Assessment of liver function in COVID-19

Introduction: COVID-19 is an infectious disease caused by the SARS-CoV-2 virus that commonly involved the respiratory system. However, the virus can affect any organ in the body including the liver. Hepatic involvement in COVID-19 could be related to the direct cytopathic effect of the virus, an uncontrolled immune reaction, sepsis, or drug-induced liver injury. Background: The current study aims to evaluate the relevance of liver enzyme derangement in COVID-19. Methods: The sample size of 165 patients, tested positive for covid 19 and underwent liver enzyme testing. These patients were categorized into mild, severe, and critical diseases based on clinical evaluation, radiological findings, and biochemical parameters. Results: Of 165 patients selected 103 (62.4%) have mild disease, 40(24.2%) have severe and 12(7.2%) suffered from the critical disease. 48(29.1%) patients show deranged liver function. 83.3% of critical patients and 45% of severe patients show deranged liver function.9.09%of patients died due to severe COVID-19 infections showing moderately to severe liver function derangement. Conclusions: This study concludes that the severity of COVID-19 disease may increase due to chronic liver disease, particularly fatty liver. Atypical ALT and AST levels during hospitalization were indicative of liver injury and correlated with the severity of patients.

Gastrointestinal features of the multisystem inflammatory syndrome in children (MIS-C) following COVID-19 infection in selected referral hospitals in Iran

Background and purpose: Multisystem Inflammatory Syndrome in Children (MIS-C) occurs after having COVID-19. The severity and outcomes of COVID-19 with gastrointestinal symptoms are higher. The aim of this study was to investigate gastrointestinal manifestations in MIS-C patients in selected referral hospitals in Iran to obtain comprehensive information about the treatment and prevention of MIS-C. Materials and methods: In this cross-sectional study, all MIS-C patients <21 years in Dec 2019 to Oct 2021 were included. The patients were identified by the Centers for Disease Control and Prevention (CDC) checklist and data were analyzed applying t-test and Chi-square in STATA11. Results: There were 225 patients with a median age of 55 months (26-96 months), including 59.56% boys and all had fever on admission. At least one gastrointestinal symptom was seen in 200 patients and the most common symptoms were vomiting (60.9%) and abdominal pain (45.77%). Almost 60% of the patients had positive RT-PCR results. Among the patients with and without gastrointestinal symptoms 85.5% and 48% were admitted to intensive care unit (ICU), respectively. There were significant differences between the two groups in respiratory symptoms, ALT, AST, NT-pro BNP, ESR, and PLT (P < 0.05). All patients without gastrointestinal symptoms were discharged but nine patients in the group with gastrointestinal symptoms deceased. Conclusion: According to the current study, gastrointestinal symptoms are common in MIS-C patients and are associated with higher rates of death and intensive care unit admission. Therefore, in providing services to COVID-19 patients, all typical and atypical signs and symptoms should be considered to prevent unnecessary interventions.

Factors affecting admission to intensive care unit of COVID-19 patients in the Kingdom of Bahrain

Objective: Coronavirus disease-2019 (COVID-19) is a newly emerging infectious disease that has become a global pandemic. This study aimed to identify the risk factors at presentation to predict intensive care unit (ICU) admissions. Materials & Methods: This retrospective observational study recruited 188 confirmed laboratory COVID-19 patients who were hospitalized in Jidhafs Maternity Hospital (JMH) from 1st June to 5th July 2020. Univariate and multivariate analyses were used to Explore risk factors associated with the increased risk of ICU admission. Results: The study revealed that older age (>60 years old) (16[38.1%], P=0.044), male gender (30 [40.0%], P=0.000) were significantly associated with the increased risk of ICU admissions. The most prevalent symptoms in admission were myalgia (13[40.6%], P=0.035), fever (39[34.2%], P=0.002) and cough (37[31.4%], P=0.032). In addition, raised serum level of alanine amino-transferase (ALAT) (34.7% vs. 20.7%, P=0.033), D-dimers (30.7% vs 12.2%, P=0.012), lactate dehydrogenase (LDH) (31.6% vs 0.0%, P=0.025) and ferritin (37.7% vs 16.7%, P=0.011) found to be important predictor of ICU admission. Conclusion: The finding indicates that older age, male gender, with increased alanine transferase (ALT), increased lactate dehydrogenase (LDH), high D-dimer and high ferritin was associated with an increased risk of ICU admissions. Identification of such factors will help to detect people who are more likely to develop severe COVID-19 disease and will help physicians to determine if patients need regular health care or ICU admission.

