Assessment and outcome of hospitalized patients during delta variant COVID-19 pandemic: A multicenter international study.

INTRODUCTION: To date, the world has experienced four waves of the Coronavirus disease- 19 (COVID-19) pandemic. Patients infected during the era of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant were the subject of this study. The objectives were to describe their clinical manifestations, explain their laboratory and radiological findings, conclude factors contributing to clinical outcomes, and evaluate treatment protocols. METHODOLOGY: Relevant data were collected retrospectively from records of patients admitted to six referral centers in four countries. Data included sociodemographic patterns, symptoms, associated comorbidities, physical examination, laboratory and radiologic findings, treatment received, and patient outcomes. RESULTS: Data analysis identified symptomatology and variables related to acquisition and infection outcome. The most prevalent symptoms were cough (81.5%), body aches (74.1%), and fever (71.6%). Independent risk factors for mortality were age, vomiting, epigastric pain, diabetes, obesity, oxygen saturation less than 90%, leukocytosis, neutrophilia, lymphopenia, thrombocytopenia, elevated creatinine, high glucose level, lung ground glass opacities with consolidation, affection of four lobes and bilateralism. Neither d-dimer nor lactate dehydrogenase nor ferritin foretells death possibility. The efficacy of the medications used was convenient. CONCLUSIONS: Assessing the clinical features of different COVID-19 waves, identifying predictors of outcomes, and concluding the efficacy of treatment protocols provide insight into patients' responses and viral behaviors, which help in the proper diagnosis and treatment of subsequent surges.

Use of the derived isohemagglutinin parameter to predict patients with COVID-19 in need of an intensive care unit.

Predicting which patients will need the intensive care unit (ICU) due to severe COVID-19 is critical in terms of disease treatment. In this study, the use of the derived isohemagglutinin (dIH) parameter calculated from isohemagglutinin (IH) values and neutrophil to lymphocyte ratios for prediction of clinical care (CLC), ICU admission and mortality status was investigated for the morbidity and mortality of COVID-19. The data of approximately 21,500 patients admitted to the hospital with the suspicion of COVID-19 were scanned retrospectively. A total of 352 patients with IH results were divided into three groups according to CLC, ICU admission and mortality. Isohemagglutinin, hemogram and biochemistry test results, demographic characteristics, chronic diseases, length of stay, treatments, ICU admission and mortality records were reviewed for all patients. The relationship between test results, demographic characteristics, clinical status and mortality was investigated using statistical methods. The dIH values of patients with ICU admission and mortality were much lower than those of CLC patients [median (min-max): 3.34 (0.14-95.8) and 0.82 (0.05-42.3) vs. 0.18 (0.01-20.6) titers, p < 0.01, respectively]. In the ROC analysis for the power of dIH to discriminate ICU admission, the cutoff was ≤ 0.68 with sensitivity 88.9%, and specificity 79.6%. It was determined that a 1-unit increase in dIH values decreased the need for ICU by 2.09 times and the mortality of those receiving ICU treatment by 2.02 times. dIH values calculated in the early stages of the disease in patients with COVID-19 can be used to estimate the clinical progression associated with ICU admission and mortality.

RT- PCR testing of upper respiratory tract samples for diagnosis of SARS-CoV-2: Between justification and overestimation, a multi-center international study.

BACKGROUND: It has been found that patients recovered from COVID 19 may still test Reverse Transcriptase- Polymerase Chain Reaction (RT- PCR) positive without being infectious; the reasons are unclear. The occurrence of false-negative results of RT- PCR interferes with a proper diagnosis. The objectives of that work were to determine factors associated with persistently detectable SARS-CoV-2 RNA among recovered hospitalized patients and to determine the incidence of false-negative RT-PCR results and associated factors. METHODS: Relevant data were collected from 482 COVID 19 patients hospitalized in six referral centers from four countries. RESULTS: The median duration of RT- PCR conversion to negative was 20 days. Out of 482 studied patients, 8.7% tested positive after more than four weeks and were considered prolonged convertors. Binary logistic regression analysis revealed headache as an independent risk factor for short conversion time while fever, hypertension, chronic obstructive pulmonary disease, lymphopenia, elevated erythrocyte sedimentation rate, and the number of lobes affected, and bilateralism were found to be independent risk factors for prolonged positivity. Eighteen patients had initial negative results then turned positive after 24-48 h. Associated factors and outcomes were identified. CONCLUSION: Identifying patients with a high likelihood of COVID-19 despite a negative RT-PCR is critical for effective clinical care. However, patient isolation resumption depending on positive RT-PCR despite clinical and radiological recovery is an overrating that greatly burdens the health sector.

Gamma-glutamyl-transferase may predict COVID-19 outcomes in hospitalised patients.

