COVID-19 Research Articles

SARS-CoV-2 disrupts host gene networks: unveiling key hub genes as potential therapeutic targets for COVID-19 management

Although the end of COVID-19 as a public health emergency was declared on May 2023, still new cases of the infection are reported and the risk remains of new variants emerging that may cause new surges in cases and deaths. While clinical symptoms have been rapidly defined worldwide, the basic body responses and pathogenetic mechanisms acting in patients with SARS-CoV-2 infection over time until recovery or death require further investigation. The understanding of the molecular mechanisms underlying the development and course of the disease is essential in designing effective preventive and therapeutic approaches, and ultimately reducing mortality and disease spreading. The current investigation aimed to identify the key genes engaged in SARS-CoV-2 infection. To achieve this goal high-throughput RNA sequencing of peripheral blood samples collected from healthy donors and COVID-19 patients was performed. The resulting sequence data were processed using a wide range of bioinformatics tools to obtain detailed modifications within five transcriptomic phenomena: expression of genes and long non-coding RNAs, alternative splicing, allel-specific expression and circRNA production. The in silico procedure was completed with a functional analysis of the identified alterations. The transcriptomic analysis revealed that SARS-CoV-2 has a significant impact on multiple genes encoding ribosomal proteins (RPs). Results show that these genes differ not only in terms of expression but also manifest biases in alternative splicing and ASE ratios. The integrated functional analysis exposed that RPs mostly affected pathways and processes related to infection-COVID-19 and NOD-like receptor signaling pathway, SARS-CoV-2-host interactions and response to the virus. Furthermore, our results linked the multiple intronic ASE variants and exonic circular RNA differentiations with SARS-CoV-2 infection, suggesting that these molecular events play a crucial role in mRNA maturation and transcription during COVID-19 disease. By elucidating the genetic mechanisms induced by the virus, the current research provides significant information that can be employed to create new targeted therapeutic strategies for future research and treatment related to COVID-19. Moreover, the findings highlight potentially promising therapeutic biomarkers for early risk assessment of critically ill patients.

Impact of perceived neighborhood social cohesion on vaccination intentions in the post-pandemic era

ObjectiveTo examine the relationship between perceived neighborhood social cohesion (NSC) and intentions to obtain seasonal influenza and COVID-19 vaccines among US adults post COVID-19 pandemic. MethodsWe conducted a cross-sectional, nationally representative survey of US residents (N = 2189) in May 2023 on their perceived NSC, COVID-19 and seasonal influenza vaccination intentions, healthcare access, perceived risk of COVID-19 or flu infection, loneliness, and trust in doctors. We used bivariate probit regressions to examine joint associations between perceived NSC and intentions to receive influenza and COVID-19 vaccines, controlling for several participant characteristics (e.g., race). Results2164 respondents provided consent to study questions. Trust-related NSC (trust in neighbors) was positively associated with intentions to become vaccinated against both influenza and COVID-19 viruses. Higher relational NSC (perception of a close-knit neighborhood) was positively associated while higher value-based NSC (perception that neighbors share the same values) was negatively associated with intentions to become vaccinated against COVID-19. Healthcare access, perceived risk of infection (COVID-19 or flu), and trust in doctors were positively associated with intentions to become vaccinated against both viruses. ConclusionsIn a post-pandemic era, higher trust-related and relational, perceived NSC (vaccine-dependent), greater access to healthcare, higher perceived risk of infection, and greater trust in doctors were related to higher influenza and COVID-19 vaccination intentions, while higher value-based NSC was related to lower COVID-19 vaccination intentions among US adults. Thus, specific aspects of NSC, healthcare access barriers, misinformation on infection risk, and medical mistrust may influence an individual's willingness and ultimate decision to become vaccinated.

