% had received > 3 doses. Of these patients with HF-PAC, 34% contracted COVID-19 infection post discharge, and 8.8% died owing to the infection. Of the mortality group, 42.9% patients were not vaccinated, and 28.6% received 1 vaccine dose, and their vaccination rate was lower than in the survival group [p = 0.01]. Conclusions: The COVID-19 pandemic had a significant impact on patients enrolled in the HF-PAC program; receiving more than 3 doses of the COVID-19 vaccine was associated with a significant reduction in mortality rates among these patients. [ABSTRACT FROM AUTHOR]

Background/Objectives: The COVID-19 pandemic reduced in-person pediatric visits in the United States by over 50%, while telehealth visits increased significantly. The national use of telehealth for children and the factors influencing their use have been rarely studied. This study aimed to investigate the prevalence of telehealth use during the COVID-19 pandemic and explore the potential factors linked to its use at the state level. Methods: A cross-sectional study of the National Survey of Children's Health (2021–22) sponsored by the federal Maternal and Child Health Bureau was performed. We used the least absolute shrinkage and selection operator (LASSO) regression to predict telehealth use during the pandemic. A bar map showing the significant factors from the multivariable regression was created. Results: Of the 101,136 children, 15.25% reported using telehealth visits due to COVID-19, and 3.67% reported using telehealth visits due to other health reasons. The Northeast states showed the highest telehealth use due to COVID-19. In the Midwest and Southern states, children had a lower prevalence of telehealth visits due to other health reasons. The LASSO regressions demonstrated that telehealth visits were associated with age, insurance type, household income, usual source of pediatric preventive care, perceived child health, blood disorders, allergy, brain injury, seizure, ADHD, anxiety, depression, and special needs. Conclusions: This study demonstrated significant variability in the use of telehealth among states during the COVID-19 pandemic. Understanding who uses telehealth and why, as well as identifying access barriers, helps maximize telehealth potential and improve healthcare outcomes for all. [ABSTRACT FROM AUTHOR]

Background/Objectives: The strict preventive measures implemented globally during the COVID-19 pandemic affected mental health, with most countries reporting a rise in depression and suicide. This study examined factors affecting depression among Korean adults based on quarantine experiences during 2020 and identified key areas for mental health support. Methods: Data were obtained from South Korea's 2020 Community Health Survey. Responses from 219,228 adults (1893 with quarantine experience and 217,335 without) to questions about quarantine experience, depression (Korean version of PHQ-9 score ≥ 10 or a response of 'several days' or more on item 9), and individual/environmental factors were analyzed. Complex sampling analysis, including descriptive statistics and logistic regression, was conducted using SPSS 29.0. Results: This study found that 158 (weighted 7.5%) of those with quarantine experience, and 12,833 (weighted 5.8%) without quarantine experience, reported depression. Regardless of quarantine, being female, having a low income, a history of depression, and increased stress were associated with a higher depression rate, while good subjective health was linked to lower depression rates. Smoking, living-alone, and a lack of sleep among non-quarantined individuals were linked to increased depression risk, while adequate physical activity was linked to reduced risk. Interestingly, alcohol consumption and being overweight (BMI 23–<25) were associated with lower depression rates. Environmental factors, like unmet medical needs and reduced daily activity, were linked to increased depression. Strong social support and social distancing adherence were associated with reduced depression. Conclusions: These findings underscore the importance of targeted interventions considering quarantine experiences to reduce depression during pandemics. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic significantly impacted the well-being of the general population. However, more information is needed regarding the relationship between participation-related outcomes. This study aimed to analyze the impact of the pandemic on occupational balance (OB) and health-related quality of life (HRQoL) before and after social restrictions and to explore their relationship with COVID-19 diagnosis. Methods: We conducted a study among individuals diagnosed with COVID-19, assigning a healthy control group with the same sociodemographic characteristics using the EQ-5D-5L and the Occupational Balance Questionnaire (OBQ). Results: The final sample size consisted of 61 participants in the COVID-19 diagnosis group (50.8% male; mean age 34.6 ± 14.17 years) and 57 healthy participants (50.8% male; mean age 33.7 ± 13.77 years). There were no differences in the sociodemographic variables between the groups. Significant differences were found between groups both before the pandemic and 1 year after confinement measures in HRQoL and OBQ (p < 0.005). The regression model indicated significant associations (p < 0.001) between HRQoL and both current OB and COVID-19 diagnosis. However, the OBQ scores from before the pandemic did not show a significant association with HRQoL (p = 0.336). Conclusions: In conclusion, social restrictions from the COVID-19 pandemic negatively impacted HRQoL in our sample even 1 year after confinement, with COVID-19 diagnosis and occupational imbalance predicting worse outcomes, highlighting the need for targeted interventions not only for the current situation but also for possible future public health crises. [ABSTRACT FROM AUTHOR]