First-in-class small molecule drugs in 2022

2022 is the third year of the global COVID-19 pandemic, and its troubles on new drug discovery are gradually apparent. 37 new drugs were approved by the FDA's Center for Drug Evaluation and Research (CDER) last year, down from the peak of 50 new drug approvals in 2021. Notably, first-in-class drugs still occupy a dominant position this year, with a total of 21 drugs. Among them, 7 are first-in-class small molecule drugs. Although the total number of new drug approvals in 2022 sharply decreased, some first-in-class small molecule drugs were regarded as significant, including mitapivat, the first oral activator targeting the pyruvate kinase (PK);mavacamten, the first selective allosteric inhibitor targeting the myocardial beta myosin ATPase;deucravacitinib, the first deuterated allosteric inhibitor targeting the tyrosine kinase 2 (TYK2);and lenacapavir, the first long-acting inhibitor targeting the HIV capsid. Generally, the research of first-in-class drugs needs to focus on difficult clinical problems and can treat some specific diseases through novel targets and biological mechanisms. There are tremendous challenges in the research processes of new drugs, including biological mechanism research, target selection, molecular screening, lead compound identification and druggability optimization. Therefore, the success of first-in-class drugs development has prominent guidance significance for new drug discovery. This review briefly describes the discovery background, research and development process and therapeutic application of 3 firstin- class small molecule drugs to provide research ideas and methods for more first-in-class drugs.Copyright © 2023, Chinese Pharmaceutical Association. All rights reserved.

Restrospective study of hemogram profile in effusive feline infectious peritonitis

Feline Infectious Peritonitis (FIP) is highly mortality disease in cats. The reliable and fast diagnosis is crucial to the best prognosis. The aim of this study to evaluate the hemogram profile in cats infected with effusive FIP. Twenty cats had been diagnosed effusive FIP at Animal Clinic Department of Internal Medicine, Faculty Veterinary Medicine, Universitas Gadjah Mada were used in the study. The diagnosis were based on clinical examination, ultrasound, x-ray, rivalta test, and rapid test. The hemogram profile were analyzed include routine hematology and serum biochemistry. Hemogram profile in effusive FIP showed the decreased hematocrit, hyperproteinemia, and leukocytosis with an average 22.9+or-7.4%;9.0+or-2.2 g/dL;22425+or-4116 cells/mm3 respectively. Erythrocyte, hemoglobin and fibrinogen levels were still in the normal range. The results of differential leukocytes revealed that 90% cats had neutrophilia and 75% lymphopenia with an average 20066+or-3337 cells/mm3 and 1861+or-1818 cells/mm3 respectively. The blood chemistry profile showed 60% of cats experienced increase in SGPT and SGOT with an average 138.4+or-72.3 IU/L and 101+or-60.5 IU/L respectively. Hyperglobulinemia was found in 90% samples with an average 6.7+or-0.8 g/dL. All cats have a low albumin:globulin ratio with an average 0.3+or-0.1. The hemogram profile of effusive FIP were: leukocytosis, neutrophilia, lymphopenia, hyperglobulinemia, and decreased albumin-globulin ratio..

Characteristics of albumin levels and liver function in patients with COVID-19 at H. Adam Malik Hospital, Medan

Background: COVID-19 (Corona Virus Disease-2019) pandemic has a high mortality rate especially in Medan, Indonesia. Serum albumin and liver function tests are believed to be predictive biomarkers for prognosis in patients with infectious diseases, including COVID-19. This study aimed to investigate the association between the mortality events and severely ill COVID-19 patients' serum albumin and liver enzymes. Method: This is a cross-sectional study using secondary data from the medical records of H. Adam Malik Hospital patients with COVID-19 who were confirmed by RT-PCR from August to December 2020. All patients were analyzed for age, sex, hypoalbuminemia, increased liver enzymes and outcome using Chi-square tests (P <0.05). Results: The average age of severe COVID-19 patients at H. Adam Malik Hospital ranged from 41 to 60 years, with more women prevalence than men. Most of the patients had hypoalbuminemia (84.2%), an increase in AST (59.4)% and ALT (45.5%). There was no significant association between hypoalbuminemia and the disease outcome (P =0.12). There was a significant association between elevated liver enzymes and mortality in severely ill COVID-19 patients (P <0.001). Conclusion: We found that hypoalbuminemia is common in patients with severe COVID-19. However, we found that albumin levels had no association with the patients' mortality rate. Liver enzymes levels appear to be a predictive biomarker for outcomes in COVID-19 patients of H. Adam Malik Hospital. We found that higher ALT and AST levels were associated with significantly higher mortality.

