Mechanisms and implications of COVID-19 transport into neural tissue

The neuropathogenicity of COVID-19 was reported shortly after detection of the virus when patients began reporting symptoms of diminished taste and smell, headaches, mental status changes, and more. As the virus spread, increasing data on viral symptoms in conjunction with novel theories on COVID-19 virulence factors indicated that the virus had neurotropic properties. Several mechanisms have been proposed detailing severe acute respiratory syndrome coronavirus disease 2019 (SARS-CoV-2) transport past the blood–brain barrier and into neural tissue. This chapter offers a comprehensive review of possible neurotropic mechanisms including transport via the angiotensin-converting enzyme 2 (ACE-2) receptor, transportation directly past or through the blood–brain barrier, transsynaptic neuronal transfer, and olfactory conduction. © 2023 Elsevier Inc. All rights reserved.

Immune enhancers for COVID-19

SARS-CoV-2, also known as COVID-19, is a novel coronavirus that began sweeping the globe at the end of 2019, causing mild illness in some patients while leading to devastating shock, immune dysregulation, multiorgan failure, and even death in others. Immune dysregulation may lead to increased susceptibility to severe disease from COVID-19. Immune enhancers could aid in immune regulation and protect against severe COVID-19 infection. Herbal supplements, spices, and lifestyle modifications have been shown to enhance immune responses to a number of pathogens, which may include COVID-19. These immune enhancers could be used adjunctively with vaccines, social distancing, and pharmacologic treatments to prevent life-threatening infection in susceptible patients. © 2023 Elsevier Inc. All rights reserved.

Bibliometric analysis of publication trends in the COVID-19 pandemic

Purpose of Study The COVID-19 pandemic has presented a major challenge to the global medical community resulting in many necessary changes in worldwide research publication trends. As focus and funding of research have shifted throughout the pandemic, so too have publication types, topics, and country-wide research output. While changes during the pandemic have undoubtedly had an impact on publications, these impacts and their implication for long-term research have been poorly characterized. We aim to illustrate these shifting changes in publications during the COVID-19 pandemic. Methods Used Publications were accessed using PubMed Advanced Search Criteria. The beginning of the COVID-19 pandemic was set as the date of the first reported case in Wuhan on 12/31/2019. Searches were conducted on 9/10/ 2021. We generated searches based on type of publication, country affiliation of the first author, date ranges, and specific topics such as 'COPD' or 'Diabetes'. We analyzed the changes in publications during the 4 months before the first case of COVID-19 and every 4 months thereafter. Results were analyzed using SPSS. Summary of Results In the two years before the pandemic, 3541.9 PubMed-indexed articles were published per day, while 4379.9 such articles have been published each day during the pandemic. Covid-19 resulted in net increases relative to baseline in case reports, reviews, and retracted publications with net decreases in clinical trials, multicenter studies, and randomized control trials in most yearly tertiles relative to the 4 months before Covid-19. Meta-analysis and observational studies demonstrated initial net increases followed by subsequent net decreases. The largest percent decrease in publication type relative to baseline has been seen in Phase I (- 82.6%) and Phase IV (-80.5%) clinical trials. In the first yearly tertile, China had the largest percent increase in publications relative to baseline (38.4%) followed by Italy in the second tertile (32.0%) and India in the third tertile (43.5%). Increases in daily publications were seen in many research topics including diabetes (32.8/day), asthma (4.6/day), heart disease (2.9/day), and COPD (2.4/day). Conclusions COVID-19 has caused a shift in research focus and funds towards pandemic-related research. This has emphasized lower evidence research, such as case reports, and shifted focus away from high evidence studies, such as clinical trials and meta-analysis. Production of high-evidence studies does not appear to be recovering as the pandemic continues. Research output of individual countries appears to coincide with COVID-19 related infection surges in each respective country. Despite new emphasis on Covid-related research, many important topics such as diabetes and heart disease have experienced increases in publications.

