Mastocytosis and COVID19 infection and vaccination: A pediatric series

Introduction: Mastocytosis encompasses a heterogeneous group of diseases characterized by an accumulation of clonal mast cells (MC) in the skin and/or internal organs, and symptoms of MC activation. This MC activation can be elucidated by several factors, including infections or vaccination. Objective(s): We present our experience with COVID infection and vaccination in a series of 133 patients with pediatric mastocytosis. Method(s): Between January 1998 and December 2022, 133 pediatric patients have been referred to our hospital owing to clinically suspected MC disorder, mainly with mastocytosis in the skin. The final diagnoses of mastocytosis were established by the presence of typical skin lesions together with an increase of MC numbers in a biopsy from lesional skin or activating KIT mutations in lesional skin tissue. Serum baseline tryptase and total immunoglobulin E levels were measured, and patients underwent a comprehensive allergy workup to confirm atopic status and history of anaphylaxis. Regarding vaccination, REMA's (Spanish Network on Mastocytosis) protocol was followed. Result(s): 13 patients with COVID infection were identified, of which 25 (56,8%) were female and 0% had symptoms of MC activation. All of them had an asymptomatic or mild course of COVID infection. None of the patients experimented MC activation symptoms during viral illness. Regarding COVID vaccination, all patients received premedication with antihistamine 60 minutes prior vaccination. No one experimented immediate reactions and only one patient (0,75%) referred worsening of MC activation symptoms (baseline pruritus, urtication and brain fog) only after the first doses, recovering without changes in his treatment (oral cromoglycate and antihistamine) in two months. Discussion(s): Although MC have been implicated in the pathogenesis of cytokine storm in COVID19, there is no clinical evidence of SARSCoV- 2-induced MC activation, perhaps related to the fact that bone marrow MC lack angiotensin-converting enzyme 2 receptors.

Public Attitudes, Awareness and Fears Related to the Spread of COVID-19 in Bulgaria

The pandemic caused by COVID-19 has led to radical lifestyle changes worldwide, particularly in the Republic of Bulgaria, and was a factor for global changes in economics, politics, healthcare and daily life. Aim(s): The aim of the study was to analyze the public attitudes, awareness and fears related to the COVID-19 disease in the Republic of Bulgaria. Material(s) and Method(s): The survey was conducted between August 1st, 2022 and September 1st, 2022 via an anonymous questionnaire consisting of 24 closed questions. A total of 1861 people, aged 18-69 years and older, took part in the survey after being selected randomly. The data were statistically processed via MS Excel. Result(s): The main source of information to the respondents on issues related to COVID-19 was the Internet (29,8%), followed by TV (26%) and the specialized website (Single information portal) - 15,9%. More than one-third (35,1%) of the respondents was afraid of getting infected and an equal share of participants reported that they have been infected with COVID-19. More than half of the respondents (52,5%) adhered to all the provisions of the governmental bodies related to limiting the COVID-19 pandemic. The most frequent symptom of post- COVID-19 syndrome was being easily fatigued (26,7%), followed by shortness of breath (13,4%) and persistent cough (11,6%). Conclusion(s): The survey could be useful in understanding what were the public attitudes, awareness and fears related to the COVID-19 disease in the Republic of Bulgaria during the pandemic.Copyright © 2023 D. Penchev et al., published by Sciendo.

SARS-CoV-2 Infection Increases the Gene Expression Profile for Alzheimer's Disease Risk

The COVID-19 pandemic is a global outbreak of coronavirus, an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). One in five adults who have had COVID-19 in the past was still experiencing any one of the symptoms of long COVID like headache, brain fog, fatigue, and shortness of breath. Up to 30% of individuals with mild to severe infection show diverse neurological symptoms, including dementias. Hence, it is very much important to characterize the neurotropism and neurovirulence of the SARS-CoV-2 virus. This helps us understand the mechanisms involved in initiating inflammation in the brain, further leading to the development of earlyonset Alzheimer's disease and related dementias (ADRDs). In our brain gene expression analysis, we found that severe COVID-19 patients showed increased expression of innate immune response genes and genes that are implicated in AD pathogenesis. To study the infection-induced ADRDs, we used a mouse-adapted strain of the SARS-CoV-2 (MA10) virus to infect mice of different age groups (3, 6, and 20 Months). In this study, we found that aged mice showed evidence of viral neurotropism, prolonged viral infection, increased expression of tau aggregator FKBP51, interferoninducible gene Ifi204, and complement genes like C4 and C5AR1. Brain histopathology also showed the AD signature including tau-phosphorylation, tau-oligomerization, and alpha-synuclein expression in aged MA10-infected mice. The results from gene expression profiling of SARS-CoV-2 infected and AD brains and studies with MA10 aged mice show that COVID-19 infection increases the risk of AD in the aged population. Furthermore, this study helps us to understand the crucial molecular markers that are regulated during COVID infection that could act as major players in developing ADRDs. Future studies will be involved in understanding the molecular mechanisms of ADRD in response to COVID infection and developing novel therapies targeting AD.

