Correlation of SARS-CoV-2 fecal negative with gastrointestinal eubiosis in asymptomatic, mild and moderate cases of COVID-19 in Lagos, Nigeria (preprint)

Background: The severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2) when disseminated to the gastrointestinal (GI) tract through the bidirectional gut-lung crosstalk can cause alterations in GI microbiota composition and diversity. There is, however, paucity of data linking SARS-CoV-2 fecal negative with GI microbial balance. This study investigated the association of the GI bacterial composition with clinically defined asymptomatic, mild/moderate COVID-19 fecal negative individuals. A total of twelve (12) fecal samples comprising COVID-19 nasopharyngeal (NP) positive (P) (n=7) and negative (N) (n=5) consenting participants were collected and analyzed. The extracted RNA from the stool samples of NP positive were used as templates for the RT-qPCR detection of SARS-CoV-2 nucleocapsid (N) and open reading frame (ORF1ab) genes, while DNA from all samples (n=12) was used for the 16S bacterial rRNA metagenomics analysis. The Pielou index and Shannon index were used to assess the alpha diversity of the two groups (P and N) using the Kruskal-Wallis significance test, while the beta taxonomic diversity was assessed with the Bray-Curtis diversity index using the Permutational Multivariate Analysis of Variance (PERMANOVA) for the significance test. Taxonomic classification was performed using the Greengenes database trained for the hyper variable 4 of the 16S rRNA (gg_2022_10_backbone. v4. nb). Results: Participants positive for nasopharyngeal COVID-19 RT-PCR (ages 17-74 years) reported none (n=2, 28.5%), mild (n=4, 57.1%) and moderate (n=1, 14.3%) clinical symptoms. The viral genes were not detected with uniformity and richness of bacterial species in stool samples from positive and negative COVID-19 without significant differences in alpha diversity, Pielou (p=0.223), Shannon index (p = 0.062), and beta taxonomic diversity (PERMANOVA p=0.357). The taxonomic classification showed 14 phyla, 276 genera and 448 species in the samples, with Firmicutes, Bacteroidota, and Proteobacteria as the most abundant phyla. The most dominant species were beneficial microbes such as Prevotella copri, Phocaeicola vulgatus, and the immunomodulatory, anti-inflammatory bacterium Faecalibacterium prausnitzii. Conclusions: This study did not reveal any differences in the gut bacterial community of SARS-CoV-2 fecal negative, asymptomatic, mild and moderate COVID-19 compared to the apparently healthy control.

Rox Index Variation as Predictor of Outcomes in COVID-19 Patients. Calderón Hospital Quito (preprint)

Background: During the pandemic, Emergency departments were overcrowded with critically ill patients and confronted ethical dilemmas to assign respiratory support to them due to scarce resources. Quick tools to evaluate patients at admission were needed; many scores were used but inaccurate to predict outcomes. The Rox Index is an easy and fast score that reflects the respiratory status in acute respiratory failure patients, this score could predict the outcome of covid 19 patients. Hypothesis: The 24-hour difference in the Rox Index discriminate accurately the mortality and needs for mechanical ventilation of patients with covid-19. Methods: Study design: Prospective analytic study. Population: 204 Patients admitted to the emergency department from May to August 2020. Data were collected from the clinical records. The Rox Index was calculated at admission and 24h later, the difference was used to establish the outcome, a logistic regression model adjusting for age, sex, presence of comorbidities and disease severity to build and perform ROC analysis. Results: Difference in respiratory ROX Index between admission and 24h is a good predictor for death AUC 0.92 and for mechanic ventilation AUC: 0.75. Each decrease in one unit of the difference at 24h had an Odds Ratio for death risk: 1.48 (95%CI: 1.31-1.67) and for mechanic ventilation: 1.16 (95%IC: 1.1-1.23). Conclusion: The 24-hour variation of Rox Index has good predictive value and allows healthcare professionals to identify which patients will benefit from invasive treatment, especially in low resource settings where emergency physicians deal with survival.