Natural Products as Inhibitors of Coronavirus: An Update

Abstract: In the past couple of decades, several corona virus infections have alarmed the world claiming deaths of huge population over the globe. Effective anti-viral agents have been researched for treatment of COVID-19 infection. Vaccination has come up as an ultimate prevention against SARS-CoV-2virus as many vaccines have been recommended by WHO to be used for prevention from COVID-19. Alternative treatment strategies to combat infection include drug repurposing as well as supportive therapies. Traditional medicines being used from ancient times for different disease conditions provide a wealth of chemical diversity. Different classes of natural products are being utilized to study their antiviral properties and contributed in past for different viral diseases. The aim of current review is to enumerate different secondary metabolites and their pharmacophoric features against corona viruses that can be further optimized to develop more potent inhibitors specific to SARS-CoV-2. This review systematically evaluates natural products and their synthetic/ semisynthetic analogs belonging to terpenoids, polyphenols, saponins, and alkaloids having antiviral activity against coronaviruses. The information obtained from scope of Indian medicinal plants is also discussed which may be evaluated in future against SARS-CoV-2. Thus, it is proposed that the natural products may be used to develop potential inhibitors using the knowledge gained from similar studies to prevent morbidity and mortalities due to SARS-CoV-2.

Favipiravir pharmacokinetics in Thai adults with mild COVID-19: A sub-study of interpatient variability and ethnic differences in exposure.

This sub-study sought to characterize the pharmacokinetics (PK) of favipiravir (FPV) within Thai adults and quantitatively assess differences in exposure to those previously reported in other populations as a basis to understand putative differences in efficacy between studies conducted in different regions. It was nested within a prospective trial of adults with symptomatic COVID-19 infection without pneumonia receiving 1800 mg FPV twice-daily on day 1 and 800 mg twice-daily thereafter. Individual PK profiles were fitted with a one-compartment disposition model (first-order absorption). Eight adults (seven female) with a median age of 39 years and BMI of 27.9 kg/m2 were included. Seven adults achieved plasma concentrations above the EC90 invitro target (25 mg/L), with minimum-maximum concentrations decreasing with repeat dosing. The mean FPV apparent clearance observed in this study was 1.1 L/h (coefficient of variation [CV]: 60%), apparent volume of distribution 20.6 L (CV: 40%), absorption rate constant 6.1 h (CV: 100%), and 2.4 daily % change in apparent clearance (CV: 315%). Higher exposures were observed in these Thai adults compared with data from previous studies in Chinese, Japanese, and Turkish populations, respectively. Current FPV doses recommended in Thailand achieved target plasma concentrations with higher exposures than those described previously in other populations. The limited sample size prohibits firm conclusions from being drawn but the presented data warrants confirmation with a view to interrogate the appropriateness of doses used in randomized clinical trials that failed to demonstrate efficacy.

Pulmonary embolism after SARS-CoV-2 vaccination

BackgroundDuring the COVID-19 vaccination campaign in Sweden, pulmonary embolism (PE) was a frequently reported suspected serious ADR. The aim was to estimate risk of PE following vaccination for COVID-19 in the Swedish population aged 18 to 84 years. MethodsPopulation-based cohort study using the CoVacSafe-SE established platform including national registers. PE-case definition: Individuals discharged from inpatient-care or visiting specialized outpatient-care with a main diagnosis of PE occurring between 27-Dec-2020 and 31-Dec-2022 without simultaneous diagnosis of COVID-19 infection. Time-to-event analysis was performed using multi-variable Cox’ proportional hazard’s models. Hazard Ratios (HR) adjusted for age, sex and co-morbidities were modelled.The vaccines were BNT162b2/Comirnaty®, mRNA1273/Spikevax® and ChAdOx1 nCoV-19/Vaxzevria® without regard to variants. Doses number one to five were studied. ResultsEighty percent of the study-population (≈6.1 million people) received at least two doses of COVID-19 vaccine. A total of 12,456 cases of PE were identified. Twenty-eight days after vaccinations we observed 99 cases after 701,455 1st doses of ChAdOx1 nCoV-19, HRadj, 1.29 (95%-CI, 1.05–1.59). Corresponding for BNT162b2 was 361 cases after 4,708,284 1st doses of BNT162b2 HRadj of 1.19 (95%-CI, 1.06–1.34) driven by age group 65–84; HR adj, 1.24 (95%-CI, 1.07–1.44). No increased risks were observed for mRNA1273. ConclusionIn this nation-wide study, no strong associations were found between COVID-19 vaccinations and pulmonary embolism. Small increases in relative risk for the earliest doses of vaccines may be associated with prioritizing the frailest groups of people in the vaccination campaign, thus selection bias or unmeasured residual confounding is possible.

The Potential Roles of Ficus carica Extract in the Management of COVID-19 Viral Infections: A Computer-aided Drug Design Study.

