Nirmatrelvir/ritonavir or Molnupiravir for treatment of non-hospitalized patients with COVID-19 at risk of disease progression.

BACKGROUND: In randomized controlled trials, Nirmatrelvir/ritonavir (NMV/r) and Molnupiravir (MPV) reduced the risk of severe/fatal COVID-19 disease. Real-world data are limited, particularly studies directly comparing the two agents. METHODS: Using the VA National COVID-19 database, we identified previously uninfected, non-hospitalized individuals with COVID-19 with ≥1 risk factor for disease progression who were prescribed either NMV/r or MPV within 3 days of a positive test. We used inverse probability of treatment weights (IPTW) to account for providers' preferences for a specific treatment. Absolute risk difference (ARD) with 95% confidence intervals were determined for those treated with NMV/r vs. MPV. The primary outcome was hospitalization or death within 30 days of treatment prescription using the IPTW approach. Analyses were repeated using propensity-score matched groups. RESULTS: Between January 1 and November 30, 2022, 9,180 individuals were eligible for inclusion (6,592 prescribed NMV/r; 2,454 prescribed MPV). The ARD for hospitalization/death for NMV/r vs MPV was -0.25 (95% CI -0.79 to 0.28). There was no statistically significant difference in ARD among strata by age, race, comorbidities, or symptoms at baseline. Kaplan-Meier curves did not demonstrate a difference between the two groups (p-value = 0.6). Analysis of the propensity-score matched cohort yielded similar results (ARD for NMV/r vs. MPV -0.9, 95% CI -2.02 to 0.23). Additional analyses showed no difference for development of severe/critical/fatal disease by treatment group. CONCLUSION: We found no significant difference in short term risk of hospitalization or death among at-risk individuals with COVID-19 treated with either NMV/r or MPV.

Early trajectories of virological and immunological biomarkers and clinical outcomes in patients admitted to hospital for COVID-19: an international, prospective cohort study.

BACKGROUND: Serial measurement of virological and immunological biomarkers in patients admitted to hospital with COVID-19 can give valuable insight into the pathogenic roles of viral replication and immune dysregulation. We aimed to characterise biomarker trajectories and their associations with clinical outcomes. METHODS: In this international, prospective cohort study, patients admitted to hospital with COVID-19 and enrolled in the Therapeutics for Inpatients with COVID-19 platform trial within the Accelerating COVID-19 Therapeutic Interventions and Vaccines programme between Aug 5, 2020 and Sept 30, 2021 were included. Participants were included from 108 sites in Denmark, Greece, Poland, Singapore, Spain, Switzerland, Uganda, the UK, and the USA, and randomised to placebo or one of four neutralising monoclonal antibodies: bamlanivimab (Aug 5 to Oct 13, 2020), sotrovimab (Dec 16, 2020, to March 1, 2021), amubarvimab-romlusevimab (Dec 16, 2020, to March 1, 2021), and tixagevimab-cilgavimab (Feb 10 to Sept 30, 2021). This trial included an analysis of 2149 participants with plasma nucleocapsid antigen, anti-nucleocapsid antibody, C-reactive protein (CRP), IL-6, and D-dimer measured at baseline and day 1, day 3, and day 5 of enrolment. Day-90 follow-up status was available for 1790 participants. Biomarker trajectories were evaluated for associations with baseline characteristics, a 7-day pulmonary ordinal outcome, 90-day mortality, and 90-day rate of sustained recovery. FINDINGS: The study included 2149 participants. Participant median age was 57 years (IQR 46-68), 1246 (58·0%) of 2149 participants were male and 903 (42·0%) were female; 1792 (83·4%) had at least one comorbidity, and 1764 (82·1%) were unvaccinated. Mortality to day 90 was 172 (8·0%) of 2149 and 189 (8·8%) participants had sustained recovery. A pattern of less favourable trajectories of low anti-nucleocapsid antibody, high plasma nucleocapsid antigen, and high inflammatory markers over the first 5 days was observed for high-risk baseline clinical characteristics or factors related to SARS-CoV-2 infection. For example, participants with chronic kidney disease demonstrated plasma nucleocapsid antigen 424% higher (95% CI 319-559), CRP 174% higher (150-202), IL-6 173% higher (144-208), D-dimer 149% higher (134-165), and anti-nucleocapsid antibody 39% lower (60-18) to day 5 than those without chronic kidney disease. Participants in the highest quartile for plasma nucleocapsid antigen, CRP, and IL-6 at baseline and day 5 had worse clinical outcomes, including 90-day all-cause mortality (plasma nucleocapsid antigen hazard ratio (HR) 4·50 (95% CI 3·29-6·15), CRP HR 3·37 (2·30-4·94), and IL-6 HR 5·67 (4·12-7·80). This risk persisted for plasma nucleocapsid antigen and CRP after adjustment for baseline biomarker values and other baseline factors. INTERPRETATION: Patients admitted to hospital with less favourable 5-day biomarker trajectories had worse prognosis, suggesting that persistent viral burden might drive inflammation in the pathogenesis of COVID-19, identifying patients that might benefit from escalation of antiviral or anti-inflammatory treatment. FUNDING: US National Institutes of Health.