Background/Objectives: Social isolation (SI) and loneliness (L) are the long-standing critical concerns impacting the mental well-being of older adults. The COVID-19 pandemic has exacerbated existing vulnerabilities, leading to a notable rise in perceived social isolation (PSI) and its associated risks among an aging population. Reportedly, nearly 35% of older Americans felt lonely before the pandemic, with the pandemic further intensifying these feelings. This commentary examines the multifaceted factors contributing to PSI, including demographic and socio-economic characteristics. Methods: We outline the health risks associated with PSI, including cardiovascular diseases and mental health conditions. Results: This commentary addresses the potential of information and communication technology (ICT) to alleviate loneliness, despite significant barriers such as the digital divide and technological anxiety among older adults. Conclusions: This commentary advocates targeted digital literacy interventions and theoretical frameworks to enhance technology adoption and mitigate PSI, ultimately aiming to improve health outcomes and quality of life for the aging population. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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). Conclusion: 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. [ABSTRACT FROM AUTHOR]

Although edible insects (EIs) are encouraged as a sustainable source of protein, their consumption is not as generalised as other types of food that are internationally accepted. While in some regions of the world, EIs are part of the gastronomic and cultural traditions, in other regions, people are not so receptive to this type of food, and some people even express some disgust towards it. Hence, this research focused on the habits of the participants regarding the consumption of insects as well as their perceptions about EIs being or not a part of the local culture or gastronomic patrimony. A questionnaire survey was implemented in fourteen countries (Brazil, Croatia, Greece, Latvia, Lebanon, Lithuania, Mexico, Poland, Portugal, Romania, Serbia, Slovenia, Spain, and Turkey), and globally, 7222 adult participants responded to the questionnaire. SPSS software (version 28) was used to process the data and carry out chi-square tests and Factor Analyses (FA). The obtained results showed significant differences between countries for all the questions included in the survey, either those regarding the habits of the participants or their opinions about the facts linked with EI tradition or cultural aspects. It was found that participants from Mexico consume EIs more than in all other countries and that strong motivations that would lead to consumption among those who do not consume include curiosity and food shortage. The solution obtained with FA considering the ten statements of the scale consisted of two factors: F1—Culture and Tradition of EIs (α = 0.675) and F2—Acceptance of EIs (α = 0.614). In conclusion, the consumption of EIs and the perceptions of people are highly variable according to geographic location and cultural environment. [ABSTRACT FROM AUTHOR]

Background: The difference in the immune response to severe acute respiratory syndrome coro-navirus 2 (SARS-CoV-2) in patients with mild versus severe disease remains poorly understood. Recent scientific advances have recognised the vital role of both B cells and T cells; however, many questions remain unanswered, particularly for T cell responses. T cells are essential for helping the generation of SARS-CoV-2 antibody responses but have also been recognised in their own right as a major factor influencing COVID-19 disease outcomes. The examination of T cell receptor (TCR) family differences over a 12-month period in patients with varying COVID-19 disease severity is crucial for understanding T cell responses to SARS-CoV-2. Methods: We applied a machine learning approach to analyse TCR vb family responses in COVID-19 patients (n = 151) across multiple timepoints and disease severities alongside SARS-CoV-2 infection-naïve (healthy control) individ-uals (n = 62). Results: Blood samples from hospital in-patients with moderate, severe, or critical disease could be classified with an accuracy of 94%. Furthermore, we identified significant variances in TCR vb family specificities between disease and control subgroups. Conclusions: Our findings suggest advantageous and disadvantageous TCR repertoire patterns in relation to disease severity. Following validation in larger cohorts, our methodology may be useful in detecting protective immunity and the assessment of long-term outcomes, particularly as we begin to unravel the immunological mechanisms leading to post-COVID complications. [ABSTRACT FROM AUTHOR]

Background: Even after the development of vaccines, SARS-CoV-2 continues to cause severe pneumonia all over the world. Consequently, in order to improve the management of patients and optimize the use of resources, predictors of disease severity and lung complications after COVID-19 pneumonia are urgently needed. Blood cell count is an easily available and reproducible biomarker. With this study, we aimed to explore the role of eosinophils in predicting disease behavior and pulmonary sequelae at first follow-up with computed tomography (CT). Methods: we evaluated blood cell count and other inflammatory markers, both at baseline and during hospitalization, in a large population of hospitalized COVID-19 patients. Results: 327 patients were finally enrolled, 214 were classified as low-intensity medical care (LIMC) and 113 as high-intensity medical care. Eosinophils were higher at discharge in the HIMC group [0.1 (0–0.72) vs. 0.05 (0–0.34) × 109/L; p < 0.0001]. Moreover, in the multivariable analysis, age ≥ 62 years (OR 1.76 (1.05–2.8) p = 0.03) and Δ eosinophils ≥ 0.05 (OR 1.75 (1.05–2.9) p = 0.03) were two independent predictors of residual lung abnormalities in the whole patient population at first follow-up. Conclusions: an eosinophil increase during hospitalization could be a potential predictor of pulmonary sequelae in surviving patients after COVID-19 pneumonia. [ABSTRACT FROM AUTHOR]

