Search

RaTG13 is phylogenomically the closest related coronavirus to SARS-CoV-2; consequently, understanding the provenance of this high-value genome sequence is important in understanding the origin of SARS-CoV-2. While RaTG13 was described as being generated from a Rhinolophus affinis fecal swab obtained from a mine in Mojiang, Yunnan, numerous investigators have pointed out that this is inconsistent with the low proportion of bacterial reads in the sequencing dataset. Metagenomic analysis confirms that only 10.3% of small-subunit (SSU) rRNA sequences in the dataset are bacterial, which is inconsistent with a fecal sample. In addition, the bacterial taxa present in the sample are shown to be inconsistent with fecal material. The assembly of mitochondrial SSU rRNA sequences in the dataset produces a sequence 98.7% identical to R. affinis mitochondrial SSU rRNA, indicating that the sample was generated from R. affinis or a closely related species. In addition, 87.5% of the reads in the dataset map to the Rhinolophus ferrumequinum genome, and 62.2% of these map to protein-coding genes, indicating that the dataset represents a Rhinolophus sp. transcriptome rather than a fecal swab sample. Differential gene expression analysis reveals that the pattern of expressed genes in the RaTG13 dataset is similar to that of RaTG15, which was also collected from the Mojiang mine. GO enrichment analysis reveals the overexpression of spermatogenesis- and olfaction-related genes in both datasets. This observation is consistent with a mating plug found in female Rhinolophid bats and suggests that RaTG13 was mis-sampled from such a plug. A validated natural provenance of the RaTG13 dataset throws into relief the unusual features of the SARS-CoV-2 genome.

Background: To evaluate analgesic practices in perioperative treatment during the SARS-CoV-2 pandemic; recording parameters collected in the PAIN OUT database, and to compare COVID and no-COVID data. Methods: Data were analyzed for 277 patients (87 COVID-19 confirmed diagnosis and 190 non-COVID): years aged, gender, minutes of surgery duration, Likert Scale punctuation, hours in severe pain, minimum and maximum pain intensity, interference with sleep quality, anxiety, need for help, nausea, drowsiness, itching, dizziness, perception of care, pain relief, participation, satisfaction, and information received. Results: Postoperative mortality 1 month after surgery was recorded at 25.3% in COVID-19. Significant differences were found in postoperative pain intensity (p = 0.019), time with severe pain (p < 0.01), lower sleep quality (p < 0.01), and better outcomes in functional items (p < 0.01); there were more side effects and satisfaction with pain relief (p < 0.01) in COVID-patients than with no COVID-19 patients. Conclusions: In conclusion, COVID-19 patients presented greater intensity and duration of severe postoperative pain, greater somnolence, pruritus, and dizziness, lower physical activity limitation, and higher quality index.

The COVID-19 pandemic, instigated by the emergence of the novel coronavirus, SARS-CoV-2, created an incomparable global health crisis. Due to its highly virulent nature, identifying potential therapeutic agents against this lethal virus is crucial. PLpro is a key protein involved in viral polyprotein processing and immune system evasion, making it a prime target for the development of antiviral drugs to combat COVID-19. To expedite the search for potential therapeutic candidates, this review delved into computational studies. Recent investigations have harnessed computational methods to identify promising inhibitors targeting PLpro, aiming to suppress the viral activity. Molecular docking techniques were employed by researchers to explore the binding sites for antiviral drugs within the catalytic region of PLpro. The review elucidates the functional and structural properties of SARS-CoV-2 PLpro, underscoring its significance in viral pathogenicity and replication. Through comprehensive all-atom molecular dynamics (MD) simulations, the stability of drug–PLpro complexes was assessed, providing dynamic insights into their interactions. By evaluating binding energy estimates from MD simulations, stable drug–PLpro complexes with potential antiviral properties were identified. This review offers a comprehensive overview of the potential drug/lead candidates discovered thus far against PLpro using diverse in silico methodologies, encompassing drug repurposing, structure-based, and ligand-based virtual screenings. Additionally, the identified drugs are listed based on their chemical structures and meticulously examined according to various structural parameters, such as the estimated binding free energy (ΔG), types of intermolecular interactions, and structural stability of PLpro–ligand complexes, as determined from the outcomes of the MD simulations. Underscoring the pivotal role of targeting SARS-CoV-2 PLpro in the battle against COVID-19, this review establishes a robust foundation for identifying promising antiviral drug candidates by integrating molecular dynamics simulations, structural modeling, and computational insights. The continual imperative for the improvement of existing drugs and exploring novel compounds remains paramount in the global efforts to combat COVID-19. The evolution and management of COVID-19 hinge on the symbiotic relationship between computational insights and experimental validation, underscoring the interdisciplinary synergy crucial to this endeavor.

Long COVID comprises persistent symptoms that extend beyond four weeks post-SARS-CoV-2 infection. The potential association between long COVID and the endorsement of COVID-19 conspiracy theories has not been explored, particularly in Arab countries, where high endorsement of these theories has been reported. This study aimed to explore the association between endorsing COVID-19 conspiracy theories and the prevalence of self-reported long COVID symptoms among adults in Jordan and Kuwait in addition to other Arab countries. The study employed a cross-sectional design using Computer-Assisted Web Interviewing (CAWI), conducted in Arabic. Recruitment utilized convenience-based snowball sampling via social media and the survey was distributed in July 2024. Long COVID manifestations were assessed across ten recognized symptoms, and belief in conspiracy theories was measured using a five-point Likert scale across five items. The final study sample comprised 755 respondents, the majority of whom self-reported a history of confirmed COVID-19 diagnosis at least once (n = 493, 65.2%). The results indicated a neutral average attitude towards COVID-19 conspiracy theories (mean score = 15.18 ± 4.64 out of 30.00). Participants with high COVID-19 conspiracy theories scores were more likely to report high (aOR = 6.85, p < 0.001) or middle long COVID symptoms (aOR = 2.82, p = 0.008) compared to those with lower scores. Additional predictors of higher long COVID reporting included female sex, lower household income, frequent COVID-19 infections, and hospitalizations. The study results revealed a significant correlation between the endorsement of COVID-19 conspiracy theories and a higher frequency and magnitude of long COVID symptom reporting. The findings also highlighted the influence of sociodemographic factors and COVID-19 infection history on long COVID reporting, which suggests that public health strategies should address these factors to mitigate long COVID challenges effectively.

The global pandemic sparked by the emergence of SARS-CoV-2 and its variants has imposed a substantial burden of morbidity and mortality. Central to the battle against these viral threats is the immune response, with a spotlight on the pivotal role played by neutralizing antibodies. This comprehensive review delves into current research, unravelling the dual functionality of neutralizing antibodies acting as formidable barriers to viral replication and crucial facilitators of adaptive immune memory. Beyond this dual purpose, the review illuminates the nuanced variability characterizing neutralizing antibody responses to SARS-CoV-2. Emphasizing the dynamic nature of these responses, the review advocates for the plausible challenges in targeted therapeutic interventions. This review also attempts to compare various vaccination approaches and their impact on SARS-CoV-2, as well as offer insights into various Omicron variations. Recognizing the ever-evolving viral landscape, this exploration underscores the necessity of flexible approaches to address the diverse challenges posed by SARS-CoV-2 and its variants, contributing valuable insights to the ongoing global efforts in pandemic mitigation and public health safeguarding.