Differential associations of fine and coarse particulate air pollution with cause-specific pneumonia mortality: A nationwide, individual-level, case-crossover study.

BACKGROUND: The connections between fine particulate matter (PM2.5) and coarse particulate matter (PM2.5-10) and daily mortality of viral pneumonia and bacterial pneumonia were unclear. OBJECTIVES: To distinguish the connections between PM2.5 and PM2.5-10 and daily mortality due to viral pneumonia and bacterial pneumonia. METHODS: Using a comprehensive national death registry encompassing all areas of mainland China, we conducted a case-crossover investigation from 2013 to 2019 at an individual level. Residential daily particle concentrations were evaluated using satellite-based models with a spatial resolution of 1 km. To analyze the data, we employed the conditional logistic regression model in conjunction with polynomial distributed lag models. RESULTS: We included 221,507 pneumonia deaths in China. Every interquartile range (IQR) elevation in concentrations of PM2.5 (lag 0-2 d, 37.6 µg/m3) was associated with higher magnitude of mortality for viral pneumonia (3.03%) than bacterial pneumonia (2.14%), whereas the difference was not significant (p-value for difference = 0.38). An IQR increase in concentrations of PM2.5-10 (lag 0-2 d, 28.4 µg/m3) was also linked to higher magnitude of mortality from viral pneumonia (3.06%) compared to bacterial pneumonia (2.31%), whereas the difference was not significant (p-value for difference = 0.52). After controlling for gaseous pollutants, their effects were all stable; however, with mutual adjustment, the associations of PM2.5 remained, and those of PM2.5-10 were no longer statistically significant. Greater magnitude of associations was noted in individuals aged 75 years and above, as well as during the cold season. CONCLUSION: This nationwide study presents compelling evidence that both PM2.5 and PM2.5-10 exposures could increase pneumonia mortality of viral and bacterial causes, highlighting the more robust effects of PM2.5 and somewhat higher sensitivity of viral pneumonia.

Clinical manifestations, prognostic factors, and outcomes of adenovirus pneumonia after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Severe pneumonia is one of the most important causes of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adenovirus (ADV) is a significant cause of severe viral pneumonia after allo-HSCT, and we aimed to identify the clinical manifestations, prognostic factors, and outcomes of ADV pneumonia after allo-HSCT. METHODS: Twenty-nine patients who underwent allo-HSCT at the Peking University Institute of Hematology and who experienced ADV pneumonia after allo-HSCT were enrolled in this study. The Kaplan-Meier method was used to estimate the probability of overall survival (OS). Potential prognostic factors for 100-day OS after ADV pneumonia were evaluated through univariate and multivariate Cox regression analyses. RESULTS: The incidence rate of ADV pneumonia after allo-HSCT was approximately 0.71%. The median time from allo-HSCT to the occurrence of ADV pneumonia was 99 days (range 17-609 days). The most common clinical manifestations were fever (86.2%), cough (34.5%) and dyspnea (31.0%). The 100-day probabilities of ADV-related mortality and OS were 40.4% (95% CI 21.1%-59.7%) and 40.5% (95% CI 25.2%-64.9%), respectively. Patients with low-level ADV DNAemia had lower ADV-related mortality and better OS than did those with high-level (≥ 106 copies/ml in plasma) ADV DNAemia. According to the multivariate analysis, high-level ADV DNAemia was the only risk factor for intensive care unit admission, invasive mechanical ventilation, ADV-related mortality, and OS after ADV pneumonia. CONCLUSIONS: We first reported the prognostic factors and confirmed the poor outcomes of patients with ADV pneumonia after allo-HSCT. Patients with high-level ADV DNAemia should receive immediate and intensive therapy.

IFITM3 rs12252 polymorphism association with COVID-19 severity and mortality in a Brazilian sample: an update and a meta-analysis.

This study investigated the association between the IFITM3 rs12252 polymorphism and the severity and mortality of COVID-19 in hospitalized Brazilian patients. A total of 102 COVID-19 patients were included, and the outcomes of interest were defined as death and the need for mechanical ventilation. Genotypes were assessed using Taqman probes. No significant associations were found between the rs12252 polymorphism and COVID-19 outcomes in the original sample, both for death and the need for mechanical ventilation. A meta-analysis, incorporating previous studies that used death as a severity indicator, revealed no association in the allelic and C-recessive models. However, due to the rarity of the T allele and its absence in the sample, further replication studies in larger and more diverse populations are needed to clarify the role of rs12252 in COVID-19 prognosis.

Pronounced benefits of JAK inhibition with baricitinib in COVID-19 pneumonia in obese but not lean subjects.

