Coronavirus disease (COVID-19) in patients with type 2 diabetes mellitus: clinical and laboratory peculiarities

This study aims to study the clinical-laboratory peculiarities of the coronavirus disease (COVID-19) course in patients with type 2 diabetes mellitus (DM). There were examined 60 patients with the coronavirus disease COVID-19. Patients were divided into two groups: group I - 30 patients with the coronavirus disease (COVID-19) with concomitant type 2 diabetes mellitus;group II - 30 patients with coronavirus disease (COVID-19) without diabetes mellitus;control group - 20 people. There were studied peculiarities of clinical-laboratory changes in patients with coronavirus disease with type 2 diabetes mellitus. General clinical laboratory tests, determination of biochemical parameters, coagulogram, ferritin, CRP, procalcitonin, D-dimer and endothelin-1 were performed. Blood saturation was measured. Out of the instrumental methods, an ultrasound examination of the lungs and RTG of thoracic organs was performed. Patients were admitted on the 5.46+/-0.87 day of the disease. The length of the hospital stay for patients of group I was 19.9+/-1.66 bed days and 14.7+/-0.91 bed days for the patients of group II. A severe course of the disease was observed in 83.3% of patients of group I and 33.3% of group II;a moderate severity course was observed in 16.7% of patients with concomitant DM and 66.7% of patients without concomitant DM. Respiratory failure (RF) of 1 degree was observed in 30% of patients of group 1, RF of the 2 degree - in 16.7% of patients, and RF of the 3 degree - in 10% of patients. In patients without DM, RF of 1 degree - was in 30% of patients, and RF of the 2 degree - was in 13.3% of patients. The laboratory diagnostic methods determined that the levels of leukocytes, D-dimer, endothelin-1, IL-6, procalcitonin, and ferritin were higher in patients with concomitant type 2 DM. In patients with type 2 DM, the course of the coronavirus disease is more severe and longer, with the development of pneumonia and respiratory failure. It is accompanied by leukocytosis, lymphopenia, increased ESR, prothrombin index, IL-6, CRP level, procalcitonin and endothelin-1. Copyright © 2023 The Authors.

Demographic Characteristics, Laboratory Findings, Radiological Features, and Outcomes of Patients with COVID-19: A Single-center Descriptive Study

BACKGROUND: The coronavirus disease 2019 (COVID-19) has resulted in a global crisis, affecting hundreds of millions of individuals, with Indonesia reporting a significant increase in cases in July 2021. AIM: This study aims to describe the clinical, laboratory findings, radiological features, and outcomes of hospitalized patients with COVID-19. METHOD(S): This retrospective study was carried out using 606 hospitalized COVID-19 patients who were admitted to the isolation ward in a hospital in South Jakarta, Indonesia, from January 1 to April 30, 2021. RESULT(S): The median age of the patients was 45 years, 55.6% were male, and 85.5% had non-severe diseases, with the most common presenting symptoms being fever, cough, and gastrointestinal symptoms. Patients with severe disease were significantly older (p < 0.001), most of them have hypertension (p < 0.05) and diabetes (p < 0.001), have an increased CRP (p < 0.001), high ferritin (p < 0.001), and increased D-dimer (p < 0.001). Compared to patients who survived, patients who had died were older (p < 0.001), had hypertension (p = 0.013), increased CRP (p < 0.001), high ferritin (p = 0.002), and increased D-dimer (p = 0.006). CONCLUSION(S): These results showed that older age, comorbidities, and a higher level of CRP, ferritin, and D-dimer increased the risk of severe disease and poor clinical outcomes in hospitalized COVID-19 patients.Copyright © 2023 Wulyo Rajabto, Prasna Pramita, Hilman Tadjoedin, Donnie Lumban Gaol, R. A. Sri Hardini, Nirmala Purbasari Tarigan, Vitya Chandika, Rumuat Semuel Wullul Manangka, Maria Pyrhadistya.

Impact of Covid-19 on the Prevalence of Intrahepatic Cholestasis of Pregnancy

Background: The virulent pathogen SARS-CoV-2 first appeared in the Chinese province of Hubei in December 2019. Pregnant women were a high-risk population in the pandemic because immune system alterations that occur during pregnancy make them more vulnerable to foreign infections. Late-pregnancy cholestasis is a dangerous liver condition that can cause the foetus to experience potentially fatal problems like early birth and stillbirth. In the present study we were testing the Bile acid level during pregnancy patients after covid pandemic. Objective(s): To evaluate the prevalence of intrahepatic cholestasis in pregnant patients after Covid -19 pandemic. Material(s) and Method(s): This cross-sectional study was conducted at department of Dr.fida painless and General Hospital Peshawar from jan 2022 to Dec 2022. We enrolled 186 pregnant patients after fulfilling the inclusion criteria. 5 ml blood sample were also taken from the patients. Serum was extracted and Bile acid test were performed in clinical laboratory. Data were collected in predesign questionnaire. Result(s): Total 186 patients were enrolled in the study with mean age of 37.18+/-6.39 years (Range 18-45 years). The mean value of all enrolled patients was 31.38+/-5.79 with minimum and maximum value of bile acids 20 micromol/L and 40.6.00 micromol/L. In our study 95 (56.5%) of patients belongs to 36 to 45 years of age group followed by age group of 26 to 35 years in which 60 (35.7%) patients and 13 (7.7%) patients were belongs to age group of 18 to 25 years. Practical implication: This study will help the clinical practitioner to take care of pregnant patients in order to avoid the prevalence of intrahepatic cholestasis. Conclusion(s): It is concluded from this research study that prevalence of intrahepatic cholestasis in pregnancy has increased after Covid-19 pandemic.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

