Differences between sexes concerning COVID-19-related pneumonia.

INTRODUCTION: Pneumonia is both the most common type of lower respiratory tract infection and a major cause of morbidity and mortality worldwide. The COVID-19 pandemic caused by the SARS-CoV-2 raised an extremely serious concern, because its most frequent clinical presentation was pneumonia. Features such as sex play an active role in the incidence and outcomes of pneumonia. This study aimed to evaluate differences between sexes concerning COVID-19-related pneumonia. METHODS: This was a retrospective, multicentre study that enrolled 340 consecutive adult patients admitted to hospital for COVID-19-related pneumonia. Of these patients, 219 were males (64.4%) and 121, females (35.6%). Primary endpoints were differences between both sexes as per clinical features, laboratory and radiologic results, and inhospital and 30-day mortality. Secondary outcomes included differences between both sexes and factors associated with mortality. RESULTS: Males admitted to the COVID-19 Unit were older than females (74.5 ± 15.7 vs. 64.5 ± 11.9). Cardiovascular disorders were more frequent in males (19.17% vs 13.25%), whereas obesity was more common in females (54.5% vs 37.45%). In-hospital and 30-day mortality were higher in males than in females (23.3% vs 15.7%; 24.6% vs 19.8%, respectively). No differences were observed in hospital stay; however, males had a longer ICU stay when compared with females (11.04±5.4 vs 7.05±3.4). Variables associated with a higher mortality rate included older age, a lower number of lymphocytes upon admission and higher levels of ferritin and troponin upon admission. CONCLUSIONS: Males had significantly higher mortality and longer ICU stay than females. More comorbidities in males than in females could explain the difference in mortality rates. The protective role of genetic factors can partially explain the better outcomes observed in female patients with COVID-19.

Respiratory viruses: their importance and lessons learned from COVID-19.

Respiratory virus infection can cause severe illnesses capable of inducing acute respiratory failure that can progress rapidly to acute respiratory distress syndrome (ARDS). ARDS is related to poor outcomes, especially in individuals with a higher risk of infection, such as the elderly and those with comorbidities, i.e. obesity, asthma, diabetes mellitus and chronic respiratory or cardiovascular disease. Despite this, effective antiviral treatments available for severe viral lung infections are scarce. The coronavirus disease 2019 (COVID-19) pandemic demonstrated that there is also a need to understand the role of airborne transmission of respiratory viruses. Robust evidence supporting this exists, but better comprehension could help implement adequate measures to mitigate respiratory viral infections. In severe viral lung infections, early diagnosis, risk stratification and prognosis are essential in managing patients. Biomarkers can provide reliable, timely and accessible information possibly helpful for clinicians in managing severe lung viral infections. Although respiratory viruses highly impact global health, more research is needed to improve care and prognosis of severe lung viral infections. In this review, we discuss the epidemiology, diagnosis, clinical characteristics, management and prognosis of patients with severe infections due to respiratory viruses.

Early Recognition of Low-Risk SARS-CoV-2 Pneumonia: A Model Validated With Initial Data and Infectious Diseases Society of America/American Thoracic Society Minor Criteria.

BACKGROUND: A shortage of beds in ICUs and conventional wards during the COVID-19 pandemic led to a collapse of health care resources. RESEARCH QUESTION: Can admission data and minor criteria by the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) help identify patients with low-risk SARS-CoV-2 pneumonia? STUDY DESIGN AND METHODS: This multicenter cohort study included 1,274 patients in a derivation cohort and 830 (first wave) and 754 (second wave) patients in two validation cohorts. A multinomial regression analysis was performed on the derivation cohort to compare the following patients: those admitted to the ward (assessed as low risk); those admitted to the ICU directly; those transferred to the ICU after general ward admission; and those who died. A regression analysis identified independent factors for low-risk pneumonia. The model was subsequently validated. RESULTS: In the derivation cohort, similarities existed among those either directly admitted or transferred to the ICU and those who died. These patients could, therefore, be merged into one group. Five independently associated factors were identified as being predictors of low risk (not dying and/or requiring ICU admission) (ORs, with 95% CIs): peripheral blood oxygen saturation/Fio2 > 450 (0.233; 0.149-0.364); < 3 IDSA/ATS minor criteria (0.231; 0.146-0.365); lymphocyte count > 723 cells/mL (0.539; 0.360-0.806); urea level < 40 mg/dL (0.651; 0.426-0.996); and C-reactive protein level < 60 mg/L (0.454; 0.285-0.724). The areas under the curve were 0.802 (0.769-0.835) in the derivation cohort, and 0.779 (0.742-0.816) and 0.801 (0.757-0.845) for the validation cohorts (first and second waves, respectively). INTERPRETATION: Initial biochemical findings and the application of < 3 IDSA/ATS minor criteria make early identification of low-risk SARS-CoV-2 pneumonia (approximately 80% of hospitalized patients) feasible. This scenario could facilitate and streamline health care resource allocation for patients with COVID-19.

