COVID-19 in hospitalized solid organ transplant recipients in a nationwide registry study.

OBJECTIVES: Underlying immunodeficiency has been associated with worse clinical presentation and increased mortality in patients with COVID-19. We evaluated the mortality of solid organ transplant (SOT) recipients (SOTR) hospitalized in Spain due to COVID-19. METHODS: Nationwide, retrospective, observational analysis of all adults hospitalized because of COVID-19 in Spain during 2020. Stratification was made according to SOT status. The National Registry of Hospital Discharges was used, using the International Classification of Diseases, 10th revision coding list. RESULTS: Of the 117,694 adults hospitalized during this period, 491 were SOTR: kidney 390 (79.4%), liver 59 (12%), lung 27 (5.5%), and heart 19 (3.9%). Overall, the mortality of SOTR was 13.8%. After adjustment for baseline characteristics, SOTR was not associated with higher mortality risk (odds ratio [OR] = 0.79, 95% confidence interval [CI] 0.60-1.03). However, lung transplantation was an independent factor related to mortality (OR = 3.26, 95% CI 1.33-7.43), while kidney, liver, and heart transplantation were not. Being a lung transplant recipient was the strongest prognostic factor in SOT patients (OR = 5.12, 95% CI 1.88-13.98). CONCLUSION: This nationwide study supports that the COVID-19 mortality rate in SOTR in Spain during 2020 did not differ from the general population, except for lung transplant recipients, who presented worse outcomes. Efforts should be focused on the optimal management of lung transplant recipients with COVID-19.

Increased incidence of giant cell arteritis and associated stroke during the COVID-19 pandemic in Spain: A nation-wide population study.

INTRODUCTION: SARS-CoV-2 infection and COVID-19 vaccines might have increased the incidence of giant-cell arteritis (GCA) and the risk of associated stroke in Spain. METHODS: Retrospective nation-wide observational analysis of all adults hospitalized with GCA in Spain during 5 years (Jan-2016 and Dec-2021). The incidence and proportion of admissions with or because of GCA and GCA-associated stroke were compared between pre-pandemic (2016-2019) and pandemic (2020 and 2021) years. Sensitivity analyses were conducted for the different COVID-19 waves and vaccine timing schedules. RESULTS: A total of 17,268 hospital admissions in patients diagnosed with GCA were identified. During 2020 there were 79.3 and 8.1 per 100,000 admissions of GCA and GCA-associated stroke, respectively. During 2021 these figures were 80.8 and 7.7 per 100,00 admissions, respectively. As comparison, yearly admissions due to GCA and GCA-associated stroke were 72.4 and 5.7 per 100,00, respectively, during the pre-pandemic period (p < 0.05). Coincident with the third wave of COVID-19 (and first vaccine dosing), the rate of GCA-associated stroke admissions increased significantly (from 6.7 to 12%; p < 0.001). Likewise, there was an increase in GCA-associated stroke (6.6% vs 4.1%, p = 0.016) coincident with the third dose vaccination (booster) in patients older than 70 at the end of 2021. In multivariate analysis, only patients admitted during the third COVID-19 wave (and first vaccine dosing) (OR = 1.89, 95% CI 1.22-2.93), and during the third vaccination dosing in patients older than 70 (booster) (OR = 1.66, CI 1.11-2.49), presented a higher GCA-associated stroke risk than the same months of previous years after adjustment by age, sex, classical cardiovascular risk factors and COVID-19 diagnosis. CONCLUSIONS: The COVID-19 pandemic led to an increased incidence of GCA during 2020 and 2021. Moreover, the risk of associated stroke significantly risen accompanying times of COVID-19 vaccine dosing, hypothetically linked to an increased thrombotic risk of mRNA-SARS-CoV-2 vaccines. Hence, forthcoming vaccine policies and indications must weigh the risk of severe COVID-19 with the risk of flare or stroke in patients with GCA.

Predictors of in-hospital mortality in HIV-infected patients with COVID-19.

BACKGROUND: Underlying immunodeficiency is associated with severe COVID-19, but the prognosis of persons with HIV (PWH) with COVID-19 is under debate. METHODS: Nationwide, retrospective, observational analysis of all hospitalizations with COVID-19 during year 2020 in Spain. Stratification was made according to HIV status. The National Registry of Hospital Discharges was used with the ICD-10 coding list. RESULTS: A total of 117,694 adults were hospitalized with COVID-19 during 2020. Only 234 (0.2%) were HIV-positives. More than 95% were on antiretroviral therapy. Compared to HIV-negatives, PWH were younger (mean age 53.2 vs 66.5 years-old; p < 0.001) and more frequently male (74.8% vs 56.6%; p < 0.001). Most co-morbidities predisposing to severe COVID-19 (diabetes, hypertension, dementia, cardiovascular disease) were more frequent in HIV-negatives. In contrast, the rate of baseline liver disease was over 6-fold higher in PWH (27.4% vs 4.4%; p < 0.001). In-hospital mortality was lower in PWH (9.4% vs 16%; p = 0.004). In multivariate analysis, older age, dementia and especially advanced liver disease (RR: 7.6) were the major determinants of death in PWH hospitalized with COVID-19. CONCLUSION: HIV-infected patients hospitalized in Spain with COVID-19 during 2020 had better survival than HIV-negatives, most likely explained by younger age and lower rate of co-morbidities. However, advanced liver disease was a major predictor of death in PWH hospitalized with COVID-19.

