COVID-19: comparison lung CT signs and biochemical parameters in the groups of patients with three-time positive RT-PCR and with triple negative RT-PCR test during the period of hospitalization.

Research goal. Comparative characteristics of the dynamics of CT semiotics and biochemical parameters of two groups of patients: with positive RT-PCR and with triple negative RT-PCR. Reflection of the results by comparing them with the data already available in the literature. The aim of the study is to compare the dynamics of CT semiotics and biochemical parameters of blood tests in two groups of patients: with positive RT-PCR and with triple negative RT-PCR. We also reflect the results by comparing them with the data already available in the literature. Materials and methods. We have performed a retrospective analysis of CT images of 66 patients: group I (n1 = 33) consists of patients who had three- time negative RT-PCR (nasopharyngeal swab for SARS-CoV-2 RNA) during hospitalization, and group II (n2 = 33) includes patients with triple positive RT-PCR. An important selection criterion is the presence of three CT examinations (primary, 1st CT and two dynamic examinations - 2nd CT and 3rd CT) and at least two results of biochemistry (C-reactive protein (CRP), fibrinogen, prothrombin time, procalcitonin) performed in a single time interval of +/- 5 days from 1st CT, upon admission, and +/- 5 days from 3st CT. A total of 198 CT examinations of the lungs were analyzed (3 examinations per patient). Results. The average age of patients in the first group was 58 +/- 14.4 years, in the second - 64.9 +/- 15.7 years. The number of days from the moment of illness to the primary CT scan 6.21 +/- 3.74 in group I, 7.0 (5.0-8.0) in group II, until the 2nd CT scan - 12.5 +/- 4, 87 and 12.0 (10.0-15.0), before the 3rd CT scan - 22.0 (19.0-26.0) and 22.0 (16.0-26.0), respectively. In both groups, all 66 patients (100%), the primary study identified the double-sided ground-glass opacity symptom and 36 of 66 (55%) patients showed consolidation of the lung tissue. Later on, a first follow-up CT defined GGO not in all the cases: it was presented in 22 of 33 (67%) patients with negative RT-PCR (group I) and in 28 of 33 (85%) patients with the positive one (group II). The percentage of studies showing consolidation increased significantly: up to 30 of 33 (91%) patients in group I, and up to 32 of 33 (97%) patients in group II. For the first time, radiological symptoms of "involutional changes" appeared: in 17 (52%) patients of the first group and in 5 (15%) patients of the second one. On second follow-up CT, GGO and consolidations were detected less often than on previous CT: in 1 and 27 patients of group I (3% and 82%, respectively) and in 6 and 30 patients of group II (18% and 91%, respectively), although the consolidation symptom still prevailed significantly . The peak of "involutional changes" occurred on last CT: 31 (94%) and 25 (76%) patients of groups I and II, respectively.So, in the groups studied, the dynamics of changes in lung CT were almost equal. After analyzing the biochemistry parameters, we found out that CRP significantly decreased in 93% of patients (p < 0.001) in group I;in group II, there was a statistically significant decrease in the values of C-reactive protein in 81% of patients (p = 0.005). With an increase in CT severity of coronavirus infection by one degree, an increase in CRP by 41.8 mg/ml should be expected. In group I, a statistically significant (p = 0.001) decrease in fibrinogen was recorded in 77% of patients;and a similar dynamic of this indicator was observed in group II: fibrinogen values decreased in 66% of patients (p = 0.002). Such parameters as procalcitonin and prothrombin time did not significantly change during inpatient treatment of the patients of the studied groups (p = 0.879 and p = 0.135), which may indicate that it is inappropriate to use these parameters in assessing dynamics of patients with a similar course of the disease. When comparing the outcomes of the studied groups, there was a statistically significant higher mortality in group II - 30.3%, in group I - 21.2% (p = 0.043). Conclusion. According to our data, a course of the disease does not significantly differ in the groups o patients with positive RT-PCR and three-time negative RT-PCR. A negative RT-PCR analysis may be associated with an individual peculiarity of a patient such as a low viral load of SARS-CoV-2 in the upper respiratory tract. Therefore, with repeated negative results on the RNA of the virus in the oro- and nasopharynx, one should take into account the clinic, the X-ray picture and biochemical indicators in dynamics and not be afraid to make a diagnosis of COVID-19.Copyright © 2021 ALIES. All rights reserved.

