Challenges and strategies with international recruitment in early phase gene therapy trials

The Children's NIHR Clinical Research Facility at Royal Manchester Children's Hospital has been involved in numerous early phase gene therapy trials for diseases such as GM1 gangliosidosis, Gaucher disease, MPSIIIA and MPSII. These trials have necessitated international recruitment which brings challenges for both site and families. In addition, we also actively recruited participants during the Covid-19 global pandemic, amplifying these challenges. A typical patient journey on one of these trials would involve being approached soon after diagnosis due to the rapid progression of these diseases and the need for early intervention. The family would then relocate to the UK with relatively short notice and commence an intensive period of screening involving a lot of extensive information for them to retain and invasive procedures for the patient. Some of these families will speak no English at all which is an additional barrier to managing the parental anxiety and expectations of the trial and its outcome. Once eligibility is confirmed the families are then faced with an extended stay in the UK without the support of their extended family/community. This impacts parent's employment and other siblings who may or may not be with them and who may also be affected by the same disease. Following administration of the gene therapy, participants then commence intensive follow up often associated with immunosuppressants. Close working with the local clinicians is essential for patient safety and trial integrity. Good engagement with families once they have returned to their home country is vital in obtaining continuing trial data and ensuring retention and compliance with attending future visits. Follow up visits are essential for safety and efficacy data for the progression of gene therapy trials. Travel restrictions brought about by the covid 19 pandemic exacerbated these challenges but with good communication and engagement we have mostly overcome them.

ENDOTHELIAL INFLAMMATION AND DYSFUNCTION INDUCED BY SARS-COV-2 SPIKE PROTEIN 1 INVOLVE ADAM17 AND INTERFERON ACTIVATION PATHWAYS

Objective: COVID19 is associated with vascular inflammation. IFN-alpha (IFNa) and IFN-lambda3 (IFNl3) are potent cytokines produced in viral infections. Their effects involve interferon-stimulated genes (ISGs) and may influence expression of angiotensin-converting enzyme 2 (ACE2), the receptor for S-protein (S1P) of SARS-CoV-2. We hypothesized that S1P-induced immune/inflammatory responses in endothelial cells (EC) are mediated via IFN-activated pathways Design and methods: Human ECs were stimulated with S1P (1 mg/mL), IFNa (100ng/mL) or IFNl3 (100IU/mL). Because ACE2, ADAM17 and TMPRSS2 are important for SARS-CoV-2 infection, we used inhibitors of ADAM17 (marimastat, 3.8 nM), ACE2 (MLN4760, 440pM), and TMPRSS2 (camostat, 50 mM). Gene and protein expression was investigated by real-time PCR and immunoblotting, respectively. Vascular function was assessed in mesenteric arteries from wild-type (WT) normotensive and hypertensive (LinA3) mice and in ISG15-deficient (ISG15KO) mice. Results: S1P increased expression of IFNa (3-fold), IFNl3 (4-fold) and ISGs (2-fold) in EC (p < 0.05). EC responses to IFNa (ISG15: 16-fold) were greater than to IFNl3 (ISG15: 1.7-fold) (p < 0.05). S1P increased gene expression of IL-6 (1.3-fold), TNFa (6.2-fold) and IL-1b (3.3-fold), effects that were amplified by IFNs. Only the ADAM17 inhibitor marimastat inhibited S1P effects. IFNa and IFNl3 increase protein expression of ADAM17 (27%) and TMPRSS2 (38%). No changes were observed on ACE2 expression. This was associated with increased phosphorylation of Stat1 (134%), Stat2 (102%), ERK1/2 (42%). EC production of IL-6 was increased by IFNa (1,230pg/mL) and IFNl3 (1,124pg/mL) vs control (591pg/mL). Nitric oxide generation and eNOS phosphorylation (Ser1177) were reduced by IFNa (40%) and IFNl3 (40%). Vascular functional responses demonstrated that endothelium-dependent vasorelaxation (% Emax) in vessels from WT-mice stimulated with IFNa (67%) and IFNl3 (71%) were reduced vs control (82%) (p < 0.05). Responses were not altered in vessels from ISG15KO mice. Increased contraction was observed only in vessels from hypertensive mice treated with IFNa (9.1 ± 0.5mN vs control: 7.3 ± 0.3mN) (p < 0.05). Conclusions: In ECs, S1P, IFNa and IFNl3 increased ISG15 and IL-6 by mechanisms dependent on ADAM17. IFNs amplifies endothelial cell inflammatory responses and induced vascular dysfunction through ISG15-dependent mechanisms, with augmented effects in hypertension. Our findings demonstrate that S1P induces immune/inflammatory responses that may be important in endotheliitis associated with COVID-19. This may be especially important in the presence of cardiovascular risk factors, including hypertension.

