NETosis, the process through which neutrophils release neutrophil extracellular traps (NETs), has emerged as a crucial mechanism in host defense and the pathogenesis of autoimmune responses. During the SARS-CoV-2 pandemic, this process received significant attention due to the central role of neutrophil recruitment and activation in infection control. However, elevated neutrophil levels and dysregulated NET formation have been linked to coagulopathy and endothelial damage, correlating with disease severity and poor prognosis in COVID-19. Moreover, it is known that SARS-CoV-2 can induce persistent low-grade systemic inflammation, known as long COVID, although the underlying causes remain unclear. It has been increasingly acknowledged that excessive NETosis and NET generation contribute to further pathophysiological abnormalities following SARS-CoV-2 infection. This review provides an updated overview of the role of NETosis in autoimmune diseases, but also the relationship between COVID-19 and long COVID with autoimmunity (e.g., latent and overt autoimmunity, molecular mimicry, epitope spreading) and NETosis (e.g., immune responses, NET markers). Finally, we discuss potential therapeutic strategies targeting dysregulated NETosis to mitigate the severe complications of COVID-19 and long COVID.

IntroductionCOVID-19, caused by the SARS-CoV-2 virus, has resulted in a global public health crisis with a wide spectrum of clinical manifestations, ranging from asymptomatic infections to severe pneumonia. This study explores the association between various biomarkers and COVID-19 progression, aiming to identify early indicators of disease severity and enhance patient management.Materials and MethodsThe study included 750 confirmed COVID-19 patients categorized into four groups based on disease severity. Patients were recruited at the General Hospital in Tešanj, Bosnia and Herzegovina. All biochemical, hematological and coagulation parameters were analyzed using standard IFCC protocols.ResultsThe study identified significant differences in biochemical, hematological, and coagulation biomarkers across varying COVID-19 severities. Key markers such as C-reactive protein (CRP), D-dimer, lymphocyte count, erythrocyte sedimentation rate (ESR), and platelet count were analyzed. Elevated CRP and D-dimer were strongly linked to severe cases, while decreased lymphocyte count, elevated ESR, and platelet abnormalities were also associated with increased disease severity.ConclusionsOur study highlights the vital role of specific biochemical, hematological and coagulation parameters in predicting COVID-19 severity. Integrating these findings into clinical practice could enhance timely risk stratification, early intervention, and improved outcomes for affected individuals.

There are two methods of studying multiple mediation: network-based and analysis of coefficients in regression equations.

This tutorial shows how multiple mediation analysis can be conducted through first constructing causal networks; and then evaluating the direct and mediated impact within the network. The proposed method is demonstrated in the context of diagnosing COVID-19 from its symptoms.

822 individuals who had completed a COVID-19 test were recruited through listservs and via employees and patients of Virginia Commonwealth University Health Center. Participants reported their symptoms and which symptom(s) occurred first. A Causal Network model was established through a repeated chain of regressions in four steps: First, we identified the order of occurrence of symptoms. Second, COVID-19 test results were LASSO regressed on symptoms and demographic variables, establishing direct effects. Third, the direct effects were LASSO regressed on prior symptoms and demographic variables, establishing indirect effects. Fourth, the joint distribution of the variables in the network was simulated by evaluating regression equations at factorial combinations of their direct effects. Fifth, the mediated effect was calculated through twin modeling, where the model derived from the real data was compared to the counterfactual model that represented 'what if' there was no mediation.

The 10-fold cross-validated area under the receiver curve for the network model was 0.82, which is a moderate to high level of accuracy. The network model identified later symptoms (e.g., chills) mediated the effect of earlier symptoms (e.g. fever).

A network-based multiple mediation analysis led to new insights by integrating findings of 19 separate regressions into a single network model. The procedure showed how artificial intelligence can help in triage of COVID-19 patients from their symptoms, before any home or laboratory tests.

Interstitial capillary congestion and diffuse alveolar damage (DAD) were frequently observed in patients who died from Coronavirus disease-19 (COVID-19). The research question pertains to observing these findings in COVID-19-positive patients lacking pulmonary symptoms. The histological examination of lung samples from COVID-19-positive patients who do not succumb to COVID-19-related pulmonary complications can provide an answer. This study analyzed postmortem lung autopsy samples from individuals who did not succumb to COVID-19-related pulmonary complications. The research article aimed to examine the morphological variations in postmortem lung samples of COVID-19 patients who did not succumb to the disease, and to compare these changes with those observed in cases of COVID-19-related deaths, utilizing existing English literature.

This prospective study included subjects who died without complications from COVID-19-related injuries, had positive real-time polymerase chain reaction throat swabs, and exhibited no pulmonary manifestation of COVID-19 disease. A comprehensive histomorphological analysis of the lung samples was conducted.

A total of 20 subjects were enrolled in this study. Capillary congestion was the most prevalent histomorphological change observed in lung autopsies, seen in 90% (18/20) of cases, followed by emphysema in 75% (15/20) and the acute phase of DAD in 25% (5/20) of cases. Acute bronchopneumonia and fibrotic nodules were identified in 20% (4/20) and 10% (2/20) of the study population, respectively.

In postmortem lung autopsy of COVID-19-positive patients lacking symptomatic pulmonary issues, capillary congestion, diffuse alveolar destruction, and emphysema were prevalent. The findings indicate that COVID-19 exhibits varied responses to damage and inflammation that do not correlate with mortality. This study enhances the understanding of pathophysiological lung tissue variations in COVID-19 patients who have non-COVID-19-related deaths, potentially educating forensic pathologists and supporting future research endeavors.

Anti-infective agents are a class of drugs used to prevent, treat, or control infections caused by microorganisms such as bacteria, viruses, fungi, and parasites. They play a crucial role in modern medicine, helping to reduce the severity of infections and, in many cases, save lives. This study aims at the design and synthesis of hybrid compounds containing quinoxaline, pyrrolidine, and an azo bridge to combat antimicrobial resistance, and evaluating their antimicrobial, antifungal, and antiviral activities against various pathogenic strains. Eight most potent bactericidal derivatives 2, 4, 5, 7, 9, 11, 12, and 13 were further assessed for their antibiofilm activity. Additionally, these compounds were tested for their inhibitory effects on DNA gyrase using a DNA supercoiling assay with IC50 ranging from 26.57 to 84.84 μM when compared to ciprofloxacin as standard drug. The antiviral activities were performed against HSV-1, H1N1 and SARS-CoV-2 viruses, which showed that compound 9 has the highest antiviral activity with IC50 = 0.32 µM, IC50 = 1.76 µM and 1.06 µM, respectively, as well as the best safety profile with CC50 = 30000 µM. Compound 9 displayed the highest SI value against HSV-1, H1N1 and SARS-CoV-2 with values of 93685, 17,034 and 28368, respectively. Compound 9 inhibited RdRp and spike glycoprotein (IC50 = 2.437 ± 0.102 and 1425.1 ± 55.3 nM; respectively). The physicochemical and pharmacokinetic properties of the most active compounds were screened to identify those with optimal drug-like characteristics. Molecular docking studies were conducted on the most effective compounds to elucidate their binding interactions and mechanisms of action.