High transferability of neutralizing antibodies against SARS-CoV-2 to umbilical cord blood in pregnant women with BNT162b2 XBB.1.5 vaccine - a retrospective cohort study (preprint)

Coronavirus disease 2019 (COVID-19), when contracted by pregnant women, can lead to severe respiratory illness, rapid disease progression, and higher rates of intensive care unit admission. COVID-19 infection during pregnancy is associated with an increased risk of preterm delivery, cesarean section, fetal dysfunction, preeclampsia, and perinatal death. Additionally, vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from pregnant women to their fetuses has been observed. While severe infections in neonates and infants are rare, newborns can experience serious consequences from COVID-19, despite their suboptimal humoral immune system protection. The amino acids in the structural proteins of SARS-CoV-2 are subjected to constant mutation. Since around January 2023, COVID-19, caused by infection with omicron-type SARS-CoV-2 variants, has been prevalent globally. Omicron-type SARS-CoV-2 variants can evade the immune response triggered by traditional mRNA-based COVID-19 vaccines, such as BNT162b2. Therefore, vaccination with a vaccine (BNT162b2 XBB.1.5) that can provide protection against omicron-type SARS-CoV-2 variants is recommended. Therefore, we examined the titers of anti-spike glycoprotein of SARS-CoV-2 IgG and IgA in the blood and umbilical cord blood obtained from pregnant women vaccinated with BNT162b2 XBB.1.5. The results showed that anti-spike glycoprotein of SARS-CoV-2 IgG and IgA titers were highest in the blood and cord blood obtained from pregnant women vaccinated with BNT162b2 XBB.1.5 at late gestational age (28-34 weeks). No serious side effects or adverse events caused by vaccination of pregnant women with BNT162b2 XBB.1.5 were observed in either pregnant women or newborns. In the future, to validate our findings, large cohort clinical studies involving numerous pregnant women must be conducted.

VOLUME VERSUS PRESSURE TARGETED NON-INVASIVE VENTILATION IN AMYOTROPHIC LATERAL SCLEROSIS (VOP ALS): study protocol for a randomised controlled trial (preprint)

Introduction Amyotrophic lateral sclerosis (ALS) is a rare, idiopathic, progressive, neuromuscular disease. The prevalence in England and Wales is between 4 and 5 cases per 100,000. A significant proportion of ALS cases are complicated by respiratory and sleep impairment which can reduce health related quality of life (HRQOL) and survival. Non-invasive ventilation (NIV) is the standard of care to treat respiratory and sleep symptoms. Patients who are compliant with NIV have improved survival, HRQOL and reduced symptoms. Different modes of NIV are available and broadly fall into two categories: pressure support ventilation (PSV) and volume assured pressure support (VAPS) ventilation. A clinically enhanced version of VAPS in the form of intelligent volume assured pressure support with automatic EPAP (iVAPS-AE) is now widely available and although spontaneous timed (ST) mode is the preferred choice in ALS, to date no one mode has been shown to be superior. In this single-centre randomised controlled trial we will explore the differences in NIV compliance and effect on HRQOL, between ST and iVAPS-AE NIV modes in patients diagnosed with respiratory failure due to ALS. We also want to explore the optimal NIV mode for patients diagnosed with ALS. This trial is still in the data collection phase and has the potential to guide changes in clinical respiratory practice in ALS. Methods and Analysis VOP ALS is a single blinded, single centre, RCT exploring the impact of iVAPS-AE on patient outcomes compared to ST-mode in patients diagnosed with ALS related respiratory impairment. Primary outcome is mean NIV compliance and secondary outcome is health reported quality of life, both measured over 90 days. The study aimed to recruit 40 patients, but it was revised to 15 because of the COVID-19 pandemic. The analysis will be mainly descriptive by treatment arms and summarised with 95% confidence interval. Ethics and Dissemination VOP ALS is sponsored in the UK by University Hospitals Coventry and Warwickshire NHS Trust and has been granted ethical approval by Northwest - Haydock Research Ethics Committee Ethics Committee (REC ref: 21/NW/0326). Publication of results in a peer-reviewed journal and conference presentations are expected. Trial Registration Number: NCT05328492. Registered 4th April 2022 - Retrospectively registered, https://clinicaltrials.gov/study/NCT05328492