Circulating pyruvate is a potent prognostic marker for critical COVID-19 outcomes.

Background: Coronavirus-19 (COVID-19) disease is driven by an unchecked immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus which alters host mitochondrial-associated mechanisms. Compromised mitochondrial health results in abnormal reprogramming of glucose metabolism, which can disrupt extracellular signalling. We hypothesized that examining mitochondrial energy-related signalling metabolites implicated in host immune response to SARS-CoV-2 infection would provide potential biomarkers for predicting the risk of severe COVID-19 illness. Methods: We used a semi-targeted serum metabolomics approach in 273 patients with different severity grades of COVID-19 recruited at the acute phase of the infection to determine the relative abundance of tricarboxylic acid (Krebs) cycle-related metabolites with known extracellular signaling properties (pyruvate, lactate, succinate and α-ketoglutarate). Abundance levels of energy-related metabolites were evaluated in a validation cohort (n=398) using quantitative fluorimetric assays. Results: Increased levels of four energy-related metabolites (pyruvate, lactate, a-ketoglutarate and succinate) were found in critically ill COVID-19 patients using semi-targeted and targeted approaches (p<0.05). The combined strategy proposed herein enabled us to establish that circulating pyruvate levels (p<0.001) together with body mass index (p=0.025), C-reactive protein (p=0.039), D-Dimer (p<0.001) and creatinine (p=0.043) levels, are independent predictors of critical COVID-19. Furthermore, classification and regression tree (CART) analysis provided a cut-off value of pyruvate in serum (24.54 µM; p<0.001) as an early criterion to accurately classify patients with critical outcomes. Conclusion: Our findings support the link between COVID-19 pathogenesis and immunometabolic dysregulation, and show that fluorometric quantification of circulating pyruvate is a cost-effective clinical decision support tool to improve patient stratification and prognosis prediction.

Serum total bilirubin and aminotransferases in patients with COVID-19 in Nellore district of South Andhra Pradesh

BACKGROUND: Corona virus disease-19 (COVID -19) infection is an acute infectious disease caused by a newly discovered beta corona virus, severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). While the primary target organ is the lungs, involvement of many other organs is often evident in patients with COVID-19. There is emerging evidence to suggest association of SARS-CoV-2 infection with development of many liver abnormalities. The purpose of this study was to evaluate the prevalence of abnormal liver parameters in COVID-19 patients and their variation in moderate and severe cases. METHODS: This is a retrospective study. All patients with COVID -19, between the ages 20-75 years, encountered between April and May 2021, were included for the study and compared with age-matched controls. Severity of infection was defined based on the presence of symptoms, oxygen saturation, need for respiratory and intensive care support. Liver parameters such as serum total bilirubin (TBIL), serum aminotransferases, alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) were analysed. Inflammatory markers such as C-reactive protein (CRP) and D-dimer were also included for assay. RESULTS: A total of 52 patients were encountered during the study period. Of these, 29% (15/52) required intensive care. Abnormal liver parameters were observed in 14 (27%) patients, and were significantly elevated compared to healthy controls. Liver dysfunction was markedly profound in severe infection than those with moderate disease. Higher levels of CRP and D-dimer were noted in severe patients of COVID-19. CONCLUSIONS: Mild liver abnormalities in the form of elevated ALT and AST are seen in COVID-19 patients suggesting mild or no liver injury. These abnormal parameters do not generally lead to significant liver function impairment/failure and no specific treatment is required.

Laboratory and clinical findings in hospitalized pregnant women with COVID-19 based on disease outcome during the outbreak of Delta variant in Ardabil (summer and autumn 2021)