The conventional processes of drug discovery are too expensive, timeconsuming and the success rate is limited. Searching for alternatives that have evident safety and potential efficacy could save money, time and improve the current therapeutic regimen outcomes. Clinical phytotherapy implies the use of extracts of natural origin for prophylaxis, treatment, or management of human disorders. In this work, the potential role of common Fig (Ficus carica) in the management of COVID-19 infections has been explored. The antiviral effects of Cyanidin 3-rhamnoglucoside which is abundant in common Figs have been illustrated on COVID-19 targets. The immunomodulatory effect and the ability to ameliorate the cytokine storm associated with coronavirus infections have also been highlighted. This work involves various computational studies to investigate the potential roles of common figs in the management of COVID-19 viral infections. Two molecular docking studies of all active ingredients in common Figs were conducted starting with MOE to provide initial insights, followed by Autodock Vina for further confirmation of the results of the top five compounds with the best docking score. Finally, Molecular dynamic simulation alongside MMPBSA calculations were conducted using GROMACS to endorse and validate the entire work.

Cross-sectional and longitudinal genotype to phenotype surveillance of SARS-CoV-2 variants over the first four years of the COVID-19 pandemic

Continued phenotyping and ongoing molecular epidemiology are important in current and future monitoring of emerging SARS-CoV-2 lineages. Herein we developed pragmatic strategies to track the emergence, spread and phenotype of SARS-CoV-2 variants in Australia in an era of decreasing diagnostic PCR testing and focused cohort-based studies. This was aligned to longitudinal studies that span 4 years of the COVID-19 pandemic. Throughout 2023, we partnered with diagnostic pathology providers and pathogen genomics teams to identify relevant emerging or circulating variants in the New South Wales (NSW) community. We monitored emerging variants through viral culture, growth algorithms, neutralisation responses and changing entry requirements defined by ACE2 and TMPRSS2 receptor use. To frame this in the context of the pandemic stage, we continued to longitudinally track neutralisation responses at the population level using pooled Intravenous Immunoglobulins (IVIG) derived from in excess of 700,000 donations. In antibodies derived from recent individual donations and thousands of donations pooled in IVIGs, we observed continued neutralisation across prior and emerging variants with EG.5.1, HV.1, XCT and JN.1 ranked as the most evasive SARS-CoV-2 variants. Changes in the type I antibody site at Spike positions 452, 455 and 456 were associated with lowered neutralisation responses in XBB lineages. In longitudinal tracking of population immunity spanning three years, we observed continued maturation of neutralisation breadth to all SARS-CoV-2 variants over time. Whilst neutralisation responses initially displayed high levels of imprinting towards Ancestral and early pre-Omicron lineages, this was slowly countered by increased cross reactive breadth to all variants. We predicted JN.1 to have a marked transmission advantage in late 2023 and this eventuated globally at the start of 2024. We could not attribute this advantage to neutralisation resistance but rather propose that this growth advantage arises from the preferential utilisation of ACE2 pools that cannot engage TMPRSS2 at its Collectrin-Like Domain (CLD). The emergence of many SARS-CoV-2 lineages documented at the end of 2023 was found to be initially associated with lowered neutralisation responses. This continued to be countered by the gradual maturation of cross-reactive neutralisation responses over time. The later appearance and dominance of the divergent JN.1 lineage cannot be attributed to a lack of neutralisation responses alone, and our data supports that its dominance is a culmination of both lowered neutralisation and changes in ACE2/TMPRSS2 entry preferences. This work was primarily supported by Australian Medical Foundation research grants MRF2005760 (ST, GM & WDR), MRF2001684 (ADK and ST) and Medical Research Future Fund Antiviral Development Call grant (WDR), Medical Research Future Fund COVID-19 grant (MRFF2001684, ADK & SGT) and the New South Wales Health COVID-19 Research Grants Round 2 (SGT).

