Similarities between long COVID and cognitive impairment and potential implications; Results from the 2022 BRFSS (preprint)

BackgroundCOVID has been linked to cognitive issues with brain fog a common complaint among adults reporting long COVID (symptoms lasting 3 or more months). ObjectiveTo study similarities and differences between cognitive impairment (CI) (the cognitive disability measure) and long COVID. MethodsUsing 2022 BRFSS data from 50 states and 169,894 respondents in 29 states with COVID vaccine data, respondents with CI and long COVID were compared in unadjusted analysis and logistic regression. Apparent vaccine effectiveness was compared in the 29 states. ResultsPrevalence of long COVID was 7.4% (95% CI 7.3-7.6) and CI was 13.4% (13.2-13.6) with both rates higher among women, ages 18-64 years, Hispanics, American Indians, ever smokers, those with depression, e-cigarette users, and those with more of the co-morbidities of diabetes, asthma, COPD, and obesity. The strong association between long COVID and CI was confirmed. Apparent vaccine effectiveness of 3 or more doses vs <3 was 38% for long COVID and 35% for CI, in both cases reducing rates for 3 or more doses to those comparable to adults with 0 comorbidities and showing dose response gradients. For CI, apparent vaccine effectiveness was similar for respondents with or without long COVID. Logistic regression confirmed most results except the magnitude of vaccine effectiveness on CI was reduced in some models while vaccine effectiveness for long COVID was confirmed. ConclusionsMore research is needed to understand the apparent effectiveness of COVID vaccines on CI but, if confirmed, results could expand the list of non-infectious outcomes for which mRNA vaccines can be effective.

The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication (preprint)

SARS-CoV-2 infection leads to vastly divergent clinical outcomes ranging from asymptomatic infection to fatal disease. Co-morbidities, sex, age, host genetics and vaccine status are known to affect disease severity. Yet, how the inflammatory milieu of the lung at the time of SARS-CoV-2 exposure impacts the control of viral replication remains poorly understood. We demonstrate here that immune events in the mouse lung closely preceding SARS-CoV-2 infection significantly impact viral control and we identify key innate immune pathways required to limit viral replication. A diverse set of pulmonary inflammatory stimuli, including resolved antecedent respiratory infections with S. aureus or influenza, ongoing pulmonary M. tuberculosis infection, ovalbumin/alum-induced asthma or airway administration of defined TLR ligands and recombinant cytokines, all establish an antiviral state in the lung that restricts SARS-CoV-2 replication upon infection. In addition to antiviral type I interferons, the broadly inducible inflammatory cytokines TNF and IL-1 precondition the lung for enhanced viral control. Collectively, our work shows that SARS-CoV-2 may benefit from an immunologically quiescent lung microenvironment and suggests that heterogeneity in pulmonary inflammation that precedes or accompanies SARS-CoV-2 exposure may be a significant factor contributing to the population-wide variability in COVID-19 disease outcomes.

Duration of effectiveness of the COVID-19 vaccine in Japan: A retrospective cohort study using large- scale population-based registry data (preprint)

Background Most evidence of the waning of vaccine effectiveness is limited to a relatively short period after vaccination.Methods Data obtained from a linked database of healthcare administrative claims and vaccination records maintained by the municipality of a city in the Kanto region of Japan were used in this study. The study period extended from April 1, 2020, to December 31, 2022. The duration of the effectiveness of the COVID-19 vaccine was analyzed using a time-dependent piecewise Cox proportional hazard model using the age, sex and history of cancer, diabetes, chronic obstructive pulmonary disease, asthma, chronic kidney disease, and cardiovascular disease as covariates.Results Among the 174,757 eligible individuals, 14,416 (8.3%) were diagnosed with COVID-19 and 936 (0.54%) were hospitalized for COVID-19. Multivariate analysis based on the time-dependent Cox regression model revealed a lower incidence of COVID-19 in the one-dose group (hazard ratio, 0.76 [95% confidence interval, 0.63–0.91]), two-dose (0.89 [0.85–0.93]), three-dose (0.80 [0.76–0.85]), four-dose (0.93 [0.88–1.00]), and five-dose (0.72 [0.62–0.84]) groups. A lower incidence of COVID-19-related hospitalization was observed in the one-dose group (0.42 [0.21–0.81]), two-dose (0.44 [0.35–0.56]), three-dose (0.38 [0.30–0.47]), four-dose (0.20 [0.14–0.28]), and five-dose (0.11 [0.014–0.86]) groups. Multivariable analyses based on the time-dependent piecewise Cox proportional hazard model revealed significant preventive effects of the vaccine at 0–1, 1–2, 2–3, 3–4, 7–8, ≥ 12 months for the incidence of COVID-19 and 0–1, 1–2, 2–3, 3–4, 4–5, 5–6, 7–8, and 9–10 months for hospitalization.Conclusions Vaccine effectiveness showed gradual attenuation with time after vaccination; however, protective effects against the incidence of COVID-19 and hospitalization were maintained for 4 months and ≥ 6 months, respectively. These results may aid in formulating routine vaccination plans after the COVID-19 pandemic.