Background: This study analyzed weaning characteristics and assessed the association of clinical and ultrasonographic indices—maximum inspiratory pressure (MIP), rapid shallow breathing index (RSBI), peak flow expiratory (PFE), diaphragm-thickening fraction (DTF), diaphragm thickness (DT), diaphragm excursion (DE), diaphragm-RSBI (D-RSBI), and lung ultrasound (LUS) patterns—with weaning failure. Methods: This retrospective cohort study included critically ill COVID-19 patients aged 18 and older who had been on invasive mechanical ventilation for at least 48 h and undergoing weaning. Exclusion criteria included absence of ultrasound assessments, neuromuscular diseases, and chronic cardio-respiratory dysfunction. Results: Among 61 patients, 44.3% experienced weaning failure, 27.9% failed the spontaneous breathing trial (SBT), 16.4% were re-intubated within 48 h, and 28% required tracheostomy. Weaning failure was associated with prolonged ventilation (29 vs. 7 days, p < 0.001), extended oxygen therapy, longer ICU stays, and higher ICU mortality. These patients had higher pressure support, lower oxygenation levels, a higher RSBI, and a lower MIP. While PEF, DTF, DE, and D-RSBI showed no significant differences, both right and left diaphragm thicknesses and the inspiratory thickness of the left diaphragm were reduced in failure cases. LUS scores were significantly higher before and after SBT in the failure group. Bivariate analysis identified RSBI [OR = 1.04 (95% CI = 1.01–1.07), p = 0.010], MIP [OR = 0.92 (95% CI = 0.86–0.99), p = 0.018], and LUS [OR = 1.15 (95% CI = 0.98–1.35), p = 0.025] as predictors of weaning failure; however, these associations were not confirmed in multivariate analysis. Conclusions: Ultrasound provides supplementary information during weaning, but no definitive association between ultrasound indices and weaning failure was confirmed in this study. [ABSTRACT FROM AUTHOR]

Background: The neutrophil-to-lymphocyte ratio (NLR) is an independent predictor of the severity of coronary heart disease and COVID-19. This study aims to assess the predictive ability of the NLR in patients with in-stent restenosis after COVID-19. Materials and Methods: a cross-sectional study included 931 patients who underwent repeated myocardial revascularization between May 2020 and May 2023. The 420 patients of the main group had in-stent restenosis, of which 162 patients had COVID-19 previously. The control group included 511 patients without stent restenosis (107 patients had COVID-19 previously). All reported events were verified by hospital electronic records from the Complex Medical Information System. Results: The mean values of the NLR were 2.51 and 2.68 in the study groups, respectively. A statistically significant positive relationship in both groups was found between the NLR and troponin, D-dimer, C-reactive protein, creatinine, ALT, and AST. A statistically significant positive relationship was found between NLR and myocardial infarction (MI) in patients of both groups (p = 0.004; p < 0.001, respectively) and a negative relationship with the ejection fraction (p = 0.001; p < 0.036, respectively). An evaluation of the predictive ability of the clinical and laboratory predictors of recurrent myocardial infarction shows a high degree of utility of this model. The area under the ROC curve for AUC for NLR was 0.664 with 95% CI from 0.627 to 0.700 (p < 0.001). Conclusions: NLR is one of the significant factors for predicting the development of adverse outcomes in patients with revascularized myocardium after COVID-19. [ABSTRACT FROM AUTHOR]