This review explores the synergistic potential of natural products and nanotechnology for viral infections, highlighting key antiviral, immunomodulatory, and antioxidant properties to combat pandemics caused by highly infectious viruses. These pandemics often result in severe public health crises, particularly affecting vulnerable populations due to respiratory complications and increased mortality rates. A cytokine storm is initiated when an overload of pro-inflammatory cytokines and chemokines is released, leading to a systemic inflammatory response. Viral mutations and the limited availability of effective drugs, vaccines, and therapies contribute to the continuous transmission of the virus. The coronavirus disease-19 (COVID-19) pandemic has sparked renewed interest in natural product-derived antivirals. The efficacy of traditional medicines against pandemic viral infections is examined. Their antiviral, immunomodulatory, anti-inflammatory, and antioxidant properties are highlighted. This review discusses how nanotechnology enhances the efficacy of herbal medicines in combating viral infections.

Understanding the progression and recovery process of COVID-19 is crucial for guiding public health strategies and developing targeted interventions. This longitudinal cohort study aims to elucidate the dynamics of COVID-19 severity progression and evaluate the impact of underlying health conditions on these transitions, providing critical insights for more effective disease management.

Data from 4549 COVID-19 patients admitted to Seoul National University Boramae Medical Center between February 5th, 2020, and October 30th, 2021, were analyzed using a 5-state continuous-time Markov multistate model. The model estimated instantaneous transition rates between different levels of COVID-19 severity, predicted probabilities of state transitions, and determined hazard ratios associated with underlying comorbidities.

The analysis revealed that most patients stabilized in their initial state, with 72.2% of patients with moderate symptoms remaining moderate. Patients with hypertension had a 67.6% higher risk of progressing from moderate to severe, while those with diabetes had an 89.9% higher risk of deteriorating from severe to critical. Although transition rates to death were low early in hospitalization, these comorbidities significantly increased the likelihood of worsening conditions.

This study highlights the utility of continuous-time Markov multistate models in assessing COVID-19 severity progression among hospitalized patients. The findings indicate that patients are more likely to recover than to experience worsening conditions. However, hypertension and diabetes significantly increase the risk of severe outcomes, underscoring the importance of managing these conditions in COVID-19 patients.

Non-specific symptoms, such as headaches and sleep problems, are more common after disasters. They can become chronic, and impact emotional and physical functioning. However, limited research has focused on such symptoms in the context of a pandemic. This study investigated the association between perceived impact of the COVID-19 pandemic, and prevalence, duration, and severity of health symptoms.

A cross-sectional survey using validated questionnaires was conducted shortly after the first COVID-19 wave in 2020, with nearly 46,000 adult participants from Utrecht, the Netherlands. Negative binomial regression analyses were performed to assess the relationship between pandemic-related factors and symptom reports, adjusting for demographics, chronic conditions, lifestyle, and socio-economic status.

Perceived impact of the pandemic on stress levels, loneliness, anxiety and depression was consistently and significantly associated with symptom report, duration, and perceived severity. Incidence rate ratio's (IRR) varied from 1.17 to 1.29. Delayed care during the pandemic was associated with severity of symptoms (IRR = 1.63; 99% confidence intervals (CI): 1.20-2.20). People that (suspected) got COVID-19 infected were at higher risk of symptom report, duration, and perceived severity (IRR around 1.20-1.28).

As with other disasters, the perceived impact of an immediate threat such as a pandemic can influence health symptoms, independent of health or socio-demographic factors. Understanding symptom patterns and risk factors can assist healthcare professionals and policymakers in identifying vulnerable groups, symptoms profiles, and improving care and support during and after pandemics.

SARS-CoV-2 responsible for the COVID-19 pandemic, infiltrates the human body by binding to the ACE2 receptor in the respiratory system cell membranes, leading to severe lung tissue damage. An analog of ACE2, ACE1, has gained attention due to its well-known Deletion/Insertion (D/I) polymorphism, which seems to be associated with COVID-19 outcomes. This study aims to reveal the allelic and genotypic frequencies of the rs4646994 polymorphism in the Moroccan population and investigate the association between COVID-19 outcomes and both genotypic and demographic data.

We screened 162 Moroccan COVID-19 patients for the ACE1 gene D/I polymorphism using PCR amplification of the ACE1 polymorphic region within intron 16. Statistical analysis of the relationship between COVID-19 outcomes and each of the genetic and demographic data was performed using R software. The D allele was present in 74% of subjects. Homozygous (II) and heterozygous (DI) genotypes for the Insertion allele were present in 41.4% and 5.6% of patients, respectively. The median age in the COVID-19 'critical symptoms' category was significantly higher and gradually decreased with less severe symptoms. Similarly, males were significantly overrepresented in the 'critical symptoms' category, while females predominated in the 'mild symptoms' category.

The present study reports the prevalence of ACE1 D/I alleles for the first time in the Moroccan population and confirms the strong association of severe COVID-19 outcomes with male sex and older age. Moreover, this work is the first to explore the relationship between ACE1 D/I polymorphism and COVID-19 clinical outcomes in North African adults. The lack of a significant association may be due to cohort size or population-specific factors. A comprehensive investigation in a larger North African cohort is highly recommended.

Disease prediction using computer-based methods is now an established area of research. The importance of technological intervention is necessary for the better management of disease, as well as to optimize use of limited resources. Various AI-based methods for disease prediction have been documented in the literature. Validated AI-based systems support diagnoses and decision making by doctors/medical practitioners. The resource-efficient dissemination of the symptoms identified and the diagnoses undertaken is the requirement of the present-day scenario to support paperless, yet seamless, information sharing. The representation of symptoms using grammar provides a novel way for the resource-efficient encoding of disease diagnoses. Initially, symptoms are represented as strings, and, in terms of grammar, this is called a sentence. Moreover, the conversion of the generated string containing the symptoms and the diagnostic outcome to a QR code post encryption makes it portable. The code can be stored in a mobile application, in a secure manner, and can be scanned wherever required, universally. The patient can carry the medical condition and the diagnosis in the form of the QR code for medical consultations. This research work presents a case study based on two diseases, influenza and coronavirus, to highlight the proposed methodology. Both diseases have some common and overlapping symptoms. The proposed system can be implemented for any kind of disease detection, including clinical and diagnostic imaging.

Invasive mold infections (IMI) have become common in patients with severe COVID-19 pneumonia, which are difficult to diagnose and treat, with a high mortality rate.

The aim of this study was to determine risk factors for invasive mold infections associated with COVID-19.

In this prospective, case-control study, patients treated for severe COVID-19 pneumonia in intensive care units with invasive mold infection were compared with severe COVID-19 pneumonia patients with no secondary infection (bacterial or fungal). Demographics, treatments received and outcomes were compared.