Neurogastroenterology & Motility Manifestations After COVID-19 Infection: A Case Series

Introduction: In a subset of Covid19-convalescent patients, a multitude of long-term sequelae are increasingly being reported. We report 4 cases with varying neuro-GI and motility manifestations after recent COVID-19 infection. Case Description/Methods: Case 1: A 23-year-old man contracted COVID-19 and had a protracted course of respiratory illness. Despite resolution of respiratory symptoms and dysgeusia, he continued to experience early satiety, postprandial nausea, vomiting and unintentional weight loss. Gastric Emptying Scan (GES) revealed gastroparesis (Figure A). Dietary modification and metoclopramide led to symptomatic improvement. Case 2: A 39-year-old woman with migraines, suffered from Covid-19 infection where anosmia and respiratory symptoms lasted for 2 weeks. Despite resolution of initial symptoms, she started experiencing nausea and vomiting, and reported stereotypical symptoms with complete absence of vomiting between episodes. Endoscopic examination, CT head and GES were normal. Urine tox screen was negative for cannabinoids. She responded favorably to amitriptyline and ondansetron. Case 3: A 47-year-old man started experiencing severe constipation associated with abdominal pain and bloating soon after being diagnosed with COVID-19. Three months after resolution of respiratory symptoms, in addition to constipation, he began reporting postprandial fullness, early satiation and epigastric pain. GES showed gastroparesis ( figure B) and a Sitzmarks Study revealed delayed colonic transit (Figure C). Prucalopride was started, leading to improvement in symptoms. Case 4: A 74-year-old woman with obesity and diabetes, was hospitalized and intubated for severe respiratory distress due to COVID-19. After discharge, she had persistent symptoms of brain fog, fatigue, dyspnea as well as diarrhea and abdominal cramping, persisting despite loperamide and dicyclomine. C. difficile toxin, random colonic biopsies and H2 breath test were unremarkable. Her symptoms eventually improved with rifaximin. Discussion(s): We report 4 cases with post-COVID gastroparesis, cyclical vomiting syndrome, pan-gut dysmotility, and post-infectious IBS phenotypes.The pathophysiology of post-infectious-gut-brain disorders is still obscure. The current conceptual framework implicates acquired neuropathy, altered motility, intestinal barrier disruption and persistent intestinal inflammation. Similar pathophysiology may be involved in COVID-19 infection leading to sustained neurogastroenterological dysfunction and gut dysmotility.

One-Year Long-Term Follow up for Post-Acute Sequelae of Covid-19 Pots Patients

Background: Persistence of orthostatic tachycardia, palpitations, and fatigue beyond 4 weeks of an acute COVID-19 infection has been termed Post-Acute Sequelae of COVID-19 (PASC) POTS. We have previously reported 6-month outcomes of PASC POTS. Long-term management and outcomes of these patients is unknown. Objective(s): To examine the long-term management and outcomes of PASC POTS patients. Method(s): We conducted a retrospective study of all patients who were diagnosed with POTS at Cardiology, Neurology, and Rehabilitation Post-COVID clinic after a COVID-19 infection between March 1, 2020, and November 1, 2022, at the University of Texas Health San Antonio. We examined COVID history, POTS diagnosis, management, and one-year outcomes of post-COVID POTS patients. Result(s): In 42 patients that were diagnosed with PASC POTS, 33 had a one-year follow-up. 100% were female, 60.6% were Caucasian. Average age was 40.6 + 11 years while the average BMI was 31.9 + 10.4 kg/m2. The most common symptoms were fatigue (87.9%), palpitations (75.7%), brain fog (72.7%), orthostatic tachycardia, exercise intolerance, and dyspnea (70%). The mean heart rate change with 10-minute standing test was 42.68 + 26.73 beats per minute. At 12-months follow-up, the most common symptom was still fatigue (66.7%), palpitations (45.5%), orthostatic tachycardia, and orthostatic intolerance (42.4%). All patients were managed with increased salt and fluid intake, lower compression stockings and rehabilitation. Fifty five percent of patients were treated with Enhanced External Counter Pulsation (EECP), 42% were treated with beta blockers, 18% with fludrocortisone, 15% with midodrine, and 15% with Pyridostigmine. At 1 year follow-up, 33% of patients reported improvement in their symptoms, 33% reported worsening of symptoms, 24% reported stable symptoms, and 9% had resolution. Conclusion(s): PASC POTS patients continue to experience adverse symptoms even at one year. Physical therapy and rehabilitation and pharmacological therapy appear improve symptoms in a minority of patients.Copyright © 2023