An Interplay between Oxidative Stress (Lactate Dehydrogenase) and Inflammation (Anisocytosis) Mediates COVID-19 Severity Defined by Routine Clinical Markers.

Viral infections activate the innate immune response and the secretion of inflammatory cytokines. They also alter oxidative stress markers, which potentially can have an involvement in the pathogenesis of the disease. The aim of this research was to study the role of the oxidative stress process assessed through lactate dehydrogenase (LDH) on the severity of COVID-19 measured by oxygen saturation (SaO2) and the putative interaction with inflammation. The investigation enrolled 1808 patients (mean age of 68 and 60% male) with COVID-19 from the HM Hospitals database. To explore interactions, a regression model and mediation analyses were performed. The patients with lower SaO2 presented lymphopenia and higher values of neutrophils-to-lymphocytes ratio and on the anisocytosis coefficient. The regression model showed an interaction between LDH and anisocytosis, suggesting that high levels of LDH (>544 U/L) and an anisocytosis coefficient higher than 10% can impact SaO2 in COVID-19 patients. Moreover, analysis revealed that LDH mediated 41% (p value = 0.001) of the effect of anisocytosis on SaO2 in this cohort. This investigation revealed that the oxidative stress marker LDH and the interaction with anisocytosis have an important role in the severity of COVID-19 infection and should be considered for the management and treatment of the oxidative phenomena concerning this within a precision medicine strategy.

Systemic Autoimmune Diseases in Patients Hospitalized with COVID-19 in Spain: A Nation-Wide Registry Study.

We aimed to evaluate the clinical outcome of Systemic Autoimmune Diseases (SADs) patients hospitalized with COVID-19 in Spain, before the introduction of SARS-CoV-2 vaccines. A nationwide, retrospective and observational analysis of the patients admitted during 2020, based on the ICD10 codes in the National Registry of Hospital Discharges, was performed. Among 117,694 patients, only 892 (0.8%) presented any type of SAD before COVID-19-related admission: Sjogren's Syndrome constituted 25%, Systemic Vasculitides 21%, Systemic Lupus Erythematosus 19%, Sarcoidosis 17%, Systemic Sclerosis 11%, Mixed and Undifferentiated Connective Tissue Disease 4%, Behçet's Disease 4% and Inflammatory Myopathies 2%. The in-hospital mortality rate was higher in SAD individuals (20% vs. 16%, p < 0.001). After adjustment by baseline conditions, SADs were not associated with a higher mortality risk (OR = 0.93, 95% CI 0.78-1.11). Mortality in the SADs patients was determined by age (OR = 1.05, 95% CI 1.04-1.07), heart failure (OR = 1.67, 95% CI 1.10-2.49), chronic kidney disease (OR = 1.29, 95% CI 1.05-1.59) and liver disease (OR = 1.97, 95% CI 1.13-3.44). In conclusion, the higher COVID-19 mortality rate seen in SADs patients hospitalized in Spain in 2020 was related to the higher burden of comorbidities, secondary to direct organ damage and sequelae of their condition. Whilst further studies should evaluate the impact of baseline immunosuppression on COVID-19 outcomes in this population, efforts should be focused on the optimal management of SAD to minimize the impact of the organ damage that has been shown to determine COVID-19 prognosis.

Interaction of ACEI antihypertensive agent's administration with the inflammatory status at admission concerning COVID-19 clinical stay outcomes.

Interactions between anti-hypertensive agents (ACEI), comorbidities, inflammation, and stress status may impact hospital stay duration in COVID-19 patients. This retrospective study analyzed epidemiological data, comorbidities, metabolic/inflammatory markers, and clinical information from 165 SARS-CoV-2 positive patients. In a multiple linear regression model, an IL-6 higher than 100 mg/L, glucose at admission (baseline levels at the hospital entry), and the interaction between ACEI administration and LDH predicted the days of hospital admission (P < 0.001). In conclusion, hypertensive patients suffering more severe inflammatory condition assessed by LDH levels clinically benefited more and reduced the hospital stay when prescribed ACEI agents than those with lower systemic baseline inflammation at admission.