Modeling the relative influence of socio-demographic variables on post-acute COVID-19 quality of life: an application to settings in Europe, Asia, Africa, and South America (preprint)

Long-term COVID-19 complications are a globally pervasive threat, but their plausible social drivers are often not prioritized. Here, we use data from a multinational consortium to quantify the relative contributions of social and clinical factors to differences in quality of life among participants experiencing long COVID and measure the extent to which social variables impacts can be attributed to clinical intermediates, across diverse contexts. In addition to age, neuropsychological and rheumatological comorbidities, educational attainment, employment status, and female sex were identified as important predictors of long COVID-associated quality of life days (long COVID QALDs). Furthermore, a great majority of their impacts on long COVID QALDs could not be tied to key long COVID-predicting comorbidities, such as asthma, diabetes, hypertension, psychological disorder, and obesity. In Norway, 90% (95% CI: 77%, 100%) of the effect of belonging to the highest versus lowest educational attainment quintile was not attributed to intermediate comorbidity impacts. The same was true for 86% (73%, 100%) of the protective effects of full-time employment versus all other employment status categories (excluding retirement) in the UK and 74% (46%,100%) of the protective effects of full-time employment versus all other employment status categories in a cohort of four middle-income countries (MIC). Of the effects of female sex on long COVID QALDs in Norway, UK, and the MIC cohort, 77% (46%,100%), 73% (52%, 94%), and 84% (62%, 100%) were unexplained by the clinical mediators, respectively. Our findings highlight that socio-economic proxies and sex may be as predictive of long COVID QALDs as commonly emphasized comorbidities and that broader structural determinants likely drive their impacts. Importantly, we outline a multi-method, adaptable causal machine learning approach for evaluating the isolated contributions of social disparities to long COVID quality of life experiences.

SARS-CoV-2 booster vaccine dose significantly extends humoral immune response half-life beyond the primary series (preprint)

SARS-CoV-2 lipid nanoparticle mRNA therapeutics continue to be administered as the predominant therapeutic intervention to reduce COVID-19 disease pathogenesis. Quantifying the kinetics of the secondary immune response from subsequent doses beyond the primary series, and understanding how dose-dependent immune waning kinetics vary as a function of age, sex, and various comorbidities, remains an important question. We study anti-spike IgG waning kinetics in 152 individuals who received an mRNA-based primary series and a subset of 137 individuals who then received a booster dose. We find the booster dose elicits a 71-84\% increase in the median Anti-S half life over that of the primary series. We find the Anti-S half life for both primary series and booster doses drops as a function of increased year of age. However, we stress that although chronological age continues to be a good proxy for vaccine-induced humoral waning, immunosenescence is likely not the mechanism, rather, more likely the mechanism is related to the presence of noncommunicable diseases, which also accumulate with age, that affect immune regulation. We are able to independently reproduce recent observations that those with pre-existing asthma exhibit a stronger primary series humoral response to vaccination than compared to those that do not, and further find this result is sustained for the booster dose. Finally, via a single-variate Kruskal-Wallis Test we find no difference between male and female decay kinetics, however, a multivariate approach utilizing Lasso regression for feature selection reveals a statistically significant (p-value <10 -3 ), albeit small, bias in favour of longer-lasting humoral immunity amongst males.