EKG changes in severe hypercalcemia mimicking Brugada's syndrome

Case Report A 62-year-old Caucasian, female patient with history of celiac disease and chronic pain s/p spinal cord stimulator presented to our institution to follow up on abnormal lab findings. The patient presented to her PCP with complaints of worsening weakness, nausea, vomiting, constipation, polydipsia, and occasional palpitations. Labs resulted a severely elevated serum calcium level (17 mg/dL), increased BUN (32), and elevated Cr (1.8) indicating acute kidney injury. Full workup was initiated. Vitamin D, 25-Hydroxy level returned greater than 209 and PTH resulted in a normal range of 22. Detailed history revealed that the patient was taking 50,000 units of vitamin D3 by mouth six times/ week for six months. Fear surrounding the current COVID- 19 pandemic prompted the exorbitant intake of vitamin D supplementation in hopes of immune improvement. Bisphosphonate were contraindicated due to AKI.Volume expansion with normal saline and calcitonin successfully decreased the patient's serum calcium. Discussion The diagnostic criteria for reversible Brugada pattern, recently classified as Brugada phenocopy, includes four mandatory components. Primarily, an ECG tracing delineating type 1 or type 2 Brugada morphology. Secondarily, the presence of an underlying condition that is identifiable and reversible. Third, complete resolution of the ECG pattern upon elimination or correction of the underlying condition. Fourth, a low probability for Brugada syndrome determined by the lack of symptoms, clinical history, and family history. Our patient experienced severe hypercalcemia with palpitations that prompted an ECG. The abnormal ECG produced was read independently by two interventional cardiologists and a cardiac electrophysiologist who all concluded the ST segment and T wave deviations were consistent with Brugada pattern type 1. Importantly, the ECG was compared to one from a year prior which showed a normal rate and rhythm. There was complete resolution on repeat ECG once serum calcium was returned to reference range. The patient did not experience Brugada specific symptoms of syncope, seizures, nocturnal agonal breathing, or sudden cardiac death. No family history suggested Brugada syndrome or cardiac issues. Electronic medical record documentation tracked over the last 5 years showed no concerns for prior arrhythmias or syncope. Additionally, the patient does not fit the epidemiological profile of a male of Southeast Asian decent which is classically associated with Brugada syndrome. To our knowledge, this is the first documented presentation of Brugada phenocopy induced by severe hypercalcemia secondary to vitamin D toxicity. Conclusion Although the mechanism is not completely understood, severe hypercalcemia can cause a reversible type 1 Brugada pattern on ECG. Careful consideration of vitamin supplementation must be discussed with patients to avoid potentially fatal cardiac outcomes.

Identifying systemic lupus erythematosus presenting as hemorrhagic oral bullae in a covid positive pediatric patient

