Coronavirus Disease 2019 Infection Research Articles

Machine learning prediction of the case-fatality of COVID-19 and risk factors for adverse outcomes in patients with non-small cell lung cancer.

Since the emergence of coronavirus disease 2019 (COVID-19) across the globe, patients with cancer have been found to have an increased risk of infection with COVID-19 and are highly likely to experience a severe disease course. This study analyzed the clinical outcomes of COVID-19 in patients with non-small cell lung cancer (NSCLC) and identified the risk factors for adverse outcomes. The study included patients diagnosed with COVID-19 between January 2020 and April 2022 at the Samsung Medical Center in Seoul, Republic of Korea, who have a history of NSCLC. The case-fatality rate and risk factors for COVID-19 were analyzed using a machine-learning prediction method. Additionally, the study investigated the effect of COVID-19 on the systemic treatment of patients with advanced-stage NSCLC. Overall, 1,127 patients were included in this study, with 10.3% of the patients being older than 75 years; of these patients, 51.8% were ex- or current smokers. Among the 584 patients cured after surgery, 91 had stable disease after concurrent chemo-radiotherapy, and 452 had recurrent or metastatic NSCLC. Among 452 patients with recurrent or metastatic NSCLC, 387 received systemic treatment in a palliative setting during COVID-19. Of these, 188 received targeted therapy, 111 received cytotoxic chemotherapy, 63 received immunotherapy +/- chemotherapy, and 26 received other agents. Among them, 94.6% of patients continued systemic treatment after the COVID-19 infection. Only one patient discontinued treatment because of complications of the COVID-19 infection, and 18 patients changed their systemic treatment because of disease progression. The case fatality rates were 0.86% for patients with early-stage NSCLC, 4.4% for patients with locally advanced NSCLC, and 9.96% for patients with advanced NSCLC. The factors associated with fatalities included palliative chemotherapy, type of palliative chemotherapy, age (≥75 years), diabetes, smoking history, history of lung radiotherapy, hypertension, sex, and chronic obstructive pulmonary disease (COPD). The predictive model using logistic regression and eXtreme Gradient Boosting (XGB) performed well [area under the curve (AUC) for logistic regression =0.84 and AUC for XGB =0.84]. The case fatality rate in patients with NSCLC was 4.8%, while most patients with advanced NSCLC continued to receive systemic treatment. However, patients with risk factors require careful management of COVID-19 complications.

The level of implementation of COVID-19 measures in workplaces: Ideas for the future

Objective: The initial phases of Coronavirus Disease 2019 (COVID-19) pandemic required a wide range of preventive measures for various settings, including workplaces. The evaluation of workplace applications may guide all stakeholders for future similar outbreaks. This study aimed to evaluate the practice of Turkish occupational safety and health (OSH) professionals regarding COVID-19. Materials and Methods: The study included responses of OSH professionals who were members of three national organizations. Data were collected during the third peak of COVID-19 cases in Turkey. Results: Of 457 respondents, 92.6% reported at least one infected worker, and 12.7% reported mortality among workers due to COVID-19. Multiple regression analyses revealed an association with workplace size ≥250 for any COVID-19 infection among workers (OR=6.70, 95% CI:2.64–16.98, p<0.001) and for COVID-19 related mortality (OR=3.37, 95% CI:1.59–7.13, p=0.002). Moreover, working in governmental business enterprises was related to COVID-19 related mortality (OR=4.83, 95% CI:2.33–10.01, p<0.001). The mean number of available measures was significantly lower (p<0.001) in governmental business enterprises, the service sector, and workplaces with less than 250 workers. Conclusion: The results indicate a need for improvement in small- and large-sized workplaces, governmental business enterprises, and service sector workplaces.

SARS-CoV-2 Induced Interleukin -18 Response among Presumptive Covid-19 Patients in Kano State, Nigeria