Cardiac manifestations of post-COVID syndrome in children and adolescents.

The aim of the research. To study the features of cardiovascular system disorders in post-covid syndrome (PCS) in children and adolescents after a mild form of coronavirus infection (COVID-19). Material and methods. From 260 children and adolescents after a mild form of COVID-19, a total of 30 patients aged 7-17 years with cardiac manifestations of PCS were selected. Therewith, 32 patients with an uncomplicated form of the disease were selected to form a comparison group. In 3 and 6 months after disease onset, a comprehensive examination of patients was performed with a questionnaire on the subjective scale for MFI-20 assessment asthenia (Multidimensional Fatigue Inventory-20), electrocardiography (ECG), echocardiography;daily monitoring of ECG and blood pressure. The biochemical blood test included assay of creatine phosphokinase-MB (CPK-MB), troponin I and lactate dehydrogenase (LDH). Results. The incidence of PCS with cardiac manifestations amounted to 11.5 %. After 3 months from the disease onset, complaints of pain and discomfort in the chest, palpitations, fatigue, and poor exercise tolerance persisted. Asthenic syndrome was diagnosed in 70 % of patients. The "general asthenia" indicator totalled14 [12;16] points (p<0.001) and was associated with the age of patients (r=+0.5;p<0.05). Arrhythmic syndrome and conduction disorders were detected in 67% of children. Labile arterial hypertension and hypotension occurred in 23 % of the adolescents. The increase in CPK-MB remained in 17% of the children, LDH - in 10%. In the sixth month after the onset of the disease, there were no significant differences in the results of the examination in the observation groups. However, a decrease in the level of resistance within 6 months was recorded in 43.3% of the schoolchildren with PCS (p<0.001). Conclusion. The data obtained indicate the need for early verification of cardiopathies in children with COVID-19, determination of a set of therapeutic and rehabilitation measures as well as ECG monitoring.Copyright © 2022, Krasnoyarsk State Medical University. All rights reserved.

Prognostic criteria for the development of severe clinical forms of COVID-19 in medical organization workers

Employees of medical organizations are one of the risk groups for infection with a new coronavirus infection (COVID-19), including with the development of severe clinical forms. The aim of the study was to analyze the clinical manifestations of a new coronavirus infection in medical workers with the determination of laboratory markers for the development of severe COVID-19. Material and methods. The study included 186 medical workers who had COVID-19 in 2020. In 67 people (observation group), the disease occurred in the form of pneumonia, in 119 people (comparison group) - acute respiratory infection caused by SARS-CoV-2. In the acute period of the disease, a laboratory examination was carried out: a general clinical blood test, CD-typing of lymphocyte subpopulations, assessment of biochemical parameters, determination of parameters of the hemostasis system and cytokine levels. Using the binary logistic regression method, we have built multifactor models. To determine the threshold values of the indicators, we used ROC analysis. Statistical processing of materials was carried out using Microsoft Office 2016 and IBM SPSS Statistics (version 26). The differences were considered statistically significant at p<0.05. Results and discussion. The most frequent clinical manifestations of COVID-19 were: weakness, fever, myalgia, arthralgia, difficulty in nasal breathing, serous-mucous discharge from the nose, sore throat, cough, feeling of "tightness" in the chest, shortness of breath, headache, pain in the eyeballs, dizziness, anosmia, ageusia and dyspeptic manifestations in the form of diarrhea, nausea or vomiting. Markers associated with the development of severe pneumonia associated with COVID-19 have been identified. Threshold values of laboratory parameters for predicting the severe course of COVID-19 were determined: the number of platelets (less than 239x109/l), lymphocytes (less than 1.955x109/l), cytotoxic T-lymphocytes (less than 0.455x109/l), T-helper cells (less than 0.855x109/l), NK-cells (less than 0.205x109/l), ESR (more than 11.5 mm/h), LDH (more than 196 units/l), total protein (less than 71.55 g/l), D-dimer (more than 0.325 mcg/ml), CRP (more than 4.17 mg/l), IL-6 (more than 3.63 pg/l). Conclusion. The data obtained make it possible to predict the possibility of developing a severe variant of the COVID-19 course.Copyright © 2022 Infectious Diseases: News, Opinions, Training. All rights reserved.

