DETERMINATION OF DIAGNOSTIC ACCURACY OF BIOCHEMICAL PARAMETERS (CRP, LDH & FERRITIN) IN THE DIAGNOSIS OF COVID-19 IN SUSPECTED COVID CASES

Objective: To determine the diagnostic accuracy of the Lactate Dehydrogenase, C-Reactive Protein and Ferritin in suspected patients of COVID-19. Study Design: Cross-sectional validation study. Place and Duration of Study: Pathology department of Combined Military Hospital Lahore in the month of May 2020. Methodology: We included 101 adult (>18 years) symptomatic suspected COVID-19 patients of both genders. Children, pregnant women and asymptomatic patients were excluded from study. Age, gender and results of Reverse Transcriptase Polymerase Chain Reaction, Lactate Dehydrogenase, C-Reactive Protein, ferritin were recorded. Results: Lactate Dehydrodenase had highest sensitivity (75%) with positive predictive value of 71.6% and diagnostic accuracy of 65.3% among three biochemical parameters studied. Receiver Operator Characteristic curve was studied. Area under curve of Lactate Dehydrogenase (AUC=0.65) and Ferritin (AUC=0.59) reflected their ability to prognosticate the presence of COVID19 disease. However, C-Reactive Protein (AUC=0.42) appeared to be a poor predictor of the disease. Conclusion: Raised serum Lactate Dehydrogenase (>490 U/L) and Ferritin (>152 ng/L) levels can be used to predict the Reverse Transcriptase Polymerase Chain Reaction positivity for COVID-19 in the population of suspected patients of COVID19. However, C-Reactive Protein is a poor predictor of COVID-19.

P06.04 Transcriptome-wide network analysis predicts the role of lactate dehydrogenase C in breast cancer cell survival and immune dysfunction

BackgroundCancer testis antigens (CTAs) are lucrative anti-cancer targets given their restricted expression patterns and known roles as mediators of cancer hallmarks, including cancer metabolism, proliferation, survival, and cell motility. Lactate dehydrogenase C (LDHC) is a CTA with upregulated expression in poor prognosis subtypes of breast cancer, however its tumorigenic role is less understood. We recently reported that silencing LDHC reduces breast cancer cell survival through a dysregulated DNA damage response, thus highlighting its potential as an anti-cancer target with limited off-target effects. This study aimed to explore the changes in the transcriptome of breast cancer cells and immune-related mediators upon in vitro LDHC targeting.Materials and MethodsWe silenced LDHC expression in breast cancer cell lines and investigated the downstream effects on the tumor cell transcriptome. Differentially expressed genes were subjected to regulatory network analyses. We further assessed the secretory profile of cytokines and immune checkpoint expression in LDHC-silenced cells and used the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm to determine the effect of the interaction between LDHC expression and cytotoxic T lymphocyte (CTL) infiltration in the METABRIC breast cancer cohort.ResultsNetwork analysis to investigate the effects of silencing LDHC on the tumor cell transcriptome identified 47 up- and 55 down-regulated transcripts (2.0-fold change, adj p<0.05). Differentially expressed genes in the LDHC-silenced cells were particularly enriched in canonical pathways regulating cell cycle checkpoint control, BRCA1-mediated DNA damage response and NF-kb signaling in response to infection. Upstream regulator analyses revealed the altered expression profile was associated with mTOR (p=1.27e-5, z=2.242) and CASP3 (p=3.2e-4, z=2.250) pathways, which in the presence of LDHC are predicted to activate TP53, Myc, NF-KB complex, STAT1/3, PRKC, CDK2, FOXO3 and HIF-1a while inhibiting SMAD3, PTEN, ATM, IL18 and BCL2. Consequentially, the observed network-wide changes on LDHC silencing are predicted to negatively influence cellular growth and proliferation, cell migration and cell infiltration. The LDHC-associated network indicated a higher-level regulation by miR378a-3p (p=1.4e-7, z=-3.117), affecting the downstream mechanistic in LDHC-expressing cells. Interestingly, the miR378a causal network also indicated inhibition of the immune response in LDHC-positive cells. TIDE analysis indicated that high expression of LDHC in the METABRIC Her2 breast cancer cohort (TIDE score=1.97, p=0.049), and to a lesser extent in triple negative breast cancer (TIDE score=0.466, p=0.642), decreases the beneficial effect between CTLs and overall survival observed in LDHC Low tumors. Concurrently, LDHC-silenced cells displayed a pro-inflammatory gene expression and cytokine profile and down-regulated the expression of PD-L1 and Gal-9 immune checkpoints.ConclusionsOur findings provide an indication of potential CTL dysfunction in breast tumors with high LDHC expression and suggests that therapeutic targeting of LDHC may inhibit tumor growth while releasing the anti-tumor immune response in breast cancer.Disclosure InformationA. Naik: None. J. Decock: None.