Study’s Novelty/Excerpt This study evaluates Interleukin-18 (IL-18) as a potential biomarker for COVID-19 by comparing its serum levels in COVID-19-positive patients and healthy controls. The research uniquely identifies significantly elevated IL-18 levels in COVID-19 patients, demonstrating a strong statistical association with the infection (t value 6.16, p <0.00010). These findings underscore the potential of IL-18 in the prognosis and clinical management of COVID-19, offering new insights into its role in the disease's pathophysiology and its utility as a biomarker. Full Abstract Coronaviruses have a history of causing severe outbreaks with life-threatening consequences, including Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and the recent coronavirus disease 2019 (COVID-19). COVID-19 first broke out in Wuhan (China) in December 2019). The disease was later declared a pandemic, and so far, more than 222 countries have been affected, with over 771 million confirmed cases and total deaths of over 7.05 million. Some immunological markers were reported elsewhere as directly related to COVID-19 pathophysiology and stand a chance to be considered biomarkers. Interleukin 18 (IL-18) is a proinflammatory cytokine and a member of the interleukin-1 family, produced by macrophages at the early stage of viral infections. However, aberrant IL-18 production can lead to severe pathological injury. Hence, there is a need to assess the feasibility of interleukin -18 as a biomarker for COVID-19. Forty-five individuals diagnosed with COVID-19 and 45 healthy controls screened using a COVID-19 antigen rapid test kit and confirmed by one-step real-time PCR were recruited for this study. Blood samples were collected from the patients and controls, and the samples were analyzed for IL-18 using the ELISA technique. This study revealed a higher level of IL-18 in COVID-19-positive patients (206.42 ± 13.2 pg/mL) compared to the control group (97.96 ± 14.4 pg/mL). Serum level IL-18 was statistically associated with COVID-19 infection (t value 6.16, p <0.00010). The study demonstrates the importance of IL-18 in the COVID-19 cohort, inferentially implying its potential in the prognosis and clinical management of COVID-19.

Evaluation of menstrual irregularities following COVID-19 infection or vaccination: The impact of COVID anxiety and associated risk factors.

There has been significant interest in the changes in menstrual cycles following coronavirus disease 2019 (COVID-19) infection or vaccination. This study aimed to investigate the evidence for such changes and their potential risk factors. We used a descriptive study design and gathered data by sharing an online survey questionnaire on social media platforms. The questionnaire included questions regarding sociodemographic factors, menstrual cycle changes, and COVID-19 anxiety. The study population comprised women aged 18 to 49 years from Izmir. All data analyses were performed using Statistical Package for the Social Sciences 21.0. The risk factors influencing menstrual irregularities were determined after the COVID binary logistic regression analysis, including univariate and multivariate models. Among the 465 participants, those with an associate's degree had a significantly higher risk of menstrual irregularities than those with a high school diploma (P = .012). Anxiety scores emerged as a significant risk factor for menstrual cycle irregularities (P = .026). However, neither COVID-19 infection nor vaccination resulted in significant changes in the menstrual cycle characteristics (P > .05). Other sociodemographic variables, such as age, body mass index, and smoking, were not significantly associated with menstrual cycle changes(P > .05). The study findings suggest that educational level and anxiety may play a role in menstrual irregularities, whereas COVID-19 infection or vaccination itself may not directly affect menstrual cycle.

Prediction equations for detecting COVID-19 infection using basic laboratory parameters.

Coronavirus disease 2019 (COVID-19) emerged as a global pandemic during 2019 to 2022. The gold standard method of detecting this disease is reverse transcription-polymerase chain reaction (RT-PCR). However, RT-PCR has a number of shortcomings. Hence, the objective is to propose a cheap and effective method of detecting COVID-19 infection by using machine learning (ML) techniques, which encompasses five basic parameters as an alternative to the costly RT-PCR. Two machine learning-based predictive models, namely, Artificial Neural Network (ANN) and Multivariate Adaptive Regression Splines (MARS), are designed for predicting COVID-19 infection as a cheaper and simpler alternative to RT-PCR utilizing five basic parameters [i.e., age, total leucocyte count, red blood cell count, platelet count, C-reactive protein (CRP)]. Each of these parameters was studied, and correlation is drawn with COVID-19 diagnosis and progression. These laboratory parameters were evaluated in 171 patients who presented with symptoms suspicious of COVID-19 in a hospital at Kharagpur, India, from April to August 2022. Out of a total of 171 patients, 88 and 83 were found to be COVID-19-negative and COVID-19-positive, respectively. The accuracies of the predicted class are found to be 97.06% and 91.18% for ANN and MARS, respectively. CRP is found to be the most significant input parameter. Finally, two predictive mathematical equations for each ML model are provided, which can be quite useful to detect the COVID-19 infection easily. It is expected that the present study will be useful to the medical practitioners for predicting the COVID-19 infection in patients based on only five very basic parameters.