Human Anti-Ace2 Monoclonal Antibodies as Pan-Sarbecovirus Prophylactic Agents

Background: Human monoclonal antibodies from convalescent individuals that target the SARS-CoV-2 spike protein have been deployed as therapeutics against SARS-CoV-2. However, nearly all of these antibodies have been rendered obsolete by SARS-CoV-2 variants that evolved to resist similar, naturally occurring antibodies. Moreover, Most SARS-CoV-2 specific antibodies are inactive against divergent sarbecoviruses Methods: By immunizing mice that carry human immunoglobulin variable gene segments we generated a suite of fully human monoclonal antibodies that bind the human ACE2 receptor (hACE2) rather than the viral spike protein and were engineered to lack effector functions such as ADCC. Result(s): These ACE2 binding antibodies block infection by all hACE2 binding sarbecoviruses, including emergent SARS-CoV-2 variants, with a potency that of the most potent spike binding therapeutic antibodies. Structural and biochemical analyses revealed that the antibodies target an hACE2 epitope that engages SARS-CoV-2 spike. Importantly, the antibodies do not inhibit hACE2 enzymatic activity, nor do they induce ACE depletion from cell surfaces. The antibodies exhibit favorable pharmacology in human ACE2 knock in mice and provide near complete protection of hACE2 knock-in mice against SARS-CoV-2 infection. Conclusion(s): ACE2 binding antibodies should be useful prophylactic and treatment agents against any current and future SARS-CoV-2 variants, as well as hACE2-binding sarbecoviruses that might emerge as future pandemic threats.

Nanopore single-molecule analysis of biomarkers: Providing possible clues to disease diagnosis

Biomarker detection has attracted increasing interest in recent years due to the minimally or non-invasive sampling process. Single entity analysis of biomarkers is expected to provide real-time and accurate biological information for early disease diagnosis and prognosis, which is critical to the effective disease treatment and is also important in personalized medicine. As an innovative single entity analysis method, nanopore sensing is a pioneering single-molecule detection technique that is widely used in analytical bioanalytical fields. In this review, we overview the recent progress of nanopore biomarker detection as new approaches to disease diagnosis. In highlighted studies, nanopore was focusing on detecting biomarkers of different categories of communicable and noncommunicable diseases, such as pandemic COVID-19, AIDS, cancers, neurologic diseases, etc. Various sensitive and selective nanopore detecting strategies for different types of biomarkers are summarized. In addition, the challenges, opportunities, and direction for future development of nanopore-based biomarker sensors are also discussed.Copyright © 2023 Elsevier B.V.

Features of clinical and laboratory changes in adolescents in the dynamics of novel coronavirus infection.

The relevance of research on a novel coronavirus infection is associated with an increase in the incidence among children since 2021, which may be due to the accumulation of mutations in the virus genome and its evolution towards increased contagiousness, replicative ability, and evasion of immune protection. While there are many studies in adults, data analyzing the clinical course of the disease in pediatric patients infected with SARS-CoV-2 are limited, particularly regarding adolescents. Objective. To study the clinical and laboratory features of the course of a novel coronavirus infection in hospitalized adolescents in Novosibirsk during the first, second and third waves of the pandemic. Materials and methods. A retrospective analysis of case histories of 125 children treated at Novosibirsk Children's Clinical Hospital No 6 with a confirmed diagnosis of coronavirus infection during three pandemic waves was carried out (June- August 2020, October-December 2020, June-August 2021). Based on these time intervals, three groups of adolescents admitted to the hospital during the first, second, and third waves of coronavirus infection were formed. SARS-CoV-2 RNA in nasopharyngeal and oropharyngeal scrapings was determined using the PCR-RT method. Biochemical and general clinical studies were performed in accordance with the guidelines of the Ministry of Health of the Russian Federation. Statistical processing was carried out using the Satistika 7.0 software package (StatSoft, USA). Differences between the groups were assessed using the Z-test and the Mann-Whitney U test. Differences between the compared series were considered statistically significant with a probability level of 95%. Results. It was shown that during three pandemic waves (June 2020 - August 2021), more than half of the hospitalized children were adolescents. At the same time, regardless of the pandemic wave, intoxication, catarrhal and intestinal syndromes predominated in hospitalized adolescents. CNS injury symptoms were significantly less frequent in the first wave, as were skin rashes. Cough in the third wave was observed in 100% of hospitalized adolescents. The average values of the parameters of complete blood count, as well as CRP, D-dimer and ferritin had no statistically significant differences in different pandemic waves, but there was a significant variation in individual values within the groups in each wave.Copyright © 2022, Dynasty Publishing House. All rights reserved.

