Risk factors for the in­hospital and 1­year mortality of elderly patients hospitalized due to COVID­19­related pneumonia.

Coronavirus disease 2019 (COVID-19) is characterized by poor outcomes and a high mortality rate, particularly among elderly patients. Since the beginning of the pandemic, an older age has been recognized as a critical risk factor for disease severity, with increasing mortality rates in each decade of life. This phenomenon may be a consequence of a poor previous health status, with a higher prevalence of pre-existing comorbidities and a higher degree of frailty. The majority of studies on the outcomes and risk factors of elderly patients refer to the first waves of the pandemic and the predictors of in-hospital mortality in these patients. The aim of the present study was to provide a detailed description of the clinical characteristics and management of a cohort of elderly patients (≥65 years of age) who were hospitalized with COVID-19-related pneumonia in all phases of the pandemic, presenting their outcomes, and investigating predictors of in-hospital and out-of-hospital mortality over a period of 1 year in this particularly vulnerable population. A total of 1,124 elderly patients (603 males, 53.7%) with a mean age of 78.51±7.42 years and a median Charlson comorbidity index (CCI) of 5 were included in the study. Of these patients, 104 (9.3%) were hospitalized during the period of prevalence of the original strain Wuhan, 385 (34.3%) were hospitalized during the period of prevalence of the Alpha variant, 221 (19.7%) were hospitalized during the period of prevalence of the Delta variant, and 414 (36.8%) were hospitalized during the period of prevalence of the Omicron variant. Overall, the in-hospital mortality rate was 33.4% (375 patients), and the 1-year mortality rate was 44.7% (502 patients). The majority of patients had not been vaccinated or had not completed full vaccination against severe acute respiratory syndrome coronavirus-2 (843 patients, 75%), given the period of infection. Age, immature granulocytes, lactate dehydrogenase (LDH) levels, ferritin levels, chest X-ray score, as well as the absence of full vaccination, cough and fatigue, were statistically significantly and independently associated with in-hospital mortality, while age, LDH levels, ferritin levels, alanine aminotransferase levels, CCI, chest X-ray score, the absence of cough and fatigue, and a history of dementia were statistically significantly and independently associated with 1-year mortality. On the whole, the present study demonstrates that both the in-hospital mortality and 1-year mortality rates of elderly patients hospitalized due to COVID-19-related pneumonia are high.

Predictors of COVID­19­associated mortality among hospitalized elderly patients with dementia.

The mortality of elderly patients with dementia hospitalized with coronavirus disease 2019 (COVID-19)-associated pneumonia is high. The mortality rate of these patients continues to be high following their discharge. However, data on the outcomes of these patients in all phases of the pandemic are limited. The aim of the present study was to examine the clinical characteristics and the in-hospital and 90-day mortality rates of elderly patients with dementia hospitalized due to COVID-19-associated pneumonia during all phases of the pandemic. During the time period between February 15, 2021 to July 15, 2022, 105 elderly patients (≥65 years old) with dementia of various etiologies were hospitalized due to COVID-19-associated pneumonia. The patient characteristics and in-hospital outcomes within 90 days of admission were recorded. The mean age of the patients was 84.03±7.61 years and 60 (57.1%) patients were females. A total of 52 (49.5%) patients were hospitalized during the omicron variant period, 27 (25.7%) were fully vaccinated (three doses) and 38 (36.2%) patients succumbed during their hospitalization. In total, 52 (49.5%) patients succumbed within the first 90 days of admission. According to the univariate regression analysis, the omicron variant [hazard ratio (HR), 2.126; 95% confidence interval (CI), 1.073-4.213; P=0.031] and the absence of full vaccination (HR, 6.231; 95% CI, 1.500-25.87; P=0.012) were associated with a higher in-hospital mortality. In the multivariate regression analysis, only the absence of complete vaccination was an independent predictor of mortality (HR, 5.182; 95% CI, 1.205-22.28; P=0.027). According to the univariate regression analysis, age (HR, 1.045; 95% CI, 1.006-1.085; P=0.023) and the lack of complete vaccination (HR, 3.254; 95% CI, 1.294-8.181; P=0.012) were associated with 90-day mortality; in addition, by multivariate regression analysis, age (HR, 1.047; 95% CI, 1.007-1.048; P=0.021) and the absence of full vaccination (HR, 3.286; 95% CI, 1.307-8.265; P=0.011) exhibited an independent association with the 90-day mortality rate. Based on the findings presented herein, the in-hospital and 90-day mortality rates of elderly patients with dementia and COVID-19-associated pneumonia is high. An older age and the lack of complete vaccination are independently associated with poor outcomes.