Covid-19 and headache characteristics

Background & Objective: Studies have shown that the most common neurologic symptom in patients with COVID-19 is headache, which may even be the first and only symptom. This study aimed to determine headache characteristics such as frequency, duration and localization, as well as the relationship of systemic inflammation with headaches in patients with COVID-19. Methods: A total of 202 patients hospitalized for COVID-19, consisting of 101 patients with headaches and 101 patients with no headache, were included in the study. Demographic characteristics, symptoms, clinical findings, and laboratory results were evaluated. In the group with headaches, visual analog scale (VAS) scores, duration, severity, and localization of pain were recorded. Results: One hundred nineteen (58.9%) of the patients had no headache in their previous medical history, whereas 21.3% (43/202) had a migraine history. Most of the patients with headache experienced short-term attacks of moderate-severity headaches (47.1%) that were pressing in nature (59%), and generalized (32.4%). We divided our patients into two groups according to pain severity: one of patients with mild-to-moderate headache and one of those with severe headache.. Pain characteristics were compared between the groups, and it was observed that the pain duration was longer in the group with severe pain (p<0.001). When the groups with and without headaches were compared, no significant differences were found between the groups regarding inflammatory markers such as lymphocyte count, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer levels. Conclusion: The headache in our patients with COVID-19 was mostly new-onset, of moderate severity, compressive in nature, and generalized. Inflammatory markers were unrelated to the presence and severity of the headaches.

Evaluation of the relation between cardiac biomarkers and thorax computed tomography findings in COVID-19 patients

Background: Troponin levels may be elevated in COVID-19 infection. The aim of this study was to the explore relation between troponin levels and COVID-19 severity. Materials, methods & Results: One hundred and forty consecutive patients with COVID-19 pneumonia were included. Diagnosis of COVID-19 pneumonia was based on positive chest computed tomography (CT) findings. Quantitative PCR test was performed in all patients. Only 74 patients were quantitative PCR-positive. Twenty four patients had severe CT findings and 27 patients had progressive disease. These patients had significantly lower albumin and higher ferritin, D-dimer, lactate dehydrogenase, C-reactive protein, and high-sensitivity cardiac troponin I (hs-cTnI). Conclusion: COVID-19 patients with severe CT findings and progressive disease had higher hs-cTnI levels suggesting the use of hs-cTnI in risk stratification.

A simple tool to help ruling-out Covid-19 in the emergency department: derivation and validation of the LDH-CRP-Lymphocyte (LCL) score

After the outbreak of the Covid-19 pandemic, cases of SARSCoV- 2 infections may gradually decrease in the next months. Given the reduced prevalence of the disease, Emergency Departments (ED) are starting to receive more and more non- Covid19 patients. Thus, a way to quickly discriminate ED patients with potential Covid-19 infection from non-Covid19 patients is needed in order to keep potentially contagious patients isolated while awaiting second-level testing. In this paper, we present the derivation and validation of a simple, practical, and cheap score that could be helpful to rule out Covid-19 among ED patients with suspicious symptoms (fever and/or dyspnoea). The LCL score was derived from a cohort of 335 patients coming to the ED of our hospital from March 16th to April 1st, 2020. It was then retrospectively validated in a similar cohort of 173 patients admitted to our ED during April. The score is based on blood values of lactate dehydrogenase, C-reactive protein, and lymphocyte count. The LCL score performed well both in the derivation and in the validation cohort, with an AUC respectively of 0.81 (95% CI: 0.77 – 0.86) and of 0.71 (95% CI: 0.63 – 0.78), given the difference in Covid- 19 prevalence between the two cohorts (57% vs 41% respectively). An LCL score equal to 0 had a negative predictive value of 0.92 in the derivation cohort and of 0.81 in the validation cohort, with a negative likelihood ratio respectively of 0.08 and 0.36 for Covid- 19 exclusion. This score could, therefore, constitute a useful tool to help physicians manage patients in the ED.

Ischemic Stroke in Patients with COVID-19 Disease: A Report of 10 Cases from Iran

Ischemic stroke seems to be one of the most serious neurologic complications in patients with COVID-19 infection. Herein, we report a series of 10 ischemic stroke patients with concomitant COVID-19 disease. Out of 10, 8 had large infarcts (3 massive middle cerebral artery, 2 basilar artery, 2 posterior cerebral artery, and 1 internal carotid artery infarct territory). Two had cardiogenic embolic stroke due to atrial fibrillation. Almost half of our patients did not have a vascular risk factor. Nine did not have fever and were diagnosed with COVID-19 upon admission for stroke. Stroke occurred in the first week of respiratory symptoms with moderate pulmonary involvement. Most Patients did not have hypoxia and did not establish respiratory failure or acute respiratory distress syndrome. The blood pressures were low and hemorrhagic transformation did not occur even after antiplatelet or anticoagulant therapy. Patients had markedly increased levels of lactate dehydrogenase, C-reactive protein, and D-dimer. Three patients died. It seems that ischemic strokes in COVID-19 patients tend to occur as large infarct and can be seen in patients with mild to moderate pulmonary involvement.