Twenty patients were included in the IMI group and 19 patients in the control group. Invasive aspergillosis was observed in 13 patients (65.0%) while mucormycosis was observed in seven patients (35.0%). Demographics and clinical characteristics were similar between IMI and control group (p>0.005). The 28-day mortality was 60.0% in the IMI group and 15.8% in the control group (p=0.005). The use of steroids has been identified as the most important risk factor for developing IMI (90.0% vs. 15.8%, OR: 25.712, p=0.009).

Rationale use of steroids, with appropriate indication, dose and duration is important in the treatment of severe COVID-19 pneumonia.

In this study, we introduce a novel approach that integrates interpretability techniques from both traditional machine learning (ML) and deep neural networks (DNN) to quantify feature importance using global and local interpretation methods. Our method bridges the gap between interpretable ML models and powerful deep learning (DL) architectures, providing comprehensive insights into the key drivers behind model predictions, especially in detecting outliers within medical data. We applied this method to analyze COVID-19 pandemic data from 2020, yielding intriguing insights. We used a dataset consisting of individuals who were tested for COVID-19 during the early stages of the pandemic in 2020. The dataset included self-reported symptoms and test results from a wide demographic, and our goal was to identify the most important symptoms that could help predict COVID-19 infection accurately. By applying interpretability techniques to both machine learning and deep learning models, we aimed to improve understanding of symptomatology and enhance early detection of COVID-19 cases. Notably, even though less than 1% of our cohort reported having a sore throat, this symptom emerged as a significant indicator of active COVID-19 infection, appearing 7 out of 9 times in the top four most important features across all methodologies. This suggests its potential as an early symptom marker. Studies have shown that individuals reporting sore throat may have a compromised immune system, where antibody generation is not functioning correctly. This aligns with our data, which indicates that 5% of patients with sore throats required hospitalization. Our analysis also revealed a concerning trend of diminished immune response post-COVID infection, increasing the likelihood of severe cases requiring hospitalization. This finding underscores the importance of monitoring patients post-recovery for potential complications and tailoring medical interventions accordingly. Our study also raises critical questions about the efficacy of COVID-19 vaccines in individuals presenting with sore throat as a symptom. The results suggest that booster shots might be necessary for this population to ensure adequate immunity, given the observed immune response patterns. The proposed method not only enhances our understanding of COVID-19 symptomatology but also demonstrates its broader utility in medical outlier detection. This research contributes valuable insights to ongoing efforts in creating interpretable models for COVID-19 management and vaccine optimization strategies. By leveraging feature importance and interpretability, these models empower physicians, healthcare workers, and researchers to understand complex relationships within medical data, facilitating more informed decision-making for patient care and public health initiatives.

Despite herbal medicine being popular across the Mediterranean basin, there is no evidence in favor of COVID-19 infection. This study investigates the utilization and effects of medicinal plants in Italy, Lebanon, and Tunisia during COVID-19 and its effects on post-COVID-19 pandemics. We used a tailored, web-based "Google Form" questionnaire with the random sampling method. We gathered 812 complete responses (Italy: 116, Lebanon: 557, and Tunisia: 139), revealing diverse demographics and symptom experiences. Fatigue prevailed across all groups (89.0-94.2%), while psychological impacts ranged from 20.1% to 30.9%, with higher rates in Lebanon. Post-COVID-19 symptoms affected 22.4% (Italy), 48.8% (Lebanon), and 31.7% (Tunisia). General use of herbs was consistent (41.4-50.4%), with 23.3% (Italy), 50.2% (Lebanon), and 65.5% (Tunisia) employing herbs for COVID-19 therapy. Notably, in Lebanon, Za'atar, a thyme-like plant, correlated with reduced symptoms, suggesting potential protective effects that are likely due to its polyphenol richness. This study underscores the persistent reliance on traditional medicinal plants remedies in the Mediterranean area, with regional variations. Further exploration of herbal compounds for COVID-19-like symptoms is warranted.

Severe acute respiratory coronavirus-2 (SARS-CoV-2) emerged in 2019 as a new virus and caused worldwide outbreaks, quickly turning into a pandemic disease called coronavirus disease-19 (COVID-19). All the existing methodologies were used for developing vaccines for this virus. But sporadic infections of this virus and the emergence of new strains to date suggest the incomplete protection offered by the developed vaccines and the need for new research. In this direction, we identified five epitopes present in the non-RBD region and on the surface of the spike protein by in silico analysis. They are epitope I (aa 80-90), epitope II (aa 262-270), and a small protein with three epitopes (aa 1059-1124). Antigenicity scores of these epitopes were found to be higher than the full length spike protein and its RBD region. These epitopes showed high conserveness across the emerging strains, high immunogenicity, non-toxicity, no homology with human sequences and high affinity for MHC class I & II molecules. Antibodies raised against these epitopes interacted with the bacterially expressed spike protein in western blotting. The antiserum of COVID-19 recovered participants reacted with the developed epitopes (small protein). Furthermore, in the presence of the respective antiserum and COVID-19 convalescent serum, these epitopes successfully fixed the complement, implying a possible role in innate immunity. The epitopes were also found to activate the peripheral blood mononuclear cells (PBMCs) isolated from the blood samples of COVID-19 recovered/vaccinated participants, suggesting a possible role in adaptive immunity. The need for the new SARS-CoV-2 vaccines is further highlighted in light of current reports about the side effects of a developed vaccine (AstraZeneca) and the circulating new strains. The epitopes presented in this study represent the potential immunogens and expect certain pitfalls of the existing vaccines would be sealed.

The COVID-19 pandemic has led to an increase in the prevalence of anxiety, stress and depression among affected people. This study was conducted with the aim of investigating the clinical effectiveness of guided breathing exercises in reducing anxiety, stress and depression in patients with COVID-19. A quasi-experimental study design was used, involving a sample of COVID-19 patients who underwent guided breathing exercises as a complementary therapy. After simple sampling, eligible subjects were randomly divided into two groups: intervention (30 patients) and control (30 patients) using random block method. The Depression Anxiety Stress Scale-21 (DASS-21) questionnaire was administered before and after the intervention to evaluate changes in anxiety, stress, and depression levels. The results of this study demonstrated that clinically guided breathing exercises had a significant effect on reducing anxiety and stress in COVID-19 patients. The intervention significantly reduced anxiety and stress scores (p < 0.001). However, there was no significant reduction in depression scores among patients who participated in guided breathing exercises (p = 0.946). Guided breathing exercises are an effective complementary technique in reducing the level of anxiety and stress in COVID-19 patients. Moreover, the exercises may provide a worthy non-pharmacological approach to managing psychological distress in COVID-19 patients.