Worldwide Clinical and Real-World Exposure to Baricitinib

Introduction: Baricitinib (BARI), an oral selective JAK inhibitor, is approved in many geographies for adults with rheumatoid arthritis or alopecia areata and for patients as young as age 2 years with atopic dermatitis or juvenile idiopathic arthritis. It is also approved in the US for hospitalized patients with COVID-19 infection. We report the worldwide clinical trial and real-world exposure to BARI across a range of diseases, ages and racial backgrounds. Methods: Real-world patient exposure estimates were calculated based on total mg sold, average daily dose, and average length of therapy as reported to regulatory agencies through the cumulative timeframe ending Jan. 31, 2024. Clinical trial exposures were based on actual exposures from completed trials through Feb. 13, 2024, and estimates were made for ongoing blinded trials based on the enrolment/randomization schemes Results: In the real-world setting, an estimated 1,836,600 patients have been exposed to the following BARI doses: 1 mg, ~2,000 (0.1%); 2 mg, ~524,900 (28.6%); 4 mg, ~1,309,600 (71.3%). Of these estimated exposures, ~ 57% were for COVID-19 with the remaining for all other indications combined. Across 59 clinical trials (completed and ongoing), an estimated 14,660 subjects (548 healthy volunteers and 14,112 patients) have received BARI since June 2008. Exposures from completed studies include 10,276 patients (62% female), 399 of whom were <18 yrs of age (≤1 month, N=4; 1 month - ≤2 yrs, N=24; >2 - ≤12 yrs, N=111; >12 - ≤18 yrs, N=260), 8820 were >18 to ≤65 yrs, 1027 were >65 yrs, and 30 had age unknown. An additional 467 adolescent and pediatric patients down to the age of 2 have been treated with BARI for atopic dermatitis in an ongoing clinical trial, bringing the total number of patients <18 years of age to 866 across dermatologic, rheumatologic, other autoimmunologic, and acute infectious diseases (excluding alopecia areata for which there is an ongoing pediatric trial). Clinical trial exposures by racial and ethnic background are as follows: Asian, N=2,491; Black, N=450; Caucasian, N=6,237; other, N=496; multiple, N=135; unknown, N=467. Conclusion: There has been extensive real-world exposure to BARI across indications and populations, and BARI is a well-studied molecule in clinical trials, across varied disease states, racial populations and ages. Since average daily dose and length of therapy may vary over time, real-world exposures are only an estimate of total patients receiving BARI. Exposures in clinical trials include patients as young as less than 1 month of age up to patients over the age of 65 years. While these exposures do not indicate efficacy or safety, they provide data to establish the overall profile of the drug and can inform on its performance over time across a variety of populations.

Self-poisoning in young Australians: The impact of COVID-19 and recent trends following easing of restrictions

Introduction: Self-poisoning is the most common form of hospitalised self-harm in young people and has been increasing over the last decade. The COVID-19 pandemic was associated with further increases in self-harm in adolescents. There are limited data on changes after pandemic restrictions ended. This study aimed to describe recent trends in self-poisoning in young people. Setting: Australia 2018–2023. Methods: A retrospective analysis of self-poisoning calls to Australia’s poisons information centres. Intentional poisoning exposures in people aged 5–19 years were included in the main analysis. We also examined intentional poisonings in people aged 20 and over for comparison. We used interrupted time-series analysis to estimate the impact of COVID-19 (March 2020) and ‘re-opening’ (December 2021), when many restrictions were lifted in Australia. We compared effects in the jurisdictions with most disruptions and lockdowns with other jurisdictions. Results: There were 201,755 self-poisonings documented, 64% female, with 19,946 children (aged 5–14, 9.9%) and 44,388 adolescents (aged 15–19, 22.0%). There was a steep increase in the rate of poisoning in female children and adolescents – with the annual increase being 1.361 (95% confidence interval = [1.074, 1.735]) and 1.154 (95% confidence interval = [1.049, 1.283]) times faster than pre-pandemic trends in these two groups between March 2020 and December 2021. Following relaxation of restrictions, there was a sudden drop and then slow decline in self-poisonings (despite rising COVID-19 infection rates). There was an overall 29.6% increase in intentional poisonings in young people over the study period. This is markedly more pronounced among young females (37.0%) vs males (11.2%). There were substantial jurisdictional variations, with larger increases in Victoria, Tasmania and the Australian Capital Territory. Conclusion: There has been a marked increase in child and adolescent female self-poisonings over the last 6 years, with increases strongly associated with COVID-19 pandemic restrictions but persisting after their removal.