Clinical Characteristics of Deceased with COVID-19 Infection: Data from the Largest COVID-19 Dedicated Hospital in Bangladesh

The death t toll of the coronavirus disease 2019 (COVID-19) has been considerable. Several risk factors have been linked to mortality due to COVID-19 in hospitals. This study aimed to describe the clinical characteristics of patients who either died from COVID-19 at Dhaka Medical College Hospital in Bangladesh. In this retrospective study, we reviewed the hospital records of patients who died or recovered and tested positive for COVID-19 from May 3 to August 31, 2020. All patients who died during the study period were included in the analysis. A comparison group of patients who survived COVID-19 at the same hospital during the same period was systematically sampled. All available information was retrieved from the records, including demographic, clinical, and laboratory variables. Of the 3115 patients with confirmed COVID-19 during the study period, 282 died.The mean age of patients who died was higher than that of those who survived (56.7 vs 52.6 years). Approximately three-fourths of deceased patients were male. History of smoking (risk ratio 2.3;95% confidence interval: 1.6-3.4), comorbidities (risk ratio: 1.5;95% confidence interal:1.1-2.1), chronic kidney disease (risk ratio: 3.2;95% confidence interval: 1.7-6.25), and ischemic heart disease (risk ratio:1.8;95% confidence interval: 1.1-2.9) were higher among the deceased than among those who survived. Mean C-reactive protein and D-dimer levels [mean (interquartile range), 34 (21-56) vs. 24 (12-48);and D-dimer [1.43 (1-2.4) vs. 0.8 (0.44-1.55)] were higher among those who died than among those who recovered. Older age, male sex, rural residence, history of smoking, and chronic kidney disease were found to be important predictors of mortality. Early hospitalization should be considered for patients with COVID-19 who are older, male, and have chronic kidney disease. Rapid referral to tertiary care facilities is necessary for high-risk patients in rural settings.Copyright © 2023 Hoque MM.

Impact of Covid Vaccination on Hospitalized Covid-19 Patients - a Renal and Extra-Renal Outcome Study

Introduction: Covid-19 vaccinations are effective as preventive measures against the COVID-19 pandemic infection. There are different types of COVID-19 vaccines available worldwide. The impacts of different types COVID-19 vaccination on hospitalized patients remained uncertain at the early stage of the outbreak. This study examines the clinical outcomes of vaccinated and vaccine naive hospitalized COVID-19 patients. Method(s): This is a retrospective study of hospitalized COVID-19 patients admitted into University Malaya Medical Center from January 2021 until June 2021. Data on patients who were>= 18 years old and hospitalized for >= 48 hours for confirmed COVID-19 infection were captured. Clinical parameters and demographic of patients were collected from electronic medical records (EMR). Vaccine status was determined based on EMR entry and retrospective phone interviews. 2 cohorts of patients were classified based on their COVID vaccination status, and outcome analysis was done with appropriate statistical methods. Result(s): A total of 1529 patients were captured with a male-to-female ratio of 759 (49.6%) and 770 (50.3%). The median age was 55 (IQR: 36-66). 182 patients (12%) received COVID-19 vaccination before admission. The types of COVID vaccination received by patients were Pfizer (n=127;8.4%), AstraZeneca (n=27;1.8%), and Sinovac (n=28;1.8%) respectively.107 patients (7.1%) received two doses of vaccine, 72 patients had one dose (4.7%), and three were injected with three doses (0.2%). Biochemical analysis showed that the vaccination naive group has a higher median of lymphocyte counts (17 vs. 2.02;p<0.001), ferritin (363 vs 221;p=0.001), serum creatinine (67 vs 63;p=0.032). Renal outcome data revealed that unvaccinated patients had more incidence of acute kidney injury (AKI) (92.9% vs 7.1%;p=0.002) and increased level proteinuria (88.5% vs 11.5%;p= 0.011). Covid-19 vaccination group had lower incidence rate of pneumonia (8.9% vs 91.1%;p<0.001), lower ventilator use (4.8% vs 95.2%;p=0.01), and lower ICU admission (5.1% vs 94.9%;p<0.001) compared to vaccine-naive group. The mortality rate was lower 5.2% (n=7) in COVID-19 vaccination compared to 94.8% (n=127) vaccine-naive group;p=0.012. [Formula presented] Conclusion(s): In our study, COVID-19 vaccination effectively lowered the incidence of AKI, pneumonia, ICU admission, and mortality translating to better overall outcome. No conflict of interestCopyright © 2023

