Coronavirus Disease 2019 Disease Research Articles

Causal associations of COVID‐19 on neurosurgical diseases risk: a Mendelian randomization study

Many researchers have explored the potential association between one neurosurgical disease and coronavirus disease 2019 (COVID-19), but few systematically analyzed the association and causality between COVID-19 and various neurosurgical diseases. A Mendelian randomization analysis was conducted to evaluate the causal association between COVID-19 (including critically ill COVID‐19, hospitalized COVID‐19, and respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection) and 30 neurosurgical diseases within European populations. The consequences of inverse variance weighted models suggest that genetic susceptibility of critically ill COVID-19 may increase the risk of cerebral infarction (odds ratio [OR] = 1.02; p‐value = 0.006), genetic susceptibility of SARS-CoV-2 infection may increase the risk of stroke (OR = 1.02; p‐value = 0.047), and conversely, genetic susceptibility of hospitalized COVID-19 may reduce the risk of pituitary adenoma and craniopharyngioma (OR = 0.90; p‐value = 0.032). In addition, evidences revealed potential associations between genetic susceptibility of COVID-19 and spinal stenosis (OR = 1.03; p‐value = 0.028), diffuse brain injury (OR = 1.21; p‐value = 0.040) and focal brain injury (OR = 1.12; p‐value = 0.040). By testing for heterogeneity and pleiotropy, the above causal conclusions are robust. In summary, our analysis shows that COVID-19 has an independent and powerful causal influence on multiple neurosurgical disorders.

Phenotypic changes in immune cells induced by granulocyte and monocyte adsorptive apheresis in patients with severe COVID-19: An exvivo study.

SARS-CoV-2 causes systemic immune dysfunction, leading to severe respiratory dysfunction and multiorgan dysfunction. Granulocyte and monocyte adsorptive apheresis (GMA) therapy is designed to regulate an excessive inflammatory response and has been proposed as a potential therapeutic strategy for coronavirus disease 2019 (COVID-19). We aimed to investigate a targeted subset of granulocytes and monocytes to be removed after GMA therapy in patients with severe COVID-19 infection. We established an exvivo experimental system to study the effects of GMA. Blood samples were collected into EDTA-treated tubes and a mixture of blood samples and cellulose acetate beads was used in GMA. After GMA, blood samples were removed, and the granulocyte and monocyte subtypes before and after GMA were determined by CyTOF mass cytometry. To analyze mass cytometry data with a self-organizing map, hierarchical clustering was used to determine the appropriate number of metaclusters from t-distributed stochastic neighbor embedding. We included seven patients with severe COVID-19 and four age- and sex-matched volunteers. Granulocyte subsets removed by GMA strongly expressed CD11b, CD16, and CD66b, and weakly expressed CD11c, consistent with mature and activated neutrophils. Monocyte subsets strongly expressed CD14, weakly expressed CD33 and CD45RO, and did not express CD16. These subsets were indicated to promote the release of inflammatory cytokines and activate T cells. The identification of the granulocyte and monocyte subsets removed after GMA in patients with severe COVID-19 may help explain the potential mechanism underlying the effectiveness of GMA in COVID-19 and other inflammatory diseases.

People who use drugs show no increase in pre-existing T-cell cross-reactivity toward SARS-CoV-2 but develop a normal polyfunctional T-cell response after standard mRNA vaccination.

People who use drugs (PWUD) are at a high risk of contracting and developing severe coronavirus disease 2019 (COVID-19) and other infectious diseases due to their lifestyle, comorbidities, and the detrimental effects of opioids on cellular immunity. However, there is limited research on vaccine responses in PWUD, particularly regarding the role that T cells play in the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we show that before vaccination, PWUD did not exhibit an increased frequency of preexisting cross-reactive T cells to SARS-CoV-2 and that, despite the inhibitory effects that opioids have on T-cell immunity, standard vaccination can elicit robust polyfunctional CD4+ and CD8+ T-cell responses that were similar to those found in controls. Our findings indicate that vaccination stimulates an effective immune response in PWUD and highlight targeted vaccination as an essential public health instrument for the control of COVID-19 and other infectious diseases in this group of high-risk patients.

