Integrative Systems Immunology Analysis Reveals Elevated Anti-AGTR1 Levels with Accumulating COVID-19 Symptoms (preprint)

The coronavirus disease 2019 (COVID-19) displays a broad spectrum of symptoms, with the underlying reasons for this variability still not fully elucidated. Our study investigates the potential association between specific autoantibodies (AABs), notably those that targeting G protein-coupled receptors (GPCRs) and renin-angiotensin system (RAS) related molecules, and the diverse clinical manifestations of COVID-19, commonly observed in patients with autoimmune conditions, including rheumatic diseases, such as systemic sclerosis. In a cross-sectional analysis, we explored the relationship between AAB levels and the presence of key COVID-19 symptoms. Hierarchical clustering analysis revealed a robust correlation between certain AABs and symptoms such as fever, muscle ache, anosmia, and dysgeusia, which emerged as significant predictors of disease severity. Specifically, AABs against CHRM5 and CXCR3 were strongly linked to fever, while AABs against CHRM5 and BDKRB1 correlated with muscle ache. Anosmia was predominantly associated with AABs against F2R and AGTR1, while dysgeusia was linked to AABs against BDKRB1 and AGTR1. Furthermore, we observed a rise in AAB levels with the accumulation of these symptoms, with the highest levels detected in patients presenting all four predictors. Multinomial regression analysis identified AABs targeting AGTR1 as a key predictor for one or more of these core symptoms. Additionally, our study indicated that anti-AGTR1 antibodies triggered a concentration-dependent degradation of eGC, which could be mitigated by the AGTR1 antagonist Losartan. This suggests a potential mechanistic connection between eGC degradation, the observed COVID-19 symptoms, and rheumatic diseases. In conclusion, our research underscores a substantial correlation between AABs, particularly those against GPCRs and RAS-related molecules, and the severity of COVID-19 symptoms. These findings open avenues for potential therapeutic interventions in the management of COVID-19.

Exploring the experiences of COVID-19 survivors with a history of admission to the respiratory intensive care unit (RICU): A phenomenological study in Iran (preprint)

COVID-19 is still spreading around the world. To this end, the present study sought to explore the experiences of COVID-19 survivors with a history of admission to ICUs in southern Iran. This study was conducted using descriptive phenomenology on twelve COVID-19 survivors with a history of admission to the ICU. The patients were selected using purposive sampling. The data were collected through face-to-face semistructured interviews with the patients. The collected data were analyzed using the seven steps of Colaizzi analysis. Data analysis revealed 3 main themes: better resources and facilities, unpleasant physical and psychological experiences, and pain relievers. COVID-19 survivors who were admitted to the RICU reported that they had many positive and negative experiences. Thus, health officials, experts, nurses, and physicians need to pay special attention to the problems faced by COVID-19 patients admitted to ICUs.

A Case Report of Acute Lymphoblastic Leukaemia (ALL)/Lymphoblastic Lymphoma (LBL) Following the Second Dose of Comirnaty®: An Analysis of the Potential Pathogenic Mechanism Based on of the Existing Literature (preprint)

In this report we describe the case of a healthy, young, athletic woman who developed acute lymphoblastic leukaemia (ALL)/lymphoblastic lymphoma (LBL) after receiving the second dose of the Pfizer/BioNTech modified mRNA (modRNA) COVID-19 genetic vaccine (marketed as Comirnaty®). The first dose of the genetic vaccine did not appear to illicit any noticeable side effects, but within 24 hours of the second dose the patient suffered widespread and intensifying bone pain, fever, vomiting, and general malaise. Due to the persistence of the symptoms, the patient underwent a series of tests and examinations including a full laboratory workup, a consult with a clinical immunologist and rheumatologist, a Positron Emission Tomography (PET) imaging, as well as an osteomedullary biopsy. These together led to a definitive diagnosis of ALL. A time interval of 16 weeks from the second vaccination to the diagnosis of cancer was noted. Several similar cases with identical pathology which developed after the modRNA COVID-19 vaccination, are described in case reports in the scientific literature. The massive and indiscriminate use of genetic vaccines to fight COVID-19 is raising serious concerns about their safety and about the technology platform as a whole for this purpose. Growing evidence is accumulating regarding the biodistribution and persistence of the modRNA which can reach, thanks to the lipid nanoparticles, a multitude of tissues and organs of the body, including the bone marrow and other blood-forming organs and tissues. Moreover, there is evidence that the modRNA vaccines display a particular tropism for the bone marrow, influencing the immune system at multiple levels and being able to trigger not only autoimmune-based pathologies, but also neoplastic mechanisms. The aim of this article is to assess, on the basis of the available scientific literature, the risk of developing haematopoietic cancers after modRNA vaccination, and to investigate the potential genetic mechanisms involved in the pathogenesis of disease.