Clinical course of COVID-19 infection in a melanoma patient treated with nivolumab and bempegaldesleukin: a case report.

The exact impact of immune checkpoint inhibitors in the course and outcome of COVID-19 in cancer patients is currently unclear. Herein, we present the first description of an elderly melanoma patient who developed COVID-19 pneumonia while under treatment with nivolumab and bempegaldesleukin in combination with an investigational PEGylated interleukin (IL-2). We present the clinical characteristics and the laboratory and imaging findings of our patient during the course of COVID-19 pneumonia. Moreover, we discuss the currently available data regarding the mechanism of action of immune checkpoint inhibitors and IL-2 analogs in the treatment of COVID-19. The administration of these agents did not have a negative effect on the outcome of COVID-19 pneumonia in an elderly melanoma patient.

Immune checkpoint inhibitors represent a major advance in the treatment of several solid malignancies, including melanoma. Bempegaldesleukin is an investigational PEGylated IL-2 that is being evaluated, in combination with nivolumab, in the management of a variety of cancers. The immunomodulation caused by these agents may also modify the immune response in COVID-19. Currently available data regarding the impact of immune checkpoint inhibitors in reducing the severity of COVID-19 in patients with cancer are mixed, whereas no clinical data are available for bempegaldesleukin. Herein, we report the case of an elderly female melanoma patient who developed COVID-19 pneumonia while under treatment with nivolumab and bempegaldesleukin. The administration of these agents did not have a negative effect on the outcome of COVID-19 pneumonia in our patient.

Prevalence of abnormal liver biochemistry and its impact on COVID-19 patients' outcomes: a single-center Greek study.

Background: Abnormalities in aminotransferases are frequently observed in hospitalized COVID-19 patients, but their clinical impact is poorly characterized. Methods: A total of 1046 patients hospitalized to the non-intensive care unit ward with documented COVID-19 were included retrospectively. Demographic, clinical and laboratory characteristics on admission and during hospital stay, including the presence of liver injury (LI), defined as aspartate aminotransferase (AST) >200 IU/L, were recorded. Results: On admission, 363 (34.7%) and 269 (25.7%) patients had abnormal AST and ALT values (i.e., >40 IU/L), respectively, while during hospitalization 53 (5%) patients fulfilled the criteria for LI. In multivariate logistic regression analysis, AST (odds ratio [OR] 1.023, 95% confidence interval [CI] 1.016-1.029; P<0.001), and ferritin (OR 1.01, 95%CI 1.001-1.02; P<0.001) were the baseline factors independently associated with the development of LI during hospital stay. One hundred twenty-three (11.7%) patients died during hospitalization. The independent variables associated with mortality were: age (hazard ratio [HR] 1.043, 95%CI 1.029-1.056; P<0.001), ferritin (HR 1.1, 95%CI 1.05-1.2; P<0.001), platelets (HR 0.996, 95%CI 0.994-0.999; P=0.003), and administration of remdesivir (HR 0.50, 95%CI 0.30-0.85; P=0.009). The patients with abnormal baseline AST (i.e., >40 IU/L), compared to those with normal AST values, had worse outcomes (log rank test: 8.8, P=0.003). Conclusions: Elevated aminotransferases are commonly seen in COVID-19 patients. They possibly reflect disease severity and may be associated with in-hospital mortality.

A Simple Prognostic Score for Critical COVID-19 Derived from Patients without Comorbidities Performs Well in Unselected Patients.