Three types of coatings (contact-based, release-based, and combined coatings with both contact-based and release-based actions) were prepared and tested for the ability to inactivate SARS-CoV-2. In these coatings, quaternary ammonium surfactants were used as active agents since quaternary ammonium compounds are some of the most commonly used disinfectants. To provide contact-based action, the glass and silicon surfaces with covalently attached quaternary ammonium cationic surfactant were prepared using a dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride modifier. Surface modification was confirmed by attenuated total reflection infrared spectroscopy, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy, and contact angle measurements. The grafting density of the modifier was estimated by XPS and elemental analysis. To provide release-based action, the widely used quaternary ammonium cationic disinfectant, benzalkonium chloride (BAC), and a newly synthesized cationic gemini surfactant, C18-4-C18, were bound non-covalently to the surface either through hydrophobic or electrostatic interactions. Virus titration revealed that the surfaces with combined contact-based and release-based action and the surfaces with only release-based action completely inactivate SARS-CoV-2. Coatings containing only covalently bound disinfectant are much less effective; they only provide up to 1.25 log10 reduction in the virus titer, probably because of the low disinfectant content in the surface monolayer. No pronounced differences in the activity between the flat and structured surfaces were observed for any of the coatings under study. Comparative studies of free and electrostatically bound disinfectants show that binding to the surface of nanoparticles diminishes the activity. These data indicate that SARS-CoV-2 is more sensitive to the free disinfectants. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has led to an increased fear of infection, social isolation, financial concerns, and feelings of loneliness and uncertainty. Studies reveal that the pandemic has had a significant negative impact on mental health. This systematic review aimed to investigate the prevalence of depression, anxiety, and stress symptoms among students in Croatia during the COVID-19 pandemic. Methods: A systematic review was conducted following PRISMA guidelines. A literature search was performed on August 5, 2024, using the electronic databases Scopus, PubMed, Web of Science, and PsycINFO. The search utilized the Boolean logical operator expression ('depression' AND 'anxiety' AND 'stress' AND 'COVID-19' AND 'Croatia' AND 'student'). Results: Out of one hundred and fifty-four identified studies, five met the inclusion criteria and were included in the review. The studies used the Generalized Anxiety Disorder 7-item scale (GAD-7), the Patient Health Questionnaire-9 (PHQ-9), and the Depression, Anxiety, and Stress Scale-21 (DASS-21) to assess mental health. The results indicate a high prevalence of symptoms of depression, anxiety, and stress among students in Croatia during the pandemic. Conclusion: A high prevalence of negative affective emotions was observed among students in Croatia during the pandemic. This finding underscores the importance of developing effective strategies for the early identification and management of mental disorders among students, irrespective of the pandemic's conclusion. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the effects of pulmonary rehabilitation (PR) and additional progressive muscle relaxation (PMR) techniques in patients with long-term COVID-19 symptoms. Methods: We included 61 patients with long COVID-19 symptoms and randomly assigned them to two groups: PR only (group 1 with 30 subjects) and PR with PMR (group 2 with 31 subjects). The PR program consisted of gradual aerobic conditioning, strength training, and breathing exercises. Group 2 received additional 20 min daily sessions of progressive muscle relaxation techniques. Results: Following a 21-day intervention, it was observed that both groups had noteworthy improvements in lung function, exercise capacity, and sleep quality with statistical significance (p < 0.0001). Group 2 showed significant improvements in overall health (as measured by the General Health Questionnaire-12), patient health (as assessed by the Patient Health Questionnaire-9), general anxiety levels (as indicated by the Generalized Anxiety Disorders Scale-7), and sleep quality (as measured by the Pittsburgh Sleep Quality Index), with statistical significance (p < 0.0001), compared to group 1. Moreover, the statistical analysis demonstrated no significant difference in exercise capacity improvement between group 1 and group 2, as indicated by a p-value of 0.1711. Conclusions: The addition of progressive muscle relaxation to pulmonary rehabilitation significantly enhances mental health outcomes, particularly in reducing anxiety and improving sleep quality, for patients with long-term COVID-19 symptoms. These findings suggest that incorporating PMR into PR programs offers a valuable non-pharmacological approach to improving overall patient well-being during long-term COVID-19 recovery. [ABSTRACT FROM AUTHOR]

Background: Severe COVID-19 can lead to a decline in pulmonary and physical functions simultaneously. Patients experiencing significant ambulatory dysfunction often face restrictions in participating in gait training, resulting in insufficient benefits from cardiopulmonary rehabilitation. This underscores the need for tailored rehabilitation approaches that address their specific conditions. Method: This study presents a case examining the impact of combining pulmonary rehabilitation with robot-assisted gait training (RAGT) on pulmonary and physical functions in a patient with severe COVID-19 pneumonia. A 56-year-old male patient with severe COVID-19 pneumonia exhibited impaired pulmonary function, reduced lower extremity strength, compromised balance, and significant limitations in functional ambulation. He underwent an inpatient pulmonary rehabilitation program combined with RAGT for 5 weeks, participating in 30 min RAGT sessions a total of 22 times. The patient showed improvements in his pulmonary function, lower extremity strength, balance, exercise capacity, and functional mobility, along with a reduction in symptoms such as dyspnea and fatigue. Conclusions: The combination of RAGT with pulmonary rehabilitation is a treatment method that can be applied without complications and has the potential to improve pulmonary and physical functions in patients with ambulatory dysfunction due to COVID-19. [ABSTRACT FROM AUTHOR]