Misdiagnosis of Clostridioides difficile Infections by Standard-of-Care Specimen Collection and Testing among Hospitalized Adults, Louisville, Kentucky, USA, 2019-20201.

Although Clostridioides difficile infection (CDI) incidence is high in the United States, standard-of-care (SOC) stool collection and testing practices might result in incidence overestimation or underestimation. We conducted diarrhea surveillance among inpatients >50 years of age in Louisville, Kentucky, USA, during October 14, 2019-October 13, 2020; concurrent SOC stool collection and CDI testing occurred independently. A study CDI case was nucleic acid amplification test‒/cytotoxicity neutralization assay‒positive or nucleic acid amplification test‒positive stool in a patient with pseudomembranous colitis. Study incidence was adjusted for hospitalization share and specimen collection rate and, in a sensitivity analysis, for diarrhea cases without study testing. SOC hospitalized CDI incidence was 121/100,000 population/year; study incidence was 154/100,000 population/year and, in sensitivity analysis, 202/100,000 population/year. Of 75 SOC CDI cases, 12 (16.0%) were not study diagnosed; of 109 study CDI cases, 44 (40.4%) were not SOC diagnosed. CDI incidence estimates based on SOC CDI testing are probably underestimated.

Effectiveness of Colchicine among Patients with Covid-19 Infection: A Randomised, Open Labelled, Clinical Trial

Background/Aims In November 2019, there were abundant cases of COVID-19 for which the first case was reported in Wuhan, China. Cytokine storm syndrome is the severe immune reaction that may cause a severe tissue response in COVID-19 patients. Colchicine has an important role in inhibiting activation of NLRP3 inflammasome that predispose to decrease cytokine production. This study aimed to evaluate whether colchicine is effective in treatment of COVID-19 patients or not. Methods A randomized, open labelled, clinical trial of colchicine for the treatment of COVID-19, allocated between 8th May to 18th June 2021. Patients with mild, moderate, or severe COVID-19 infection;confirmed by real time PCR (RT-PCR) and/or lung involvement confirmed by computed tomography scan compatible with COVID- 19. The colchicine tablet dosage was 0.5mg twice daily for 14 days added to the standard treatment versus control group who received standard treatment without colchicine, with the trial registration ID: NCT04867226. The study was conducted in Erbil City, Iraq with the endpoints being clinical, laboratory parameters duration of hospitalization and side effects. Results 80 patients participated in the study. Fewer patients in the colchicine group had musculoskeletal symptoms (17.5%, p: 0.001) in comparison to the patients, who received control treatment. The serum ferritin level in most of patients who treated with colchicine returned to normal in contrast to the control group, whose serum ferritin level was still high (p: 0.041). Similarly, the average of CRP and D-dimer after treatment among the colchicine group participants was significantly lower than the control group, the P-values were 0.011 and 0.043, respectively. The colchicine group patients stayed for a shorter duration at the hospital (18.4 days) compared to the control group (24.24 days). Pvalue was 0.009. In addition to that the response and cure rate were higher in the colchicine group (56%) in the comparison to control group (43.1%) Table 1: Laboratory Parameters with musculoskeletal symptoms and duration of hospitalization of both Treatment Regimens. Conclusion The colchicine drug can be effective in treating patients with COVID-19 infection by improving musculoskeletal symptoms and inhibiting inflammatory biomarkers;it is also effective in reducing duration of hospitalization. (Table Presented).

The use of enterosorbents in the immunorehabilitation of patients who have had a new coronavirus infection COVID-19

Post-covid syndrome is characterized by a spectrum of persistent symptoms that do not disappear for many months, which may be due to an inadequate immune system response. This leads to a discussion of potentially new methods immunorehabilitation with the use of effective enterosorbents. The aim of the study was to assess the clinical effectiveness of enterosorbents and immunological parameters of patients with a long-term "post-covid syndrome" who have undergone a new coronavirus infection COVID-19. In n pilot monitored open non-randomized experimental clinical observationanl study 33 patients who had a novel coronavirus infection with COVID-19 underwent comprehensive treatment with the inclusion of azoximer bromide (Polyoxidonium) and colloidal silicon dioxide (Polisorb MP). Analysis of clinical and laboratory data showed that after immunorehabilitation, most of the indicators characterizing the state of the immune system in patients who had COVID-19 were restored to control values. And the use of enterosorbents in complex immunorehabilitation therapy is justified and confirmed by the relief of dyspeptic and asthetovegetative syndromes, which makes it possible to recommend it for use in complex treatment.Copyright © 2021 Infectious Diseases: News, Opinions, Training. All rights reserved.