We aimed to search for laboratory predictors of critical COVID-19 in consecutive adults admitted in an academic center between 16 September 2020−20 December 2021. Patients were uniformly treated with low-molecular-weight heparin, and dexamethasone plus remdesivir when SpO2 < 94%. Among consecutive unvaccinated patients without underlying medical conditions (n = 241, 49 year-old median, 71% males), 22 (9.1%) developed critical disease and 2 died (0.8%). White-blood-cell counts, neutrophils, neutrophil-to-lymphocyte ratio, CRP, fibrinogen, ferritin, LDH and γ-GT at admission were each univariably associated with critical disease. ROC-defined cutoffs revealed that CRP > 61.8 mg/L, fibrinogen > 616.5 mg/dL and LDH > 380.5 U/L were each associated with critical disease development, independently of age, sex and days from symptom-onset. A score combining higher-than-cutoff CRP (0/2), LDH (0/1) and fibrinogen (0/1) predicted critical disease (AUC: 0.873, 95% CI: 0.820−0.926). This score performed well in an unselected patient cohort (n = 1228, 100% unvaccinated) predominantly infected by the alpha variant (AUC: 0.718, 95% CI: 0.683−0.753), as well as in a mixed cohort (n = 527, 65% unvaccinated) predominantly infected by the delta variant (AUC: 0.708, 95% CI: 0.656−0.760). Therefore, we propose that a combination of standard biomarkers of acute inflammatory response, cell death and hypercoagulability reflects the severity of COVID-19 per se independently of comorbidities, age and sex, being of value for risk stratification in unselected patients.

Radiologically suspected COVID-19-associated organizing pneumonia responding well to corticosteroids: A report of two cases and a review of the literature.

Organizing pneumonia (OP) is a type of diffuse interstitial lung disease, which may be induced in the context of several clinical conditions, such as drug reactions, infections, autoimmune diseases and cancer. Coronavirus disease 2019 (COVID-19)-associated OP has been reported as a late-stage consequence of the infection or a histological form of COVID-19-associated pneumonia. Autopsies and postmortem lung biopsies have demonstrated that the majority of patients with COVID-19-associated pneumonia develop secondary OP, and COVID-19-associated pneumonia and OP have common radiological features. The diagnosis of COVID-19-associated OP should be suspected in patients with severe acute respiratory syndrome coronavirus 2 infection who exhibit clinical deterioration despite optimal care, or who have aggravating symptoms following an initial recovery. The use of corticosteroids is a typical treatment for OP. However, to date, at least to the best of our knowledge, there are a few reports regarding the role of corticosteroids in COVID-19-associated pneumonia; thus, the optimal time for administration, the dose and treatment duration have not yet been determined. The present study presents two cases of patients with COVID-19, who exhibited clinical deterioration following the initial phase of infection and with radiological characteristics of OP who received corticosteroids and had a favorable outcome. The early diagnosis of COVID-19-associated OP may lead to targeted treatment, decreased requirements for ventilatory support and an improved survival rate.

Biomarkers predicting the 30­day mortality of patients who underwent elective surgery and were infected with SARS­CoV­2 during the post­operative period: A retrospective study.