A Case Report and Literature Review of New-Onset Myasthenia Gravis after COVID-19 Infection

Myasthenia gravis (MG) is an autoimmune disorder affecting the neuromuscular junction caused by a B-cell-mediated, T-cell-dependent immunologic attack at the end plate of the postsynaptic membrane. Attack on muscle acetylcholine receptors (AChR) of the postsynaptic membrane due to the AChR, muscle-specific tyrosine kinase, or lipoprotein receptor-related peptide 4 antibodies lead to symptoms of painless, fluctuating weakness of muscle groups and often begins with ocular signs and symptoms. Coronavirus disease 2019 (COVID-19) is an acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus closely related to SARS-CoV. Serious neurologic complications are infrequent and diverse with reported cases of stroke, encephalitis/meningitis, Guillain-Barré syndrome, acute disseminated encephalomyelitis, ataxia, and unspecified limb weakness. MG is a rarely reported sequela of COVID-19 infection. To date, there are 15 reported cases of post-COVID-19 MG. In this article, we present a case of post-COVID-19 MG and a concise review of other reported cases. An 83-year-old Caucasian male with a medical history of atrial fibrillation status post-ablation and non-ischemic cardiomyopathy was initially admitted for COVID-19 pneumonia. He was treated with remdesivir, convalescent plasma, and supplemental oxygen therapy but did not require invasive mechanical intubation. One month after discharge, he started experiencing fatigue with muscle weakness and progressive dyspnea. He progressed to develop dysphonia, especially at the end of the day. After extensive workup, he was diagnosed with MG with a positive antibody against the AChR. The chronological events of developing slowly worsening muscular weakness after recovering from COVID-19 infection and positive AChR antibody led to the diagnosis of post-COVID-19 new-onset MG. Post-COVID-19 fatigue, long-term use of steroids, and intensive care unit-related physical deconditioning ....

The Protective Role of IL-17 and IL-22 in COVID-19 Infection.

The development of a cytokine storm in Coronavirus Disease 2019 (COVID-19) infection can make the disease fatal. We hypothesize that this excessive cytokine production impairs mucosal healing. IL-17 and IL-22 are cytokines that play a key role in protecting and regenerating mucosal tissues.IL-17 and IL-22 support each other and the imbalance between them plays a role in the pathogenesis of many rheumatologic diseases. To investigate whether COVID-19 severity is related to IL17, IL-22, and the IL-17/IL-22 ratio. The study was planned prospectively and included 69 patients with active COVID-19 infection.Three groups were created: patients with upper respiratory tract infection, pneumonia, and cytokine storm. Blood samples were taken from the patients upon their first admission and serum levels of IL-17 and IL-22 were measured using the enzyme-linked immunosorbent assay (ELISA). We assessed the relationship between IL17, IL22, IL17/IL22 ratio, clinical and lung involvement by comparing them with the healthy group. The levels of IL-17 were significantly higher in COVID-19 patients with upper respiratory tract infection compared to the control group (p=0.027). IL17/IL-22 ratio significantly increased in patients with cytokine storm compared to the healthy controls (p=0.027). Serum levels of IL-22 were negatively correlated with the CO-RADS score (r=-0.31, p=0.004), while IL-17/IL-22 ratio was positively correlated with the CO-RADS score (r= 0.29, p=0.008). Levels of IL-17, IL-22 and IL-17/IL-22 may provide valuable insights into the progression of COVID-19.

Troponin-I as a Prognostic Marker in Patients with Coronavirus Disease 2019: Insights from a Single-center Investigation

Background: Troponin-I is conventionally correlated with myocardial injury, but its relevance in assessing the severity of coronavirus disease 2019 (COVID-19) and its implications for patient management remains an area of ongoing investigation. This study was designed to assess the correlation between troponin-I levels and the disease severity among patients with COVID-19. Materials and Methods: This retrospective study was conducted at a tertiary care center in India between April 2020 and November 2021. The patients with reverse transcription-polymerase chain reaction who tested positive for COVID-19 infection, and who underwent troponin-I examination at presentation were included in the study. A comparison of baseline clinical characteristics among patients who survived and who did not survive post-COVID-19 was done, and risk factors associated with mortality among hospitalized patients were analyzed. Results: A total of 1673 patients were enrolled in this study. Of these, 1431 patients survived, and 242 patients did not survive post-COVID-19. The mean age of the patients with troponin-I levels ≤0.06 ng/ml was 49.66 ± 17.88 years and that of patients with troponin-I levels >0.06 ng/ml was 60.13 ± 20.04 years. The nonsurvival rate was high in patients aged >50 years compared to the patients aged ≤50 years (81.4% vs. 18.6%; P < 0.001). The mortality rate was high in patients with troponin-I levels >0.06 ng/ml compared to the patients with troponin-I levels ≤0.06 ng/ml (51.7% vs. 48.3%; P < 0.001). Breathlessness (odds ratio [OR]: 26.901; P < 0.001), cut-off troponin-I levels (OR: 8.246; P < 0.001), and other comorbidities (OR: 8.246; P < 0.001) were independently correlated with mortality among hospitalized patients with COVID-19. Conclusion: This study demonstrated that elevated troponin-I level at presentation was associated with disease severity and increased mortality in patients with COVID-19.

