SARS-CoV2 Infection Research Articles

Regulatory T Cell Phenotype Related to Cytokine Expression Patterns in Post-COVID-19 Pulmonary Fibrosis and Idiopathic Pulmonary Fibrosis.

Post-coronavirus disease 19 lung fibrosis (PCLF) shares common immunological abnormalities with idiopathic pulmonary fibrosis (IPF), characterized by an unbalanced cytokine profile being associated with the development of lung fibrosis. The aim of the present study was to analyze and compare the different subsets of CD4- and CD8-T cells, along with specific cytokine expression patterns, in peripheral blood (PB) from patients affected by PCLF and IPF and healthy controls (HCs). One-hundred patients followed at the Rare Lung Disease Center of Siena University Hospital were enrolled. Eight HCs were recruited. PB samples were collected, and CD4- and CD8-T subsets were analyzed through flow cytometry. Multiplex bead-based LEGENDplex™ were used for cytokine quantification. Higher CD8 percentages were observed in IPF than in HCs and PCLF (p = 0.020 and p = 0.007, respectively). PCLF subgroup showed higher Th-naïve, Th-effector, Tc-naïve, and Tc-reg percentages than IPF (p < 0.001; p = 0.018; p = 0.005; p = 0.017, respectively). Th-naïve and Tc-naïve inversely correlated with Tc-reg (p < 0.0001, r = -0.61 and p = 0.005, r = -0.39, respectively). Tc-naïve-PD1 and Tc-effector-PD1 percentages were higher in PCLF than IPF (p < 0.001), while Tfh-reg and Tfc-reg were significantly higher in IPF than PCLF (p < 0.001). IL-4, IL-2, TNF-α, and IL-17A were more expressed in PCLF than IPF (p < 0.001). IL-8 directly correlated with Tc-naïve percentages in PCLF (p = 0.018, r = 0.35). A variety of immune cells is involved in the development and progression of pulmonary fibrosis confirming an immunological similarity between IPF and PCLF. T-reg cells play a key role in the worsening of the disease. High cytokine values showed a pro-fibrotic environment in PCLF patients, suggesting dysregulation of the immune system of these patients. Moreover, the immunological similarity between IPF and PCLF patients suggests that SARS-CoV2 infection may trigger the activation of biological pathways common with IPF.

A Prospective Hospital Based Study of Placental Changes to Identify Antenatal and Perinatal Transmission of Sars CoV2 Infection

A Prospective Hospital Based Study of Placental Changes to Identify Antenatal and Perinatal Transmission of Sars CoV2 Infection

The association between different timeframes of air pollution exposure and COVID-19 incidence, morbidity and mortality in German counties in 2020

BackgroundAmbient air pollution is a known risk factor for several chronic health conditions, including pulmonary dysfunction. In recent years, studies have shown a positive association between exposure to air pollutants and the incidence, morbidity, and mortality of a COVID-19 infection, however the time period for which air pollution exposure is most relevant for the COVID-19 outcome is still not defined. The aim of this study was to analyze the difference in association when varying the time period of air pollution exposure considered on COVID-19 infection within the same cohort during the first wave of the pandemic in 2020.MethodsWe conducted a cross-sectional study analyzing the association between long- (10- and 2-years) and short-term (28 days, 7 days, and 2 days) exposure to NO2 and PM2.5 on SARS-CoV-2 incidence, morbidity, and mortality at the level of county during the first outbreak of the pandemic in spring 2020. Health data were extracted from the German national public health institute (Robert-Koch-Institute) and from the German Interdisciplinary Association for Intensive Care and Emergency Medicine. Air pollution data were taken from the APExpose dataset (version 2.0). We used negative binomial models, including adjustment for risk factors (age, sex, days since first COVID-19 case, population density, socio-economic and health parameters).ResultsWe found that PM2.5 and NO2 exposure 28 days before COVID-19 infection had the highest association with infection, morbidity as well as mortality, as compared to long-term or short-term (2 or 7 days) air pollutant exposure. A 1 μg/m3 increase in PM2.5 was associated with a 31.7% increase in incidence, a 20.6% need for ICU treatment, a 23.1% need for mechanical ventilation, and a 55.3% increase in mortality; an increase of 1 μg/m3 of NO2 was associated with an increase for all outcomes by 25.2 – 29.4%.ConclusionsOur findings show a positive association between PM2.5 and NO2 exposure and the clinical course of a SARS-CoV2 infection, with the strongest association to 28 days of exposure to air pollution. This finding provides an indication as to the primary underlying pathophysiology, and can therefore help to improve the resilience of societies by implementing adequate measures to reduce the air pollutant impact on health outcomes.Trial registrationNot applicable.