The coronavirus disease 2019 (COVID-19) pandemic is a significant global concern that has had major implications for the healthcare system. Patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) undergoing elective or emergency surgical procedures have a substantial risk of mortality and peri-operative complications. The present study aimed to describe the characteristics of patients who underwent elective surgery and developed nosocomial SARS-CoV-2 infection post-surgery. Patients who underwent thoracic, upper and lower abdominal or peripheral elective surgery with a polymerase chain reaction diagnosis of COVID-19, at 3-7 days after the surgery, were enrolled in the present retrospective study. Demographics, vaccination status against SARS-CoV-2, Charlson comorbidity index (CCI) and laboratory data were recorded upon admission to the hospital unit. In total, 116 subjects (80 males, 36 females; mean age, 67.31±16.83 years) fulfilling the inclusion criteria were identified. Among the 116 participants, 14 (12.1%) were intubated. From the 116 individuals analyzed, 84 were alive after 30 days (survivors), and 32 had succumbed to the disease (non-survivors). The mortality rate was 27.6% (32/116). The non-survivors had an older age and a higher CCI score. At the evaluation upon admission to the hospital unit, the survivors presented with higher serum albumin levels and a higher number of blood lymphocytes. In addition, the survivors exhibited lower levels of lactate dehydrogenase, aspartate aminotransferase, alkaline phosphatase (ALP) and C-reactive protein (CRP), as well as a higher neutrophil to lymphocyte ratio (NLR) and CRP to albumin ratio (CAR) (P<0.05). The patients that were intubated had higher levels of gamma glutamyl-transferase (GGT), ALP and ferritin, as well as a higher NLR and platelet to lymphocyte ratio upon admission to the hospital unit (P<0.05). According to the Cox proportional hazards multivariate regression analysis, the only independent predictors of mortality and intubation were ALP and GGT upon admission, respectively (P<0.05). On the whole, the findings of the present study suggest that more stringent guidelines are required in order to prevent infection during the post-operative period.

Comparison of liver function test- and inflammation-based prognostic scores for coronavirus disease 2019: a single center study.

BACKGROUND: Although several liver- and inflammation-based scores to predict the clinical course of patients with coronavirus disease 2019 (COVID-19) have been evaluated, no direct comparison regarding their predictive ability has been performed. METHODS: 1038 patients (608 males, age 63.5 ± 17 years) hospitalized with documented COVID-19 infection to the non-ICU ward, were included retrospectively. Clinical and laboratory characteristics on admission including evaluation of Fibrosis-4 (FIB-4) score and C-Reactive Protein (CRP) to albumin ratio (CAR) were recorded. RESULTS: One hundred and twenty-four patients (11.9%) died during hospitalization after 8 (3-72) days. In multivariate analysis, FIB-4 (hazard ratio, 1.11; 95% confidence interval (CI), 1.034-1.19; P = 0.004), was independently associated with mortality, with very good discriminative ability (area under the receiver operating characteristic curve curve, 0.76). The patients with FIB-4 &gt;2.67 (n = 377), compared to those with ≤2.67 (n = 661), had worse survival (log-rank 32.6; P &lt; 0.001). Twenty-four (6.8%) of 352 patients with possible nonalcoholic fatty liver disease (NAFLD) (defined as Hepatic Steatosis Index &gt;36) died during hospitalization. In multivariate analysis, CAR was an independent risk factor (1) for mortality (hazard ratio, 1.014; 95% CI, 1.002-1.025; P = 0.021), (2) the need for high-flow nasal cannula with or without intubation (hazard ratio, 1.016; 95% CI, 1.004-1.027; P = 0.007) and (3) development of acute kidney injury (hazard ratio, 1.017; 95% CI, 1.006-1.028; P = 0.002). In addition, the patients with possible NAFLD and CAR &gt;12 (n = 154), compared to those with CAR ≤12 (n = 198), had worse survival (log-rank 5.1; P = 0.024). CONCLUSIONS: FIB-4 was an independent factor for mortality with better performance compared to other liver function test- and inflammation-based scores in patients with COVID-19, while CAR was the only score independently associated with the clinical course in COVID-19 patients with possible NAFLD.