The impact of corona virus disease-2019 (COVID-19) vaccination on patients with systemic rheumatic diseases attending a tertiary care university-based hospital

BackgroundSafety and efficacy of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine among systemic rheumatic diseases (SRDs) remain a serious concern. Aim of the workTo explore different corona virus disease-2019 (COVID-19) vaccine adverse reactions, post-vaccination COVID-19 infection, disease flare and acceptability of vaccine among patients with SRDs. Patients and methodsThis study was conducted on 750 patients with SRDs attending the Rheumatology Department, Cairo University Hospitals (December 2022 – February 2023). All patients were subjected to full clinical history, COVID-19 infection, vaccine history, adverse events, disease flare and assessment of their acceptability to the vaccine. ResultsThe mean age of the patients was 41.6 ± 11.7 years with a female:male 8.4:1 and 52.5 % were educated. 414 (55.2 %) received COVID-19 vaccine. Only 26 (6.3 %) suffered from post-vaccination COVID- 19 infection (one mild attack). The causes for not receiving the vaccine were either due to unacceptability (78.9 %) or doctors’ advice (21.1 %). 64.8 % received inactivated virus vaccines (64.8 %) and 87.9 % received two doses. The commonest local and systemic side effects were pain (73.9 %) and headache (30.2 %). Only four (0.96 %) patients reported disease flare. There was a significant difference between the diagnosis, type of vaccines and some of the adverse effects of the vaccines such as pain (p = 0.019) and fever (p = 0.021), redness (p = 0.007) and swelling (p = 0.013). ConclusionThe efficacy and safety of SARS-CoV-2 vaccine among Egyptian patients with SRDs is confirmed. There were significant differences in certain vaccine side effects especially pain, fever, redness and swelling. Most patients well tolerated the COVID-19 vaccine providing reassurance.

Overview of COVID-19 Infection, Treatment, and Prevention in Children.

Coronavirus disease 2019 (COVID-19), caused by the novel respiratory virus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-was declared a global pandemic by the World Health Organization on 11 March 2020. Since then, substantial gains have been made in our understanding of COVID-19 epidemiology, disease presentation, and management. While children tend to have less severe disease courses compared to adults, children can still develop severe COVID-19 infections, particularly in those with underlying medical conditions such as obesity, chronic lung disease, or prematurity. In addition, children are at risk of severe complications of COVID-19 infection, such as multisystem inflammatory syndrome in children (MIS-C) or long COVID. The case definitions of MIS-C and long COVID have continued to evolve with the increased understanding of these new entities; however, improved methods of diagnosis and determination of the optimal management are still needed. Furthermore, with the continued circulation of SARS-CoV-2 variants, there remains a need for clinicians to remain up-to-date on the latest treatment and prevention options. The purpose of this review is to provide an evidence-based review of what we have learned about COVID-19 in children since the start of the pandemic and how best to counsel children and their families on the best methods of prevention.

Impact of ACE I gene insertion/deletion, A-240T polymorphisms and the renin–angiotensin–aldosterone system on COVID-19 disease