Pandemic modelling: The impact of social distancing in Nordic countries

Background: Without pharmacologic interventions, the preferred strategy to combat COVID-19 is to slow the virus' spread via social distancing measures. The components of social distancing include: school closure, restrictions on gatherings, non-essential business closure, stay at home orders and limitations on travel. Most countries have implemented many of these restrictions. Conversely, Sweden has not initiated these restrictions and instead has recommended that citizens avoid mass gatherings, which presents an opportunity to examine the effects of the components of social distancing on mortality in Nordic countries. Purpose: Investigate the impact of social distancing measures on fatalities associated with COVID-19. Method: COVID-19 fatalities, as reported by the World Health Organisation, were recorded for each of the Nordic countries from 6th February 2020 to 30th April 2020. The fatalities were compared using a Cox proportional hazard regression analysis. Results: The normalised fatalities ranged significantly (1.87 to 129 deaths/population/km2) in the Nordic countries. Sweden was found to have a significantly higher risk of COVID-19 related mortality at the α=0.05 level as compared to Finland (HR=0.15;p<0.001) and Norway and Denmark (HR=0.23;p=0.002). Conclusion: The population-density normalised mortality in Sweden was significantly greater than other Nordic countries, possibly due to differences in the implementation of social distancing policies.

Longitudinal Alpha-gal IgE Levels in a University of Virginia Employee Cohort

Rationale: The alpha-gal syndrome (AGS) is caused by IgE to galactose-α-1,3-galactose (α-Gal) and is strongly linked to tick bites. To date there have been limited studies on the natural history of AGS and α-Gal sensitization. Here we monitored α-Gal IgE levels over time among sensitized individuals in an employee vaccine cohort unselected for allergic disease. Methods: University of Virginia employees were recruited for an IRB-approved COVID-19 vaccine study. Study subjects provided blood samples and answered a questionnaire capturing medical history including diet and allergy history. α-Gal IgE (cut-off 0.1 kU/L) and total IgE were assayed in banked serum by ImmunoCAP and slopes calculated by linear regression. Results: Of the 266 subjects in the study, 46 (17%) were sensitized to alpha-gal. 38 sensitized subjects had two or more samples separated by at least 100 days. Of these, 68% were female, median age was 55.6 and α-Gal IgE levels dropped over time in 25 (66%). Median rate of decay among subjects with decreasing titers was 53%/year (IQR 46-61). Of the 38 sensitized subjects, 12 (32%) reported interval tick bites over the course of the study. The correlation between α-Gal IgE slopes and total IgE slopes was moderately strong (Pearson's R = 0.60, P<0.001). Conclusions: α-Gal IgE levels decrease over time in many subjects, with a median decay rate of 53%/year. Although α-Gal specific IgE is often only a small fraction of total IgE, both track closely with each other over time, likely a reflection of changes in IgE relating to tick bites.

106. Adolescent Social Networks and School Engagement Across the High School Transition

Purpose: Attending and meaningfully engaging in school is a critical component of adolescence with broad implications for future health and well-being. Social network analysis offers powerful techniques to examine how the quality and structure of social relationships affect adolescent health and education. Peer and adult relationships impact adolescent health-affecting behaviors such as substance use and violence involvement, with potential for beneficial or deleterious effects. Social networks may similarly confer risk or protection for school engagement, an urgent issue of adolescent health considering COVID-19-related school disruptions. We describe adolescent social network quality and structure and examine associations between social network characteristics and school engagement during the transition from middle to high school. Methods: We analyzed data from an ongoing randomized trial of the Advancement via Individual Determination (AVID) college readiness program across 5 public high schools in Southern California. Participants completed baseline surveys at the end of 8th/beginning of 9th grade and follow-up surveys at the end of 9th grade. The Student Engagement Instrument assessed school engagement and egocentric social network surveys assessed adolescent social network quality (e.g., network composition, peer behavior) and structure (e.g., centrality, density). Multilevel mixed-effects models examined associations between baseline social network characteristics and concurrent and future school engagement. Models were adjusted for gender, ethnicity, prior AVID participation, study arm, and baseline school engagement as appropriate. Results: Baseline participants (n=431) were 60.6% female and 82.8% identified as Latinx. 418 participants completed follow-up surveys;retention rate=97.0%. Mean school engagement was 3.26 at baseline (SD=0.53;range 1-4) and 3.14 at follow-up (SD=0.52). Across all individuals in participants' social networks, 68.7% were peers, 24.5% were adults, and 55.4% were identified as sources of support. Across all peers in participants' social networks, 9.1% engaged in substance use and 82.6% were highly engaged in school. Overall social network characteristics associated with concurrent school engagement included a greater proportion of coaches (β=3.01;95%CI 0.01-6.02) and sources of support (β=0.20;95%CI 0.03-0.37). Peer social network characteristics associated with concurrent school engagement included a greater proportion of peers highly engaged in school (β=0.40;95%CI 0.20-060), a lower proportion of peers who use substances (β=-0.25;95%CI -0.50-0.00), and lower peer network density (β=-0.40;95%CI -0.72–0.08). Overall social network characteristics associated with future school engagement included a greater proportion of teachers (β=0.94;95%CI 0.05-1.82) and sources of support (β=0.28;95%CI 0.11-0.44). Peer social network characteristics associated with future school engagement included a greater proportion of peer sources of support (β=0.17;95%CI 0.03-0.32) and a lower proportion of peers who disrupt class (β=-0.29;95%CI -0.56–0.03). Conclusions: Building or bolstering connections to supportive peers and adults may serve to enhance adolescents' school engagement. Similar to other adolescent health-affecting behaviors, school engagement may be positively or negative influenced by the behaviors of peers in adolescents' social circles. Network-based interventions that target multiple associated social network-mediated behaviors, such as school engagement and substance use, may be particularly beneficial to adolescent health. Sources of Support: NIH/NICHD (T32HD071834), UPMC Children's Hospital of Pittsburgh Scholar Award, NIH/NIDA (1K23DA040733-01A1), Robert Wood Johnson Foundation (E4A 74086).