Major candidate variables to guide personalised treatment with steroids in critically ill patients with COVID-19: CIBERESUCICOVID study.

PURPOSE: Although there is evidence supporting the benefits of corticosteroids in patients affected with severe coronavirus disease 2019 (COVID-19), there is little information related to their potential benefits or harm in some subgroups of patients admitted to the intensive care unit (ICU) with COVID-19. We aim to investigate to find candidate variables to guide personalized treatment with steroids in critically ill patients with COVID-19. METHODS: Multicentre, observational cohort study including consecutive COVID-19 patients admitted to 55 Spanish ICUs. The primary outcome was 90-day mortality. Subsequent analyses in clinically relevant subgroups by age, ICU baseline illness severity, organ damage, laboratory findings and mechanical ventilation were performed. High doses of corticosteroids (≥ 12 mg/day equivalent dexamethasone dose), early administration of corticosteroid treatment (< 7 days since symptom onset) and long term of corticosteroids (≥ 10 days) were also investigated. RESULTS: Between February 2020 and October 2021, 4226 patients were included. Of these, 3592 (85%) patients had received systemic corticosteroids during hospitalisation. In the propensity-adjusted multivariable analysis, the use of corticosteroids was protective for 90-day mortality in the overall population (HR 0.77 [0.65-0.92], p = 0.003) and in-hospital mortality (SHR 0.70 [0.58-0.84], p < 0.001). Significant effect modification was found after adjustment for covariates using propensity score for age (p = 0.001 interaction term), Sequential Organ Failure Assessment (SOFA) score (p = 0.014 interaction term), and mechanical ventilation (p = 0.001 interaction term). We observed a beneficial effect of corticosteroids on 90-day mortality in various patient subgroups, including those patients aged ≥ 60 years; those with higher baseline severity; and those receiving invasive mechanical ventilation at ICU admission. Early administration was associated with a higher risk of 90-day mortality in the overall population (HR 1.32 [1.14-1.53], p < 0.001). Long-term use was associated with a lower risk of 90-day mortality in the overall population (HR 0.71 [0.61-0.82], p < 0.001). No effect was found regarding the dosage of corticosteroids. Moreover, the use of corticosteroids was associated with an increased risk of nosocomial bacterial pneumonia and hyperglycaemia. CONCLUSION: Corticosteroid in ICU-admitted patients with COVID-19 may be administered based on age, severity, baseline inflammation, and invasive mechanical ventilation. Early administration since symptom onset may prove harmful.

Severe Infections Due to Respiratory Viruses.

Severe viral infections may result in severe illnesses capable of causing acute respiratory failure that could progress rapidly to acute respiratory distress syndrome (ARDS), related to worse outcomes, especially in individuals with a higher risk of infection, including the elderly and those with comorbidities such as asthma, diabetes mellitus and chronic respiratory or cardiovascular disease. In addition, in cases of severe viral pneumonia, co-infection with bacteria such as Streptococcus pneumoniae and Staphylococcus aureus is related to worse outcomes. Respiratory viruses like influenza, rhinovirus, parainfluenza, adenovirus, metapneumovirus, respiratory syncytial virus, and coronavirus have increasingly been detected. This trend has become more prevalent, especially in critically ill patients, due to the availability and implementation of molecular assays in clinical practice. Respiratory viruses have been diagnosed as a frequent cause of severe pneumonia, including cases of community-acquired pneumonia, hospital-acquired pneumonia, and ventilator-associated pneumonia. In this review, we will discuss the epidemiology, diagnosis, clinical characteristics, management, and prognosis of patients with severe infections due to respiratory viruses, with a focus on influenza viruses, non-influenza viruses, and coronaviruses.