Impact of the severe acute respiratory syndrome coronavirus 2 pandemic on the incidence of type 1 diabetes mellitus in children in Yamanashi, Japan (preprint)

It is hypothesized that the biopsychosocial stress associated with the severe acute respiratory syndrome coronavirus 2 pandemic (SARS-CoV-2), in combination with the immunologic effects of SARS-CoV-2 and pancreatic β-cell dysfunction, may have contributed to the onset of type 1 diabetes (T1D) in children. We documented the incidence rates of T1D in Yamanashi Prefecture, Japan, from 1986 to 2018 and expanded our analysis to include cases from 2019 to 2022 to assess the influence of coronavirus disease 2019 (COVID-19) on the incidence of T1D. The annual increase in standardized incidences of T1D among 0- to 14-year-olds was 2.089% per year from 1986 to 2019 (p = .0772) and 2.183% per year from 1986 to 2022 (p = .0331). For the 5-9 year age group, the annual increase in crude incidence from 1986 to 2019 was 6.607% per year (p < .01), and from 1986 to 2022, it was 6.270% per year (p < .001). In Yamanashi Prefecture, Japan, the incidence of pediatric T1D increased during the COVID-19 pandemic from 2020 to 2022. However, this trend was an extension of the increase prior to 2019, suggesting that no direct or indirect effect of COVID-19 on this trend was identified.

Protein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV (preprint)

Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic betacoronavirus that causes severe and often lethal respiratory illness in humans. The MERS-CoV spike (S) protein is the viral fusogen and the target of neutralizing antibodies, and has therefore been the focus of vaccine design efforts. Currently there are no licensed vaccines against MERS-CoV and only a few candidates have advanced to Phase I clinical trials. Here we developed MERS-CoV vaccines utilizing a computationally designed protein nanoparticle platform that has generated safe and immunogenic vaccines against various enveloped viruses, including a licensed vaccine for SARS-CoV-2. Two-component protein nanoparticles displaying MERS-CoV S-derived antigens induced robust neutralizing antibody responses and protected mice against challenge with mouse-adapted MERS-CoV. Electron microscopy polyclonal epitope mapping and serum competition assays revealed the specificities of the dominant antibody responses elicited by immunogens displaying the prefusion-stabilized S-2P trimer, receptor binding domain (RBD), or N-terminal domain (NTD). An RBD nanoparticle vaccine elicited antibodies targeting multiple non-overlapping epitopes in the RBD, whereas anti-NTD antibodies elicited by the S-2P- and NTD-based immunogens converged on a single antigenic site. Our findings demonstrate the potential of two-component nanoparticle vaccine candidates for MERS-CoV and suggest that this platform technology could be broadly applicable to betacoronavirus vaccine development.

Accelerated brain age in young to early middle-aged adults after mild to moderate COVID-19 infection (preprint)

Cognitive decline is a common adverse effect of the Coronavirus Disease of 2019 (COVID-19), particularly in the post-acute disease phase. The mechanisms of cognitive impairment after COVID-19 (COGVID) remain unclear, but neuroimaging studies provide evidence of brain changes, many that are associated with aging. Therefore, we calculated Brain Age Gap (BAG), which is the difference between brain age and chronological age, in a cohort of 25 mild to moderate COVID-19 survivors (did not experience breathlessness, pneumonia, or respiratory/organ failure) and 24 non-infected controls (mean age = 30 +/- 8) using magnetic resonance imaging (MRI). BAG was significantly higher in the COVID-19 group (F = 4.22, p = 0.046) by 2.65 years. Additionally, 80% of the COVID-19 group demonstrated an accelerated BAG compared to 13% in the control group (X2 = 20.0, p < 0.001). Accelerated BAG was significantly correlated with lower cognitive function (p < 0.041). Females in the COVID-19 group demonstrated a 99% decreased risk of accelerated BAG compared to males (OR = 0.015, 95% CI: 0.001 to 0.300). There was also a small (1.4%) but significant decrease in risk for accelerated BAG associated with longer time since COVID-19 diagnosis (OR = 0.986, 95% CI: 0.977 to 0.995). Our findings provide a novel biomarker of COGVID and point to accelerated brain aging as a potential mechanism of this adverse effect. Our results also offer further insight regarding gender-related disparities in cognitive morbidity associated with COVID-19.