Introduction: Due to the high risk of Covid-19 disease, especially delta variant in pregnant women, as well as the novelty of this epidemic in the world and the lack of similar studies in Iran and the region, it seems necessary to perform a study on mortality rate and laboratory and clinical findings of the disease in pregnant women. Therefore, this study was performed aimed to determine the laboratory and clinical findings in hospitalized pregnant women with Covid -19 based on disease outcome during the outbreak of Delta variant (summer and autumn 2021) in Ardabil province. Methods: In this cross-sectional and descriptive study, all pregnant women with Covid-19 admitted to the hospitals of Ardabil province in summer and autumn 2021 at the time of delta outbreak were included. Finally, 187 infected pregnant mothers were studied. Demographic information, clinical signs and laboratory findings were studied in all mothers. Data were analyzed by SPSS (version 24) and Fisher Exact test and Pearson Correlation. P<0.05 was considered statistically significant. Results: Of the 187 infected pregnant women, 8 mothers died. Comorbidity was observed in 41 pregnant women. The most common clinical finding was shortness of breath (Dyspnea) and cough, and the most common laboratory finding was lymphopenia. Comparing the cured and dead mothers according to laboratory findings using Fisher's exact test showed that the difference between ALT (p <0.05), lactate dehydrogenase (p <0.001), AST (p <0.001), BS (P <0.05), creatinine (p <0.05) and total bilirubin (p <0.05) were statistically significant between the two groups. Conclusion: Infection to delta variant of Covid-19 disease resulted in 187 hospitalizations and 8 deaths of pregnant mothers in Ardabil province. Shortness of breath (Dyspnea) and cough were the most common clinical findings and lymphopenia was the most common laboratory finding.

Study of liver function test in COVID-19 patients and its correlation with inflammatory markers from Hubballi, Karnataka

BACKGROUND: Since its reporting in December 2019, SARC-COV-2 (COVID -19) has infected more than 230 million people over the world by colonising the respiratory tract, however very little is known about its effect on liver and how the liver injury affects disease prognosis. This study was done to assess the hepatic profile in SARC-COV-2 infection along with inflammatory markers. METHODS: This is a single centred prospective observational study. 400 patients with real time polymerase chain reaction (PCR) confirmed COVID 19 infection admitted in KIMS, Hubballi were taken for study. Patients with decompensated liver disease were excluded from the study. Clinical examination and laboratory investigations including liver function test (LFT), renal function test (RFT), complete blood count (CBC), chest X-ray, D-dimer, ferritin, lactate dehydrogenase (LDH), C reactive protein (CRP) was done for all the patients. RESULTS: Out of the 400 covid-19 positive patients admitted, 286 (71.5%) had abnormal liver enzymes. Significantly raised liver enzymes were seen in males. Raised liver enzymes and inflammatory markers were associated with poor outcome of the disease. Significant reduced albumin was associated with poor outcome of the disease. Significantly raised aspartate transaminase (AST), alanine transaminase (ALT) levels were associated with increased severity of the disease. (P = 0.009 and 0.029 respectively). Significant positive relation was found between liver profile and inflammatory markers. CONCLUSIONS: Majority of patients admitted with SARS-CoV-2 had deranged liver profile. Higher proportion of abnormal liver enzymes were seen in males. Degree of liver injury increases with increasing severity of the disease. Even though abnormal liver enzymes were positively associated with elevated inflammatory markers and severity of the disease, more studies are needed to study implications of liver injury in prognosis of SARS-CoV-2 infection.

Comparison of clinical manifestations, liver function, and antibody levels between omicron variant infection patients vaccinated and not vaccinated with COVID-19 vaccine