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic is driven by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to an enormous burden on patient morbidity and mortality. The renin–angiotensin–aldosterone system (RAAS) plays a significant role in various pulmonary diseases. Since SARS-CoV-2 utilizes the angiotensin-converting enzyme (ACE)2 receptor to exert its virulence and pathogenicity, the RAAS is of particular importance in COVID 19.MethodsOur preliminary study investigates retrospectively the influence of selected ACE-polymorphisms (I/D location at intron 16 in the B-coding sequence (rs4646994) and A-240T (rs 4291) at the A-promoter) as well as ACE1 and ACE2 serum levels on disease severity and the inflammatory response in inpatients and outpatients with COVID-19.ResultsOur study included 96 outpatients and 88 inpatients (65.9% male, mean age 60 years) with COVID-19 from April to December 2020 in four locations in Germany. Of the hospitalized patients, 88.6% participants were moderately ill (n = 78, 64% male, median age 60 years), and 11.4% participants were severely ill or deceased (n = 10, 90% male, median age 71 years). We found no polymorphism-related difference in disease, in age distribution, time to hospitalization and time of hospitalization for the inpatient group. ACE1 serum levels were significantly increased in the DD compared to the II polymorphism and in the TT compared to the AA polymorphism. There was no significant difference in ACE 1 serum levels l between moderately ill and severely ill patients. However, participants requiring oxygen supplementation had significantly elevated ACE1 levels compared to participants not requiring oxygen, with no difference in ACE2 levels whereas females had significantly higher ACE2 levels.ConclusionsAlthough there were no differences in the distribution of ACE polymorphisms in disease severity, we found increased proinflammatory regulation of the RAAS in patients with oxygen demand and increased serum ACE2 levels in women, indicating a possible enhanced anti-inflammatory immune response.Clinical trial registration: PreBiSeCov: German Clinical Trials Register, DRKS-ID: DRKS00021591, Registered on 27th April 2020.

Outcomes of patients with COVID-19 and coronary artery disease and heart failure: findings from the Philippine CORONA study

BackgroundPatients with coronavirus disease 2019 (COVID-19) and coronary artery disease (CAD) or heart failure (HF) are more likely to have poor outcomes. This study aimed to determine the characteristics and outcomes of COVID-19 patients with CAD/HF across various institutions in the Philippines.MethodsWe utilized the data from the Philippine CORONA Study and compared the outcomes of admitted COVID-19 patients with CAD/HF versus those without. The Student’s t test, Mann-Whitney U test, binary logistic regression and multivariate regression analysis were utilized. Odds ratios (OR) and Kaplan-Meier curves were generated.ResultsWe included a total of 512 patients with COVID-19 had CAD/HF and 10,369 were without. CAD/HF was significantly associated with COVID severity, all-cause mortality, death from cardiac causes, respiratory failure, and prolonged hospitalization. After adjusting for confounders, the presence of CAD/HF was still associated with death from a cardiac cause (OR 2.22, 95% CI 1.49–3.3, p < 0.01).ConclusionsThe presence of CAD or HF was significantly associated with severity of COVID disease, all-cause mortality, death from cardiac causes, respiratory failure, and prolonged hospitalization.

COVID-19 impairs oxygen delivery by altering red blood cell hematological, hemorheological, and oxygen transport properties.

Introduction: Coronavirus disease 2019 (COVID-19) is characterized by impaired oxygen (O2) homeostasis, including O2 sensing, uptake, transport/delivery, and consumption. Red blood cells (RBCs) are central to maintaining O2 homeostasis and undergo direct exposure to coronavirus in vivo. We thus hypothesized that COVID-19 alters RBC properties relevant to O2 homeostasis, including the hematological profile, Hb O2 transport characteristics, rheology, and the hypoxic vasodilatory (HVD) reflex. Methods: RBCs from 18 hospitalized COVID-19 subjects and 20 healthy controls were analyzed as follows: (i) clinical hematological parameters (complete blood count; hematology analyzer); (ii) O2 dissociation curves (p50, Hill number, and Bohr plot; Hemox-Analyzer); (iii) rheological properties (osmotic fragility, deformability, and aggregation; laser-assisted optical rotational cell analyzer (LORRCA) ektacytometry); and (iv) vasoactivity (the RBC HVD; vascular ring bioassay). Results: Compared to age- and gender-matched healthy controls, COVID-19 subjects demonstrated 1) significant hematological differences (increased WBC count-with a higher percentage of neutrophils); RBC distribution width (RDW); and reduced hematocrit (HCT), Hb concentration, mean corpuscular volume (MCV), and mean corpuscular hemoglobin concentration (MCHC); 2) impaired O2-carrying capacity and O2 capacitance (resulting from anemia) without difference in p50 or Hb-O2 cooperativity; 3) compromised regulation of RBC volume (altered osmotic fragility); 4) reduced RBC deformability; 5) accelerated RBC aggregation kinetics; and (6) no change in the RBC HVD reflex. Discussion: When considered collectively, homeostatic compensation for these RBC impairments requires that the cardiac output in the COVID cohort would need to increase by ∼135% to maintain O2 delivery similar to that in the control cohort. Additionally, the COVID-19 disease RBC properties were found to be exaggerated in blood-type O hospitalized COVID-19 subjects compared to blood-type A. These data indicate that altered RBC features in hospitalized COVID-19 subjects burden the cardiovascular system to maintain O2 delivery homeostasis, which appears exaggerated by blood type (more pronounced with blood-type O) and likely plays a role in disease pathogenesis.