Objectives: This study aims to examine the serological and infectious characteristics of the Xokós indigenous community in Brazil, both prior to and following COVID-19 immunization; Methods: Immunofluorescence assays were employed to identify the SARS-CoV-2 viral antigen, while IgM and IgG antibody tests for COVID-19 were utilized to assess the participants’ infectious and serological profiles in July 2020, before the commencement of the COVID-19 vaccination campaign, and in March 2022, during the booster dose vaccination campaign; Results: The majority of participants (n = 22) were female, with an average age of 42.20 years. The most prevalent comorbidity was hypertension (60%; n = 9), followed by hypertension associated with diabetes (20%; n = 3). No statistically significant correlation was found between the timing of vaccination and the levels of antigens or IgM. However, the prevalence of reactive antigens and IgM was 13.3% (n = 4) in the pre-vaccination group and 3.3% (n = 1) in the post-vaccination group. A statistically significant difference in IgG production was observed before and after vaccination (χ2(1) = 39.095, p < 0.01), as well as differences in IgG antibody detection before and after vaccination and in the vaccines used. Participants showed a higher probability of reactive IgG antibodies following vaccination; Conclusions: Our data demonstrate the beneficial effects of vaccination on the indigenous community, highlighting that continued immunization is a crucial step in protecting indigenous health and preventing severe outbreaks and deaths associated with the disease.

COVID-19, a novel infectious disease caused by the emergence of the SARS-CoV-2 virus in 2020, has had a profound impact on healthcare, both at the individual and population level. The impact at the population level was felt most acutely during the emergency phase of the pandemic, with hospital capacity issues leading to widespread disruptions and delays in the delivery of healthcare services such as screening programs and elective surgeries. While hospitals are no longer being acutely overwhelmed by COVID-19 patients, the impact of the virus on vulnerable patient populations such as cancer patients continues to be of ongoing consequence. Cancer patients remain at high risk of hospitalization, ICU admission, and death due to COVID-19, even in the era of vaccination. Infection prevention and risk mitigation strategies such air quality control, masking, testing, vaccination, and treatment should therefore be integrated into the usual care and counseling of cancer patients moving forward to avoid preventable morbidity and mortality from this infection and ensure the safety of this vulnerable cohort as they navigate their cancer diagnosis and treatment in the era of COVID-19.

The COVID-19 pandemic is caused by a novel and rapidly mutating coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although several drugs are already in clinical use or under emergency authorization, there is still an urgent need to develop new drugs. Through the mining and analysis of 2776 genomes of the SARS-CoV-2 virus, we identified papain-like protease (PLpro), which is a critical enzyme required for coronavirus to generate a functional replicase complex and manipulate post-translational modifications on host proteins for evasion against host antiviral immune responses, as a conserved molecular target for the development of anti-SARS-CoV-2 therapy. We then made an infection model using the NCI-H1299 cell line stably expressing SARS-CoV-2 PLpro protein (NCI-H1299/PLpro). To investigate the effect of targeting and degrading PLpro mRNA, a compact CRISPR-Cas13 system targeting PLpro mRNA was developed and validated, which was then delivered to the aforementioned NCI-H1299/PLpro cells. The results showed that CRISPR-Cas13 mediated mRNA degradation successfully reduced the expression of viral PLpro protein. By combining the power of AAV and CRISPR-Cas13 technologies, we aim to explore the potential of attenuating viral infection by targeted degradation of important viral mRNAs via safe and efficient delivery of AAV carrying the CRISPR-Cas13 system. This study demonstrated a virus-against-virus gene therapy strategy for COVID-19 and provided evidence for the future development of therapies against SARS-CoV-2 and other RNA viral infections.

Despite the recent pandemic, the origin of its causative agent, SARS-CoV-2, remains controversial. This study identifies several prototype SARS-CoV-2 variants (proto-variants) that are descendants of the Wuhan variant. A thorough evaluation of the evolutionary histories of the genomes of these proto-variants reveals that most mutations in proto-variants were biased toward mutations that change the amino acid sequence. While these nonsynonymous substitutions (N mutations) were common in SARS-CoV-2 proto-variants, nucleotide changes that do not result in an amino acid change, termed synonymous substitutions (S mutations), dominate the mutations found in other RNA viruses. The N mutation bias in the SARS-CoV2 proto-variants was found in the spike gene as well as several other genes. The analysis of the ratio of N to S mutations in general RNA viruses revealed that the probability that an RNA virus spontaneously evolves a proto-variant is between 1.5 × 10−9 and 2.7 × 10−26 under natural conditions. These results suggest that SARS-CoV-2 variants did not emerge via a canonical route.

Background: Multisystem inflammatory syndrome in children (MIS-C) occurs after SARS-CoV-2 infection, with gastrointestinal symptoms a prominent feature. This syndrome has been proposed to be triggered by persistent SARS-CoV-2 antigenemia due to increased intestinal epithelial permeability. We obtained evidence for this in this study. Methods: In a single-centre study, we recruited 83 children and analysed blood samples to quantify the circulating markers of increased intestinal permeability following SARS-CoV-2 infection. Publicly available proteomics MIS-C datasets were also accessed to assess the evidence for increased intestinal permeability. We further quantified SARS-CoV-2 antigenemia and the humoral response to SARS-CoV-2 spike protein. Results: Following SARS-CoV-2 infection, healthy children demonstrated no dysregulation of the intestinal epithelial barrier. In MIS-C, considerable increases in markers of epithelial dysfunction were observed, with similar increases noted in febrile controls. Furthermore, we found little evidence of persistent SARS-CoV-2 antigenemia in MIS-C. Conclusions: Our results suggest that although increased intestinal epithelial permeability is a feature of MIS-C, it is not unique to the condition, and persistent SARS-CoV-2 antigenemia does not occur.

The emergence of mRNA vaccines for SARS-CoV-2 has opened a new page in vaccine development. Nevertheless, concerns of experts have been expressed about unintentional side effects on the gut microbiota (GM). Previous studies showed that this virus acts as a bacteriophage, which infects and destroys specific bacterial strains in the GM. The present manuscript hypothesizes that the synthetic spike protein could create changes in the composition and the functioning of the GM by entering the intestinal cells after vaccination and impairing the symbiotic relationship between intestinal cells and the GM. An experimental protocol to test the hypothesis is suggested.

Determining the number of cases of an epidemic is the first function of epidemiological surveillance. An important underreporting of cases was observed in many locations during the first wave of the COVID-19 pandemic. To estimate this underreporting in the COVID-19 outbreak of Borriana (Valencia Community, Spain) in March 2020, a cross-sectional study was performed in June 2020 querying the public health register. Logistic regression models were used. Of a total of 468 symptomatic COVID-19 cases diagnosed in the outbreak through anti-SARS-CoV-2 serology, 36 cases were reported (7.7%), resulting in an underreporting proportion of 92.3% (95% confidence interval [CI], 89.5–94.6%), with 13 unreported cases for every reported case. Only positive SARS-CoV-2 polymerase chain reaction cases were predominantly reported due to a limited testing capacity and following a national protocol. Significant factors associated with underreporting included no medical assistance for COVID-19 disease, with an adjusted odds ratio [aOR] of 10.83 (95% CI 2.49–47.11); no chronic illness, aOR = 2.81 (95% CI 1.28–6.17); middle and lower social classes, aOR = 3.12 (95% CI 1.42–6.85); younger age, aOR = 0.97 (95% CI 0.94–0.99); and a shorter duration of illness, aOR = 0.98 (95% CI 0.97–0.99). To improve the surveillance of future epidemics, new approaches are recommended.