Cough is one of the most common symptoms observed in patients presenting with COVID-19, persisting for an extended duration following SARS-CoV-2 infection. We aim to describe the distribution of airway microbiota and explore its role in patients with post-COVID-19 chronic cough. A total of 57 patients experiencing persistent cough after infection were recruited during the Omicron wave of SARS-CoV-2 in China. Airway microbiota profiling is assessed in nasopharyngeal swab, nasal lavage, and induced sputum samples at 4 and 8 weeks after SARS-CoV-2 infection. Our findings reveal that bacterial families Staphylococcaceae, Corynebacteriaceae, and Enterobacteriaceae are the most prevalent in the upper airway, while Streptococcaceae, Lachnospiraceae, and Prevotellaceae emerge as the most prevalent bacterial families in the lower airway. An increase in the abundance of Staphylococcus in nasopharyngeal swab samples and of Streptococcus in induced sputum samples is observed after one month. Furthermore, the abundance of Staphylococcus identified in nasopharyngeal swab samples at the baseline period emerges as an insightful predictor for improvement in cough severity. In conclusion, dynamic alterations in the airway microbial composition may contribute to the post-COVID-19 chronic cough progression, while the compositional signatures of nasopharyngeal microbiota could reflect the improvement of this disease.

The spread of the SARS-CoV-2 virus has had an unprecedented impact, both by posing a serious risk to human health and by amplifying the burden on the global economy. The rapid identification of the SARS-CoV-2 virus has been crucial to preventing and controlling the spread of SARS-CoV-2 infections. In this study, we propose a multilayered plasmonic nanotrap (MPNT) device for the rapid identification of single particles of SARS-CoV-2 virus in ultra-high sensitivity by surface-enhanced Raman scattering (SERS). The MPNT device is composed of arrays of concentric cylindrical cavities with Ag/SiO2/Ag multilayers deposited on the top and at the bottom. By varying the diameter of the cylinders and the thickness of the multilayers, the resonant optical absorption and local electric field were optimized. The SERS enhancement factors of the proposed device are of the order of 108, which enable the rapid identification of SARS-CoV-2 N protein in concentrations as low as 1.25 × 10-15－12.5 × 10-15 g mL-1 within 1 min. The developed MPNT SERS device provides a label-free and rapid detection platform for SARS-CoV-2 virus. The general nature of the device makes it equally suitable to detect other infectious viruses.

Pregnancy is a critical time for women, making them more susceptible to infectious diseases like COVID-19. This study aims to determine the immunogenicity of COVID-19 in pregnant women who have been infected compared to those who have received the inactive COVID-19 vaccine.

In this retrospective cohort study, pregnant women who received the inactivated COVID-19 vaccine (Sinopharm) and those with a history of COVID-19 infection during pregnancy were studied. Participants who had experienced stillbirth, received different COVID-19 vaccines, or had intrauterine fetal death were excluded from the study. Overall, the study included 140 participants. The participants were divided into two groups of 70 participants - pregnant women who received the Sinopharm vaccine and pregnant women who had COVID-19 infection during pregnancy. Before delivery, blood samples were collected from all mothers to evaluate the maternal immunoglobulin G (IgG) level. Blood samples were also taken from the baby's umbilical cord during delivery to measure the newborn's IgG level. Additionally, blood samples were collected from babies whose mothers showed signs of acute infection to measure their IgM levels and evaluate vertical transmission.

The study found a significant relationship between the mean level of maternal IgG and umbilical cord IgG within the groups (P < 0.001). The highest levels of maternal IgG (2.50 ± 2.17) and umbilical cord IgG (2.43 ± 2.09) were observed in pregnant women with a previous COVID-19 infection and no history of vaccination (P < 0.001). Only one baby was born with a positive IgM, and this baby was born to a mother who showed signs of COVID-19 infection in the last five days of pregnancy. The mother was 28 years old, with a BMI of 33; it was her first pregnancy, and she gave birth to a male newborn at term.

Administering an inactivated vaccine during pregnancy can generate immunity in both the mother and the child. However, the vaccine's immunity level may not be as potent as that conferred by COVID-19 infection during pregnancy. Nonetheless, the risk of vertical transmission of COVID-19 is considered minimal and can be classified as negligible.

The aim of the study was to conduct of relationship of acute-phase proteins (APPs) with the severity of COVID-19 defined by National Institutes of Health and according to the criteria of MEWS scale, with the presence of a cytokine storm, oxygen therapy and patient survival. We enrolled 96 patients with COVID-19 and 30 healthy people. The samples were taken on the day of admission and after 9 days on average. Not only commonly used APPs such as CRP, procalcitonin and ferritin and also rarely assayed proteins such as transferrin, haptoglobin, α1-acid glycoprotein and α1-antitrypsin, were tested in the study. The levels of APPs depends on the severity of COVID-19 disease, on the presence of cytokine storm and used oxygen therapy. The greatest APPs changes occurred in the most advanced form of the disease, with the presence of a cytokine storm and the most intense oxygen therapy. The results obtained from MEWS scale were not consistent with National Institutes of Health scores. Studies in the second samples showed the quenching of the acute phase reactions and the effectiveness of oxygen therapy. Only two of the examined APPs i.e. procalcitonin and transferrin, differed between surviving and non-surviving patients, and these two predispose to the role of prognostic factors in Covid-19. In conclusion, the concentration of not all acute-phase proteins depends on the severity of COVID-19 disease, presence of cytokine storm, the used of oxygen therapy and only some of them (procalcitonin and transferrin) are related to the survival outcomes. Of the newly tested acute-phase proteins, only transferrin shows significance as a marker of disease severity and mortality in COVID-19 disease.

Objective: The COVID-19 pandemic has posed significant global health challenges. Despite extensive research efforts, the inflammatory response triggered by SARS-CoV-2 remains to be further explored and understood. Our study aims to examine the changes in serum concentrations of pro-inflammatory adipokines-visfatin and leptin-in COVID-19 patients in relation to a healthy control group. Patients/Materials/Subjects and Methods: The study consisted of forty COVID-19 patients and twenty-four healthy patients in the control group. Two serum samples were collected: upon admission and on the seventh day of hospitalization. Concentrations of visfatin and leptin in the serum, alongside routine biochemical parameters, were measured using enzyme immunoassay or enzyme-linked immunosorbent assay kits. The Shapiro-Wilk test was used to assess normality. Differences between independent groups were compared using the Mann-Whitney U test and Kruskal-Wallis ANOVA. Correlations were evaluated with Spearman's rank correlation coefficient. Results: Our findings revealed significantly lower visfatin levels in COVID-19 patients compared to the control group upon admission (4.29 ng/mL, (3.0-6.88 ng/mL) vs. 37.16 ng/mL (24.74-50.12 ng/mL), p < 0.001 for visfatin 1 and 52.05 ng/mL, (31.2-69.66 ng/mL) vs. 37.16 ng/mL (24.74-50.12 ng/mL), p = 0.048 for visfatin 2). The visfatin level of COVID-19 patients returned to the normal levels, established in the control group. However, there was no significant difference in leptin levels between the two groups (p = 0.270 for leptin 1 and p = 0.129 for leptin 2). There was a positive correlation between BMI and leptin concentration (r = 0.66 and p = 0.00). Moreover, it was discovered that COVID-19 independently reduces visfatin levels during the first day of illness. Conclusions: The results of our research suggest that the onset of COVID-19 infection is correlated to visfatin levels. Association with leptin levels remains inconclusive. Further research is imperative to elucidate the intricate role of visfatin and leptin in SARS-CoV-2 infection and their potential as biomarkers for COVID-19 severity and prognosis.

