Metformin in COVID-19: Is There a Role Beyond Glycemic Control?

Context: The coronavirus disease 2019 (COVID-19) pandemic is still a cause of worldwide health concern. Diabetes and its associated comorbidities are risk factors for mortality and morbidity in COVID-19. Selecting the right antidiabetic drug to achieve optimal glycemic control might mitigate some of the negative impacts of diabetes. Metformin continues to be the most widely administered antidiabetic agent. There is evidence of its beneficial outcome in COVID-19 independent of its glucose-lowering effect. Evidence Acquisition: A thorough literature search was conducted in PubMed, Google Scholar, Scopus, and Web of Science to identify studies investigating metformin in COVID-19. Result(s): Several overlapping mechanisms have been proposed to explain its antiviral properties. It could bring about conformational changes in the angiotensin-converting enzyme-2 receptor and decrease viral entry. The effects on the mammalian target of the rapamycin pathway and cellular pH have been proposed to reduce viral protein synthesis and replication. The immunomodulatory effects of metformin might counter the detrimental effects of hyperinflammation associated with COVID-19. Conclusion(s): These findings call for broader metformin usage to manage hyperglycemia in COVID-19.Copyright © 2023, International Journal of Endocrinology and Metabolism.

Transmission Probability of SARS-CoV-2 in Office Environment Using Artificial Neural Network

In this paper, curve-fitting and an artificial neural network (ANN) model were developed to predict R-Event. Expected number of new infections that arise in any event occurring over a total time in any space is termed as R-Event. Real-time data for the office environment was gathered in the spring of 2022 in a naturally ventilated office room in Roorkee, India, under composite climatic conditions. To ascertain the merit of the proposed ANN and curve-fitting models, the performances of the ANN approach were compared against the curve fitting model regarding conventional statistical indicators, i.e., correlation coefficient, root mean square error, mean absolute error, Nash-Sutcliffe efficiency index, mean absolute percentage error, and a20-index. Eleven input parameters namely indoor temperature ( $T_{In}$ ), indoor relative humidity ( $RH_{In}$ ), area of opening ( $A_{O}$ ), number of occupants ( $O$ ), area per person ( $A_{P}$ ), volume per person ( $V_{P}$ ), $CO_{2}$ concentration ( $CO_{2}$ ), air quality index ( $AQI$ ), outer wind speed ( $W_{S}$ ), outdoor temperature ( $T_{Out}$ ), outdoor humidity ( $RH_{Out}$ ) were used in this study to predict the R-Event value as an output. The primary goal of this research is to establish the link between $CO_{2}$ concentration and R-Event value;eventually providing a model for prediction purposes. In this case study, the correlation coefficient of the ANN model and curve-fitting model were 0.9992 and 0.9557, respectively. It shows the ANN model's higher accuracy than the curve-fitting model in R-Event prediction. Results indicate the proposed ANN prediction performance (R = 0.9992, RMSE = 0.0018708, MAE = 0.0006675, MAPE = 0.8643816, NS = 0.9984365, and a20-index = 0.9984300) is reliable and highly accurate to predict the R-event for offices.

IMPROVING THE PROVISION OF GASTROENTEROLOGY TEACHING TO NON-SPECIALIST TRAINEES

Introduction As more specialists become dual accredited in internal medicine, non-gastroenterology specialists have greater exposure to gastroenterology patients over the course of their training, especially via the acute take. Simultaneously, the COVID pandemic has meant most regular local teaching has moved online with varying quality. This project aimed to evaluate 1) whether a standardised protocol can be used to successfully deliver large scale digital gastroenterology teaching that 2) is non-inferior when compared with traditional face to face teaching. Methods Teaching was delivered to internal medical trainees on the acute management of ulcerative colitis and chronic liver disease. Two sessions were delivered a year apart, initially regionally, and then nationally. This was delivered via Zoom, using a standardised protocol based on guidelines to ensure consistency, with live-polled multiple-choice questions to encourage interaction. Each session was followed by Q&A related to that topic. Feedback was taken after each session. Outcome measures analysed were: number in attendance, whether viewers would recommend this teaching to others, whether they thought it ran smoothly, and how they felt about it when compared with face-to-face teaching as measured on a Likert scale. Given the subjective nature of our hypotheses, we accept that these are surrogate markers. Results 171 trainees attended the initial regional teaching session and 469 the subsequent session. Following the first session, 98.9% of trainees would recommend the teaching to others, rising to 99.7% after the second session. 99% and 99.5% respectively agreed or strongly agreed with the statement the initial session ran smoothly, while 84.5% and 88.8% agreed or strongly agreed that digital teaching was as effective as face to face. The benefits of digital teaching were no travel (90%) ability to watch later (86%), whereas the downsides were loss of social interaction (60%) and harder to get study leave (39%). Conclusions Gastroenterology teaching for non-specialists can be delivered successfully at a large scale using a standardised protocol for digital teaching. The vast majority of trainees felt that digital sessions were as effective as face-to-face teaching with a lack of travel and flexibility on viewing time the main reported benefits.