OBJECTIVE: Obesity and age are strongly linked to severe COVID-19 pneumonia where immunomodulatory agents including Janus kinase inhibitors have shown benefits but the efficacy of such therapy in viral pneumonia is not well understood. We evaluated the impact of obesity and age on survival following baricitinib therapy for severe COVID-19. METHODS: A post hoc analysis of the COV-BARRIER multicentre double-blind randomised study of baricitinib versus placebo (PBO) with an assessment of 28-day mortality was performed. All-cause mortality by day 28 was evaluated in a Cox regression analysis (adjusted to age) in three different groups according to body mass index (BMI) (<25 kg/m2, 25-30 kg/m2 and >30 kg/m2) and age <65 years and ≥65 years. RESULTS: In the high BMI group (>25 kg/m2), baricitinib therapy showed a significant survival advantage compared with PBO (incidence rate ratio (IRR) for mortality by day 28 0.53 (95% CI 0.32 to 0.87)) and 0.66 (95% CI 0.46 to 0.94) for the respective <65 years and ≥65 years, respectively. The 28-day all-cause-mortality rates for BMI over 30 were 5.62% for baricitinib and 9.22% for PBO (HR=0.6, p<0.05). For BMI under 25 kg/m2, irrespective of age, baricitinib therapy conferred no survival advantage (IRR of 1.89 (95% CI 0.49 to 7.28) and 0.95 (95% CI 0.46 to 1.99) for <65 years and ≥65 years, respectively) ((mortality 6.6% baricitinib vs 8.1 in PBO), p>0.05). CONCLUSION: The efficacy of baricitinib in COVID-19 pneumonia is linked to obesity suggesting that immunomodulatory therapy benefit is associated with obesity-associated inflammation.

The Role of TLR-2 in Lethal COVID-19 Disease Involving Medullary and Resident Lung Megakaryocyte Up-Regulation in the Microthrombosis Mechanism.

Patients with COVID-19 have coagulation and platelet disorders, with platelet alterations and thrombocytopenia representing negative prognostic parameters associated with severe forms of the disease and increased lethality. METHODS: The aim of this study was to study the expression of platelet glycoprotein IIIa (CD61), playing a critical role in platelet aggregation, together with TRL-2 as a marker of innate immune activation. RESULTS: A total of 25 patients were investigated, with the majority (24/25, 96%) having co-morbidities and dying from a fatal form of SARS-CoV-2(+) infection (COVID-19+), with 13 men and 12 females ranging in age from 45 to 80 years. When compared to a control group of SARS-CoV-2 (-) negative lungs (COVID-19-), TLR-2 expression was up-regulated in a subset of patients with deadly COVID-19 fatal lung illness. The proportion of Spike-1 (+) patients found by PCR and ISH correlates to the proportion of Spike-S1-positive cases as detected by digital pathology examination. Furthermore, CD61 expression was considerably higher in the lungs of deceased patients. In conclusion, we demonstrate that innate immune prolonged hyperactivation is related to platelet/megakaryocyte over-expression in the lung. CONCLUSIONS: Microthrombosis in deadly COVID-19+ lung disease is associated with an increase in the number of CD61+ platelets and megakaryocytes in the pulmonary interstitium, as well as their functional activation; this phenomenon is associated with increased expression of innate immunity TLR2+ cells, which binds the SARS-CoV-2 E protein, and significantly with the persistence of the Spike-S1 viral sequence.

Severe Human Parainfluenza Virus Community- and Healthcare-Acquired Pneumonia in Adults at Tertiary Hospital, Seoul, South Korea, 2010-2019.

The characteristics of severe human parainfluenza virus (HPIV)-associated pneumonia in adults have not been well evaluated. We investigated epidemiologic and clinical characteristics of 143 patients with severe HPIV-associated pneumonia during 2010-2019. HPIV was the most common cause (25.2%) of severe virus-associated hospital-acquired pneumonia and the third most common cause (15.7%) of severe virus-associated community-acquired pneumonia. Hematologic malignancy (35.0%), diabetes mellitus (23.8%), and structural lung disease (21.0%) were common underlying conditions. Co-infections occurred in 54.5% of patients admitted to an intensive care unit. The 90-day mortality rate for HPIV-associated pneumonia was comparable to that for severe influenza virus-associated pneumonia (55.2% vs. 48.4%; p = 0.22). Ribavirin treatment was not associated with lower mortality rates. Fungal co-infections were associated with 82.4% of deaths. Clinicians should consider the possibility of pathogenic co-infections in patients with HPIV-associated pneumonia. Contact precautions and environmental cleaning are crucial to prevent HPIV transmission in hospital settings.

Outcome of pregnant women admitted to critical care unit with confirmed severe COVID-19: A center experience.