Hepatotoxicity From Marijuana Gummies

Introduction: We report a case of drug-induced liver injury (DILI) induced by cannabis gummies containing Corydalis Rhizome. Case Description/Methods: A 37-year-old female presented to her primary care clinic with recurrent fevers, night sweats, and myalgias for 7 weeks accompanied by eye redness, brain fog, headache, nausea, and abdominal pain. She denied rashes, tick-bites, cough, dyspnea, chest pain, joint swelling, or genitourinary symptoms. Past medical history was notable for IBS, migraines, and anxiety. She reported edible marijuana use four times a week, rare alcohol use, and denied tobacco use. She denied a family history of liver disease. Physical exam was notable for tachycardia to 110 and scleral injection with the remainder of vitals and exam unremarkable. Initial labs were notable for AST 61, ALT 44 and CRP of 12. CBC, BMP, urinalysis, ESR, blood cultures, blood smear for parasite screen, tests for Lyme disease, Babesia, Tularemia, Anaplasma, Ehrlichia, Rickettsia, EBV, HIV, RPR, ANA, CMV, parvovirus B19, and chest x-ray were all negative. The patient was referred to infectious disease with further testing for West Nile, Leptospira, lymphocytic choriomeningitis virus, and COVID-19 returning negative. Repeat LFTs showed worsening transaminitis with ALT 979 and AST 712, alkaline phosphatase 88, total bilirubin 0.7, and albumin 4.9. Hepatitis workup including hepatitis A, B, and C, HSV, EBV, VZV serologies, AMA, ASMA, antiLKM Ab, acetaminophen level, INR, iron panel, CPK, TSH, and abdominal ultrasound were all normal. It was later discovered that her marijuana gummies contained Corydalis rhizome extract known to be hepatotoxic. Cessation of this drug was strongly advised. She was discharged with hepatology follow-up and underwent a liver biopsy showing patchy periportal and lobular inflammation with extension across the limiting plate, hepatocyte injury and apoptosis, and increased lipofuscin for age compatible with mild to moderate hepatitis. She had complete recovery after cessation of Corydalis-containing gummies. (Figure) Discussion: Our patient consumed '1906 Midnight', an American cannabis brand containing Corydalis rhizopus 100 mg, advertised to improve sleep, pain, and have a liver protective effect. A Korean systematic review on herbal-induced liver injury reported that Corydalis was the 3rd most frequent causative herb, with 36 cases. Although there are several personal accounts on social networking sites and other websites, there are no American-based publications reported on DILI from Corydalis. (Table Presented).

Computerized Cognitive Testing in Long COVID Patients With Prolonged Symptoms of Brain Fog and Cognitive Impairment

Purpose: To identify cognitive impairments in patients (pts) with long COVID using the Cambridge Brain Sciences (CBS) computerized cognitive test (CCT) commonly used to evaluate cognitive function after concussions and traumatic brain injuries. Method(s): Retrospective review from May 2021-Sept 2022 of 16 (4 male, 12 female) patients with long COVID, ages 13- 66 (avg 46), with average of 10 months from COVID infection to time of evaluation. Cognitive (cog) performance and concussion profile symptom scores were assessed with CBS CCT and the Concussion Clinical Profiles screening tool (CP screen) respectively. Result(s): The total CP symptom score average was 34/89 (ranging 7-68) in the cohort. The predominant profile was cog fatigue scoring (1.8/3) on average. CBS CCT tested cog impairment (CI) and was divided into 5 categories (0-4): no CI, borderline (scores between the 21st-30th percentile), mild (1 test < / = 20th percentile), moderate (2-3 tests < / = 20th percentile), and severe CI (>3 tests,/520th percentile). Data showed 2/16 (13%) patients had no CI, 5/16 (31%) had borderline CI, 5/16 (31%) had mild CI, 3/16 (19%) had moderate CI, and 1/16 (6%) pts had severe CI. Although not significant, there was a positive correlation between CI and cog profile score (P = 0.3149) when performing a linear regression test. Deficits were most common in the CBS CTT composites of grammatical reasoning/verbal processing and attention, with 4/16 patients scoring < 20th percentile for each test. The lowest average percentile scores for the cohort were in visuospatial processing and verbal short-term memory. Conclusion(s): Most long COVID patients assessed with CCT demonstrated signs of CI, in particular in verbal processing and memory, followed by visual processing. In addition to the CCT results illustrating CI, the top CP profile of cognitive fatigue in this cohort suggests that the brain fog experienced by long COVID patients may be quantified. Significance: CCT may be a useful tool in assessing and quantifying those with Long COVID with chronic symptoms of cognitive fog, fatigue, or impairment. Targeted interventions aimed at specific deficits can aid in treatment and recovery.