Case Report A previously healthy 13 year-old female presented with painful, oral mucosal bullae filled with sanguinous fluid. She was initially (mis)diagnosed with angina bullosa haemorrhagica (ABH) and was provided symptomatic treatment. After a CBC demonstrated severe thrombocytopenia, anemia, and leukopenia, the patient was admitted for further workup including Coombs and COVID-19 PCR, which were both positive. Given a remote family history of Lupus and increasing right knee pain, further diagnostic testing was ordered. These results demonstrated a positive ANA, anti-Smith, anti-chromatin, anti-RNP, increased dsDNA and increased SM/RMP, confirming Lupus as the etiology of this patient's presentation. A form of Blistering Systemic Lupus Erythematosus (BSLE) was likely responsible for the patient's oral manifestations. The patient was discharged on Prednisone 30 mg twice per day after receiving 60 g IVIG and 3 days of high dose pulse corticosteroids. Discussion This outlines the case of a thirteen yearold girl with SLE with an initial presentation of blood-filled oral mucosal lesions. The patient's COVID-19 positive status, young age, and atypical presentation added to the intricacy of her case. After presenting with blood-filled bullae in the oral cavity, the patient was initially suspected of having Angina Bullosa Haemorrhagica (ABH). ABH is a rare condition that presents with painful or painless blood-filled oral vesicles or bullae that rupture spontaneously and heal without scarring. The patient's abnormal CBC ruled out ABH and suggested a diagnosis of Evan's syndrome, a disorder in which cytopenias are present in two or more cell lines. Before SLE was determined to be the cause of the patient's cytopenias, the etiology of her Evan's syndrome was attributed to her COVID-19 positive status. Rarely, Lupus has been reported to present with vesicles and bullae in a syndrome known as BSLE. Upon an extensive review of the literature, only four articles mentioned oral bullae in a pediatric patient with SLE and not a single article mentioned hemorrhagic bullae in pediatric SLE patients. Conclusion A deeper understanding of the variety of cutaneous manifestations of SLE is essential for disease diagnosis and management. The present study details the first ever reported case of SLE presenting with blood-filled oral bullae in a pediatric patient. Novel presentations of SLE such as this reinforce the need for a collaborative, inter-specialty approach to diagnosis and treatment of autoimmune disease. This case reinforces the utility of a centralized database for recording unique autoimmune manifestations in order to aid in physicians' diagnosis and expediency of treatment. Lastly, this case should support an increase in a clinician's degree of suspicion for underlying autoimmune disease when dealing with unique cutaneous presentations of autoimmune diseases like SLE.

Post-COVID myalgic encephalomyelitis in chronic heart disease patient: A case series

Purpose of Study Myalgic encephalomyelitis (ME), also called chronic fatigue syndrome, is a condition characterized by severe fatigue that impairs a patient's ability to perform common daily activities. Criteria for ME include 6 months of fatigue-limited daily activities, unrefreshing sleep, and symptom exacerbation following physical or mental strain, and orthostatic intolerance. New reports indicate that ME incidence may be higher in specific patient populations. This study was designed to investigate the association between ME and Cardiovascular disease in patients recovering from COVID-19 infection. Methods Used The patient population used for this study includes 19 patients that were referred to the Amarillo Heart Group in Amarillo, TX who also tested positive for Covid-19 at least 6 months prior to September 1, 2021. The patients that fit this timeline were asked a series of standardized questions and rate the severity of their symptoms on a scale of 0 to 5, with 0 being the absence of symptoms and 5 being the most severe. Two sets of questions were created and named Life Spheres Criteria (4 questions) and Symptoms Criteria (3 questions) based on the 2015 IOM Diagnostic Criteria for CFS. Rating more than 1 Life Spheres question as a 3 or higher or rating all 3 Symptoms Criteria questions as a 3 or higher indicated Chronic Fatigue Syndrome. Information from the survey, including time since infection, demographics, and question scores, were analyzed. Summary of Results Our study included 10 women and 10 men, with the average amount of time since Covid-19 infection being 328.17 ± 41.36 days. Worsening of symptoms with mild exertion was the most commonly endorsed criteria (3.58 ± 1.64) and the least common criterion was fatigue reducing activity in school (2.00 ± 1.94). Women scored higher in every category except reduced activity in school when compared to men. However, there was no significant difference in symptom scores between the two groups with the Combined Fatigue Score being 2.89 ± 1.47 for women and 2.67 ± 1.59 for men. Nearly all symptom scores significantly positively correlated with one another, meaning if one category was high it was likely for other categories to be high as well. Ultimately, when looking at the Cumulative Pearson Correlation Scores, reduced social life, difficulty concentrating, and symptoms worsening with mild exertion were found to be most predictive of a high Combined Fatigue Score. Conclusions In this case series, over 80% of patients met the criteria for Post-COVID Myalgic Encephalomyelitis. While the link between ME and both COVID-19 and cardiovascular disease has been established, little is known about the severity of ME in patients who have a history of both cardiovascular disease and COVID-19 infection. To our knowledge, this is the first study to examine ME in patients with both of these predisposing conditions. A high degree of clinical suspicion for ME should be used when screening and treating cardiac patients who have been infected with COVID-19.