Subset of DN Memory B Cells Expressing Low Levels of Inhibitory Receptor BTLA Is Enriched in SLE Patients.

The dialogue between T and B cells can be regulated by different mechanisms, such as co-inhibitory receptors, which therefore play a crucial role in preventing autoimmune diseases such as systemic lupus erythematosus (SLE). B and T lymphocyte attenuator (BTLA) is a co-inhibitory receptor expressed on many myeloid and lymphoid cells. Although peripheral B cells express a very high amount of BTLA, previous works in the context of autoimmunity mainly focused on T cells, and whether BTLA expression on B cells plays a role in the lupus pathogenesis is still unclear. In the present study, we examine the expression of BTLA, as well as its ligand HVEM (Herpesvirus Entry Mediator), on various B cell subsets in lupus patients compared to healthy controls (HCs). We evidenced the existence of double-negative (DN; IgD-CD27-) memory B cells expressing very low levels of BTLA, which are enhanced in active lupus patients. An in-depth analysis revealed that these BTLAlow DN cells mainly correspond to the newly reported DN3 B cell subset, originally described in the context of SARS-CoV2 infection. These cells display an activated and antibody-secreting cell phenotype, and we propose that their low BTLA expression may favor their expansion and rapid differentiation into plasmablasts in lupus patients.

Predictors of sepsis in hospitalized COVID-19 patients

BackgroundViral sepsis has been suggested as a precise term to define multisystem dysregulated immune response and clinical sequelae in severe and critical COVID-19 cases. This work aimed to determine predictors of sepsis in those patients and to report their outcomes.MethodologyThis prospective observational clinical study took place on 120 patients aged more than 18 years old, both genders, and hospitalized patients with laboratory-verified SARS CoV-2 infection. Enrolled patients were allocated into two groups: sepsis group (n = 49) and no sepsis group (n = 71).ResultsCOVID-19 severity, National Early Warning Score (NEWS) risk, and Quick Sepsis-related Organ Failure Assessment (qSOFA) score were significantly elevated in sepsis group. Glasgow Coma Scale was significantly reduced in sepsis group (P < 0.05). Mortality, length of hospital stay, ICU admission, and ventilatory support were significantly higher in sepsis group (P < 0.05). Serum procalcitonin was significantly elevated in sepsis group (P < 0.05). Serum procalcitonin can significantly predict sepsis at cutoff > 0.5 µg/L with 89.8% sensitivity and 90% specificity. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pH (decreased in sepsis group), heart rate (HR), platelets count, lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), qSOFA score, serum procalcitonin, and duration of hospitalization (increased in sepsis group) were independent predictors of sepsis.ConclusionsIn COVID-19 patients, decreased SBP, DBP, MAP, and pH while increased HR, respiratory rate, platelets, LDH, ESR, qSOFA score, serum procalcitonin, and duration of hospitalization were found to be independent predictors of sepsis.

