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.

Non-HIV-related comorbidities and uncontrolled HIV replication are independent factors increasing the odds of hospitalization due to COVID-19 among HIV-positive patients in Poland.

PURPOSE: Immunocompromised patients are postulated to be at elevated risk of unfavorable outcomes of COVID-19. The exact effect of HIV infection on the course of COVID-19 remains to be elucidated. The aim of the study was to describe the epidemiological and clinical aspects of SARS-CoV-2 infection in HIV-infected individuals. METHODS: The HIV-positive patients who were diagnosed with SARS-CoV-2 infection were identified through thirteen specialist HIV clinics routinely following them due to HIV treatment. The data were collected between November 2020 and May 2021 through an on-line electronical case report form (SurveyMonkey®). The collected information included demographics, lifestyle, comorbidities, HIV care history, COVID-19 clinical course and treatment. Logistic regression models were used to identify factors associated with the odds of death or hospitalization due to COVID-19. RESULTS: One hundred and seventy-three patients with HIV-SARS-CoV-2 coinfection were included in the analysis. One hundred and sixty-one (93.1%) subjects had a symptomatic course of the disease. Thirty-nine (23.1%) of them were hospitalized, 23 (13.3%) necessitated oxygen therapy. Three (1.8%) patients required admission to the intensive care unit and 6 (3.5%) patients died. The presence of comorbidities and an HIV viral load of more than 50 copies/mL were linked to the increased odds of hospitalization (OR 3.24 [95% CI 1.27-8.28]) and OR 5.12 [95% CI 1.35-19.6], respectively). CONCLUSIONS: As depicted by our analyses, HIV-positive patients with comorbidities and/or uncontrolled HIV replication who are diagnosed with SARS-CoV-2 infection should be considered of high risk of poor COVID-19 outcome and followed up carefully.

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.

Improved survival in ICU in severe COVID-19 associated with amantadine use – retrospective study

Introduction Possible immunomodulatory effect of amantadine in patients treated in intensive care units (ICU), mostly among patients with brain injuries or vascular diseases was observed in several studies. Potential antiviral effect of amantadine against SARS CoV-2 was discarded in clinical trials, however immunomodulatory potential was not studied. Objectives: 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. Patients and 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 to controls (91%, n=91), p= 0.001. In multivariate models administration of amantadine was independently associated with lower mortality rate [HR: 0.220 (CI: 0.146 – 0.333), p = 0.001)]. Furthermore, survival was improved in patients who received amantadine late - administration of amantadine after 5th day was independently associated with lower mortality [HR: 0.560 (CI: 0.313 – 0.999), p = 0.050). Conclusions In patients treated in ICU with severe respiratory failure administration of amantadine associated with lower mortality, which may be associated with potential anti-inflammatory and immunomodulatory effects of this agent.

IgA-Based Secretory Response in Tears of COVID-19 Patients: A Potential Biomarker of Pro-Inflammatory State in Course of SARS-CoV-2 Infection.

Mucosal immunity, including secretory IgA (sIgA), plays an important role in the early defence against SARS-CoV-2 infection. However, a comprehensive evaluation of the local immune response in tears in relation to blood antibody reservoirs has not yet been conducted. A total of 179 symptomatic laboratory-confirmed COVID-19 patients were included in this single-centre study. Conjunctival swabs were analysed by a reverse transcription polymerase chain reaction for the detection of SARS-CoV-2 RNA. In parallel, tear samples collected by Schirmer test strips and plasma samples were analysed by ELISA to detect anti-S1 IgA levels. The concentrations of selected inflammatory cytokines in tears were determined by a magnetic bead assay. Anti-SARS-CoV-2 sIgA was present in the tears of 81 (45.25%) confirmed COVID-19 patients, and the tear IgA levels were correlated with the plasma IgA levels (Rs = +0.29, p = 0.0003). SARS-CoV-2 RNA in the conjunctival sac was identified in 18 COVID-19 patients (10%). Positive correlations between the tear IgA level and the concentrations of several cytokines TNF-α (Rs = +0.23, p = 0.002), IL-1ß (Rs = +0.25, p < 0.001), IL-2 (Rs = +0.20, p = 0.007), IL-4 (Rs = +0.16, p = 0.04), IL-5 (Rs = +0.36, p < 0.001), IL-6 (Rs = +0.32, p < 0.001), IL-8 (Rs = +0.31, p < 0.001), VEGF (Rs = +0.25, p < 0.001) and GM-CSF (Rs = +0.27, p < 0.001) were also found. Quantitative tear film-based sIgA could potentially serve as a rapid and easily accessible biomarker of external mucosal immunity to SARS-CoV-2. The concentration of sIgA is directly related to individual host immune responses to SARS-CoV-2 infection.