OBJECTIVES: To explore the traits and risk factors of pregnant women admitted to intensive care units (ICUs) with COVID-19. Moreover, the study classifies outcomes based on differing levels of required respiratory support during their intensive care stay. METHODS: This retrospective and descriptive study included all pregnant women with COVID-19 admitted to the adult critical care unit at a specialized tertiary hospital in Riyadh, Saudi Arabia. Between January 2020 and December 2022. A total of 38 pregnant women were identified and were eligible for our study. RESULTS: The mean age of the patients was 32.9 (19-45) years, and the average Acute Physiology and Chronic Health Evaluation IV (APACHI IV) score was 49.9 (21-106). Approximately 60.5% of the patients suffered from superimposed infections during their ICU stay. Approximately 81.6% patients were delivered by C-section, 33 of the newborns survived, and 5 died. The crude mortality rate among pregnant women in our cohort was 15.8%. Patients treated with high-flow nasal cannula (HFNC) were mostly discharged or delivered normally, while the mechanical ventilation (MV) and extracorporeal membrane oxygenation groups mostly underwent C-sections. Most of the surviving newborns were on HFNC and MV. Patients with multiple infections had the longest ICU stay and had the highest risk of death. CONCLUSION: The results of this study highlight the characteristics of pregnant women admitted to the ICU at a specialized tertiary healthcare center in Saudi Arabia. The APACHI IV scores accurately predicted patient's mortality, duration of MV, and length of ICU stay. In our study, we shared our experience of managing severe COVID-19 infections in pregnant patients.

Invasive group A streptococcal infection can be fatal to pregnant women in restricted medical resources remote areas-Emergent alert after COVID-19 pandemic.

Invasive group A streptococcal (iGAS) infection is a leading cause of maternal death. The increase in the number of patients with iGAS in Japan is markedly greater than before the coronavirus pandemic. We encountered a case of iGAS infection, on a remote island with restricted medical resources, in a third-trimester pregnant woman, resulting in both maternal and fetal death. A 34-year-old woman was admitted via a local general hospital with a high fever. Intrauterine fetal death disseminated intravascular coagulation, and septic shock were confirmed. Broad-spectrum antibiotics were started, and the patient was returned to the local general hospital. Eight hours after arrival, the patient died of circulatory and respiratory dysfunction complications. iGAS infections in remote areas may directly lead to life-threatening conditions and should be treated as an emergency, comparable to the serious conditions of placental abruption or placenta previa.

Mortality risk in patients with obesity and COVID-19 infection: a systematic review and meta-analysis.

Obesity is a risk factor for severe respiratory diseases, including COVID-19 infection. Meta-analyses on mortality risk were inconsistent. We systematically searched 3 databases (Medline, Embase, CINAHL) and assessed the quality of studies using the Newcastle-Ottawa tool (CRD42020220140). We included 199 studies from US and Europe, with a mean age of participants 41.8-78.2 years, and a variable prevalence of metabolic co-morbidities of 20-80 %. Exceptionally, one third of the studies had a low prevalence of obesity of <20 %. Compared to patients with normal weight, those with obesity had a 34 % relative increase in the odds of mortality (p-value 0.002), with a dose-dependent relationship. Subgroup analyses showed an interaction with the country income. There was a high heterogeneity in the results, explained by clinical and methodologic variability across studies. We identified one trial only comparing mortality rate in vaccinated compared to unvaccinated patients with obesity; there was a trend for a lower mortality in the former group. Mortality risk in COVID-19 infection increases in parallel to an increase in BMI. BMI should be included in the predictive models and stratification scores used when considering mortality as an outcome in patients with COVID-19 infections. Furthermore, patients with obesity might need to be prioritized for COVID-19 vaccination.

Therapeutic high-dose vitamin D for vitamin D-deficient severe COVID-19 disease: randomized, double-blind, placebo-controlled study (SHADE-S).

BACKGROUND: efficacy of therapeutic cholecalciferol supplementation for severe COVID-19 is sparingly studied. OBJECTIVE: effect of single high-dose cholecalciferol supplementation on sequential organ failure assessment (SOFA) score in moderate-to-severe COVID-19. METHODS: participants with moderate to severe COVID-19 with PaO2/FiO2 ratio < 200 were randomized to 0.6 million IU cholecalciferol oral (intervention) or placebo. OUTCOMES: primary outcome was change in Day 7 SOFA score and pre-specified secondary outcomes were SOFA and 28-day all-cause mortality. RESULTS: in all, 90 patients (45 each group) were included for intention-to-treat analysis. 25(OH)D3 levels were 12 (10-16) and 13 (12-18) ng/ml (P = 0.06) at baseline; and 60 (55-65) ng/ml and 4 (1-7) ng/ml by Day 7 in vitamin D and placebo groups, respectively. The SOFA score on Day 7 was better in the vitamin D group [3 (95% CI, 2-5) versus 5 (95% CI, 3-7), P = 0.01, intergroup difference - 2 (95% CI, -4 to -0.01); r = 0.4]. A lower all-cause 28-day mortality [24% compared to 44% (P = 0.046)] was observed with vitamin D. CONCLUSIONS: single high-dose oral cholecalciferol supplementation on ICU admission can improve SOFA score at Day 7 and reduce in-hospital mortality in vitamin D-deficient COVID-19. ClinicalTrials.gov  id: NCT04952857 registered dated 7 July 2021. What is already known on this topic-vitamin D has immunomodulatory role. Observational and isolated intervention studies show some benefit in COVID-19. Targeted therapeutic vitamin D supplementation improve outcomes in severe COVID-19 is not studied in RCTs. What this study adds-high-dose vitamin D supplementation (0.6 Million IU) to increase 25(OH)D > 50 ng/ml is safe and reduces sequential organ failure assessment score, in-hospital mortality in moderate to severe COVID-19. How this study might affect research, practice or policy-vitamin D supplementation in vitamin D-deficient patients with severe COVID-19 is useful may be practiced.