Real-World Effectiveness and Safety of Tixagevimab-Cilgavimab: A Target Trial Emulation Study.

Immunocompromised individuals are at high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent severe or fatal coronavirus disease 2019 (COVID-19), yet they have suboptimal responses to mRNA and inactivated COVID-19 vaccines. The efficacy of tixagevimab-cilgavimab in reducing symptomatic SARS-CoV-2 infection was demonstrated in phase III clinical trials. Nevertheless, real-world data on the effectiveness and safety of tixagevimab-cilgavimab remain limited. The aim was to evaluate the effectiveness and safety of tixagevimab-cilgavimab among immunocompromised individuals. Adults who were immunocompromised or receiving immunosuppressive therapies were included in this target trial emulation using territory-wide electronic health records in Hong Kong. A sequential trial emulation approach was adopted to compare effectiveness and safety outcomes between individuals who received tixagevimab-cilgavimab and individuals who did not. A total of 746 tixagevimab-cilgavimab recipients and 2980 controls were included from 1 May 2022 to 30 November 2022. Tixagevimab-cilgavimab significantly reduced the risk of COVID-19 infection (hazard ratio [HR] 0.708, 95% confidence interval [CI] 0.527-0.951) during a median follow-up of 60 days. No significant difference was observed in the risk of COVID-19-related hospitalisation. Zero versus eight COVID-19 mortality cases and zero versus two severe COVID-19 cases were observed in tixagevimab-cilgavimab recipients and controls, respectively. Notably, significant risk reduction in COVID-19 infection was also observed among immunocompromised individuals who had been previously vaccinated with three or more doses of COVID-19 vaccine, or had no prior COVID-19 infection history. Tixagevimab-cilgavimab was effective in reducing COVID-19 infection among immunocompromised patients during the Omicron wave. Findings were consistent among individuals who previously received three or more doses of COVID-19 vaccine, or had no previous history of COVID-19 infection.

A critical review of health and financial implications of obesity during the COVID-19 pandemic

The coronavirus disease 2019 (COVID-19) was reported in Wuhan, China, in December 2019. There is a link between increased mortality and obese individuals with the disease. The disease has been claimed to have disproportionately affected non-Hispanic blacks and Hispanics. The rise in food accessibility and the drop in the relative cost of junk food items are the two most significant changes in dietary patterns. Around the world, 2.8 million people die from being overweight or obese, and those with more body fat also have a higher risk of diabetes (44%) and heart disease (23%). Obesity weakens the immune system because adipose cells infiltrate the bone marrow, spleen, and thymus. Obesity was substantially more common among COVID-19 patients who were hospitalized than those who were not hospitalized. Over 900,000 adults in the United States are hospitalized due to a COVID-19 infection. Hospitalizations in 271,700 (30.2%) cases have been attributed to obesity. Obese patients may be experiencing reduced thoracic expansion following bariatric surgery. Less tracheal collapse and air-trapping at end-expiration chest CT were observed post-surgery, and patients reported reduced dyspnea. COVID-19 is estimated to cost the European Union €13.9 billion in secondary care, with 76% of that cost attributed to treatment for overweight and obese individuals. The average price per hospitalized patient also increased with increasing body mass index (BMI). Screening for obesity, preventive measures, and recommendations for healthy lifestyle changes should be of the utmost importance to decrease both the health and financial implications of COVID-19.