Prospective Clinical Surveillance for Severe Acute Respiratory Illness in Kenyan Hospitals during the COVID-19 pandemic (preprint)

There are limited data from sub-Saharan Africa describing the pattern of admissions to public hospitals with severe acute respiratory infections during the COVID-19 pandemic. We conducted a prospective longitudinal hospital-based sentinel surveillance between May 2020 and December 2022 at 16 public hospitals in Kenya. All patients aged above 18 years admitted to adult medical wards in the participating hospitals were included. Demographic and clinical characteristics, COVID-19 infection and vaccination status and outcome data were collected. Of the 52,714 patients included in the study, 18,001 (35%) were admitted with severe acute respiratory illness (SARI). The mean age was 51 years. Patients were equally distributed across sexes. Pneumonia was the most common diagnosis at discharge. Hypertension, HIV and diabetes mellitus were the most common comorbidities. COVID-19 test results were positive in 2,370 (28%) of the 8,517 (47%) patients that underwent testing. Overall inpatient case fatality for SARI was 21% (n=3,828). After adjusting for age, sex and presence of a comorbidity, SARI patients had higher inpatient mortality compared to non-SARI patients regardless of their COVID-19 status (aHR 1.31, 95% CI 1.19 - 1.46). COVID-19 positive SARI patients had a higher inpatient mortality rate compared to their negative counterparts (aHR 1.31, 95% CI 1.12 - 1.54, p value < 0.0001). COVID-19 vaccine effectiveness against mortality due to SARI after adjusting for age, sex and presence of a comorbidity was 34% (95% CI 11% - 51%). We have provided a comprehensive description of the pattern of admissions with respiratory illnesses in Kenyan hospitals during the COVID-19 pandemic period. We have demonstrated the utility of routine surveillance activities within public hospitals in low-income settings which if strengthened can enhance the response to emerging health threats.

Spatiotemporal Patterns of Nitrogen Dioxide and Aerosol Optical Depth: A Case Study of Lahore Division (preprint)

To understand the relationships among atmospheric trace gases, aerosol variability, and climate change, as well as to inform next-generation climate change and air quality models, a precise understanding of the intricate relationships between these variables and their sources is needed. Therefore, this study aimed to investigate the spatiotemporal variability of tropospheric nitrogen dioxide (NO2), aerosol optical depth (AOD), and particulate matter (PM2.5) retrieved from both satellite and ground-based data for the period of 2006 − 2023. Tropospheric NO2, obtained from the Ozone Monitoring Instrument (OMI)/Aura, has shown that the Lahore Division frequently has high annual mean NO2 concentrations (3.87 − 6.34 x1015 molecules.cm− 2). Seasonally, winters (4.86 − 8.09x1015 molecules.cm− 2) and autumns (4.18 − 6.85 x1015 molecules.cm− 2) are mainly affected by high NO2 levels during 2021 − 2023 due to intense biomass and crop residue burning activities. Satellite AOD from data Moderate Resolution Imaging Spectroradiometer (MODIS)/Tera indicated that summers and autumns have greater AOD levels, with a mean value of 0.59 − 0.69. More variability in AOD was recorded just after the COVID − 19 lockdown. The NO2 − AOD correlation plots (maps) indicated a positive correlation coefficient R = 0.13 (0.02 to 0.19) in 2023, attributed to more NOx emissions. High concentrations of PM2.5 were recorded specifically in December and January, with the highest average AQI 374.96 µgm− 3, occurring on December 2022, which are the consequences of smog formation and other respiratory disorders during the winter season.