Host genetic variations have been identified as potential influencers of COVID-19 infection. This study aimed to examine the association between transmembrane serine protease type 2 (TMPRSS2) rs2070788 single nucleotide polymorphism (SNP) and the prognosis of COVID-19 in Iranian populations.

This case-control study was performed on 756 COVID-19 patients and 59 healthy individuals across Iran. Clinical data, blood samples, and the presence of the TMPRSS2 rs2070788: G>A SNP were determined using T-ARMS-PCR. Additionally, serum levels of tumor necrosis factor α (TNF-α), C-reactive protein (CRP), interleukin-6 (IL-6), and IL-1β were evaluated in the collected blood samples.

No significant association was found between the genotypes and allele frequencies of TMPRSS2 rs2070788 SNP and susceptibility to or mortality from COVID-19 infection. However, we observed a substantial increase in IL-6 and CRP levels associated with the severity of COVID-19, while no such trend was observed for IL-1β and TNF-α. This study showed a considerable rise in TNF-α and IL-1β serum levels exclusively in COVID-19 patients with TT rs2070788 TMPRSS2 SNP genotype compared to healthy controls.

In this study conducted across multiple cities in Iran, no significant association was found between the TMPRSS2 rs2070788 SNP genotypes and COVID-19 severity or mortality.

The complication of hydropneumothorax and colovesical fistula is rare, especially in patients with tuberculosis (TB) and COVID-19. This particular situation poses a management difficulty, and can significantly threaten the patient's life without a clear diagnosis and timely treatment. We report a 28-year-old woman with pulmonary and intestinal TB with COVID-19 complicated with hydropneumothorax and colovesical fistula (CVF) which worsened her condition. Treatment for this patient was given according to the diagnosis. Her condition improved and she was discharged after 30 days of hospitalization, while elective surgery for CVF was not performed because there were no clinical symptoms complained of by this patient after completing TB treatment (9 months after hospital discharge). This case report highlights the importance of considering pulmonary and intestinal TB with COVID-19 as the cause of hydropneumothorax and CVF. Early and complex diagnosis is essential for proper management, as well as the efficacy of medical therapy and treatment for controlling such advanced stages of the disease. A complex condition with many symptoms can overlap with other diseases. Clinicians should consider the clinical symptoms, radiological imaging, and standard or supporting examination for accurate diagnosis to find the etiology of the diseases. Complete treatment for TB should be considered as the treatment choice (nonsurgical therapy) for CVF caused by TB before deciding on surgical intervention.

With the emergence of novel variants, Omicron variant caused a different clinical picture than the previous variants and little evidence was reported regarding perioperative outcomes after Omicron variants. The aim of the study was to evaluate the postoperative outcomes of gastrointestinal cancer patients following Omicron variants infection and also to determine the timing of surgery after infection recovery. A total of 124 patients who underwent gastrointestinal cancer surgery with prior SARS-CoV-2 infection between December 2022 and February 2023 were retrospectively reviewed. 174 cases underwent the same operation during December 2018 and February 2019 as control group. SARS-CoV-2-infected patients were further categorized into three groups based on infected time (1-3 weeks; 4-6 weeks; and ≥ 7 weeks). 90.3% of SARS-CoV-2-infected patients had mild symptoms. The COVID-19 vaccination rate was 71.0%, with a full vaccination rate of 48.4%. There were no significant differences in 30-day morbidity and mortality. There was also no significant difference in pulmonary complications, cardiovascular complications, and surgical complications between the three different diagnosis time groups. In conclusion, reducing waiting time for elective surgery was safe for gastrointestinal cancer patients in the context of an increased transmissibility and milder illness severity with Omicron variant.

To assess the association of single nucleotide polymorphisms (SNPs) in the ACE2 and TMPRSS2 genes with COVID-19 severity and key biomarkers.

The study involved 750 COVID-19 patients from Bosnia and Herzegovina, divided into three groups: mild, moderate, and severe cases. Genetic variations within the ACE2 (rs2285666) and TMPRSS2 (rs2070788) genes were examined with real-time polymerase chain reaction. Biochemical markers were determined with standard procedures.

There was a significant difference in the rs2070788 genotype distribution between patients with mild and moderate symptoms, but not between other groups. For the rs2285666 polymorphism, no significant difference in genotype distribution was found. In patients with mild symptoms, carriers of the GG genotype of rs2070788 had significantly higher total bilirubin levels than carriers of the AA genotype. Similarly, carriers of the TT genotype of rs2285666 had significantly higher activated partial thromboplastin time and international normalized ratio, and lower lactate dehydrogenase levels compared with the CC genotype. Among patients with severe symptoms, carriers of the GG genotype showed significantly higher potassium levels than carriers of the AA genotype, while carriers of the TT genotype showed significantly higher erythrocyte count as well as hemoglobin and hematocrit levels compared with the CC genotype.

This study highlights the role of genetic factors, particularly SNPs in the ACE2 and TMPRSS2 genes, in determining COVID-19 severity, aiding patient risk assessment and prognosis.

Introduction Chest pain is a common presenting complaint among children presenting to the ED, and serious underlying illnesses are found in only a small minority of cases. Due to the lack of established guidelines, the workup of these patients is institution or physician-dependent. Unlike adults with chest pain, workup among children tends to be minimal unless elements in the history and physical exam trigger it. We hypothesize that the emergence of COVID-19-related multisystem inflammatory syndrome in children (MISC) may have increased variability in how these patients are evaluated in the ED. Objective To determine if there has been a change in the approach to evaluating children presenting to the ED with chest pain since the emergence of the COVID-19 pandemic. Materials and methods This retrospective cohort study was conducted in a pediatric emergency department (PED) at a 400-bed urban academic community hospital. Medical records of children <21 years old who presented to the ED with chest pain from January to July in both 2019 and 2020 were reviewed. Patients with chest pain due to acute asthma exacerbations were excluded. Data about patient demographics, the number and types of tests utilized, and clinical management, including therapies and disposition, were collected. The subjects seen during 2019 were labeled as the 'pre-pandemic group' and those seen in 2020 as the 'pandemic group'. The number and type of tests utilized, therapeutic interventions, and disposition during the two study periods were subjected to analyses. Results Of the 180 patients evaluated for chest pain, 32 were excluded due to physician-diagnosed asthma-related chest pain. The study thus included the remaining 148 patients. There was no statistical association between the pre-pandemic and pandemic groups for presenting features of fever, cough, tachycardia, tachypnea, time of presentation to the ED, electrocardiogram (EKG) performance, and chest X-ray. However, the pandemic group showed a statistically significant increase in lab tests and hospitalizations compared to the pre-pandemic group. There was a statistically significant increase in the performance of complete blood counts (CBC), C-reactive protein (CRP), lactic dehydrogenase (LDH), serum ferritin, creatinine kinase-MB (CK-MB), troponin, B-natriuretic peptide (BNP), and D-dimers. Conclusion Since the onset of the COVID-19 pandemic, there has been a trend toward more extensive lab workups for patients presenting with acute chest pain in the ED.