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.

Epigenetic activation of antiviral sensors and effectors of interferon response pathways during SARS-CoV-2 infection.

Recent studies have shown that methylation changes identified in blood cells of COVID-19 patients have a potential to be used as biomarkers of SARS-CoV-2 infection outcomes. However, different studies have reported different subsets of epigenetic lesions that stratify patients according to the severity of infection symptoms, and more importantly, the significance of those epigenetic changes in the pathology of the infection is still not clear. We used methylomics and transcriptomics data from the largest so far cohort of COVID-19 patients from four geographically distant populations, to identify casual interactions of blood cells' methylome in pathology of the COVID-19 disease. We identified a subset of methylation changes that is uniformly present in all COVID-19 patients regardless of symptoms. Those changes are not present in patients suffering from upper respiratory tract infections with symptoms similar to COVID-19. Most importantly, the identified epigenetic changes affect the expression of genes involved in interferon response pathways and the expression of those genes differs between patients admitted to intensive care units and only hospitalized. In conclusion, the DNA methylation changes involved in pathophysiology of SARS-CoV-2 infection, which are specific to COVID-19 patients, can not only be utilized as biomarkers in the disease management but also present a potential treatment target.

Programmed Cell Death-1/Programmed Cell Death-1 Ligand as Prognostic Markers of Coronavirus Disease 2019 Severity.

Current research proves that immune dysregulation is a common feature of coronavirus disease 2019 (COVID-19), and immune exhaustion is associated with increased disease mortality. Immune checkpoint molecules, including the programmed cell death-1 (PD-1)/PD-1 ligand (PD-L1) axis, may serve as markers of disease severity. Accordingly, in this study, we evaluated the expression of PD-1/PD-L1 in patients with COVID-19. Blood immunophenotypes of hospitalized patients with moderate (n = 17, requiring oxygen support) and severe (n = 35, requiring mechanical ventilation in the intensive care setting) COVID-19 were compared and associated with clinical, laboratory, and survival data. The associations between severity and lymphocyte profiles were analysed at baseline and after 7 and 14 days of in-hospital treatment. Forty patients without COVID-19 infection were used as controls. For PD-1-positive T and B lymphocyte subsets, notable increases were observed between controls and patients with moderate or severe COVID-19 for CD4+PD-1+ T cells, CD8+PD-1+ T and CD19+PD-1+ B cells. Similar trends were observed for PD-L1-positive lymphocytes, namely, CD4+PD-L1+ T cells, CD8+PD-L1+ T cells and CD19+PD-L1+ B cells. Importantly, all markers associated with PD-1 and PD-L1 were stable over time for the analysed time points in the moderate and severe COVID-19 groups. Increased abundances of PD-1+ and PD-L1+ lymphocytes were associated with disease severity and mortality and were stable over time in patients with moderate to severe COVID-19. These immune exhaustion parameters may be attractive biomarkers of COVID-19 severity.

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.