Early Bacterial Identification among Intubated Patients with COVID-19 or Influenza Pneumonia: A European Multicenter Comparative Clinical Trial.

Rationale: Early empirical antimicrobial treatment is frequently prescribed to critically ill patients with coronavirus disease (COVID-19) based on Surviving Sepsis Campaign guidelines.Objectives: We aimed to determine the prevalence of early bacterial identification in intubated patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia, as compared with influenza pneumonia, and to characterize its microbiology and impact on outcomes.Methods: A multicenter retrospective European cohort was performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation >48 hours were eligible if they had SARS-CoV-2 or influenza pneumonia at ICU admission. Bacterial identification was defined by a positive bacterial culture within 48 hours after intubation in endotracheal aspirates, BAL, blood cultures, or a positive pneumococcal or legionella urinary antigen test.Measurements and Main Results: A total of 1,050 patients were included (568 in SARS-CoV-2 and 482 in influenza groups). The prevalence of bacterial identification was significantly lower in patients with SARS-CoV-2 pneumonia compared with patients with influenza pneumonia (9.7 vs. 33.6%; unadjusted odds ratio, 0.21; 95% confidence interval [CI], 0.15-0.30; adjusted odds ratio, 0.23; 95% CI, 0.16-0.33; P < 0.0001). Gram-positive cocci were responsible for 58% and 72% of coinfection in patients with SARS-CoV-2 and influenza pneumonia, respectively. Bacterial identification was associated with increased adjusted hazard ratio for 28-day mortality in patients with SARS-CoV-2 pneumonia (1.57; 95% CI, 1.01-2.44; P = 0.043). However, no significant difference was found in the heterogeneity of outcomes related to bacterial identification between the two study groups, suggesting that the impact of coinfection on mortality was not different between patients with SARS-CoV-2 and influenza.Conclusions: Bacterial identification within 48 hours after intubation is significantly less frequent in patients with SARS-CoV-2 pneumonia than patients with influenza pneumonia.Clinical trial registered with www.clinicaltrials.gov (NCT04359693).

The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity.

The zoonotic SARS-CoV-2 virus that causes COVID-19 continues to spread worldwide, with devastating consequences. While the medical community has gained insight into the epidemiology of COVID-19, important questions remain about the clinical complexities and underlying mechanisms of disease phenotypes. Severe COVID-19 most commonly involves respiratory manifestations, although other systems are also affected, and acute disease is often followed by protracted complications. Such complex manifestations suggest that SARS-CoV-2 dysregulates the host response, triggering wide-ranging immuno-inflammatory, thrombotic, and parenchymal derangements. We review the intricacies of COVID-19 pathophysiology, its various phenotypes, and the anti-SARS-CoV-2 host response at the humoral and cellular levels. Some similarities exist between COVID-19 and respiratory failure of other origins, but evidence for many distinctive mechanistic features indicates that COVID-19 constitutes a new disease entity, with emerging data suggesting involvement of an endotheliopathy-centred pathophysiology. Further research, combining basic and clinical studies, is needed to advance understanding of pathophysiological mechanisms and to characterise immuno-inflammatory derangements across the range of phenotypes to enable optimum care for patients with COVID-19.

Trends in mortality of hospitalised COVID-19 patients: A single centre observational cohort study from Spain.