(1) Background: The SARS-CoV-2 papain-like protease (PLpro) remains an underexplored antiviral target so far. The reduced efficacy of approved treatments against novel variants highlights the importance of developing new agents. This review aims to provide a comprehensive understanding of phytochemicals as inhibitors of PLpro, identify gaps, and propose novel insights for future reference. (2) Methods: A thorough literature search was conducted using Google Scholar, ScienceDirect, and PubMed. Out of 150 articles reviewed, 57 met inclusion criteria, focusing on SARS-CoV-2 PLpro inhibitors, excluding studies on other coronaviruses or solely herbal extracts. Data were presented class-wise, and phytochemicals were grouped into virtual, weak, modest, and potential inhibitors. (3) Results: Approximately 100 phytochemicals are reported in the literature as PLpro inhibitors. We classified them as virtual inhibitors (70), weak inhibitors (13), modest inhibitors (11), and potential inhibitors (6). Flavonoids, terpenoids, and their glycosides predominated. Notably, six phytochemicals, including schaftoside, tanshinones, hypericin, and methyl 3,4-dihydroxybenzoate, emerged as potent PLpro inhibitors with favorable selectivity indices and disease-mitigation potential; (4) Conclusions: PLpro stands as a promising therapeutic target against SARS-CoV-2. The phytochemicals reported in the literature possess valuable drug potential; however, certain experimental and clinical gaps need to be filled to meet the therapeutic needs.

Coronavirus disease 2019 (COVID-19) is an infection characterized by the dysregulation of systemic cytokine levels. The measurement of serum levels of inflammatory cyto-/chemokines has been suggested as a tool in the management of COVID-19. The aim of this study is to highlight the significance of measured levels of interleukin (IL)-1α, IL-1β, IL-6, IL-8, IL-10, IL-12(p70), IL-27, interferon (IFN)γ, interferon gamma-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α in serum samples from infected and recovered subjects, possibly predictive of severity and/or duration of the disease. Serum samples from healthy (HD), positive at hospital admittance (T0), and recovered subjects (T1, 31–60, or 70–200 days post-negativization) were collected and tested through a bead-based cytometric assay and confirmed through ELISA. IL-10 levels were increased in the T0 group compared to both HD and T1. IL-27 significantly decreased in the 31–60 group. IL-1β significantly increased in the 70–200 day group. TNF-α significantly decreased in T0 compared to HD and in the 31–60 group versus HD. IP-10 significantly increased in T0 compared to HD. These results suggest that IP-10 could represent an early marker of clinical worsening, whereas IL-10 might be indicative of the possible onset of post-COVID-19 long syndrome.

Background: The prognostic significance of liver dysfunction in COVID-19 patients remains unclear. In this study, we investigated the association between liver function test results and severe disease progression in COVID-19 patients. Methods: This retrospective study included consecutive Japanese COVID-19 patients admitted between February 2020 and July 2021. Predictive variables for severe disease progression were identified by multivariate logistic regression analysis. Severe disease-free survival was estimated with the Kaplan–Meier method and Cox regression analysis. Aspartate aminotransferase (AST) was divided into three grades: grade 1, AST < 30 U/L; grade 2, 30 U/L ≤ AST < 60 U/L; and grade 3, AST > 60 U/L. Results: Among 604 symptomatic patients, 141 (23.3%) developed severe disease at a median of 2 days postadmission. The median hospital stay was 10 days, and 43 patients (7.1%) died during hospitalization. Multivariate regression analysis revealed that hypertension, decreased lymphocyte count, and elevated LDH, CRP, and AST levels (grade 2 and grade 3 relative to grade 1) were the significant predictive variables. Severe disease-free survival time was significantly different between the different AST grades (hazard ratio (HR): grade 2 vs. grade 1, 4.07 (95% confidential interval (CI): 2.06–8.03); grade 3 vs. grade 1, 7.66 (95% CI: 3.89–15.1)). Conclusions: The AST level at admission was an independent risk factor for severe disease in hospitalized Japanese patients with COVID-19.

The emergence of COVID-19 has evolved into a global pandemic, causing an unprecedented public health crisis marked by unprecedented levels of morbidity never seen in the recent past. Considerable research efforts have been made in the scientific community to establish an optimal method to identify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and to understand the induced immune response. This review examined the development of serological tests during the COVID-19 pandemic, considering the factors affecting sensitivity and specificity, which are key to promote an efficient vaccination strategy for public health. The market has witnessed the introduction of various serological tests for the detection of SARS-CoV-2, such as the chemiluminescence immunoassay (CLIA), which emerged as a powerful and rapid tool to monitor the antibody response before and after vaccination or infection. Therefore, developing serological tests by studying antibody trends and persistence is essential for creating long-term strategies. Our analysis underscores the multifaceted applications of serological tests in pandemic management with a focus on the critical insights they provide into antibody dynamics that help in managing the ongoing pandemic and shaping future public health initiatives, providing a basis for optimizing the future response to viral threats.

The coronavirus disease 2019 (COVID-19) pandemic has significantly affected older adults. Identifying host COVID-19 susceptibility genes in elderly populations remains a challenge. Here, we aimed to identify host genetic factors influencing the susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We genotyped 12 single-nucleotide polymorphisms (SNPs) previously associated with the innate immune response in a total of 97 elderly (age > 65 years) residents of three long-term care facilities located in Barcelona, Spain. Individuals were PCR-tested during the SARS-CoV-2 outbreaks between September and November 2020. SARS-CoV-2 PCR tests revealed infections in 81 residents. Importantly, the 16 uninfected residents remained SARS-CoV-2 seronegative until vaccination (January and February 2021). After adjusting for sex and age, we found that two SNPs were significantly associated with SARS-CoV-2 infection susceptibility—MMS19 nucleotide excision repair protein homolog (MMS19)/rs2236575 (p = 0.029) and interferon-induced helicase C domain-containing 1 (IFIH1)/rs1990760 (p = 0.034). No association with SARS-CoV-2 infection was found for 10 additional genotyped SNPs, which included 4 SNPs on chromosome 12 in the gene encoding oligoadenylate synthetase (OAS). Our results indicate that MMS19/rs2236575_A and IFIH1/rs1990760_TC genetic variants were associated with a resistance to SARS-CoV-2 infection in a cohort of institutionalized seniors.

Background: Accurate and rapid testing for COVID-19 is critical for effective disease management and control. The One-Step-COVID-2019-Test was developed as a rapid serological test to detect antibodies against SARS-CoV-2. Objective: To estimate the accuracy of the rapid serological test for COVID-19 using One-Step-COVID-2019. Methods: We conducted a population-based serological survey with a stratified sampling of 593 adults between October and December 2020, prior to mass vaccination and during a period of limited availability of rapid tests. Participants provided 7.5 mL of serum, which was tested using the One-Step-COVID-2019-Test for IgM-IgG antibodies without distinction, as well as an in-house ELISA for IgG against the spike protein. Statistical analysis accounted for sampling weights, with accuracy assessed through sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), Youden index, and kappa coefficient, using ELISA as the reference standard. McNemar’s test identified significant differences between the test results. Results: The ELISA-based prevalence of infection was 11.1%. The One-Step-COVID-2019-Test showed low sensitivity (27.0–30.8%) but high specificity (89.9–96.6%), with poor agreement (kappa: 0.290–0.337), particularly among asymptomatic individuals. Conclusions: The One-Step-COVID-2019 rapid test for COVID-19 demonstrated inadequate performance, characterized by low sensitivity and poor reliability, making it unsuitable for effective serological surveillance.

Viral infections caused by exposure to viruses such as Epstein–Barr, cytomegalovirus, or Parvovirus B19 have always been considered predisposing environmental factors for the onset of autoimmune diseases. More recently, autoimmune mechanisms such as molecular mimicry, T-cell activation, transient immunosuppression and inflammation have also been observed in cases of SARS-CoV-2 infection. Several newly diagnosed autoimmune disorders have been reported post-COVID-19, such as COVID-19-associated multisystemic inflammatory syndrome in children (MIS-C), type 1 diabetes mellitus, systemic lupus erythematosus, or rheumatoid arthritis. In this article, we present a new case of paediatric systemic lupus erythematosus (SLE) with haematological (macrophage activation syndrome), renal (stage 2), cutaneous (urticarial vasculitis) and digestive involvement, onset three and a half months post-COVID-19. In the dynamics, de novo infection generated by Epstein–Barr exposure was associated. The diagnosis was confirmed based on EULAR/ACR 2019 criteria. The aim of the article is to present a possible correlation between SARS-CoV-2 and Epstein–Barr as extrinsic factors in triggering or activating paediatric systemic lupus erythematosus. Keywords: paediatric systemic lupus erythematosus; post-COVID-19; Epstein–Barr; SARS- CoV-2; case report; paediatric patient.