Worse Arterial Stiffness, and Not Endothelial Dysfunction, Is Associated with Pasc

Background: COVID-19 survivors can experience lingering symptoms known as PASC that appear in different phenotypes. The etiology remains elusive and endothelial dysfunction has been postulated as a main driver of PASC. Method(s): Prospective cohort including COVID- and COVID+ with (COVID+PASC+) or without (COVID+PASC-) PASC. We measured endothelial function using Endopat, an FDA approved test, with derived reactive hyperemic index RHI (endothelial dysfunction<=1.67) and arterial elasticity (augmentation index standardized at 75 bpm or AI@75;(lower =better). PASC symptoms were categorized into three non-exclusive phenotypes: Cardiopulmonary CP (postexertional malaise, shortness of breath, cough, palpitations), Neurocognitive N (change in smell/taste, neuropathy, 'brain fog', headache), and General G (fatigue, gastrointestinal or bladder problems). Result(s): We included 491 participants with 109 of the 186 with confirmed COVID+ experiencing PASC. Median number of days between COVID diagnosis and study visit was 249 days (IQR: 144, 510). Among COVID+PASC+, the median number of symptoms was 7.0 (IQR: 3.0,13.0);97 experienced symptoms categorized as G, 90 as N, and 87 as CP. COVID+ PASC+ had the lowest RHI (1.77+/-0.47) and the largest proportion [46.79% (n=51)] with RHI<=1.67 (Figure). AI@75 was the lowest in COVID- (3.11+/-15.97) followed by COVID+PASC- (3.57 +/- 16.34). Within COVID+PASC+, the mean AI@75 among G was 10.11+/-14.85, 11.36+/-14.67 with N, and highest (12.01 +/- 14.48) with CP. Symptoms' number was positively associated with AI@75 (p=0.01). The estimated mean difference in AI@75 between COVID+ PASC+ with CP and COVID+ PASC- was 8.44+/-2.46 (p=0.001), between COVID+ PASC+ with CP phenotype and COVID- was 8.9+/-1.91 (p< .0001), and between COVID+ PASC+ with CP phenotype and COVID+ PASC without CP phenotype was 7.51+/-3.75 (p=0.04) Conclusion(s): PASC was associated with worse arterial elasticity and within PASC, the cardiopulmonary phenotype had the highest arterial stiffness. (Figure Presented).