Outcome of Cardiovascular Diseases in Coronavirus Disease 2019 Patients in a Tertiary Care Hospital in South India

Abstract Context: Coronavirus disease 2019 (COVID-19), an infection involving the respiratory system caused by severe acute respiratory syndrome coronavirus 2, caused significant mortality and morbidity in the population. Certain studies showed that patients with cardiovascular diseases (CVDs) tend to have worse prognoses. Hence, this study was conducted to determine the role of CVD as a risk factor in COVID-19 disease. Objectives: The primary objective was to determine the CVD as a risk factor for death among COVID-19 patients. Materials and Methods: This retrospective cohort study was conducted in a tertiary care hospital in South India including all patients above 18 years of age who were admitted with COVID-19 disease in the hospital from March 2021 to June 2022. The data were retrieved from the medical records department of the hospital and were recorded in a predesigned data extraction sheet. Statistical Analysis Used: Baseline clinical characteristics were shown as mean (standard deviation), median (range), or number (%), with a comparison of characteristics in subjects stratified by case and control through the nonparametric Mann–Whitney U test for continuous variables and Chi-square or Fisher’s exact test for binary variables. Results: The study included 1127 COVID-19 patients, 86.2% were discharged, and 13.8% died. Patients aged over 60 years were hospitalised the most (53.2%), with a 16.2% mortality rate. Mild cases (62.9%) had a 2.96% mortality rate, whereas severe/intensive care unit (ICU) cases (10.5%) had a 65.3% mortality rate. Patients with preexisting CVD had a higher mortality rate (32.27%) compared to those without CVD (6.53%). Among specific CVD conditions, coronary artery disease (CAD) patients had a 15.07% mortality rate, while those without CAD had a 13.58% mortality rate, showing no significant difference. Patients with hypertension (HTN) (45.7%) and diabetes (53.2%) had higher mortality rates of 17.08% and 16.66%, respectively, compared to those without these conditions. Other factors such as angina, congestive heart failure, peripheral vascular disease, cerebrovascular accidents (CVA), and chronic kidney disease also showed varying impacts on patient outcomes. Conclusions: In our study, 972 (86.2%) patients were discharged and 155 (13.8%) patients were deceased. There was more mortality in male patients (15.4%). Mortality was more in patients &lt;40 years old (21.6%). Severe cases had the greatest number of deaths (65.3%). Patients hospitalised for more than seven days had the highest death percentage (21.6%). More deaths were found in patients with preexisting CVDs, HTN, and diabetes mellitus. Thus, similar kinds of studies are needed in the future for a further warrant and a better understanding of the COVID-19 outcome in patients with CVDs.

Substance P - a regulatory peptide with defense and repair functions. Results and perspectives for the fight against COVID-19.