36. Adolescent Mental Health and Big Tech: Investigating Policy Avenues to Regulate Harmful Social Media Algorithms

Purpose: Adolescents are using social media now more than ever, especially given the ongoing COVID-19 pandemic. A growing body of research demonstrates longitudinal associations between social media use and poor mental health outcomes among adolescents, including anxiety, suicidality, depression, poor body image, and eating disorders. One driving factor in the role of social media on mental health concerns is social media platforms' use of algorithms, which drive increasingly extreme content to vulnerable youth users over time;however, little is known about what specific policy action could be taken, and on what legal basis, to prevent the harms caused by social media to adolescents. The purpose of this study was to inform the development of practical, evidence-based policy strategies to regulate social media platforms' use of algorithms. Methods: We assembled a team of adolescent health researchers and legal scholars specializing in First Amendment law. Two separate narrative reviews were conducted to inform the legal research and summarize the evidence of the harms of social media on adolescents' (1) neurodevelopment (e.g., cognitive control, reward processing, neuronal activity);and (2) mental health (e.g., eating disorders, depression, cyberbullying). Legal scholars conducted reviews of federal and state legal precedent, with a focus on First Amendment rulings, to investigate avenues for the regulation of social media platforms' use of algorithms. Finally, the adolescent health and legal research teams conducted virtual consultations with stakeholders in business regulation, technology, and federal and state government, including state lawmakers and attorneys general, to inform the findings. Results: The findings of the narrative reviews highlight the significant harm posed to adolescents by social media algorithmic practices. Rigorous studies find that social media use poses negative effects for mental health (e.g., body dissatisfaction, anxiety, depression) among youth who exhibit high use in early adolescence, frequently use image-based platforms, and who are girls. Normal processes of brain development in mid adolescence may heighten vulnerability to exaggerated emotional responses to platform algorithmic practices, such as feeds that are tailored to user behavior and content that becomes increasingly extreme the longer a session continues. These harms provide justification for legal approaches to regulate social media platform practices and protect adolescent mental health. Furthermore, our legal research indicates that states rather than the federal government are more able and likely to adopt innovative and effective legal strategies that could survive constitutional scrutiny (i.e., the First Amendment). One policy innovation that holds the most promise to protect adolescent mental health would be for states to compel social media companies to conduct algorithm risk audits by objective third parties and publicly disclose the results. Algorithm risk audits are a promising avenue to mitigate the harms caused to adolescent mental health resulting from social media platform algorithms. Conclusions: Our legal analysis has generated viable policy recommendations and actions that state lawmakers and attorneys general can take to protect adolescents from the harms of dangerous social media algorithms. Sources of Support: This study was funded by the Becca Schmill Foundation.

Mild COVID-19: a silent threat

Case Report: Pulmonary embolism (PE) is a form of venous thromboembolism (VTE) which causes an obstruction of the pulmonary vasculature. Massive PE can be a fatal, accounting for over 100,000 death/year in the US. Incidence of PEs is increased in COVID-19 infections, due to a hypercoagulable state resulting from endothelial injury, stasis and increase in prothrombic factors. We report a case of a 48-year-old male with past medical history of mild form of COVID-19 infection approx. 6 months back. He was brought to the ED after cardiac arrest resuscitated in the ambulance. 3 days prior to the cardiac arrest he presented in the ED for nonspecific upper respiratory tract symptoms, for which he received symptomatic treatment. During that visit all the workup was negative except for sinus tachycardia. The cause of patient's cardiac arrest was found to be massive bilateral PE leading to right ventricular strain, shock, and HFrEF (20%). Our patient received thrombolytic, ECMO, thrombectomy, anticoagulation, and required complex treatment for several complication during hospitalization. Was eventually discharged home recovered. COVID-19 pandemic has been one of the worst in human history, causing millions of deaths. Symptoms of COVID-19 infection vary from mild upper respiratory disease to respiratory failure or severe VTEs. Multiple studies including a large national study in Sweden reported COVID-19 being an independent risk factor for VTEs, risk extending up to 180 days after COVID-19 infection, especially in unvaccinated population as seen in our patient. New variants of SARS-Cov 2 pose a challenge to control the spread of COVID-19 infection. As more studies support COVID-19 infection association with hypercoagulability status, varied nonspecific symptomology of PE remains a diagnostic and treatment dilemma. Physicians should have low threshold for investigating PEs in patients with unexplained sinus tachycardia or non-specific respiratory distress, especially in an unvaccinated post-COVID-19 patient, including historical mild forms of infection. Many studies have arguably advocated "treatment to prevent thrombotic events” in post COVID- 19 infection, however, vaccination remains the corner stone to reduce morbidity and mortality associated with serious thrombotic events like massive PEs in patients exposed to COVID1-19.

