Evaluation of Lactobacillus Coryniformis K8 Consumption by Health Care Workers Exposed to COVID-19 (LactoCor2 Project): Protocol for a Randomized Controlled Trial.

BACKGROUND: Lactobacillus coryniformis K8 CECT5711 has immune-modulating properties, enhances the immune response to viral antigens leading to the production of specific antibodies, and has anti-inflammatory activity, which may help to prevent uncontrolled inflammatory processes leading to respiratory and other organ failures. OBJECTIVE: The purpose of this study is to evaluate the effect of the consumption of a probiotic strain on the incidence and severity of COVID-19 in health personnel who carry out their professional work among patients with infection or suspected infection by SARS-CoV-2. METHODS: This is a double-blind randomized clinical trial in which the experimental group will receive a capsule of L coryniformis K8 per day (3×109 colony former units/day), and the control group will receive a daily placebo capsule consisting of maltodextrin. A sample size of 314 volunteers was calculated. Volunteers must meet the following inclusion criteria: older than 20 years and active health personnel caring for patients with COVID-19, including all professionals such as medical doctors, nurses, and caretakers at the 2 referral hospitals that treat patients with COVID-19. The main outcome of the clinical trial will be the incidence of symptomatic infection by SARS-CoV-2 in personnel who care for patients with suspected or confirmed COVID-19. RESULTS: The study had to be extended to the 2 referral hospitals that treat patients with COVID-19 in the province of Granada (Andalusia, Spain); Hospital San Cecilio and Hospital Virgen de las Nieves. A total of 255 individuals met the inclusion criteria and were randomly assigned to one of the 2 groups. CONCLUSIONS: The results of this randomized controlled trial will provide valuable information regarding the administration of L coryniformis K8 against COVID-19, including whether there are fewer infectious processes due to this virus or, in case of occurrence, whether the disease is milder in participants taking the probiotic strain. TRIAL REGISTRATION: ClinicalTrials.gov NCT04366180; http://www.clinicaltrials.gov/ct2/show/NCT04366180. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/37857.

Analyzing the role of ACE2, AR, MX1 and TMPRSS2 genetic markers for COVID-19 severity.

BACKGROUND: The use of molecular biomarkers for COVID-19 remains unconclusive. The application of a molecular biomarker in combination with clinical ones that could help classifying aggressive patients in first steps of the disease could help clinician and sanitary system a better management of the disease. Here we characterize the role of ACE2, AR, MX1, ERG, ETV5 and TMPRSS2 for trying a better classification of COVID-19 through knowledge of the disease mechanisms. METHODS: A total of 329 blood samples were genotyped in ACE2, MX1 and TMPRSS2. RNA analyses were also performed from 258 available samples using quantitative polymerase chain reaction for genes: ERG, ETV5, AR, MX1, ACE2, and TMPRSS2. Moreover, in silico analysis variant effect predictor, ClinVar, IPA, DAVID, GTEx, STRING and miRDB database was also performed. Clinical and demographic data were recruited from all participants following WHO classification criteria. RESULTS: We confirm the use of ferritin (p < 0.001), D-dimer (p < 0.010), CRP (p < 0.001) and LDH (p < 0.001) as markers for distinguishing mild and severe cohorts. Expression studies showed that MX1 and AR are significantly higher expressed in mild vs severe patients (p < 0.05). ACE2 and TMPRSS2 are involved in the same molecular process of membrane fusion (p = 4.4 × 10-3), acting as proteases (p = 0.047). CONCLUSIONS: In addition to the key role of TMPSRSS2, we reported for the first time that higher expression levels of AR are related with a decreased risk of severe COVID-19 disease in females. Moreover, functional analysis demonstrates that ACE2, MX1 and TMPRSS2 are relevant markers in this disease.

Relevance of TMPRSS2, CD163/CD206, and CD33 in clinical severity stratification of COVID-19.