Laboratory findings predictive of critical illness in hospitalized COVID-19 patients in Tunisia

Background COVID-19 disease has spread rapidly worldwide, causing high mortality. Accessible biomarkers capable of early identification of patients at risk of severe form are needed in clinical practice. The aim of the study was to determine the biological markers that predict a critical condition. Methods Retrospective study including patients with confirmed COVID-19 hospitalized between September 2020 and June 2021. The primary endpoint was progression to critical status within 7 days from admission. We defined two groups: Critical group: Patients who developed a critical condition or died or transferred to the ICU before or at 7th day. Non-critical group: Patients who remained in non-critical respiratory status until 7th day or discharged before or at 7th day. Results Our study included 456 patients, with a sex ratio of 1.32 and an average age of 62 years. At the 7th day of hospitalization, 115 (25.2%) patients were in the critical group and 341 (74.8%) patients were in the non-critical group. The univariate logistic regression indicated that laboratory findings between non-critical and critical groups showed that C-reactive protein (CRP) (p=0.047), D-Dimer (p=0.011), creatinine (0.026), creatine kinase (p=0.039), lactate dehydrogenase (p=0.04), and troponin (p=0.001) were all higher among patients in critical group. However, lymphocyte (p<0.001) and platelet (p<0.001) counts were significantly lower among the critical group. Multivariate logistic regression model, identified four independent risk factors: lymphopenia (OR=2.771, 95%CI=1.482-5.181, p=0.001), Neutrophil to Lymphocyte Ratio (NLR) (OR=2.286, 95%CI=1.461-3.578, p<0.001), thrombocytopenia (OR=1.944, 95%CI=1.092-3.459, p=0.024), and CRP>71.5 (OR=1.598, 95% CI=1.042-2.45, p=0.032) were associated to critical group. Conclusions Our results show the predictive value of lymphopenia, thrombocytopenia, high NLR and CRP levels to evaluate the prognosis of COVID-19 pneumonia. A prognostic score could be proposed for guiding clinical care and improving patient outcomes.

Placental Histopathological Changes and the Level of Anti-Spike Antibody After Covid-19 Vaccination During Pregnancy: A Case Series

Background: COVID-19 infection during pregnancy could be associated with placental histopathological changes such as vascular diseases and malperfusion. There are studies showing that mRNA vaccines are not associated with significant placental pathological changes. Our objective was to evaluate the placental histopathology in pregnant women who received Sinopharm, an inactivated virus vaccine, during pregnancy. Case Presentation: The study included placental samples collected from mothers who gave birth of living singletons through elective cesarean sections performed between March 2022 and May 2022 at Imam Khomeini Hospital Complex. The study included women who had no history of positive reverse transcription polymerase chain reaction (RT-PCR) testing for COVID-19 during pregnancy, and had received at least one dose of COVID-19 vaccine during their pregnancy. Humoral levels of anti-SARS-CoV-2 spike IgG were measured in both the mothers and neonates. Results: The study included 20 mother-neonate pairs. The mean maternal age was 34±3.6 years, and all mothers received Sinopharm vaccine as their first and second doses. The last vaccine dose was administered during pregnancy, with 3 mothers receiving it in the first trimester, 9 in the second trimester, and 8 in the third trimester. The histopathological findings in the placental samples included decidual vasculopathy, subchorionic thrombosis, and chronic histiocytic intervillositis. All mothers and neonates, except one pair, were positive for anti-spike antibody. Conclusion: Multiple abnormal histopathological findings were reported in placenta of vaccinated mothers. However, similar to previous studies, these placental findings are considered mild lesions and have been observed in both vaccinated and unvaccinated mothers.

Determination of spontaneous and stimulated cytokine production in cell culture in patients with COVID-19 associated multisystem inflammatory syndrome