Spectrum of Acute Necrotizing Hemorrhagic Encephalitisin COVID-19 patients: A case series and Review

Objective: N/A Background: Severe Acute Respiratory Syndrome Corona Virus 2 (SARS CoV-2) an ongoing pandemic has affected over 200 million people worldwide and caused over 4.5 million deaths. COVID-19 related acute encephalopathy has been known to exist and is thought to be multifactorial, most often related to underlying systemic inflammation, ischemic strokes, hypoxic injury or direct viral invasion and is associated with increased mortality. Design/Methods: We report a case series of three young patients with acute necrotizing hemorrhagic encephalitis (ANHE) after COVID-19 infection and a review of literature. Two of the cases (without preexisting comorbidities) had self-limiting disease that improved with resolution of systemic illness, and one (with preexisting comorbidities) had pathological evidence of fungal invasion who improved only after antifungal therapy. Results: N/A Conclusions: Acute necrotizing hemorrhagic encephalitis is a potential complication of COVID19 and is multifactorial, mediated by cytokines, host inflammatory response, superimposed infections, hypoxemia, hypercoagulability and possibly direct viral invasion. Clinical course may range from mild self-limiting illness to severe encephalitis with co-infection with other pathogens. Low threshold for neuroimaging, even with mild neuropsychiatric symptoms like headaches, can help in early diagnosis and prompt management, potentially preventing further complications.

Acute Inflammatory Demyelinating Polyneuropathy as the first presenting feature of COVID 19 infection

Objective: To describe a case of a 58-year-old patient who presented to the hospital with Acute Inflammatory demyelinating Polyneuropathy (AIDP) as the first symptom of SARS COVID-19 infection without other classic manifestations of COVID-19 infection. Background: COVID-19 associated Guillain Barre syndrome is now widely reported. In our literature review, the majority of GBS patients had preceding respiratory symptoms of COVID19 but our patient had no other systemic involvement, and his symptoms started noticeably within a short duration of exposure. Design/Methods: Case report. Results: 58-year-old male patient presented to the hospital with bilateral lower extremity weakness, facial diplegia and dysphagia. Patient was tested positive for COVID-19 infection three days prior to the symptom onset due to a work-related exposure. He denied having any flu-like symptoms except generalized weakness. Patient reported progressive lower leg weakness started three days back with associated numbness and radicular pain up to T4 level. On examination, the patient had facial diplegia, areflexia and bilateral lower limb ataxia with the strength of about 3/5. CSF analysis showed albuminocytological dissociation. MRI brain and spine showed faint enhancement of lower lumbar roots. GQ1b antibody was positive on Ganglioside panel. With the clinical criteria and laboratory evidence, patient was diagnosed with AIDP. Patient was started on IVIG but due to lack of improvement after four doses patient was switched to therapeutic plasma exchange. He underwent a total of 7 sessions of plasmapheresis with improvement of motor and sensory symptoms. Conclusions: Although most cases were symptomatic for COVID-19, patients without respiratory or systemic symptoms raises a significant healthcare concern, namely the importance of SARS COVID-19 testing in all patients with suspected GBS during this global pandemic. Early diagnosis of COVID-19 associated GBS is also essential for rapid case isolation.