Objective: To compare the clinical manifestations, liver function, and antibody levels between Omicron variant infection patients vaccinated and not vaccinated with COVID-19 vaccine. Methods: Totally 430 convalescent COVID-19 patients infected with Omicron variant in Tianjin were selected, including 150 patients vaccinated with Corona Vaccine(Sinovac group), 185 patients vaccinated with BBIBP-CorV(Beijing biological group), 41 patients vaccinated with Ad5-nCoV vaccine(CanSino group), 16 patients vaccinated with Anhui Zhifei, Changchun Bio, Lanzhou Bio, Shandong Bio, other adenovirus vector vaccines or mixed vaccination(other group), and 38 unvaccinated patients(unvaccinated group). The clinical manifestations, liver function indexes [alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(TB), albumin(ALB), total protein(TP), lactate dehydrogenase(LDH)], and antibody levels(IgG, IgM)were compared retrospectively. Results: There was no statistical difference in the sex composition ratio among groups(P > 0.05). The age of the Beijing biological group was significantly lower than that of other groups, and the proportion of time less than 3 months from the last vaccination to admission in the Beijing biological group and CanSino group was significantly higher than that in the Sinovac group and other groups(all P < 0.01). A total of 110 children aged less than 16 years were enrolled, including 7, 88, 0, 1 and 14 cases in the Sinovac group, Beijing biological group, CanSino group, other group, and unvaccinated group, respectively. There were 6 asymptomatic cases, 13 moderate cases, 91 mild cases and 0 severe case. There was no significant difference in the abnormal rate of ALT between Beijing biological group and unvaccinated group(P > 0.05), but the abnormal rates of ALT were higher in the Sinovac group and CanSino group than in the unvaccinated group and Beijing biological group(all P < 0.05). The abnormal rate of AST in the unvaccinated group was higher than that in other groups(P < 0.05). There were no significant differences in AST, TP or TB among the groups(all P > 0.05). The levels of ALT were higher in the Sinovac group and CanSino group than in Beijing biological Group and unvaccinated group, the level of ALB in the unvaccinated group was lower than that in the other groups, and the level of LDH in the Beijing biological group was higher than those in the Sinovac group and CanSino group(both P < 0.05). The IgG and IgM antibody levels of the unvaccinated group were significantly lower than those of the Sinovac group, Beijing biological group and CanSino group(all P < 0.05). Conclusions: Omicron variant infection patients vaccinated with BBIBP-CorV are younger and have a higher proportion of mild conditions, which can protect the liver function of patients to a certain extent. Patients vaccinated with different COVID-19 vaccines can produce higher levels of IgG and IgM antibodies than the unvaccinated patients.

Surveillance of adverse effects of Tocilizumab for COVID-19

Background: Tocilizumab (TCZ) is a new therapeutic alternative for severe cases of COVID-19 pneumonia. Aim: To evaluate the cumulative incidence (CI) of suspected adverse drug reactions (ADR) from TCZ in adult patients with COVID-19. Material and methods: An active pharmacological surveillance protocol was carried out in patients older than 18 years old, who received at least one dose of TCZ between May and August 2020 at a clinical hospital. Non-infectious ADRs were categorized according to the Common Terminology Criteria for Adverse Events and the development of infection was classified as present or absent. Causality and preventability of ADRs were determined with the Naranjo Algorithm and the modified Schumock & Thornton criteria, respectively. Results: The CI of ADRs caused by TCZ was 69.6% (95% confidence intervals (CI): 63.5-76.6). A rise in alanine and aspartate aminotransferases and the development of infections were the most frequent adverse events. Seventy-four percent were considered mild in severity. Sixty two percent of suspected non-infectious ADRs were classified as probable and all the infectious events as Possible. Of the ADRs observed, 33% were preventable. Conclusions: The occurrence of ADRs after the use of TCZ is frequent, of mild severity, and in one third of the cases, preventable. We suggest monitoring blood count, liver function tests and ruling out infection prior to TCZ administration.

The association between chest CT severity scores, CO-RADS, vitamin D levels and other laboratory parameters of COVID-19 patients

Objective: This study determined the correlation between several laboratory variables, chest computed tomography severity score (CTSS), and coronavirus disease-2019 (COVID-19) Reporting and Data System (CO-RADS) in COVID-19 patients. Materials and Methods: Ninety-one patients with COVID-19 infection verified by polymerase chain reaction test, presented to the emergency department with COVID-19 symptoms, and had a thoracic computed tomography (CT) scan at the time of admission were included in this retrospective study. 25-hydroxyvitamin D [25(OH)D] levels, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-dimer, glucose, ferritin, creatinine, alanine aminotransferase, aspartate aminotransferase, phosphorous, and calcium levels recorded and CO-RADS and CTSS data. The correlation of laboratory parameters with radiological findings was analyzed. Results: A positive correlation was found between CTSS and age, ESR, CRP, D-dimer while a negative correlation was found between CTSS and lymphocyte count. Patients with high CTSS levels had higher ESR, CRP, D-dimer, ferritin values and lower lymphocyte count, and lower calcium levels. Patients with typical CO-RADS involvement had higher sedimentation, CRP, glucose, and ferritin levels and lower lymphocyte count. No significant correlation was determined between the 25(OH)D level, CO-RADS, and CTSS. Conclusion: The results of this study highlight that the reduced lymphocyte count, high D-dimer, sedimentation, ferritin, and CRP levels are predictors of severe lung involvement in COVID-19 patients. Hypocalcemia can also be considered a marker of severe lung involvement evaluated by CT in COVID-19 patients. the association between vitamin D deficiency and COVID-19 pneumonia should be investigated in future studies.