Value of increased soluble suppressor tumorigenicity biomarker 2 (sST2) on admission as an indicator of severity in patients with COVID-19 / Valor del aumento del biomarcador supresor soluble de tumorigenicidad 2 (sST2) al ingreso como indicador de gravedad en pacientes con COVID-19

Background Soluble suppressor of tumorigenicity-2 (sST2) is a biomarker for heart failure and pulmonary injury. We hypothesize that sST2 could help predict severity of SARS-CoV-2 infections. Methods sST2 was analyzed in patients consecutively admitted for SARS-CoV-2 pneumonia. Other prognostic markers were also measured. In-hospital complications were registered, including death, ICU admission, and respiratory support requirements. Results 495 patients were studied (53% male, age: 57.6±17.6). At admission, median sST2 concentrations was 48.5ng/mL [IQR, 30.6–83.1ng/mL] and correlated with male gender, older age, comorbidities, other severity biomarkers, and respiratory support requirements. sST2 levels were higher in patients who died (n=45, 9.1%) (45.6 [28.0, 75.9]ng/mL vs. 144 [82.6, 319] ng/mL, p<0.001) and those admitted to ICU (n=46, 9.3%) (44.7 [27.5, 71.3] ng/mL vs. 125 [69.0, 262]ng/mL, p<0.001). sST2 levels>210ng/mL were a strong predictor of complicated in-hospital courses, with higher risk of death (OR, 39.3, CI95% 15.9, 103) and death/ICU (OR 38.3, CI95% 16.3–97.5) after adjusting for all other risk factors. The addition of sST2 enhanced the predictive capacity of mortality risk models. Conclusions sST2 represents a robust severity predictor in COVID-19 and could be an important tool for identifying at-risk patients who may benefit from closer follow-up and specific therapies (AU)

Antecedentes El supresor soluble de tumorigenicidad 2 (sST2) es un biomarcador de insuficiencia cardiaca y daño pulmonar. Nuestra hipótesis es que la determinación de sST2 al ingreso podría ayudar a predecir la gravedad de la infección por SARS-CoV-2. Métodos Se analizó la concentración de sST2 en pacientes ingresados por neumonía por SARS-CoV-2, junto con otros biomarcadores pronósticos conocidos. Asimismo, se registraron las complicaciones durante la estancia hospitalaria, incluidas la muerte, el ingreso en Unidad de Cuidados Intensivos (UCI) y los requerimientos de soporte respiratorio. Resultados Se estudiaron 495 pacientes (53% hombres, edad 57,6 ± 17,6). Al ingreso, la mediana de la concentración de sST2 fue 48,5 ng/mL (índice intercuartílico [IQR] 30,6-83,1 ng/mL) y correlacionó con el género masculino, una mayor edad, comorbilidades, otros biomarcadores de gravedad, así como necesidad de soporte respiratorio. Los niveles de sST2 fueron mayores en pacientes que fallecieron (n = 45, 9,1%) (45,6 [28,0, 75,9] ng/mL vs. 144 [82,6, 319] ng/mL, p < 0,001) y aquellos que requirieron ingreso en UCI (n = 46, 9,3%) (44,7 [27,5, 71,3] ng/mL vs. 125 [69,0, 262] ng/mL, p < 0,001). Así, los valores de sST2 > 210 ng/mL se han demostrado como un fuerte predictor de complicaciones, con un mayor riesgo de fallecimiento (odds ratio [OR], 39,3, intervalo de confianza [IC] 95% 15,9, 103) y fallecimiento o ingreso en UCI (OR 38,3, IC 95% 16,3-97,5), tras el ajuste por todos los demás factores de riesgo. La adición de la determinación de los niveles de sST2 mejoró la potencia predictiva de los modelos de riesgo desarrollados. Conclusiones El sST2 representa un predictor robusto de la gravedad en pacientes con COVID-19 y podría convertirse en una herramienta importante para la identificación de pacientes en riesgo que podrían beneficiarse de un mayor seguimiento y terapias específicas (AU)

Outcomes of vaccinated versus unvaccinated COVID-19 patients in Israel during the Omicron and Delta waves—A retrospective cohort study / Resultados de pacientes con COVID-19 vacunados vs. no vacunados en Israel durante las olas de ómicron y delta: Un estudio de cohorte retrospectivo