Quality of Care at childbirth during the COVID-19 pandemic: findings of the IMAgiNE EURO study in Belgium (preprint)

Objectives To examine quality of maternal and newborn care (QMNC) around childbirth in facilities in Belgium during the COVID-19 pandemic and trends over time. Design A cross-sectional observational study. Setting Data of the IMAgiNE EURO study in Belgium. Participants Women giving birth in a Belgian facility from March 1, 2020, to May 1, 2023, responded a validated online questionnaire based on 40 WHO standards-based quality measures organised in four domains: provision of care, experience of care, availability of resources, and organizational changes related to COVID 19. Primary and secondary outcome measures Quantile regression analysis was performed to assess predictors of QMNC; trends over time were tested with the Mann Kendall test. Results 897 women were included in the analysis, 67%(n=601) with spontaneous vaginal birth, 13.3%(n=119) with instrumental vaginal birth and 19.7%(n=177) with cesarean section. We found high QMNC scores but also specific gaps in all domains of QMNC. On provision of care, 21.0%(n=166) of women who experienced labor and 14.7%(n=26) of women with a cesarean reported inadequate pain relief; 64.7%(n=74) of women with an instrumental birth reported fundal pressure and 72.3% (n=86) reported that forceps or vacuum cup was used without their consent. On experience of care, 31.1%(n=279) reported unclear communication, 32.9%(n=295) reported that they were not involved in choices,11.5%(n=104) stated not being treated with dignity and 8.1%(n=73) experienced abuse. Related to resources, almost half of the women reported an inadequate number of healthcare professionals (46.2%, n=414). The multivariable analyses showed significantly lower QMNC scores for women with an instrumental vaginal birth. Over time there was a significant increase in QMNC score for experience of care and key organizational changes due to COVID-19. Conclusions and relevance Although overall QMNC scores were high, findings also suggest gaps in QMNC. Underlying causes of these gaps should be explored to design appropriate interventions and policies.

The Effectiveness of Socially Assistive Robots in Improving Children’s Pain and Negative Affectivity during Needle-based Invasive Treatment: A Systematic Review and Meta-analysis (preprint)

Background The ability of socially assistive robots (SARs) to treat dementia and Alzheimer’s disease has been verified. Currently, to increase the range of their application, there is an increasing amount of interest in using SARs to relieve pain and negative emotions among children in routine medical settings. However, there is little consensus regarding the use of these robots. Objective This study aimed to evaluate the effect of SARs on pain and negative affectivity among children undergoing invasive needle-based procedures. Design This study was a systematic review and meta-analysis of randomized controlled trials that was conducted in accordance with the Cochrane Handbook guidelines. Methods The PubMed, Embase, EBSCO, Web of Science, Cochrane Library, Embase, CNKI, and WanFang databases were searched from inception to January 2024 to identify relevant randomized controlled trials (RCTs). We used the Cochrane Risk of Bias tool 2.0 (RoB2.0) to assess the risk of bias among the included studies, and we used RevMan 6.3 software to conduct the meta-analysis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used to assess the quality of the evidence. Results Ten RCTs involving 815 pediatric subjects were selected for this review and reported outcomes related to pain and emotions during IV placement, port needle insertion, flu vaccination, blood sampling, and dental treatment. Children undergoing needle-related procedures with SARs reported less anxiety (SMD= -0.36; 95% CI= -0.64, -0.09; P = 0.01) and fewer distressed avoidance behaviors (SMD= -0.67; 95% CI= -1.04, -0.30; P = 0.0004) than did those receiving typical care. There were nonsignificant differences between these groups in terms of in pain (SMD = -0.02; 95% CI = − 0.81, 0.78; P = 0.97) and fear (SMD = 0.38; 95% CI= -0.06, 0.82; P = 0.09). The results of exploratory subgroup analyses revealed no statistically significant differences based on the intervention type of robots or anesthetic use. Conclusions The use of SARs is a promising intervention method for alleviating anxiety and distress among children undergoing needle-related procedures. However, additional high-quality randomized controlled trials are needed to further validate these conclusions. Registrations The protocol of this study has been registered in the database PROSPERO (registration ID: CRD42023413279).