Clinical improvement 2 years after starting elexacaftor/tezacaftor/ivacaftor in patients with advanced lung disease

Background: With the introduction of new cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy (elexacaftor/tezacaftor/ ivacaftor), peoplewith CF experiencing severe lung disease can experience significant improvements in clinical symptoms. Method(s): This single-center institutional review board-approved retrospective chart review identified patients with advanced lung disease who met criteria for a compassionate use or expanded access program because of high risk of death or transplant need within 2 years. Clinical data collection for all patients began at baseline, 2 to 4 weeks after therapy initiation, and continued every 3 months for 2 years. Datawere collected on demographic characteristics, clinic progress notes, clinical labs, forced expiratory volume in 1 minute (FEV1),weight, body mass index, respiratory colonization, and hospitalizations after drug initiation. Patients also completed sinus and chest computed tomography (CT) to track clinical changes. Result(s): Eighteen people with CF (aged 15-49, 56% male) from a large midwestern CF center who initiated drug therapy between July and September 2019 in an inpatient hospital or clinic setting were identified. Clinical markers (Table 1) indicated that modulator therapy was well tolerated and not discontinued by any participant;safety lab values did not indicate medical concern or discontinuation. There were 90 admissions for the group in the 2 years before therapy and 17 admissions during the 2 years after, although seven of the posttherapy admissions were for nonrespiratory indications. Monitoring results indicated the safety of modulator therapy because there were no adverse clinical occurrences or laboratory events, and all patients presented with universal stabilization. There have been no deaths and no transplants. Unlike lumacaftor/ivacaftor, therewere no problems with chest tightness or any difficulty with troublesome increases in expectoration burden or choking during initiation of therapy. Most had significant reduction in or loss of spontaneous cough and sputum production. The impact on microbial colonization is unclear, because even in this severe group, inability to produce sputum on command led to considerable missing data in follow-up, leaving colonization status at follow-up unclear. Conclusion(s): This study focused on people with CF who qualified for modulator therapy based on advanced lung disease. Initiation of modulator therapy was deemed safe and resulted in objective positive changes in nutrition;cough;FEV1);and subjective reports of clinical status, level of activity, and reduction in burden of treatment. No evidence was found of difficulty managing the increased expectoration during initial therapy. Limitations were noted in missing data during the COVID-19 pandemic, small sample size, and delayed follow-up for drug monitoring.(Table Presented) Clinical indicators before and after modulator therapy *Completed post-drug initiation (earlier than 12 months), **24 months before and after therapy initiationCopyright © 2022, European Cystic Fibrosis Society. All rights reserved

Safety and tolerability of losmapimod for the treatment of FSHD

Evaluate the safety and tolerability of losmapimod in the treatment for FSHD. FSHD is a relentless, variably progressive disease leading to accumulation of disability over decades. Fulcrum is developing losmapimod, a small molecule p38 alpha/beta MAPK inhibitor, to treat FSHD. Losmapimod has been generally well-tolerated in more than 3,600 subjects across multiple clinical studies, including >100 subjects with FSHD. Fulcrum has assessed losmapimod in FSHD in one completed phase 1 study (FIS 001-2018) and two ongoing Phase 2 studies in the open label extension period (FIS 001-2019 and FIS 002-2019). Subjects aged 18-65 years with genetically confirmed FSHD1, clinical severity score 2-4, and MRI-eligible muscles for biopsy were exposed to losmapimod 7.5 or 15 mg twice daily PO for 14 days and up to 76 weeks. In study FIS 001-2018, 6 subjects were exposed to 7.5 mg and 11 subjects to 15 mg twice daily dosing for 14 consecutive days. In studies FIS 001-2019 and FIS 002-2019, 14 and 77 subjects respectively, received at least one dose of losmapimod 15 mg twice daily for up to 76 weeks. A total of 108 subjects with FSHD1 have been exposed to losmapimod, with approximately 131 patient-years of exposure. Fifty-seven subjects have been exposed to losmapimod for 12 to 18 months, and 30 have been exposed for over 18 months. Most adverse events (AEs) observed during the studies were considered of mild to moderate in severity. The most common AEs were alanine aminotransferase (ALT) increase, headache, dizziness, dry skin, eczema and gastrointestinal disorders. The majority of AEs resolved with continued dosing. Dosing has been paused for 14 days in four subjects (3 in FIS 001-2019 and 1 in FIS 002-2019) subjects due to COVID-19 infection. There were no reported drug related SAEs, deaths, discontinuations due to AEs, or clinically significant changes in vital signs, clinical laboratory results, or ECG parameters. Losmapimod given as up to 15 mg twice daily in >100 subjects with FSHD1 for up to 76 weeks has been generally well-tolerated, consistent with that previously reported in other patient populations. Therefore, the benefit-risk profile of losmapimod for the treatment of FSHD remains favorable.Copyright © 2022