Objective: This cross-sectional-survey-based study aimed to investigate the severity of side-effects from Coronavirus disease (COVID-19) mRNA (Pfizer, Moderna), viral vector DNA (Oxford-AstraZeneca, J&J/Janssen), inactivated virus (Sinopharm, Sinovac), and other vaccines among healthcare workers (HCWs) in Saudi Arabia, focusing on their impact on work attendance. Methods: A total of 894 HCWs residing in Saudi Arabia participated in this study from March 2023 to May 2023. Participants completed an online questionnaire assessing demographic information, vaccination status, comorbidities, vaccine side-effects, and missed work information after vaccination. Descriptive statistics and chi-square tests were used for data analysis. Results: The majority of participants were female (83.7%) and aged 25–34 years (42.8%). Most participants were predominantly vaccinated with mRNA vaccines. Common side-effects included pain at the injection site, fatigue, fever, and chills. However, no significant association was found between vaccine type, side-effects, and work absenteeism. While demographic factors such as age and healthcare profession did not influence work absenteeism, variations were observed among different racial groups. Conclusion: COVID-19 vaccination among HCWs in Saudi Arabia is associated with common side-effects, but their impact on work attendance is not significant. Understanding these implications can inform strategies to support the healthcare workforce and mitigate the impact on patient care and staffing during the ongoing COVID-19 pandemic.

SARS-CoV-2, the causative agent of the COVID-19 pandemic, has had a global impact, affecting millions over the last three years. Pre-existing lung diseases adversely affect the prognosis of infected COVID-19 patients, and agricultural workers routinely exposed to inhalable organic dusts have substantial increased risk for developing chronic lung diseases. In previous studies, we characterized the protein kinase C (PKC)-dependent airway inflammation mediated by organic dust extract (ODE) derived from dust collected from swine confinement facilities in in vitro and in vivo models. Here, we studied the effect of ODE on SARS-CoV-2 pseudoviral infection in mice and human bronchial epithelial cells (BEAS-2B). In wild-type (WT) and transgenic mice expressing the human angiotensin I-converting enzyme 2 (ACE2) receptor (SARS-CoV-2 entry receptor), ODE increased ACE2 shedding by ADAM-17 in the lungs. After repeated ODE treatments, the increased soluble ACE2 correlated to higher pseudovirus titer in the mouse lungs. In the human bronchial epithelial cells, ODE augmented PKCα activity in WT cells, and membrane ACE2 expression was diminished in PKCα-dominant negative cells. Unlike in the mice, increasing membrane ACE2 levels by treating with PKCα or ADAM-17 inhibitors and a low dose of ODE enhanced pseudoviral entry in vitro. Following viral entry, IL-8 secretion by the cells was diminished in a PKCα- and ADAM-17-independent manner. Together, the complex mechanisms involved in the synergistic effects of agricultural dust and SARS-CoV-2 highlight the importance of studying dust-mediated changes to immunity against circulating pathogens.

The COVID-19 pandemic has revealed a diverse spectrum of clinical manifestations in the pediatric population, including the rare but notable presentation of unilateral parotitis. This comprehensive review explores the complexities surrounding SARS-CoV-2-associated unilateral parotitis in children. It addresses the initial clinical presentation, diagnostic challenges, treatment strategies, and the wider epidemiological impacts of this unusual symptom. The review synthesizes the available literature, providing insights into the pathophysiological mechanisms underlying this atypical manifestation and its implications for pediatric healthcare during the pandemic. Through the rigorous analysis of reported cases, this study underscores the need for increased awareness and a broad differential diagnosis among clinicians. It also emphasizes the importance of continued research to delineate the full clinical spectrum of COVID-19 in children.

Regardless of the containment of the SARS-CoV-2 pandemic, it remains paramount to comprehensively understand its underlying mechanisms to mitigate potential future health and economic impacts, comparable to those experienced throughout the course of the pandemic. The angiotensin-converting enzyme 2 (ACE2) provides anchorage for SARS-CoV-2 binding, thus implicating that ACE and ACE2 might contribute to the variability in infection severity. This study aimed to elucidate predisposing factors influencing the disease course among people infected by SARS-CoV-2, focusing on angiotensin-converting enzyme (ACE) and ACE2 polymorphisms. Notably, despite similar demographics and comorbidities, COVID-19 patients exhibit substantial differences in prognosis. Genetic polymorphisms in ACE and ACE2 have been implicated in disease progression, prompting our investigation into their role in COVID-19 evolution. Using next-generation sequencing (NGS), we analyzed ACE and ACE2 genes in a sample group comprising six subjects infected by SARS-CoV-2. Our findings revealed a correlation between specific polymorphisms and COVID-19 outcomes. Specifically, ACE and ACE2 intronic deletions were observed in all deceased patients, suggesting a potential association with mortality. These results highlight the significance of genetic factors in shaping the clinical course of COVID-19, emphasizing the importance of further research into the impact of genetic variations on COVID-19 severity.

The emergence of SARS-CoV-2 in 2019 led to a global pandemic with a significant impact on healthcare systems. Healthcare workers were particularly vulnerable due to frequent contact with COVID-19 patients. Despite vaccination, they remained at higher risk as the vaccines provided limited protection against infection with viral variants, like Delta or Omicron BA.1 and BA.5. Three years after the onset of the pandemic, we evaluated SARS-CoV-2 infection frequencies among healthcare workers with varying levels of patient contact: high-risk (frequent COVID-19 patient contact), intermediate-risk (non-COVID-19 patient contact), and low-risk (no patient contact). We assessed their cellular and humoral immune responses based on their vaccination status and number of prior infections. SARS-CoV-2-specific antibodies were measured by immunoglobulin ELISA, and neutralizing antibody titers were determined against the viral variants D614G, Delta, and Omicron BA.1 and BA.5. Cellular immune responses were analyzed using an interferon-γ ELISpot. Notably, three years into the pandemic, healthcare workers in daily contact with COVID-19 patients did not have higher infection rates compared to healthcare workers with non-COVID-19 patient contact or no patient contact. Immune responses were similar across all groups, highlighting the effectiveness of vaccination and current hygiene standards in preventing virus transmission from patients to staff.

SARS-CoV-2 is an obligatory intracellular pathogen that requires a lipid bilayer membrane for its transport to build its nucleocapsid envelope and fuse with the host cell. The biological membranes are constituted by phospholipids (PLs), and vitamin E (Vit E) protects them from oxidative stress (OS). The aim of this study was to demonstrate if treatment with Vit E restores the modified profile of the FA in PLs in serum from patients with coronavirus disease-19 (COVID-19). We evaluated Vit E, total fatty acids (TFAs), fatty acids of the phospholipids (FAPLs), total phospholipids (TPLs), 8-isoprostane, thromboxane B2 (TXB2), prostaglandins (PGE2 and 6-keto-PGF1α), interleukin-6 (IL-6), and C-reactive protein (CRP) in serum from 22 COVID-19 patients before and after treatment with Vit E and compared the values with those from 23 healthy subjects (HSs). COVID-19 patients showed a decrease in Vit E, TPLs, FAPLs, and TFAs in serum in comparison to HSs (p ≤ 0.01), and Vit E treatment restored their levels (p ≤ 0.04). Likewise, there was an increase in IL-6 and CRP in COVID-19 patients in comparison with HSs (p ≤ 0.001), and treatment with Vit E decreased their levels (p ≤ 0.001). Treatment with Vit E as monotherapy can contribute to restoring the modified FA profile of the PLs in the SARS-CoV-2 infection, and this leads to a decrease in lipid peroxidation, OS, and the inflammatory process.