To date, the pathogenesis of COVID-19 associated multisystem inflammatory syndrome (MIS-C) remains unclear. Despite this, it becomes obvious that the pathogenesis of MIS-C is directly related to a certain immune dysregulation, however, a clear understanding of the mechanisms of this dysregulation has not yet been formulated. In order to identify the cytokine profile in patients with MIS-C, spontaneous and stimulated production of certain cytokines in cell culture was identified. Materials and methods. The study was conducted in the following study groups: group 1 — patients with MIS-C (n = 52); group 2 (comparison group) — patients with COVID-19 associated pneumonia (n = 15); group 3 (control group) — conditionally healthy patients (n = 23). The following stimulating agents were used: S58 — recombinant antigen Spike_SARS-Cov-2; NP is a recombinant NP antigen of the coronavirus SARS-CoV-2 and a standard mitogen. Results. Тhe absence of the initially expected hyperproduction of the main pro-inflammatory cytokines (IL-6, IL-8, TNF-α, etc.) was recorded. Statistically significant developments were recorded between patients of the study groups in the spontaneous production of MCP-1, in particular, the indicated indicator was 40010.82 (19698.1; 64812.1); 643.7 (214.6; 1695.4) and 622.7 (214.6; 1068.1), respectively. The indicated spontaneous hyperproduction of MCP-1 in patients with MIS-C allows us to consider as a probable completely new theory of the pathogenesis of MIS-C associated with dysregulation of the type 2 immune response. The presence of statistically significant differences, primarily in the spontaneous production of this cytokine, can apparently be explained by the presence of genetically determined determinants associated with subsequent dysfunction of the Th2 helper immune response, a potential trigger for which is a previous COVID-19 infection. Thus, further study of the immunopathogenesis of COVID-19 associated MIS-C is required.

A Case of Acute Necrotizing Encephalitis Misdiagnosed as Opium Poisoning: A Case Report

Introduction: The coronavirus has been associated with significant neurologic complications, including encephalopathy, seizures, ataxia, and motor or sensory deficits. Among these complications, acute necrotizing encephalopathy (ANE) is a rare condition linked to viral infections such as influenza, HHV-6, and COVID-19. This study presents a unique case of ANE in a COVID-19 patient, initially misdiagnosed as opium poisoning. Despite the reduction in pandemic cases, COVID-19 continues to present serious side effects, emphasizing the need to recognize potential neurological manifestations of the virus. Increased awareness and accurate diagnosis are essential for managing these complex cases. Case Presentation: This case study involves a 29-year-old female patient presenting with loss of consciousness and other symptoms that led to a diagnosis of COVID-19-related acute necrotizing encephalitis. Initial suspicions of opium poisoning were ruled out, and imaging tests revealed bilateral ground-glass opacities (GGO) and consolidation in the chest, along with abnormal findings in the brain. The patient was treated with glucocorticoid pulse therapy and IVIG, resulting in symptom improvement, though some neurological deficits persisted at discharge. This case underscores the importance of considering COVID-19 in cases of acute encephalitis and highlights the neurological complications associated with the virus. Conclusions: This study explores ANE as a severe manifestation of COVID-19 infection, focusing on the diverse neurological presentations associated with ANE in COVID-19 patients and a case initially misdiagnosed as opium poisoning. Through a case study of a patient with ANE, characterized by loss of consciousness and meiotic pupils, the research emphasizes the need for early detection and appropriate treatment. Findings suggest that ANE in COVID-19 patients can present with varied symptoms, posing diagnostic challenges. The study underscores the value of timely intervention with glucocorticoid pulse therapy and gamma globulin injection to improve patient outcomes. These findings highlight the necessity for increased awareness among healthcare providers to promptly recognize ANE in COVID-19 patients, aiding in timely and effective intervention.

Lessons Learned From Clinical Trials of Immunotherapeutics for COVID-19.

The COVID-19 pandemic caused by the SARS-CoV-2 virus was arguably one of the worst public health disasters of the last 100 years. As many infectious disease experts were focused on influenza, MERS, ZIKA, or Ebola as potential pandemic-causing agents, SARS-CoV-2 appeared to come from nowhere and spread rapidly. As with any zoonotic agent, the initial pathogen was able to transmit to a new host (humans), but it was poorly adapted to the immune environment of the new host and resulted in a maladapted immune response. As the host-pathogen interaction evolved, subsequent variants of SARS-CoV-2 became less pathogenic and acquired immunity in the host provided protection, at least partial protection, to new variants. As the host-pathogen interaction has changed since the beginning of the pandemic, it is possible the clinical results discussed here may not be applicable today as they were at the start of the pandemic. With this caveat in mind, we present an overview of the immune response of severe COVID-19 from a clinical research perspective and examine clinical trials utilizing immunomodulating agents to further elucidate the importance of hyperinflammation as a factor contributing to severe COVID-19 disease.

A cross-sectional study of fundus lesion characteristics in patients with acute visual impairment caused by COVID-19 infection.