Real-Life Practice of Kelleni’s Protocol in Treatment and Post Exposure Prophylaxis of SARS CoV-2 Omicron HV.1 and JN.1 Subvariants (preprint)

This brief report discusses the ongoing real-world practice using nitazxoanide, NSAIDs and/or azithromycin (Kelleni’s protocol) to manage the evolving manifestations of SARS CoV-2 Omicron EG.5.1, its descendant HV.1 as well as BA.2.86 and its descendant JN.1 subvariants in Egypt. These subvariants are well-known for their highly evolved immune-evasive properties and the manifestations include some peculiar manifestations as persistent cough besides high fever in young children as well as persistent severe cough, high fever, change of voice and marked bone aches in high risk groups of adults. It’s suggested that the ongoing SARS CoV-2 evolution is continuing to mostly affect the high risk groups of patients, to some of whom we’ve also successfully prescribed nitazoxanide and/or NSAIDs for post-exposure prophylaxis of all household contacts. We also continue to recommend starting the immune-modulatory antiviral Kelleni’s protocol as soon as possible in the course of infection and adjusting it in a personalized manner to be more aggressive from the beginning for the high risk patients, at least until the currently encountered surge of infections subsides.

Interventions for the management of post COVID-19 condition (long COVID): Protocol for a living systematic review & network meta-analysis (preprint)

Background: Up to 15% of survivors of COVID-19 infection experience long-term health effects, including fatigue, myalgia, and impaired cognitive function, termed post COVID-19 condition or long COVID. Several trials that study the benefits and harms of various interventions to manage long COVID have been published and hundreds more are planned or are ongoing. Trustworthy systematic reviews that clarify the benefits and harms of interventions are critical to promote evidence-based practice. Objective To create and maintain a living systematic review and network meta-analysis addressing the benefits and harms of pharmacologic and non-pharmacologic interventions for the treatment and management of long COVID. Methods Eligible trials will randomize adults with long COVID, to pharmacologic or non-pharmacologic interventions, placebo, sham, or usual care. We will identify eligible studies by searches of MEDLINE, EMBASE, CINAHL, PsycInfo, AMED, and CENTRAL, from inception, without language restrictions. Reviewers will work independently and in duplicate to screen search records, collect data from eligible trials, including trial and patient characteristics and outcomes of interest, and assess risk of bias. Our outcomes of interest will include fatigue, pain, post-exertional malaise, changes in education or employment status, cognitive function, mental health, dyspnea, quality of life, patient-reported physical function, recovery, and serious adverse events. For each outcome, when possible, we will perform a frequentist random-effects network meta-analysis. When there are compelling reasons to suspect that certain interventions are only applicable or effective for a subtype of long COVID, we will perform separate network meta-analyses. The GRADE approach will guide our assessment of the certainty of evidence. We will update our living review biannually, upon the publication of a seminal trial, or when new evidence emerges that may change clinical practice. Conclusion This living systematic review and network meta-analysis will provide comprehensive, trustworthy, and up-to-date summaries of the evidence addressing the benefits and harms of interventions for the treatment and management of long COVID. We will make our findings available publicly and work with guideline producing organizations to inform their recommendations.

Clinical characterization of new-onset chronic musculoskeletal pain in Long COVID: a cross-sectional study (preprint)

Purpose: New-onset chronic musculoskeletal (MSK) pain is one of the common persistent symptoms in Long COVID (LC). This study investigated its clinical characteristics, underlying mechanisms, and impact on function, psychological health, and quality of life. Patients and methods: 30 adults (19 female, 11 male) with LC and new-onset chronic MSK pain underwent clinical examination, Quantitative Sensory Testing (QST), and blood tests for inflammatory markers, and completed the following outcome measures: Timed Up and Go test (TUG), handgrip strength test, COVID-19 Yorkshire Rehabilitation Scale (C19-YRS), Brief Pain Inventory (BPI), Pain Self-Efficacy Questionnaire (PSEQ), Pain Catastrophizing Scale (PCS), International Physical Activity Questionnaire - short form (IPAQ-sf), Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire (PHQ-9), and EuroQol Five Dimensions health-related quality of life (EQ-5D-5L). Results: New-onset chronic MSK pain was widespread and continuous in nature, and worse in the joints. When compared to normative values reported in the literature: a) QST revealed mechanical hyperalgesia, heightened temporal summation of pain, and hypoesthesia to vibration stimuli, which is strongly suggestive of central sensitization; b) Plasma cytokine assays indicated distinct pro- inflammatory profiles; c) TUG time indicated reduced balance and mobility; d) handgrip strength revealed general weakness; e) physical activity was lower ; and f) there were moderate levels of depression and anxiety with lower self-efficacy scores and lower levels of pain catastrophizing. LC symptoms were of moderate severity (44.8/100), moderate functional disability (22.8/50) and severely compromised overall health (2.6/10) when compared to pre-COVID scores. Conclusion: New-onset chronic MSK pain in LC tends to be widespread, constant, and associated with weakness, reduced function, depression, anxiety, and reduced quality of life. There is associated central sensitization and proinflammatory state in the condition. Further research is essential to explore the longitudinal progression and natural evolution of the new-onset chronic MSK pain in LC.