Programmed Cell Death-1/Programmed Cell Death-1 Ligand as Prognostic Markers of Coronavirus Disease 2019 Severity

Current research proves that immune dysregulation is a common feature of coronavirus disease 2019 (COVID-19), and immune exhaustion is associated with increased disease mortality. Immune checkpoint molecules, including the programmed cell death-1 (PD-1)/PD-1 ligand (PD-L1) axis, may serve as markers of disease severity. Accordingly, in this study, we evaluated the expression of PD-1/PD-L1 in patients with COVID-19. Blood immunophenotypes of hospitalized patients with moderate (n = 17, requiring oxygen support) and severe (n = 35, requiring mechanical ventilation in the intensive care setting) COVID-19 were compared and associated with clinical, laboratory, and survival data. The associations between severity and lymphocyte profiles were analysed at baseline and after 7 and 14 days of in-hospital treatment. Forty patients without COVID-19 infection were used as controls. For PD-1-positive T and B lymphocyte subsets, notable increases were observed between controls and patients with moderate or severe COVID-19 for CD4+PD-1+ T cells, CD8+PD-1+ T and CD19+PD-1+ B cells. Similar trends were observed for PD-L1-positive lymphocytes, namely, CD4+PD-L1+ T cells, CD8+PD-L1+ T cells and CD19+PD-L1+ B cells. Importantly, all markers associated with PD-1 and PD-L1 were stable over time for the analysed time points in the moderate and severe COVID-19 groups. Increased abundances of PD-1+ and PD-L1+ lymphocytes were associated with disease severity and mortality and were stable over time in patients with moderate to severe COVID-19. These immune exhaustion parameters may be attractive biomarkers of COVID-19 severity.

Increased proinflammatory cytokines in tears correspond with conjunctival SARS-CoV-2 positivity in symptomatic COVID-19 patients.

Tear fluid cytokine levels may serve as biomarkers of innate immune system response against SARS-CoV-2 infection. Therefore, our aim was to analyze panel of selected inflammatory cytokines in tears of COVID-19 patients in relation to presence of SARS-CoV-2 viral load in conjunctival secretions. In this study concentrations of TNF-α, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p70, GM-CSF, and IFN-γ were determined by a magnetic bead assay in tear film collected from 232 symptomatic COVID-19 patients. SARS-CoV-2 ocular infection was confirmed based on positive conjunctival swab-based RT-PCR testing. Viral RNA in conjunctival sac was detected in 21 patients (9%). No relation between presence and the duration of ophthalmic symptoms and SARS-CoV-2 infection detected in conjunctival secretions was found. The tear film concentrations of IFN-γ, TNF-α, IL-5, IL-8 and GM-CSF were found to be significantly greater among patients with positive conjunctival swab results as compared to the group negative for SARS-CoV-2 in conjunctival sac. Our current data depict a group of inflammatory mediators in human tears, which may play a significant role in ocular pathology of SARS-CoV-2 conjunctival infection.

SARS-CoV-2 Whole-Genome Sequencing by Ion S5 Technology-Challenges, Protocol Optimization and Success Rates for Different Strains.

The COVID-19 pandemic demonstrated how rapidly various molecular methods can be adapted for a Public Health Emergency. Whether a need arises for whole-genome studies (next-generation sequencing), fast and high-throughput diagnostics (reverse-transcription real-time PCR) or global immunization (construction of mRNA or viral vector vaccines), the scientific community has been able to answer all these calls. In this study, we aimed at the assessment of effectiveness of the commercially available solution for full-genome SARS-CoV-2 sequencing (AmpliSeq™ SARS-CoV-2 Research Panel and Ion AmpliSeq™ Library Kit Plus, Thermo Fisher Scientific). The study is based on 634 samples obtained from patients from Poland, with varying viral load, assigned to a number of lineages. Here, we also present the results of protocol modifications implemented to obtain high-quality genomic data. We found that a modified library preparation protocol required less viral RNA input in order to obtain the optimal library quantity. Concurrently, neither concentration of cDNA nor reamplification of libraries from low-template samples improved the results of sequencing. On the basis of the amplicon success rates, we propose one amplicon to be redesigned, namely, the r1_1.15.1421280, for which less than 50 reads were produced by 44% of samples. Additionally, we found several mutations within different SARS-CoV-2 lineages that cause the neighboring amplicons to underperform. Therefore, due to constant SARS-CoV-2 evolution, we support the idea of conducting ongoing sequence-based surveillance studies to continuously validate commercially available RT-PCR and whole-genome sequencing solutions.