Superantigens, Antigen Precision and Their Applications (preprint)

The aim of this study was to find a method to identify epidemic and sporadic pathogen strains. The method includes A. detecting the antigenic amino acid sequence of the pathogen strain to determine the primary superantigen. B. If the primary superantigen contains tryptophan, the pathogen strain is an epidemic strain. C. If the primary superantigen does not contain tryptophan amino acid, it is a sporadic strain. D. Determine the outbreak time interval between the pathogen strain and the reference strain based on the increase in antigen precision between the pathogen strain and the reference strain. Results: The method can predict whether a series of infectious diseases will become epidemic or scattered, as well as the date of outbreak, such as severe acute respiratory syndrome 1 (SARS I), Middle East Respiratory Syndrome (MERS) and Coronavirus Disease 2019 (COVID-19, SARS II).

Prognostic factors for mortality, ICU, MIS-C and hospital admission due to SARS-CoV-2 in paediatric patients: A systematic review and meta-analysis (preprint)

ABSTRACT Background: There is a paucity of data on the factors associated with severe COVID-19 disease, especially in children. This systematic review and meta-analysis aim to identify the risk factors for acute adverse outcomes of COVID-19 within paediatric populations, using the recruitment setting as a proxy of initial disease severity. Methods: A systematic review and meta-analysis were performed representing published evidence from the start of the pandemic up to 14 February 2022. Our primary outcome was the identification of risk factors for adverse outcomes, stratified by recruitment setting (community, hospital). No geographical restrictions were imposed. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to evaluate the certainty in the body of evidence for each meta-analysis. In anticipation of significant clinical and methodological heterogeneity in the meta-analyses, we fitted logistic regression models with random effects. Findings: Our review identified 47 studies involving 94,210 paediatric cases of COVID-19. Infants up to 3 months were more likely to be hospitalised than older children. Gender and ethnicity were not associated with an increased likelihood of adverse outcomes among children within the community setting. Concerning comorbidities, having at least one pre-existing disease increased the odds of hospitalisation. Concerning BMI, underweight children and severely obese were noted to have an increased likelihood of hospital admission. The presence of metabolic disorders and children with underlying cardiovascular diseases, respiratory disorders, neuromuscular disorders and neurologic conditions were also more likely to be hospitalised. Concerning underlying comorbidities, paediatric hospitalised patients with congenital/genetic disease, those obese, with malignancy, cardiovascular diseases and respiratory disease were associated with higher odds of being admitted to ICU or ventilated. Interpretation: Our findings suggest that age, male, gender, and paediatric comorbidities increased the likelihood of hospital and ICU admission. Obesity, malignancy, and respiratory and cardiovascular disorders were among the most important risk factors for hospital and ICU admission among children with COVID-19. The extent to which these factors were linked to actual severity or where the application of cautious preventive care is an area in which further research is needed.

The Human Phospholipase B-II Precursor (HPLBII-P) in Urine as a Novel Biomarker of Glomerular Activity in COVID-19 and Diabetes Mellitus (preprint)

The human phospholipase B-II precursor (HPLBII-P) was originally purified from white blood cells but is also found in other cellular structures such as kidney glomeruli and tubuli. The objective of this report was to investigate the relationship of HPLBII-P in urine to acute kidney injury in patients with COVID-19 Methods Urine was collected at admission from 132 COVID-19 patients admitted to the intensive care units (ICU) because of respiratory failure. HPLBII-P was measured by a sensitive ELISA. For comparison, HNL was measured in urine, by the ELISA configured with mabs 763/8F, as a sign of tubular affection in addition to routine biomarkers of kidney disease Results Overall, the concentrations of urinary HPLBII-P were almost 3-fold higher in COVID-19 patients as compared to healthy controls (p

Impact of mechanical power on mortality in ventilated critically ill patients. Retrospective study with continuous real-life data (preprint)