Rhinovirus infection of airway epithelial cells uncovers the non-ciliated subset as a likely driver of genetic susceptibility to childhood-onset asthma (preprint)

Asthma is a complex disease caused by genetic and environmental factors. Epidemiological studies have shown that in children, wheezing during rhinovirus infection (a cause of the common cold) is associated with asthma development during childhood. This has led scientists to hypothesize there could be a causal relationship between rhinovirus infection and asthma or that RV-induced wheezing identifies individuals at increased risk for asthma development. However, not all children who wheeze when they have a cold develop asthma. Genome-wide association studies (GWAS) have identified hundreds of genetic variants contributing to asthma susceptibility, with the vast majority of likely causal variants being non-coding. Integrative analyses with transcriptomic and epigenomic datasets have indicated that T cells drive asthma risk, which has been supported by mouse studies. However, the datasets ascertained in these integrative analyses lack airway epithelial cells. Furthermore, large-scale transcriptomic T cell studies have not identified the regulatory effects of most non-coding risk variants in asthma GWAS, indicating there could be additional cell types harboring these 'missing regulatory effects'. Given that airway epithelial cells are the first line of defense against rhinovirus, we hypothesized they could be mediators of genetic susceptibility to asthma. Here we integrate GWAS data with transcriptomic datasets of airway epithelial cells subject to stimuli that could induce activation states relevant to asthma. We demonstrate that epithelial cultures infected with rhinovirus significantly upregulate childhood-onset asthma-associated genes. We show that this upregulation occurs specifically in non-ciliated epithelial cells. This enrichment for genes in asthma risk loci, or 'asthma heritability enrichment' is also significant for epithelial genes upregulated with influenza infection, but not with SARS-CoV-2 infection or cytokine activation. Additionally, cells from patients with asthma showed a stronger heritability enrichment compared to cells from healthy individuals. Overall, our results suggest that rhinovirus infection is an environmental factor that interacts with genetic risk factors through non-ciliated airway epithelial cells to drive childhood-onset asthma.

Causal relationship between COVID-19 and the risk of asthma: A Mendelian Randomisation study (preprint)

Background Existing research has focused on new-onset asthma and viral infections, particularly respiratory syncytial virus (RSV). However, studies on whether COVID-19 can induce asthma are limited.Methods We performed bidirectional two-sample Mendelian Randomization (MR) to assess the potential causal relationship between COVID-19 and asthma using genome-wide association study (GWAS) summary data obtained from the COVID-19 Host Genetic Initiative GWAS Meta-analysis Round 5 (release date: 18 January 2021). Several methods (random-effects inverse variance weighted, weighted median, MR-Egger regression, and MR-PRESSO) were used to ensure the robustness of the causal effects. Heterogeneity was measured using Cochran's Q value. Horizontal pleiotropy was evaluated using MR-Egger regression and leave-one-out analyses.Results We observed a significant causal association between COVID-19 hospitalisation and asthma (odds ratio (OR) = 1.042, 95% Confidence Interval (CI) = 1.004–1.081, p = 0.031), indicating a significantly increased risk of COVID-19 hospitalisation associated with asthma. However, no statistically significant causal relationships were observed for COVID-19 susceptibility (OR = 1.023, 95% CI = 0.931–1.124, p = 0.637), COVID-19 severity (OR = 1.006, 95% CI = 0.978–1.035, p = 0.669), and asthma.Conclusions COVID-19 can trigger the onset of asthma. Individuals experiencing prolonged coughing, chest tightness, or difficulty in breathing long after recovery from COVID-19 should remain vigilant about the possibility of developing asthma.

Comparing surveyed adults with long COVID and those with just a positive test helps put COVID into perspective (preprint)