Fungal pneumonia in COVID-19 patients: Risk factors and early prediction

Objective To determine the risk factors for developing secondary fungal pneumonia in moderate to severe coronavirus disease 2019 (COVID-19) cases. Using predictors of fungal infection helps to guide the diagnosis and treatment in these cases and save their lives. Patients and methods A total of 257 patients with moderate to severe COVID-19 pneumonia were examined in this retrospective study at Al Qassimi Hospital of EHS. An assessment of clinical, laboratory, and radiologic findings was performed upon admission. The data were collected and analyzed. Results Overall, 32% of critically ill COVID cases had fungal infection;47% of them were candida, whereas aspergillosis and yeast were positive in 26.5% each. At the time of hospitalization, computed tomography chest findings had a strong correlation with fungal culture results in COVID-19 cases. Fungal infection in COVID-19 cases correlated strongly with metabolic acidosis, high erythrocyte sedimentation rate, high blood sugar, need for mechanical ventilation at admission, vasopressor use, renal replacement, long duration of steroid treatment, long stay in ICU, and long duration on mechanical ventilation. The longer the duration of PCR positivity, the higher the incidence of positive sputum fungal culture result. Conclusion COVID-19-infected patients with other risk factors for fungal infections should always be considered to have fungal infections if pathogenic organisms are isolated from respiratory secretions or other microbiological or immunological markers appear positive. Computed tomography chest finding in COVID-19 cases is an important predictor for fungal infection.Copyright © 2023 The Egyptian Journal of Chest Diseases and Tuberculosis.

Safety and Pharmacokinetics of a Novel Double Prodrug Asc10 in Healthy Subjects

Background: ASC10 is an oral double prodrug of the active antiviral ribonucleoside analog, ASC10-A (also known as beta-d-N4-hydroxycytidine), which is a potent inhibitor of SARS-CoV-2. ASC10 is rapidly metabolized into ASC10-A in vivo after oral dosing. Here, we report the results of the first-in-human, phase 1 study to determine the safety, tolerability, and pharmacokinetics (PK) of ASC10 in healthy subjects, and to assess the food effect on the pharmacokinetics. Method(s): This study included 2 parts. Part 1 (multiple-ascending-dose) consisted of 6 cohorts (8 or 12 subjects per cohort). Eligible subjects were randomized in a 3:1 ratio to receive either twice-daily (BID) doses of 50 to 800 mg ASC10 or placebo for 5.5 days, and were then followed for 7 days for safety. In Part 2 (food effect), 12 subjects were randomized in a 1:1 ratio to either 800 mg ASC10 in the fed state followed by 800 mg in the fasted state, or vice versa, with a 7-day washout period between doses. PK blood samples were collected and measured for ASC10-A along with ASC10 and molnupiravir. Safety assessments included monitoring of adverse events (AEs), measurement of vital signs, clinical laboratory tests, and physical examinations. Result(s): ASC10-A was the major circulating metabolite ( >99.94%) in subjects after oral dosing of ASC10. ASC10-A appeared rapidly in plasma, with a median Tmax of 1.00 to 2.00 h, and declined with a geometric t1/2 of approximately 1.10 to 3.04 h. After multiple dosing for 5.5 days, both Cmax and AUC of ASC10-A increased in a dose-proportional manner from doses of 50 to 800 mg BID without accumulation. of ASC10-A in the fed state occurred slightly later, with a median of 3.99 h postdose versus 2.00 h (fasted state). However, Cmax and AUC were very similar or the same between fed and fasted states. Thus, administration of ASC10 with food is unlikely to have an effect on exposure. The incidence of AEs was similar between subjects receiving ASC10 or placebo (both 66.7%) and 95.0% of AEs were mild. There were no serious adverse events as well as no clinically significant findings in clinical laboratory, vital signs, or electrocardiography. Conclusion(s): Results of this study showed that ASC10 was well tolerated, and the increase in plasma exposure of ASC10-A was dose proportional across the range of doses tested with no accumulation and no food effect. 800 mg ASC10 BID is selected for further studies in patients infected with SARS-CoV-2.

Ai-Based Prediction of Lung Tissue Involvement Is Predicitive of Covid-19 Severity