To investigate the characteristics of acute visual dysfunction and fundus lesions in patients with COVID-19 pneumonia. A retrospective case series study was conducted. Data from 48 patients (96 eyes) with COVID-19 infection who presented to our ophthalmology department with acute onset visual disturbance between December 5, 2022, and February 28, 2023 were collected. Asymptomatic patients and those who had already recovered were excluded. Data collected included patient demographics, ophthalmic examinations, multicolor imaging (MCI), infrared autofluorescence (IR), spectral-domain optical coherence tomography (OCT), fundus fluorescein angiography (FFA). Of the 48 patients, 15 were male and 33 were female, with a mean age of 32 years. All patients had bilateral involvement. OCT showed hyperreflective signals in the outer plexiform layer and outer nuclear layer of the macular region in all 96 eyes of 48 patients (100%). Additionally, 66 eyes of 33 patients (68.8%) of eyes demonstrated abnormal reflectivity in the ellipsoid and interdigitation zones. MCI revealed petaloid or wedge-shaped hyperreflective areas in the macula in 46 (47.9%) of eyes, corresponding to hyporeflective areas on IR. Cotton-wool spots were observed in the peripapillary or posterior pole area in 54 (56.3%) of eyes. COVID-19 infection can lead to acute, bilateral, symmetric, and widespread retinal damage. Characteristic findings can be observed in ophthalmological examinations such as OCT, MCI, and IR.

Shared genetic architecture between COVID-19 and irritable bowel syndrome: a large-scale genome-wide cross-trait analysis

BackgroundIt has been reported that COVID-19 patients have an increased risk of developing IBS; however, the underlying genetic mechanisms of these associations remain largely unknown. The aim of this study was to investigate potential shared SNPs, genes, proteins, and biological pathways between COVID-19 and IBS by assessing pairwise genetic correlations and cross-trait genetic analysis.Materials and methodsWe assessed the genetic correlation between three COVID-19 phenotypes and IBS using linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL) methods. Two different sources of IBS data were combined using METAL, and the Multi-trait analysis of GWAS (MTAG) method was applied for multi-trait analysis to enhance statistical robustness and discover new genetic associations. Independent risk loci were examined using genome-wide complex trait analysis (GCTA)-conditional and joint analysis (COJO), multi-marker analysis of genomic annotation (MAGMA), and functional mapping and annotation (FUMA), integrating various QTL information and methods to further identify risk genes and proteins. Gene set variation analysis (GSVA) was employed to compute pleiotropic gene scores, and combined with immune infiltration algorithms, IBS patients were categorized into high and low immune infiltration groups.ResultsWe found a positive genetic correlation between COVID-19 infection, COVID-19 hospitalization, and IBS. Subsequent multi-trait analysis identified nine significantly associated genomic loci. Among these, eight genetic variants were closely related to the comorbidity of IBS and COVID-19. The study also highlighted four genes and 231 proteins associated with the susceptibility to IBS identified through various analytical strategies and a stratification approach for IBS risk populations.ConclusionsOur study reveals a shared genetic architecture between these two diseases, providing new insights into potential biological mechanisms and laying the groundwork for more effective interventions.

Effectiveness of training on health care workers' knowledge, attitude and practice regarding COVID-19 infection prevention and control, Yemen, 2021.

Although several training courses for Health Care Workers (HCWs) on COVID-19 were conducted in Yemen, no evaluation has been done to assess the effectiveness of such training on the Knowledge, Attitude and Practice (KAP) of HCWs. Therefore, this study aimed to assess the effectiveness of training on the KAP of HCWs toward infection prevention and control (IPC) for COVID-19, determine the relationship between the change in the KAP of HCWs, and identify the associated factors with the change in KAP. A cross-sectional study was conducted from April to December 2021. It was conducted among 186 HCWs working at COVID-19 isolation centers and caring for COVID-19 patients, in all Yemen's governorates. The data were collected one week before and immediately after the training session. SPSS version 26 was used for data entry and analysis. The median, interquartile range (IQR) and median difference were calculated. The Wilcoxon Signed Ranks Test was used to estimate the significant difference between KAP pre- and post-training scores. Kurskal-Wallis and Mann-Whitney U tests were used to assess the associated factors. Spearman's correlation coefficient test was used to assess the statistical relationship between the change in KAP. A P value < 0.05 was considered statistically significant. Out of 186 HCWs, 181 HCWs filled the pre- and post-assessment, with a response rate of 97.3%. The median difference (IQR) in the KAP scores were 3.0 (1.0 and 6.0), 1.0 (-1.0 and 4.0) and 2.0 (-1.0 and 5.0), respectively. However, there are statistical difference in the KAP scores between the pre- and post-training (p value = 0.000, 0.004 and 0.000, respectively). There are significant positive correlations between the change in knowledge, attitude and practice (all p values < 0.01). A significantly change in knowledge was found among those working in epidemiological surveillance (p value = 0.031). This evaluation concludes that the training program is effective in improving the KAP of HCWs toward IPC for COVID-19. It provides scientific evidence about the importance of training courses for HCWs during the COVID-19 pandemic. Further study is recommended to evaluate the retention of the KAP after a period of training.