Severe acute respiratory syndrome corona virus 2 (SARS CoV-2) is the cause of Corona virus disease 2019 (COVID-19), which turned into a pandemic in late 2019 and early 2020. SARS CoV-2 causes endothelial cell destruction and swelling, microthrombosis, constriction of capillaries, and malfunction of pericytes, all of which are detrimental to capillary integrity, angiogenesis, and healing processes. Cytokine storming has been connected to COVID-19 disease. Hypoxemia and tissue hypoxia may arise from impaired oxygen diffusion exchange in the lungs due to capillary damage and congestion. This personal view will look at how inflammation and capillary damage affect blood and tissue oxygenation, cognitive function, and the duration and intensity of COVID-19 disease. The general effects of microvascular injury, hypoxia, and capillary damage caused by COVID-19 in key organs are also covered in this point of view. Once initiated, this vicious cycle leads to diminished capillary function, which exacerbates inflammation and tissue damage, and increased inflammation due to hypoxia. Brain damage may result from low oxygen levels and high cytokines in brain tissue. In this paper we give a summary in this direction with focus on the role of the neuropeptide Substance P. On the basis of this, we discuss selected approaches to the question: "How Substance P is involved in the etiology of the COVID-19 and how results of our research could improve the prevention or therapy of corona? Thereby pointing out the role of Substance P in the post-corona syndrome and providing novel concepts for therapy and prevention.

Coronavirus disease appropriate behavior among medical representatives

Background: The coronavirus disease 2019 (COVID-19) crisis has brought many appropriate changes in the behavior of the people in India. It posed deleterious effects on nearly every industry and business sector and pharmaceutical industry is no exception. Medical representatives were facing challenges in contacting health-care providers and other concerned individuals for sales efforts during the pandemic affecting their work behaviors and outputs. Therefore, it is highly important that MRs have adequate knowledge about the COVID-19 appropriate behaviors (CABs). Aims and Objectives: The objective of our study was to assess the perception of COVID-19 appropriate behaviors (CAB), among medical representatives. Materials and Methods: The study was conducted during lockdown for a period of 3 months from May to July 2021. After obtaining Institutional approval using the CAB, published by the Ministry of Health and Family Welfare, a questionnaire was designed and along with the consent form was sent to Medical Representatives to collect the information on CAB. Data from all consented voluntary participants using self-administered Google forms were collected. The data collected were reversibly coded and confidentiality of participants was maintained. Results: A total of 88 number of medical representatives (n = 88) participated in the study. Of these, 96.50% were males and all were &lt;50 years. Graduated participants constituted 96.6% (n = 85). Only 67.10% perceived it as a serious disease. Greeting without physical contact was practiced by 57 (64.7%), Namaste, by 56 (63.3%). Avoiding touching hands, nose, and mouth was considered very important by 68.9%. Covering nose and mouth when you cough or sneeze with handkerchief was considered important for 96.6%. Avoiding touching eyes, nose, and mouth was considered “not important at all” and slightly important by 2.2% and 5.6%, respectively. Discourage and avoiding crowd was thought as not important at all by 3.4% and slightly important by 2.3%. Conclusion: The medical representatives are well informed about COVID-19 disease and it is spread but only 2/3rd of the participants regarded COVID-19 as a serious condition and practiced various CABs to prevent infection spread. They considered national news and doctors as the main source of information.

Effectiveness of Rational Emotive Behavior Therapy on Death Anxiety and Depression During the COVID-19 Disease: A Historical Approach.

This research study investigated the effectiveness of Rational Emotive Behavior Therapy (REBT) on depression and anxiety during the coronavirus disease 2019 (COVID-19) pandemic in Nigeria. REBT is used in correcting irrational beliefs and behaviors. This study adopted a randomized pretest, post-test, control group design. Two trial-tested instruments covering; depression, anxiety, and irrational beliefs were for data collection. Data obtained with the instruments were analyzed using mean, standard deviation, and analysis of variance. The study revealed that REBT was effective in reducing depression and death anxiety in COVID-19 patients. The result of this study also showed that the introduction of REBT helped to curb the spread of COVID-19 disease by letting Nigerians to know that the existence, mode of spread, and consequences of the disease is real and not a myth.

