ABO blood group as a determinant of COVID-19 and Long COVID: An observational, longitudinal, large study.

BACKGROUND: An association of ABO blood group and COVID-19 remains controversial. METHODS: Following STROBE guidance for observational research, we explored the distribution of ABO blood group in patients hospitalized for acute COVID-19 and in those with Long COVID. Contingency tables were made and risk factors were explored using crude and adjusted Mantle-Haentzel odds ratios (OR and 95% CI). RESULTS: Up to September 2022, there were a total of 5,832 acute COVID-19 hospitalizations in our hospital, corresponding to 5,503 individual patients, of whom blood group determination was available for 1,513 (27.5%). Their distribution by ABO was: 653 (43.2%) group 0, 690 (45.6%) A, 113 (7.5%) B, and 57 (3.8%) AB, which corresponds to the expected frequencies in the general population. In parallel, of 676 patients with Long COVID, blood group determination was available for 135 (20.0%). Their distribution was: 60 (44.4%) from group 0, 61 (45.2%) A, 9 (6.7%) B, and 5 (3.7%) AB. The distribution of the ABO system of Long COVID patients did not show significant differences with respect to that of the total group (p ≥ 0.843). In a multivariate analysis adjusting for age, sex, ethnicity, and severity of acute COVID-19 infection, subgroups A, AB, and B were not significantly associated with developing Long COVID with an OR of 1.015 [0.669-1.541], 1.327 [0.490-3.594] and 0.965 [0.453-2.058], respectively. The effect of the Rh+ factor was also not significant 1,423 [0.772-2,622] regarding Long COVID. CONCLUSIONS: No association of any ABO blood subgroup with COVID-19 or developing Long COVID was identified.

Clinical Profile and Determinants of Mortality in Patients with Interstitial Lung Disease Admitted for COVID-19.

BACKGROUND: Concern has risen about the effects of COVID-19 in interstitial lung disease (ILD) patients. The aim of our study was to determine clinical characteristics and prognostic factors of ILD patients admitted for COVID-19. METHODS: Ancillary analysis of an international, multicenter COVID-19 registry (HOPE: Health Outcome Predictive Evaluation) was performed. The subgroup of ILD patients was selected and compared with the rest of the cohort. RESULTS: A total of 114 patients with ILDs were evaluated. Mean ± SD age was 72.4 ± 13.6 years, and 65.8% were men. ILD patients were older, had more comorbidities, received more home oxygen therapy and more frequently had respiratory failure upon admission than non-ILD patients (all p < 0.05). In laboratory findings, ILD patients more frequently had elevated LDH, C-reactive protein, and D-dimer levels (all p < 0.05). A multivariate analysis showed that chronic kidney disease and respiratory insufficiency on admission were predictors of ventilatory support, and that older age, kidney disease and elevated LDH were predictors of death. CONCLUSIONS: Our data show that ILD patients admitted for COVID-19 are older, have more comorbidities, more frequently require ventilatory support and have higher mortality than those without ILDs. Older age, kidney disease and LDH were independent predictors of mortality in this population.

DFV890: a new oral NLRP3 inhibitor-tested in an early phase 2a randomised clinical trial in patients with COVID-19 pneumonia and impaired respiratory function.