Comparative analysis of clinical features of SARS-CoV-2 and adenovirus infection among children

Background The new emerging coronavirus disease 2019 (COVID-19) overall shares similar symptoms with other common respiratory viral infections. We aimed in this study to compare COVID-19 and human adenovirus (HAdV) infections in pediatric patients regarding the frequencies of major clinical symptoms and the potential disparities in laboratory and imaging parameters. Methods Following a case–control-like design, we built 72 age-matched pediatric COVID-19 and HAdV patient pairs. Their early symptoms and laboratory and imaging characteristics were then retrieved and compared. Results Fever and cough were the most common symptoms for both infections but were seen more often in HAdV than in COVID-19 patients (92% vs. 66% and 60% vs. 18%, respectively). Compared with COVID-19 patients, children with HAdV infection had statistically significantly higher values of neutrophil count, neutrophil percentage, activated partial thromboplastin time, prothrombin time, lactate dehydrogenase, C-reactive protein, procalcitonin but lower values of lymphocyte percentage, total bilirubin, potassium and sodium. Thoracic computed tomography also revealed more anomalies in HAdV patients than in COVID-19 patients (95% vs. 67%). Conclusions COVID-19 is an overall less symptomatic and less severe infection at admission compared to HAdV respiratory infection in pediatric population.

The Sperm Specific Form of Lactate Dehydrogenase (LDHC4) is Required for Fertility and is an Attractive Target for Male Contraception (A Review)

There has been a recent upsurge in interest about contraceptive development, evidenced by the Contraceptive Special Issue of Biology of Reproduction [1], with research funding from the Male Contraceptive Initiative (MCI), and the Bill and Melinda Gates Foundation. Support from the Contraceptive Research Branch of the Eunice Kennedy Shriver National Institutes of Child Health and Human Development (NICHD) continues with a marked change in focus in the funding announcements. This has motivated me to reflect on research, mostly from my laboratory starting in the 1960’s to the present, on the development of a male contraceptive based on the sperm specific glycolytic enzyme, Lactate Dehydrogenase C (LDHC4). This review considers the rationale behind this research, the development paths pursued, obstacles encountered and the renewed interest in going forward toward development of a male contraceptive mediated by inhibition of the sperm specific form of Lactate dehydrogenase (LDHC). I will address how some papers published many years ago are relevant to present goals of non-hormonal contraception and will mention innovative technology now available that can advance this project. This review presumably will serve as an instructive guide for a research program with a focused program related to contraception. As an aside, many of the citations in this review are to most of the 26 publications in Biology of Reproduction co-authored by this investigator and collaborators from 1974 through 2020 not long after the first issue of BOR which was published in April 1969.

What is New in COVID-19 and What We Need to Do Against This Pandemic Infection? A Comparative Review

Background: Initially, large number of COVID-19 cases reported from Wuhan City, China, reflected that this is likely the zoonotic origin of COVID-19. In March, 2020; it has since been declared a serious pandemic infection by the World Health Organization (WHO). Objective: The main objective of this review was to addressed what gaps still exist. Many researchers have reported the many common characteristics of COVID-19 virus in comparison with other pandemic viruses, while the major differences are discussed in this review. Method: In this review, we investigated the general characteristics of COVID-19 its diagnosis and other preventive measures in comparison with other pandemic viruses that we know or we need to know. Results: All reported corona viruses belong to the one genus and family Coronavirus and Coronaviridae. The COVID-19 virus spreads easily and exponentially multiple times compares to other viruses. It can be divided into four antigenic groups, HKU1, NL63, 229E and OC43. The case mortality rate of this pandemic is 1.68%, compared to other pandemics in their first outbreaks, including the great pandemic influenza (0.2%), SARS-CoV (10%), MERS-CoV (34%), and Ebola (50%). Laboratory findings related to COVID-19 include elevated levels of D-dimer, Alanine transaminase (ALT), LDH (lactate dehydrogenase), C-reactive protein (CRP), creatine kinase and prothrombin times. Conclusion: This comparison based review will help to understand the biology, potential risk and preventive measures of COVID-19 and provide cognizance about what we need to do against this pandemic which victimized more than 200 countries up to the present time.