Background: During COVID-19 epidemics several artificial-intelligence neural networks (ANN) systems were developed classify the risk of disease progression to respiratory failure and death, providing aid for clinical decision. However, for optimal results these models should link multiple medical data in a simple model. In this study we analyse the in-hospital mortality and mechanical ventilation risk using combination ANN based rapid computed tomography assessment tool and selected clinical variables. Method(s): Data of 4317 COVID-19 hospitalized patients including 266 cases required mechanical ventilation were analysed using newly constructed and locally trained ANN algorithm. Demographic, clinical, laboratory, and ANNbased lung inflammation data were analysed using proportional Cox Hazards model and estimate in-hospital mortality and intensive care admission risk. Result(s): Overall in-hospital mortality associated with ANN-assigned percentage of the lung involvement (HR 5.72 (95%CI: 4.4-7.43), p< 0.001 for the patients with >50% of lung tissue affected by COVID-19 pneumonia), age category (HR 5.34 (95%CI: 3.32-8.59) for cases >80 years, p< 0.001), procalcitonin > 2 (HR: 2.1 (95%CI: 1.59-2.76) ng/ml p< 0.001, C-reactive protein level category (max. HR 2.11 (95%CI: 1.25-3.56) for CRP >100 mg/dL, p=0.004), estimated glomerular filtration rate (max HR 1.82 (95%CI: 1,37-2,42), p< 0.001 for eGFR < 30 ml/min) and troponin increase above upper limit normal level (HR: 2.14 (95%: 1.69-2.72, p< 0.001) (Figure 1). Furthermore, risk of mechanical ventilation also associated with ANN-based percentage of lung inflammation (HR 13.2 (8.65-20.4), p< 0.001 for patients with >50% involvement), age, procalcitonin > 2 ng/ml (HR: 1.91 (95%CI: 1.14-3.2), p=0.14 estimated glomerular filtration rate (HR 1.82 (1.2-2.74), p=0.004 for eGFR < 30 ml/min) but also clinical variables, including (HR: 2.5 (95%CI: 1.91-3.27), p< 0.001), cardiovascular and cerebrovascular disease (HR: 3.16 (95%CI: 2.38-4.2), p< 0.001), and chronic pulmonary disease (HR: 2.31 (95%CI: 1.44-3.7), p< 0.001). Conclusion(s): ANN-based lung tissue involvement was the strongest predictor of unfavorable outcomes in COVID-19, and represent valuable support tools for clinical decisions. (Figure Presented).

IDENTIFICATION OF CLINICAL FEATURES ASSOCIATED WITH SARS-CoV-2 REINFECTIONS

Background: Over 600 million of COVID-19 cases have been reported. A remarkable fragment of these cases are reinfections, which are mostly explained by the genomic variability of the SARS-CoV-2 variants. However, little is known about other factors fostering these reinfections. Method(s): We recorded clinical and demographic data from subjects (N=3303, March 2020 - March 2022) with at least 2 PCR+ events separated by >=90 days, analyzed by the Microbiology Department, Northern Metropolitan Clinical Laboratory from Germans Trias i Pujol Hospital (Spain). Data collected included: age, sex, comorbidities, adjusted morbidity group (GMA), hospitalization, symptomatology, NAAT (PCR, TMA) tests, antigen tests, serology, and vaccination. Temporal data was encoded using Python, and demographic characterization was performed under R. Result(s): We identified 2344 cases of confirmed reinfections, where the 2 PCR+ events were separated by >=90 days and a negative test was obtained between episodes. 72.2% of reinfected subjects were females with a median age of 45 IQR [28-63] years. Age density analysis showed three peaks at 24, 45, and 85 years, probably mostly composed of young people, who usually are less cautious, healthcare workers, and people living in nursing homes, respectively, being all of them groups prone to be tested. Regarding health status, 86.2% of participants had at least one chronic condition, with 40.5% of patients having chronic conditions in >=4 systems based on GMA assessment. Interestingly, 75.2% of reinfected subjects < 26 years had at least one chronic condition. 121 (4.2%) participants were hospitalized during a COVID-19 episode, highlighting 8.3% (N=10) of them hospitalized during the reinfection (half of them vaccinated before hospitalization), and 5% (N=6) of them during both infections. The severity of the second infection may be caused by a diminished acquired immunity after the first infection. Time between reinfections density analysis provided three peaks at ~200, ~400, and ~600 days, corresponding with time between waves. A decrease of reinfections was observed between 40 and 100 days after vaccination, which would be the period of highest protection against reinfection. Conclusion(s): SARS-CoV-2 reinfections are more prevalent among women. Importantly, people with an undermined health status, independently of age, are more sensitive to reinfections, but in most of the cases no hospitalization was required. Finally, vaccination seems to have a short protective effect on reinfection.

Community pharmacist-provided test and treat programs for acute infectious conditions

Community pharmacists' roles have expanded in recent years to include offering test and treat programs where they perform testing on Clinical Laboratory Improvement Amendment (CLIA)-waived point-of-care testing (POCT) devices to diagnose specific acute infectious conditions, such as influenza and group A streptococcus (GAS) pharyngitis, and then potentially prescribe and dispense appropriate antimicrobials. Availability of these services in pharmacies has several benefits, including increased access to care, decreased overutilization of other health care services, and decreased antimicrobial resistance. States have different requirements for collaborative practice agreements and reimbursement for these clinical services in community pharmacies. Several studies have looked at outcomes related to community pharmacies implementing test and treat programs for influenza and/or GAS. Other studies looked at outcomes related to implementing testing for SARS-CoV-2 and referring for treatment. Most studies described successful implementation and barriers to integration of these programs into pharmacy workflow. Some studies showed that patients want these services to be offered in community pharmacies and are willing to pay for the services. Data show that these services are cost effective compared to physician provider-based treatment. Newer CLIA-waived POCT technology may increase implementation of these services, but studies are needed to evaluate their utility in community pharmacies. Pharmacy schools should implement widespread training on these devices, and research should continue in this area to test the use of newer technology (i.e., multiplexed devices) and their economic impact.Copyright © 2023 Pharmacotherapy Publications, Inc.