IMPACT OF SARS-COV-2 INFECTION TO RISK AND SEVERITY OF HYPERTENSION IN PREGNANCY AND ITS OUTCOME TO THE NEW BORN

Objective: To determine relationship of SARS-CoV-2 infection to the risk and severity of preeclampsia, as well as its impact on newborns. Design and method: We performed a systematic search in databases (PubMed, ScienceDirect, ProQuest, and Cochrane Library) for studies examining impact of SARS-CoV-2 infection on pregnancy. Included studies were evaluated for risk of bias based on the Newcastle Ottawa Score. A meta-analysis was conducted using the data extracted from each study. Review Manager (RevMan) 5.4 was utilized to compute the summary of odds ratios (OR), mean differences (MD), and 95% confidence intervals (CI) for the outcomes. Our outcomes of interest are preeclampsia, preeclampsia with severe features, eclampsia, fetal distress and still birth. The other outcomes are preterm birth (< 37 week), instrumental labor, sectio caesaria and birth defect. Results: We identified twenty two observational studies involving 1,025,048 pregnancy patients. Based on the analysis, SARS-CoV-2 infection in pregnancy significantly increased the risk of preeclampsia [OR 2.01(95% CI 1.59-2.53;p < 0.00001;I2 = 82%)], and the severity was based on the high prevalence of preeclampsia with severe features [OR 3.04(95% CI 1.19-7.78;p = 0.02;I2 = 91%)] and eclampsia [OR 17.73(95% CI 13.83-22.72;p < 0.00001;I2 = 0%)]. Poor outcome in newborns in terms of incidence of preterm birth [OR 1.65(95% CI 1.54- 1.76;p < 0.00001;I2 = 86%)], fetal distress [OR 19.18(95% CI 17.14-21.45;p < 0.00001;I2 = 99%)] and still birth [OR 2.12(95% CI 1.74-2.59;p < 0.00001;I2 = 0%)], were also significantly associated with SARS-CoV-2 infection. Conclusions: SARS-CoV-2 infection during pregnancy increases the risk and severity of preeclampsia and gives a poor outcome in newborn.

THE EFFECT OF COMMON SURGICAL MASKS ON UNATTENDED BLOOD PRESSURE CHANGES IN DRUG TREATED HYPERTENSIVE PATIENTS

Objective: While there are several studies that have focused on the role of face masks in preventing airborne transmission of SARS-CoV-2, few data are available on their effects on physiological measures, and no study has examined their effects on blood pressure (BP). The purpose of our study was to investigate the effect of surgical masks on BP in drug-treated hypertensive patients who had a routine follow-up visit to a university hospital outpatient hypertension clinic. Design and method: The study included already treated hypertensive patients aged > 18 years, while the exclusion criteria were atrial fibrillation or any other arrhythmia affecting the BP measurement, an arm circumference > 42 cm, mental disorders, Parkinson disease, pregnancy, intolerance to the BP measurement method, or unwillingness to participate. A new surgical mask was provided to all participants to replace the face mask that was already in use. After the routine mask-on office BP measurement, patients were left alone and randomized to automated office BP measurement, with measurements taken after first wearing a mask for 10 min, then without wearing the mask for 10 min, and vice versa. Results: A total number of 265 patients were included in the study. Among the participants, 115 were women (43.4%), the mean age was 62 ± 12 years, and the mean office BP was 134 ± 15 / 81 ± 12 mmHg. There was no significant difference between mask-on unattended systolic BP (133 ± 15 mmHg) and mask-off unattended systolic BP (132 ± 15 mmHg) (P = 0.13) or between mask-on unattended diastolic BP (77 ± 13 mmHg) and mask-off unattended diastolic BP (76 ± 13 mmHg) (P = 0.32). Moreover, there was no difference in the heart rate (mask-on first, 69 ± 11 bpm;mask-off first, 69 ± 11 bpm, P = 0.7). Conclusions: Common surgical masks do not affect systolic/diastolic BP levels during unattended BP measurements in treated hypertensive patients.