Background: Alexithymia, a predictor in chronic illnesses, like cardiovascular and bipolar disorder (CD–BD), could be improved with a virtual reality (VR) cognitive remediation program. This secondary analysis of a previous randomized controlled trial (RCT) evaluates alexithymia improvement and its factors in an experimental group versus a control group, exploring extensions to individuals with comorbid non-psychiatric chronic conditions. Methods: A feasibility cross-over RCT (ClinicalTrials.gov NCT05070065) enrolled individuals aged 18–75 with mood disorders (BD, DSM-IV), excluding those with relapses, epilepsy, or severe eye conditions due to potential risks with VR. Alexithymia levels were measured using the Toronto Alexithymia Scale with 20 items (TAS-20). Results: The study included 39 individuals in the experimental group and 25 in the control group, with no significant age or sex differences observed. Significantly improved alexithymia scores were noted in the experimental group compared to controls (F = 111.9; p < 0.0001) and in subgroups with chronic non-psychiatric comorbidities (F = 4.293, p = 0.048). Scores were particularly improved for difficulty in identifying feelings (F = 92.42; p < 0.00001), communicating feelings (F = 61.34; p < 0.00001), and externally oriented thinking (F = 173.12; p < 0.00001). Conclusions: The findings highlight alexithymia enhancement in BD, even with comorbid non-psychiatric chronic diseases. Given its impact on BD progression and related conditions, like CD, developing and evaluating VR-based tools in this context is suggested by these findings. [ABSTRACT FROM AUTHOR]

Background: The outbreak of the COVID-19 pandemic caught healthcare systems in many countries unprepared. Shortages of personnel, medicines, disinfectants, and intensive care unit (ICU) capacities, combined with inadvertent use of antibiotics and emergence of drug-resistant secondary infections, led to a surge in COVID-19-related mortality. Objective: We aimed to evaluate the prevalence of secondary bacterial infections and the associated antibiotic resistance in a temporary established ICU dedicated to COVID-19 patients. We also assessed the utility of clinical and routine laboratory data as predictors of secondary infections and mortality in these patients. Methods: We examined the medical records of 243 patients admitted to the COVID-19 Medical Support Unit of Târgu Mures, Romania, between 1 August 2020 and 31 January 2021. Results: Among the 243 patients admitted to the COVID-19 Medical Support Unit of Târgu Mures between 1 August 2020 and 31 January 2021, 59 (24.3%) presented secondary infections. Acinetobacter baumannii and Klebsiella pneumoniae were the most frequent isolates (31.1% and 18.9%, respectively), most of them multidrug resistant. Chronic obstructive pulmonary disease had a higher prevalence in patients who developed secondary infections (p = 0.012). Secondary infections were associated with longer stay in the ICU and with higher mortality (p = 0.006 and p = 0.038, respectively). Conclusions: Early identification of secondary infections and proper use of antibiotics are necessary to limit the spread of multidrug-resistant microorganisms in COVID-19 patients admitted in the ICU. [ABSTRACT FROM AUTHOR]