Introduction Initiation of global vaccination significantly reduced the morbidity and mortality of COVID-19. During the Omicron wave, approximately 70% of the Israeli adult population was fully vaccinated, but the efficacy of the vaccine was questioned. Methods We conducted a retrospective cohort study of all adult patients admitted to the COVID-19 departments in Rabin Medical Center, during the Delta wave and the Omicron wave. Patients were matched in the 2 waves using the inverse probability of treatment weighting (IPTW) method and risk for mechanical ventilation and 30-day all-cause mortality was assessed. Results Vaccination had a significant effect on 30-day mortality in the Delta and Omicron waves with adjusted OR of 0.35 (0.17–0.70) and 0.5 (0.27–0.95) respectively. Nonetheless, the rate of mechanical ventilation was similar between the groups with OR of 0.75 (0.52–1.09) and 0.64 (0.40–1.01). Vaccination status did not change the length of admission in both waves. Conclusion We observed a decreased risk for 30-day mortality among vaccinated patients during the Delta and Omicron waves in Israel. This association, even though consistent, was of a lesser magnitude during the Omicron wave (AU)

Introducción La iniciación de la vacunación global redujo significativamente la morbilidad y la mortalidad de la COVID-19. Durante la ola de ómicron, aproximadamente 70% de la población adulta israelí estaba completamente vacunada, pero se cuestionó la eficacia de la vacuna. Métodos Realizamos un estudio de cohorte retrospectivo de todos los pacientes adultos ingresados en los departamentos de COVID-19 en el Centro Médico Rabin, durante las olas de delta y ómicron. Los pacientes fueron emparejados en las dos olas utilizando el método de ponderación inversa de probabilidad de tratamiento (IPTW) y se evaluó el riesgo de ventilación mecánica y la mortalidad por todas las causas a los 30 días. Resultados La vacunación tuvo un efecto significativo en la mortalidad a los 30 días en las olas de delta y ómicron con odds ratio (OR) ajustadas de 0,35 (0,17-0,70) y 0,5 (0,27-0,95), respectivamente. Sin embargo, la tasa de ventilación mecánica fue similar entre los grupos con OR de 0,75 (0,52-1,09) y 0,64 (0,40-1,01). El estado de vacunación no cambió la duración del ingreso en ambas olas.Conclusión Observamos un menor riesgo de mortalidad a los 30 días entre los pacientes vacunados durante las olas de delta y ómicron en Israel. Esta asociación, aunque constante, fue de menor magnitud durante la ola de ómicron (AU)

Impacto de los días transcurridos desde el inicio de los síntomas hasta la hospitalización en la mortalidad hospitalaria por COVID-19: el tiempo importa / Impact of days elapsed from the onset of symptoms to hospitalization in COVID-19 in-hospital mortality: Time matters

Antecedentes La COVID-19 muestra diferentes fases clínicas y fisiopatológicas a lo largo del tiempo. El efecto de los días transcurridos desde el comienzo de los síntomas (DTCS) hasta la hospitalización sobre los factores pronósticos de la COVID-19 sigue siendo incierto. Analizamos el impacto en la mortalidad de los DTCS hasta la hospitalización y cómo se comportan otros factores pronósticos independientes al tener en cuenta dicho tiempo transcurrido. Métodos En este estudio de cohortes nacional retrospectivo se incluyó a pacientes con COVID-19 confirmada entre el 20 de febrero y el 6 de mayo de 2020. Los datos se recopilaron en un registro normalizado de captura de datos en línea. Se realizó una regresión de Cox uni y multifactorial en la cohorte general y el modelo multifactorial final se sometió a un análisis de sensibilidad en un grupo de presentación precoz (PP) < 5 DTCS y otro de presentación tardía (PT) ≥ 5 DTCS). Resultados En el análisis se incluyó a 7.915 pacientes con COVID-19, 2.324 en el grupo de PP y 5.591 en el de PT. Los DTCS hasta la hospitalización fueron un factor pronóstico independiente de mortalidad intrahospitalaria en el modelo de regresión de Cox multifactorial junto con otras nueve variables. Cada incremento en un DTCS supuso una reducción del riesgo de mortalidad del 4,3% (RRI = 0,957; IC 95%, 0,93-0,98). En cuanto a las variaciones de otros factores predictivos de la mortalidad en el análisis de sensibilidad, únicamente el índice de comorbilidad de Charlson siguió siendo significativo en el grupo de PP, mientras que únicamente el dímero D lo siguió siendo en el grupo de PT. Conclusiones Al atender a pacientes con COVID-19 hay que tener en cuenta los DTCS hasta la hospitalización porque la necesidad de hospitalización precoz confiere un mayor riesgo de mortalidad. Los diferentes factores pronósticos varían con el tiempo y deberían estudiarse dentro de un marco temporal fijo de la enfermedad (AU)