BACKGROUND: Coronavirus-associated acute respiratory distress syndrome (CARDS) has limited effective therapy to date. NLRP3 inflammasome activation induced by SARS-CoV-2 in COVID-19 contributes to cytokine storm. METHODS: This randomised, multinational study enrolled hospitalised patients (18-80 years) with COVID-19-associated pneumonia and impaired respiratory function. Eligible patients were randomised (1:1) via Interactive Response Technology to DFV890 + standard-of-care (SoC) or SoC alone for 14 days. Primary endpoint was APACHE II score at Day 14 or on day-of-discharge (whichever-came-first) with worst-case imputation for death. Other key assessments included clinical status, CRP levels, SARS-CoV-2 detection, other inflammatory markers, in-hospital outcomes, and safety. FINDINGS: Between May 27, 2020 and December 24, 2020, 143 patients (31 clinical sites, 12 countries) were randomly assigned to DFV890 + SoC (n = 71) or SoC alone (n = 72). Primary endpoint to establish clinical efficacy of DFV890 vs. SoC, based on combined APACHE II score, was not met; LSM (SE), 8·7 (1.06) vs. 8·6 (1.05); p = 0.467. More patients treated with DFV890 vs. SoC showed ≥ 1-level improvement in clinical status (84.3% vs. 73.6% at Day 14), earlier clearance of SARS-CoV-2 (76.4% vs. 57.4% at Day 7), and mechanical ventilation-free survival (85.7% vs. 80.6% through Day 28), and there were fewer fatal events in DFV890 group (8.6% vs. 11.1% through Day 28). DFV890 was well tolerated with no unexpected safety signals. INTERPRETATION: DFV890 did not meet statistical significance for superiority vs. SoC in primary endpoint of combined APACHE II score at Day 14. However, early SARS-CoV-2 clearance, improved clinical status and in-hospital outcomes, and fewer fatal events occurred with DFV890 vs. SoC, and it may be considered as a protective therapy for CARDS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04382053.

Biomarkers of Fibrosis in Patients with COVID-19 One Year After Hospital Discharge: A Prospective Cohort Study.

Beyond the acute infection of coronavirus disease (COVID-19), concern has arisen about long-term effects of SARS-CoV-2 infection. The aim of our study was to analyze if there is any biomarker of fibrogenesis in COVID-19 pneumonia patients capable of predicting post-COVID pulmonary sequelae. We conducted a multicenter, prospective, observational cohort study of patients admitted to hospital with bilateral COVID-19 pneumonia. We classified patients in two groups according to severity, and blood samples to measure MMP1, MMP7, periostin and VEGF, respiratory function tests and HRCT imaging were obtained at 2 and 12 months after hospital discharge. A total of 135 patients were evaluated at 12 months. Median age was 61 (IQR: 19) years and 58.5% were men. We found between-group differences in age, radiological involvement, length of hospital stay and inflammatory laboratory parameters. Differences were found between 2 and 12 months in all functional tests, including improvements in FVC% (98.0 vs. 103.9; p=0.001) and DLCO<80% (60.9% vs. 39.7%; p=0.001). At 12 months, 63% of patients had complete HRTC resolution, but fibrotic changes persisted in 29.4%. Biomarker analysis demonstrated differences at 2 months in periostin (ng/mL) (0.8893 vs. 1.437; p<0.001) and MMP-7 (ng/mL) (8.7249 vs. 15.2181; p<0.001). No differences were found at 12 months. In multivariable analysis, only 2-month periostin was associated with 12-month fibrotic changes (OR: 1.0013 95% CI: 1.0006-1.00231; p=0.003) and 12-month DLCO impairment (OR: 1.0006 95% CI: 1.0000-1.0013; p=0.047). Our data suggest that early periostin post-discharge could predict the presence of fibrotic pulmonary changes.

Impact of the COVID-19 pandemic in mortality due to respiratory diseases: A comparative analysis of 2021 and 2020 vs 2019 in Spain.