Objective: Coronavirus disease 2019 (COVID-19) can cause intubation and ventilatory support due to respiratory failure, and extubation failure increases mortality risk. This study, therefore, aimed to explore the feasibility of using specific biochemical and ventilator parameters to predict survival status among COVID-19 patients by using machine learning. Methods: This study included COVID-19 patients from Taipei Medical University-affiliated hospitals from May 2021 to May 2022. Sequential data on specific biochemical and ventilator parameters from days 0–2, 3–5, and 6–7 were analyzed to explore differences between the surviving (successfully weaned off the ventilator) and non-surviving groups. These data were further used to establish separate survival prediction models using random forest (RF). Results: The surviving group exhibited significantly lower mean C-reactive protein (CRP) levels and mean potential of hydrogen ions levels (pH) levels on days 0–2 compared to the non-surviving group (CRP: non-surviving group: 13.16 ± 5.15 ng/mL, surviving group: 10.23 ± 5.15 ng/mL; pH: non-surviving group: 7.32 ± 0.07, survival group: 7.37 ± 0.07). Regarding the survival prediction performanace, the RF model trained solely with data from days 0–2 outperformed models trained with data from days 3–5 and 6–7. Subsequently, CRP, the partial pressure of carbon dioxide in arterial blood (PaCO2), pH, and the arterial oxygen partial pressure to fractional inspired oxygen (P/F) ratio served as primary indicators in survival prediction in the day 0–2 model. Conclusions: The present developed models confirmed that early biochemical and ventilatory parameters—specifically, CRP levels, pH, PaCO2, and P/F ratio—were key predictors of survival for COVID-19 patients. Assessed during the initial two days, these indicators effectively predicted the likelihood of successful weaning of from ventilators, emphasizing their importance in early management and improved outcomes in COVID-19-related respiratory failure. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic necessitated rapid and widespread vaccination efforts, which proved critical in reducing the severity and mortality of the virus. However, the interplay between vaccinations, pre-existing skin conditions, and other comorbidities still needs to be explored. This study investigated the occurrence and severity of adverse events following immunization (AEFIs) with COVID-19 vaccines in individuals with chronic skin diseases and comorbidities within a Central European cohort. Methods: An anonymous online survey was conducted between May 2022 and February 2023, targeting students and employees of universities in Wrocław, Poland. A total of 513 respondents were analyzed, focusing on AEFIs following the first, second, and third doses of COVID-19 vaccines and the effects of COVID-19 on conditions such as atopic dermatitis, psoriasis, vitiligo, acne vulgaris, rosacea, and various comorbidities. Results: COVID-19 vaccination effectively protected against severe disease across all doses. The analysis revealed no significant impact of either COVID-19 infection or vaccination on the course of selected skin diseases and comorbidities. The reporting of AEFIs to the Sanitary Inspection was notably low. The Moderna and Pfizer mRNA-based vaccines were associated with a higher reported number of AEFIs, particularly after the second and third doses, compared to AstraZeneca, which exhibited fewer adverse events after subsequent doses. Conclusions: COVID-19 vaccination is both safe and effective, even in patients with pre-existing skin conditions and comorbidities. Vaccine selection may benefit from considering individual health profiles, and better reporting of AEFIs is needed to enhance vaccine safety monitoring. [ABSTRACT FROM AUTHOR]