Background: Approximately 13.8% and 6.1% of coronavirus disease 2019 (COVID-19) patients require hospitalization and sometimes intensive care unit (ICU) admission, respectively. There is no biomarker to predict which of these patients will develop an aggressive stage that we could improve their quality of life and healthcare management. Our main goal is to include new markers for the classification of COVID-19 patients. Methods: Two tubes of peripheral blood were collected from a total of 66 (n = 34 mild and n = 32 severe) samples (mean age 52 years). Cytometry analysis was performed using a 15-parameter panel included in the Maxpar® Human Monocyte/Macrophage Phenotyping Panel Kit. Cytometry by time-of-flight mass spectrometry (CyTOF) panel was performed in combination with genetic analysis using TaqMan® probes for ACE2 (rs2285666), MX1 (rs469390), and TMPRSS2 (rs2070788) variants. GemStone™ and OMIQ software were used for cytometry analysis. Results: The frequency of CD163+/CD206- population of transitional monocytes (T-Mo) was decreased in the mild group compared to that of the severe one, while T-Mo CD163-/CD206- were increased in the mild group compared to that of the severe one. In addition, we also found differences in CD11b expression in CD14dim monocytes in the severe group, with decreased levels in the female group (p = 0.0412). When comparing mild and severe disease, we also found that CD45- [p = 0.014; odds ratio (OR) = 0.286, 95% CI 0.104-0.787] and CD14dim/CD33+ (p = 0.014; OR = 0.286, 95% CI 0.104-0.787) monocytes were the best options as biomarkers to discriminate between these patient groups. CD33 was also indicated as a good biomarker for patient stratification by the analysis of GemStone™ software. Among genetic markers, we found that G carriers of TMPRSS2 (rs2070788) have an increased risk (p = 0.02; OR = 3.37, 95% CI 1.18-9.60) of severe COVID-19 compared to those with A/A genotype. This strength is further increased when combined with CD45-, T-Mo CD163+/CD206-, and C14dim/CD33+. Conclusions: Here, we report the interesting role of TMPRSS2, CD45-, CD163/CD206, and CD33 in COVID-19 aggressiveness. This strength is reinforced for aggressiveness biomarkers when TMPRSS2 and CD45-, TMPRSS2 and CD163/CD206, and TMPRSS2 and CD14dim/CD33+ are combined.

Characteristics and clinical outcome in 312 patients with moderate to severe pneumonia due to SARS-COV-2 and hyperinflammation treated with anakinra and corticosteroids: A retrospective cohort study.

OBJECTIVE: To assess the clinical outcome (death and/or Intensive Care Unit (ICU) admission) based on the time from hospital admission to the administration of anakinra and the possible usefulness of a "simplified" SCOPE score to stratify the risk of worse prognosis in our cohort of patients with moderate/severe SARS-CoV-2 pneumonia, both vaccinated and unvaccinated, that received anakinra and corticosteroids. In addition, the clinical, analytical, and imaging characteristics of patients at admission are described. METHODS: Retrospective cohort study of 312 patients admitted to Hospital Clínico San Cecilio in Granada for moderate/severe pneumonia caused by SARS-CoV-2 that received anakinra and corticosteroids between March 2020 and January 2022. Clinical and analytical data were collected as well as the patient outcome at 30 and 60 days after admission. Three treatment groups were established according to the time from hospital admission to administration of anakinra: early (1st-2nd day), intermediate (3rd-5th day), and late (after the 5th day). RESULTS: The median age was 67.4 years (IQR 22-97 years) and 204 (65.4%) were male. The most common comorbidity was hypertension (58%). The median time from the start of symptoms to anakinra administration was 6 days (IQR 5-10) and the SaFi (SaO2/FiO2) was 228 (IQR 71-471). The cure rate was higher in the early-onset anakinra group versus the late-onset group (73% vs 56.6%). The latter had a higher percentage of deaths (27.4%) and a greater number of patients remained hospitalized for a month (16%). On admission, the patients had elevated C-reactive protein (CRP), ferritin, and D-dimer values and decreased total lymphocytes. Analytical improvement was observed at both 72 hours and one month after treatment. 42 (13.5%) required ICU admission, and 23 (7.3%) orotracheal intubation. At 60 days, 221 (70.8%) were discharged, 87 (27.8%) had died and 4 (1.4%) remained hospitalized. The mean dose of anakinra was 1000 mg (100-2600 mg) with differences found between the dose administered and the clinical outcome. There were no differences in the primary outcome based on vaccination. A simplified SCOPE score at the start of anakinra administration was lower in patients with better clinical evolution. CONCLUSIONS: Early treatment with anakinra and corticosteroids was associated with a better outcome regardless of vaccination status. A simplified SCOPE was found to be a good prognostic tool.

Dexamethasone versus weight-adjusted methylprednisolone in patients with moderate-severe SARS-CoV-2 pneumonia. / Dexametasona frente a metilprednisolona ajustada al peso en pacientes con neumonía moderada-grave por SARS-CoV-2.