INTRODUCTION: We previously reported an increase in respiratory mortality in 2020 in Spain after COVID-19. It is unclear if this rise is sustained in the longer-term. We aimed to determine whether respiratory mortality in 2021 in Spain returned to pre-pandemic levels. MATERIAL AND METHODS: In an observational, large study using official National Institute of Statistics data, we explored deaths due to respiratory diseases, that is, all causes of death by the standard WHO list of diseases of the respiratory system plus COVID-19, tuberculosis and lung cancer. Using the latest available official data of Spain, we analyzed changes in the mortality pattern in Spain from January 2019 to December 2021. We endorsed STROBE guidance for observational research. RESULTS: There were 98,714 deaths due to respiratory diseases in 2021 in Spain, corresponding to 21.9% of all deaths, becoming second in the ranking of causes of death. Respiratory diseases mortality in Spain has not returned to pre-pandemic levels in 2021, still with an increase of 30.3% (95% CI 30.2-30.4) compared to rates in 2019. All respiratory-specific causes of death decreased in 2021, except for lung cancer, that increased in women and decreased in men compared to 2019 (both p<0.05). In a multivariate analysis some established risk factors for respiratory diseases mortality were confirmed, such as male gender and older age; further, an association with reduced mortality in rural Spain was observed, still with a large geographical variability. CONCLUSIONS: The COVID-19 pandemic has had a lasting impact on deaths due to respiratory diseases and certain specific causes of death in 2021, and it has disproportionately affected certain regions.

Use of N-Acetylcysteine at high doses as an oral treatment for patients hospitalized with COVID-19.

Infection by SARS-CoV-2 causing coronavirus disease 2019 (COVID-19) can be associated with serious and life-threatening conditions, including acute respiratory distress syndrome (ARDS). Severity and mortality have been related to a cytokine storm, an imbalance of oxidative stress, and a pro-thrombotic state.We conducted an observational retrospective cohort study from a community-based large population of hospitalized COVID-19 PCR + patients admitted from March 01, 2020, to January 24, 2021, with integrated primary to tertiary care information in Castilla la Mancha, Spain. We explored the potential benefits of the antioxidant, anti-inflammatory and anti-thrombotic drug N-acetylcysteine (NAC) administered orally in high doses (600 mg every 8 h), added to standard of care in COVID-19 patients by using the free text information contained in their electronic health records (EHRs).Out of 19,208 patients with a diagnosis of COVID-19 hospitalized, we studied 2071 (10.8%) users of oral NAC at high doses. COVID-19 patients treated with NAC were older, predominantly male, and with more comorbidities such as hypertension, dyslipidemia, diabetes, and COPD when compared with those not on NAC (all p < 0.05). Despite greater baseline risk, use of NAC in COVID-19 patients was associated with significantly lower mortality (OR 0.56; 95%CI 0.47-0.67), a finding that remained significant in a multivariate analysis adjusting by baseline characteristics and concomitant use of corticosteroids. There were no significant differences with the use of NAC on the mean duration of hospitalization, admission to the intensive care unit or use of invasive mechanical ventilation. The observed association signaling to better relevant outcomes in COVID-19 patients treated with NAC at high doses should be further explored in other settings and populations and in randomized controlled trials.

Genitourinary tract symptoms in patients admitted with COVID-19: Exploring changes in frequency by determinants and pandemic waves.

Background: Urothelial cells exhibit increased expression of angiotensin-converting enzyme-2 receptor, which is the binding site of severe acute respiratory syndrome coronavirus 2 to cells. The frequency and distribution of genitourinary tract symptoms in patients diagnosed with coronavirus disease 2019 (COVID-19) is unknown. Objective: We explored trends in genitourinary tract symptoms by gender and each of six pandemic waves in patients admitted for COVID-19, and related them with severity, death and length of hospitalization. Design Setting and Participants: A retrospective study took place in our institution of COVID-19 admitted patients. Only patients with RT-PCR or antigen test confirmed SARS-CoV-2 infection were included. Demographic, clinical, and genitourinary symptoms were explored. Outcome Measurements and Statistical Analysis: COVID-19 patients with genitourinary tract symptoms were compared with those without. Statistical comparisons were conducted by parametric and nonparametric tests for quantitative variables, and χ 2 test for qualitative variables. Results and limitations: Out of a total of 4,661 COVID-19 patients, genitourinary symptoms were found in 21,1%. These symptoms were more frequent in patients admitted for longer than 30 days, except for urinary incontinence (UI) and erectile dysfunction (ED). Acute kidney injury (AKI) and urinary tract infections (UTI) had a higher presence in the 5th (16.7%; 12.8% respectively) and 3rd wave (13.3%; 12.6% respectively). Genitourinary symptoms were higher for those patients admitted in critical care units. Frequency of AKI, UI, UTI and acute urinary retention (AUR) were higher for patients who were finally deceased (26.2%; 3.5%; 13.6% and 3.6% respectively). Conclusions: A high frequency of genitourinary symptoms in patients admitted for COVID-19 was observed, whose frequency and distribution varied according to pandemic waves. Specific genitourinary conditions were associated with worse outcomes and poorer prognosis.