AIM: In this study, we aimed to define the predictive role of liver function tests at admission to the hospital in outcomes of hospitalised patients with COVID-19. MATERIAL AND METHOD: In this multicentric retrospective study, a total of 269 adult patients (≥18 years of age) with confirmed COVID-19 who were hospitalised for the treatment were enrolled. Demographic features, complete medical history and laboratory findings of the study participants at admission were obtained from the medical records. Patients were grouped regarding their intensive care unit (ICU) requirements during their hospitalisation periods. RESULTS: Among all 269 participants, 106 were hospitalised in the ICU and 66 died. The patients hospitalised in ICU were older than patients hospitalised in wards (P = .001) and expired patients were older than alive patients (P = .001). Age, elevated serum D-dimer, creatinine and gamma-glutamyl transferase (GGT) levels at admission were independent factors predicting ICU hospitalisation and mortality in COVID-19 patients. CONCLUSION: In conclusion, in hospitalised patients with COVID-19, laboratory data on admission, including serum, creatinine, GGT and d-dimer levels have an important predictive role for the ICU requirement and mortality. Since these tests are readily available in all hospitals and inexpensive, some predictive formulas may be calculated with these parameters at admission, to define the patients requiring intensive care.

Assessment of severity and mortality of COVID-19 with anti-A1 and anti-B IgM isohaemagglutinins, a reflection of the innate immune status.

AIMS: The relationship between the innate immune system that creates the polysaccharide antibody response and COVID-19 is not fully understood. In this study, it was aimed to determine the predictive values of isohaemagglutinins in COVID-19 severity/mortality. METHODS: Approximately 15 440 patients diagnosed with COVID-19 were examined, and a total of 286 patients with anti-B and anti-A1 IgM isohaemagglutinins test results were randomly enrolled in the study. These patients were stratified into two groups according to anti-A1 (n: 138 blood type B or O) and anti-B (n: 148 blood type A) IgM isohaemagglutinins. Anti-A1 or/and anti-B IgM, biochemical parameters, symptoms, chronic diseases, hospitalisation status, intubation status, admission to intensive care unit (ICU) and exitus status were recorded and evaluated for all patients. RESULTS: Anti-A1 IgM and anti-B IgM were significantly lower in ICU patients (7.5 ± 9.9 vs 18.0 ± 20.4 and 5.5 ± 6.3 vs 19.3 ± 33.6 titres, respectively; P < .01) and in exitus patients (3.8 ± 3.6 vs 16.7 ± 18.7 and 3.5 ± 4.7 vs 16.9 ± 29.6 titres respectively; P < .01). In the ROC analysis performed to differentiate between exitus and discharge within groups, the sensitivity of anti-B IgM and anti-A1 IgM at cut-off ≤4 was 88.9% and 79.6%, specificity 66.0% and 73.4%, and AUC 0.831 and 0.861, respectively (P < .01). Anti-A1 IgM decreased the mortality risk 0.811 times per unit while anti-B IgM decreased 0.717 times (P < .01). CONCLUSION: Anti-B and anti-A1 isohaemagglutinins, which are an expression of the innate immune system, can be used to predict the severity and mortality of COVID-19 disease.

Long-term proton pump inhibitor use is a risk factor for mortality in patients hospitalized for COVID-19

Background and aim: The aim of this study is to evaluate whether the long-term (≥4 weeks) use of proton pump inhibitors (PPIs) is a risk factor for intubation requirement and mortality in patients hospitalized for COVID-19. Materials and methods: In this multicentric retrospective study, a total of 382 adult patients (≥18 years of age) with confirmed COVID-19 who were hospitalized for treatment were enrolled. The patients were divided into two groups according to the periods during which they used PPIs: the first group included patients who were not on PPI treatment, and the second group included those who have used PPIs for more than 4 weeks. Results: The study participants were grouped according to their PPI usage history over the last 6 months. In total, 291 patients did not use any type of PPI over the last 6 months, and 91 patients used PPIs for more than 4 weeks. Older age (HR: 1.047, 95% CI: 1.026­1.068), current smoking (HR: 2.590, 95% CI: 1.334­5.025), and PPI therapy for more than 4 weeks (HR: 1.83, 95% CI: 1.06­2.41) were found to be independent risk factors for mortality. Conclusion: The results obtained in this study show that using PPIs for more than 4 weeks is associated with negative outcomes for patients with COVID-19. Patients receiving PPI therapy should be evaluated more carefully if they are hospitalized for COVID-19 treatment.

