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.

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.

Plitidepsin in adult patients with COVID-19 requiring hospital admission: A long-term follow-up analysis

Introduction The APLICOV-PC study assessed the safety and preliminary efficacy of plitidepsin in hospitalized adult patients with COVID-19. In this follow-up study (E-APLICOV), the incidence of post-COVID-19 morbidity was evaluated and any long-term complications were characterized. Methods Between January 18 and March 16, 2022, 34 of the 45 adult patients who received therapy with plitidepsin in the APLICOV-PC study were enrolled in E-APLICOV (median time from plitidepsin first dose to E-APLICOV enrollment, 16.8 months [range, 15.2–19.5 months]). All patients were functionally autonomous with regard to daily living (Barthel index: 100) and had normal physical examinations. Results From the APLICOV-PC date of discharge to the date of the extension visit, neither Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5) grade 3-4 complications nor QT prolongation or significant electrocardiogram (EKG) abnormalities were reported. Five (14.7%) patients had another COVID-19 episode after initial discharge from APLICOV-PC, and in 2 patients (5.9%), previously unreported chest X-ray findings were documented. Spirometry and lung-diffusion tests were normal in 29 (85.3%) and 27 (79.4%) patients, respectively, and 3 patients needed additional oxygen supplementation after initial hospital discharge. None of these patients required subsequent hospital readmission for disease-related complications. Discussion In conclusion, plitidepsin has demonstrated a favorable long-term safety profile in adult patients hospitalized for COVID-19. With the constraints of a low sample size and a lack of control, the rate of post-COVID-19 complications after treatment with plitidepsin is in the low range of published reports. (ClinicalTrials.gov Identifier: NCT05121740;https://clinicaltrials.gov/ct2/show/NCT05121740).

Plitidepsin in adult patients with COVID-19 requiring hospital admission: A long-term follow-up analysis.

Introduction: The APLICOV-PC study assessed the safety and preliminary efficacy of plitidepsin in hospitalized adult patients with COVID-19. In this follow-up study (E-APLICOV), the incidence of post-COVID-19 morbidity was evaluated and any long-term complications were characterized. Methods: Between January 18 and March 16, 2022, 34 of the 45 adult patients who received therapy with plitidepsin in the APLICOV-PC study were enrolled in E-APLICOV (median time from plitidepsin first dose to E-APLICOV enrollment, 16.8 months [range, 15.2-19.5 months]). All patients were functionally autonomous with regard to daily living (Barthel index: 100) and had normal physical examinations. Results: From the APLICOV-PC date of discharge to the date of the extension visit, neither Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5) grade 3-4 complications nor QT prolongation or significant electrocardiogram (EKG) abnormalities were reported. Five (14.7%) patients had another COVID-19 episode after initial discharge from APLICOV-PC, and in 2 patients (5.9%), previously unreported chest X-ray findings were documented. Spirometry and lung-diffusion tests were normal in 29 (85.3%) and 27 (79.4%) patients, respectively, and 3 patients needed additional oxygen supplementation after initial hospital discharge. None of these patients required subsequent hospital readmission for disease-related complications. Discussion: In conclusion, plitidepsin has demonstrated a favorable long-term safety profile in adult patients hospitalized for COVID-19. With the constraints of a low sample size and a lack of control, the rate of post-COVID-19 complications after treatment with plitidepsin is in the low range of published reports. (ClinicalTrials.gov Identifier: NCT05121740; https://clinicaltrials.gov/ct2/show/NCT05121740).

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.

SARS-CoV-2 Viremia Precedes an IL6 Response in Severe COVID-19 Patients: Results of a Longitudinal Prospective Cohort.

Background: Interleukin 6 (IL6) levels and SARS-CoV-2 viremia have been correlated with COVID-19 severity. The association over time between them has not been assessed in a prospective cohort. Our aim was to evaluate the relationship between SARS-CoV-2 viremia and time evolution of IL6 levels in a COVID-19 prospective cohort. Methods: Secondary analysis from a prospective cohort including COVID-19 hospitalized patients from Hospital Universitario La Princesa between November 2020 and January 2021. Serial plasma samples were collected from admission until discharge. Viral load was quantified by Real-Time Polymerase Chain Reaction and IL6 levels with an enzyme immunoassay. To represent the evolution over time of both variables we used the graphic command twoway of Stata. Results: A total of 57 patients were recruited, with median age of 63 years (IQR [53-81]), 61.4% male and 68.4% Caucasian. The peak of viremia appeared shortly after symptom onset in patients with persistent viremia (more than 1 sample with > 1.3 log10 copies/ml) and also in those with at least one IL6 > 30 pg/ml, followed by a progressive increase in IL6 around 10 days later. Persistent viremia in the first week of hospitalization was associated with higher levels of IL6. Both IL6 and SARS-CoV-2 viral load were higher in males, with a quicker increase with age. Conclusion: In those patients with worse outcomes, an early peak of SARS-CoV-2 viral load precedes an increase in IL6 levels. Monitoring SARS-CoV-2 viral load during the first week after symptom onset may be helpful to predict disease severity in COVID-19 patients.

Impact of the SARS-CoV-2 Virus Pandemic on Patients with Bronchiectasis: A Multicenter Study.