Immunosuppression in Chronic Autoimmune Neurological Disorders during the COVID-19 Pandemic

Objective: To study the risk of acquiring Corona Virus Disease 2019 (COVID-19) and its outcomes in patients on immunosuppressive therapy (IST) for chronic autoimmune neuromuscular disorders (aNMD) and multiple sclerosis (MS). Background: NA Design/Methods: We used TriNetX, a global health collaborative clinical research platform collecting real-time electronic medical records data, which has one of the largest known global COVID-19 database. We included patients with chronic autoimmune neuromuscular disorders (aNMD) [myasthenia gravis (MG), inflammatory myositis, and chronic inflammatory neuropathies (CIN)] and MS, based on the International Classification of Disease-10 (ICD-10) coding for one year before January 20th, 2020. We examined the use of IST, rate of COVID-19, hospitalization, intubation, and mortality among the patients with aNMD and MS. Results: A total of 33,451 patients with aNMD and 42,899 patients with MS were included. Among them, 111 (0.33%) patients with aNMD and 115 patients (0.27%) with MS had COVID19. About one third of them required hospitalization. IST did not appear to have a significant impact on overall infection risk in either group;however, risk of hospitalization for immunosuppressed patients with aNMD was higher (Odds ratio 2.86, p-value 0.011). Conclusions: IST use does not appear to make patients with aNMD and MS more vulnerable to COVID-19. IST may be continued during the pandemic, as previously suggested by expert opinion guidelines. However, it is important to consider individualizing immunotherapy regimens in some cases. Additional physician reported registry-based data is needed to further confirm these findings.

Clinicohaematological Patterns of Anemia and Correlation with Clinical Conditions in Children Aged 5 to 12 Years in Tertiary Care Centre

Objective: To classify the haematological pattern, severity of anemia in children 5-12 years age admitted and to find its correlation with the clinical conditions. Methods Crossectional study of 160 patients in two years was done. Patients satisfying the inclusion criteria were selected for study. Relevant clinical data were recorded in a structured proforma including detailed history was recorded with particular symptoms suggestive of anemia such as weakness and easily fatigability, breathlessness on exertion and pica. A thorough clinical examination of every child was done followed by routine investigations for anemia Results Patients between 7-8 year were found to be the most affected. Anemia was found to be more common in female children as compared to male children (F:M=1.13). Anemia is more common in undernourished child. Most common presenting symptoms were gastrointestinal including vomiting, diarrhea and pain abdomen. Most common sign was Pallor followed by other common signs included signs of dehydration associated with diarrhea, hepatosplenomegaly. microcytic hypochromic anemia was the most common morphological type of anemia and macrocytic anemia was the least common.Thalassemia cases were most common among hemolytic anemias. Iron Deficiency Anemia (Nutritional Anemia) was the most common etiology of anemia. Conclusion Dietary deficits affect children aged 5 to 12, creating financial, emotional, and psychological burden for patients and their families, as well as depleting critical national resources. As a result, screening for these illnesses, as well as early detection of anemia and related problems, is essential.

Efficacy of WBC and Platelet Parameters in Predicting Survival in Patients with COVID-19 Infection

Introduction: Coronavirus disease 2019 (COVID-19) is an infectioncaused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). Since there is activation of both inflammatory and thrombotic pathways in this disease, indices derived from routinelymeasured blood parameters, whose role is established in severe sepsis,are being evaluated worldwide as potential prognostic markers.Aims &Objectives: In this study we aimed to evaluate the role ofAbsolute Neutrophil count (ANC), Absolute Lymphocyte Count(ALC), Mean platelet volume (MPV), platelet distribution width(PDW), Plateletcrit (PCT), Platelet-large cell ratio(P-LCR), Neutrophil Platelet ratio (NPR) and Platelet Lymphocyte ratio (PLR) inpredicting survival amongst patients admitted with COVID-19infection.Materials &Methods: We conducted a retrospective chart review ofall moderate to severely ill adult patients admitted with COVID-19pneumonia admitted at All India Institute of Medical Sciences,Bhopal, a tertiary care hospital in Central India from April 2020-November 2020. Information about their demography, clinical features, laboratory investigations and in-hospital survival were collectedfrom charts.Result: The study included 1331 patients, out of these 1181 weresurvivors (389 females;792 males) and 150 were non survivors (35females;115 males). Amongst the various parameters studied ANC,NPR and PCT were found to be significantly lower amongst thesurvivors as compared to the non survivors whereas ALC was significantly higher amongst the survivors.Conclusions: The results of the current study showed that ANC,ALC, NPR and PCT can be used as useful cost-effective prognosticmarkers in patients with COVID-19 infection.