Introduction: Among adults who test positive for COVID-19, some develop long COVID (symptoms lasting [≥]3 months), and some do not. We compared 3 groups on selected measures to help determine strategies to reduce COVID impact. Methods: Using Stata and data for 385,617 adults from the 2022 Behavioral Risk Factor Surveillance System, we compared adults reporting long COVID, those with just a positive test, and those who never tested positive, on several health status and risk factor measures plus vaccination rates (data for 178,949 adults in 29 states). Results: Prevalence of just COVID was 26.5% (95% CI 26.2-26.8) and long COVID was 7.4% (7.3-7.6). Compared with adults with just COVID those with long COVID had worse rates for 13 of 17 measures of chronic disease, disability, and poor health status, while those with just COVID had the best results for 15 of the 17 measures among all 3 groups. The 5 risk factors (obesity, diabetes, asthma, cardiovascular disease, and COPD) previously associated with COVID deaths, increased long COVID but not just COVID rates, which were highest among younger and higher income adults. Adults with long COVID had the highest rate among the 3 groups for any COVID risk factors and data from 29 states showed they had the lowest rates for [≥]3 vaccine doses of 35.6%, vs. 42.7% and 50.3% for those with just a positive test, and neither, respectively. Vaccination with [≥]3 vaccines vs. <3 reduced long COVID rates by 38%, and just COVID rates by 16%. Conclusions: Results show the seriousness of long COVID vs. just a positive test and that increasing vaccine coverage by targeting adults with risk factors shows promise for reducing COVID impact.

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.

Children with allergic asthma sensitized to house dust mites getting better health during COVID-19 pandemic (preprint)

Background: Since December 2019, 2019 novel corona virus (2019-nCov) disease (COVID-19) has extended to most parts of China with more than 80 thousand cases. From Feb 1 to Mar 31 of 2020, all children were asked to stay indoors in China. Then how it affected allergic asthma (AA) sensitized to house dust mites (HDM) in children was interestingly to clarify. Objective: To investigate the changes of clinical characteristics of children with AA sensitized to HDM during COVID-19 pandemic. Method: The data including asthma symptom scores(SS), visual analog scores (VAS), asthma quality of life questionnaire (AQLQ) and medicine scores (MS) as well as respiratory infections, cares, staying up late and diets, collected from children with AA sensitized to HDM from Feb 1 to Mar 31 of 2019 and 2020 retrospectively, were analyzed. Results: There were 85 children with AA sensitized to HDM included in this research. Compared with SS, VAS, AQLQ and MS of the patients from Feb 1 to Mar 31 of 2019, SS, VAS, AQLQ and MS of the patients improved significantly (p<0.05) during COVID-19 pandemic. No respiratory infections occurred among them and they got better cares, had better diets and stayed up late less during COVID-19 pandemic. Conclusion: During COVID-19 pandemic, children with AA sensitized to HDM got better health for staying indoors, which might be associated with no respiratory infections, better cares, better diets and less staying up late.

Long COVID Disability Burden in US Adults: YLDs and NIH Funding Relative to Other Conditions (preprint)