CLINICAL RESEARCH IN LATIN AMERICA: FROM SPONSORED TO INVESTIGATOR INITIATED RESEARCH

Latin American clinical researchers had participated in many controlled clinical trials in the 80 s and 90 s sponsored initiated that confirmed the place of calcium channel blockers and RAS blockade in hypertension treatment. Later, non-inferiority or superiority trials like ONTARGET, Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial and VALUE, Valsartan Antihypertensive Long-term Use Evaluation were performed worldwide including Latin-American countries. In the last decade, the absence of new drugs in the pipeline and sponsors portfolios at one side, and the recommendation of fixeddose combination as initial treatment tool at the other could be supposed as main causes of a dramatic reduction in sponsored hypertension research. At the same time, a huge increase in investigator initiated research was observed. Scientific national and regional societies in many cases fueled this increase. In this scenario, the Cardiovascular Risk Factor Multiple Evaluation in Latin America, CARMELA study was the first large-scale population-based study that assessed cardiovascular risk factor prevalence in 7 Latin American cities and its relationship to hypertension mediated organ damage. CARMELA is an example of an epidemiological study investigator initiated supported by a sponsor in Latin America The FOCUS study, Fixed-Dose Combination Drug for Secondary Cardiovascular Prevention was another example of an investigator initiated research supported by a private company. FOCUS was funded by the 7th Framework Programme European Commission Consortium with the participation of the Centro Nacional De Investigaciones Cardiovasculares CNIC Madrid, Spain, World Heart Federation, Federación Argentina De Cardiología, and some European research organizations, supported by FERRER Internacional. FOCUS help to understand the reasons of treatment non-adherence in Latin American countries and also to recognize the potential benefits of fixed-dose combinations in secondary prevention. More recently, the Interamerican Society of Cardiology SIAC developed the CorCOVID Latam study which aim was to study changes in lifestyle habits, treatment adherence, and mental health status in patients with cardiometabolic disease, but no clinical evidence of COVID-19 during the pandemic. This study is a good example of the feasibility of non-sponsored research in Latam supported by a regional scientific society structure and members. Five publications related to gender differences in the impact of the pandemic in Latam, Influenza and Pneumococcal vaccination during the pandemic, and the psychological impact in more than 4 thousand patients were the fruit of this society research initiative.

FACTORS AFFECTING HOME BLOOD PRESSURE AND HEART RATE VARIABILITY POST-COVID INFECTION

Objective: There is a scarcity of data on the factors that influence home blood pressure (BP) and heart rate (HR) variability. This study was undertaken to determine the factors that influence home BP and HR fluctuation post COVID infection in the urban Indian population. Designs and Methods: We conducted a cross-sectional study among 1000 patients between the ages of 30 and 80 who were previously infected with COVID- 19 infection, but not hospitalized. These patients were guided and trained to measure BP at home. BP and HR readings were taken at home twice a day, in the morning and evening, for seven days (28 measurements). The SD of morning minus evening, and first minus second readings was used to calculate BP and HR variability. Results: Old age, cardiovascular illness, diabetes, and high home blood pressure were all found to be independent predictors of an increased morning than evening home blood pressure variability. Old age, and high home blood pressure were all independent determinants of greater day-to-day home blood pressure variability, while old age, female sex, cardiovascular disease, and high home blood pressure were all independent determinants of greater first versus second home blood pressure variability. Young age, and high home HR, on the other hand, were all independent drivers of increased morning vs evening variability. Young age, female sex, and a high home HR were also independent predictors of first versus second home HR variability. Conclusion: Considering home BP and HR fluctuation have prognostic value, it is critical for clinicians to understand the underlying reasons for these variables. Doctors should focus on alcohol, diabetes, and cardiovascular disease prevention counseling for their high-risk patients. (Table Presented).

CRT-100.87 Impact of COVID 19 on Patients Admitted for ACS: A Nationwide Inpatient Sample Database Study

Background: COVID rapidly became a multisystemic infection with varied cardiovascular complications including Acute Coronary Syndrome. Current literature is limited on the impact of COVID on ACS patients. Methods: We queried the national inpatient sample (NIS) from 2020 to identify patients who were admitted for ACS and stratified them based on the presence or absence of COVID. The adjusted odds ratios (aOR) of in-hospital outcomes and resource utilization were calculated using chi-square statistics in the software STATA v.17. Results: Out of 883940 patients analyzed, who were admitted for ACS, 3900 patients had COVID. On adjusted analysis, patients with COVID had significantly elevated In-Hospital mortality (aOR, 2.91 CI 2.25-3.79), MACCE (aOR 2.53, CI 1.90-3.10), cardiac arrest (aOR 3.34, CI 1.1-10.1) with longer length of stay (6.34 ± 0.39 vs 4.48 ± 0.02). Interestingly, the outcome PCA (aOR, 0.39 CI 0.33-0.46) showed significant improvement. Interestingly, mean costs were elevated in patients without COVID at $105,550.8 vs $98597.7 in patients without COVID. In terms of trends, as exposure increased through the year with the highest levels in December, the mortality also increased (April 18.52% vs 25.64%). Interestingly, the cardiac arrest percentage decreased from April 2020 (7.4%) to Dec 2020 (1.98%) as well as MCS in April 202 (11.11%)vs December 2020 (3.47%) in patients exposed to COVID. Conclusions: In patients admitted for ACS, the presence of COVID significantly increases the risk of MACCE, in-hospital mortality, and cardiac arrest. Prospective trials are necessary for the identification of risk factors to improve clinical outcomes in these patients. Key words: COVID, Sars-2 coronavirus. Coronavirus. ACS. Acute Coronary Syndrome. [Formula presented]