A GBD 2019 study of health and Sustainable Development Goal gains and forecasts to 2030 in Spain.

This study aimed to report mortality, risk factors, and burden of diseases in Spain. The Global Burden of Disease, Injuries, and Risk Factors 2019 estimates the burden due to 369 diseases, injuries, and impairments and 87 risk factors and risk factor combinations. Here, we detail the updated Spain 1990-2019 burden of disease estimates and project certain metrics up to 2030. In 2019, leading causes of death were ischaemic heart disease, stroke, chronic obstructive pulmonary disease, Alzheimer's disease, and lung cancer. Main causes of disability adjusted life years (DALYs) were ischaemic heart disease, diabetes, lung cancer, low back pain, and stroke. Leading DALYs risk factors included smoking, high body mass index, and high fasting plasma glucose. Spain scored 74/100 among all health-related Sustainable Development Goals (SDGs) indicators, ranking 20 of 195 countries and territories. We forecasted that by 2030, Spain would outpace Japan, the United States, and the European Union. Behavioural risk factors, such as smoking and poor diet, and environmental factors added a significant burden to the Spanish population's health in 2019. Monitoring these trends, particularly in light of COVID-19, is essential to prioritise interventions that will reduce the future burden of disease to meet population health and SDG commitments.

Prehospital Respiratory Early Warning Score for airway management in-ambulance: A score comparison.

BACKGROUND: Prehospital Respiratory Early Warning Scores to estimate the requirement for advanced respiratory support is needed. To develop a prehospital Respiratory Early Warning Score to estimate the requirement for advanced respiratory support. METHODS: Multicentre, prospective, emergency medical services (EMS)-delivered, longitudinal cohort derivationvalidation study carried out in 59 ambulances and five hospitals across five Spanish provinces. Adults with acute diseases evaluated, supported and discharged to the Emergency Department with high priority were eligible. The primary outcome was the need for invasive or non-invasive respiratory support (NIRS or IRS) in the prehospital scope at the first contact with the patient. The measures included the following: epidemiological endpoints, prehospital vital signs (respiratory rate, pulse oximetry saturation, fraction of inspired oxygen, systolic and diastolic mean blood pressure, heart rate, tympanic temperature and consciousness level by the GCS). RESULTS: Between 26 Oct 2018 and 26 Oct 2021, we enrolled 5793 cases. For NIRS prediction, the final model of the logistic regression included respiratory rate and pulse oximetry saturation/fraction of inspired oxygen ratio. For the IRS case, the motor response from the Glasgow Coma Scale was also included. The REWS showed an AUC of 0.938 (95% CI: 0.918-0.958), a calibration-in-large of 0.026 and a higher net benefit as compared with the other scores. CONCLUSIONS: Our results showed that REWS is a remarkably aid for the decision-making process in the management of advanced respiratory support in prehospital care. Including this score in the prehospital scenario could improve patients' care and optimise the resources' management.