Small-molecule inhibition of SARS-CoV-2 NSP14 RNA cap methyltransferase.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1. The rapid development of highly effective vaccines2,3 against SARS-CoV-2 has altered the trajectory of the pandemic, and antiviral therapeutics4 have further reduced the number of COVID-19 hospitalizations and deaths. Coronaviruses are enveloped, positive-sense, single-stranded RNA viruses that encode various structural and non-structural proteins, including those critical for viral RNA replication and evasion from innate immunity5. Here we report the discovery and development of a first-in-class non-covalent small-molecule inhibitor of the viral guanine-N7 methyltransferase (MTase) NSP14. High-throughput screening identified RU-0415529, which inhibited SARS-CoV-2 NSP14 by forming a unique ternary S-adenosylhomocysteine (SAH)-bound complex. Hit-to-lead optimization of RU-0415529 resulted in TDI-015051 with a dissociation constant (Kd) of 61 pM and a half-maximal effective concentration (EC50) of 11 nM, inhibiting virus infection in a cell-based system. TDI-015051 also inhibited viral replication in primary small airway epithelial cells and in a transgenic mouse model of SARS CoV-2 infection with an efficacy comparable with the FDA-approved reversible covalent protease inhibitor nirmatrelvir6. The inhibition of viral cap methylases as an antiviral strategy is also adaptable to other pandemic viruses.

Early combination of sotrovimab with nirmatrelvir/ritonavir or remdesivir is associated with low rate of persisting SARS CoV-2 infection in immunocompromised outpatients with mild-to-moderate COVID-19: a prospective single-centre study

Background Immunocompromised patients are at high risk of developing persisting/prolonged COVID-19. Data on the early combined use of antivirals and monoclonal antibodies in this population are scarce. Research design and methods We performed an observational, prospective study, enrolling immunocompromised outpatients with mild-to-moderate COVID-19, treated with a combination of sotrovimab plus one antiviral (remdesivir or nirmatrelvir/ritonavir) within 7 days from symptom onset. Primary outcome was hospitalization within 30 days. Secondary outcomes were: needing for oxygen therapy; development of persistent infection; death within 60 days and reinfection or relapse within 90 days. Results We enrolled 52 patients. No patient was hospitalized within 30 days of disease onset, required oxygen administration, died within 60 days, or experienced a reinfection or clinical relapse within 90 days. The clearance rates were 67% and 97% on the 14th day after the end of therapy and at the end of the follow-up period, respectively. Factors associated with longer infection were initiation of therapy 3 days after symptom onset and enrollment for more than 180 days from the beginning of the study. However, only the latter factor was independently associated with a longer SARS-CoV-2 infection, suggesting a loss of efficacy of this strategy with the evolution of SARS-CoV-2 variants. Conclusions Early administration of combination therapy with a direct antiviral and sotrovimab seems to be effective in preventing hospitalization, progression to severe COVID-19, and development of prolonged/persisting SARS-CoV-2 infection in immunocompromised patients.

Altered plasma levels of the SARS-CoV-2-related proteins ACE2 and TMPRSS2 in patients with Crohn’s disease

The SARS-CoV-2 coronavirus infects cells through the cellular receptor angiotensin-converting enzyme 2 (ACE2), and the protease TMPRSS2 for the priming of viral spike protein. Thus, changes in these key proteins due to chronic conditions can increase risk for SARS-CoV2 infection; but significance of changes may differ is these changes correspond to full-length species or proteolytic fragments. Here, we determined that full-length ACE2 decreased in the plasma of uninfected Crohn’s disease (CD) patients before treatment onset compared to controls. TMPRSS2 is mostly presented in plasma as full-length species and as an active peptidase fragment, but also as a prodomain fragment, which is the unique species remarkably decreased in plasma from CD patients. Patients treated with the anti-TNFα adalimumab showed recovery in ACE2 levels, while those treated with infliximab, or with the anti-IL-12/23 ustekinumab, still displayed a decrease in full-length species, as well as in cleaved fragments. Patients treated with azathioprine displayed similar ACE2 levels to that of controls, except a decrease in one of the ACE2 fragments. Uniquely, patients treated with azathioprine or with ustekinumab showed partial recovery in the reduction of the TMPRSS2-prodomain fragment characterized in treatment-naïve patients. Our data suggest that CD and common therapies are not related to increased susceptibility for SARS-CoV-2.