Bacterial infections in patients hospitalized with COVID-19.

Bacterial infections may complicate the course of COVID-19 patients. The rate and predictors of bacterial infections were examined in patients consecutively admitted with COVID-19 at one tertiary hospital in Madrid between March 1st and April 30th, 2020. Among 1594 hospitalized patients with COVID-19, 135 (8.5%) experienced bacterial infectious events, distributed as follows: urinary tract infections (32.6%), bacteremia (31.9%), pneumonia (31.8%), intra-abdominal infections (6.7%) and skin and soft tissue infections (6.7%). Independent predictors of bacterial infections were older age, neurological disease, prior immunosuppression and ICU admission (p < 0.05). Patients with bacterial infections who more frequently received steroids and tocilizumab, progressed to lower Sap02/FiO2 ratios, and experienced more severe ARDS (p < 0.001). The mortality rate was significantly higher in patients with bacterial infections as compared to the rest (25% vs 6.7%, respectively; p < 0.001). In multivariate analyses, older age, prior neurological or kidney disease, immunosuppression and ARDS severity were associated with an increased mortality (p < 0.05) while bacterial infections were not. Conversely, the use of steroids or steroids plus tocilizumab did not confer a higher risk of bacterial infections and improved survival rates. Bacterial infections occurred in 8.5% of patients hospitalized with COVID-19 during the first wave of the pandemic. They were not independently associated with increased mortality rates. Baseline COVID-19 severity rather than the incidence of bacterial infections seems to contribute to mortality. When indicated, the use of steroids or steroids plus tocilizumab might improve survival in this population.

Severe Lymphopenia as a Predictor of COVID-19 Mortality in Immunosuppressed Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has a high mortality in certain group of patients. We analysed the impact of baseline immunosuppression in COVID-19 mortality and the role of severe lymphopenia in immunocompromised subjects. METHODS: We analysed all patients admitted with COVID-19 in a tertiary hospital in Madrid between March 1st and April 30th 2020. Epidemiological and clinical data, including severe lymphopenia (<500 lymphocytes/mm3) during admission, were analysed and compared based on their baseline immunosuppression condition. RESULTS: A total of 1594 patients with COVID-19 pneumonia were hospitalised during the study period. 166 (10.4%) were immunosuppressed. Immunocompromised patients were younger (64 vs. 67 years, p = 0.02) but presented higher rates of hypertension, diabetes, heart, neurological, lung, kidney and liver disease (p < 0.05). They showed more severe lymphopenia (53% vs 24.1%, p < 0.001), lower SapO2/FiO2 ratios (251 vs 276, p = 0.02) during admission and higher mortality rates (27.1% vs 13.5%, p < 0.001). After adjustment, immunosuppression remained as an independent factor related to mortality (Odds Ratio (OR): 2.24, p < 0.001). In the immunosuppressed group, age (OR = 1.06, p = 0.01), acute respiratory distress syndrome (ARDS) (OR = 12.27, p = 0.017) and severe lymphopenia (OR = 3.48, p = 0.04) were the factors related to high mortality rate. CONCLUSION: Immunosuppression is an independent mortality risk factor in COVID-19. Severe lymphopenia should be promptly identified in these patients.

[Evolution of patients infected with SARS-CoV-2 according to previous metabolic status]. / Evolución de la infección por SARS-CoV-2 en función del estado metabólico previo del paciente.

INTRODUCTION: Introduction: coronavirus disease 2019 (COVID-19) encompasses a wide spectrum of symptoms, including respiratory, gastrointestinal, hematological, and dermatological manifestations. The virus interaction with cells located in the respiratory tract causes the release of inflammatory mediators, whose involvement could be exacerbated by co-existing obesity, diabetes, and cardiovascular events. Objectives: the objective of this research was to analyze the clinically metabolic status in patients who have suffered COVID-19 disease in order to predict the outcome. Methods: this research is a retrospective study based on a cohort of 165 consecutively admitted patients with criteria for COVID-19 pneumonia according to WHO guidelines at the Hospital Universitario Puerta de Hierro between March and April 2020. Recorded variables included demographic and epidemiological data plus diagnoses as well as morbid complications during hospitalization. The Biochemistry Unit Laboratory carried out laboratory analyses according to validated operational procedures. The statistical tests included univariate and multivariate models adjusted for baseline characteristics and clinically relevant features. Results: the most frequent comorbidity in our cohort was arterial hypertension (44.0 %), followed by dyslipidemia (32.1 %), obesity (30.9 %), and diabetes mellitus (20.0 %). The association between admission to the intensive care unit (ICU) with body mass index (BMI) in a multivariate model was statistically significant, evidencing that obese subjects (BMI ≥ 30 kg/m2) have a 19 % higher risk of requiring ICU care. The univariate model revealed a statistically significant association between obesity and ICU admission and length of hospital stay (p < 0.05). The relationship between baseline blood glucose and in-hospital mortality was also statistically significant (p = 0.03), as well as with total cholesterol and ICU admission (p = 0.007). Conclusions: obesity is related to a longer time of hospitalization and a higher rate of admissions to the ICU. Low total cholesterol levels and abnormal baseline blood glucose were risk factors for ICU requirement and in-hospital mortality. Patient categorization based on obesity could be valuable in the development of a precision medicine model within the COVID-19 pandemic.