The COVID-19 pandemic has been one of the most impactful events in our lifetime, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple SARS-CoV-2 variants were reported globally, and a wide range of symptoms existed. Individuals who contract COVID-19 continue to suffer for a long time, known as long COVID or post-acute sequelae of COVID-19 (PASC). While COVID-19 vaccines were widely deployed, both unvaccinated and vaccinated individuals experienced long-term complications. To date, there are no treatments to eradicate long COVID. We recently conceived a new approach to treat COVID in which a 15-amino-acid synthetic peptide (SPIKENET, SPK) is targeted to the ACE2 receptor binding domain of SARS-CoV-2, which prevents the virus from attaching to the host. We also found that SPK precludes the binding of spike glycoproteins with the receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) of a coronavirus, murine hepatitis virus-1 (MHV-1), and with all SARS-CoV-2 variants. Further, SPK reversed the development of severe inflammation, oxidative stress, tissue edema, and animal death post-MHV-1 infection in mice. SPK also protects against multiple organ damage in acute and long-term post-MHV-1 infection. Our findings collectively suggest a potential therapeutic benefit of SPK for treating COVID-19.

The COVID-19 pandemic and tuberculosis have epidemiological similarities, being transmitted airborne, favored by direct contact, crowded environments, and vulnerable biological status.

We performed a retrospective study of 45 cases of pulmonary tuberculosis associated with COVID-19 (TB+COV+) compared to 45 cases with tuberculous monoinfection (TB+COV-), hospitalized during 2021-2022.

The demographic characteristics were similar in the two groups, predominating men, a median age of 51 years, living in rural areas, medium level of education and smoking. Common symptoms of the two groups were cough, weight loss, profuse sweating, loss of appetite and hemoptysis, while fever, headache, myo-arthralgias, and digestive symptoms characterized the TB+COV+ forms. The scores of radiological lesions in the TB+COV+ compared to TB+COV- group were significantly higher and persistent, revealing more frequent bilateral extensive lung lesions. There were no significant differences in the biological parameters between the two groups. Mortality was 2.2%, regardless of the association of COVID-19. The frequency of infections with Clostridioides difficile was higher in TB+COV+ cases.

The co-infection of COVID-19 had a mild impact on the clinical and biological expression of tuberculosis diagnosed in a pandemic context.

Background and Objectives: The concurrent occurrence of tuberculosis and COVID-19 coinfection poses significant clinical complexities, warranting a nuanced approach to diagnosis, management, and patient care. Materials and Methods: A retrospective, cross-sectional study was conducted on two groups: one comprising 32 patients with pulmonary TB (PTB) and COVID-19 co-infection, and one including 100 patients with COVID-19 alone. Data was collected from medical records, including patient history, clinical parameters, laboratory, imaging results, and patient outcome. Results: A lower BMI emerges as a significant marker suggesting underlying PTB in patients with SARS-CoV-2 co-infection. Type 2 diabetes mellitus increases the risk of death in PTB-SARS-CoV-2 co-infection. Co-infected patients show lymphocytopenia and higher neutrophil levels, CRP, transaminases, and D-dimer levels. Elevated CRP and ALT levels are linked to increased co-infection likelihood. Certain parameters like SpO2, CRP, ALT, AST, and D-dimer effectively differentiate between co-infected and COVID-19 patients. Platelet-to-lymphocyte ratio is notably higher in co-infected individuals. Lesion severity on imaging is significantly associated with co-infection, highlighting imaging's diagnostic importance. Longer hospital stays are linked to co-infection but not significantly to death risk. Conclusions: Certain clinical and biological factors may serve as potential indicators of PTB co-infection in patients with SARS-CoV-2.

Severe acute respiratory syndrome-related Coronavirus 2 (SARS-CoV-2) has infected more than 762 million people to date and has caused approximately 7 million deaths all around the world, involving more than 187 countries. Although currently available vaccines show high efficacy in preventing severe respiratory complications in infected patients, the high number of mutations in the S proteins of the current variants is responsible for the high level of immune evasion and transmissibility of the virus and the reduced effectiveness of acquired immunity. In this scenario, the development of safe and effective drugs of synthetic or natural origin to suppress viral replication and treat acute forms of COVID-19 remains a valid therapeutic challenge. Given the successful history of flavonoids-based drug discovery, we developed esters of substituted cinnamic acids with quercetin to evaluate their in vitro activity against a broad spectrum of Coronaviruses. Interestingly, two derivatives, the 3,4-methylenedioxy 6 and the ester of acid 7, have proved to be effective in reducing OC43-induced cytopathogenicity, showing interesting EC50s profiles. The ester of synaptic acid 7 in particular, which is not endowed with relevant cytotoxicity under any of the tested conditions, turned out to be active against OC43 and SARS-CoV-2, showing a promising EC50. Therefore, said compound was selected as the lead object of further analysis. When tested in a yield reduction, assay 7 produced a significant dose-dependent reduction in viral titer. However, the compound was not virucidal, as exposure to high concentrations of it did not affect viral infectivity, nor did it affect hCoV-OC43 penetration into pre-treated host cells. Additional studies on the action mechanism have suggested that our derivative may inhibit viral endocytosis by reducing viral attachment to host cells.

The Corona Virus Disease (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has quickly spread worldwide and resulted in significant morbidity and mortality. Although most infections are mild, some patients can also develop severe and fatal myocarditis. In eukaryotic RNAs, 5-methylcytosine (m5C) is a common kind of post-transcriptional modification, which is involved in regulating various biological processes (such as RNA export, translation, and stability maintenance). With the rapid development of m5C modification detection technology, studies related to viral m5C modification are ever-increasing. These studies have revealed that m5C modification plays an important role in various stages of viral replication, including transcription and translation. According to recent studies, m5C methylation modification can regulate SARS-CoV-2 infection by modulating innate immune signaling pathways. However, the specific role of m5C modification in SARS-CoV-2-induced myocarditis remains unclear. Therefore, this review aims to provide insights into the molecular mechanisms of m5C methylation in SARS-CoV-2 infection. Moreover, the regulatory role of NSUN2 in viral infection and host innate immune response was also highlighted. This review may provide new directions for developing therapeutic strategies for SARS-CoV-2-associated myocarditis.