BACKGROUND: We aimed to describe changes in characteristics and treatment strategies of hospitalised patients with COVID-19 and detail the mortality trend over time. METHODS: Observational cohort study of all consecutive patients admitted ≥ 48 h to Hospital Clinic of Barcelona for COVID-19 (1 March-30 September 2020). FINDINGS: A total of 1645 consecutive patients with COVID-19 were assessed over a 7-month period. Overall mortality (≤30 days) was 9.7% (159 patients), 7.7% in patients hospitalised in regular wards and 16.7 % in patients requiring ICU admission. Overall mortality decreased from 11.6% in the first month to 1.4% in the last month, reflecting a progressive, significant downward trend (p for trend <0.001). Patients' age changed over time, peaking in June. Most changes in the use of antivirals and anti-inflammatory treatments were documented. Age (OR 1.1, CI 1.1-1.12), chronic heart disease, (OR 1.7, CI 1.1-2.9), D-dimer>700 ng/mL (OR 2.3, CI 1.3-4.1), ferritin>489 ng/mL (OR 1.9; CI 1.5-3.2), C-RP>7 mg/dL (OR 2.6; CI 1.5-4.6), and shorter duration from symptom onset to hospital admission (OR 1.11; CI 1.04-1.17) were factors associated with 30-day mortality at hospital admission. Conversely, hospital admission in the last months (OR 0.80; CI 0.65-0.98) was significantly associated with lower mortality. INTERPRETATION: In-hospital mortality has decreased in patients with COVID-19 over the last, few months, even though main patient characteristics remain similar. Several changes made when managing patients may explain this decreasing trend. Our study provides current data on mortality of patients hospitalised with COVID-19 that might be useful in establishing quality of standard of care. FUNDING: EIT Health, European Union´s Horizon 2020 Research and Innovation Programme), EDRD. PPA [CM18/00132], NGP [FI19/00133], and CGV [FIS PI18/01061], have received grants from Ministerio de Sanidad y Consumo, ISCIII.

CONTEXTO: Nuestro objetivo es describir los cambios en las características y las estrategias de tratamiento de los pacientes hospitalizados por COVID-19, y detallar la tendencia de la mortalidad en el tiempo. MÉTODOS: Estudio observacional de cohortes de todos los pacientes consecutivos, ingresados por COVID-19 durante más de 48 horas, en el Hospital Clínic de Barcelona (del 1 de marzo al 30 de septiembre de 2020). RESULTADOS: Un total de 1645 pacientes consecutivos fueron evaluados durante un período de 7 meses. La mortalidad global (≤30 días) fue del 9.7% (159 pacientes): 7.7% en pacientes hospitalizados en salas convencionales, y 16.7% en pacientes que requirieron ingreso en UCI. La mortalidad global disminuyó del 11.6% en el primer mes al 1.4% en el último mes evaluado, reflejando una progresiva y significativa tendencia a la baja (p para la tendencia <0.001). La edad de los pacientes ha cambiado con el tiempo, habiendo alcanzado su pico en junio. La mayoría de cambios en el uso de antivirales y antiinflamatorios se han documentado. La edad (OR 1.1; CI 1.1­1.12), cardiopatía crónica (OR 1.7; CI 1.1­2.9), dímero-D>700 ng/mL (OR 2.3; CI 1.3­4.1), ferritina>489 ng/mL (OR 1.9; CI 1.5­3.2), PCR>7 mg/dL (OR 2.6; CI 1.5­4.6), y una menor duración desde el inicio de síntomas a la hospitalización (OR 1.11; CI 1.04­1.17) fueron factores asociados a la mortalidad intrahospitalaria a 30 días. Por el contrario, el ingreso hospitalario previo en los últimos meses (OR 0.80; CI 0.65­0.98) se asoció significativamente a una menor mortalidad. DISCUSIÓN: La mortalidad intrahospitalaria ha disminuido en los pacientes con COVID-19 durante los últimos meses, incluso siendo similares las características de los pacientes. Algunos cambios realizados en el manejo de estos pacientes podrían explicar esta tendencia decreciente. Nuestro estudio aporta datos actualizados en la mortalidad de los pacientes hospitalizados con COVID-19, que podrían ser útiles de cara a establecer unos cuidados estándar de calidad. FINANCIACIÓN: EIT Health, European Union´s Horizon 2020 Research and Innovation Programme, EDRD. PPA [CM18/00132], NGP [FI19/00133] y CGV [FIS PI18/01061], han recibido becas del Ministerio de Sanidad y Consumo, ISCIII.