Tracking Persistent Symptoms in Scotland (TraPSS): A Longitudinal Prospective Cohort Study of COVID-19 Recovery After Mild Acute Infection (preprint)

Background: COVID-19 disease results in disparate responses between individuals and has led to the emergence of Long-COVID, characterized by persistent and cyclical symptomology. To understand the complexity of Long-COVID, the importance of symptom surveillance and prospective longitudinal studies is evident. Methods: A 9-month longitudinal prospective cohort study was conducted within Scotland (n=287), using a mobile app to determine the proportion of recovered individuals, those with persistent symptoms, common symptoms, and associations with gender and age. Results: 3.1% of participants experienced symptoms at month 9, meeting the criteria for Long-COVID, as defined by the NICE terminology. Fatigue, cough, and muscle pain were the most common symptoms at baseline, with fatigue persisting the longest, while symptoms like cough improved rapidly. Older age increased the likelihood of reporting pain and cognitive impairment. Female gender increased the likelihood of headaches and post-exertional malaise (PEM), and increased recovery time from fatigue and PEM. Conclusions: The majority of people fully recover from acute COVID-19, albeit often slowly. Age and gender play a role in symptom burden and recovery rates, emphasizing the need for tailored approaches to Long-COVID management. Further analysis is required to determine the characteristics of the individuals still reporting ongoing symptoms months after initial infection to identify risk factors and potential predictors for the development of Long-COVID.

Predictors of moderate-to-severe side-effects following COVID-19 mRNA booster vaccination: A prospective cohort study among primary health care providers in Belgium. (preprint)

Background COVID-19 vaccine effectiveness declines months after vaccination. Therefore, it is likely that during the next few years, people may be repeatedly offered a booster vaccine to enhance humoral immunity levels. A growing number of people are questioning whether the benefits of a booster vaccine outweigh the side-effects.Objective This study aims (1) to identify the most frequently reported side-effects after different doses of COVID-19 mRNA vaccines, (2) and the longest lasting symptoms; and (3) to predict the likelihood of having moderate-to-severe side-effects after a booster COVID-19 mRNA vaccine given individual- and vaccine-specific characteristics.Design, setting, and participants : Secondary analysis of a prospective cohort study in primary health care providers (PHCPs) in Belgium conducted between December 2020 and December 2021, and in February-March 2023.Methods In nine subsequent surveys over a period of 2 years vaccine dose-number and side-effects after COVID-19 vaccines were collected. A Generalized Estimation Equations approach on the data of the first and second booster dose was used to investigate the probability of having moderate-to-severe side-effects after mRNA booster vaccination. Predictive performance of a binary classifier was assessed by looking at discrimination (i.e., quantified in terms of the area under the receiver operating characteristic curve). The final prediction model was validated using data with regard to the third booster by assessing misclassification rate, sensitivity and specificity.Results In total, 11% of the PHCPs had moderate-to-severe side-effects after their booster COVID-19 mRNA vaccine. The most common side-effects of COVID-19 mRNA doses included fatigue, local pain at the injection site, general pains, and headache. These side-effects typically lasted for a median of 1 to 2 days. The final model included five predictors: sex, alcohol consumption, history of moderate-to-severe side-effects after any previous dose, recent COVID-19 infection, and the booster dose-number (first, second). Having experienced moderate-to-severe side-effects after any previous dose was the strongest predictor of moderate-to-severe side-effects following an mRNA vaccine booster, with an odds ratio (OR) of 3.64 (95% CI: 2.80–4.75). The OR for female sex was 1.49 (95% CI: 1.21–1.84) implying that females have a higher odds of moderate-to-severe side-effects following booster vaccination. The differences in effect for booster dose-number, alcohol consumption and recent COVID-19 infection was not significant.Conclusion and Relevance: COVID-19 mRNA booster vaccination implies a low prevalence of moderate-to-severe side-effects among PHCPs, with a short median duration of symptoms if any. The strongest predictors are a history of moderate-to-severe side-effects after any previous dose and being female. These reassuring findings can help addressing concerns about booster vaccination and encourage their uptake.Trial Registration: NCT04779424

Changes in opioid prescribing during the COVID-19 pandemic in England: cohort study of 20 million patients in OpenSAFELY-TPP (preprint)