Background Over the past decade, numerous studies on potential factors contributing to ventilation-induced lung injury have been carried out. Mechanical power has been pointed out as the parameter that encloses all ventilation-induced lung injury-contributing factors. However, studies conducted to date provide data regarding mechanical power during the early hours of mechanical ventilation that may not correspond to the real scenario. Methods Retrospective observational study conducted at a single center in Spain. Patients admitted to the intensive care unit, > o = 18 years of age, and ventilated for over 24 hours were included. We extracted the mechanical power values throughtout the entire mechanical ventilation period from the clinical information system every two minutes. First, we calculate the cutoff-point for mechanical power beyond which there was a greater change in the probability of death. After, the sum of time values above the safe cut-off point was calculated to obtain the value in hours. We analyzed if the number of hours the patient was under ventilation with a mechanical power above the safe threshold was associated with mortality, invasive mechanical ventilation days, and intensive care unit length of stay. We repeated the analysis in different subgroups based on the degree of hypoxemia and in patients with SARS CoV-2 pneumonia. Results The cut-off point of mechanical power at with there is a higher increase in mortality was 18J/min. The greater the number or hours patients were under mechanical power > 18 J/min the higher the mortality in all the study population, in patients with SARS CoV-2 pneumonia and in mild to moderate hyopoxemic respiratory failure. The risk of death inceases 0.1% for each our with mechanical power exceeding 18 J/min. The number of hours with mechanical power > 18 J/min also affected the days of invasive mechanical ventilation and intensive care unit length of stay. Conclusions Continuous monitoring of mechanical power using an automated clinical information system shows that the number of hours with mechanical power > 18 J/min increases mortality in critically ill patients.

Divergences in Antiviral Therapy for Diabetic Patients with COVID-19 (preprint)

Abstract: Background: Patients with diabetes are particularly susceptible to COVID-19 infection, which can result in severe respiratory illness. Methods: This study conducted a comparative as-sessment of the impact of antiviral therapy using molnupiravir and favipiravir in COVID-19 pa-tients with underlying diabetes. A cohort of one hundred individuals infected with SARS-CoV-2, diagnosed with diabetes, and consecutively admitted, was included in the present study. These patients were treated with antivirals according to local guidelines: Group F (51 cases) was treated with favipiravir – 10 days and Group M (49 cases) was treated with molnupiravir – 5 days. Re-sults: In Group F, the average hospitalization was higher than in Group M (11.29±2.27 vs. 7.14±3.16, p

COVID-related Constrictive Pericarditis Requiring Pericardiectomy: A Case Report (preprint)

Background The COVID-19 pandemic was primarily considered a respiratory malady in the early phases of the outbreak. However, as more patients suffer from this illness, a myriad of symptoms emerge in organ systems separate from the lungs. Among those patients with cardiac involvement, myocarditis, pericarditis, myocardial infarction, and arrhythmia were among the most common manifestations. Pericarditis with pericardial effusion requiring medical or interventional treatments has been previously reported in the acute setting. Notably, chronic pericarditis with pericardial thickening resulting in constriction requiring sternotomy and pericardiectomy has not been published to date.Case Presentation A patient with COVID-19-associated constrictive pericarditis three years after viral infection requiring pericardiectomy was reported. The COVID-19 infection originally manifested as anosmia and ageusia. Subsequently, the patient developed dyspnea, fatigue, right-sided chest pressure, bilateral leg edema, and abdominal fullness. Following recurrent right pleural effusions and a negative autoimmune work-up, the patient was referred for cardiothoracic surgery for pericardiectomy when radiographic imaging and hemodynamic assessment were consistent with constrictive pericarditis. Upon median sternotomy, the patient’s pericardium was measured to be 8 mm thick. Descriptions of the clinical, diagnostic, and therapeutic features are provided. Within the first week after the operation, the patient’s dyspnea resolved; one month later, leg edema and abdominal bloating were relieved.Conclusions Although an association between COVID-19 and cardiac complications has been established, this case adds another element of virus severity and chronic manifestations. The need for sternotomy and pericardiectomy to treat COVID-19-related constrictive pericarditis is believed to be the first reported diagnosis.