BackgroundLong COVID (LC) is novel, debilitating and likely chronic. Yet, scant data exist about its disability burden to guide scientific research and public health planning. We estimated Long COVIDs non-fatal disease burden in US adults and its FY2024 actual: burden-commensurate research funding from the National Institutes of Health (NIH) relative to other conditions, and biological sex. MethodsWe present YLDs/100,000 for 70 NIH Research, Condition, and Disease Categories (RCDCs). Prevalence of disabling Long COVID was obtained from cross sectional surveys of representative samples of US adults, from September 2022 to August 2023. Disabling Long COVID was defined as incident symptoms persisting more than 3 months post-COVID, that significantly compromise daily activities. We calculated burden-commensurate funding for the top YLD conditions and for female vs. male dominant conditions. FindingsDisabling Long COVID was reported by 1.5% (n= 10,401) of n=757,580 respondents: Compared to the overall sample, those with disabling LC disproportionately identify as female (64.4% vs. 51.4%) and experiencing disability (80.8% vs. 52.9%) anxiety (57.5% vs. 23.8%) and depression (51.3% vs.18.5%). It ranked in the top 25% of YLDs at 320/100,000, between Alzheimers (279.4/100,000) and asthma (355.7/100,000) but received just 10% of its actual: YLD-commensurate funding. Only 5 conditions received less actual: burden: commensurate funding, including Myalgic Encephalitis/Chronic Fatigue Syndrome (<1%), another post-viral, female-dominant condition. InterpretationLC has debilitated 3.8 million (weighted frequency) US adults. Research funding for it, like other female dominant conditions, lags behind its disability burden. Research in ContextEvidence before this study - We analyzed Long-COVIDs (LC) non-fatal disease burden in the US--represented by YLD (years lived with disability= prevalence x disability weight) -- and National Institutes of Health (NIH) research 2024 funding relative to other conditions. We searched PubMed through 11/28/2023 for Long COVID prevalence (US), and Long COVID disability and disease burden (not US-specific). The keywords "years lived with disability" + "COVID" yielded n= 38 articles (11/29/23); but most referenced "disability-adjusted life years" (DALYs) in other countries. Similarly, "disease burden" + Long COVID yielded 23 papers, but no US YLD data. See Supplement 1 for meta-analyses, systematic reviews and US studies of Long COVID prevalence and impact. We instead sourced YLD data from the US Census Bureaus Household Pulse Survey (HPS) and the Institute for Health Metrics and Evaluation (IHME) /Global Burden of Disease (GBD) Long COVID Study Group. The HPS queries adults about Long COVID-related symptoms and their impact on daily activities. We applied the IHME/GBDs estimated Long COVID disability weight of 0.21 and harmonized it with our LC case definition from the HPS data in consultation with IHME/GBD researchers. To harmonize IHME/GBD disability weights for non-LC diseases/conditions with the NIHs terminology, we consulted with NIH staff. LC definition and measurement affects prevalence and burden estimates; our use of high-quality data sources and transparency in reporting how they were applied reduces the risk of biased assumptions. Added value of this study- Long COVID is a chronic debilitating condition. While there is ample research on COVIDs acute illness and loss of life, there are no population-based data on its disability burden. We provide that data. To guide scientific research and public health planning, we report YLDs associated with disabling Long COVID (i.e., symptoms significantly limit activity), and; compare it to other conditions YLDs, NIH funding, and female-vs. male-dominance. It ranked in the top 25% of YLDs at 320/100,000, between Alzheimers (279.4/100,000) and asthma (355.7/100,000) but received just 10% of its YLD-commensurate funding. Only 5 conditions received less burden-commensurate funding; 3/5 were female-dominant, including Myalgic Encephalitis/Chronic Fatigue Syndrome (ME/CFS) at <1%, another post-viral condition that shares significant overlap with Long COVID. Overall, median funding/YLD was >= 5 times greater for male-vs. female-dominant conditions. Implications of all the available evidence-Nearly 4 million US adults (weighted frequency) live with disabling Long COVID. They disproportionately identify as female and as having a disability, anxiety and depression. Yet NIH funding for diagnostic and treatment research for Long COVID hasnt kept pace with its disability burden.

Prevalence of COVID-19 and long COVID - Results from the 2022 Behavioral Risk Factor Surveillance System, 50 states. (preprint)

Recent MMWR results estimate long COVID prevalence at 6.0% in June 2023, while the percentage of those with COVID reporting long COVID was 11.0%. The 2022 Behavioral Risk Factor Surveillance System addressed COVID (positive test) and long COVID (symptoms lasting [≥]3 months) in a population-based sample from each state and DC. Results for 385,617 adults indicated 34.4% had ever had COVID, 21.9% of whom reported long COVID, representing 7.4% of all adults. State rates ranged from 25.4% - 40.8% for COVID and 4.1%-11.1% for long COVID. Groups with high rates for both included women, younger adults, those with children in the household, plus those reporting obesity, asthma, chronic obstructive pulmonary disease (COPD), diabetes, or cardiovascular disease (CVD). Highest adjusted odds ratios for COVID were 2.34 (95% CI 2.20-2.49) for age 18-24 years vs. age 65+ while for long COVID it was 2.81 (2.53-3.13) for 3+ of the 5 conditions. Most frequently reported problems for those with long COVID were fatigue (26.0%), shortness of breath (18.8%), loss of taste or smell (17.2%), and memory problems (9.9%). Results show the need for state-based data and suggest a focus on younger adults is needed to address COVID and long COVID.