Background: The COVID-19 pandemic led to disruptions in healthcare delivery, including postponement of elective procedures and difficulty accessing in-person care, which may have increased the need for strong pharmacological pain relief in some patients. Methods: With NHS England approval, we used routine clinical data from >20 million general practice adult patients in OpenSAFELY-TPP. We used interrupted time series analysis to quantify trends in prevalent and incident opioid prescribing prior to the pandemic (January 2018-February 2020) and changes during the COVID-19 lockdown period (March 2020-March 2021) and recovery period (April 2021-June 2022). We identified how these changes varied in people living in care homes, and by age, sex, deprivation, ethnicity, and geographic region. Results: The median number of people prescribed an opioid per month was 50.9 per 1000 patients prior to the pandemic. We observed little change in overall prescribing after the start of the pandemic, except for a temporary increase in March 2020. There was a 9.8% (95%CI -14.5%, -6.5%) reduction in new opioid prescribing from March 2020, sustained to the end of the study period. Reductions in new prescribing were observed for all demographics except people 80+ years. Among care home residents, in April 2020 new opioid prescribing increased by 112.5% (95%CI 92.2%, 134.9%) and parenteral opioid prescribing increased by 186.3% (95%CI 153.1%, 223.9%). Conclusion: Changes in opioid prescribing during the COVID-19 pandemic were mostly consistent across subgroups with the exception of differences by age and care home residence. Among people in care homes, increases in parenteral opioid prescribing likely reflect use to treat end-of-life COVID-19 symptoms. Further research is needed to understand what is driving the reduction in new opioid prescribing and its relation to changes to health care provision during the pandemic.

Evaluating Nirmatrelvir-Ritonavir (Paxlovid®) in Outpatient COVID-19 Treatment: Safety, Tolerability, and Adherence Insights from Primary Healthcare Clinics (preprint)

Objective: This study aims to fill this gap by evaluating the safety, tolerability, and adherence of patients prescribed Paxlovid® in outpatient settings, focusing on its use in managing category 2 COVID-19 patients across three primary healthcare clinics in Selangor, Malaysia. Design: Retrospective cross-sectional study Setting: Data were collected from the Paxlovid® pharmacy registry and medical records at Klinik Kesihatan Seksyen 7, Klinik Kesihatan Seksyen 19, and Klinik Kesihatan Kelana Jaya between April 1, 2022, and November 30, 2022. Participants: This study analysed data from 415 category 2 COVID-19 patients aged ≥18 years old. Primary and secondary outcomes: Parameters assessed included patient demographics, dosing, current medication, changes in drug regimen, adherence, and ADR. Pharmacists follow-ups were conducted on days 3 and 5 post-medication initiation. Results: The majority (79.5%) of the cohort experienced ADR, predominantly dysgeusia, diarrhoea, body ache, vomiting, and nausea. Despite these, the ADR were generally well-tolerated, with no severe impacts reported. High adherence was observed, with 96.9% of patients completing the 5-day regimen. The primary reasons for non-adherence included adverse effect intolerability, dosing ambiguity, forgetfulness, concerns about ADR, and perceived health improvement. Notable medications interacting with Paxlovid® were simvastatin, amlodipine, and atorvastatin, and 21.7% of 23 concurrent medications were found not complying to the recommended interventions by the University of Liverpool COVID-19 Drug Interaction database. Conclusion: Nirmatrelvir-ritonavir (Paxlovid®) demonstrates a high level of safety and tolerability in outpatient COVID-19 patients, with optimal adherence observed. This study underscores the vital role of healthcare professionals in managing Paxlovid® within primary healthcare and highlights the need for broader research and direct patient involvement to enhance treatment strategies against COVID-19.

Long-term symptoms after SARS-CoV-2 infection in a cohort of people living with HIV (PLWH): a real-life study (preprint)