COVID-19 inhibits spermatogenesis in the testes by inducing cellular senescence.

Introduction: COVID-19 (SARS-CoV-2) has been linked to organ damage in humans since its worldwide outbreak. It can also induce severe sperm damage, according to research conducted at numerous clinical institutions. However, the exact mechanism of damage is still unknown. Methods: In this study, testicular bulk-RNA-seq Data were downloaded from three COVID-19 patients and three uninfected controls from GEO to evaluate the effect of COVID-19 infection on spermatogenesis. Relative expression of each pathway and the correlation between genes or pathways were analyzed by bioinformatic methods. Results: By detecting the relative expression of each pathway and the correlation between genes or pathways, we found that COVID-19 could induce testicular cell senescence through MAPK signaling pathway. Cellular senescence was synergistic with MAPK pathway, which further affected the normal synthesis of cholesterol and androgen, inhibited the normal synthesis of lactate and pyruvate, and ultimately affected spermatogenesis. The medications targeting MAPK signaling pathway, especially MAPK1 and MAPK14, are expected to be effective therapeutic medications for reducing COVID-19 damage to spermatogenesis. Conclusion: These results give us a new understanding of how COVID-19 inhibits spermatogenesis and provide a possible solution to alleviate this damage.

ETAVOPIVAT TREATMENT FOR UP TO 12 WEEKS IN PATIENTS WITH SICKLE CELL DISEASE IS WELL TOLERATED AND IMPROVES RED BLOOD CELL HEALTH

Background: Etavopivat, an investigational, once-daily, selective, activator of erythrocyte pyruvate kinase (PKR) increases PKR activity, resulting in decreased 2,3-DPG and increased ATP in red blood cells (RBCs) of healthy volunteers and patients (pts) with sickle cell disease (SCD).1,2 Aims: We report results of an open-label (OL) extension cohort from a Phase 1 study (NCT03815695) designed to characterize the safety and clinical activity of etavopivat at a maximal pharmacodynamic dose in pts with SCD. Methods: 15 pts were enrolled to receive etavopivat 400 mg once daily for 12 wks, followed by a 4-wk follow-up. Assessments included safety, pharmacokinetics, pharmacodynamics, RBC health parameters and systemic markers of SCD pathophysiology. Results: Of 15 pts (age 32.3 ±10.1 yr;HbSS/SC n=13/2), 14 completed 12-wks of treatment (tx);1 pt discontinued tx after ∼2 wks. Etavopivat 400 mg once daily was generally well tolerated. Adverse events (AEs) reported during tx and follow-up were commonly low grade (Gr) and consistent with pts' SCD. Gr1-2 AEs in >2 pts (n [%]) were sickle cell pain events (9 [60%]);headache (5 [33%]);and upper respiratory tract infection (3 [20%]). The Gr3-4 AE in >1 pt was sickle cell vaso-occlusion (VOC;4 [27%]). On-tx serious adverse events (SAEs;1 pt each) were Gr3 VOC post Gr3 COVID (not tx-related) and Gr3 left femoral deep vein thrombosis (possibly related, resulting in tx discontinuation as stated above). SAEs (1 pt each) during the 4-wk follow-up were Gr3 acute chest syndrome + Gr3 VOC, Gr3 non-cardiac chest pain and Gr3 syncope (all unrelated). Observed increases in ATP and decreases in 2,3-DPG were durable over 12 wks of etavopivat tx. Etavopivat tx normalized hemoglobin (Hb)S-oxygen affinity to that of HbA. Etavopivat tx over 12 wks improved overall sickle RBC health, demonstrated by a reduction in point of sickling as well as improved measures of deformability and hydration of sickle RBCs (all P<0.01;Figure). Etavopivat tx over 12 wks was associated with a sustained significant increase in Hb compared with baseline (BL;P<0.0001), with mean maximal increase of 1.5 (range 0.7-2.3) g/dL. Ontx increase in Hb >1g/dL was achieved in 11 (73%) pts, for whom the mean maximal Hb increase was 1.8 (1.2-2.3) g/dL. Absolute reticulocytes, indirect bilirubin and lactate dehydrogenase significantly decreased from BL and were sustained over the 12wk period (all P<0.05), indicative of increased RBC lifespan and decreased hemolysis. Several markers of disease activity significantly decreased from BL during daily etavopivat tx, including the inflammatory marker tumor necrosis factor-α , which decreased by 35% (P<0.001). Based on preliminary exploratory analysis with an aggregate duration of etavopivat exposure of 3.32 pt-yrs in the OL cohort, a decrease in the trend for VOC Hospitalizations was observed: annualized historical and on-tx VOC Hospitalization rates were 0.93 and 0.30, respectively;the 1 on-tx VOC Hospitalization was COVID-related. Summary/Conclusion: Etavopivat 400 mg once daily for up to 12 wks demonstrated a tolerable safety profile and showed improvements in various markers of RBC health in pts with SCD. Rapid and sustained increases in Hb were associated with decreases in reticulocyte counts and markers of hemolysis, supporting increased sickle RBC lifespan and improved anemia. Together, these results support further evaluation of etavopivat in the Phase 2/3 Hibiscus Study (NCT04624659) currently enrolling pts. (Figure Presented).