The unprecedented introduction and spread of SARS-CoV-2, responsible for the COVID-19 epidemic, had many varied and unanticipated consequences for the United States and other countries. In addition to the direct effects of human infection, multiple industries, commodities, and jobs were impacted. This review describes the impact on an academic institution, with a chronological account of events related to constantly changing perceptions and understanding of the pandemic. Although a personal account, the objective is to document how leadership was able to adjust to circumstances in order to support research activities, student education, and the academic goals of our land grant university. It is hoped that these examples will inspire and better prepare us for a subsequent event and avoid what for the COVID-19 situation might be summarized as a progression from procrastination-pandemic-panic-pandemonium-endemic

Background and Objectives: SARS-CoV-2 is the pathogen that causes COVID-19 disease. Although the rate of COVID-19 reinfection is significant, the possible factors associated with this condition remain to be fully elucidated. The aim of the study was to identify clinical and serological factors associated with SARS-CoV-2 reinfection. Materials and Methods: We followed up on 120 patients with mild COVID-19 for one year. Various clinical data were collected, and serum levels of IgG anti-SARS-CoV-2 Spike antibodies were tested on days 21, 60, 90, and 180. The diagnosis of COVID-19 was based on symptomatology and the detection of viral RNA in nasal swabs using real-time PCR. Results: We observed eleven episodes of reinfection. Although no clinical or demographic characteristics were associated with reinfection, significantly higher levels of anti-Spike antibodies and a seropositive status at day 90 were significantly associated with the absence of reinfection. Moreover, the symptoms during the COVID-19 episode associated with seropositivity at day 90 were mainly headache, sneezing, anosmia, and runny nose. Conclusions: SARS-CoV-2 reinfection is not associated with the clinical or demographic characteristics of COVID-19 patients. Furthermore, our findings suggest that the presence and levels of IgG anti-Spike antibodies at day 90 of infection play a protective role against reinfection. Serological immunity at day 90 influences the response to vaccination.

NSAIDs and paracetamol are commonly used as antipyretic treatments, which may impair renal and hepatic function, respectively. Both organ systems are also negatively affected by COVID-19. In two retrospective case–control studies, we investigated whether COVID-19 is a risk factor for the development of renal or hepatic function impairment after NSAID and paracetamol use, respectively. In the NSAID study, we defined cases as patients with a decrease of ≥15% in the estimated glomerular filtration rate (eGFR). We matched them using a 1:2 ratio with controls who did not show a decrease in the eGFR. For the paracetamol study, we matched patients with ALT or ALP ≥ 3x, the upper limits of normal, using a 1:3 ratio with controls whose liver enzymes did not increase. In both studies, we selected demographic data, comorbidities, drug doses, and laboratory values as predictors in addition to SARS-CoV-2 test status. We applied different machine learning models to predict renal and hepatic function impairment. From the cohort of 12,263 unique adult inpatients, we found 288 cases of renal function impairment, which were matched with 576 controls, and 213 cases of liver function impairment, which were matched with 639 controls. In both case–control studies, testing positive for SARS-CoV-2 was not an independent risk factor for the studied adverse drug effects.

Under the aegis of the National Infectious Diseases Act, the virus transitioned from a category 2 menace to category 5, analogous to seasonal influenza. For this classification to be appropriate, a comprehensive assessment of the immune status of the Japanese population must be conducted to ensure adequacy. The current study has investigated the protracted immune responses of healthcare workers (HCWs) to SARS-CoV-2 in Japan. One year subsequent to the systematically implemented SARS-CoV-2 vaccination campaign among HCWs, humoral and cellular immune responses were sustained at levels as high as or higher than those immediately following the third booster vaccination. Persisting immunity has highlighted the resilience and lasting memory exhibited in HCW defense against the virus, suggesting that the classification of SARS-CoV-2 infection as a category 5 in Japan has appeared judicious.

In vaccine development, many use the spike protein (S protein), which has multiple “spike-like” structures protruding from the spherical structure of the coronavirus, as an antigen. However, there are concerns about its effectiveness and toxicity. When S protein is used in a vaccine, its ability to attack viruses may be weak, and its effectiveness in eliciting immunity will only last for a short period of time. Moreover, it may cause “antibody-dependent immune enhancement”, which can enhance infections. In addition, the three-dimensional (3D) structure of epitopes is essential for functional analysis and structure-based vaccine design. Additionally, during viral infection, large amounts of extracellular vesicles (EVs) are secreted from infected cells, which function as a communication network between cells and coordinate the response to infection. Under conditions where SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) molecular vaccination produces overwhelming SARS-CoV-2 spike glycoprotein, a significant proportion of the overproduced intracellular spike glycoprotein is transported via EVs. Therefore, it will be important to understand the infection mechanisms of SARA-CoV-2 via EV-dependent and EV-independent uptake into cells and to model the infection processes based on 3D structural features at interaction sites.

In the SARS-CoV-2 lineage, RNA elements essential for its viral life cycle, including genome replication and gene expression, have been identified. Still, the precise structures and functions of these RNA regions in coronaviruses remain poorly understood. This lack of knowledge points out the need for further research to better understand these crucial aspects of viral biology and, in time, prepare for future outbreaks. In this research, the in silico analysis of the cis RNA structures that act in the alpha-, beta-, gamma-, and deltacoronavirus genera has provided a detailed view of the presence and adaptation of the structures of these elements in coronaviruses. The results emphasize the importance of these cis elements in viral biology and their variability between different viral variants. Some coronavirus variants in some groups, depending on the cis element (stem-loop1 and -2; pseudoknot stem-loop1 and -2, and s2m), exhibited functional adaptation. Additionally, the conformation flexibility of the s2m element in the SARS variants was determined, suggesting a coevolution of this element in this viral group. The variability in secondary structures suggests genomic adaptations that may be related to replication processes, genetic regulation, as well as the specific pathogenicity of each variant. The results suggest that RNA structures in coronaviruses can adapt and evolve toward different viral variants, which has important implications for viral adaptation, pathogenicity, and future therapeutic strategies.

COVID-19, caused by the SARS-CoV-2 virus, is a highly pathogenic emerging infectious disease. Healthcare personnel (HCP) are presumably at higher risk of acquiring emerging infections because of occupational exposure. The prevalence of COVID-19 in HCP is unknown, particularly in low- to middle-income countries like El Salvador. The goal of this study was to determine the seroprevalence of anti-SARS-CoV-2 antibodies among HCP in El Salvador just prior to vaccine rollout in March 2021. We evaluated 2176 participants from a nationally representative sample of national healthcare institutions. We found 40.4% (n = 880) of the study participants were seropositive for anti-spike protein antibodies. Significant factors associated with infection included younger age; living within the central, more populated zone of the country; living in a larger household (≥7 members); household members with COVID-19 or compatible symptoms; and those who worked in auxiliary services (i.e., housekeeping and food services). These findings provide insight into opportunities to mitigate SARS-CoV-2 risk and other emerging respiratory pathogens in HCP in El Salvador.