The roles of bun/d-dimer and bun/lactate ratios in indicating mortality in intensive care patients with COVID-19

Aim: Coronavirus disease 2019 (COVID-19) is an epidemic disease with variable symptoms and high mortality rates. Therefore, patient follow-up is very significant. We aimed to investigate whether blood urea nitrogen (BUN), D-dimer and lactate parameters, which are laboratory tests used in follow-up, predict mortality. Material(s) and Method(s): The study included 173 COVID-19 patients hospitalized in the pandemic intensive care unit from March 2020 to June 2020. We retrospectively recorded patient age, gender, comorbidity, radiological involvement, oxygen demand, APACHE scores, in-hospital mortality status, BUN, lactate, and D-dimer levels, BUN/D-dimer ratio (BDR), BUN/lactate ratio (BLR). Then we made the statistical comparison between the groups by grouping the patients as discharged and deceased. Result(s): Among the patients included in the study, 107 (61.8%) were male and 66 (38.2%) were female. The mean ages between those discharged and those who died in the hospital were 73 and 67.5 years, respectively, and there was a statistically significant difference. The median BUN, d-dimer, lactate and BDR, BLR values of the patients in the non-survivor group were significantly higher than those in the survivor group. BLR had the highest diagnostic ratio (25.03) for estimating in-hospital COVID-19 mortality. Discussion(s): We found that BUN, BDR, and BLR levels were reliable predictors of in-hospital mortality in COVID-19 patients. However, BLR was a potent risk assessment tool, especially in defining the risk of in-hospital death.Copyright © 2022, Derman Medical Publishing. All rights reserved.

Association of Interleukin-6 (IL-6) and High-Density Lipoprotein Cholesterol (HDL-C) with Disease Severity of Coronavirus Disease 2019 (COVID-19)

Introduction: IL-6 is the key molecule of cytokine storm in COVID-19. Dyslipidemia is a common complication in patients with Coronavirus disease 2019 (COVID-19), but the association of dyslipidemia with the severity of COVID-19 is still unclear. In this study, we aimed to investigate the biochemical alterations of High-Density Lipoprotein Cholesterol (HDL-C), and Interleukin-6 (IL-6) in COVID-19 patients and their relationships with the disease severity. Material(s) and Method(s): We conducted a retrospective single-institutional study of 99 consecutive confirmed cases of COVID-19. Serum IL-6 and HDL-C concentrations, demographic and clinical profile were collected during hospital stay. Duration of study was from September 2020 to August 2021. Descriptive statistics were applied to summarize the demographic data. Results are reported as mean with standard deviation. Receiver operating characteristic curve (ROC) analysis was used to compare biochemical markers. Result(s): Serum HDL-C levels had a significant positive correlation with SpO2 with correlation coefficient r = 0.589. Serum IL-6 had a negative correlation with SpO2 with correlation coefficient r =-0.632. The AUC for IL6 and HDL-C in predicting COVID severity is 0.982 and 0.985 respectively. Conclusion(s): HDL-C is decreased and IL-6 is increased with the disease severity.Copyright © 2023, Dr Yashwant Research Labs Pvt Ltd. All rights reserved.

Recent progress in microfluidic biosensors with different driving forces

Microfluidic biosensors integrating fluid control, target recognition, as well as signal transduction and output, have been widely used in the field of disease diagnosis, drug screening, food safety and environmental monitoring in the past two decades. As the central part and technical characteristics of microfluidic biosensors, the fluid control is not only associated with accuracy and convenience of the sensors, but also affects the material selection and working mode of the sensors. This review summarizes the fluid driving forces for microfluidic biosensors, including gravity, capillary force, centrifugal force, pressure, light, sound, electrical, and magnetic forces. Then, the recent advances in microfluidic biosensors for the detection of viruses, cells, nucleic acids, proteins and small molecules are discussed. Finally, we propose the current challenges and future perspectives of microfluidic biosensors. We hope this review can provide readers with a new perspective to understand the technical characteristics and application potential of microfluidic biosensors.Copyright © 2022 Elsevier B.V.