Randomized controlled trial to study the safety and efficacy of probiotics supplementation in addition to the standard treatment in novel coronavirus (SARS‑CoV‑2) positive patients

Background: The severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) infection spread at a catastrophic rate, rapidly becoming a pandemic. Apart from the symptoms related to viral infection, a few patients with Coronavirus Disease 2019 (COVID-19) also experienced gastrointestinal symptoms. There was initial evidence of intestinal microbial dysbiosis in COVID-19 cases, and a few international studies showed the benefits of probiotics in reducing gastrointestinal (GI) symptoms and favorably altering the course of COVID-19 disease. Aims and Objectives: This study was planned to investigate if probiotics show any beneficial effects on COVID-19 disease in Indian patients. Materials and Methods: A prospective, randomized, open-label study was conducted to evaluate the effect of probiotic supplements added to the existing standard treatment in patients with the novel coronavirus SARS-CoV2 and compared them with the control group. Ninety patients were included in this study and were observed on day 1, day 3, day 5, day 10, day 14, and day of discharge for progression or recovery. Patients were monitored for symptom progression, the need for oxygen therapy, ventilation needs, etc. Results: There was no significant difference in the parameters at baseline in either of the groups. Cough was significantly less in group A (the standard control group) compared to group B (the probiotic group) only on day 5. No significant difference in the number of patients with coughs was seen on the other days. Other important parameters were not significantly different on any day of observation. Conclusion: The study results do not support the use of probiotics for the treatment of GI symptoms related to COVID19 and do not alter the course of COVID-19 disease or symptoms so as to be used as adjunct therapy for COVID-19 patients.

Convergence of inflammatory response: Salivary cytokine dynamics in coronavirus disease 2019 and periodontal disease.

Periodontal disease is associated with immune dysregulation, and cytokines released can add on to the coronavirus disease 2019 (COVID-19)-associated cytokine storm, further worsening the related adverse outcomes. Specific studies investigating cytokine levels in COVID-19 patients with periodontal disease are lacking. Examining the correlation between these conditions could aid in categorizing risk categories, determining referrals, and strengthening oral hygiene protocols. The current study sought to evaluate cytokine levels in the saliva of COVID-19-positive patients with and without periodontal disease. Twenty-six COVID-19-positive patients were subjected to periodontal examination, saliva collection, and assessment of cytokine levels through cytokine bead-based multiplex assay, using fluorescence-encoded beads with flow cytometry (BD FACS LSRFortessa). Eleven cytokines were assessed (interleukin [IL] 2, 4, 6, 10, 17A, and interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-α), chemokine ligand 2 (CCL2/monocyte chemoattractant protein-1), C-X-C motif chemokine ligand (CXCL) 8/IL 8, CXCL 9/monokine-induced gamma interferon [MIG]), and CXCL 10 (chemokine IFN-gamma inducible protein 10 kDa). The cytokine levels of the recruited subjects were also compared graphically with the salivary cytokine levels reported in the literature for health, COVID-19, and periodontal disease alone. Out of 26 COVID-19-positive patients, 17 had periodontal disease. Levels of all cytokines were raised in patients with both diseases when compared to values reported in literature for health, periodontal disease alone, or COVID-19 alone. However, there was no statistical difference among the recruited subjects for IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-gamma, TNF-α, CCL2, CXCL 8, and CXCL 10. MIG levels were found to be higher in periodontally healthy, COVID-19-positive subjects (P = 0.01). Periodontal disease might contribute to the COVID-19-induced cytokine storm, potentially amplifying its impact.

Evaluation of willingness to obtain of Covid 19 vaccine in patients with multiple sclerosis.

Assessing vaccine willingness and understanding sources of vaccine hesitancy in individuals with multiple sclerosis (MS) helps healthcare providers approach patients more effectively while respecting their autonomy to encourage coronavirus disease 2019 (COVID-19) vaccination. A descriptive-analytical cross-sectional study using a researcher-made checklist was conducted on MS patients referred to Neshat Clinic of Hamadan during the years 2020-2021. The checklist contained questions about demographic information, MS phenotype, duration of illness, expanded disability status scale (EDSS) score, and COVID-19 vaccination status. The expanded disability status scale (EDSS) is the most commonly used instrument for measuring disability in patients with multiple sclerosis (MS). The EDSS scale ranges from 0 to 10 in increments of 0.5 units, denoting advanced points of disability. Based on the results, 20 individuals (10%) were in the vaccine non-acceptance group, while 181 individuals (90%) were in the vaccine acceptance group. A significant number of relapsing and remitting (RR) type MS patients (90.7%) and all primary progressive (PP) type MS patients (100%) accepted the vaccine. In comparison, vaccine non-acceptance in the secondary progressive (SP) group was relatively higher (20.7%) compared to other types of MS, and this difference was significant (P < 0.05). Additionally, there was a statistically significant relationship between the history of COVID-19 and vaccine acceptance (P < 0.05). The study results demonstrated a high rate of COVID-19 vaccine acceptance among MS patients. MS phenotype, previous infection experiences, and other influences allow for COVID-19 vaccine acceptance among MS patients. This information can improve health programs and communication strategies for COVID-19 and future possible infectious disease vaccination in individuals with MS.