Various vaccine platforms have been approved for broad use to prevent the transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. However, these vaccines exhibit distinct differences in immunogenicity and efficacy, which decline after vaccination and are further exacerbated by the emergence of virus variants and mutants. This study reports the immunization outcomes against the SARS-CoV-2 virus by assessing the immune responses and safety of different SARS-CoV-2 vaccines co-administered in BALB/c mice. Vaccine combinations comprising mRNA/adenovirus26-vector, mRNA/inactivated, adenovirus26-vector/inactivated, and mRNA/adenovirus26-vector/inactivated vaccines were prepared in optimized doses, and their activities upon immunization evaluated in comparison with individual mRNA, adenovirus26-vectored, and inactivated vaccines. Fourteen- and 28-days post-immunization, we measured spike-specific IgG response using Enzyme-Linked Immunosorbent Assay (ELISA), cytokine expression profiles through Quantitative real-time polymerase chain reaction (RT-PCR), and evaluated safety through histopathological examination. The mRNA/Vector/Inactivated group exhibited slightly higher anti-spike IgG levels, albeit not statistically significant (p > 0.132). Importantly, this regimen induced elevated IL-6 and IFN-γ mRNA expression levels (p < 0.0001) compared to immunization with individual vaccines. In summary, this study demonstrated that co-administering the mRNA/adenovirus26 vector/inactivated SARS-CoV-2 vaccines improved spike-specific IgG response, triggered significantly enhanced IL-6 and IFN-γ mRNA expression levels, and proved safe in mice.

Apart from providing user-friendly applications that support digitized healthcare routines, the use of wearable devices has proven to increase the independence of patients in a healthcare setting. By applying machine learning techniques to real health-related data, important conclusions can be drawn for unsolved issues related to disease prognosis. In this paper, various machine learning techniques are examined and analyzed for the provision of personalized care to COVID-19 patients with mild symptoms based on individual characteristics and the comorbidities they have, while the connection between the stimuli and predictive results are utilized for the evaluation of the system’s transparency. The results, jointly analyzing wearable and electronic health record data for the prediction of a daily dyspnea grade and the duration of fever, are promising in terms of evaluation metrics even in a specified stratum of patients. The interpretability scheme provides useful insight concerning factors that greatly influenced the results. Moreover, it is demonstrated that the use of wearable devices for remote monitoring through cloud platforms is feasible while providing awareness of a patient’s condition, leading to the early detection of undesired changes and reduced visits for patient screening.

COVID-19 is no longer a public health emergency of international concern, but long COVID’s effects are yet to be fully understood. Hence, globally, SARS-CoV-2 is still a profound threat to public health and of perilous nature as a zoonotic disease. Timely vaccination provided to individuals worldwide during the pandemic phase was under a certain degree of control; however, few studies have reported the effectiveness of vaccines administered in Mexico, and its surveillance is paramount. Furthermore, an unknown proportion of Mexican individuals have not yet received any vaccine, and the circulation of the Omicron, Pirola, and FLiRT variants is ongoing. A cross-sectional serology survey study design was employed, involving 150 individuals from Southern Mexico (Oaxaca) whose humoral immune responses after vaccination were tested by an ELISA; the receptor-binding domain of the SARS-CoV-2 spike protein served as a recombinant antigen in the ELISA. One hundred thirty-nine out of 150 individuals (92.6%; 95%-CI = 87–95%) examined were positive for the ELISA, but in 11 individuals, the vaccines did not induce any immune response. Interestingly, the immune responses (antibody prevalence and levels) of females (58%) were higher (T= −2.21; p-value = 0.02) than those of males (41%). However, in this sample population of Southern Mexico, age, vaccine type, comorbidity, and body mass index did not have any effect (p > 0.05) after COVID-19 vaccination. Taking all results together, here, we present factors that affected immune responses of individuals during the first vaccination campaign in Oaxaca, Mexico; however, vaccine surveillance during the post-pandemic phase needs further investigation.

The COVID-19 pandemic in Ukraine, from March 2020 to June 2022, witnessed distinct waves, each characterized by an increase in cases and fatalities. Next-generation sequencing has been used to understand the impact of viral variants on the pandemic situation in Ukraine. We analyzed SARS-CoV-2 genome sequencing data to identify viral variants circulating during each wave. By integrating epidemiological information, we established associations between viral variants and disease spread. The adoption of next-generation sequencing for SARS-CoV-2 surveillance in Ukraine, despite limited resources, yielded adequate and trustworthy results, reflecting the pandemic situation. After the Russian military invasion of Ukraine in February 2022, a large number of refugees crossed the border with neighboring countries. Mutation analysis on sequencing data from Ukraine and Poland was used to estimate the exchange of SARS-CoV-2 variants between the countries during this period. Omicron subvariants detected in both countries were similar. The analysis of SARS-CoV-2 sequences from Poland and Ukraine revealed shared nucleotide mutations that can be used to identify the directions of spreading.

Enisamium is an orally available therapeutic that inhibits influenza A virus and SARS-CoV-2 replication. We evaluated the clinical efficacy of enisamium treatment combined with standard care in adult, hospitalized patients with moderate COVID-19 requiring external oxygen. Hospitalized patients with laboratory-confirmed SARS-CoV-2 infection were randomly assigned to receive either enisamium (500 mg per dose, four times a day) or a placebo. The primary outcome was an improvement of at least two points on an eight-point severity rating (SR) scale within 29 days of randomization. We initially set out to study the effect of enisamium on patients with a baseline SR of 4 or 5. However, because the study was started early in the COVID-19 pandemic, and COVID-19 had been insufficiently studied at the start of our study, an interim analysis was performed alongside a conditional power analysis in order to ensure patient safety and assess whether the treatment was likely to be beneficial for one or both groups. Following this analysis, a beneficial effect was observed for patients with an SR of 4 only, i.e., patients with moderate COVID-19 requiring supplementary oxygen. The study was continued for these COVID-19 patients. Overall, a total of 592 patients were enrolled and randomized between May 2020 and March 2021. Patients with a baseline SR of 4 were divided into two groups: 142 (49.8%) were assigned to the enisamium group and 143 (50.2%) to the placebo group. An analysis of the population showed that if patients were treated within 4 days of the onset of COVID-19 symptoms (n = 33), the median time to improvement was 8 days for the enisamium group and 13 days for the placebo group (p = 0.005). For patients treated within 10 days of the onset of COVID-19 symptoms (n = 154), the median time to improvement was 10 days for the enisamium group and 12 days for the placebo group (p = 0.002). Our findings suggest that enisamium is safe to use with COVID-19 patients, and that the observed clinical benefit of enisamium is worth reporting and studying in detail.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a human pathogenic virus that encodes for a helicase (SC2Hel) that is essential for viral replication. SC2Hel has the ability to unravel dsRNA or dsDNA in an NTP-dependent manner from the 5′ to 3′ directionality. The standard helicase assay from studies involving SARS-CoV and SARS-CoV-2 have relied on the concept of fluorescence resonance energy transfer. Adding to the collection of helicase assays, herein, we have developed a novel tetrazolium-based colorimetric assay system for the detection of ADP that is produced via SC2Hel activity. This SC2Hel assay combines three enzyme-coupled steps involving the ADP-dependent Thermococcus litoralis glucokinase (TlGlcK), Leuconostoc mesenteroides glucose-6-phosphate dehydrogenase (LmG6PDH), and Clostridium kluyveri diaphorase (CkDIA). Iodonitrotetrazolium chloride (INT), a colorimetric tetrazolium reagent, was used in the final step of the assay that converted into INT-formazan during reduction. INT-formazan in the assay’s buffered solution at pH 7.6 exhibited an intense colorimetric response at a wavelength maximum of 505 nm. The assay exhibited excellent performance characteristics as it revealed a Z’ factor of 0.87 and it has the potential to be further adopted into high-throughput screening studies for therapeutic drug discovery research.