OBJECTIVES: To compare the 30-day outcome (mortality and/or ICU admission) of patients admitted for moderate-severe SARS-CoV-2 pneumonia treated with dexamethasone after the Recovery study versus those treated with weight-adjusted methylprednisolone. METHODS: Retrospective cohort study of 65 patients with moderate-severe pneumonia who received dexamethasone 6 mg/day (DXM group) versus 80 treated with weight-adjusted methylprednisolone (MTPN group). RESULTS: Twenty-one (32.3%) patients in the DXM group died vs. 8 (10%) in the MTPN group (p-value < 0.001) and 29 (44.6%) in the DXM group required ICU admission vs. 2 (2.5%) of the MTPN group (p-value < 0.001). There were no baseline differences regarding sociodemographic characteristics with a higher mean qSOFA in the MTPN group. The hazard ratio for mortality and ICU admission adjusted for age, sex, and admission CRP was 2.189 (1.082-4.426; 95% CI) and 10.589 (2.139-48.347; 95% CI) for the DXM group, respectively, vs. MTPN group. CONCLUSIONS: Mortality and admission to the ICU were lower in patients treated with weight-adjusted methylprednisolone compared to those treated with dexamethasone.

Dexamethasone versus weight-adjusted methylprednisolone in patients with moderate-severe SARS-CoV-2 pneumonia Dexametasona frente a metilprednisolona ajustada al peso en pacientes con Neumonía moderada-grave por SARS-CoV-2

Objectives To compare the 30-day outcome (mortality and/or ICU admission) of patients admitted for moderate-severe SARS-CoV-2 pneumonia treated with dexamethasone after the Recovery study versus those treated with weight-adjusted methylprednisolone. Methods Retrospective cohort study of 65 patients with moderate-severe pneumonia who received dexamethasone 6 mg/day (DXM group) versus 80 treated with weight-adjusted methylprednisolone (MTPN group) Results 21 (32.3%) patients in the DXM group died vs 8 (10%) in the MTPN group (p-value < 0.001) and 29 (44.6%) in the DXM group required ICU admission vs 2 (2,5%) of the MTPN group (p-value <0.001). There were no baseline differences regarding sociodemographic characteristics with a higher mean qSOFA in the MTPN group. The hazard ratio for mortality and ICU admission adjusted for age, sex, and admission CRP was 2.189 (1.082-4.426;95% CI) and 10.589 (2.139-48.347;95% CI) for the DXM group, respectively., vs MTPN group. Conclusions Mortality and admission to the ICU were lower in patients treated with weight-adjusted methylprednisolone compared to those treated with dexamethasone.

Dexamethasone versus weight-adjusted methylprednisolone in patients with moderate-severe SARS-CoV-2 pneumonia.

Objectives: To compare the 30-day outcome (mortality and/or ICU admission) of patients admitted for moderate-severe SARS-CoV-2 pneumonia treated with dexamethasone after the Recovery study versus those treated with weight-adjusted methylprednisolone. Methods: Retrospective cohort study of 65 patients with moderate-severe pneumonia who received dexamethasone 6 mg/day (DXM group) versus 80 treated with weight-adjusted methylprednisolone (MTPN group). Results: 21 (32.3%) patients in the DXM group died vs 8 (10%) in the MTPN group (p-value < 0.001) and 29 (44.6%) in the DXM group required ICU admission vs 2 (2,5%) of the MTPN group (p-value <0.001). There were no baseline differences regarding sociodemographic characteristics with a higher mean qSOFA in the MTPN group. The hazard ratio for mortality and ICU admission adjusted for age, sex, and admission CRP was 2.189 (1.082-4.426; 95% CI) and 10.589 (2.139-48.347; 95% CI) for the DXM group, respectively, vs. MTPN group. Conclusions: Mortality and admission to the ICU were lower in patients treated with weight-adjusted methylprednisolone compared to those treated with dexamethasone.