FACTORS AFFECTING DEVELOPMENT OF AKI AMONG COVID-19 HYPERTENSIVE PATIENTS

Objective: To determine risk factors associated with development of AKI with regards to mortality rate among covid-19 patients taking in consideration risk factors such as age, sex and chronic diseases like diabetics considering renal function to outcome. Design and method: This is a retrospective cohort study using de-identified data retrieved from clinical records of patients from two COVID 19 isolation centers. Medical history, demographic data, symptoms, disease complications and laboratory investigations were extracted from clinical records of 406 confirmed COVID 19 hospitalized patients in the period between Feb 2020 and July 2021. Continuous variables were presented as means ± standard deviation (SD) while categorical variables were presented as percent proportions. Logistic regression was used to determine risk factors associated with development of AKI with regards to mortality factors rate among covid 19 hypertensive patients. Result: Out of 406 hospitalized COVID-19 patients, 59.6% had a history of hypertension. Logistic regression was used to analyze risk factors associated with AKI among hypertensive and non hypertensive patients of covid-19. Age factor is highly significant factor for development of AKI for hypertensive (odd ratio [OR]: 4.89, 95% confidence interval [CI]: (1.93-1.36, P = 0.001) and non-hypertensive patients (odd ratio [OR]: 4.73, 95% confidence interval [CI]: (1.58-4.18, P = 0.001). Urea (odd ratio [OR]: 3.06, 95% confidence interval [CI]: (1.63-5.76, P = 0.001), creatinine (odd ratio [OR]: 3.39, 95% confidence interval [CI]: (1.82-6.32, P > 0.001) and potassium[K] (odd ratio [OR]: 2.17, 95% confidence interval [CI]: (2.23-3.83, P = 0.035) are highly significantly increased for hypertensive covid- 19 patients, whereas urea, creatinine and K are not significantly changed for non-hypertensive covid-19 patients Gender and morbidity factor (diabetes mellitus) has no significant effect for AKI development for hypertensive and non-hypertensive covid-19 patients. AKI is considered as a risk factor death among COVID-19 patients (OR:284, CI:1.56-5.15, p = 0.001). Conclusion: The present study indicates that 71% of patients with AKI are hypertensive. The results also highlight the alarming high incidents of hypertension in the studied population. On conclusion hypertension is considered as highly morbidity factor for development of AKI.

Virtual Healthcare Is Everywhere, But Are Caregivers Satisfied With Virtual Learning And Does It Have A Role Moving Forward?

Rationale: Covid-19 introduced a shift towards telemedicine in paediatric healthcare. In-person education opportunities were therefore reduced. Virtual education opportunities are developing, but do caregivers want these permanently? This study assesses caregivers' experiences following an online anaphylaxis education session. Methods: This project uses data collected as part of the ongoing TEAAM study (Telemedicine as an Educational tool for caregivers regarding Auto-Injectors and Anaphylaxis Management). TEAAM examines the efficacy of online education in improving caregiver anaphylaxis knowledge using a virtual session (with a trainer and video resources), and pre- and post- intervention surveys. The TEAAM population consists of a convenience sample of caregivers of children attending allergy clinic, who have a food allergy and have been prescribed adrenaline. 65 caregivers have completed a post-intervention questionnaire in which we assessed their satisfaction level, perceived benefits, issues and comparison to in-person education. Results: 98.5%(64) of caregivers found participation beneficial (mean satisfaction score 4.7/5). Benefits included time saved (n=55,84.6%), and money saved (n=33,50.8%) due to less travel, having access to education while awaiting appointments (n=54,83.1%), and reduced exposure to infection (n=28,43.1%). During sessions, 78.5%(50) expressed no issues. 3.1%(2) had issues logging in. 9.2%(6) mentioned trainer difficulties in sharing screens. Qualitative comments showed confidence in online education platforms e.g., "I definitely think sessions like this are the way forward”. Only 1 caregiver believed it would be more useful if delivered in-person. Conclusions: Caregivers found online allergy education sessions worthwhile and would like them to continue. Moving forward, we need to build user-friendly, distance-learning resources and ensure staff are adequately trained.