Features of chronic urticaria after COVID-19 mRNA vaccine over time

BackgroundNew onsets of chronic urticaria (CU) have been reported after repeated immunizations, mainly with the Moderna mRNA-1273 vaccine (Spikevax). This study aims to evaluate patients with CU after COVID-19 mRNA vaccination. The contribution of SARS-Cov2 infection, atopy and IgE against the vaccine was analyzed.MethodsWe monitored the features of patients who developed CU after vaccination through two surveys conducted in 2022 and 2023. Fifty individuals with CU underwent blood tests, and their results were compared with individuals without a history of urticaria (N = 135). The presence of anti-vaccine IgE was tested in 185 individuals with basophil activation tests (BAT). We assessed anti-SARS-Cov2 humoral response, and the presence of IgEs against common respiratory allergens (Phadiatop) as a surrogate for atopy.ResultsPost-vaccination CU occurs after a median interval of 10 days and significantly more after the Spikevax booster, affecting middle-aged individuals (median 41, 66% females). In 2023, CU was still active in 53% of the cases. Inducible forms of CU, primarily dermographism, are reported in 54% (2022) and 61% (2023) of the cases. BAT positivity is not specific to CU, anti-nucleocapsid positivity, or atopy but is significantly associated with higher anti-spike neutralizing activities and younger age. Four CU patients tolerate an additional dose of mRNA vaccine with no disease exacerbation/recurrence.ConclusionsThe spikevax booster induces anti-vaccine IgE independently of CU, the latter being not directly associated with COVID-19 infection nor atopy. The tolerance to a new booster in 4/4 patients suggests that the Spikevax vaccine indirectly triggers CU in predisposed individuals.

Neurological Sequelae of Post-COVID-19 Fatigue: A Narrative Review of Dipeptidyl Peptidase IV-Mediated Cerebrovascular Complications.

Coronavirus disease 2019 (COVID-19) has been a global pandemic affecting millions of people's lives, which has led to 'post-COVID-19 fatigue'. Alarmingly, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) not only infects the lungs but also influences the heart and brain. Endothelial cell dysfunction and hypercoagulation, which we know occur with this infection, lead to thrombo-inflammation that can manifest as many myriad cardio-cerebrovascular disorders, such as brain fog, fatigue, cognitive dysfunction, etc. Additionally, SARS-CoV-2 has been associated with oxidative stress, protein aggregation, cytokine storm, and mitochondrial dysfunction in neurodegenerative diseases. Accordingly, the identification of molecular targets involved in these actions could provide strategies for preventing and treating this disease. In particular, the very common enzyme dipeptidyl peptidase IV (DPPIV) has recently been identified as a candidate co-receptor for the cell entry of the SARS-CoV-2 virus with its involvement in infection. In addition, DPPIV has been reported as a co-receptor for some viruses such as Middle East respiratory syndrome-coronavirus (MERS-CoV). It mediates immunologic reactions and diseases such as type 2 diabetes mellitus, obesity, and hypertension, which have been considered the prime risk factors for stroke among other types of cardio-cerebrovascular diseases. Unlike angiotensin-converting enzyme 2 (ACE2), DPPIV has been implicated in aggravating the course of infection due to its disruptive effect on inflammatory signaling networks and the neuro-glia-vascular unit. Regarding the neurological, physiological, and molecular grounds governing post-COVID-19 fatigue, this review focuses on DPPIV as one of such reasons that progressively establishes cerebrovascular grievances following SARS-CoV infection.

A critical analysis of UK media characterisations of Long Covid in children and young people.

Long Covid is the continuation or development of symptoms related to a SARSCoV2 infection. Those with Long Covid may face epistemic injustice, where they are unjustifiably viewed as unreliable evaluators of their own illness experiences. Media articles both reflect and influence perception and subsequently how people regard children and young people (CYP) with Long Covid, and may contribute to epistemic injustice. We aimed to explore how the UK media characterises Long Covid in CYP through examining three key actor groups: parents, healthcare professionals, and CYP with Long Covid, through the lens of epistemic injustice. A systematic search strategy resulted in the inclusion of 103 UK media articles. We used an adapted corpus-assisted Critical Discourse Analysis in tandem with thematic analysis. Specifically, we utilised search terms to locate concordances of key actor groups. In the corpus, parents highlighted minimisation of Long Covid, barriers to care, and experiences of personal attacks. Mothers were presented as also having Long Covid. Fathers were unmentioned. Healthcare professionals emphasised the rarity of Long Covid in CYP, avoided pathologising Long Covid, and overemphasised psychological components. CYP were rarely consulted in media articles but were presented as formerly very able. Manifestations of Long Covid in CYP were validated or invalidated in relation to adults. Media characterisations contributed to epistemic injustice. The disempowering portrayal of parents promotes stigma and barriers to care. Healthcare professionals' narratives often contributed to negative healthcare experiences and enacted testimonial injustice, where CYP and parents' credibility was diminished due to unfair identity prejudice, in their invalidation of Long Covid. Media characterisations reveal and maintain a lack of societal framework for understanding Long Covid in CYP. The findings of this study illustrate the discursive practices employed by journalists that contribute to experiences of epistemic injustice. Based on our findings, we propose recommendations for journalists.