Back to the Future: Immune Protection or Enhancement of Future Coronaviruses. (preprint)

Before the emergence of SARS-CoV-1, MERS-CoV, and most recently SARS-CoV-2, al-ready four other coronaviruses have been circulating in the human population. The alpha coronaviruses NL63 and 229E and the beta coronaviruses OC34 and HKU1. These circulating coronaviruses all cause mild respiratory illness during the winter seasons and most people are already infected in early life. Could antibodies and/or T cells, es-pecially against the beta coronaviruses have offered some form of protection against SARS-CoV-2? Related is the question whether survivors of SARS-CoV-1 or MERS-CoV would be relatively protected against SARS-CoV-2. More importantly, would humoral and cellular immunological memory, generated during the SARS-CoV-2 pandemic, ei-ther by infection or vaccination offer protection against future coronaviruses? Or rather than protection, could antibody dependent enhancement have taken place, a mecha-nism by which circulating corona antibodies enhance the severity of COVID-19? An-other related phenomenon, the original antigen sin, would also predict that the effec-tivity of the immune response to future coronaviruses would be impaired because of reactivation of memory against irrelevant epitopes. Current available evidence indicates that latter scenarios are highly unlikely and that especially cytotoxic memory T cells directed against conserved epitopes of human coronaviruses could at least offer partial protection against future coronaviruses.

Covid-19 lockdown: management of children with recurrent wheezing and asthma in Spain. (preprint)

Introduction: The effect of lockdown measures due to COVID-19 pandemic in children with respiratory underlying conditions are still unclear. We analyzed the impact of lockdown measures in the management and evolution of children with asthma and preschool wheeze during the first wave of COVID-19. Matherial and Methods: observational study carried out in children with recurrent wheezing or asthma before and after the implementation of the lockdown by using: a questionnaire aimed to examine pre-existing respiratory disorders, step treatment (according to Spanish Guide for Asthma Management) and level of asthma control before/after lockdown (CAN questionnaire), COVID history and laboratory testing including IgG SARS-CoV-2. Results: we enrolled 475 asthmatic and preschool wheezers (60.6% males), mean age 5.6 years. There were not differences in asthma treatment comparing both periods, since 81.7% maintained the same treatment (p=0.103). According to CAN questionnaire 87.7% remained well controlled during confinement. Nearly a third of children (34.9%) needed reliever treatment, mainly in older children. Determination of IgG SARS-CoV-2 was performed in 233 children (49.1%) of whom 17 (7.3%) tested positive. Seven patients positive to IgG SARS-CoV-2 were assisted in the emergency department and two required hospital admission. Conclusions: During the COVID-19 lockdown most of the children with asthma and recurrent wheezing maintained their preventive treatments unchanged and remained well controlled from their underlying disease. Our results suggest that children that tested positive to IgG SARS-CoV-2 showed significant increase in paediatric hospital admissions and attendances to urgent care settings.

Analysis of long-term antibody response in COVID-19 patients by symptoms grade, gender, age, BMI, and treatments regimens (preprint)

Objective: The severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and the resulting COVID-19 pandemic pose significant challenges in terms of diagnosis and recurrent infections. Literature data suggest that age, gender and BMI factors are associated with immune response. The first aim of the study was to analyze the change in antibody titer at 15-day intervals until 60 days post symptom onset (PSO) The second aim was to analyze relationship between antibody titer and symptom grade, gender, age, BMI, therapeutic drugs, vitamin supplements, and herbal therapies. Materials and methods: Blood samples were collected from 43 patients (5 mild, 21 moderate, 17 severe diseases), 18 women (41.9 %), and 25 men (58.1 %), on 15, 30, 45, and 60 days PSO after COVID-19 infection. The serum antibody titers were determined by measuring the COVID-19 IgG antibodies by ELISA. Associations between the duration of symptoms, demographic and clinical parameters, medications and vitamins used, and herbal therapies were evaluated by interviewing the participants. Results: Within the first 15 days of illness, 81.4% of the patients were positive. From day 45 PSO, seropositivity was 89.5%. The anti-SARS-CoV-2 antibody titers were statistically higher in men than women at all-time (p<0.01). Antibody titer was higher in older participants compared to younger participants (p<0.02). Plaquenil or Favipiravir use did not effect antibody response (p>0.05). Men had higher fever (p=0.006), shortness of breath (p=0.004), and chest pain (p=0.03) than women. Conclusion: We found powerful antibody response by sixty days PSO, as well as higher antibody response and severity of symptoms in men gender. Data also showed that SARS-CoV-2 antibodies are higher in individuals with older age, whereas BMI, coexisting chronic disease, and drug used had no effect on antibody titers.

