Artificial neural network based prediction of the lung tissue involvement as an independent in-hospital mortality and mechanical ventilation risk factor in COVID-19.

INTRODUCTION: During COVID-19 pandemic, artificial neural network (ANN) systems have been providing aid for clinical decisions. However, to achieve optimal results, these models should link multiple clinical data points to simple models. This study aimed to model the in-hospital mortality and mechanical ventilation risk using a two step approach combining clinical variables and ANN-analyzed lung inflammation data. METHODS: A data set of 4317 COVID-19 hospitalized patients, including 266 patients requiring mechanical ventilation, was analyzed. Demographic and clinical data (including the length of hospital stay and mortality) and chest computed tomography (CT) data were collected. Lung involvement was analyzed using a trained ANN. The combined data were then analyzed using unadjusted and multivariate Cox proportional hazards models. RESULTS: Overall in-hospital mortality associated with ANN-assigned percentage of the lung involvement (hazard ratio [HR]: 5.72, 95% confidence interval [CI]: 4.4-7.43, p < 0.001 for the patients with >50% of lung tissue affected by COVID-19 pneumonia), age category (HR: 5.34, 95% CI: 3.32-8.59 for cases >80 years, p < 0.001), procalcitonin (HR: 2.1, 95% CI: 1.59-2.76, p < 0.001, C-reactive protein level (CRP) (HR: 2.11, 95% CI: 1.25-3.56, p = 0.004), glomerular filtration rate (eGFR) (HR: 1.82, 95% CI: 1.37-2.42, p < 0.001) and troponin (HR: 2.14, 95% CI: 1.69-2.72, p < 0.001). Furthermore, the risk of mechanical ventilation is also associated with ANN-based percentage of lung inflammation (HR: 13.2, 95% CI: 8.65-20.4, p < 0.001 for patients with >50% involvement), age, procalcitonin (HR: 1.91, 95% CI: 1.14-3.2, p = 0.14, eGFR (HR: 1.82, 95% CI: 1.2-2.74, p = 0.004) and clinical variables, including diabetes (HR: 2.5, 95% CI: 1.91-3.27, p < 0.001), cardiovascular and cerebrovascular disease (HR: 3.16, 95% CI: 2.38-4.2, p < 0.001) and chronic pulmonary disease (HR: 2.31, 95% CI: 1.44-3.7, p < 0.001). CONCLUSIONS: ANN-based lung tissue involvement is the strongest predictor of unfavorable outcomes in COVID-19 and represents a valuable support tool for clinical decisions.

Immune restoration affects 10-year survival in people living with HIV/AIDS.

INTRODUCTION: In recent years, a reduction in the life expectancy gap between people living with HIV (PLWH) and the general population has been observed, irrespective of CD4 lymphocyte count, due to widespread access to antiretroviral treatment. The increase in the life expectancy of PLWH has increased awareness of both the ageing process and gender discrepancies in immune restoration and survival. MATERIALS AND METHODS: Longitudinal data were collected for 2240 patients followed up at the Hospital for Infectious Diseases in Warsaw, Poland (n = 1482), and the Department of Acquired Immunodeficiency, Pomeranian Medical University, Szczecin, Poland (n = 758). Immune restoration was measured from the time of starting combination antiretroviral therapy until achieving 500 CD4 lymphocytes/µL, 800 CD4 lymphocytes/µL, and CD4/CD8 lymphocyte ratios of > 0.8 and > 1.0. Full recovery was achieved when the patient was restored to both 800 CD4 lymphocytes/µL and a CD4/CD8 lymphocyte ratio > 1.0. RESULTS: For all endpoints, immune restoration had a protective effect by reducing mortality. Patients who achieved immune restoration had a greater chance of reduced mortality than those who did not achieve immune restoration: for CD4 count > 500 cells/µL, HR = 5.4 (interquartile range: 3.09-9.41), p < 0.001; for CD4 > 800 cells/µL, HR = 5.37 (2.52-11.43), p < 0.001; for CD4/CD8 ratio > 0.8, HR = 3.16 (1.81-5.51), p < 0.001; for CD4/CD8 ratio > 1.0, HR = 2.67 (1.49-5.24), p = 0.001, and for full immune recovery, HR = 3.62 (1.63-8.04), p = 0.002. CONCLUSIONS: Immune restoration remains a powerful factor in improving the survival of PLWH, regardless of the speed of recovery.

Improved survival in intensive care unit in severe COVID-19 associated with amantadine use - retrospective study.