Adaptive Immunity Dysregulation Is Associated to the Development of Long Covid

Background: The pathogenetic mechanisms behind the development of long- COVID (LC) are largely unknown. Because both plasma SARS-CoV-2 RNAemia and dysregulated immunity have been correlated with COVID-19 severity, we evaluated whether they are associated with LC. Method(s): We consecutively enrolled unvaccinated hospitalized COVID-19 patients during acute-COVID-19 (T0) in March-October 2020 who either developed LC at a follow-up visit 2-3 months from virologic clearance (T1) or did not. LC was defined as persistence >=2 months after recovery of >=1 symptom: anosmia, dysgeusia, fever, gastrointestinal symptoms, dyspnoea, fatigue, musculoskeletal pain, muscle weakness, brain fog. We measured: SARS-CoV-2 RNAemia (RT-qPCR, log10(copies/mL)), magnitude (ELISA, AUC) and functionality (pseudovirus neutralization, ID50;Fc-mediated functions, %ADCC) of SARS-CoV-2-specific antibodies, SARS-CoV-2-specific B and CD4-T-cells (Immunophenotype, AIM and ICS assays). Result(s): We enrolled 48 COVID-19 individuals, 38/48 (79.2%) developed LC (LC+) and 10 did not (LC-). LC+ and LC- had similar co-morbidities and symptoms in the acute phase (Fig.1A), and the majority showed a radiologically documented SARS-CoV-2 pneumonia. The SARS-CoV-2 RNAemia did not differ between groups at both time points. The levels of RBD-specific Abs, as well as their functionality, appeared to increase over time in the LC- group but not in the LC+ (Fig.1B-D). Similarly, a trend towards increased RBD-specific B-cells was observed over time in the LC- group but not in LC+ (Fig.1E). B-cell immunophenotyping showed a significant increase over time of classical memory B cells (MBCs) at the expenses of activated MBCs (Fig.1F-G) as well as an IgA class-switching in the LC- group compared to LC+ (Fig.1H-I). Furthermore, LC+ showed a faster decline of SARS-CoV-2-specific (CD69+CD137+) CD4- TEMRA and CD4-TEM (Fig.1L-M). Finally, IFN-gamma-producing TREG of LC- individuals increased over time (Fig.1N). Conclusion(s): Acutely ill, hospitalized COVID-19 patients developing LC feature a dysregulated SARS-CoV-2-specific humoral as well as B- and T-cell response, in both magnitude and functionality, suggesting a link between dysregulated SARS-CoV-2-specific adaptive immunity and LC development. The fine understanding of the factors contributing to such dysregulation in LC patients is strongly needed, that might further inform targeted therapeutic interventions. (Figure Presented).

Differential Association of Cytomegalovirus with Acute and Post-Acute Covid-19

Background: Asymptomatic Cytomegalovirus (CMV) infection reshapes systemic immune responses and its replication can be both a consequence and cause of inflammation. As CMV resides in the same tissues affected by SARSCoV- 2, we hypothesized that asymptomatic CMV co-infection might modify the pathogenesis of both acute and post-acute COVID-19. Method(s): Participants had current or prior nucleic acid-confirmed SARS-CoV-2 infection in the COVID-19 Multi-Phenotyping for Effective Therapies (COMET, n=219), Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC, n=244) or the Long-term Impact of Infection with Novel Coronavirus (LIINC, n=327) cohorts. We assessed the relationship between CMV serostatus and odds of hospitalization and plasma SARS-CoV-2 N antigen levels during acute COVID-19 as well as post-acute "Long COVID" symptoms, defined as >=1 of 32 COVID-19-attributed symptoms present at least 60 days following initial symptom onset. Result(s): Among 758 participants, 518 were hospitalized for their acute COVID-19 episode. CMV seropositivity was independently associated with a 1.9-fold increased odds of hospitalization for acute COVID-19, after adjustment for age, sex, race, ethnicity, HIV status, prior autoimmune disease, diabetes, and obesity (p=0.01, A). Among those hospitalized, CMV seropositivity was also associated with higher plasma SARS-CoV-2 N antigen levels (median 936 vs. 323 pg/ml, P=0.03, B), which remained significant after adjustment for potential confounders, but not with ICU admission (n=209), death (n=58), or thrombotic events (n=31). In contrast to its relationship to acute COVID-19 disease severity, CMV seropositivity was independently associated with a 48% decreased odds of having neurocognitive Long COVID symptoms such has headache and brain fog 4 months after initial COVID-19 diagnosis (P=0.036). Conversely, serologic evidence of Epstein-Barr Virus (EBV) reactivation and HIV both increased the odds of these symptoms (C). Conclusion(s): CMV seropositivity is associated with a 1.9-fold higher odds of hospitalization in people with acute COVID-19 and a nearly 3-fold higher SARS-CoV-2 antigen burden in hospitalized patients. In contrast, CMV seropositivity is associated with a decreased odds of neurocognitive Long COVID symptoms, while other chronic viral co-infections like EBV reactivation and HIV are associated with an increased odds of this complication. The biologic mechanisms mediating these relationships are unknown, but warrant further investigation. (Figure Presented).