Background Our Hospital in Northern Italy assists 3817 people living with HIV (PLWH) and has faced the impact of COVID-19. Little is known about the impact of HIV infection on the risk of post-COVID-19 conditions (PCCs) onset. We aim to assess the incidence of PCC in PLWH and the factors associated with its occurrence.Methods We performed a retrospective, observational study including all PLWH > 18 years registered in the Brescia Health Protection Agency database, assessing SARS-CoV-2 burden, vaccination status, socio-demographic, and viro-immunological parameters from February 2020 until May 2022. Persistence of self-reported symptoms (clustered into gastrointestinal, respiratory, osteo-muscular, and neuro-behavioral symptoms) was evaluated after 3 months by a telephone-administered questionnaire. We estimated the associations between all variables and outcomes through univariate and multivariable logistic models.Results In the study period, 653 PLWH were diagnosed with SARS-CoV-2 infection (17.1%). We observed 19 (2.9%) reinfections, 71 (10.9%) hospitalizations, and 3 (0.5%) deaths. We interviewed 510/653 PLWH (78%), and 178 (PCCs prevalence 34.9%; CI95% 30.7–39.2) reported persistent symptoms. Asthenia/fatigue was the most reported symptom (60/178), followed by muscular pain (54/178). In the multivariate regression model, male sex was protective (adjusted OR = 0.64; CI95% 0.99–3.66), while hospitalization during acute infection was associated with an increased the risk of PCCs (adjusted OR = 1.9; CI95% 0.99–3.66). Notably, no viro-immunological variable modified the PCCs risk onset.Conclusions Our study highlights a substantial prevalence of PCCs among PLWH, three months post-SARS-CoV-2 infection, independent of viro-immunological features or vaccination status.

School-aged children’s movement behaviours and subjective health complaints in Japan: A cross-sectional study during COVID-19 pandemic-related school closure and after school reopening (preprint)

Background: Social restrictions associated with the COVID-19 pandemic have altered children’s movement behaviours and impacted their mental health. However, the influence of social restrictions on subjective health complaints remains inadequately understood. This study compared adherence to 24-hour movement behaviour guidelines and the prevalence of subjective health complaints during school closure and one year after reopening. We also examined how combinations of adherence to movement behaviour recommendations relate to subjective health complaints. Methods: A repeated cross-sectional survey was conducted at two points. The first survey in May 2020 included 1535 (766 boys and 769 girls) participants during school closures, while the second survey from May to July 2021 involved 1125 (583 boys and 542 girls) participants one year after school reopening. The questionnaire covered socio-demographics, physical activity, screen time, sleep, and subjective health complaints. Differences between periods were analysed using chi-square tests. Logistic regression models assessed the association between adherence to guidelines and subjective health complaints. Results: During school closure, children were more likely to meet ‘only sleep’ recommendations and experience irritability and lethargy symptoms as compared to one year after school reopening. Irrespective of sex, those adhering to two or all three recommendations (excluding physical activity and screen time) had a lower risk of symptoms related to physical and mental pain, fatigue, irritability, and lethargy as compared to those who met no recommendation. Conclusions: Children should meet at least one physical activity or screen time recommendation in addition to sleep recommendations for subjective health. Strategies considering the priority of each movement behaviour are crucial, even during abnormal situations, such as pandemic-related social restrictions. This study offers insightful findings concerning children’s mental health issues during unprecedented and massive disasters or crises.

Association between assisted living facility context and resident pain during the COVID-19 pandemic: A repeated cross-sectional study (preprint)

Background Resident pain has been a common quality issue in congregate care for older adults, and COVID-19-related public health restrictions may have negatively affected resident pain. Most studies have focused on nursing homes (NHs), largely neglecting assisted living (AL). AL residents are at similar risk for pain as NH resident, but with AL providing fewer services and staffing resources. Our study examined whether potentially modifiable AL home characteristics were associated with resident pain during the first two waves of the COVID-19 pandemic.Methods This repeated cross-sectional study linked AL home surveys, collected in COVID-19 waves 1 (March-June 2020) and 2 (October 2020-February 2021) from a key contact, to administrative Resident Assessment Instrument – Home Care (RAI-HC) records in these homes. Surveys assessed preparedness for COVID-19 outbreaks, availability of a registered nurse or nurse practitioner, direct care staff shortages, decreased staff morale, COVID-19 outbreaks, confinement of residents to their rooms, supporting video calls with physicians, facilitating caregiver involvement. The dependent variable (moderate daily pain or pain of a severe intensity) and resident covariates came from the RAI-HC. Using general estimating equations, adjusted for repeated resident assessments and covariates, we assessd whether AL home factors were associated with resident pain during the pandemic.Results We included 985 residents in 41 facilities (wave 1), and 1,134 residents in 42 facilities (wave 2). Pain prevalence [95% confidence interval] decreased non-significantly from 20.6% [18.6%-23.2%] (March-June 2019) to 19.1% [16.9%-21.6%] (October 2020-February 2021). Better preparedness (odds ratio = 1.383 [1.025–1.866]), confinement of residents to their rooms (OR = 1.616 [1.212–2.155]), availability of a nurse practitioner (OR = 0.761 [0.591–0.981]), and staff shortages (OR = 0.684 [0.527–0.888]) were associated with resident pain.Conclusions AL facility-level factors were associated with resident pain during the COVID-19 pandemic. Policy and management interventions can and must address such factors, providing potentially powerful levers for improving AL resident quality of care.