Anosmia and homoeopathy

Anosmia is a commonly reported symptom in COVID-19 patients that frequently occurs early in the course of the disease &amp; may persist as a long term symptom. SARS-COV2 infection has been suggested to cause the death of support cells in the olfactory epithelium with consequences for neuronal function.The article focuses on the age old concept of Ayurveda where it is advised to start feeling the senses as the day starts &amp; be aware of any changes with the comeback of Communicable Diseases (CD) such as the COVID 19 pandemic. As the CDs surged, the concept of eating while smelling the food emerged since the process of anosmia led to definitive changes in the nasal cavity that are definitive signs of COVID 19 infection. The current article sees the role of Homoeopathy of the AYUSH system in the process of anosmia due to COVID 19. Those adopting the process of healthy nasal health may use the therapeutic system of homeopathy to optimize the benefits of a healthy olfaction.After discussing the various modalities of anosmia, a homoeopathic treatment protocol is suggested on the lines of the markers mentioned above. The article aspires that this integration will help the nation to deal with the current &amp; future menace of CDs.

Abstract 4138507: Uncovering Risk Factors for Myocarditis and Cardiac Arrhythmia in Youth Post-SARS-CoV-2 Infection: Insights from the N3C Database and Advanced Machine Learning

Background: SARS-CoV2 infection has been associated with cardiovascular consequences, including myocarditis and cardiac arrhythmias. Myocarditis secondary to SARS-CoV2 infection and cardiac arrhythmias may often go unrecognized and can present with late and nonspecific symptoms. Predicting those at risk allows for prompt treatment and prevention of their potentially life-threatening consequences. Methods: The National COVID Cohort Collaborative (N3C) database was used to identify patients aged 0-30 years with COVID-19 index date between 1/1/2020 and 3/31/2022, whose sites provided data for at least six months beyond the index date. Outcomes included myocarditis and new arrythmias within 6 months of the index visit. Patients with known cardiac comorbidities were excluded. Predictors included gender, race, COVID severity as an ordinal scale, vaccination status, clinical comorbidities, and Area Deprivation Index (ADI). The data were stratified by age groups (0-4, 5-17, 18-30). Random forest models were used for data analysis and SHapley Additive exPlanations (SHAP) method was applied to optimize results. These analyses were conducted using the NCATS N3C Data Enclave. Results: Of the 1,487,741 patients in our study population, 4,105 (0.28%) had the measured outcomes; 404 had myocarditis only, 3,634 had arrhythmia only and 67 had both. Severity of COVID (SHAP 0.2344 for 0-4 years, 0.2114 for 5-17, 0.1370 for 18-30) was identified as the most important risk factor for de-novo myocarditis and arrhythmias overall. Increase in ADI (indicating lower socioeconomic status) was the second most important risk factor for the 0-4 and 5-17 age groups (SHAP: 0.0370, 0.0223). Among the 18-30 age group, race (SHAP 0.0321) and gender (SHAP 0.0289) were the second and third most important risk factors, with White and Black patients more likely to develop an event and Hispanic patients less likely. Women were less likely to develop a cardiac outcome than men. Conclusion: The severity of COVID was identified as the most important risk factor for the occurrence of myocarditis or cardiac arrhythmia within 6 months of infection. ADI, race, and gender were also identified as important, though less influential, risk factors.