Post-COVID-19 cardiovascular complications and their association with clinical characteristics, symptoms and comorbidities - the LATE-COVID study

Background: Among many complications of coronavirus disease 2019 (COVID-19) there is a wide range of cardiovascular (CV) problems ranging from mild to severe ones. Even asymptomatic patients and those with mild course of COVID-19 may develop severe CV complications. Factors leading to such state have not been extensively studied so far. Purpose(s): We aimed to assess which factors were linked to the severe complications of COVID-19. Method(s): We included 200 consecutive patients admitted to the Department of Cardiology and Adult Congenital Heart Diseases of the Polish Mother's Memorial Research Institute (PMMHRI) due to post-Covid cardiovascular complications. SARS-CoV2 infection was confirmed with real-life PCR testing. Laboratory tests, 24-hour ECG monitoring and echocardiography were performed in all patients from the investigated group. For the purposes of our study severe complications were defined as: Myocarditis, a decrease of ejection fraction >10% from the pre-disease value, thromboembolic complications, angina pectoris requiring myocardial revascularization and the new onset of atrial fibrillation of supraventricular tachycardia. Some patients presented more than one of the above. Statistical analysis was performed using the software Statistica v.13 (TIBCO Software Inc., Palo Alto, CA, USA). Data were presented as mean +/-SD or median (25th- 75th percentile) for continuous variables and as proportions for categorical variables. Comparisons between groups were performed using Student's t-test for independent variables and the Mann-Whitney U test or chi2 test with Yates's correction, as appropriate. For all calculations p-values <0.05 were considered statistically significant. Result(s): Finally, we included 200 consecutive patients (aged 54+/-16 years, 76 males - 38%), hospitalized for COVID-19 complications after a median 3 (2-6) months following the acute phase of infection. On admission patients presented with dyspnea (23%), impairment of exercise tolerance (47%), chest pain (32%), increase in blood pressure (29%), palpitations (25%), weight loss (13%), brain fog (6%), general malaise (11%), headache (5%), limb pain (13%), swelling (14%). Severe complications of COVID-19 were diagnosed in 31 patients (16%).Taking into consideration symptoms, the presence of severe COVID-19 complications was significantly associated with dyspnoea and deterioration of exercise tolerance. In comparison to patients with mild complications, severe ones were linked to age (the older patients, the higher risk), previous history of heart failure and diabetes mellitus. We did not observe statistically significant differences in severity of complications depending on smoking status (Tables 1 and 2). Conclusion(s): Previous history of heart failure and diabetes mellitus as well as symptoms (dyspnoea and deterioration of exercise tolerance) along with older age are related to more severe complications following COVID- 19.

'Long covid' is more common, underestimated, and 'core' health issue in post covid care setting: study of 6000 cases in tertiary care setting in India

Methods: observational study, included 6000 COVID-19 indoor cases confirmed with RT-PCR. Retrospective analysis with treatment records, laboratory markers as IL-6, D-dimer, Ferritin, LDH, BSL, HBA1C. All cases undergone thorough interview in 'post covid care' outdoor setting regarding symptomatology, documnted vital signs abnormality, & workup as HBA1C, BSL, TFT, KFT, ECG, chest x-ray, HRCT thorax, BMD, Echocardiography, MRI brain whichever is necessary. Statistical analysis by using Chi square test and ANOVA. Observations: Long covid manifestations were documented in 36.06% (2517/6000) post COVID cases as- Fatigue 41.95%, dyspnea 35.98%, cough 31.96%, chest discomfort 26.95%, anosmia 8.76%, joint pain & headache 11.96% , dizziness, vertigo&insomnia 22.95% &alopecia 4.18% cases, Lung fibrosis in 16.66%, minimal lung abnormality 23.65%, pulmonary embolism 7.18% cases, palpitations 25.56%, chest pain 11.3%, arrythmias 5.53%, cardiac dysfunction 24.31%, PTSD 28%, Impaired memory with or without poor concentration (brain fog) 24.03%, Anxiety and or depression 6.33%, Reduction in quality of life 33%, Diabetes mellitus-new onset26%, transient34%, uncontrolled27%, Osteoporosis38.08%, thyroid dysfunction12.1%. CT severity score, Intensive care treatment with or without oxygen and or ventilator use & Laboratory parameters (D-dimer, IL6, LDH, Ferritin) during hospitalization has significant association with long covid manifestations (p<0.00001) Conclusion(s): Long covid in underestimated, improperly evaluated and halfheartedly treated during follow-up. All treated cases needs prompt evaluation, more awareness regrding its manifestations and its impact on quality of life is must.