Clinical and laboratory characteristics of COVID-19 cases at the pandemic hospital of an anatolian province

Aim: Biochemical monitoring of COVID-19 patients is essential for assessing disease diagnosis, severity and progression, as well as monitoring therapeutic intervention. In this study, we aimed to investigate the clinical and laboratory characteristics of the cases followed up with the diagnosis of COVID-19. Material(s) and Method(s): The study included 110 patients who admitted to Kastamonu State Hospital between 1-30 April, 2020 and diagnosed with COVID-19. Demographic, clinical and laboratory data of the patients were evaluated retrospectively. Result(s): According to the presence of pneumonia, an increase in neutrophil, ALT and creatinine values, and a decrease in the leukocyte count were found to be statistically significant. When we took the cut-off value of 28.49 for CRP, 1.45 for NLR and 111.12 for PLR in our ROC analysis, all three values were found to be associated with pneumonia. In the logistic regression analysis, female gender, age over 50 years, and an NLR value above 1.45 increased the risk of pneumonia 2.6, 4.9, and 8.3 times, respectively. Discussion(s): High NLR, CRP and PLR values were found to be associated with the presence of pneumonia.Copyright © 2022, Derman Medical Publishing. All rights reserved.

Association of immature granulocytes (IG) with prognosis in severe COVID-19 patients Immature granulocytes and COVID-19

Aim: Recent research have shown that immature granulocytes (IG) can be utilized to predict severe infection, inflammation, and sepsis. As a result, the ability of IG levels to predict the severity of severe COVID-19 and its association with prognosis were studied in our study. Material and Mthods: A total of 317 patients diagnosed with severe COVID-19 in the emergency department were analyzed retrospectively. IGC and IG% levels were compared statistically between patient groups (survivors and non-survivors, those who received and did not get mechanical ventilation (MV) assistance, patients who required and did not require vasopressors, and hospital stays >=10 and <10 days). Result(s): When compared to patients who survived but did not get treatment, non-survivors who got MV and vasopressor support had substantially higher IGC and IG% values (for all p<0.001). Additionally, it was shown that the IG% of patients with hospital stays of >=10 days was substantially greater than that of patients with hospital stays of <10 days (p<0.001). While the IG% cut-off value was >0.45, it reached 75.5% sensitivity, 81.9% specificity, 87.6% NPV and 66.4% PPV for predicting mortality (AUC:0.86, p<0.001). Discussion(s): IG levels are a low-cost, easily accessible, and strong marker that may be used to predict mortality and prognosis in COVID-19 patients.Copyright © 2023, Derman Medical Publishing. All rights reserved.

Discovering a Dihydrofluorescein Analogue as a Promising Fluorescence Substrate to HRP

Horseradish peroxidase (HRP) combined with its fluorescence substrates is attracting increasing attention for biochemical analysis. Amplex red is the most widely used fluorescence substrate to HRP;however, it suffers from some drawbacks, such as nonspecific responsiveness toward carboxylesterases. Discovering a new small molecular fluorescence substrate with improved sensitivity and selectivity for HRP is thus desired. Herein, three dihydrofluorescein derivatives (DCFHs) are presented to serve as HRP substrates through fluorescence turn-on methods. The most promising one, 2,7-dichloro-9-(2-(hydroxymethyl)phenyl)-9H-xanthene-3,6-diol (DCFH-1), exhibited excellent sensitivity in the detection of HRP. Moreover, DCFH-1 does not respond to carboxylesterase, thus holding advantages over Amplex red. In the further study, the detection reagent in the commercial ELISA kits was replaced with DCFH-1 to establish a new fluorescence ELISA, which works very well in the quantification of inflammatory cytokine biomarkers from in vitro models.

Investigating novel thiazolyl-indazole derivatives as scaffolds for SARS-CoV-2 MPro inhibitors