Background COVID-19 shows different clinical and pathophysiological stages over time. Theeffect of days elapsed from the onset of symptoms (DEOS) to hospitalization on COVID-19prognostic factors remains uncertain. We analyzed the impact on mortality of DEOS to hospital-ization and how other independent prognostic factors perform when taking this time elapsedinto account. Methods This retrospective, nationwide cohort study, included patients with confirmed COVID-19 from February 20th and May 6th, 2020. The data was collected in a standardized online datacapture registry. Univariate and multivariate COX-regression were performed in the generalcohort and the final multivariate model was subjected to a sensitivity analysis in an earlypresenting (EP; <5 DEOS) and late presenting (LP; ≥5 DEOS) group. Results 7915 COVID-19 patients were included in the analysis, 2324 in the EP and 5591 in theLP group. DEOS to hospitalization was an independent prognostic factor of in-hospital mortalityin the multivariate Cox regression model along with other 9 variables. Each DEOS incrementaccounted for a 4.3% mortality risk reduction (HR 0.957; 95% CI 0.93---0.98). Regarding variationsin other mortality predictors in the sensitivity analysis, the Charlson Comorbidity Index onlyremained significant in the EP group while D-dimer only remained significant in the LP group. Conclusion When caring for COVID-19 patients, DEOS to hospitalization should be consideredas their need for early hospitalization confers a higher risk of mortality. Different prognosticfactors vary over time and should be studied within a fixed timeframe of the disease (AU)

Efficacy and safety of adding fluoxetine to the treatment regimen of hospitalized patients with non-critical COVID-19 pneumonia: A double-blind randomized, placebo-controlled clinical trial.

INTRODUCTION: Selective serotonin reuptake inhibitors are considered the drugs, whose effectiveness in viral pandemics has been studied. The aim of this study was to evaluate of adding fluoxetine to the treatment regimen of patients with COVID-19 pneumonia. METHODS: This study was a double-blind randomized placebo controlled clinical trial .36 patients in the fluoxetine and 36 patients in the placebo group were enrolled. Patients in the intervention group were first treated with fluoxetine 10 mg for 4 days and then the dose of 20 mg was continued for 4 weeks. Data analysis was conducted using SPSS V. 22.0. RESULTS: There was no statistically significant difference between the two groups in terms of clinical symptoms at the beginning of the study and also the score of anxiety and depression, oxygen saturation at the time of hospitalization, mid-hospitalization and discharge periods. The need for mechanical ventilator support (p = 1.00), the need for admission in the intensive care unit (ICU) (p = 1.00), rate for mortality (p = 1.00), and discharge with relative recovery (p = 1.00) were not significantly different between the two groups. The distribution of CRP within the study groups showed a significant decrease during different time periods (p = 0.001), and although there was no statistically significant difference between the two groups on the first day (p = 1.00) and at discharge (p = 0.585), mid-hospital CRP showed a significant decrease in the fluoxetine group (p = 0.032). CONCLUSION: Fluoxetine resulted in a faster reduction of patients' inflammation without association with depression and anxiety.

Factores asociados con la mortalidad por SARS-CoV-2 en la población mayor de 75 años de la Comunidad de Madrid / Factors associated with mortality due to SARS-CoV-2 in the population over 75 years of age in the Community of Madrid

Objetivo Diversos estudios han identificado factores asociados con el riesgo de muerte en pacientes infectados por SARS-CoV-2. Sin embargo, su tamaño muestral ha sido muchas veces limitado, y sus resultados parcialmente contradictorios. Este estudio ha evaluado los factores asociados con la mortalidad por COVID-19 en la población madrileña mayor de 75 años, en los pacientes infectados y en los hospitalizados hasta enero de 2021. Pacientes y métodos Estudio de cohortes de base poblacional con todos los residentes de la Comunidad de Madrid nacidos antes del 1 de enero de 1945 y vivos a 31 de diciembre de 2019. Se obtuvieron variables demográficas y clínicas de la historia clínica electrónica de atención primaria (AP-Madrid), de los ingresos hospitalarios a través del Conjunto Mínimo Básico de Datos (CMBD) y de la mortalidad a través del Índice Nacional de Defunciones (INDEF). Se recogieron los datos de infección, hospitalización y muerte por SARS-CoV-2 entre el 1 de marzo e 2020 y el 31 de enero de 2021. Resultados De los 587.603 sujetos incluidos en la cohorte, 41.603 (7,1%) desarrollaron una infección confirmada por SARS-CoV-2. De ellos, 22.362 (53,7% de los infectados) se hospitalizaron y 11.251 (27%) murieron. El sexo masculino y la edad fueron los factores más asociados con la mortalidad, si bien también contribuyeron numerosas comorbilidades. La asociación fue de mayor magnitud en los análisis poblacionales que en los análisis con pacientes infectados u hospitalizados. La mortalidad en los hospitalizados fue menor en la segunda ola (33,4%) que en la primera ola (41,2%) de la pandemia Conclusión La edad, el sexo y las numerosas comorbilidades se asocian con el riesgo de muerte por COVID-19. La mortalidad en los pacientes hospitalizados se redujo apreciablemente después de la primera ola de la pandemia (AU)