Causal associations between severe COVID-19 and diseases of seven organs: a proteome-wide mendelian randomization study.

The coronavirus disease 2019 (COVID-19) pandemic poses an enormous threat to public health worldwide. Many retrospective studies and case reports to date have shown associations between severe COVID-19 and diseases of multi-organs. However, the research on the causal mechanisms behind this phenomenon is neither extensive nor comprehensive. We conducted a proteome-wide Mendelian randomization (MR) study using summary statistics from a Genome-Wide Association Studies (GWAS) of severe COVID-19 and diseases related to seven organs: lung, spleen, liver, heart, kidney, testis, and thyroid, based on the European ancestry. The primary analytical method used is the radial inverse variance-weighted (radial IVW) method, supplemented with the inverse variance-weighted (IVW), weighted-median (WM), MR-Egger methods. Our findings have confirmed the association between severe COVID-19 and multiple organ-related diseases, such as Hypothyroidism, strict autoimmune (HTCBSA), Thyroid disorders (TD), and Graves' disease (GD). And we have also identified certain proteins that are associated with organ-related diseases, such as Superoxide Dismutase 2 (SOD2) and TEK Receptor Tyrosine Kinase (TEK), which are also considered potential drug targets. Phenotype scanning and sensitivity analyses were implemented to consolidate the results for Mendelian randomization. This study provides a compelling foundation for investigating COVID-19 caused diseases in future studies.

The Impact of COVID-19 Pandemic on Medical Education in a SubSaharan African Country (Kenya)

In 2019 the World was faced with a new infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), the corona virus disease 2019 (COVID-19). The disease was first reported in China in December 2019 and due to its rapid spread, the disease was declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) on 30 January 2020 and a pandemic on 11 March 2020 [1]. However, by March 2023, the disease was no longer considered as a PHEIC by WHO, but an ongoing COVID-19 disease [1]. The COVID-19 pandemic and its current status as an on-going disease will affect medical education, healthcare and the achievement of the United Nations health-related Millennium Development Goals (MDGs), especially in the low and middle income countries (LMIC)

Evaluating Biomarkers for Predicting Clinical Outcomes in COVID-19 Patients: A Systematic Review

The Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the novel human pathogen severe acute respiratory syndrome coronavirus 2, that resulted in millions of human deaths worldwide. A systematic review was conducted to identify biomarkers associated with the clinical progression of COVID-19. The search was conducted across four databases (ProQuest, PubMed, Scopus, and Web of Science) for articles published between 2020 and 2022, with 735 peer-reviewed papers identified. After screening for duplicates and relevance, 87 articles were included in this systematic review. The selected articles included various inflammatory, haematological, hepatic, respiratory, cardiac and other clinical biomarkers that were used to predict the severity and mortality risk in COVID-19 patients. In hospitalised COVID-19 patients, the blood levels of specific cytokines and chemokines were significantly higher, including pro-inflammatory cytokines such as interleukin (IL)-6, IL-8, IL-18, and tumour necrosis factor, as well as chemokines like interferon gamma-induced protein 10, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1 alpha. The levels of the anti-inflammatory cytokine IL-10 were also found to be higher, while elevated levels of C-reactive protein, procalcitonin, and ferritin in COVID-19 patients were related to the increased severity and mortality risk of the disease. Growth/differentiation factor 15 and beta-2 microglobulin were also useful biomarkers and independent risk factors for death in COVID-19 patients. The review revealed clinical biomarkers that can be used as indicators of COVID-19 disease progression and are critical to timely interventions. Understanding the clinical picture associated with biomarker profiles is necessary for future improved COVID-19 management strategies and therapeutic approaches.