COVID-19 is a global pandemic caused by infection with the SARS-CoV-2 virus. Remdesivir, a SARS-CoV-2 RNA polymerase inhibitor, is the only drug to have received widespread approval for treatment of COVID-19. The SARS-CoV-2 main protease enzyme (MPro), essential for viral replication and transcription, remains an active target in the search for new treatments. In this study, the ability of novel thiazolyl-indazole derivatives to inhibit MPro is evaluated. These compounds were synthesized via the heterocyclization of phenacyl bromide with (R)-carvone, (R)-pulegone and (R)-menthone thiosemicarbazones. The binding affinity and binding interactions of each compound were evaluated through Schrodinger Glide docking, AMBER molecular dynamics simulations, and MM-GBSA free energy estimation, and these results were compared with similar calculations of MPro binding various 5-mer substrates (VKLQA, VKLQS, VKLQG) and a previously identified MPro tight-binder X77. From these simulations, we can see that binding is driven by residue specific interactions such as pi-stacking with His41, and S/pi interactions with Met49 and Met165. The compounds were also experimentally evaluated in a MPro biochemical assay and the most potent compound containing a phenylthiazole moiety inhibited protease activity with an IC50 of 92.9 muM. This suggests that the phenylthiazole scaffold is a promising candidate for the development of future MPro inhibitors.Copyright © 2022 The Authors

Chemi-Informatic Approach to Investigate Putative Pharmacoactive Agents of Plant Origin to Eradicate COVID-19

Background: The scientific community has supported the medicinal flora of ancient as well as modern times in extracting chemicals, which holds therapeutic potential. In many previous studies, Amentoflavone discovered as an anti-viral agent, and it is present as a bioactive constituent in many plants of different families like Selaginellaceae, Euphorbiaceae, and Calophyllaceae. Withania somnifera (Ashwagandha) is already considered a significant anti-viral agent in traditional medicine, and it is the main source of Somniferine-A and Withanolide-B. Objective(s): In this study, phytochemicals such as withanolide-b, somniferine-a, stigmasterol, amentoflavone, and chavicine were analyzed to screen protein inhibitors, out of them;such proteins are involved in the internalization and interaction of SARS-CoV-2 with human cytological domains. This will help in developing a checkpoint for SARS-CoV-2 internalization. Method(s): Chemi-informatic tools like basic local alignment search tool (BLAST), AutoDock-vina, SwissADME, MDWeb, Molsoft, ProTox-II, and LigPlot were used to examine the action of pharmacoactive agents against SARS-CoV-2. The tools used in the study were based on the finest algorithms like artificial neural networking, machine learning, and artificial intelligence. Result(s): On the basis of binding energies less than equal to-8.5 kcal/mol, amentoflavone, stigmasterol, and somniferine-A were found to be the most effective against COVID-19 disease as these chemical agents exhibit hydrogen bond interactions and competitively inhibit major proteins (SARS-CoV-2 Spike, Human ACE-2 receptor, Human Furin protease, SARS-CoV-2 RNA binding protein) that are involved in its infection and pathogenesis. Simulation analysis provides more validity to the selection of the drug candidate Amentoflavone. ADMET properties were found to be in the feasible range for putative drug candidates. Conclusion(s): Computational analysis was successfully used for searching pharmacoactive phytochemicals like Amentoflavone, Somniferine-A, and Stigmasterol that can bring control over COVID-19 expansion. This new methodology was found to be efficient, as it reduces monetary expenditures and time consumption. Molecular wet-lab validations will provide approval for finalizing our selected drug model for controlling the COVID-19 pandemic.Copyright © 2022 Bentham Science Publishers.

Enhanced neutralization escape to therapeutic monoclonal antibodies by SARS-CoV-2 omicron sub-lineages.

The landscape of SARS-CoV-2 variants dramatically diversified with the simultaneous appearance of multiple subvariants originating from BA.2, BA.4, and BA.5 Omicron sub-lineages. They harbor a specific set of mutations in the spike that can make them more evasive to therapeutic monoclonal antibodies. In this study, we compared the neutralizing potential of monoclonal antibodies against the Omicron BA.2.75.2, BQ.1, BQ.1.1, and XBB variants, with a pre-Omicron Delta variant as a reference. Sotrovimab retains some activity against BA.2.75.2, BQ.1, and XBB as it did against BA.2/BA.5, but is less active against BQ.1.1. Within the Evusheld/AZD7442 cocktail, Cilgavimab lost all activity against all subvariants studied, resulting in loss of Evusheld activity. Finally, Bebtelovimab, while still active against BA.2.75, also lost all neutralizing activity against BQ.1, BQ.1.1, and XBB variants.

A CASE OF LONG-TERM TOLERANCE AFTER KIDNEY TRANSPLANTATION.