Analysis of Inflammatory Markers and Electroencephalogram Findings in Pediatric Patients with COVID-19: A Single-Center Study in Korea

Purpose: The Omicron variant wave spread rapidly from February 2022 in South Korea following the initial management of the coronavirus disease 2019 (COVID-19) outbreak. This study examined electroencephalogram (EEG) findings and serological inflammatory markers in pediatric patients with COVID-19 (Omicron variant).Methods: We retrospectively reviewed the medical records of 41 patients who presented at Gyeongsang National University Changwon Hospital between March and May 2022 and were diagnosed with COVID-19. All serological tests were performed within 24 hours of fever or seizure onset. Results: The median patient age was 3.6 years (range, 0.08 to 14.00), and the average hospital stay was 3.7 days (range, 1.0 to 7.0). Interleukin-6 (IL-6) levels were elevated above the normal range in all patients (median, 43.18 pg/mL; range, 7.0 to 190.0) and were higher among those who experienced seizures. Of the 41 total patients, 17 (41.5%; mean age, 5.4 years) visited the clinic for seizure. Three patients experienced prolonged seizures (lasting longer than 30 minutes) and received intravenous lorazepam, while eight presented with complex febrile seizures. Nine patients underwent EEG, of whom five exhibited abnormal initial findings. Linear regression demonstrated correlations between prolonged seizure duration and both serum IL-6 level and blood lymphocyte count.Conclusion: Numerous serological markers associated with the immune cascade were found to be elevated in children with COVID-19. Nevertheless, febrile seizures represent a relatively common neurological presentation among pediatric patients infected with Omicron variants. Consequently, COVID-19 infection exhibits both familiar and distinct characteristics regarding the mechanisms inducing seizures and fever in children.

Incidence, Causes, and Perinatal Outcomes of “Near-Miss” Obstetric Emergencies during the COVID-19 Pandemic: Experience from a Tertiary Referral Center of Western Rajasthan, India

Abstract Background: Pregnant women and neonates are often considered as being a vulnerable group during the coronavirus disease 2019 (COVID-19) pandemic. Several studies have compared the impact of COVID-19 on pregnant and nonpregnant women. This study aimed to examine the reasons for severe acute maternal morbidity (SAMM) and “near-miss cases” and their effects on perinatal outcomes before and during the COVID-19 pandemic. Materials and Methods: All women admitted to our facility with pregnancy-related complications for birth or in the puerperium who required critical care unit (CCU) or high dependency unit (HDU) admission were included in the study. A modified version of the World Health Organization (WHO)’s Maternal Near-Miss Screening Tool was used to identify maternal near-miss cases and other obstetric emergencies requiring CCU admission. Results: The incidence of “near-miss” obstetric emergencies was -30.7 per 1000 live births. Over the 3 years of data obtained, 152 near-miss cases were found. Thirty-five cases were seen in the pre-COVID-19 period, whereas 117 near-miss cases were noted during the COVID-19 pandemic. The most common cause of near-miss cases in both groups was severe preeclampsia (65.8%). The rate of ICU admissions was 80.3% (94/117) during COVID-19, while only three cases required ICU before the COVID-19 pandemic. There were a total of 11 maternal deaths, and all were reported during the COVID-19 pandemic. Conclusion: There was a significant increase in ICU admission rates and “near-miss” obstetric emergencies during the COVID-19 pandemic. The COVID-19 infection indirectly led to higher maternal morbidity secondary to lockdown effects on antenatal care and delayed referrals. This study will contribute to the existing literature on the impact of the COVID-19 pandemic on maternal and child health. The results will help inform policy decisions and guide the development of interventions to improve the quality of care for pregnant women during the pandemic.

The Association of Withdrawing Maintenance Renin-Angiotensin System Inhibitor on All-Cause Mortality and Intensive Care Unit Admission Among Hypertensive Patients Admitted for Mild to Moderate COVID-19 infection:A Meta-analysis of Observational Studies