Correlation of clinical, laboratory, ventilation, and outcome parameters in hospitalized Coronavirus Disease 2019-infected patients with computed tomography severity score

Context Widespread prevalence of Coronavirus Disease 2019 (COVID-19) infection with high rates of morbidity and mortality necessitates early case definition and severity grading to predict prognosis and improve disease outcome parameters. Purpose To correlate computed tomography severity score (CTSS) in COVID-19-infected patients with their clinical, laboratory, method of ventilation, and disease outcome parameters. Patients and methods A retrospective analysis was performed on 139 COVID-19-infected patients with typical or indeterminate COVID radiological patterns with a correlation between CTSS and their clinical, laboratory, ventilation, hospital stay, and survival data. Results A total of 139 cases were included, with a mean age of 59.81 +/- 12.29 years, 63.3% males, 28.77% were noncomorbid, and oxygen saturation of 82.53 +/- 6.58 SD. They were subgrouped based on CTSS. A significant correlation was found between high CTSS and oxygen saturation, C-reactive protein, ferritin, D-dimer, lymphopenia, diabetes comorbid patients, need for high-flow oxygen therapy, need for noninvasive or invasive ventilation, mortality, and number of hospital stay in days. Conclusion Different parameters are correlated with high CTSS, especially low oxygen saturation, high C-reactive protein or ferritin values, diabetes, and long hospital stay.Copyright © 2023 Wolters Kluwer Medknow Publications. All rights reserved.

Activated CD8 T-cell hepatitis in children: a single institution experience

Background: Pediatric acute liver failure is a rare and serious life-threatening situation, principally for the 30 to 50% of children in whom the etiology of their liver failure is unclear or indeterminate. Treating these patients is challenging, requiring constant assessment over time with regular evaluation for possible liver transplantation. Children with pediatric acute liver failure of undetermined etiology have lower spontaneous survival and higher rates of transplantation and death than other diagnostic groups. Emerging evidence suggests that a subgroup of patients with indeterminate pediatric acute liver failure have clinical, laboratory, and liver biopsy features of immune dysregulation with a dense infiltration of CD8 T cells. Method(s): In 2022, we received percutaneous liver biopsies from three children with acute hepatic dysfunction that showed an increased number of lymphocytes including CD8 T cells. For each case, routine H&E stains with levels, special stains and immunostains were performed. The first biopsy was from an 18-month-old male who presented with COVID infection, pancytopenia, elevated transaminases, and synthetic liver dysfunction (elevated INR). The second was from a 9-year-old female with a history of elevated liver enzymes with no clear cause. The third case was from a 2-year-old male with elevated liver enzymes, coagulopathy, and cholestasis. Result(s): The three cases showed similar histopathologic findings;an acute liver injury pattern with lobular architectural disarray, giant cell formation, reactive changes, single cell necrosis, cholestasis and marked mixed lymphocytic infiltrates. The infiltrates were predominantly composed of CD8-positive T-lymphocytes with scattered neutrophils, eosinophils and rare plasma cells. Portal areas were mildly expanded with mild bile ductular proliferation and mild to moderate lymphocytic infiltrates. Immunostains for CD8 demonstrated that the infiltrates were predominantly composed of CD8-positive T-lymphocytes. All three patients received steroids and responded to treatment evidenced by normalization of liver enzymes and function. Conclusion(s): Dense hepatic CD8 T-cell infiltration is a major finding inactivated CD8 T-cell hepatitis. However, the percentage distribution of lymphocyte subtypes in the setting of hepatitis is not well established, and CD8 T-cell infiltration has also been described in cases of drug-induced hypersensitivity reactions, viral hepatitis, hemophagocytic lymphohistiocytosis, and macrophage activation syndrome, as well as autoimmune hepatitis. Further investigation is needed to better understand the diagnostic criteria in this disease.

Ultrasonic personal spirometer appears accurate and feasible for remote monitoring