One of the most pressing challenges associated with SARS treatment is the emergence of new variants that may be transmissible, causing more severe disease or being resistant to the current standard of treatment. This study aimed to identify potential drug candidates from novel imidazole derivatives against SARS-CoV-2 main protease (Mpro), a crucial drug target for treating viral infection, using a computational approach that integrated molecular docking and dynamics simulation. In this study, we utilized AutoDock Vina within the PyRx workspace for molecular docking analysis to explore the inhibitory effects of the compounds on the Mpro, a drug target for SARS-CoV-2. The ADMET properties of these compounds, including absorption, distribution, metabolism, excretion, and toxicity, were evaluated using the SwissADME and ADMETLab servers. Each of the 18 compounds that were tested demonstrated strong binding affinities towards Mpro, with imidazolyl–methanone C10 showing the most significant binding affinity. Moreover, pyridyl–imidazole C5, thiophenyl–imidazole C1, and quinoline–imidazole C14 displayed binding affinities of −8.3, −8.2, and −7.7 Kcal/mol, respectively. These compounds interacted with specific amino acid residues (HIS A:41—CYS A:145) within the Mpro protein. To assess the stability of the ligand with the best binding affinity, molecular dynamics (MD) simulations were conducted using Schrodinger software, which revealed its stability over the simulation period. The study provides valuable insights into the potential of imidazole derivatives as SARS-CoV-2 Mpro inhibitors. All compounds including C10 display promising characteristics and hold potential as drug candidates for SARS-CoV-2. However, further optimization and experimental validation of these compounds are necessary to advance their development as effective therapeutics against viral infections.

Background: Coronavirus disease 2019 (COVID-19) can lead to severe respiratory illness, rapid disease progression, and higher rates of intensive care unit admission in pregnant women. Infection during pregnancy is associated with an increased risk of preterm delivery, cesarean section, fetal dysfunction, preeclampsia, and perinatal death. Vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from pregnant women to their fetuses has also been observed. Although severe infections in neonates and infants are rare, newborns can experience serious consequences from COVID-19 due to their suboptimal humoral immune system protection. The amino acids in the structural proteins of SARS-CoV-2 are constantly mutating. Since around January 2023, COVID-19, caused by omicron-type SARS-CoV-2 variants, has been prevalent globally. These variants can evade the immune response triggered by traditional mRNA-based COVID-19 vaccines, such as BNT162b2. Therefore, vaccination with BNT162b2 XBB.1.5, which provides protection against omicron-type SARS-CoV-2 variants, is recommended. Methods: This retrospective cohort study included 148 pregnant women who received the BNT162b2 XBB.1.5 vaccine at 30 partner medical institutions from September 2023 to January 2024. We examined the titers of anti-spike glycoprotein SARS-CoV-2 immunoglobin G (IgG) and IgA in the blood and umbilical cord blood obtained from the participants using ELISA. Findings: Anti-spike glycoprotein SARS-CoV-2 IgG and IgA titers were highest in the blood and cord blood at late gestational age (28–34 weeks). No serious side effects or adverse events were observed in either the pregnant women or their newborns. Interpretation: Pregnant women who received the BNT162b2 XBB.1.5 vaccine during gestational weeks 28 to 34 had the highest titers of anti-omicron SARS-CoV-2 variant antibodies in their blood. Moreover, these antibodies were transferred to their umbilical cord blood. To validate our findings, large cohort clinical studies involving numerous pregnant women are warranted. Funding: This study was funded by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS) and Grants-in-Aid for Medical Research from the Japan Agency for Medical Research and Development (AMED).

Bronchial asthma (BA) continues to be a difficult disease to diagnose. Various factors have been described in the development of BA, but to date, there is no clear evidence for the etiology of this chronic disease. The emergence of COVID-19 has contributed to the pandemic course of asthma and immunologic features. However, there are no unambiguous data on asthma on the background and after COVID-19. There is correlation between various trigger factors that provoke the development of bronchial asthma. It is now obvious that the SARS-CoV-2 virus is one of the provoking factors. COVID-19 has affected the course of asthma. Currently, there is no clear understanding of whether asthma progresses during or after COVID-19 infection. According to the results of some studies, a significant difference was identified between the development of asthma in people after COVID-19. Mild asthma and moderate asthma do not increase the severity of COVID-19 infection. Nevertheless, oral steroid treatment and hospitalization for severe BA were associated with higher COVID-19 severity. The influence of SARS-CoV-2 infection is one of the protective factors. It causes the development of severe bronchial asthma. The accumulated experience with omalizumab in patients with severe asthma during COVID-19, who received omalizumab during the pandemic, has strongly suggested that continued treatment with omalizumab is safe and may help prevent the severe course of COVID-19. Targeted therapy for asthma with the use of omalizumab may also help to reduce severe asthma associated with COVID-19. However, further studies are needed to prove the effect of omalizumab. Data analysis should persist, based on the results of the course of asthma after COVID-19 with varying degrees of severity.

Background. The emergence of the Omicron strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end of December 2021 has drastically increased the number of infected children in Japan, along with the number of children with febrile convulsions, but its clinical impact is unclear. Materials and Methods. We compared the frequency of SARS-CoV-2 infection in children hospitalized with febrile convulsions with the frequency of SARS-CoV-2 infection in children with fever and respiratory symptoms without convulsions. Results. In 2021 and 2022, 49 and 58 children required emergency hospitalization for febrile convulsions (FC group) with status epilepticus or cluster spasms, in which 24 and 38 children underwent a Filmarray® respiratory panel test (FA test), respectively, and others received a quantitative antigen test for SARS-CoV-2. In 2022, only six patients tested positive for SARS-CoV-2 (10.3%, 6/58). As a reference group, 655 children aged

This study explored the inhibitory potential of gallium maltolate against severe acute respiratory syndrome coronavirus 2 and main and papain-like proteases. Computational methods, including density functional theory and molecular docking, were used to assess gallium maltolate reactivity and binding interactions. Density functional theory calculations revealed gallium maltolate’s high electron-capturing capacity, particularly around the gallium metal atom, which may contribute to their activity. Molecular docking demonstrated that gallium maltolate can form strong hydrogen bonds with key amino acid residues like glutamate-166 and cysteine-145, tightly binding to main and papain-like proteases. The binding energy and interactions of gallium maltolate were comparable to known SARS-CoV-2 inhibitors like N-[(5-methyl-1,2-oxazol-3-yl)carbonyl]-L-alanyl-L-valyl-N-{(2S,3E)-5-(benzyloxy)-5-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]pent-3-en-2-yl}-L-leucinamide, indicating its potential as an antiviral agent. However, further experimental validation is required to confirm its effectiveness in inhibiting SARS-CoV-2 replication and treating COVID-19.

Background: SARS-CoV-2 is the coronavirus responsible for the COVID-19 pandemic. Even though we are no longer in a pandemic situation, people are still getting infected, some of them need hospitalization and a few of them die. Methods: We conducted a retrospective study including 445 patients who accessed the Emergency Section of Policlinico Umberto I, Rome, Italy, where they had routine blood exams. In this study, we focused on the complete blood count, serum creatinine and azotemia. The data were analyzed using ANOVA, Spearman correlation and ROC analyses. They were divided into four groups based on their clinical outcomes: (1) the emergency group (patients who had mild forms and were quickly discharged); (2) the hospital ward group (patients who were admitted to the emergency section and were then hospitalized in a COVID-19 ward); (3) the intensive care unit (ICU) group (patients who required intensive assistance after the admission in the emergency section); (4) the deceased group (patients who had a fatal outcome after admission to the emergency section). Results: We found significant changes for creatinine, azotemia, hematocrit, mean corpuscular hemoglobin concentration, basophils, monocytes, red blood cell distribution width, hemoglobin, hematocrit and red blood cell numbers using ANOVA according to their clinical outcomes, particularly for the deceased group. Also, we found linear correlations of clinical outcomes with eosinophils, hemoglobin, hematocrit, mean corpuscular hemoglobin concentration, lymphocyte, neutrophil, platelet and red blood cell number and red blood cell distribution width. Conclusions: This study discloses an early association between “classical” routine blood biomarkers and the severity of clinical outcomes in Omicron patients.