Genomic characteristics, disease outcome and heterologous vaccine effectiveness among cases with SARS CoV-2 infection

BackgroundIn the pursuit of global health security, continuous monitoring of vaccine effectiveness across various viral strains emerges as a crucial imperative. The emergence of SARS-CoV-2 major variants of concern (VOCs), including Alpha, Beta, Delta, and Omicron, has added complexity to the COVID-19 vaccination landscape.ObjectivesTo assess illness severity, evaluate vaccine efficacy across varying doses and types, and determine effectiveness against major VOCs within the population.MethodsThis retrospective cohort study, conducted in Abu Dhabi, United Arab Emirates, focuses on a cohort of 44,073 SARS-CoV-2 positive cases from February 2021 to May 2022, dominated by the Delta and Omicron variants. The study employed a nested case-control design, analyzing hospital admissions for confirmed SARS-CoV-2 infection.ResultsVaccine effectiveness was higher among heterologus-boosted individuals at 87% (95% CI:79%-93%) compared to homologus-boosted individuals at 59% (95% CI: 48%-68%) and fully vaccinated, non-boosted adults at 53% (95% CI: 46%-59%). These findings highlight the importance of heterologous boosting, particularly against rapidly evolving viral variants, offering valuable insights for refining pandemic response strategies.ConclusionThe study underscores the critical need for ongoing assessment and adaptation of vaccination strategies to the evolving viral landscape.

Long COVID and recovery from Long COVID: quality of life impairments and subjective cognitive decline at a median of 2 years after initial infection

BackgroundRecovery from SARS CoV-2 infection is expected within 3 months. Long COVID occurs after SARS-CoV-2 when symptoms are present for more than 3 months that are continuous, relapsing and remitting, or progressive. Better understanding of Long COVID illness trajectories could strengthen patient care and support.MethodsWe characterized functional impairments, quality of life (QoL), and cognition among patients who recovered from SARS-CoV-2 infection within 3 months (without Long COVID), after 3 months (Recovered Long COVID), or remained symptomatic (Long COVID). Among 7305 patients identified with previous SARS-CoV-2 infection between March 2020 and December 2021, confirmed in the medical record with laboratory test or physician diagnosis, 435 (6%) completed a single self-administered survey between March 2022 and September 2022. Multi-domain QoL and cognitive concerns were evaluated using PROMIS-29 and the Cognitive Change Index-12.ResultsNearly half the participants (47.7%) were surveyed more than 2 years from initial infection (median = 23.3 months; IQR = 18.6, 26.7) and 86.7% were surveyed more than 1 year from infection. A significantly greater proportion of the Long COVID (n = 215) group, (Current and Recovered combined), had moderate-to-severe impairment in all health domains assessed compared to those Without Long COVID (n = 220; all p < 0.05). The Recovered Long COVID group (n = 34) had significantly lower prevalence of fatigue, pain, depression, and physical and social function impairment compared to those with Current Long COVID (n = 181; all p < 0.05). However, compared to patients Without Long COVID, the Recovered Long COVID group had greater prevalences of fatigue, pain (p ≤ 0.06) and subjective cognitive decline (61.8% vs 29.1%; p < 0.01). Multivariate relative risk (RR) regression indicated Long COVID risk was greater for older age groups (RR range 1.46–1.52; all p ≤ 0.05), those without a bachelor’s degree (RR = 1.33; 95% CI = 1.03–1.71; p = 0.03), and those with 3 or more comorbidities prior to SARS-CoV-2 infection (RR = 1.45; 95% CI = 1.11–1.90; p < 0.01).ConclusionsLong COVID is associated with long-term subjective cognitive decline and diminished quality of life. Clinically significant cognitive complaints, fatigue, and pain were present even in those who reported they had recovered from Long COVID. These findings have implications for the sustainability of participation in work, education, and social activities.

Experimental Study on Video Discharge Instructions for Pediatric Fever in an Emergency Department.