Radiological and Functional Pulmonary Evolution in Post-COVID-19 Patients: An Observational Study (preprint)

COVID-19 generated a scenario for global health with multiple systemic impairments. This retrospective study evaluated the clinical, radiological, and pulmonary functional evolution in 302 post-COVID-19 patients. Regarding post-COVID-19 pulmonary symptoms, dry cough, dyspnea, and chest pain were the most frequent. Of the associated comorbidities, asthma was more frequent (23.5%). Chest Tomography (CT) initially showed a mean pulmonary involvement of 69.7%, and the evaluation in the subsequent months showed an improvement in the evolutionary image, and with less than six months post-pathology, there was a commitment of 37 .7%, from six to twelve months, 20% and after 12 months, 9.9%. And as for most of the sample, 50.3% of the patients presented CT normalization in less than six months after infection, 23% normalized between six and twelve months, and 5.2% normalized the images after twelve months, with one remaining. Percentage of 17.3% who maintained post-COVID-19 pulmonary residual sequelae. Regarding spirometry, in less than six months after the pathology, 59.3% of the patients already showed a regular exam; 12.3% normalized their function within six to twelve months, and 6.3% concluded a normal exam after twelve months of post-pathology evaluation. Only 3.6% of the patients still showed some alteration in this period.

Risk Factors for Admission into COVID-19 General Wards, Sub-Intensive and Intensive Care Units among SARS-CoV-2 Positive Subjects in the Municipality of Bologna, Italy (preprint)

This is a retrospective cohort study aimed at identifying the risk factors for the hospitalization of patients with COVID-19 in the municipality of Bologna. A total of 32500 patients that tested positive for COVID-19 from February 28/2020 to October 13/2021 in the municipality of Bologna were included. The Kaplan-Meier method was used to estimate changes during time of ICU hospitalization for all patients as well as stratifying subjects by sex. A multi-state Cox's proportional hazard model was fitted to investigate predictors of ICU and non-ICU hospitalization. Age, sex, calendar period of diagnosis, comorbidities and vaccination status of patients at the time of diagnosis were considered as candidate predictors. In general, male sex and advanced age resulted to be poor prognostic factors of COVID-19 outcomes. An exception was found for the over 80 age group which showed a decrease in the risk of ICU hospitalization compared to 70-79 (HR 0.57 95% CI 0.36 - 0.90 for DIAG->ICU; HR 0.40 95% CI 0.28 - 0.58 for HOSP->ICU). Having contracted the disease during the first wave was associated with a significant greater risk of hospitalization than during the second wave, while no difference in the risk of ICU admission was found between the second and third waves. Fully immunized patients showed a significant decrease in the risk of ICU and non-ICU hospitalization compared to the unvaccinated patients (HR 0.23 95% CI 0.16 - 0.31 for DIAG->HOSP; HR 0.10 95% CI 0.01 - 0.73 for DIAG->ICU). Chronic kidney failure and asthma were risk factors for non-ICU hospitalization. Diabetes and embolism were risk factors for both direct ICU and non-ICU hospitalization. The study of factors associated with a negative course of the COVID-19 disease allows to prevent fatal outcomes, establish priorities in the treatment of the disease and improve the management of hospital resources and the pandemic itself.

Suffocation in asthma and COVID-19: Supplementation of inhaled corticosteroids with alkaline hydrogen peroxide as an alternative to ECMO (preprint)

Suffocation syndrome is the leading cause of hypoxia and mortality in the most common lung diseases, asthma and COVID-19. Inhaled corticosteroids (ICSs) have been shown to be the main-stay of critical care in these diseases. Meanwhile, mortality from strangulated hypoxia is highest in low-income countries because ICSs are not currently available to many patients. Warm alkaline hydrogen peroxide solutions (WAHPSs) have reportedly been invented in recent years to urgently turn thick sputum, mucus, pus, serous fluid, blood clots and many other biological masses con-taining the enzyme catalase into a fluffy oxygenated foam. It has been shown that the mechanism of action of WAHPSs consists in alkaline saponification of lipid and protein-lipid complexes of bi-ological masses and their transformation into oxygen foam, because hydrogen peroxide is urgently decomposed into water and oxygen gas under the action of the biological masses catalase enzyme At that excess oxygen is absorbed into blood through lungs and increases blood oxygen saturation. Based on the described mechanism of action of WAHPSs and the high availability of their ingre-dients, it is suggested that mortality from choking and hypoxia in asthma and COVID-19 can be reduced by combining ICSs with inhaled WAHPSs, especially in poor countries. The essence of the inventions underlying the formation of WAHPSs is given.