Post-acute sequelae of COVID-19 (PASC) is a persistent complication of severe acute respiratory syndrome coronavirus 2 infection that includes symptoms, such as fatigue, cognitive impairment, and respiratory distress. These symptoms severely affect the quality of life of patients after their recovery from COVID-19. In this study, a group of machine learning algorithms analyzed the whole blood RNA-seq data from patients with different PASC levels. The purpose of this analysis was to identify the gene markers associated with PASC and the special expression patterns for different PASC levels. By comparing the quality of life of patients after the acute phase of COVID-19 and before the disease, samples in the dataset were divided into three groups, namely, "Better," "The Same," and "Worse." Each patient was represented by the expression levels of 58,929 genes. The machine learning-based workflow included six feature-ranking algorithms, incremental feature selection (IFS), and four classification algorithms. The feature ranking algorithms were in charge of assessing feature importance, whereas IFS with classification algorithms were used to extract essential genes and to construct efficient classifiers and classification rules. The expression of top genes in the results was associated with the immune response to viral infection, which is supported by the published literature. For example, patients with low CCDC18 expression and high CPED1 expression had good quality of life, whereas those with low CDC16 expression had poor quality of life.

During the COVID-19 pandemic, RNA-seq datasets were produced to investigate the virus-host relationship. However, much of these data remains underexplored. To improve the search for molecular targets and biomarkers, we performed an integrated analysis of multiple RNA-seq datasets, expanding the cohort and including patients from different countries, encompassing severe and mild COVID-19 patients. Our analysis revealed that severe COVID-19 patients exhibit overexpression of genes coding for proteins of extracellular exosomes, endomembrane system, and neutrophil granules (e.g., S100A9, LY96, and RAB1B), which may play an essential role in the cellular response to infection. Concurrently, these patients exhibit down-regulation of genes encoding components of the T cell receptor complex and nucleolus, including TP53, IL2RB, and NCL Finally, SPI1 may emerge as a central transcriptional factor associated with the up-regulated genes, whereas TP53, MYC, and MAX were associated with the down-regulated genes during COVID-19. This study identified targets and transcriptional factors, lighting on the molecular pathophysiology of syndrome coronavirus 2 infection.

Gastrointestinal pathogens (GPs) contribute significantly to the burden of illness worldwide with diarrhoea being the most common among gastrointestinal symptoms (GSs). In the COVID-19 disease, diarrhoea, could be one of the initial presenting symptoms. However, no data on the potential correlation between diarrhoea-causing pathogens and SARS-CoV-2 infection are available. Therefore, we carried out a 2-years retrospective study aimed to evaluate the prevalence of "classic" GPs among SARS-CoV-2 infected and non-infected patients with diarrhoea in Italy.

Results of SARS-CoV-2 research from nasopharyngeal and detection of GPs from stool swab samples by Allplex™ SARS-CoV-2 and GI Virus, Bacteria and Parasite Assay were analysed for all patients with diarrhoea referring to Policlinico Ospedaliero Universitario, Foggia, (Italy) from February 2022 to October 2023.

Out of the 833 involved patients, 81 (3.9%) were COVID-19 positive, while 752 (90.3%) were COVID-19 negative. Among COVID-19-positive patients, 37% (n = 30/81) were found positive for one or more GPs with a higher prevalence of protozoan parasites (18.5%) (Blastocystis ST1-ST4 subtypes, Dientamoeba fragilis genotype I), followed by bacteria (7.4%) (Campylobacter sp., Salmonella sp.). Viral pathogens were more frequent among COVID-19 negative patients (Adenovirus, Norovirus). Among GPs, Blastocystis ST3 subtype was the most prevalent registered in the 16% of patients (p = 0.0001).

Based on obtained results, a likely interaction between the classic GPs and SARS-CoV-2 infection can be speculated, driven by protozoan parasites. Moreover, these results also provide baseline data to understand more deeply Blastocystis sp. role in this scenario of dysbiosis, particularly in those cases of SARS-CoV-2 co-infection.

Diagnostic testing followed by isolation of identified cases with subsequent tracing and quarantine of close contacts-often referred to as test-trace-isolate-and-quarantine (TTIQ) strategy-is one of the cornerstone measures of infectious disease control. The COVID-19 pandemic has highlighted that an appropriate response to outbreaks of infectious diseases requires a firm understanding of the effectiveness of such containment strategies. To this end, mathematical models provide a promising tool. In this work, we present a delay differential equation model of TTIQ interventions for infectious disease control. Our model incorporates the assumption of limited TTIQ capacities, providing insights into the reduced effectiveness of testing and tracing in high prevalence scenarios. In addition, we account for potential transmission during the early phase of an infection, including presymptomatic transmission, which may be particularly adverse to a TTIQ based control. Our numerical experiments inspired by the early spread of COVID-19 in Germany demonstrate the effectiveness of TTIQ in a scenario where immunity within the population is low and pharmaceutical interventions are absent, which is representative of a typical situation during the (re-)emergence of infectious diseases for which therapeutic drugs or vaccines are not yet available. Stability and sensitivity analyses reveal both disease-dependent and disease-independent factors that impede or enhance the success of TTIQ. Studying the diminishing impact of TTIQ along simulations of an epidemic wave, we highlight consequences for intervention strategies.

The SARS-CoV-2 virus and its mutations have affected human health globally and created significant danger for the health of people all around the world. To cure this virus, the human Angiotensin Converting Enzyme-2 (ACE2) receptor, the SARS-CoV-2 main protease (Mpro), and spike proteins were found to be likely candidates for the synthesis of novel therapeutic drug. In the past, proteins were capable of engaging in interaction with a wide variety of ligands, including both manmade and plant-derived small molecules. Pyrus communis L., Ginko bibola, Carica papaya, Syrian rue, and Pimenta dioica were some of the plant species that were studied for their tendency to interact with SARS-CoV-2 main protease (Mpro) in this research project (6LU7). This scenario investigates the geometry, electronic, and thermodynamic properties computationally. Assessing the intermolecular forces of phytochemicals with the targets of the SARS-CoV-2 Mpro spike protein (SP) resulted in the recognition of a compound, kaempferol, as the most potent binding ligand, -7.7 kcal mol-1. Kaempferol interacted with ASP-187, CYS-145, SER-144, LEU 141, MET-165, and GLU-166 residues. Through additional molecular dynamic simulations, the stability of ligand-protein interactions was assessed for 100 ns. GLU-166 remained intact with 33% contact strength with phenolic OH group. We noted a change in torsional conformation, and the molecular dynamics simulation showed a potential variation in the range from 3.36 to 7.44 against a 45-50-degree angle rotation. SAR, pharmacokinetics, and drug-likeness characteristic investigations showed that kaempferol may be the suitable candidate to serve as a model for designing and developing new anti-COVID-19 medicines.