Advances in acute severe hepatitis of unknown etiology in children

Since the International Health Regulations National Focal Point for the United Kingdom alerted the WHO of ten cases of acute severe hepatitis of unknown etiology in children on April 5, 2022, relevant cases have been reported worldwide. These patients had acute hepatitis (negative for hepatitis viruses A-E) and elevated aminotransferase (AST) or alanine aminase (ALT) exceeding 500 U/L. Furthermore, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and/or adenovirus type F41 have been detected in some cases. This unknown hepatitis has been hypothesized to be induced by a viral reservoir of novel coronavirus superantigen, which repeatedly stimulates the intestines and leads to a multisystem inflammatory syndrome in children (MIS-C), which causes immune abnormalities in the presence of human adenovirus. Although this hypothesis has not been confirmed by any in vivo experimental or clinical studies, it may provide ideas for possible intervention strategies.

Clinical and laboratory features in COVID-19 patients without anti-SARS-CoV-2 antibody

Objective: The aim of this study is to investigate the clinical and laboratory features in confirmed COVID-19 patients without specific anti-SARS-CoV-2 antibody,it is important to interpret SARS-CoV-2 antibody test results correctly and provide effective management for COVID-19 patients without specific anti-SARS-CoV-2 antibody.

Clinical and radiological characteristics of adult hospitalized Coronavirus disease-2019 patients of Dhaka, Bangladesh

The severity of Coronavirus disease-2019 (COVID-19) varies among individuals and some influential factors leads to critical infections and death. This study aimed to assess various clinical data of hospitalized patients and identify the determinants of critical COVID-19 infection. This was a cross-sectional study among hospitalized COVID-19 patients confirmed by reverse transcription polymerase chain reaction (RT-PCR). Data was collected from a single Centre between January to April 2021 by experienced physicians of Ad-din Medical College Hospital. All of the laboratory tests were performed by technical experts and the data was analyzed by Statistical package for the social sciences software. Among the study participants 25% were Intensive care unit (ICU) patients and the mean age of them were higher (59 years) than non-ICU (55 years) patients. Our analysis has identified diabetes mellitus (AOR=2.5, 95%CI: 1.1-5.4) and ischemic heart disease (AOR=3.1, 95%CI: 1.1-8.9) as significant predictor of critical outcome (ICU admission). Anemia (AOR=3.3, 95%CI: 1.5-7.4), lymphopenia (AOR=2.9, 95%CI: 1.2-7.1), and thrombocytopenia (AOR=4.2, 95%CI: 2.7-12.9) was also associated critical outcome. Biomarkers of kidney injury (creatinine, blood urea nitrogen), liver damage (alanine transaminase, aspartate aminotransferase, fibrinogen) and electrolyte imbalance (sodium and potassium level) were also significantly associated with critical infection. A higher d-dimer level (2.5) was the most important predictor (AOR=11.5, 95%CI: 5.4-24.6) of critical COVID 19 infections. The study has revealed socio-demographic, comorbidity, and radiological risk factors of critical COVID-19 infections. The identified risk factors would be considered for decision making during the treatment process.

Clinical features of 51 patients with corona virus disease 2019

Objective: To investigate the clinical characteristics of corona virus disease 2019 (COVID-19) patients in Wuhan City, and the correlation between inflammatory factors and severity.

Clinical features of patients with Severe acute respiratory syndrome Coronavirus 2 Delta variant infection and abnormal liver function in Guangdong Province, China. (Theme Issue: New advances in the precise diagnosis and treatment of liver cancer.) [Chinese]

Objective: To investigate the clinical features of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant infection and abnormal liver function in Guangdong Province, China.