We present a case of long-term organ functioning (ca.10 years) after allografting of a cadaveric kidney without usage of immunosuppressing drugs. In 2005, a patient suffering from a hypertensive form of chronic glomerulonephritis, have received an allogeneic graft of cadaveric kidney compatible for AB0 system, HLA antigens (A19, B07, DR04), and negative results of cross-match test. The graft function was immediately restored, with normalization of creatinine levels achieved 4-5 days after surgery. Immunosuppression with cyclosporine, solumedrol, cellcept, metypred and simulect was performed in the hospital. Pulse therapy with solumedrol was performed on the day +20 due to the development of initial rejection signs. The postoperative period proceeded without infectious complications. The patient was discharged being recommended to take cyclosporine, Cell-Sept and Metypred. Within a year after transplantation, the patient claimed for pain in the hip joint, and, therefore, metypred was completely canceled. Subsequently, the Cellcept was replaced with a Mayfortic. In 2007, the signs of coxarthrosis were revealed at computed tomography, followed by aseptic necrosis of the the right femur head. Deforming osteoarthritis of the right hip joint was detected, and the hip replacement surgery was suggested. In 2010, due to risk of side effects from ongoing immunosuppressive therapy, e.g., joint damage, the Mayfortic was canceled. In 2012, being in fear of original Sandimmun Neoral replacement by a generic drug, the patient completely refused cyclosporine therapy. In 2021, the endoprosthetics of the right hip joint was performed, and the surgical wound healed initially. Since 2012, the patient has not completely taken immunosuppressive therapy. Over this time period, the patient has never been admitted to the hospital for impaired functioning of the organ graft. Meanwhile, he monitored his graft function on regular basis undergoing biochemical analyses, clinical examination, ultrasound studies of the graft and made regular visits to the outpatient department. In 2021, a week after hip replacement, there was a slight increase in serum creatinine, followed by further increase to 230 mmol/L in 2021, and to 310 mmol/L in March 2022. In February 2022, the patient suffered mild respiratory infection (confirmed COVID-19). In March 2022, the first clinical signs of increasing nephropathy appeared, i.e., swelling of both lower extremities, with leukocytes in urine upon routine analysis, increased blood flow resistance in the main artery of the transplant shown by ultrasound study. Due to worsening of the patient's condition, he resumed taking the prescribed immunosuppressants. Copyright © 2022, SPb RAACI.

Establishing PCR testing in Nepal for COVID-19: Challenges and opportunities

Polymerase chain reaction (PCR) invented by Kary Mullis (1983), has become the centrepiece of molecular detection of various infectious diseases including coronavirus disease 2019 (COVID-19). Many developing countries like Nepal faces various challenges and grab many future opportunities during and after establishment of molecular PCR laboratories throughout the country. This viewpoint describes the involvement of laboratory employees, development and adoption of new protocols or framework, deliberate partnership with national and international community is very efficient for the establishment of PCR laboratories. Beside this, continued alliance and nation leadership is crucial to generate a unified and sustainable PCR laboratory network in the country like Nepal. In future the established PCR laboratories can be utilized for the diagnosis of others pandemic diseases and can be used for multipurpose like in verification of infectious diseases;Oncology;Blood test;Genetic testing. Copyright © 2020, Kathmandu University. All rights reserved.

ISLH 2022 Abstract

The proceedings contain 278 papers. The topics discussed include: genotoxic preventive potential of ethanol leaves extract of Annona muricata on N-Nitroso-N-Ethylurea pro-leukemia carcinogenin mice by bone marrow micronucleus assay;performance evaluation of TOSOH G11 high performance liquid chromatography analyzer (beta thalassemia analysis mode);the accuracy of manual platelet counting;new insights in the biochemical analysis of stored irradiated blood;can somatic mutations be used in the diagnosis of myelodysplastic syndrome?;assessment of reference intervals for platelet aggregation tests on samples with low platelet counts;hematological profile of patients with COVID-19 at Oran University hospital in Algeria by hematology analyzer BC-6800;prevalence of myeloproliferative neoplasm mutations among Pakistani population;utility of reticulated platelets (RETPLTS) and their qualitative parameters on ADVIA 2120I siemens in the differential diagnosis of thrombocytopenia;evaluation of reticulated platelets (RETPLTS) and their qualitative parameters on ADVIA 2120I siemens: a new diagnostics tool;and evaluation of the ability of the differential count on two hematology analyzers to detect leukemias, verified by bone marrow and peripheral blood smear evaluation of the ability of the differential count on two hematology analyzers to detect leukemias, verified by bone marrow and peripheral blood smears.