OBJECTIVES: Possible immunomodulatory effect of amantadine in patients treated in intensive care unit (ICU), mostly among patients with brain injuries or vascular diseases was observed in several studies. The potential antiviral effect of amantadine against SARS-CoV-2 was discarded in clinical trials; however, immunomodulatory potential was not studied. The aim of the study was to investigate the effect of immunomodulatory amantadine therapy on mortality in patients with respiratory insufficiency due to COVID-19 requiring mechanical ventilation in ICU. METHODS: Retrospective analysis of 241 cases of 141 (58.5%) receiving intravenous amantadine sulfate vs 100 (41.5%) controls on standard of care only was performed. RESULTS: Overall mortality was 72.6%, being notably lower among amantadine treated patients (59.5%, n = 84) compared with controls (91%, n = 91), P-value = 0.001. In multivariate models administration of amantadine was independently associated with lower mortality rate (hazard ratio: 0.220, CI: 0.146-0.333 P-value = 0.001). Furthermore, survival was improved in patients who received amantadine; late administration of amantadine after 5th day was independently associated with lower mortality (hazard ratio: 0.560, CI: 0.313-0.999, P-value = 0.050). CONCLUSION: In patients treated in ICU with severe respiratory failure, administration of amantadine is associated with lower mortality, which may be associated with the potential anti-inflammatory and immunomodulatory effects of this agent.

Remdesivir Reduces Mortality in Hemato-Oncology Patients with COVID-19.

Introduction: Remdesivir is the first agent with proven clinical efficacy against coronavirus disease 2019 (COVID-19); however, its benefit is associated with early use, and its efficacy has been poorly studied in patients with hemato-oncological diseases, who have an increased risk of a severe course of infection. This study aimed to assess the effects of remdesivir on mortality, mechanical ventilation, and the duration of hospitalization in both the general population and in patients with hemato-oncological diseases. Materials and Methods: Longitudinal data for 4287 patients with confirmed COVID-19 were analyzed, including a subset of 200 individuals with hemato-oncological diseases. In total, 1285 (30.0%) patients received remdesivir, while the remaining patients were treated with other methods. Survival statistics for the 14- and 30-day observation time points were calculated using non-parametric and multivariate Cox models. Results: Mortality for the 14- and 30-day observation time points was notably lower among patients receiving remdesivir (7.2% vs 11.6%, p < 0.001 and 12.7% vs 16.0, p = 0.005, respectively); however, in multivariate models adjusted for age, sex, lung involvement, and lactate dehydrogenase and interleukin-6 levels, the administration of remdesivir did not reduce patient mortality at either the 14-day or 30-day time points. Among patients with haemato-oncological disease, significant survival benefit was observed at 14 and 30 days for patients treated with remdesivir (11.3% vs.16.7% and 24.2% vs 26.1%, respectively; p < 0.001). A favorable effect of remdesivir was also noted for the 14-day time point in multivariate survival analysis (HR:4.03 [95% confidence interval:1.37-11.88]; p = 0.01). Conclusion: Remdesivir significantly reduced the early mortality rate in COVID-19 patients with comorbid hemato-oncological disease, which emphasizes the need to administer this agent to immunosuppressed patients.

Tocilizumab Use among Patients Who Developed Pulmonary Embolism in the Course of Cytokine Release Storm and COVID-19 Pneumonia-A Retrospective Study.

INTRODUCTION: Thromboembolic events, including mainly pulmonary embolisms and ischemic strokes, occur in up to one-third of COVID-19 patients. As efficacy of tocilizumab (TCZ) among patients with acute pulmonary embolism (PE) was not previously investigated, this study aimed to provide such data. OBJECTIVES: The aim of the study was to investigate the effect of TCZ on mortality in patients with confirmed acute pulmonary embolism, cytokine release storm and COVID-19 pneumonia. PATIENTS AND METHODS: Longitudinal data of 4287 patients with confirmed SARS-CoV-2 infection were collected between 4 March 2020 and 16 January 2022. In this study, we retrospectively analyzed the samples and dataset of cases with confirmed acute pulmonary embolism associated with at least moderate lung involvement due to COVID-19 pneumonia. RESULTS: In the analyzed dataset, 64 adult patients were diagnosed with PE, and of these, 28 (44%) cases were treated with two 8 mg/kg doses of TCZ, and 36 (56%) did not receive this agent. The groups were balanced regarding demographics, comorbidities and the biochemical markers. Overall mortality in our study was 29.6% (n = 17). Mortality in the group treated with TCZ was 43% (n = 12) compared to 19% (n = 7) in the group without TCZ. In multivariate proportional Cox hazards models, intravenous administration of TCZ was independently associated with higher mortality (HR: 3.342 (CI: 1.077-10.370), p = 0.036). CONCLUSIONS: In patients with COVID-19 pneumonia with at least moderate lung involvement, CRS and acute pulmonary embolism, administration of TCZ is associated with increased mortality. Therefore, TCZ should be used with caution in SARS-CoV-2 cases with pulmonary embolism.

Effectiveness of Tocilizumab in Patients with Severe or Critical Lung Involvement in COVID-19: A Retrospective Study.