Data on antibody response (AR) after vaccination against SARS-CoV2 in hematopoietic stem-cell transplantation setting (HSCT) were initially scarce, mainly due to the exclusion of such patients from approval studies. Shortly after the worldwide application of vaccination against SARS-CoV-2 in vulnerable populations such as patients with hematologic malignancies, limited single-center trials, including HSCT patients, were published. However, there was a great heterogeneity between them regarding the type of underlying malignancy, co-current treatment, type of vaccine, method of AR measurement, and time point of AR measurement. Herein, we present the results of a prospective study on AR after vaccination for SARS-CoV-2 using the BNT162b2 vaccine in a cohort of 54 HSCT recipients—mostly autologous from a single Unit—along with a broad review of the current literature. In our cohort, the AR positivity rate at 1 month was 80.8% and remained positive in 85.7% of patients at 3 months after vaccination. There were only nine non-responders, who were more heavily pretreated and more frequently hypogammaglobulinemic compared to responders. High antibody titers (AT), [AT ≥ 1000 U/mL], were detected in 38.5% and 30.6% of the patients at m1 and m3, respectively. A significant decline in AT between m1 and m3 was demonstrated—p < 0.0001; median AT1 and AT3 were 480.5 and 293 U/mL, respectively. A novel finding of our study was the negative impact of IgA hypogammaglobulinemia on response to vaccination. Other negative significant factors were treatment with anti-CD20 antibody at vaccination and vaccination within 18 months from HSCT. Our data indicate that HSCT recipients elicit a positive response to the BNT162b2 vaccine against SARS-CoV-2 when vaccinated at 6 months post-transplant, and vaccination should be offered to this patient population even within the post-pandemic COVID-19 era.

Many metabolic processes at the molecular level support both viral attack strategies and human defenses during COVID-19. This knowledge is of vital importance in the design of antiviral drugs. In this study, we extracted 18 articles (2021–2023) from PubMed reporting the discovery of hub nodes specific for the liver during COVID-19, identifying 142 hub nodes. They are highly connected proteins from which to obtain deep functional information on viral strategies when used as functional seeds. Therefore, we evaluated the functional and structural significance of each of them to endorse their reliable use as seeds. After filtering, the remaining 111 hubs were used to obtain by STRING an enriched interactome of 1111 nodes (13,494 interactions). It shows the viral strategy in the liver is to attack the entire cytoplasmic translational system, including ribosomes, to take control of protein biosynthesis. We used the SARS2-Human Proteome Interaction Database (33,791 interactions), designed by us with BioGRID data to implement a reverse engineering process that identified human proteins actively interacting with viral proteins. The results show 57% of human liver proteins are directly involved in COVID-19, a strong impairment of the ribosome and spliceosome, an antiviral defense mechanism against cellular stress of the p53 system, and, surprisingly, a viral capacity for multiple protein attacks against single human proteins that reveal underlying evolutionary–topological molecular mechanisms. Viral behavior over time suggests different molecular strategies for different organs.

Despite evidence demonstrating the risks of developing diabetes mellitus because of SARS-CoV-2, there is, however, insufficient scientific data available to elucidate the relationship between diabetes mellitus and COVID-19. Research indicates that SARS-CoV-2 infection is associated with persistent damage to organ systems due to the systemic inflammatory response. Since COVID-19 is known to induce these conditions, further investigation is necessary to fully understand its long-term effects on human health. Consequently, it is essential to consider the effect of the COVID-19 pandemic when predicting the prevalence of diabetes mellitus in the future, especially since the incidence of diabetes mellitus was already on the rise before the pandemic. Additional research is required to fully comprehend the impact of SARS-CoV-2 infection on glucose tolerance and insulin sensitivity. Therefore, this article delves deeper into the current literature and links the perceived relationship between SARS-CoV-2 and diabetes. In addition, the article highlights the necessity for further research to fully grasp the mechanisms that SARS-CoV-2 utilises to induce new-onset diabetes. Where understanding and consensus are reached, therapeutic interventions to prevent the onset of diabetes could be proposed. Lastly, we propose advocating for the regular screening of diabetes and pre-diabetes, particularly for the high-risk population with a history of COVID-19 infection.

Background: Long COVID refers to the persistence or development of signs and symptoms well after the acute phase of COVID-19. Objective of the study: To investigate the long-term outcomes of the SARS-CoV-2 infection in terms of psychological, social, and relational consequences within the Italian population. Materials and methods: We conducted an observational, cross-sectional, and multicenter study using an online questionnaire distributed to a sample of the Italian population. By utilizing the Short Form 12 Health Survey (SF-12) and the Hikikomori scale, we assessed perceived quality of life and social isolation, respectively. The questionnaire also included an open-answer question: “What will you remember about the pandemic period?”. We used generative artificial intelligence to analyze and summarize the corresponding answers. Results: A total of 1097 people participated in this study. A total of 79.3% (n = 870) of participants declared that they had been hospitalized and 62.8% (n = 689) received home care. Physical symptoms included headaches (43%, n = 472) and asthma (30.4%, n = 334). Additionally, 29.2% (n = 320) developed an addiction during the pandemic and, among these, 224 claimed internet addiction while 73 declared an emotional addiction. Furthermore, 51.8% (n = 568) experienced limitations in carrying out daily life activities. According to the Hikikomori scale, participants with positive SARS-CoV-2 infection exhibited higher levels of isolation compared to the others (p < 0.001). Participants without COVID-19 showed higher levels of emotional support (p < 0.001). Our semiautomatic analysis of the open-ended responses, obtained by a procedure based on a free large language model, allowed us to deduce and summarize the main feelings expressed by the interviewees regarding the pandemic. Conclusions: The data collected emphasize the urgent need to investigate the consequences of long COVID in order to implement interventions to support psychological well-being.

The global spread of SARS-CoV-2 has increased infections among pregnant women. This study aimed to explore placental pathology alterations and angiogenic factor levels in term pregnant women after SARS-CoV-2 infection in a retrospective single-center study. Additionally, we investigated the role and underlying mechanism of the vascular inflammation-promoting, cysteine-rich protein 61 (CYR61/CCN1) in this context. All analyses were performed in term pregnant women infected with or without SARS-CoV-2. The sFlt-1, PlGF, and sEng serum levels were quantified using ELISA. Placental protein expressions were examined by immunoblot and immunostaining. Additionally, the effect of CCN1 protein on SGHPL-5 trophoblast cells was examined. We found that SARS-CoV-2 activated the inflammatory response in pregnant women, leading to pronounced vascular alterations in placental villous tissues. Elevated serum anti-angiogenic factors (sFlt-1, sEng) upon SARS-CoV-2 infection may directly contribute to these pathological changes. Upregulated CCN1 and pNF-κB in placental villous tissues of infected patients are identified as crucial factors in placental alterations. As a conclusion, CCN1 was significantly elevated in the placentas of term pregnant women infected with SARS-CoV-2. By activating a cascade of inflammatory responses, CCN1 induced the production of the anti-angiogenic factors sFlt-1 and sEng, which may lead to abnormal placental vascular architecture.

Purpose: We conducted a retrospective case series of seven male COVID-19 patients with respiratory failure and suspected OSA based on clinical features to evaluate the effects of undiagnosed obstructive sleep apnea (OSA) on COVID-19 outcomes and the response to a continuous positive airway pressure (CPAP) treatment. Cardiorespiratory polygraphy (CRP) and a continuous positive airway pressure treatment were used for diagnosis and management. They confirmed severe obstructive sleep apnea in all patients (apnea/hypopnea index > 30) and improved overnight oxygenation and symptoms at the 1-month follow-up. Conclusions: Undiagnosed obstructive sleep apnea may negatively impact COVID-19 outcomes by exacerbating respiratory failure. Recognition and treatment with continuous positive airway pressure can optimize the management of such patients.