Patient characteristics associated with clinically coded long COVID: an OpenSAFELY study using electronic health records (preprint)

Despite reports of post-COVID-19 syndromes (long COVID) are rising, clinically coded long COVID cases are incomplete in electronic health records. It is unclear how patient characteristics may be associated with clinically coded long COVID. With the approval of NHS England, we undertook a cohort study using electronic health records within the OpenSAFELY-TPP platform in England, to study patient characteristics associated with clinically coded long COVID from 29 January 2020 to 31 March 2022. We estimated age-sex adjusted hazard ratios and fully adjusted hazard ratios for coded long COVID. Patient characteristics included demographic factors, and health behavioural and clinical factors. Among 17,986,419 adults, 36,886 (0.21%) were clinically coded with long COVID. Patient characteristics associated with coded long COVID included female sex, younger age (under 60 years), obesity, living in less deprived areas, ever smoking, greater consultation frequency, and history of diagnosed asthma, mental health conditions, pre-pandemic post-viral fatigue, or psoriasis. The strength of these associations was attenuated following two-dose vaccination compared to before vaccination. The incidence of coded long COVID was higher after hospitalised than non-hospitalised COVID-19. These results should be interpreted with caution given that long COVID was likely under-recorded in electronic health records.

Deduced Respiratory Scores on COVID-19 Patients Learning from Exertion-Induced Dyspnea.

Dyspnea is one of the most common symptoms of many respiratory diseases, including COVID-19. Clinical assessment of dyspnea relies mainly on self-reporting, which contains subjective biases and is problematic for frequent inquiries. This study aims to determine if a respiratory score in COVID-19 patients can be assessed using a wearable sensor and if this score can be deduced from a learning model based on physiologically induced dyspnea in healthy subjects. Noninvasive wearable respiratory sensors were employed to retrieve continuous respiratory characteristics with user comfort and convenience. Overnight respiratory waveforms were collected on 12 COVID-19 patients, and a benchmark on 13 healthy subjects with exertion-induced dyspnea was also performed for blind comparison. The learning model was built from the self-reported respiratory features of 32 healthy subjects under exertion and airway blockage. A high similarity between respiratory features in COVID-19 patients and physiologically induced dyspnea in healthy subjects was observed. Learning from our previous dyspnea model of healthy subjects, we deduced that COVID-19 patients have consistently highly correlated respiratory scores in comparison with normal breathing of healthy subjects. We also performed a continuous assessment of the patient's respiratory scores for 12-16 h. This study offers a useful system for the symptomatic evaluation of patients with active or chronic respiratory disorders, especially the patient population that refuses to cooperate or cannot communicate due to deterioration or loss of cognitive functions. The proposed system can help identify dyspneic exacerbation, leading to early intervention and possible outcome improvement. Our approach can be potentially applied to other pulmonary disorders, such as asthma, emphysema, and other types of pneumonia.

A multicentre survey of asthma-related quality-of-life and treatment in Egypt during the COVID-19 pandemic.

Background: Asthma is a common chronic noncommunicable disease which can impair the health-related quality-of-life (HRQOL) of patients. Aims: To investigate treatment-related experiences and HRQOL of asthma patients in Egypt during the COVID-19 pandemic. Methods: A multicentre cross-sectional study was conducted from 21 July to 17 December 2020 in 3 teaching hospitals in Egypt among a convenience sample of asthma patients. We used socioeconomic and clinical variables, perceived threat level of COVID-19, experiences before and during COVID-19, the Asthma Control Questionnaire (ACQ), and the mini Asthma Quality of Life Questionnaire (mini-AQLQ) to collect data. Results: Among the 200 respondents (66.0% male; mean age 40.2 years), 80.0% had uncontrolled asthma. The greatest impairment to HRQOL was due to limitation of activity. Females reported a higher level of perceived threat from COVID-19 (Chi squared = -2.33, P = 0.02). Before the pandemic, more patients visited the clinician when they had symptoms but did so more regularly during the pandemic. Over 75% could not differentiate between asthma and COVID-19 symptoms. Perceived uncontrolled asthma and poor compliance with treatment were significantly associated with impairment of HRQOL (P < 0.05) before COVID-19. Conclusion: The COVID-19 pandemic improved some asthma-related health behaviours, but limitations in HRQOL were still evident. Uncontrolled asthma is a key factor for HRQOL and should remain a focus for all patients.