Introduction: Acute lung injury is associated with dysfunctional immune response to SARS-CoV-2. This leads to CRS, which require immunomodulatory treatments aiming to limit the excessive production of cytokines. The literature so far indicates the effectiveness of tocilizumab in patients with COVID-19-associated pneumonia, but there is no clear evidence of its effectiveness in patients with at least 50% lung involvement; therefore, we aimed to bridge this gap in knowledge. Materials and methods: Longitudinal data for 4287 patients with confirmed COVID-19 infection were collected between 1st March 2020 and 16th of January 2022. In total, 182 cases with lung involvement >50% and biochemical indicators of cytokine release storm (Il-6 >100 pg/mL) were selected and analyzed using non-parametric statistics and multivariate Cox models. Results: Among the 182 included patients, 100 (55%) were treated with TCZ, while 82 (45%) did not receive TCZ. The groups were balanced regarding demographics, lung involvement and biochemical markers. Overall mortality in the group was 63.1%. Mortality in the TCZ group was 58.0% compared to 69.5% (n = 57) in the non-TCZ group (p = 0.023). In multivariate Cox proportional hazards models, intravenous administration of tocilizumab was associated with lower probability of ICU admission (HR: 0333 (CI: 0.159−0.700, p = 0.004)) and lower mortality (HR: 0.57306 (CI: 0.354−0.927, p = 0.023)). Conclusions: Tocilizumab is effective as a treatment in the most severely ill patients, in whom the level of lung involvement by the inflammatory process can exceed 50% with coexisting biochemical indices of cytokine storm (Il-6 > 100 pg/mL).

Factors Influencing Immune Restoration in People Living with HIV/AIDS.

Introduction: Immune restoration is a key clinical aspect that is pursued in the care of human immunodeficiency virus (HIV)-infected patients. Despite effective antiretroviral treatment and undetectable viremia, immune recovery is often incomplete. Materials and methods: Data from 311 Caucasian patients were collected. SNP in CCR2(rs1799864), CX3CR1(rs3732378), HLAC-35(rs9264942), and CCR5(promoter, rs1799988); a 32bp deletion(Δ32) in CCR5; and HLA-B*5701 genotypes were correlated with clinical data and selected endpoints. Kaplan−Meier and Cox proportional hazards models were used to analyze the effects of genetic factors over time. Results: For HLA-B*5701, the effect on the CD4+/CD8+ >0.8 cell ratio was lost within 48 months (HR = 2.04, 95% CI: 1.04−4.03), and the effect on the CD4+ cell count >500 cells/µL was lost within 12 months (HR = 2.12, CI: 1.11−4.04). The effect of CCR2 GG on the CD4+/CD8+ >0.8 cell ratio was lost within 36 months (HR = 1.7, CI: 1.05−2.75). For CCR5 wt/Δ32, the effect on the CD4+/CD8+ >1.0 cell ratio was lost within 24 months (HR = 2.0, CI: 1.08−3.69), and the effect on the CD4+ >800 cells/µL cell count was lost within 18 months (HR = 1.98, CI: 1.14−4.73). Conclusions: Selected genetic polymorphisms, namely CCR2 GG and CCR5 Δ32, and the presence of the HLA-B*5701 allele positively influenced immune restoration in cART-treated patients with HIV/AIDS.

Clinical parameters, selected HLA and chemokine gene variants associated with late presentation into care of people living with HIV/AIDS.

INTRODUCTION: Late presentation into care remains a significant problem in the diagnosis of HIV infection, and may negatively impact the Joint United Nations Program HIV/AIDS elimination targets. Host genetics affects the tempo of HIV disease progression and therefore may influence clinical status at care entry. MATERIALS AND METHODS: Longitudinal data were collected for 863 Caucasian patients followed up at Pomeranian Medical University, Szczecin, Poland. Single nucleotide polymorphisms in CCR2 (rs1799864), CX3CR1 (rs3732378), HLAC-35 (rs9264942), CCR5 promoter (rs1799988) as well as 32 base pair CCR5 mutation and HLA-B*5701 genotypes were correlated with the clinical and immunologic patient status at care entry. Late presentation was defined as baseline CD4 lymphocyte count <350 cells/µL or history of AIDS-defining illness, while advanced HIV disease as baseline CD4 lymphocyte count <200 cells/µL or AIDS. RESULTS: Of the analyzed gene variants, the CCR2 (rs1799864) GG genotype was more frequent among patients presenting for care with a CD4 lymphocyte count <200/µL (82.6% for GG homozygotes vs. 74.5% for allele A carriers, p = 0.01). The presence of the heterozygous wt/Δ32 genotype at the CCR5 gene was associated with a higher frequency of asymptomatic infection (18.9% for wt/Δ32 heterozygotes vs. 12% for wt/wt homozygotes, p = 0.03). As expected, this association was also observed among late presenters compared to patients presenting for care earlier (13.7% vs. 19,7%, respectively, p = 0.04). Finally, HLA-B*5701 was less common among late presenters (5%) compared to patients who entered care early (9.6%, p = 0.01) or patients with advanced HIV disease (8.9% vs. 5.2%, p = 0.02). CONCLUSIONS: Late presentation was associated with the GG homozygous genotype at the CCR2 rs1799864 SNP, while both the HLA-B*5701 variant and the CCR5 wt/Δ32 were associated with more favorable clinical profile at care entry.