Objetivos: Comparar el desenlace clínico (mortalidad y/o ingreso en UCI) a 30 días de los pacientes ingresados por neumonía moderada-grave por SARS-CoV-2 tratados con dexametasona tras el estudio Recovery frente aquellos tratados con metilprednisolona ajustada al peso. Métodos: Estudio de cohortes retrospectivo de 65 pacientes con neumonía moderada-grave que recibieron 6 mg/día de dexametasona (grupo DXM) frente a 80 tratados con metilprednisolona ajustada al peso (grupo MTPN). Resultados: Fallecieron 21 (32,3%) pacientes del grupo DXM vs 8 (10%) del grupo MTPN (p-valor < 0,001) y 29 (44,6%) del grupo DXM requirieron ingreso en UCI vs 2 (2,5%) del grupo MTPN (p-valor < 0,001). No hubo diferencias basales respecto a características sociodemográficas con un qSOFA medio superior en el grupo MTPN. La razón de riesgo para la mortalidad y el ingreso en UCI ajustada por edad, sexo y PCR al ingreso fue de 2,189 (1,082−4,426; IC 95%) y 10,589 (2,139−48,347; IC 95%) para el grupo DXM, respectivamente, vs grupo MTPN. Conclusiones: La mortalidad e ingreso en UCI fue menor en pacientes tratados con metilprednisolona ajustada al peso frente a los tratados con dexametasona.

Therapeutic agents tested in 238 COVID-19 hospitalized patients and their relationship with mortality.

BACKGROUND AND OBJECTIVES: In the last months great efforts have been developed to evaluate the more efficient therapeutic agents in the management of patients with COVID-19. Currently, no specific drug combination has consistently demonstrated an association with mortality. The aim of this study was to assess the pattern of associations observed between the different in-hospital treatments administered to a series of 238 patients admitted for COVID-19 and their relationship with mortality. METHODS: The electronic medical records of patients that discharged or died from COVID-19 in the Hospital Universitario San Cecilio (Granada, Spain) between March 16 and April 10, 2020 were analysed. From these records, information was obtained on sex, age, comorbidities at admission, clinical information, analytical parameters, imaging tests and empirical treatments used. The outcome variable was the in-hospital mortality. To estimate the associations between the different therapeutic alternatives and the risk of mortality, Hazard Ratios adjusted for age, sex, previous pathologies and severity at discharge were estimated using Cox Regression models. RESULTS: The most frequently used combination of drugs was low molecular weight heparins, hydroxychloroquine, and ritonavir/lopinavir. None of the analysed treatments showed independent association with mortality. The drugs that showed a greater inverse association with mortality were tocilizumab and corticoids. CONCLUSIONS: The observed association patterns are consistent with previous literature. It seems necessary to design randomized controlled clinical trials that evaluate the possible protector effect of tocilizumab and corticoids in the risk of mortality for some subgroups of COVID-19 hospitalized patients.

ANTECEDENTES Y OBJETIVO: En los últimos meses se han realizado grandes esfuerzos para evaluar las terapias más eficaces en el manejo de pacientes con COVID-19. Actualmente ninguna combinación ha demostrado de manera consistente una relación clara con la mortalidad. Nuestro objetivo fue valorar el patrón de asociaciones observado entre los distintos tratamientos intrahospitalarios administrados a 238 pacientes ingresados por COVID-19 y la mortalidad. MATERIALES Y MÉTODOS: Se analizaron las historias clínicas electrónicas de aquellos pacientes dados de alta o que fallecieron por COVID-19 entre el 16 de marzo y el 10 de abril de 2020 en el Hospital Universitario San Cecilio (Granada, España). Se obtuvo información sobre sexo, edad, comorbilidades al ingreso, parámetros clínicos, analíticos, pruebas de imagen y tratamientos empíricos empleados. La variable de desenlace fue la mortalidad intrahospitalaria. Para estimar las asociaciones entre los diferentes tratamientos y el riesgo de mortalidad se estimaron, mediante modelos de regresión de Cox, hazard ratio ajustadas por edad, sexo, patologías previas y gravedad al ingreso. RESULTADOS: La combinación de fármacos más frecuentemente empleada fue la formada por heparinade bajo peso molecular (HBPM), hidroxicloroquina y ritonavir/lopinavir. Ninguno de los tratamientos utilizados mostró una asociación independiente con la mortalidad. Los fármacos que mostraron una asociación inversa de mayor magnitud fueron el tocilizumab y los corticoides. CONCLUSIONES: El patrón se asociaciones obtenido es consistente con lo reportado en la bibliografía. Parece oportuno diseñar ensayos aleatorizados que valoren el posible efecto protector de los corticoides y el tocilizumab sobre el riesgo de muerte en algunos subgrupos de pacientes hospitalizados por COVID-19.

[Therapeutic agents tested in 238 COVID-19 hospitalized patients and their relationship with mortality]. / Agentes terapéuticos utilizados en 238 pacientes hospitalizados por COVID-19 y su relación con la mortalidad.