Infections by varicella zoster virus in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)

Rationale: APECED is a life-threatening monogenic disorder characterized by multiorgan autoimmunity. Most patients harbor autoantibodies (auto-abs) to type-1 interferons (IFNs), which are important mediators of viral defense. Auto-abs to type-1 IFNs are associated with severe COVID-19 and may play a role in other viral infections including by varicella zoster virus (VZV). A recent study of 44 European APECED patients reported increased susceptibility to VZV, and a correlation between VZV recurrence and auto-abs to IFN-α. The clinical, immunophenotypic, and auto-ab characteristics of APECED patients in the USA with VZV are described. Methods: Data was obtained from 103 participants on a prospective, natural history study after informed consent. Auto-abs to IFN-α, IFN-β or IFN-ω were measured using a multiplex particle-based assay. Unpaired t tests or U Mann Whitney tests were used, with Holm correction for multiple comparisons, where appropriate. Results: Twenty-six patients reported childhood chickenpox (mean onset 5.6 years) and 2 (7.7%) required hospitalization for severe disease. Nineteen patients (18%) had at least one episode of shingles (median onset 13 years;range, 4-55 years) and 4 had >1 episode. Fifteen of the 19 patients with shingles (79%) were not receiving immunosuppressive medications during their first infection. VZV IgG levels;total and percent CD3, CD8, CD4, CD19, NK cells;and auto-abs to IFN-α, IFN-β and IFN-ω did not significantly differ between patients with or without recurrent shingles. Conclusions: A subset of APECED patients develop early-onset, recurrent VZV infections even in the absence of immunosuppression. The mechanisms underlying susceptibility to VZV in APECED require further study.

EFFECT OF THE COVID-19 PANDEMIC ON AMBULATORY BLOOD PRESSURE MEASUREMENT

Introduction: The world is currently facing the fourth wave of the COVID-19 pandemic. The aim of this study is to assess the effect of this pandemic on ambulatory blood pressure measurements (ABPM) and to investigate the effect of SARS-CoV2 infection on blood pressure (BP). Methods: We conducted a uni-centric retrospective study on the ERASME hospital ABPM register, from 2010 to 2021. The nycthemeral blood pressure (BP) profile of the pandemic period (January 2020 to October 2021) was compared with that of the previous 5 control periods from January 2010 to October 2019. We also determined the diurnal, nocturnal and 24-hour high blood pressure frequencies for each period. Furthermore, for the COVID-19 period, the BP profiles of COVID-19 positive and negative patients were compared. Finally, in COVID-19 positive patients, we compared ABPMs performed before COVID-19 infection with those performed post-infection. Results: After excluding incomplete and poor-quality ABPM, 16,977 ABPMs were selected. The COVID-19 period accounted for 10.58% of ABPMs compared with 15-20% for pré-COVID periods. We observed that diurnal (83.20 vs 81.20;p < 0.001), nocturnal (73.02 vs 71.09;p < 0.001) and 24-hour (79.51 vs 77.50;p < 0.001) diastolic BPs were higher in the COVID-19 period. In contrast, diurnal (131.64 vs 133.18;p < 0.001), nocturnal (121.07 vs 121.93;p = 0.034) and 24- hour (127.82 vs 128.97;p < 0.001) systolic BPs were lower during the pandemic. In logistic regression, diastolic diurnal (OR:1.58 [1.33-1.89];p < 0.001), nocturnal (OR:1.18 [1.02 - 1.36];p = 0.026) and 24-hour (OR:1.22 [1.01 - 1.49];p = 0.044) hypertension were associated with the COVID-19 period, when adjusted for age, gender or history of hypertension. Also, diurnal (OR:0.63 [0.55-0.71];p < 0.001) and nocturnal (OR:0.82 [0.72-0.93];p = 0.002) systolic hypertension were less frequent in the COVID-19 period. When comparing BPs between COVID- 19 positive and negative patients, there was no significant difference. When ABPMs were compared before and after infection in COVID-19 positive patients, diastolic diurnal (88.41 vs. 78.88;p = 0.001), nocturnal (77.91 vs. 70.55;p = 0.027) and 24-hour (84.57 vs. 75.99;p = 0.002) BPs were higher after COVID-19 infection. Conclusion: Our study shows that during the COVID-19 pandemic, diastolic BP was higher and systolic BP was lower compared to the pre-COVID-19 period. We also observed an increase in diastolic BP after COVID-19 infection.