INTRODUCTION: The pandemic caused by coronavirus disease 2019 (COVID-19) posed a serious challenge to all health care systems in the world. It has been found to be harmful in people with underlying cardiovascular diseases, particularly in patients with systemic hypertension, which may be due to upregulation of angiotensin-converting enzyme 2 (ACE2) expression, which may lead to increased severe acute respiratory syndrome coronavirus 2 virulence. Renin-angiotensin system inhibitor (RASI) acts by blocking the angiotensin-converting enzyme and angiotensin II type 1 receptors, which in turn affects the production of the ACE2 protein. Hence, there have been arguments on whether to continue or discontinue this medication. Given the widespread use of RASIs globally and the fact that they are generally cardioprotective, research into the safety of continuing these maintenance medications in patients hospitalized with mild to moderate COVID-19 is immensely needed. METHODS: This meta-analysis involved review of observational studies among hypertensive patients on maintenance ACE inhibitor or angiotensin-receptor blocker with confirmed mild to moderate COVID-19 infection. Analyses were performed to determine the adjusted hazard ratio of each event using the raw data obtained from each study. Random-effects model and Cochran-Mantel-Haenszel method were utilized at 95% confidence interval. To check for heterogeneity, χ2 test and I2 statistic were calculated. Cochrane ReviewManager (RevMan version 5.3) was used for data analysis, and forest plots were generated. RESULTS: At 95% confidence interval, the adjusted hazard ratios for all-cause mortality and intensive care unit (ICU) admission at 95% confidence interval were 1.64 (1.22, 2.21) and 1.93 (1.34, 2.79), respectively. The tests of overall estimate effect for both outcomes were P < 0.0001 for all-cause mortality and P = 0.0003 for ICU admission. CONCLUSION: Discontinuation of maintenance RASI during hospitalization is associated with increased all-cause mortality and ICU admission among hypertensive patients with mild to moderate COVID-19 infection. KEYWORDS: angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, coronavirus, COVID-19, renin-angiotensin system inhibitor

The long COVID and its mental health manifestations - the review of literature.

This article aims to present the overview of the situation during the coronavirus disease 2019 (COVID-19) pandemic about issues concerning the prevalence of mental disorders such as depression, anxiety, rate of suicide attempts, and long COVID (LC) infections in the general population during COVID-19 pandemic. Analysis of the literature (in English, Polish and Spanish language) on topics related to COVID-19, mental disorders (suicide attempts, depression, anxiety) and LC infection published during the 4 years (2020-2023) was done using Pubmed and PubMed Central search engine. Keywords such as "COVID-19," "mental disorders," "long COVID infection," "depression," "anxiety," "suicide attempts" were used during the search. The conduct of this review/comment followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) protocol, which corresponds to a checklist of 27 items designed to facilitate the development and reporting of a robust protocol for systematic reviews or meta-analyses. Overall 35 studies were selected and analyzed in the review on topics: including among others LC (14 studies), suicide attempts (7 studies), mental disorders (depression, anxiety) (14 studies). The main issues raised in the articles were: higher risk of LC symptoms in women, fatigue and brain fog listed as frequently encountered patient's complaints together with anxiety, depression, loneliness, especially in younger age groups and in women. Issues regarding LC, mental disorders and suicide attempts requires further research as the results vary in different countries. Int J Occup Med Environ Health. 2024;37(3):360-80.

Association between COVID-19 severity with liver abnormalities: A retrospective study in a referral hospital in Indonesia.

Coronavirus disease 2019 (COVID-19) is characterized by an acute respiratory infection with multisystem involvement and the association of its severity to liver function abnormalities is not well characterized. The aim of this study was to assess the association between the severity of COVID-19 patients and liver function abnormalities. This retrospective study included adult patients with confirmed COVID-19, which were classified as non-severe or severe according to World Health Organization guidelines. Liver function test results were compared between the severity groups. A total of 339 patients were included of which 150 (44.25%) were severe cases. The male-to-female ratio was 0.9:1 and 3:2 in the non-severe and severe groups, respectively (p=0.031). Aspartate aminotransferase (AST), alanine transaminase (ALT), and total bilirubin levels and acute liver injury (ALI) incidence were significantly higher in the severe group compared to non-severe group (p<0.001, p<0.001, p=0.025, p=0.014, respectively). In contrast, albumin levels were significantly lower (p=0.001). Multivariate analysis showed that ALI was significantly associated with human immunodeficiency virus (HIV) infection (odds ratio (OR): 5.275; 95% confidence interval (CI): 1.165-23.890, p=0.031), hemoglobin level (OR: 1.214; 95%CI: 1.083-1.361, p=0.001), and hypoalbuminemia (OR: 2.627; 95%CI: 1.283-5.379, p=0.008). Pre-existing liver diseases were present in 6.5% of patients. No significant differences were observed between the groups based on COVID-19 severity and ALI presence. Liver function test abnormalities, including ALI, are more prevalent in patients with severe COVID-19 infection. HIV infection, high hemoglobin levels, and hypoalbuminemia may be potential risk factors for ALI.