Background: The trophoblast is a significant source of vitamin D synthesis during pregnancy, with the literature suggesting its role in fetal growth. We aim to underline a possible mechanism that would explain negative fetal outcomes in COVID-19-positive mothers by examining the relationship between altered placental structure and function and throphoblast cells' vitamin D receptor levels. Methods: The study included 170 placental samples collected from women who gave birth at term without complications, divided into three groups: COVID-19-positive and unvaccinated, COVID-19-negative and vaccinated, and COVID-19-negative and unvaccinated, with exclusion criteria for any other medical complications. Immunohistochemistry (IHC) was performed to detect vitamin D receptor (VDR) expression, and immediate fetal outcomes (weight and Apgar score) were assessed. Results: We found lower gestational age at birth, lower birth weight, and reduced placental VDR (vitamin D receptor) levels in COVID-19-positive women compared to COVID-19-vaccinated and COVID-19-negative women. Conclusions: The presence of the vitamin D receptor in the placenta is related to fetal and placental growth. Its deficiency may contribute to negative fetal outcomes in COVID-19-positive cases. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic affected the health of millions of people, both directly through infection and indirectly through delayed diagnosis and treatment of non-COVID-19 illnesses. The aim of this study was to check the impact of the COVID-19 pandemic on the diagnosis and treatment of appendicitis in children. Methods: The study was carried out at the Department of Paediatric Surgery of the Marciniak Hospital (Wrocław, Poland) and covered two periods, the pre-pandemic one (P1, 01/03/2019–29/02/2020) and the pandemic one (P2, 01/03/2020–28/02/2021). Results: The number of admissions of patients with suspected appendicitis and observation-only patients decreased during the pandemic (400/289 and 226/160, respectively). Although the number of operated children was similar during both analyzed periods (P1: 174, P2: 160), the rate of surgical interventions was significantly higher during P2 (55.4%) than during P1 (43.5%) (χ2 test: p = 0.00272). The values of the variables quantifying disease progression and severity of inflammation, selected inflammation-related parameters detected by laboratory blood tests, latencies from the onset of symptoms to the admission and from the admission to the operation, and total duration of hospitalization did not differ significantly between the pre-pandemic and pandemic periods. Conclusions: These results show that the COVID-19 pandemic led to more rigorous and careful triage of pediatric patients suspected of acute appendicitis that did not have a negative impact on patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Nirmatrelvir–ritonavir was granted emergency use authorization in Israel in January 2022 to treat high-risk patients with mild-to-moderate COVID-19. The aim of the study was to assess the association between nirmatrelvir–ritonavir treatment and COVID-19-related hospitalization and healthcare resource utilization (HCRU) in a country with a high level of vaccinations compared to patients who were offered treatment and declined. Methods: The Maccabi Healthcare Services dataset was used to identify high-risk SARS-CoV-2-positive adults from January to February 2022 who received nirmatrelvir–ritonavir within 5 days of symptom onset (treatment group) or who were offered nirmatrelvir–ritonavir treatment and declined it (reference group). COVID-19-related hospitalizations and all-cause mortality and HCRU within 30 days were compared between treatment and reference groups using inverse probability of treatment weighting. Results: Treatment and reference groups included 3460 (median age, 68.4 years) and 1654 (70.2 years) patients, respectively. Patients with ≥1 dose of COVID-19 vaccine accounted for 89.5% (treatment group) and 72.1% (reference group) of the total. Treatment was associated with a lower risk of COVID-19-related hospitalization (adjusted OR, 0.59 [95% CI, 0.41,0.83]). Results were similar by age group (18–64/≥65 years) and among patients with/without vaccination in the prior 180 days. There were 11 (0.3%) versus 11 (0.7%) deaths in the treatment and reference groups, respectively. Treated patients had lower inpatient HCRU and greater less intensive outpatient HCRU (e.g., telemedicine and emergency room visits). Conclusions: Nirmatrelvir–ritonavir treatment was associated with a reduced risk of COVID-19-related hospitalization and a shift to less intensive outpatient HCRU. Comparison with a reference group of nirmatrelvir–ritonavir-eligible patients who declined treatment enabled an unbiased outcome assessment. Real-world data gathered during the Omicron BA.1 variant wave of COVID-19 in Israel support the continued use of nirmatrelvir–ritonavir for high-risk adults of all ages, regardless of previous vaccinations. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the risk of hepatitis B virus reactivation (HBVr) in COVID-19 patients receiving immunosuppressive treatment, which has been insufficiently studied to date. Secondarily, we aimed to evaluate the seroprevalence of HBV infection in COVID-19 patients. Methods: We performed HBV screening on all Romanian adults hospitalized in four COVID-19 wards between October 2021 and September 2022. We enrolled patients with positive hepatitis B core antibody (anti-HBc) without protective hepatitis B surface antibody (anti-HBs), HBV treatment, or baseline immunosuppressive conditions, and we conducted a virological follow-up on these patients at 3 months. Results: We identified 333/835 (39.9%) anti-HBc-positive patients. Follow-up was performed for 13 patients with positive hepatitis B surface antigen (HBsAg) and 19 HBsAg-negative/anti-HBc-positive patients. Among those who received immunosuppressants, 4/23 (17.4%) patients experienced HBVr: 1 out of 8 (12.5%) HBsAg-positive patients (with 1.99 log increase in HBV DNA level) and 3 out of 15 (20%) HBsAg-negative/anti-HBc-positive patients (with a de novo detectable HBV DNA level). Conclusions: Administration of COVID-19 immunosuppressants may result in a significant risk of HBVr in co-infected patients. We recommend performing an HBV triple screen panel (HBsAg, anti-HBs, anti-HBc) for all COVID-19 patients receiving immunosuppressive treatment. HBV prophylaxis may be indicated in certain patients. Larger studies are needed in order to establish appropriate and cost-effective management for these patients. [ABSTRACT FROM AUTHOR]