CASE REPORT: A RARE CASE OF ALVEOLAR HEMORRHAGE AFTER COVID-19 VACCINATION IN A PATIENT WITH RENAL-LIMITED ANTINEUTROPHIL CYTOPLASMIC ANTIBODYASSOCIATED VASCULITIS

The coronavirus disease 2019 (COVID-19) vaccination campaign has progressed worldwide. Rare but severe adverse events of COVID-19 vaccination such as anaphylaxis and myocarditis have begun to be noticed. Of note, several cases of new-onset antineutrophil cytoplasmic antibody-associated vasculitis (AAV) after COVID-19 mRNA vaccination have been reported. In contrast, relapse of AAV in remission has not been recognized enough as an adverse outcome of COVID-19 vaccination. We report, to the best of our knowledge, a first case of renal-limited AAV in remission using every 6-month rituximab administration that relapsed with pulmonary hemorrhage, but not glomerulonephritis, following the first dose of the COVID-19 vaccine. Notably, the patient received the COVID-19 vaccine more than 6 months after the last dose of rituximab according to the recommendations. Ironically, his CD19 positive B cell counts were found to be increased after admission, indicating that our case might have been prone to relapse after COVID-19 vaccination. Although our case cannot establish causality between AAV relapse and COVID-19 mRNA vaccination, a clinical vigilance for relapse of AAV especially in patients undergoing rituximab maintenance therapy following COVID-19 vaccination should be maintained. Furthermore, the elapsed time between rituximab administration and COVID-19 mRNA vaccination should be carefully adjusted based on AAV disease-activity (Nishioka et al. Front Med 2022. in press).

A FIVE-YEAR SUMMARY OF THE MMM CAMPAIGN IN NEPAL

Objective: To share the implementing experience of the May Measure (MMM) campaign in Nepal. Design and Methods: Nepal has been a part of the MMM initiative since its inception. NeDS Nepal, a not-fort profit NGO was responsible for the overall coordination of the campaign. We trained and mobilized community health workers and health science students as volunteers. Although MMM was not executed globally due to the COVID-19 pandemic in 2020, it was conducted in Nepal by following safety measures. Results: The volunteers set up screening sites in supermarkets, temples, colleges, grocery stores, primary health care clinics, banks, government offices, and meeting halls. Some of the volunteers also did house-to-house visits. Between 2017-2021, we screened over 130,000 participants. We identified > 30,000 high blood pressure participants, provided lifestyle counseling, and referred them to the health facility for further diagnosis and treatment. Out of them, ∼18000 were newly identified hypertension. Conclusions: Opportunistic screening like MMM is feasible and needed in the context of Nepal. This could potentially be embedded in the national screening program. It is also important to have a strategy for linking the patients with the health system for further diagnosis and treatment.

COMPARATIVE EFFICACY OF VARIOUS ANTICOAGULANTS IN COVID-19 INDIAN SUBJECTS: AN OBSERVATIONAL STUDY

Background: To assess the efficacy of various anticoagulants being prescribed in the COVID 19 induced hypercoagulability, so as to know optimally effective anticoagulant. Methods: This was a Indian observational study conducted in our covid centre at vijayawada,Andhra Pradesh between june 2020 to January 2021 . Results: A total of 100 COVID 19 subjects were included. The patients were found to be matched with respect to age, gender, diet and past history of various illnesses. Gender wise more males (60 patients)are affected when compared to females(40 patients). Age group more affected are less than or equal to 50yrs . Comorbidites like Diabetes(67patients),cardiac problems(62patients), dyslipidemia(62patients) were seen. Risk factors like smoking(52patients), alcoholism(50patients) noticed. Almost all subjects are RTPCR positive. IL- 6,CRP,LDH high in most subjects. Ferritin and PT/INR are normal in more subjects. Out of 100 patients oxygen is required in 48 subjects and BIPAP/CPAP required in 26 subjects. Death occurred in 24 patients (2 with CVA,22 with myocardial infraction). Mortality rate is more in vegetarians. More patients in our study belongs to CORADS score 4 and 5. D-dimer are increased in 67subjects. IL-6 are increased in 68patients . Frequency of subjects with raised D-dimer (p = 0.049) and CRP (p = 0.002) levels were found to be benefitted on receiving nattokinase. However, no other parameters such as IL-6 (p = 0.068) ferritin (p = 0.396), ESR (p = 0.278), PT/INR (p = 0.47) LDH (p = 0.34) or CORADS staging achieved such significant association. Also need of interventions such as Oxygen (p = 0.001), BIPAP/CPAP (p < 0.0001) were low in patients on nattokinase. No significant difference was noted in follow up investigations such as PT/INR (p = 0.31) and other markers (D-dimer, IL-6, LDH, CRP) (p = 0.55). No bleeding episodes were reported in subjects on nattokinase. Significant low rate of death was found in subjects who received nattokinase (p < 0.0001) and rivaroxaban (p < 0.0001). Also, significantly higher mortality rate was observed in subjects who required to be put on oxygen (p < 0.0001) as well as BIPAP/CPAP (p < 0.0001). Conclusions: Nattokinase simultaneously effects several key favourable benefits for thrombosis, hypertension, atherosclerosis, hyperlipidaemia, platelet aggregation, and neuroprotection in patients with COVID 19 infection. (Figure Presented).

Diabétiques avec COVID-19 admis à l'hôpital régional de Msaken au centre de la Tunisie

Déclaration de liens d'intérêts: Les auteurs n'ont pas précisé leurs éventuels liens d'intérêts.