Impact of COVID-19 on liver transplant recipients: A nationwide cohort study evaluating hospitalization, transplant rejection, and inpatient mortality.

The coronavirus disease 2019 (COVID-19) pandemic has posed a major public health concern worldwide. Patients with comorbid conditions are at risk of adverse outcomes following COVID-19. Solid organ transplant recipients with concurrent immunosuppression and comorbidities are more susceptible to a severe COVID-19 infection. It could lead to higher rates of inpatient complications and mortality in this patient population. However, studies on COVID-19 outcomes in liver transplant (LT) recipients have yielded inconsistent findings. To evaluate the impact of the COVID-19 pandemic on hospital-related outcomes among LT recipients in the United States. We conducted a retrospective cohort study using the 2019-2020 National Inpatient Sample database. Patients with primary LT hospitalizations and a secondary COVID-19 diagnosis were identified using the International Classification of Diseases, Tenth Revision coding system. The primary outcomes included trends in LT hospitalizations before and during the COVID-19 pandemic. Secondary outcomes included comparative trends in inpatient mortality and transplant rejection in LT recipients. A total of 15720 hospitalized LT recipients were included. Approximately 0.8% of patients had a secondary diagnosis of COVID-19 infection. In both cohorts, the median admission age was 57 years. The linear trends for LT hospitalizations did not differ significantly before and during the pandemic (P = 0.84). The frequency of in-hospital mortality for LT recipients increased from 1.7% to 4.4% between January 2019 and December 2020. Compared to the pre-pandemic period, a higher association was noted between LT recipients and in-hospital mortality during the pandemic, with an odds ratio (OR) of 1.69 [95% confidence interval (CI): 1.55-1.84), P < 0.001]. The frequency of transplant rejections among hospitalized LT recipients increased from 0.2% to 3.6% between January 2019 and December 2020. LT hospitalizations during the COVID-19 pandemic had a higher association with transplant rejection than before the pandemic [OR: 1.53 (95%CI: 1.26-1.85), P < 0.001]. The hospitalization rates for LT recipients were comparable before and during the pandemic. Inpatient mortality and transplant rejection rates for hospitalized LT recipients were increased during the COVID-19 pandemic.

The flavonoid quercetin decreases ACE2 and TMPRSS2 expression but not SARS-CoV-2 infection in cultured human lung cells.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) on host cells, via its spike protein, and transmembrane protease, serine 2 (TMPRSS2) cleaves the spike-ACE2 complex to facilitate virus entry. As rate-limiting steps for virus entry, modulation of ACE2 and/or TMPRSS2 may decrease SARS-CoV-2 infectivity and COVID-19 severity. In silico modeling suggested the natural bioactive flavonoid quercetin can bind to ACE2 and a recent randomized clinical trial demonstrated that oral supplementation with quercetin increased COVID-19 recovery. A range of cultured human cells were assessed for co-expression of ACE2 and TMPRSS2. Immortalized Calu-3 lung cells, cultured and matured at an air-liquid interface (Calu-3-ALIs), were established as the most appropriate. Primary bronchial epithelial cells (PBECs) were obtained from healthy adult males (N = 6) and cultured under submerged conditions to corroborate the outcomes. Upon maturation or reaching 80% confluence, respectively, the Calu-3-ALIs and PBECs were treated with quercetin, and mRNA and protein expression were assessed by droplet digital PCR and ELISA, respectively. SARS-CoV-2 infectivity, and the effects of pre- and co-treatment with quercetin, was assessed by median tissue culture infectious dose assay. Quercetin dose-dependently decreased ACE2 and TMPRSS2 mRNA and protein in both Calu-3-ALIs and PBECs after 4 h, while TMPRSS2 remained suppressed in response to prolonged treatment with lower doses (twice daily for 3 days). Quercetin also acutely decreased ADAM17 mRNA, but not ACE, in Calu-3-ALIs, and this warrants further investigation. Calu-3-ALIs, but not PBECs, were successfully infected with SARS-CoV-2; however, quercetin had no antiviral effect, neither directly nor indirectly through downregulation of ACE2 and TMPRSS2. Calu-3-ALIs were reaffirmed to be an optimal cell model for research into the regulation of ACE2 and TMPRSS2, without the need for prior genetic modification, and will prove valuable in future coronavirus and respiratory infectious disease work. However, our data demonstrate that a significant decrease in the expression of ACE2 and TMPRSS2 by a promising prophylactic candidate may not translate to infection prevention.