Canada needs a national COVID-19 inquiry now.

We are now in the fifth year of an ongoing pandemic, and Canada continues to experience significant surges of COVID-19 infections. In addition to the acute impacts of deaths and hospitalizations, there is growing awareness of an accumulation of organ damage and disability which is building a "health debt" that will affect Canadians for decades to come. Calls in 2023 for an inquiry into the handling of the COVID-19 pandemic went unheeded, despite relevant precedent. Canada urgently needs a comprehensive review of its successes and failures to chart a better response in the near- and long-term. While Canada fared better than many comparators in the early years of the COVID-19 pandemic, it is clearly still in a public health crisis. Infections are not only affecting Canadians' daily lives but also eroding healthcare capacity. Post-COVID condition is having accumulating and profound individual, social, and economic consequences. An inquiry is needed to understand the current evidence underlying policy choices, identify a better course of action on various fronts, and build resilience. More must be done to reduce transmission, including a serious public education campaign to better inform Canadians about COVID and effective mitigations, especially the benefits of respirator masks. We need a national standard for indoor air quality to make indoor public spaces safer, particularly schools. Data collection must be more robust, especially to understand and mitigate the disproportionate impacts on under-served communities and high-risk populations. General confidence in public health must be rebuilt, with a focus on communication and transparency. In particular, the wide variation in provincial policies has sown mistrust: evidence-based policy should be consistent. Finally, Canada's early success in vaccination has collapsed, and this development needs a careful post-mortem. A complete investigation of Canada's response to the pandemic is not yet possible because that response is still ongoing and, while we have learned much, there remain areas of dispute and uncertainty. However, an inquiry is needed to conduct a rapid assessment of the current evidence and policies and provide recommendations on how to improve in 2025 and beyond as well as guidance for future pandemics.

Evaluation of rate and severity of COVID-19 infection after vaccination in the age group of 18–25-year population: A questionnaire-based study

Objectives: Covid-19 has been a challenging and challenging pandemic for mankind, with the introduction of the novel coronavirus, SARSCov-2, in late December 2019. Vaccination has proven to be a boon in these challenging times, with the study aiming to determine the efficacy of vaccination against the novel coronavirus in terms of the number of cases affected before and after vaccination and the severity of illness in post-vaccinated Covid-affected individuals. The study aims to learn from the lessons learned during this challenging period. Material and Methods: Students between age group of 18 to 25, from Nashik District, Maharashtra State, India, were the subject of a questionnaire-based study. Using Google Form, a survey was created. Results: It was found that vaccination has reduced the number of positive Covid 19 cases and we have seen a statistically significant decrease in the number of Covid-19-affected individuals. Conclusion: In the present study, we found that the severity is reduced and a smaller number of severe cases are seen after vaccination however the sample was small so this finding was not statically significant.

QUALIDADE PARA GARANTIR A CONFIABILIDADE DOS RESULTADOS DOS TESTES DA COVID 19

Objective: To analyze and identify the main quality criteria essential to ensure the reliability of COVID-19 test results performed in clinical laboratories. Literature Review: Ensuring the quality of COVID-19 testing is vital for the effectiveness of pandemic control strategies. This involves meticulous care with the selection and implementation of tests, the formation and training of teams, and adherence to standards and good practices. Only with an ongoing commitment to quality and accuracy can we ensure that test results reflect the true situation of COVID-19 infection and aid in public health decision-making.Conclusion: To ensure the reliability of COVID-19 test results, it is essential to take a comprehensive approach that encompasses test accuracy, sample quality, rigorous validation, staff qualification, and transparency.