Objective Various studies have identified factors associated with risk of mortality in patients with SARS-CoV-2 infection. However, their sample size has often been limited and their results partially contradictory. This study evaluated factors associated with COVID-19 mortality in the population of Madrid over 75 years of age, in infected patients, and in hospitalized patients up to January 2021. Patients and Methods This population-based cohort study analyzed all residents of the Community of Madrid born before January 1, 1945 who were alive as of December 31, 2019. Demographic and clinical data were obtained from primary care electronic medical records (PC-Madrid), data on hospital admissions from the Conjunto Mínimo Básico de Datos (CMBD, Minimum Data Set), and data on mortality from the Índice Nacional de Defunciones (INDEF, National Death Index). Data on SARS-CoV-2 infection, hospitalization, and death were collected from March 1, 2020 to January 31, 2021. Results A total of 587,603 subjects were included in the cohort. Of them, 41,603 (7.1%) had confirmed SARS-CoV-2 infection, of which 22,362 (53.7% of the infected individuals) were hospitalized and 11,251 (27%) died. Male sex and age were the factors most closely associated with mortality, though many comorbidities also had an influence. The associations were stronger in the analysis of the total population than in the analysis of infected or hospitalized patients. Mortality among hospitalized patients was lower during the second wave (33.4%) than during the first wave (41.2%) of the pandemic. Conclusion Age, sex, and numerous comorbidities are associated with risk of death due to COVID-19. Mortality in hospitalized patients declined notably after the first wave of the pandemic (AU)

Diabetes might not be a risk factor for worse prognosis among hospitalized patients due to COVID-19 in a Mediterranean area / La presencia de diabetes entre los pacientes ingresados por COVID-19 podría no ser un factor de peor pronóstico

Aim: type-2 diabetes (T2DM) seems to worsen the prognosis of patients admitted for COVID-19, although most studies included Asiatic patients. We aimed to assess whether this condition applies for Mediterranean patients. Methods: a total of 90 patients admitted for COVID-19 with T2DM were retrospectively compared with 50 patients without T2DM. Results: subjects with T2DM were older than their counterparts (73.3 ± 12.4 vs 53 ± 15.7 years; p < 0.0001). Either absolute lymphocyte count (1.1 ± 0.6 vs 1.3 ± 0.7 x 109/L; p = 0.005) or hemoglobin (11.9 ± 1.6 vs 13.1 ± 2.1 g/dL; p < 0.0001) were lower among subjects with T2DM. CRP and procalcitonin were higher among subjects with T2DM (91.9 ± 71.2 vs 70.1 ± 63.3 mg/L; p = 0.002 and 0.8 ± 0.3 vs 0.4 ± 0.1 ng/mL; p < 0.0001, respectively). Albumin was lower among patients with T2DM (3.4 ± 0.5 vs 3.8 ± 0.5 g/L: p < 0.001). Length of stay was longer among subjects with T2DM (11.7 ± 7.7 vs 9.7 ± 8.6 days; p = 0.01). However, both groups were comparable regarding both the proportion of subjects who were admitted to the ICU (16.5 % vs 8 %; p = 0.1) and mortality (11 % vs 4 %; p = 0.2). Conclusions: in a Mediterranean sample, despite of age, comorbidities, nutritional status, and inflammatory markers, subjects with T2DM with a proper glycemic control admitted for COVID-19 had similar prognostic outcomes than patients without this metabolic condition (AU)

Objetivo: la diabetes de tipo 2 (DM2) parece empeorar el pronóstico de los pacientes ingresados por COVID-19, aunque la mayoría de los estudios incluyeron pacientes asiáticos. Nuestro objetivo fue evaluar si esto se aplica a los pacientes de una población Mediterránea. Métodos: un total de 90 pacientes ingresados por COVID-19 con DM2 se compararon retrospectivamente con 50 pacientes sin DM2. Resultados: los sujetos con DM2 eran mayores que sus contrapartes (73,3 ± 12,4 frente a 53 ± 15,7 años; p < 0,0001). El recuento absoluto de linfocitos (1,1 ± 0,6 vs. 1,3 ± 0,7 x 109/L; p = 0,005) o la hemoglobina (11,9 ± 1,6 vs. 13,1 ± 2,1 g/dL; p < 0,0001) fueron menores entre los sujetos con DM2. La PCR y la procalcitonina fueron mayores entre los sujetos con DM2 (91,9 ± 71,2 frente a 70,1 ± 63,3 mg/L; p = 0,002 y 0,8 ± 0,3 frente a 0,4 ± 0,1 ng/ml; p < 0,0001, respectivamente). La albúmina fue menor entre los pacientes con DM2 (3,4 ± 0,5 vs. 3,8 ± 0,5 g/L: p < 0,001). La estancia hospitalaria fue mayor entre los sujetos con DM2 (11,7 ± 7,7 frente a 9,7 ± 8,6 días; p = 0,01). Sin embargo, ambos grupos fueron comparables en cuanto a la proporción de sujetos con ingreso en la UCI (16,5 % vs. 8 %; p = 0,1) y la mortalidad (11 % vs. 4 %; p = 0,2). Conclusiones: en una muestra mediterránea, a pesar de la edad, las comorbilidades, el estado nutricional y los marcadores inflamatorios, los sujetos con DM2 con un adecuado control glucémico ingresados por COVID-19 tuvieron resultados pronósticos similares a los de los pacientes sin esta condición metabólica (AU)