Role of ACE2 Gene Expression in Renin Angiotensin System and Its Importance in Covid-19: In Silico Approach

We aimed to analyze the expression profile of ACE2 and similar genes with ACE2, predict the number of variations in ACE2, detect the suspected SNPs on ACE2 gene, and perform the pathway analysis of renin-angiotensin system (RAS) and protein absorption-digestion. Moreover, we have predicted the gene-related diseases with ACE2. STRING was used to analyze functionally similar genes with ACE2. Exome Variant Server, SIFT, Polyphen2 were used to predict the number of variations in ACE2 and detect the suspected SNPs on ACE2. KEGG database and STRING were used to draw pathway of ACE2. Then, DISEASES resource, FitSNPs, UniProt, BioXpress, IGV Browser, Ensembl Genome Browser, and UCSC Genome Browser were used to predict the ACE2 gene-related diseases and expression profile in human normal and cancer tissues. We have shown that expression of ACE2 was correlated with AGT, REN, AGTR1, AGRT2, MME2, DPP4, PRCP, MEP1A, XPNPEP2, MEP1BandACE2 is expressed in testis, kidney, heart, thyroid, colon, esophagus, breast, minor salivary gland, pancreas, lung, liver, bladder, cervix, and muscle tissues. We found 99 variations in ACE2 gene, in which no previous study has been performed. In the future, this in silico analysis should be combined with other pieces of evidence including experimental data to assign function.

Ankaferd hemostat (ABS) as a potential mucosal topical agent for the management of COVID-19 syndrome based on its PAR-1 inhibitory effect and oestrogen content.

COVID-19 due to the SARS-CoV-2 infection is a multi-systemic immune syndrome affecting mainly the lungs, oropharyngeal region, and other vascular endothelial beds. There are tremendous ongoing efforts for the aim of developing drugs against the COVID-19 syndrome-associated inflammation. However, currently no specific medicine is present for the absolute pharmacological cure of COVID-19 mucositis. The re-purposing/re-positioning of already existing drugs is a very important strategy for the management of ongoing pandemy since the development of a new drug needs decades. Apart from altering angiotensin signaling pathways, novel drug candidates for re-purposing comprise medications shall target COVID-19 pathobiology, including pharmaceutical formulations that antagonize proteinase-activated receptors (PARs), mainly PAR-1. Activation of the PAR-1, mediators and hormones impact on the hemostasis, endothelial activation, alveolar epithelial cells and mucosal inflammatory responses which are the essentials of the COVID-19 pathophysiology. In this context, Ankaferd hemostat (Ankaferd Blood Stopper, ABS) which is an already approved hemostatic agent affecting via vital erythroid aggregation and fibrinogen gamma could be a potential topical remedy for the mucosal management of COVID-19. ABS is a clinically safe and effective topical hemostatic agent of plant origin capable of exerting pleiotropic effects on the endothelial cells, angiogenesis, cell proliferation and vascular dynamics. ABS had been approved as a topically applied hemostatic agent for the management of post-surgical/dental bleedings and healing of infected inflammatory mucosal wounds. The anti-inflammatory and proteinase-activated receptor axis properties of ABS with a considerable amount of oestrogenic hormone presence highlight this unique topical hemostatic drug regarding the clinical re-positioning for COVID-19-associated mucositis. Topical ABS as a biological response modifier may lessen SARS-CoV-2 associated microthrombosis, endothelial dysfunction, oropharyngeal inflammation and mucosal lung damage. Moreover, PAR-1 inhibition ability of ABS might be helpful for reducing the initial virus propagation and mocasal spread of COVID-19.

Role of ACE2 Gene Expression in Renin Angiotensin System and Its Importance in Covid-19: In Silico Approach

Abstract We aimed to analyze the expression profile of ACE2 and similar genes with ACE2, predict the number of variations in ACE2, detect the suspected SNPs on ACE2 gene, and perform the pathway analysis of renin-angiotensin system (RAS) and protein absorption-digestion. Moreover, we have predicted the gene-related diseases with ACE2. STRING was used to analyze functionally similar genes with ACE2. Exome Variant Server, SIFT, Polyphen2 were used to predict the number of variations in ACE2 and detect the suspected SNPs on ACE2. KEGG database and STRING were used to draw pathway of ACE2. Then, DISEASES resource, FitSNPs, UniProt, BioXpress, IGV Browser, Ensembl Genome Browser, and UCSC Genome Browser were used to predict the ACE2 gene-related diseases and expression profile in human normal and cancer tissues. We have shown that expression of ACE2 was correlated with AGT, REN, AGTR1, AGRT2, MME2, DPP4, PRCP, MEP1A, XPNPEP2, MEP1BandACE2 is expressed in testis, kidney, heart, thyroid, colon, esophagus, breast, minor salivary gland, pancreas, lung, liver, bladder, cervix, and muscle tissues. We found 99 variations in ACE2 gene, in which no previous study has been performed. In the future, this in silico analysis should be combined with other pieces of evidence including experimental data to assign function.