Impact of Post-COVID-19 or Long COVID-19 on Cognition and Health

COVID-19 manifests itself as an acute but also as a chronic illness. Post-COVID-19 condition or Long COVID-19 is real. It is evident that it is a serious condition that can have at times irreversible health consequences. About 15% of adults who have had COVID-19 experienced symptoms three months or more after their initial infection. Women are twice as likely than men to get long Covid. People of ages 40-49 are more likely than other age groups to get long COVID-19. The symptoms range in severity and include brain fog, muscle pain, trouble breathing, extreme fatigue, gastrointestinal problems, and heart palpitations. It can accelerate the onset of other chronic conditions like diabetes and heart disease. So far, there is no consensus on the definition of the condition or how to diagnose and treat it. COVID-19 vaccines can reduce the risk of developing long-COVID symptoms. This paper discusses the impact of Long Covid on cognition and likely factors that are at play.

Clinical experience with the alpha2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive deficits in "Long-COVID19"

Background: Prolonged cognitive deficits ("brain fog") following COVID19 infection (long-COVID) are common and debilitating, yet there are currently no approved treatments. Cognitive impairment particularly targets the working memory and executive functions of the prefrontal cortex (PFC). The PFC has unusual neurotransmission and neuromodulation that render it vulnerable to stressors, and basic research has identified mechanisms that protect PFC connections. Based on the basic neuroscience data, we tried a combined open label treatment to bolster prefrontal function: the alpha2A-adrenoceptor agonist, guanfacine, which strengthens prefrontal connectivity, and the anti-oxidant, N- acetylcysteine (NAC), which protects mitochondria and reduces kynurenic acid blockade of NMDA receptors. Case report: Twelve patients with "brain fog" including difficulties in executive functions were treated with guanfacine (1mg, PO bedtime for the first month, increased to 2mg after 1 month, if well-tolerated) and 600 mg NAC daily. Guanfacine+NAC improved cognitive abilities in eight of the twelve patients;four patients discontinued therapy, two for unspecified reasons and two due to hypotension and/or dizziness, common side effects of guanfacine. Those who stayed on guanfacine+NAC reported improved working memory, concentration, and executive functions, including a resumption of normal workloads. One patient briefly stopped taking guanfacine due to a hypotensive episode and reported a return of cognitive deficits that abated with resumed guanfacine treatment. Conclusion(s): Although placebo-controlled trials will be needed to more rigorously demonstrate efficacy, as these agents have established safety, they may be immediately helpful in treating the large number of patients suffering from prolonged cognitive deficits following COVID19 infection.Copyright © 2022 The Author(s)

COVID-19 Outcome: A One Year Follow-Up Study of Patients who Recovered from COVID-19 at Lung Center of the Philippines

Introduction: To date, the Philippines had tallied more than 3 million COVID-19 cases with 91.5% recovery rate and 1.72% mortality rate. Some patients who recovered from COVID-19 are left struggling with symptoms which persist through weeks, months and even a year. Objective(s): To determine the clinical outcome after 1 year of COVID-19 recovered patients in terms of persistent symptoms, functional capacity, and survival status and their relationship with disease severity. Method(s): This is a cross sectional-analytical study. Subjects include those who were discharged improved from April - August 2020 at Lung Center of the Philippines. Their clinical outcome after 1 year which include persistent symptoms, functional capacity and survival status were determined and analyzed. Result(s): A total of 100 subjects were included in this study. Forty-three subjects had persistent symptoms. Fatigue (28.6%), depression (13.3%), and brain fog (11.2%) were the most frequently reported symptoms. Ninety-two (92.9%) patients had none to negligible functional capacity limitations. Ninety-seven (97%) patients survived after 1 year. Higher proportion of patients with persistent fatigue and difficulty of breathing were noted as the severity increases. Higher proportion of patients with functional scale 1-2 were noted in moderate severity group as compared to the severe and critical severity group. Conclusion(s): This one-year follow-up study of COVID-19 recovered patients revealed high proportion of survivors, very few with significant functional capacity limitations, and some with persistent symptoms. Favorable clinical outcomes after 1 year were evident in less severe disease.

Co-Occurring Physical Health Challenges in Neurodivergent Children and Young People: A Topical Review and Recommendation

Background: Neurodivergence has been established as associated with a significant number of co-occurring physical conditions, particularly for autistic individuals who are at risk for increased pain, hypermobility (including Ehlers-Danlos Syndrome) and gastrointestinal problems. However, data, so far, has been focused on adults and generally limited to discussions of condition prevalence alone. Method(s): The following article will present a topical review of the literature considering evidence for increased physical health concerns within neurodivergent populations, particularly autistic individuals, with a focus on the impact that these physical health concerns may have in an educational setting. Results and discussion: The impact of physical health concerns within neurodivergent populations in an educational setting may be concerning. Such populations may face a range of challenges in obtaining appropriate support for physical conditions. We discuss a number of said challenges including;communication challenges, misattributing physical health symptoms as a part of neurodivergence, and a history of not being believed, which limits symptomatic reporting. We further consider the potential impact these physical health concerns may have on scholastic and social development, such as impacts for attainment and attendance. Furthermore, we provide recommendations for teachers, parents/carers and other allied professionals in young people's lives, on supporting young neurodivergent people with physical health concerns.Copyright © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Developing a Long-COVID follow-up protocol in a Portuguese tertiary hospital