Deep sedation with dexmedetomidine administered by electrophysiologists during COVID-19 pandemic compared with propofol administered by anesthesiologists for transcatheter ablation of atrial fibrillation (preprint)

Background: COVID-19 pandemic, limiting the availability of anesthesiologists, has impacted heavily on the organization of invasive cardiac procedures such as transcatheter atrial fibrillation (AF) ablation. Objective We compared the safety and efficacy of deep sedation with dexmedetomidine administered by electrophysiologists without anesthesiologist supervision, against the standard protocol performed with propofol. Methods We retrospectively included all AF ablation procedures performed in 2020: 23 patients sedated with 1% propofol (2 ml bolus followed by infusion starting at 1 mg/Kg/h), 26 patients with dexmedetomidine (infusion starting at 0.7 mcg/Kg/h). Both groups additionally received 1 mcg/Kg of midazolam as a single bolus and 0.05 mg single boluses of fentanyl prior to ablation on each pair of pulmonary veins (PV). Primary outcomes were oxygen desaturation (<90%) or need for assisted ventilation/intubation, bradycardia (heart rate <45 bpm) and persistent hypotension (systolic blood pressure <90 mmHg). Results Baseline characteristics and hemodynamic variables did not differ between the two groups (all p>0.05). In 8/23 (35%) patients propofol infusion velocity reduction was necessary to maintain the hemodynamic values, compared to 7/26 (27%) with dexmedetomidine. Inter-group comparison of hemodynamic variables during the procedure showed no statistically significant difference, despite a trend in favor of dexmedetomidine (3 respiratory depressions and 3 persistent hypotension episodes with propofol vs. 0 with dexmedetomidine; p = 0.057). Conclusion Deep sedation with dexmedetomidine administered by electrophysiologists without anesthesiologist supervision is safe and effective for AF transcatheter ablation. A trend towards a lower incidence of hypotension and respiratory depression was noted when compared to propofol.

Renal consequences of the novel coronavirus disease 2019 (COVID-19) and hydrogen sulfide as a potential therapy (preprint)

The novel coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is a global pandemic which is primarily considered a respiratory illness. However, emerging reports show that the virus exhibits both pulmonary and extra-pulmonary manifestations in humans, with the kidney as a major extra-pulmonary target due to its abundant expression of angiotensin-converting enzyme 2 and transmembrane protease serine 2, which facilitate entry of the virus into cells. Acute kidney injury has become prevalent in COVID-19 patients without prior any history of kidney dysfunction. In addition, the virus also worsens kidney conditions and increases mortality of COVID-19 patients with pre-existing chronic kidney disease, renal cancer, diabetic nephropathy, end-stage kidney disease as well as dialysis and kidney transplant patients. In the search for antiviral agents for the treatment of COVID-19, hydrogen sulfide (H2S), the third established member of gasotransmitter family, is emerging as a potential candidate, possessing important therapeutic properties including antiviral, anti-inflammatory, anti-thrombotic and antioxidant properties. A recent clinical study revealed higher serum H2S levels in survivors of COVID-19 pneumonia with reduced interleukin-6 levels compared to fatal cases. In this review, we summarize the global impact of COVID-19 on kidney conditions and discuss the emerging role of H2S as a potential COVID-19 therapy.