Lung function and radiological findings 1 year after COVID-19: a prospective follow-up.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has already affected more than 400 million people, with increasing numbers of survivors. These data indicate that a myriad of people may be affected by pulmonary sequelae of the infection. The aim of this study was to evaluate pulmonary sequelae in patients with bilateral COVID-19 pneumonia according to severity 1 year after hospital discharge. METHODS: COVID-FIBROTIC is a multicenter prospective observational cohort study for admitted patients with bilateral COVID-19 pneumonia. Pulmonary functional outcomes and chest computed tomography sequelae were analyzed 12 months after hospital discharge and we classified patients into three groups according to severity. A post hoc analysis model was designed to establish how functional test changed between groups and over time. A multivariable logistic regression model was created to study prognostic factors for lung diffusion impairment and radiological fibrotic-like changes at 12 months. RESULTS: Among 488 hospitalized patients with COVID-19 pneumonia, 284 patients had completed the entire evaluation at 12 months. Median age was 60.5 ± 11.9 and 55.3% were men. We found between-group differences in male sex, length of hospital stay, radiological involvement and inflammatory laboratory parameters. The functional evaluation of pulmonary sequelae showed that severe patients had statistically worse levels of lung diffusion at 2 months but no between group differences were found in subsequent controls. At 12-month follow up, however, we found impaired lung diffusion in 39.8% unrelated to severity. Radiological fibrotic-like changes at 12 months were reported in 22.7% of patients (102/448), only associated with radiological involvement at admission (OR: 1.55, 95% CI 1.06-2.38; p = 0.02) and LDH (OR: 0.99, 95% CI 0.98-0.99; p = 0.046). CONCLUSION: Our data suggest that a significant percentage of individuals would develop pulmonary sequelae after COVID 19 pneumonia, regardless of severity of the acute process. Trial registration clinicaltrials.gov NCT04409275 (June 1, 2020).

Relevant SARS-CoV-2 viremia is associated with COVID-19 severity: Prospective cohort study and validation cohort.

Early kinetics of SARS-CoV-2 viral load (VL) in plasma determined by quantitative reverse-transcription polymerase chain reaction (RT-PCR) was evaluated as a predictor of poor clinical outcome in a prospective study and assessed in a retrospective validation cohort. Prospective observational single-center study including consecutive adult patients hospitalized with COVID-19 between November 2020 and January 2021. Serial plasma samples were obtained until discharge. Quantitative RT-PCR was performed to assess SARS-CoV-2 VL. The main outcomes were in-hospital mortality, admission to the Intensive Care Unit (ICU), and their combination (Poor Outcome). Relevant viremia (RV), established in the prospective study, was assessed in a retrospective cohort including hospitalized COVID-19 patients from April 2021 to May 2022, in which plasma samples were collected according to clinical criteria. Prospective cohort: 57 patients were included. RV was defined as at least a twofold increase in VL within ≤2 days or a VL > 300 copies/ml, in the first week. Patients with RV (N = 14; 24.6%) were more likely to die than those without RV (35.7% vs. 0%), needed ICU admission (57% vs. 0%) or had Poor Outcome (71.4% vs. 0%), (p < 0.001 for the three variables). Retrospective cohort: 326 patients were included, 18.7% presented RV. Patients with RV compared with patients without RV had higher rates of ICU-admission (odds ratio [OR]: 5.6 [95% confidence interval [CI]: 2.1-15.1); p = 0.001), mortality (OR: 13.5 [95% CI: 6.3-28.7]; p < 0.0001) and Poor Outcome (OR: 11.2 [95% CI: 5.8-22]; p < 0.0001). Relevant SARS-CoV-2 viremia in the first week of hospitalization was associated with higher in-hospital mortality, ICU admission, and Poor Outcome. Findings observed in the prospective cohort were confirmed in a larger validation cohort.

A clinical case definition of post-COVID-19 condition by a Delphi consensus.