Fever is a frequent cause of consultation in the pediatric emergency department (PED). Adequate discharge instructions are essential to guarantee good management at home and can reduce caregivers' anxiety and re-consultations. This study compares the improvement of caregivers' knowledge regarding fever between verbal discharge instructions and the addition of a video to verbal information. As a secondary outcome, we compared the rate of return visits. An experimental, prospective, single-center study was conducted in a tertiary hospital PED. Patients between 3months and 5years old with febrile syndrome were enrolled. Patients with comorbidities or SARS-COV2 infection were excluded. First, caregivers answered a written test concerning fever characteristics, management, and warning signs. Patients were assigned by simple randomization to a control group (standard verbal and written instructions) or to an intervention group (which additionally received video instructions). After discharge, investigators contacted caregivers by telephone. Caregivers were asked to answer the same questions as in the written test in addition to the need for subsequent visits (at the PED or any other healthcare facility) after discharge. Seventy-three patients were randomized to the intervention group and 77 to the control group (2 were lost during follow-up). There were no differences in the acquisition of caregiver's knowledge, with a median score improvement of 2 points in both groups (control group interquartile range (IQR) 1-2; intervention group IQR 1-3) (P =.389). In the intervention group, we observed a significant increase of correct answers in 4 out of 7 questions compared to 3 out of 7 questions in the control group. In the control group, 18.7% reconsulted compared to 10.9% in the intervention group (P =.188). Video instructions were not superior to verbal instructions at improving caregivers' knowledge of fever overall. However, more questions obtained a significant score increase in those that received video and verbal instructions. Our results suggest that the addition of video instructions could help reduce return visits.

Neurodevelopment in the First 2 Years of Life Following Prenatal Exposure to Maternal SARS-CoV-2 Infection

The effects of prenatal exposure to SARS-CoV-2 infection on child development throughout the first 2 years of life are unknown. To evaluate whether prenatal exposure to SARS-CoV-2 infection was associated with child neurodevelopmental outcomes during the first 2 years of life. This cohort study used data from the longitudinal, population-based pan-Canadian Pregnancy During the COVID-19 Pandemic cohort, which recruited participants from April 2020 to July 2022. Children were categorized as exposed to prenatal SARS-CoV-2 infection if their birthing parent had a positive polymerase chain reaction test performed by a health authority or as a healthy negative comparison if their birthing parent did not have SARS-CoV-2 antibodies in their postpartum dried blood spot sample. Prenatal SARS-CoV-2 infection. The birthing parent reported on their child's temperament at ages 6 and 24 months, developmental milestones at ages 12 and 24 months, and social-emotional milestones at ages 12 and 24 months. A total of 896 children were included, with 96 children who had been exposed to a prenatal SARS-CoV-2 infection (mean [SD] gestational age at birth, 39.20 [1.50] weeks; 45 [47%] male) and 800 were healthy negative comparisons (mean [SD] gestational age at birth, 39.47 [1.54] weeks; 388 [49%] male). In analyses of covariance adjusted for prepregnancy medical conditions and household socioeconomic status, prenatal exposure to SARS CoV-2 infection was associated with slightly higher regulatory control scores, indicating more regulation, at age 6 months (difference in means, 0.19 [95% CI, 0.02-0.36]; P = .03; ηp2 = 0.01). No significant differences were observed for the other neurodevelopmental outcomes. In mixed models adjusted for the same covariates that aimed to examine change in outcomes over time, prenatal SARS-CoV-2 infection exposure was not associated with developmental change in any neurodevelopmental outcomes between ages 6 and 24 months. In this longitudinal cohort study of multiple aspects of child neurodevelopment between ages 6 and 24 months, negligible associations between prenatal exposure to SARS-CoV-2 infection and child outcomes were observed. Follow-up research is warranted to determine whether these predominantly null effects persist into later childhood.