Factors predicting poor outcomes of patients treated with tocilizumab for COVID­19­associated pneumonia: A retrospective study.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic is a significant global issue that has major implications for the healthcare system. The mortality rates associated with SARS-CoV-2 infection vary according to the geographical region and are associated with age, comorbidities and vaccination status. Organ damage is caused by the cytokine release syndrome, which plays a crucial role in the course of coronavirus disease 2019 (COVID-19) infection. Innate and adaptive immune system stimulation in patients with COVID-19 results in inappropriate cytokine release. The anti-IL-6 receptor antagonist, tocilizumab, is used in the treatment of connective tissue diseases. The present single-center retrospective study on patients with COVID-19 admitted to hospital between September, 2020 and April, 2022 aimed to identify predictors of mortality and other unfavorable outcomes in patients treated with tocilizumab for COVID-19-associated pneumonia. Demographics, vaccination status against SARS-CoV-2, the Charlson comorbidity index (CCI), laboratory data and chest X-ray scores were recorded upon admission. In total, 174 subjects (121 males; mean age, 62.43±13.47 years) fulfilling the inclusion criteria were included. Among the 174 participants, 58 (33.3%) were intubated. The mortality rate was 35.1%. The non-survivors were older, mostly females, and had a higher CCI score. At the evaluation upon admission, the survivors presented with higher levels of alanine transferase and gamma glutamyl-transferase and with a greater number of platelets (PLTs), while patients that were intubated were also older, mostly females, and had a higher CCI score (P<0.05). Age was identified as the only independent factor predicting mortality in the Cox proportional hazards multivariate regression analysis. By performing a sub-analysis regarding sex, it was revealed that the value of PLTs was an independent factor predicting intubation and 90-day mortality in male patients, and the lymphocyte count was the only factor associated with intubation in female patients. On the whole, the data of the present study may be used to identify patient subpopulations responding to treatment with tocilizumab in prospective clinical trials.

Acute hepatitis and liver injury in hospitalized patients with COVID­19 infection.

Coronavirus disease 2019 (COVID-19) is a systemic illness with an increased host inflammatory response that affects multiple extra-pulmonary organs, including the gastrointestinal tract. Abnormalities in liver biochemistry have been observed in a significant proportion of patients with COVID-19 upon admission, and this proportion increases with hospitalization. These abnormalities are typically manifested as elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, with less frequently detected elevations in the levels of cholestatic enzymes. Elevated aminotransaminase levels have been linked to an increased risk of mortality and complications, indicating the severity of COVID-19 infection. The present study evaluated the prevalence and the baseline factors associated with the development of acute hepatitis (ΑΗ), liver injury (LI) and associated patterns, as well as the presence of abnormalities in the levels of aminotransferases at discharge in the same cohort. For this purpose, 1,304 patients with confirmed COVID-19 infection were enrolled in the study. According to the results obtained, AST levels at baseline were the only independent factor for AH during hospital stay, while AST, alkaline phosphatase and ferritin levels were independent baseline factors for the development of LI. The patients with hepatocellular, compared to those with cholestatic LI, exhibited similar survival rates, as well as similarities in the development of acute kidney injury and the need for oxygen via high-flow nasal cannula and/or mechanical ventilation. In addition, age and ALT were independent risk factors for persistent abnormal values of AST and ALT at discharge.

Comparative Immunogenicity of BNT162b2 mRNA Vaccine with Natural SARS-CoV-2 Infection.

BNT162b2 has proven to be highly effective, but there is a paucity of data regarding immunogenicity factors and comparison between response to vaccination and natural infection. This study included 871 vaccinated healthcare workers (HCW) and 181 patients with natural infection. Immunogenicity was assessed by measuring anti-SARS-CoV-2 against the RBD domain of the spike protein (anti-RBD). Samples were collected 1-2 weeks after vaccination or 15-59 days post-onset of symptoms. Post-vaccine anti-RBD concentrations were associated with age, gender, vaccination side-effects (VSE) and prior infection (Pr-CoV). Anti-RBD median levels (95%CI) were lower by 2466 (651-5583), 6228 (3254-9203) and 7651 (4479-10,823) AU/mL in 35-44, 45-54, 55-70 yrs, respectively, compared with the 18-34 yrs group. In females, the median levels were higher by 2823 (859-4787), 5024 (3122-6926) in individuals with VSE, and 9971 (5158-14,783) AU/mL in HCWs with Pr-CoV. The ratio of anti-RBD in vaccinated individuals versus those with natural infection varied from 1.0 to 19.4. The high immunogenicity of BNT162b2 is verified, although its sustainability has yet to be elucidated. The use of comparative data from natural infection serological panels, expressing the clinical heterogeneity of natural infection, may facilitate early decisions for candidate vaccines to be evaluated in clinical trials.