About a third of COVID-19 patients experience ongoing symptoms that have been referred to as long-COVID. In cooperation with Rehabilitation Medicine and Psychology departments, we developed a protocol for evaluation and further referral of the long-COVID patients that sought our Emerging Infectious Diseases (EID) consultation. The aim was to characterize the symptoms according to their frequency and to develop a screening tool that allows referral to intervention programs. Long-COVID was defined as persistent or new-onset symptoms 12 or more weeks after initial infection. In our EID consultation all patients answered a questionnaire regarding the evolution and impact on daily activities of the persistent symptoms, using a 6-point Likert scale. Participants (n=42) had a mean age of 44.8 years (IQR 18.8) and 76% were female. Ninety-five percent of the patients had a mild to moderate course of acute infection. Fatigue (78.6%), physical capacity impairment (74%), brain fog (62%), anxiety and sleep disorders (52% each) were the most frequently reported symptoms. Regarding the impact of persistent symptoms, 50% of the patients with anxiety disorders, 69% of the ones reporting brain fog and 71% of those with physical capacity impairment reported being moderately or more affected on their daily activities by that symptom. When asked "Did you recover your previous health status?" all patients answered no. As the number of new infections continues to rise worldwide, long-COVID will be a challenging burden to healthcare systems and societies. Establishing a follow-up protocol and a reliable screening tool will allow us to reach a wider population and also promote a better and patient-centered use of medical resources.

A case of cerebral amyloid angiopathy related inflammation after vaccination against SARS-CoV-2

Background: Cerebral amyloid angiopathy related inflammation (CAA-RI) is a neuroinflammatory disease that is associated with perivascular amyloid- deposition. Case presentation: A middle-aged woman with a remote history of autoimmune disorders presented with unilateral migraine headaches, dizziness, unsteadiness, and fogginess 36 hours after administration of mRNA vaccine against SARS-CoV-2. Initially, unilateral leptomeningeal enhancement on MRI on the same side of headaches raised suspicion for leptomeningeal involvement of her known cutaneous T-cell lymphoma in remission. After two relatively unremarkable CSF analyses, she underwent a brain biopsy which showed amyloid deposits in vessels instead of lymphomatous infiltration. She was diagnosed with CAA-RI, and the headache and cognitive symptoms responded well to high-dose corticosteroids with a slow taper. Discussion/conclusion: We review the clinical literature of CAA-RI and its potential association with amyloid-related imaging abnormalities (ARIA) after administration of immunotherapy against amyloid.Copyright © 2022

Neurological complications of SARS-CoV-2 infection.

SARS-CoV-2 virus was first identified in 2019 in Wuhan (China) and is responsible for the ongoing COVID-19 pandemic. Although the virus causes mild, transient symptoms of an upper respiratory tract infection in most cases, it can also lead to severe pneumonia, respiratory failure and/or death. Approximately 85% of patients experience central and peripheral neurological symptoms. In the acute phase of the disease, ischaemic strokes, intracranial haemorrhages, meningitis and encephalitis, acute demyelinating diseases and acute inflammatory polyneuropathies may occur. However, mild neurological symptoms that can persist for months and significantly affect daily functioning are much more common. These include headache and dizziness, olfactory and gustatory dysfunction, mild cognitive disturbances, as well as depressive, anxiety, and sleep disorders. Some of them are encompassed by popular terms "post-covid syndrome" and "brain fog." The pathogenesis of neurological complications of SARS-CoV-2 infection is still not fully understood;overproduction of cytokines induced by viral infection may be of great importance. There is no causal treatment, while symptomatic treatment is of limited effectiveness. Primary prevention in the form of SARS-CoV-2 vaccinations is of great importance. In the following review, we would like to present the current knowledge on epidemiology, pathology, pathogenesis and treatment of neurological complications after SARS-CoV-2 infection. Further multi-centre, large-scale clinical studies are necessary to identify the exact pathogenetic mechanismsCopyright © 2022 Sawicka et al.