In vivo characterization of ACE2 expression in Sprague-Dawley rats and cultured primary brain pericytes highlights the utility of Rattus norvegicus in the study of COVID-19 brain pathophysiology

A high number of COVID-19 patients report ongoing neurological impairments including headache, fatigue and memory impairments. Our understanding of COVID-19 disease mechanisms in the brain is limited and relies on post-mortem human tissues, in vitro studies in various cell lines (both human and animal) as well as preclinical studies in a variety of species. Notably the use of rats in the study of COVID-19 has been scarce in part due to early reports of low infectivity of the original Wuhan strain in mice and rats. Evidence has shown that subsequent strains that have mutated from the original strain are capable of infection in rats. Here we present an immunohistological characterization of ACE2 expression in the rat brain perivascular region. We found ACE2 to be expressed in pericytes but not endothelial cells or astrocytes in the perivascular space. We further examined the uptake of Omicron variants 1.1.529 and BA.2 receptor binding domains (RBD) of the SARS-CoV2 spike protein in primary brain pericytes derived from rats. We demonstrate that rat primary brain pericytes are susceptible to SARS-CoV2 spike protein uptake and induce functional changes in pericytes associated with a reduction in tight junction protein expression. These data provide evidence that rat primary cell responses to SARS-CoV2 infection are consistent with reports of infectivity in other species (transgenic mice expressing hACE2, ferrets, hamsters) and supports the use of this model organism with a long history of use in the study of disease which should be leveraged for study of COVID-19 in the brain.

Weight loss in subjects with type 2 diabetes before and after SARS-CoV2 infection - A retrospective observational study

Weight loss in subjects with type 2 diabetes before and after SARS-CoV2 infection - A retrospective observational study

Epidemiological, clinical, paraclinical, evolutionary, and therapeutic aspects of hypertensive patients infected by COVID-19: about 702 patients in our city

Abstract Introduction Hypertension (HT) is a major cardiovascular risk factor frequently observed in COVID-19 patients. This study aimed to determine the frequency of hypertensive patients infected with COVID-19 at a national hospital, describe their epidemiological, clinical, paraclinical, and therapeutic profile, their disease progression, and identify factors associated with death. Methodology A retrospective, descriptive, and analytical study was conducted over 24 months and 4 days, from 27 March 2020 to 30 March 2022, at national hospital. Included were hospitalized patients at a hospital with a confirmed COVID-19 diagnosis, known hypertensives, regardless of gender, and with a hospitalization record. COVID-19 diagnosis was based on a positive SARS-CoV-2 RT-PCR or a positive COVID Rapid Diagnostic Test. Data were collected using a survey form, with a p-value less than 0.05 considered statistically significant for bivariate analysis. Results The study enrolled 702 patients, a hospital frequency of 23.95%. The average age was 65.14 ± 12.24 years with a sex ratio of 0.81. Comorbidities were predominantly diabetes (40.5%) and dyslipidemia (4.8%). Common symptoms included cough (65%), dyspnea (42.3%), fever (47.4%), and asthenia (35.9%). Blood pressure was normal in 15.2%, high-normal in 16.8% of patients. HT was Grade I in 12.1%, Grade II in 10%, and Grade III in 6.8% of the population, with blood pressure unmeasurable in 0.3% of known hypertensive patients. SARSCOV2 infection was mild in 34.2% and moderate in 42.8% of cases. CT scans showed extensive (31.8%), severe (25.9%), moderate (25.6%), critical (8.5%), and minimal (7.9%) lung damage. Treatment mainly consisted of ACE inhibitors (29%), ACE inhibitors in combination with another antihypertensive (8.4%), and ARBs in combination with an antihypertensive (). The average hospital stay was 12.85 days with a favorable outcome in 81% and a mortality rate of 15.5%. Factors associated with death included not being vaccinated against COVID-19 (HR: 11.70; 95% CI: 1.324-103.519), critical clinical form (HR: 11.70; 95% CI: 1.324-103.519), pulmonary consolidation (HR: 8.87; 95% CI: 7.539-24.207), high creatinine (HR: 4.69; 95% CI: 1.360-16.181), critical CT thoracic level (HR: 2.42; 95% CI: 1.020-5.745), and not taking ARBs (HR: 6.02; 95% CI: 2.812-12.889). Conclusion HT can be associated with COVID-19, impacting the disease's prognosis with significant mortality. Preventing its incidence and morbidity/mortality is crucial.