BACKGROUND: Infection by SARS-CoV-2 has unquestionably had an impact on the health of patients with chronic respiratory airway diseases, such as COPD and asthma, but little information is available about its impact on patients with bronchiectasis. The objective of the present study was to analyze the effect of the SARS-CoV-2 pandemic on the state of health, characteristics, and clinical severity (including the number and severity of exacerbations) of patients with non-cystic fibrosis bronchiectasis. METHODS: This study was multicenter, observational, and ambispective (with data collected before and during the SARS-CoV-2 pandemic), and included 150 patients diagnosed with non-cystic fibrosis bronchiectasis. RESULTS: A significant drop was observed in the number and severity of the exacerbations (57% in all exacerbations and 50% in severe exacerbations) in the E-FACED and BSI multidimensional scores, in the pandemic, compared with the pre-pandemic period. There was also a drop in the percentage of sputum samples positive for pathogenic microorganisms in general (from 58% to 44.7%) and, more specifically, Pseudomonas aeruginosa (from 23.3% to 13.3%) and Haemophilus influenzae (from 21.3% to 14%). CONCLUSIONS: During the SARS-CoV-2 period, a significant reduction was observed in the exacerbations, severity, and isolations of pathogenic microorganisms in patients with bronchiectasis.

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.

SARS-CoV-2 Viremia Precedes an IL6 Response in Severe COVID-19 Patients: Results of a Longitudinal Prospective Cohort

Background Interleukin 6 (IL6) levels and SARS-CoV-2 viremia have been correlated with COVID-19 severity. The association over time between them has not been assessed in a prospective cohort. Our aim was to evaluate the relationship between SARS-CoV-2 viremia and time evolution of IL6 levels in a COVID-19 prospective cohort. Methods Secondary analysis from a prospective cohort including COVID-19 hospitalized patients from Hospital Universitario La Princesa between November 2020 and January 2021. Serial plasma samples were collected from admission until discharge. Viral load was quantified by Real-Time Polymerase Chain Reaction and IL6 levels with an enzyme immunoassay. To represent the evolution over time of both variables we used the graphic command twoway of Stata. Results A total of 57 patients were recruited, with median age of 63 years (IQR [53–81]), 61.4% male and 68.4% Caucasian. The peak of viremia appeared shortly after symptom onset in patients with persistent viremia (more than 1 sample with > 1.3 log10 copies/ml) and also in those with at least one IL6 > 30 pg/ml, followed by a progressive increase in IL6 around 10 days later. Persistent viremia in the first week of hospitalization was associated with higher levels of IL6. Both IL6 and SARS-CoV-2 viral load were higher in males, with a quicker increase with age. Conclusion In those patients with worse outcomes, an early peak of SARS-CoV-2 viral load precedes an increase in IL6 levels. Monitoring SARS-CoV-2 viral load during the first week after symptom onset may be helpful to predict disease severity in COVID-19 patients.

Efficacy of short-course colchicine treatment in hospitalized patients with moderate to severe COVID-19 pneumonia and hyperinflammation: a randomized clinical trial.

Some patients with COVID-19 pneumonia develop an associated cytokine storm syndrome that aggravates the pulmonary disease. These patients may benefit of anti-inflammatory treatment. The role of colchicine in hospitalized patients with COVID-19 pneumonia and established hyperinflammation remains unexplored. In a prospective, randomized controlled, observer-blinded endpoint, investigator-initiated trial, 240 hospitalized patients with COVID-19 pneumonia and established hyperinflammation were randomly allocated to receive oral colchicine or not. The primary efficacy outcome measure was a composite of non-invasive mechanical ventilation (CPAP or BiPAP), admission to the intensive care unit, invasive mechanical ventilation requirement or death. The composite primary outcome occurred in 19.3% of the total study population. The composite primary outcome was similar in the two arms (17% in colchicine group vs. 20.8% in the control group; p = 0.533) and the same applied to each of its individual components. Most patients received steroids (98%) and heparin (99%), with similar doses in both groups. In this trial, including adult patients with COVID-19 pneumonia and associated hyperinflammation, no clinical benefit was observed with short-course colchicine treatment beyond standard care regarding the combined outcome measurement of CPAP/BiPAP use, ICU admission, invasive mechanical ventilation or death (Funded by the Community of Madrid, EudraCT Number: 2020-001841-38; 26/04/2020).

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.

Usefulness of the CONUT index upon hospital admission as a potential prognostic indicator of COVID-19 health outcomes.

BACKGROUND: In-hospital mortality in patients with coronavirus disease 2019 (COVID-19) is high. Simple prognostic indices are needed to identify patients at high-risk of COVID-19 health outcomes. We aimed to determine the usefulness of the CONtrolling NUTritional status (CONUT) index as a potential prognostic indicator of mortality in COVID-19 patients upon hospital admission. METHODS: Our study design is of a retrospective observational study in a large cohort of COVID-19 patients. In addition to descriptive statistics, a Kaplan-Meier mortality analysis and a Cox regression were performed, as well as receiver operating curve (ROC). RESULTS: From February 5, 2020 to January 21, 2021, there was a total of 2969 admissions for COVID-19 at our hospital, corresponding to 2844 patients. Overall, baseline (within 4 days of admission) CONUT index could be scored for 1627 (57.2%) patients. Patients' age was 67.3 ±â€Š16.5 years and 44.9% were women. The CONUT severity distribution was: 194 (11.9%) normal (0-1); 769 (47.2%) light (2-4); 585 (35.9%) moderate (5-8); and 79 (4.9%) severe (9-12). Mortality of 30 days after admission was 3.1% in patients with normal risk CONUT, 9.0% light, 22.7% moderate, and 40.5% in those with severe CONUT (P < 0.05). An increased risk of death associated with a greater baseline CONUT stage was sustained in a multivariable Cox regression model (P < 0.05). An increasing baseline CONUT stage was associated with a longer duration of admission, a greater requirement for the use of non-invasive and invasive mechanical ventilation, and other clinical outcomes (all P < 0.05). The ROC of CONUT for mortality had an area under the curve (AUC) and 95% confidence interval of 0.711 (0.676-0746). CONCLUSION: The CONUT index upon admission is potentially a reliable and independent prognostic indicator of mortality and length of hospitalization in COVID-19 patients.