Introduction/Aim: Home spirometry may improve respiratory disease monitoring and management and mitigate the decline in testing exacerbated by COVID-19. Smartphone-connected spirometers could allow patients to conduct spirometry independently without the need to travel to lung function clinics. This study assessed the accuracy of a personal spirometer and the feasibility of unsupervised home spirometry. Method(s): Subjects (19-88 years) with (n = 44) and without (n = 20) respiratory disease, were recruited and supervised to perform spirometry on a standard desktop spirometer (MGC Diagnostics) and a personal ultrasonic spirometer (SpiroHome) in the clinical laboratory. Unsupervised testing was subsequently conducted using the SpiroHome at the subjects' home (2 tests/week for 3 weeks). Subjects returned to the clinic to conduct an exit survey which assessed their willingness to adopt a personal spirometer into their long-term care plan. Comparisons between desktop and personal spirometry, as well as supervised and unsupervised spirometry, were compared by Bland-Altman analysis (%Bias +/- CI) and Pearson's correlation. Result(s): The proportion of tests meeting American Thoracic Society/European Respiratory Society criteria (80%) remained constant across clinic and home spirometry sessions for subjects who completed 3 weeks of home testing (p = 0.73, Fisher's exact test, n = 61). Supervised spirometry on the SpiroHome (n = 56) reliably measured FEV 1 (-3.12+/-27.01%;r=0.98, p < 0.0001) and FVC (-0.38+/-22.91%;r=0.99, p < 0.0001) producing a small underestimation compared to desktop spirometry. Unsupervised home spirometry (when performed <24 hrs from the clinic appointment) on the SpiroHome (n = 51) produced a small underestimation of FEV 1 (-2.41+/-35.57%;r=0.96, p < 0.0001) and a slight overestimation of FVC (0.08+/-24.70%;r=0.98, p < 0.0001) compared with supervised manoeuvres in the clinical laboratory. Conclusion(s): Findings indicate that lung function assessed by SpiroHome compares well with in-clinic standard desktop spirometry across a range of diseases and severities in both the clinic and home settings. A larger cohort of subjects are being recruited to confirm the accuracy and the overall utility of personal spirometry.

Verification of the Performance of the Panbio COVID-19 Ag Rapid Test Device for Implementation in the Clinical Laboratory

Objectives: The Panbio COVID-19 Ag Rapid Test Device (Panbio COVID-19 Ag, Abbott Rapid Diagnostics) is a lateral flow immunochromatographic assay targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein in nasopharyngeal specimens for the diagnosis of coronavirus disease 2019 (COVID-19). This study aimed to verify the performance of the Panbio COVID-19 Ag for implementation in clinical laboratories. Method(s): Sixty nasopharyngeal swab specimens (30 positive and 30 negative) dipped in transport medium, and COVID-19 was confirmed using real-time RT-PCR using Allplex SARS-CoV-2 assay (Seegene), were tested using the Panbio COVID-19 Ag. Reproducibility was evaluated using positive and negative control materials. Sensitivity and specificity were calculated based on the results of realtime RT-PCR as the standard test method. Result(s): Reproducibility was confirmed by the consistent results of repeated tests of the quality control materials. The overall sensitivity and specificity of Panbio COVID-19 Ag were 50.0% and 100.0%, respectively. Panbio COVID-19 Ag demonstrated high sensitivity (88.2%) in analyzing the detection limit cycle threshold (Ct) value of 26.67 provided by the manufacturer as a positive criterion, and the sensitivity was 100.0% for the positive criterion of Ct values <25, although it was less sensitive for Ct > 25. Conclusion(s): Considering the high sensitivity for positive samples with Ct values <25 and the rapid turnaround of results, Panbio COVID-19 Ag can be used in clinical laboratories to diagnose COVID-19 in limited settings. Copyright © 2023 Ewha Womans University College of Medicine and Ewha Medical Research Institute.

Prognosis Score for Overall Survival with CAR-T Therapy in Aggressive Lymphoma

Background: Despite the transformative potential of chimeric antigen receptor T (CAR-T) therapy, more tools to assist with identifying patients with increased likelihood of benefitting from this therapy will be helpful, particularly given the logistical complexity and socio-economic demands for CAR-T relative to other therapies. Health care resource restriction during the COVID-19 pandemic highlights the need for these tools. We present a simple survival score that uses 3 readily available clinical labs: platelet (plt), absolute lymphocyte count (ALC), and Lactate dehydrogenase (LDH), to predict the risk of dying within 6 months of CAR-T therapy in patients with aggressive lymphoma. Method(s): We conducted a retrospective chart review of patients with aggressive non-Hodgkin lymphoma (NHL) who received FDA-approved CAR-T between Jan 2018 to Jan 2022 at Mayo Clinic Rochester.(Table Presented)Results: Among a total of 110 pts who received CAR-T, 27 (25%) pts died within the first 6 months post CAR-T infusion (OS <= 6 months). Disease progression was the main cause of death (18/25, 72%), followed by infection (4/25, 16%), CAR-T related (HLH/MAS, 2/25, 8%), second primary malignancy (1/25, 4%) and unknown (2/25, 8%).Baseline demographics were comparable between the OS>6months and <=6months groups (Table 1). Patients' ECOG, Karnofsky performance status and 11 labs at the time of evaluation for CAR-T therapy (initial eligibility assessment, prior to leukapheresis) were compared between those who died from any cause within 6 months of CAR-T infusion and those who did not. Hemoglobin, plt, ALC, absolute monocyte count, CRP, ferritin, and LDH were selected as clinically and/or statistically significant variables for multivariate testing. Multivariate regression with boot-strap testing identified plt, ALC, and LDH as the most predictive variables with 80.9+/-11.7% accuracy for predicting death within 6 months of CAR-T infusion. Patients were scored 0-3 using these 3 labs, with 1 point assigned for plt <= 100 X109/L, ALC <= 0.4 X109/L, or LDH > 222 U/L (upper limit of normal). OS by this survival score is shown in Figure 1.(Figure Presented)Discussion: Due to the curative potential of CAR-T, patients with broader characteristics than those treated on registration studies have been treated in standard of care practice. While an estimated 5%-10% risk of CAR-T associated deaths in the first 3 months is seen across all patients in clinical trials, predictors for early death after CAR-T in real-world patient populations can provide additional context for pts and providers when selecting treatment. This survival score is important proof of concept that a simple model using readily accessible clinical labs at the time of CAR-T evaluation could provide additional context to help with additional clinical decision-making. Multicenter prospective studies will help define and validate the definitive survival scoring system.Copyright © 2023 American Society for Transplantation and Cellular Therapy