People with COVID-19 might have sustained postinfection sequelae. Known by a variety of names, including long COVID or long-haul COVID, and listed in the ICD-10 classification as post-COVID-19 condition since September, 2020, this occurrence is variable in its expression and its impact. The absence of a globally standardised and agreed-upon definition hampers progress in characterisation of its epidemiology and the development of candidate treatments. In a WHO-led Delphi process, we engaged with an international panel of 265 patients, clinicians, researchers, and WHO staff to develop a consensus definition for this condition. 14 domains and 45 items were evaluated in two rounds of the Delphi process to create a final consensus definition for adults: post-COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset, with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include, but are not limited to, fatigue, shortness of breath, and cognitive dysfunction, and generally have an impact on everyday functioning. Symptoms might be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms might also fluctuate or relapse over time. A separate definition might be applicable for children. Although the consensus definition is likely to change as knowledge increases, this common framework provides a foundation for ongoing and future studies of epidemiology, risk factors, clinical characteristics, and therapy.

The Emergence of COVID-19 as a Cause of Death in 2020 and its Effect on Mortality by Diseases of the Respiratory System in Spain: Trends and Their Determinants Compared to 2019.

Objective: To analyze the causes of death by diseases of the respiratory system in Spain in 2020, with special interest in COVID-19; also its trends and determinants, and compare them with 2019. Material and methods: Retrospective cohort study. The coding of all those causes of death by diseases of the respiratory system were regrouped. A descriptive analysis of all deaths and by gender, age, and the 17 Autonomous Communities (CC.AA.) was performed. Also, odds ratios of death in crude and multivariate analysis by logistic regression were estimated. Results: In Spain in 2020, 60,358 deaths were attributed to "COVID-19 virus identified" and another 14,481 to "COVID-19 virus not identified (suspicious)". Regrouping the specific causes of death, in 2020 the diseases of the respiratory system caused a total of 139,880 deaths, which corresponds to 28.3% of all deaths in Spain. Compared to 2019, an increase of 68.5% was observed. By gender, deaths by diseases of the respiratory system were higher in men (32.0%) than in women (24.6%), although in specific causes the percentage was higher in women with suspected COVID-19, asthma, respiratory insufficiency and other diseases of the respiratory system. Finally, the variables associated with death from COVID-19 in the multivariate analysis were being male, increasing age (maximum at 80 years), completed studies up to secondary level, employed, and single or widowed marital status, although with a marked variation by CC.AA. Conclusions: In Spain in 2020, COVID-19 produced a large increase (68.5%) in deaths by diseases of the respiratory system compared to the previous year.

Objetivo: Analizar las causas de muerte por enfermedades del aparato respiratorio en España durante el año 2020, con especial interés en COVID-19; también sus tendencias y determinantes, y compararlas con el año 2019. Material y métodos: Estudio de cohortes retrospectivo. Se reagrupó la codificación de todas aquellas causas de muerte por enfermedades del aparato respiratorio. Se realizó un análisis descriptivo de todas las defunciones por sexo, edad en las 17 Comunidades Autónomas (CC. AA.). Además, se estimaron las odds ratios de muerte en análisis crudo y multivariado por regresión logística. Resultados: En España en el año 2020 se atribuyeron 60.358 muertes a «COVID-19 virus identificado¼ y otras 14.481 a «COVID-19 virus no identificado (sospechoso)¼. Reagrupando las causas específicas de muerte, en el año 2020 las enfermedades del aparato respiratorio provocaron un total de 139.880 muertes, lo que corresponde al 28,3% de todas las muertes en España. En comparación con el año 2019, se observó un aumento del 68,5%. Por género, las defunciones por enfermedades del aparato respiratorio fueron mayores en los varones (32,0%) que en las mujeres (24,6%), aunque en causas específicas el porcentaje fue mayor en mujeres en COVID-19 sospechosa, asma, insuficiencia respiratoria y otras enfermedades del aparato respiratorio. Finalmente, las variables asociadas a la muerte por COVID-19 en el análisis multivariante fueron el género masculino, el aumento de la edad (máximo a los 80 años), estudios completados hasta secundaria y el estado civil soltero o viudo, aunque con una marcada variación por CC. AA. Conclusiones: En España en el año 2020 la COVID-19 produjo un gran incremento (68,5%) de muertes por enfermedades del aparato respiratorio en comparación con el año anterior.