Neuropsychiatric manifestations in COVID - 19

Objective: Coronavirus infections are known to have neuro invasive potential with consequent neuropsychiatric manifestations. Since early recognition and prompt management of neuropsychiatric manifestations in these patients have a potential to decrease overall morbidity and mortality. We analyzed COVID-19 adult patients from January 20, 2020 to June 10th, 2020. 40,469 patients were diagnosed with COVID-19 among whom 9086 patients had neuropsychiatric manifestations. Background: Corona Virus 2 is a highly pathogenic coronavirus identified as causing mild to severe symptoms involving Respiratory, GI, Cardiac and tend to have neuroinvasive potential. In the largest study thus far, Mao et al reported a case series of 214 patients, where approximately one-third of these patients had neurological symptoms including stroke, encephalopathy and myopathy. We studied, 40,469 COVID-19 patients, our aim is to describe the demographics, neurological manifestations, and complications of COVID-19. Design/Methods: De-identified COVID-19 patient data was extracted using TriNetX from Jan 20, 2020 to June 10 2020. Study population included patients with age 18 years or older with a positive diagnosis of COVID-19 Results: Of the total 40,469 COVID-19 patients, (22.5%) patients had neuropsychiatric manifestations. The most common neurologic manifestations included headaches (3.7%) and sleep disorders (3.4%). Other manifestations were encephalopathy (2.3%), myalgia (2.0%), pain (1.8%), loss of taste and smell (1.2%), stroke and transient ischemic attack (TIA) (1.0%), dizziness (0.9%), extrapyramidal and movement disorders (0.7%), seizures (0.6%), polyneuropathy (0.6%), and nerve root and plexus disorders (0.4%). Common psychiatric manifestations included anxiety and other related disorders (4.6%), mood disorders (3.8%). Less than 1% of all psychiatric manifestations included emotional state symptoms and signs (0.8%), suicidal ideation (0.2%). Conclusions: Potential mechanisms of neuropsychiatric manifestation include direct CNS infiltration, cytokine network dysregulation, peripheral immune cell transmigration, and postinfectious autoimmune response. Clinicians need to be aware of these manifestations in COVID- 19 patients, given the morbidity and mortality of neuropsychiatric involvement.

Underutilization of health care for strokes during the COVID-19 outbreak

Objective: To analyze impact of COVID-19 Pandemic on acute stroke care. Background: At the offset of Pandemic, a decrease in utilization of healthcare in medical emergencies like acute ischemic stroke and Myocardial Infarction was observed. Design/Methods: We collected stroke data from TriNetX network research platform. We analyzed number of ischemic stroke patients greater than 18 years, intravenous tissue plasminogen activator (IV tPA) administration and mechanical thrombectomy (MT) in Study group (SG) from 20 January 2020 to 16 May 2020 and compared them with two control groups (CGs): control group 1 (CG1) from 20 January 2019 to 16 May 2019 and control group 2 (CG2) from 25 September 2019 to 19 January 2020. We used Bonferroni's method to correct for multiple comparisons and alpha of 0.01 was considered significant. Results: There was 43% decrease in number of stroke patients in SG compared to CG1 and 25.5% decrease compared to CG2. In the SG, there was drop in number of IV tPA administrations 51% and 35%, and MT by 39% and 27% compared to CG1 and CG2 respectively. Likelihood of stroke patients receiving IV tPA was higher in both CGs compared to the SG (X =8.95, p=0.002 for CG1, and X =6.59, p=0.010 for CG2). There was no significant difference in MT between groups. There were 287 (0.8%) stroke patients with diagnosis of COVID-19 in SG. When COVID-19 positive patients were compared to COVID-19 negative patients, younger patients were significantly overrepresented in COVID-19 positive group (X =8.75, p=0.003). Conclusions: There was substantial drop in number of stroke patients seeking medical help in the SG, suggesting that people with strokes were not presenting to hospitals during study period, likely due to concerns contracting SARS-CoV2 in hospital. Younger patients were overrepresented in COVID-19 strokes suggesting possible increased risk of strokes due to hypercoagulable state with COVID-19.

Reflections on running an International Public Health Film Competition during the COVID-19 pandemic and implications for future film festivals

The COVID-19 pandemic has had a substantial impact on the film industry in 2020. Films that tell the story of the pandemic by giving independent commentaries are important to our understanding of life during these rare public health events. However, it is unclear what effects the pandemic would have on the production of these films. In this Letter we describe a unique global collaboration that saw the launch of an International Public Health Film Competition during the first wave of the pandemic in early 2020 to collect the ‘best health-related’ stories told through film. We reflect on the process followed for this competition and provide insights for future film competitions/ festivals. © 2021 Informa UK Limited, trading as Taylor & Francis Group.