Post-COVID-19 pulmonary fibrosis with prognostic risk factors: A study in the hilly state of North India

Context: Coronavirus disease 19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). As it is a novel coronavirus infection, its acute as well as long-term pulmonary alterations in terms of radiological imaging and pathology need to be explored. Aim: To analyze the risk factors associated with the development of pulmonary fibrosis in post-COVID-19 patients. Settings and Design: A retrospective study in a tertiary center in a hilly state of North India. Methods and Material: A retrospective study was carried out in a hilly state of North India during the second wave of the COVID-19 pandemic. A baseline computed tomography (CT) within 1 month and a follow-up CT within 3–6 months of the onset of patients’ symptoms was done. The patients were assigned two groups based on the presence of fibrosis [reticular pattern (inter/intralobular septal thickening), parenchymal bands, bronchiectasis, and/ or honeycombing] on follow-up CT. The patients’ demographic profiles, clinical records, blood laboratory findings, treatment given, baseline CT, and follow-up CT findings were compared between the fibrosis and non-fibrosis groups. Statistical analysis used: The data entry was done in the Microsoft EXCEL spreadsheet, and the final analysis was done with the use of Statistical Package for Social Sciences (SPSS) software, IBM manufacturer, Chicago, USA, ver 25.0. Results: Of the total 72 patients, two had no abnormality on baseline CT. Forty (57.14%) out of 70 patients already had fibrosis on baseline CT, which increased to involve 47 (67.14%) patients on follow-up CT. It was analyzed that old age, smoking, comorbid status, low SpO2, longer hospitalization, lymphopenia, and increased severity of COVID-19 disease were independent risk factors for the development of pulmonary fibrosis in post-COVID-19 pneumonia. Conclusions: A better understanding of the underlying mechanism and pathogenesis can help in filling up of gaps in risk stratification of COVID-19.

The heat shock protein 90 inhibitor RGRN-305 attenuates SARS-CoV-2 spike protein-induced inflammation in vitro but lacks effectiveness as COVID-19 treatment in mice.

The inhibition of heat shock protein 90 (HSP90), a molecular chaperone, has been proposed to be a potential novel treatment strategy for Coronavirus disease 2019 (COVID-19). In contrast to other studies, our data demonstrated that RGRN-305, a HSP90 inhibitor, exacerbated the cytopathic effect and did not reduce the viral shedding in VeroE6-hTMPRSS2 cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Likewise in a murine model of SARS-CoV-2, transgenic mice treated orally with RGRN-305 exhibited reduced survival by the end of the experiment (day 12) as 14% (1/7) survived compared to 63% (5/8) of those treated with drug-vehicle. Animal weight was not reduced by the RGRN-305 treatment. Interestingly, we demonstrated that inhibition of HSP90 by RGRN-305 significantly dampened the inflammatory response induced by SARS-CoV-2 spike protein in human macrophage-like cells (U937) and human lung epithelial cells (A549). Measured by quantitative real-time PCR, the mRNA expression of the proinflammatory cytokines TNF, IL1B and IL6 were significantly reduced. Together, these data suggest that HSP90 inhibition by RGRN-305 exacerbates the SARS-CoV-2 infection in vitro and reduces the survival of mice infected with SARS-CoV-2, but exhibits strong anti-inflammatory properties. This data shows that while RGRN-305 may be helpful in a 'cytokine storm', it has no beneficial impact on viral replication or survival in animals as a monotherapy. Further animal studies with HSP90 inhibitors in combination with an anti-viral drug may provide additional insights into its utility in viral infections and whether HSP90 inhibition may continue to be a potential treatment strategy for COVID-19 disease.