Laboratory markers and radiological signs of mild versus severe COVID-19 patients

Background Coronavirus disease 2019 (COVID-19), a global pandemic that has spread worldwide in a dramatic manner since its first emergence in December 2019 from Wuhan, China. To date, there is still lack of an appropriate protocol that predicts cases who are impending to develop severe COVID-19. Hence, this work was an attempt to determine the potential association of the clinical, laboratory, and radiological parameters with the severity of COVID-19 and the ability of these parameters to predict the severe cases. Patients and methods This is a retrospective study that was based on recruiting the data from the files of patients who attended the chest outpatient clinic, or admitted to the chest department or the ICU of our institution. The study included adult patients who were diagnosed with COVID-19. Patients were categorized into two groups: severe/critical cases and mild/moderate disease cases. Data concerning the patient history, clinical picture, and radiological data were obtained and analyzed. Results Eighty adult patients with COVID-19 were included in this study. They were classified into severe/critical (40 patients) or mild/moderate disease (40 patients). Patients with severe/critical COVID-19 disease were significantly older in age and had higher comorbidities, prevalence, higher incidence of cough, dyspnea, gastrointestinal tract symptoms and fatigue, elevated total leukocyte count, lower relative lymphocytes, lower absolute lymphocytes and higher neutrophils, higher blood glucose levels, higher alanine transaminase, higher aspartate aminotransferase and lower serum albumin, reduced Ca levels, elevated lactate dehydrogenase, serum ferritin, D-dimer, and C-reactive protein levels. They had significantly higher computed tomographic (CT) scores and CT chest with greater than 50% lesions or progressive lesions. The mortality rate was 10%, all of which were from the severe disease group. Conclusion The current study is confirming an overall substantial association between severe COVID-19 and older age, chronic diseases, CT imaging pattern, and severity score, leukocyte count, lymphopenia, blood glucose, serum albumin, alanine transaminase, aspartate aminotransferase, calcium levels, C-reactive protein, D-dimer, lactate dehydrogenase, and ferritin. These results highlighted the importance of using clinical, laboratory, and radiological features for monitoring of COVID-19 patients.Copyright © 2023 The Egyptian Journal of Chest Diseases and Tuberculosis.

Systemic reaction triggered by SARS-COV- 2 infection in a patient with chronic autoimmune urticaria

Case report: Chronic urticaria is defined as the presence of urticaria for a period exceeding six weeks. Infections are known as possible triggers for urticaria manifestations, and, as such, SARS-CoV- 2 infection can be recognized as causative. An 8-year- old boy, with a previous history of idiopathic chronic urticaria, came to the Emergency Department for the appearance of generalized urticaria and lips angioedema associated with vomit and shortening of breath normal vital signs by age. Thus, due to the significant reaction, intravenous corticosteroids and antihistamines were promptly administered, with a rapid improvement of symptoms. Since the systemic reaction, the tryptase dosage was performed with the identification of an elevation at the time of the arrival and a complete normalization after the twelfth hour from the beginning of the reaction. Figure 1 shows the kinetic of the tryptase over time. SARS-CoV2 swab was performed before hospitalization and a positive test was identified. To investigate the etiopathogenesis of reaction, the patient was submitted to the extensive clinical, laboratory, and instrumental investigations that revealed only a positive in vitro basophil activation test (BAT) as evidence of functional serum histamine-releasing autoantibodies that are directed against IgE or high-affinity IgE receptors. The viral infection did not need any medication, and the urticaria was resolute in a couple of days. Daily treatment with oral antihistamines was then prescribed, and no further urticarious episodes occurred. A negative SARS-CoV- 2 swab was detected within 12 days of beginning symptoms. Approximately 40% of patients with idiopathic chronic urticaria have circulating antibodies versus IgE epitopes or the IgE receptor, but as it occurs in many autoimmune conditions, the presence of autoantibodies does not necessarily result in a disease phenotype. It is demonstrated that infections can elicit an autoimmune condition, and as our report shows, SARS-CoV2 could explain the reaction observed in our patient. The autoimmune precondition could have been the primer of the systemic reaction, pre-activating the mastocyte degranulation, as the tryptase elevation demonstrated. On the other hand, the SARS-CoV2 virus reducing the ACE2 expression, due to virus endocytosis, could create an imbalance in the RAS system, increasing the bradykinin levels. Bystander activation of pre-activated mastocytes caused by an inflammatory environment could explain the systemic reaction described above.