INTRODUCCIÓN: Introducción: la enfermedad por COVID-19 engloba un amplio espectro de síntomas entre los que destacan los trastornos respiratorios, digestivos, hematológicos y dermatológicos. La interacción del virus con las células ubicadas en el tracto respiratorio provoca la liberación de mediadores inflamatorios cuya producción podría estar relacionada con la obesidad, la diabetes y los eventos cardiovasculares. Objetivos: analizar el estado metabólico al ingreso de los pacientes infectados por SARS-CoV-2 y su capacidad para predecir el desenlace clínico. Métodos: este trabajo consiste en un estudio retrospectivo basado en una cohorte de 165 pacientes ingresados consecutivamente en el Hospital Universitario Puerta de Hierro Majadahonda entre marzo y abril de 2020 con criterios de neumonía COVID-19 según las pautas de la OMS. Las variables registradas incluyeron datos socio-demográficos y epidemiológicos, herramientas diagnósticas y complicaciones durante el ingreso hospitalario. El Servicio de Bioquímica del centro realizó los análisis de laboratorio empleando procedimientos validados. El estudio estadístico incluye modelos univariantes y multivariados, ajustados por las características basales clínicamente relevantes de la población. Resultados: la comorbilidad más frecuente en nuestra población fue la hipertensión arterial (44,0 %), seguida por la dislipemia (32,1 %), la obesidad (30,9 %) y la diabetes mellitus (20,0 %). En el análisis multivariante, la asociación del ingreso en la Unidad de Cuidados Intensivos (UCI) con el índice de masa corporal (IMC) resultó estadísticamente significativa, con un 19 % más de riesgo en aquellos pacientes con IMC ≥ 30 kg/m2. El modelo univariante reveló la asociación estadísticamente significativa de la obesidad y el ingreso en la UCI con la duración de la estancia hospitalaria (p < 0,05). La relación entre glucemia basal y mortalidad intrahospitalaria también resultó estadísticamente significativa (p = 0,03). Los niveles bajos de colesterol total se asociaron a una tasa mayor de ingresos en la UCI (p = 0,007). Conclusiones: la obesidad se asocia a una mayor estancia hospitalaria y necesidad de ingreso en la UCI en los pacientes infectados por el SARS-CoV-2. El descenso en las cifras de colesterol total y una glucemia basal alterada son factores de riesgo del ingreso en la UCI y la mortalidad intrahospitalaria. La categorización en función del grado de obesidad de los pacientes podría ser de utilidad en el desarrollo de un modelo de medicina de precisión en el contexto de la COVID-19.

Inflammatory-Related Clinical and Metabolic Outcomes in COVID-19 Patients.

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) infection elicits inflammatory manifestations that relate with a "cytokine storm." OBJECTIVE: The aim of this research was to assess the role of circulating interleukin 6 (IL-6) levels and other inflammatory markers in patients with coronavirus disease 2019 (COVID-19) on metabolic functions and accompanying clinical complications. Patients and Methods. A total of 165 patients diagnosed with COVID-19 pneumonia were examined for medical features and inflammatory markers such as blood IL-6, CRP, ferritin, LDH, neutrophil/lymphocyte index (NLI), D-Dimer, and Red Cell Distribution Width (RDW). Regression analyses concerning electronically collected medical data were adjusted by appropriate factors and confounding variables. Results. Plasma IL-6 determinations evidenced a consistent association with hospital stay days, Intensive Care Unit (ICU) admission, and mortality rates. Similar trends were found for other proinflammatory variables, where ferritin and NLI showed a remarkable value as surrogates. Hyperglycaemia and the Charlson Comorbidity Index Score were positively associated with the inflammatory response induced by the SARS-COV-2 infection. An unhealthy lifestyle such as smoking and alcoholic drinks consumption as well as excessive body adiposity influenced inflammatory-related outcomes in the screened patients. CONCLUSION: IL-6 together with other inflammatory biomarkers accompanied poor clinical and metabolic outcomes in COVID-19-infected patients. IL-6 may result in a suitable proxy to individually categorise patients in order to manage this infectious pandemic.