Effectiveness and Safety of COVID-19 Vaccines, including Vaccination Issues in Trinidad and Tobago: A Systematic Review (preprint)

Vaccination against the SARS-CoV2 virus has shown great promise in managing the spread and severity of Covid-19. While these vaccines were able to provide a favourable response in controlling the SARS-CoV2 infection, its use came with accompanying side effects. This systematic review aimed to determine the effectiveness of the different Covid-19 vaccine subtypes and discover the side effects associated with each vaccine elsewhere but specially in Trinidad and Tobago. For this systematic review, the keywords “Pfizer-BioNTech OR Moderna OR Oxford-AstraZeneca OR Janssen OR Sinopharm OR Novavax AND Covid-19 vaccine efficacy” and “Covid-19 vaccines AND Trinidad and Tobago” were researched under PubMed, MEDLINE and other internet sources through which other notable journals, and documents were discovered and searched similarly as outlined previously. In doing so, 65 relevant articles were included as part of this review. Of the studies examined, overall the vaccine with the greatest VE was found to be Pfizer-BioNTech (95%), followed by Moderna (94.1%), Novavax (89.7%), AstraZeneca (70.4%), Sinopharm (67%) and finally Janssen (66.9%). The use of Pfizer-BioNTech or Moderna was most efficacious in response to the different Covid-19 variants. Some side effects were common for all vaccine types however adverse effects were more commonly seen with vaccination by mRNA vaccines, Pfizer-BioNTech and Oxford-Astrazeneca. Researchers targeted individuals aged 18 and above residing in various geographical areas of TT, specifically focusing on those who had not received the COVID-19 vaccine and expressed hesitancy towards it. Convenience sampling was used to select the study participants, and formal in-depth virtual interviews were conducted on a one-to-one basis, employing a semi-structured questionnaire to guide the discussions. The interviews were meticulously recorded and transcribed, following the principles of reflexive thematic analysis, to distill key insights from the participants' responses. The study's findings, derived from the perspectives of 25 participants, illuminated a complex tapestry of reasons underlying vaccine hesitancy in Trinidad and Tobago. Notably, prominent themes emerged, including fear, doubts regarding vaccine efficacy, a perceived inadequacy of information, a sense of susceptibility to the virus, deep-seated mistrust, alternative herbal remedies, and religious reservations. Interestingly, the motivations expressed by these vaccine-hesitant individuals for potentially receiving the vaccine in the future were rooted in notions of necessity, an increased sense of susceptibility to the virus, a desire to reach a certain health benchmark, and a need for assurance regarding the vaccine's safety and effectiveness. This comprehensive exploration of vaccine hesitancy in TT provides valuable insights for public health officials and policymakers in crafting targeted strategies to address this critical issue within the local context. Conclusion: The findings of this study determined that vaccination against the SARS-CoV2 virus provided beneficial outcomes against infection, Covid-19 related hospitalizations, ICU admissions and mortality. While vaccination was deemed highly appropriate in managing the spread of the SARS-CoV2 virus and enhancing the outcomes in infected persons, the effectiveness of the different vaccine platforms indicated that certain vaccine platforms are preferential to others in different populations. In terms of vaccine efficacy, nucleic acid vaccines such as Pfizer-BioNTech and Moderna showed the greatest effectiveness while inactivated whole virus vaccines such as Sinopharm and viral vectors like Janssen had the least effectiveness. The side effects, joint/muscle soreness, pain at the injection site, shoulder pain, headaches, fever, chills, weakness, epistaxis, renal and certain cardiovascular events were common for all vaccine types. Adverse effects were more frequent and severe with the mRNA vaccines by Pfizer-BioNTech and Oxford-Astrazeneca than inactivated whole virus vaccines. The data collected in this research can be very useful to help individuals make a decision on which vaccine would be appropriate for them. More long-term studies are needed to better gauge the scope of side effects for each vaccine type.