Hospital Readmission in Patients with COVID-19

Background: During the Coronavirus Disease 2019 (COVID-19) pandemic, the demand for hospital beds has exceeded substantially. Thus, we aimed to conduct this study to identify factors associated with the risk of readmission in order to introduce the best discharge plan for patients with high risk of hospital readmission. Methods: This is a multicenter, case-control study including 1357 patients hospitalized with COVID-19 infection. Age-sex-matched case and control groups were paired at 1:2 ratios, and COVID-19 readmission rate was assessed. Moreover, the logistic regression analysis was applied to determine the factors associated with readmission. Results: Of the 1357 patients, 99 (7.29%) subjects were readmitted. The most common cause of readmission was respiratory distress. The median (interquartile) of the interval between hospital discharge and the second admission was 5 (2-16) days. Upon adjusting with the main risk factors, having at least one underlying disease and being treated with the corticosteroid were significantly associated with a higher rate of readmission (OR: 2.76, 95%CI: 1.30- 5.87) and (OR: 8.24, 95%CI: 3.72-18.22), respectively. Conclusion: Identification of risk factors of COVID 19 readmission will improve resource utilization and patient care.

Clinical characteristics and outcomes of hospitalized kidney transplant recipients with COVID-19 infection in China during the Omicron wave: a single-center cohort study.

BACKGROUND: Following the short-term outbreak of coronavirus disease 2019 (COVID-19) in December 2022 in China, clinical data on kidney transplant recipients (KTRs) with COVID-19 are lacking. METHODS: We conducted a single-center retrospective study to describe the clinical features, complications, and mortality rates of hospitalized KTRs infected with COVID-19 between Dec. 16, 2022 and Jan. 31, 2023. The patients were followed up until Mar. 31, 2023. RESULTS: A total of 324 KTRs with COVID-19 were included. The median age was 49 years. The median time between the onset of symptoms and admission was 13 d. Molnupiravir, azvudine, and nirmatrelvir/ritonavir were administered to 67 (20.7%), 11 (3.4%), and 148 (45.7%) patients, respectively. Twenty-nine (9.0%) patients were treated with more than one antiviral agent. Forty-eight (14.8%) patients were treated with tocilizumab and 53 (16.4%) patients received baricitinib therapy. The acute kidney injury (AKI) occurred in 81 (25.0%) patients and 39 (12.0%) patients were admitted to intensive care units. Fungal infections were observed in 55 (17.0%) patients. Fifty (15.4%) patients lost their graft. The 28-d mortality rate of patients was 9.0% and 42 (13.0%) patients died by the end of follow-up. Multivariate Cox regression analysis identified that cerebrovascular disease, AKI incidence, interleukin (IL)‍-6 level of >6.8 pg/mL, daily dose of corticosteroids of >50 mg, and fungal infection were all associated with an increased risk of death for hospitalized patients. CONCLUSIONS: Our findings demonstrate that hospitalized KTRs with COVID-19 are at high risk of mortality. The administration of immunomodulators or the late application of antiviral drugs does not improve patient survival, while higher doses of corticosteroids may increase the death risk.

Histopathological impact of SARS-CoV-2 on the liver: Cellular damage and long-term complications.

Coronavirus disease 2019 (COVID-19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome, multiple organ failure, and death. Despite extensive studies on the pathogenicity of SARS-CoV-2, its impact on the hepatobiliary system remains unclear. While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels, the exact source of this damage is not fully understood. Proposed mechanisms for injury include direct cytotoxicity, collateral damage from inflammation, drug-induced liver injury, and ischemia/hypoxia. However, evidence often relies on blood tests with liver enzyme abnormalities. In this comprehensive review, we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients, drawing from liver biopsies, complete autopsies, and in vitro liver analyses. We present evidence of the direct impact of SARS-CoV-2 on the liver, substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes, including mitochondrial swelling, endoplasmic reticulum dilatation, and hepatocyte apoptosis. Additionally, we describe the diverse liver pathology observed during COVID-19 infection, encompassing necrosis, steatosis, cholestasis, and lobular inflammation. We also discuss the emergence of long-term complications, notably COVID-19-related secondary sclerosing cholangitis. Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.