Discovered in late 2019, the SARS-CoV-2 coronavirus has caused the largest pandemic of the 21st century, claiming more than seven million lives. In most cases, the COVID-19 disease caused by the SARS-CoV-2 virus is relatively mild and affects only the upper respiratory tract; it most often manifests itself with fever, chills, cough, and sore throat, but also has less-common mild symptoms. In most cases, patients do not require hospitalization, and fully recover. However, in some cases, infection with the SARS-CoV-2 virus leads to the development of a severe form of COVID-19, which is characterized by the development of life-threatening complications affecting not only the lungs, but also other organs and systems. In particular, various forms of thrombotic complications are common among patients with a severe form of COVID-19. The mechanisms for the development of thrombotic complications in COVID-19 remain unclear. Accumulated data indicate that the pathogenesis of severe COVID-19 is based on disruptions in the functioning of various innate immune systems. The key role in the primary response to a viral infection is assigned to two systems. These are the pattern recognition receptors, primarily members of the toll-like receptor (TLR) family, and the complement system. Both systems are the first to engage in the fight against the virus and launch a whole range of mechanisms aimed at its rapid elimination. Normally, their joint activity leads to the destruction of the pathogen and recovery. However, disruptions in the functioning of these innate immune systems in COVID-19 can cause the development of an excessive inflammatory response that is dangerous for the body. In turn, excessive inflammation entails activation of and damage to the vascular endothelium, as well as the development of the hypercoagulable state observed in patients seriously ill with COVID-19. Activation of the endothelium and hypercoagulation lead to the development of thrombosis and, as a result, damage to organs and tissues. Immune-mediated thrombotic complications are termed "immunothrombosis". In this review, we discuss in detail the features of immunothrombosis associated with SARS-CoV-2 infection and its potential underlying mechanisms. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) patients face different health challenges when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general population, due to both their immunocompromised state and the immunosuppressive therapies they receive. This systematic literature review, which follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) paradigm, explores the interactions between RA and SARS-CoV-2 infection, focusing on immunologic issues, disease management, vaccination, and adverse outcomes. In order to obtain the most relevant information, we systematically reviewed the specific literature from 1 January 2021 to 31 December 2023, based on the PRISMA method, by which we eventually selected 35 eligible articles, to which we added other ISI-indexed studies to enrich our results further. Consequently, we performed a funnel analysis to evaluate the potential for publication bias. Firstly, the data collected revealed the impact of the pandemic on RA diagnoses and the fear of face-to-face medical consultations that delayed adequate treatment. Secondly, cardiovascular and metabolic comorbidities increase the risk of prolonged COVID-19 symptoms, hospitalization, and severe COVID-19 outcomes for RA patients. With respect to immunosuppressive treatment used to control RA, it was observed that glucocorticoids (especially high-dose usage) and Rituximab (RTX) predispose the patients to poor SARS-CoV-2 outcomes, as opposed to Baricitinib and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) inhibitors. COVID-19 vaccination has proven effective and generally safe for RA patients in some studies, although therapies with Methotrexate (MTX), Abatacept (ABA), and RTX have been associated with impaired vaccine immune response. This systematic literature review brings updated and thorough information with respect to the immunological, clinical, and management of a complex immune-mediated inflammatory disease (IMID) like RA in the setting of COVID-19 and underlines the challenges faced by this group of patients. The lessons learned can be extended beyond the pandemic in shaping a more informed and compassionate healthcare system and offering long-term medical care for patients with RA. [ABSTRACT FROM AUTHOR]

The present study aimed to identify in patients with severe COVID-19 and acute respiratory distress syndrome (ARDS) the association between rs3804099 and rs3804100 (TLR2) and evaluate the expression of TLR-2 on the cell surface of innate and adaptive cells of patients' carriers of C allele in at least one genetic variant. We genotyped 1018 patients with COVID-19 and ARDS. According to genotype, a subgroup of 12 patients was selected to stimulate peripheral blood mononuclear cells (PBMCs) with spike and LPS + spike. We evaluated soluble molecules in cell culture supernatants. The C allele in TLR2 (rs3804099, rs3804100) is not associated with a risk of severe COVID-19; however, the presence of the C allele (rs3804099 or rs3804100) affects the TLR-2 ability to respond to a spike of SARS-CoV-2 correctly. The reference group (genotype TT) downregulated the frequency of non-switched TLR-2+ B cells in response to spike stimulus; however, the allele's C carriers group is unable to induce this regulation, but they produce high levels of IL-10, IL-6, and TNF-α by an independent pathway of TLR-2. Findings showed that TT genotypes (rs3804099 and rs3804100) affect the non-switched TLR-2+ B cell distribution. Genotype TT (rs3804099 and rs3804100) affects the TLR-2's ability to respond to a spike of SARS-CoV-2. However, the C allele had increased IL-10, IL-6, and TNF-α by stimulation with spike and LPS. [ABSTRACT FROM AUTHOR]

The emergence of hitherto unknown viral pathogens presents a great challenge for researchers to develop effective therapeutics and vaccines within a short time to avoid an uncontrolled global spread, as seen during the coronavirus disease 2019 (COVID-19) pandemic. Therefore, rapid and simple methods to identify immunogenic antigens as potential therapeutical targets are urgently needed for a better pandemic preparedness. To address this problem, we chose the well-characterized Modified Vaccinia virus Ankara (MVA)-T7pol expression system to establish a workflow to identify immunogens when a new pathogen emerges, generate candidate vaccines, and test their immunogenicity in an animal model. By using this system, we detected severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) nucleoprotein (N)-, and spike (S)-specific antibodies in COVID-19 patient sera, which is in line with the current literature and our observations from previous immunogenicity studies. Furthermore, we detected antibodies directed against the SARS-CoV-2-membrane (M) and -ORF3a proteins in COVID-19 patient sera and aimed to generate recombinant MVA candidate vaccines expressing either the M or ORF3a protein. When testing our candidate vaccines in a prime-boost immunization regimen in humanized HLA-A2.1-/HLA-DR1-transgenic H-2 class I-/class II-knockout mice, we were able to demonstrate M- and ORF3a-specific cellular and humoral immune responses. Hence, the established workflow using the MVA-T7pol expression system represents a rapid and efficient tool to identify potential immunogenic antigens and provides a basis for future development of candidate vaccines. [ABSTRACT FROM AUTHOR]