BACKGROUND AND OBJECTIVES: In the last months great efforts have been developed to evaluate the more efficient therapeutic agents in the management of patients with COVID-19. Currently, no specific drug combination has consistently demonstrated an association with mortality. The aim of this study was to assess the pattern of associations observed between the different in-hospital treatments administered to a series of 238 patients admitted for COVID-19 and their relationship with mortality. METHODS: The electronic medical records of patients that discharged or died from COVID-19 in the Hospital Universitario San Cecilio (Granada, Spain) between March 16 and April 10, 2020 were analysed. From these records, information was obtained on sex, age, comorbidities at admission, clinical information, analytical parameters, imaging tests and empirical treatments used. The outcome variable was the in-hospital mortality. To estimate the associations between the different therapeutic alternatives and the risk of mortality, hazard ratios adjusted for age, sex, previous pathologies and severity at discharge were estimated using Cox regression models. RESULTS: The most frequently used combination of drugs was low molecular weight heparins, hydroxychloroquine, and ritonavir/lopinavir. None of the analysed treatments showed independent association with mortality. The drugs that showed a greater inverse association with mortality were tocilizumab and corticoids. CONCLUSIONS: The observed association patterns are consistent with previous literature. It seems necessary to design randomized controlled clinical trials that evaluate the possible protector effect of tocilizumab and corticoids in the risk of mortality for some subgroups of COVID-19 hospitalized patients.

Sociodemographic, clinical and laboratory factors on admission associated with COVID-19 mortality in hospitalized patients: A retrospective observational study.

BACKGROUND: To identify and quantify associations between baseline characteristics on hospital admission and mortality in patients with COVID-19 at a tertiary hospital in Spain. METHODS AND FINDINGS: This retrospective case series included 238 patients hospitalized for COVID-19 at Hospital Universitario Clínico San Cecilio (Granada, Spain) who were discharged or who died. Electronic medical records were reviewed to obtain information on sex, age, personal antecedents, clinical features, findings on physical examination, and laboratory results for each patient. Associations between mortality and baseline characteristics were estimated as hazard ratios (HR) calculated with Cox regression models. Series mortality was 25.6%. Among patients with dependence for basic activities of daily living, 78.7% died, and among patients residing in retirement homes, 80.8% died. The variables most clearly associated with a greater hazard of death were age (3% HR increase per 1-year increase in age; 95%CI 1-6), diabetes mellitus (HR 2.42, 95%CI 1.43-4.09), SatO2/FiO2 ratio (43% HR reduction per 1-point increase; 95%CI 23-57), SOFA score (19% HR increase per 1-point increase, 95%CI 5-34) and CURB-65 score (76% HR increase per 1-point increase, 95%CI 23-143). CONCLUSIONS: The patients residing in retirement homes showed great vulnerability. The main baseline factors that were independently associated with mortality in patients hospitalized for COVID-19 were older age, diabetes mellitus, low SatO2/FiO2 ratio, and high SOFA and CURB-65 scores.

Clinical Factors, Preventive Behaviours and Temporal Outcomes Associated with COVID-19 Infection in Health Professionals at a Spanish Hospital.

The novel coronavirus disease (COVID-19) outbreak has quickly spread around the world, with Spain being one of the most severely affected countries. Healthcare professionals are an important risk group given their exposure. The aims of this study were to determine the prevalence of symptoms, main concerns as patients, preventive behaviours of healthcare professionals, and the different temporal outcomes associated with the negativization of PCR results. A total of 238 professionals were analysed and follow-up was conducted from 11 March to 21 April 2020 through clinical records, in-depth surveys, and telephone interviews. Symptoms, concerns, and preventive measures were documented, and temporal outcomes (start and end of symptoms, first positive PCR, and negativization of PCR) were analysed through survival analyses. A high prevalence of gastrointestinal symptoms (especially in women and older professionals), fever, cough, and fatigue were reported. The main concern was contagion in the work and home environment. Professionals (especially men) reported low use of face masks before the pandemic. Our analysis indicates that the median times for the negativization of PCR testing to confirm the resolution of infection is 15 days after the end of symptoms, or 25 days after the first positive PCR test. Our results suggest that these times are longer for women and for professionals aged ≥55 years, therefore follow-up strategies should be optimized in light of both variables. This is the first study we are aware of to report factors associated with the time to negativization of PCR results. We present the first rigorous estimates of time outcomes and hope that these data can be valuable to continue feeding the prediction models that are currently being developed. Similar studies are required to corroborate our results.