Post-obturation Analgesia requirements in patients vaccinated against Covid-19: a short observational study. (preprint)

Aim: To evaluate the need for Post obturation analgesia (acetaminophens) requirements in patients vaccinated against Covid-19, as the role of the NASID’s is still controversial, and the most recommended drug is acetaminophens after Covid-19 Vaccination. Material and Methods: 50 patients vaccinated against Covid-19 undergoing root canal treatments for symptomatic pulpits in molar teeth, were divided into two groups of 25 each on the basis of gender (Group M for males and Group F for females.) Each patient was given a prescription for 650 mg of acetaminophen tablets to be taken 8 hourly with instructions to avail the same only if needed for pain. They were instructed to keep a record of the number of tablets consumed as per record sheet 1, and if the pain did not subside then a stronger analgesic Ketorolac DT 10mg twice a day had to be taken and recorded. In case the pain was accompanied by swelling, the patient was given a prescription of amoxicillin 500mg TDS along with analgesics. Results: In Group M and Group F the mean number of analgesic tablets required was 0.44±0.65, 0.80±1.08 respectively, and the difference was statistically insignificant (p=0.360). The statistical analysis was done by student’s t-test using SPSS (Statistical Package for Social Sciences) Version 20.0 statistical Analysis Software. Conclusion: Within the limitations of this study, this is concluded that acetaminophen is effective in relieving post-obturation pain in patients vaccinated against COVID-19. Keywords: NSAID’s, Acetaminophen, Root Canal Treatment, COVID-19 vaccination, Covisheild

Menstrual Symptom Disorders After COVID-19 in Relation To Anxiety and Long COVID Symptoms (preprint)

Aim: and objectives: Coronavirus disease (COVID-19) can affect the menstrual cycle and menstrual volume. We aimed to examine the changes in menstrual symptoms of women who had recovered from COVID-19 and determine the factors affecting these changes. Methods: A questionnaire, prepared using Google Forms, was completed online in May 18-31, 2021 by 180 women (26.08±6.62 years) who had recovered from COVID-19. Menstrual symptoms, menstrual pain severity, fatigue severity and anxiety levels of the participants were assessed with Menstrual Symptom Questionnaire (MSQ), Visual Analogue Scale (VAS) and Fatigue Severity Scale (FSS), Coronavirus Anxiety Scale (CAS), respectively. Results: Post-COVID-19 individuals’ MSQ total scores and subgroup scores, FSS scores and menstrual pain showed a statistically significant increase compared to pre-COVID-19 (p < 0.001 for all). Multiple linear regression analysis identified age at menarche and change in FSS and VAS scores as significant contributors to 38.4% of the variance explained in the significant regression for change in MSQ score (F (3.176) = 38.23, p < 0.001). Individuals with prolonged fatigue, muscle–joint pain and dyspnea symptoms showed increased MSQ total scores (p = 0.006, p = 0.009, p = 0.046 respectively) and negative effects/somatic complaints subgroup scores (p = 0.004, p = 0.002, p = 0.017 respectively). Also, individuals with prolonged gastrointestinal symptoms showed increased pain symptoms (p = 0.029) and coping methods subgroup scores (p = 0.002), while those with prolonged muscle and joint pain showed increased coping methods (p = 0.022) subgroup scores. Conclusion: In this study, we observed worsened menstrual symptoms, fatigue, and menstrual pain severity in women recovered from COVID-19. In addition, age at menarche and fatigue and menstrual pain scores differences after COVID-19 were determiners of the changes in menstrual symptoms. Menstrual symptoms were more severe in women who have prolonged fatigue, dyspnea, muscle–joint pain, and gastrointestinal symptoms.

COVID-19 induced Multisystem Inflammatory Syndrome in Adult and Acute Limb Ischemia. (preprint)

The patient presented with a chief complaint of lower extremity pain was found to be positive SARS-CoV-2 test. Contrast-enhanced computed tomography scans showed endocarditis, vasculitis and lower extremity ischemia. Despite we treated the patient with dexamethasone, the patient died.

Cytokine Storm Fatal Acute Kidney Infection Triggered by COVID-19 (SARS CoV-2) Infection: A Review (preprint)

Acute kidney infection (AKI) occurred by tubular necrosis and glomerular dysfunction caused by many factors. SARS CoV-2 infection identified to cause fatal AKI. This paper aims to review the effect of covid-19 infection on the failure of the kidney and its mechanism. It identified that the SARS-CoV-2 received by the targeted cell by Angiotensin-converting enzyme 2 (ACE2). After the virus received by the target cells, it induces the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-1, and interferons (IFN) by immune cells and causes cytokine storm. The pro-inflammatory cytokines are again responsible to induce the secretion of cyclooxygenase‑2 (COX‑2), which causes inflammation and pain as well it stimulates the iNOS enzyme to produce NO which allows the vasodilation of renal arteries. The increased production of NO by iNO enhanced the vasodilation of arteries, and allows the adhesion of neutrophils to the artery, and causes damage to glomerulus and tubules. Hence, the most likely sustainable intervention could be the application of angiotensin-converting enzyme 2 (ACE2) inhibition by the receptors of the target cells in these vital organs to reduce sever destruction during treatment at the early stage of infection.