COVID-19 remains a significant international public health concern. Yet, the mechanisms through which symptomatology emerges remain poorly understood. While SARS-CoV-2 infection may induce prolonged inflammation within the central nervous system, the evidence primarily stems from limited small-scale case investigations. To address this gap, our study capitalized on longitudinal UK Biobank neuroimaging data acquired prior to and following COVID-19 testing (N = 416 including n = 224 COVID-19 cases; Mage = 58.6). Putative neuroinflammation was assessed in gray matter structures and white matter tracts using non-invasive Diffusion Basis Spectrum Imaging (DBSI), which estimates inflammation-related cellularity (DBSI-restricted fraction; DBSI-RF) and vasogenic edema (DBSI-hindered fraction; DBSI-HF). We hypothesized that COVID-19 case status would be associated with increases in DBSI markers after accounting for potential confound (age, sex, race, body mass index, smoking frequency, and data acquisition interval) and multiple testing. COVID-19 case status was not significantly associated with DBSI-RF (|β|'s < 0.28, pFDR >0.05), but with greater DBSI-HF in left pre- and post-central gyri and right middle frontal gyrus (β's > 0.3, all pFDR = 0.03). Intriguingly, the brain areas exhibiting increased putative vasogenic edema had previously been linked to COVID-19-related functional and structural alterations, whereas brain regions displaying subtle differences in cellularity between COVID-19 cases and controls included regions within or functionally connected to the olfactory network, which has been implicated in COVID-19 psychopathology. Nevertheless, our study might not have captured acute and transitory neuroinflammatory effects linked to SARS-CoV-2 infection, possibly due to symptom resolution before the imaging scan. Future research is warranted to explore the potential time- and symptom-dependent neuroinflammatory relationship with COVID-19.

The effect of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) virus in the neonatal period on developing brain is still unknown. This study aims to investigate the long-term neurodevelopmental outcomes of newborns exposed to SARS-CoV-2 & Delta variant.

At a tertiary referral center, a prospective observational cohort research was carried out. All babies who were equal to or more than 34 gestational weeks gestation and were admitted to the NICU between January 2021 and January 2022 due to SARS-CoV-2 infection (Delta - or Delta +) were included in the study. Infants who were hospitalized for non-SARS-CoV-2 reasons at similar dates and who had no history of invasive mechanical ventilation were incorporated as a control group using a 2:1 gender and gestational age match. Thirty infants were assigned to the study group and sixty newborns to the control group based on the sample size calculation. These toddlers' neurodevelopment was evaluated between the ages of 18 and 24 months using the Bayley-II scale.

We enrolled 90 infants. SARS-CoV-2-positive infants had poorer psychomotor development index (PDI) scores and significantly greater mildly delayed performances (MDPs) at 18-24 months (PDI p = 0.05, MDPs p = 0.03, respectively). Delta variant showed statistically significant lower MDI and PDI scores (MDI p=0.03, PDI p=0.03, respectively). A smaller head circumference of SARS-CoV-2-positive toddlers was detected in the first year (p < 0.001), which improved at the second age.

SARS-CoV-2-positive neonates revealed lower PDI scores and greater MDPs at 18th-24th months. The effect is most noticeable in Delta variant. Longer-term examination of neurodevelopmental outcomes and reevaluation of these children between the ages of 5 and 12 are critical.

The TAS2R38 gene is well known for its function in bitter taste sensitivity, but evidence also suggests a role in innate immunity. TAS2R38 may be relevant in coronavirus disease 2019 (COVID-19), but research findings are inconsistent. The objective of this study was to explore whether common TAS2R38 haplotypes are associated with COVID-19 infection and symptomatology in the Canadian Longitudinal Study on Aging (CLSA). Data from the CLSA COVID-19 Questionnaire and Seroprevalence sub-studies were utilized with CLSA genetic data for common TAS2R38 haplotypes related to bitter taste sensitivity. Haplotypes were categorized into three diplotype groups: [P]AV homozygotes, [P]AV/[A]VI heterozygotes, and [A]VI homozygotes. No significant differences were observed between diplotypes and COVID-19 infection frequency. Among self-reported COVID-19 cases (n = 76), and in uncorrected exploratory analyses, heterozygotes were less likely to report experiencing sinus pain compared to [P]AV homozygotes. Among seroprevalence-confirmed cases (n = 177), [A]VI homozygotes were less likely to report experiencing a sore/scratchy throat compared to [P]AV homozygotes. However, both observations were non-significant upon correction for multiple testing. In this study, TAS2R38 haplotypes were not significantly associated with COVID-19 infection or symptomatology. Nevertheless, in light of some exploratory patterns and conflicting evidence, additional research is warranted to evaluate links between TAS2R38 and innate immunity.

Interest in the coronavirus disease 2019 (COVID-19) has progressively decreased lately, mainly due to the great effectivity of vaccines. Furthermore, no new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants able to circumvent the protection of these vaccines, while presenting high transmissibility and/or lethality, have appeared. However, long COVID has emerged as a huge threat to human health and economy globally. The human microbiota plays an important role in health and disease, participating in the modulation of innate and adaptive immune responses. Thus, multiple studies have found that the nasopharyngeal microbiota is altered in COVID-19 patients, with these changes associated with the onset and/or severity of the disease. Nevertheless, although dysbiosis has also been reported in long COVID patients, mainly in the gut, little is known about the possible involvement of the microbiota in the development of this disease. Therefore, in this work, we aim to fill this gap in the knowledge by discussing and comparing the most relevant studies that have been published in this field up to this point. Hence, we discuss that the relevance of long COVID has probably been underestimated, and that the available data suggest that the microbiota could be playing a pivotal role on the pathogenesis of the disease. Further research to elucidate the involvement of the microbiota in long COVID will be essential to explore new therapeutic strategies based on manipulation of the microbiota.

In the present study, we have examined different aspects and potentials of stem cells for the management of patients infected with COVID-19.

The novel coronavirus disease (COVID-19) has been reported in most of the countries and territories (>230) of the world with .686 million confirmed cases (as of Apr. 22, 2023). While the scientific community is working to develop vaccines and develop drugs against the COVID-19 pandemic, novel alternative therapies may reduce the mortality rate. Recently, the application of stem cells for critically ill COVID-19 patients in a small group of patients has been examined.

We searched PubMed, Web of Science, and Google Scholar up to July 2022. Those studies that reviewed COVID-19 and cell therapy potentials were entered into the study. Moreover, some recently published patents were exploited and reviewed. Patentscope, USPTO, Espacenet, Free Patents Online, and Google Patents were used for patent searches.

Cell-based therapy as a modality of regenerative medicine is considered one of the most promising disciplines in the fields of modern science and medicine. Such an advanced technology offers endless possibilities for transformative and potentially curative treatments for some of the most life-threatening diseases. This therapeutic tool can be useful to reduce the rate of mortality. There have been several published patents for different stem cell therapy platforms in recent years.

Stem cell therapy could be considered a safe and effective therapeutic strategy to reduce death cases in patients infected with COVID-19. Besides, stem cell therapy might increase the pulmonary functions in the patients, it suppresses the occurring inflammations and ameliorates the symptoms.