Evaluating Ocular Symptoms and Tear Film Cytokine Profiles in Symptomatic COVID-19 Patients.

BACKGROUND: This study investigated the presence and duration of ophthalmic symptoms in the early phase of COVID-19 to assess the corresponding local immune response on the ocular surface. METHODS: The study included data from 180 COVID-19 patients and 160 age-matched healthy controls. The main finding was the occurrence of ophthalmological manifestations at the time of admission to the hospital and during the preceding 7 days. Tear film concentrations of TNF-α, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p70, GM-CSF, and IFN-γ were determined by a magnetic bead assay. RESULTS: Among the COVID-19 patients, 12.64% had at least one ocular symptom at the time of admission, and 24.14% had symptoms within the preceding 7 days (p < 0.001 vs. controls). We found that the COVID-19 patients complained more frequently about eye tearing (p = 0.04) and eye pain (p = 0.01) than controls. A multivariate analysis of the patients and controls adjusted for age and sex revealed that COVID-19 was an independent factor associated with higher VEGF and IL-10 tear film concentrations (ß = +0.13, p = 0.047 and ß = +0.34, p < 0.001, respectively) and lower IL-1ß, IL-8, and GM-CSF levels (ß = -0.25, p < 0.001; ß = -0.18, p = 0.004; and ß = -0.82, p = 0.0 respectively). CONCLUSIONS: SARS-CoV-2 does not attract a strong local response of the conjunctival immune system; therefore, ophthalmic symptoms may not constitute a substantial element in the clinical picture of novel COVID-19 infection.

Phylodynamic Dispersal of SARS-CoV-2 Lineages Circulating across Polish-German Border Provinces.

INTRODUCTION: The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has evolved into a worldwide outbreak, with significant molecular evolution over time. Large-scale phylodynamic studies allow to map the virus spread and inform preventive strategies. AIM: This study investigates the extent of binational dispersal and dynamics of SARS-CoV-2 lineages between seven border provinces of the adjacent countries of Poland and Germany to reconstruct SARS-CoV-2 transmission networks. METHODS: Following three pandemic waves from March 2020 to the end of May 2021, we analysed a dataset of 19,994 sequences divided into B.1.1.7|Alpha and non-Alpha lineage groups. We performed phylogeographic analyses using the discrete diffusion models to identify the pathways of virus spread. RESULTS: Based on population dynamics inferences, in total, 673 lineage introductions (95% HPD interval 641-712) for non-Alpha and 618 (95% HPD interval 599-639) for B.1.1.7|Alpha were identified in the area. For non-Alpha lineages, 5.05% binational, 86.63% exclusively German, and 8.32% Polish clusters were found, with a higher frequency of international clustering observed for B.1.1.7|Alpha (13.11% for binational, 68.44% German and 18.45% Polish, p < 0.001). We identified key transmission hubs for the analysed lineages, namely Saxony, West Pomerania and Lower Silesia. CONCLUSIONS: Clustering patterns between Poland and Germany reflect the viral variant transmission dynamics at the international level in the borderline area. Tracing the spread of the virus between two adjacent large European countries may provide a basis for future intervention policies in cross-border cooperation efforts against the spread of the pandemics.

Immune Signature of COVID-19: In-Depth Reasons and Consequences of the Cytokine Storm.

In the beginning of the third year of the fight against COVID-19, the virus remains at least still one step ahead in the pandemic "war". The key reasons are evolving lineages and mutations, resulting in an increase of transmissibility and ability to evade immune system. However, from the immunologic point of view, the cytokine storm (CS) remains a poorly understood and difficult to combat culprit of the extended number of in-hospital admissions and deaths. It is not fully clear whether the cytokine release is a harmful result of suppression of the immune system or a positive reaction necessary to clear the virus. To develop methods of appropriate treatment and therefore decrease the mortality of the so-called COVID-19-CS, we need to look deeply inside its pathogenesis, which is the purpose of this review.

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).

Management of SARS-CoV-2 infection: recommendations of the Polish Association of Epidemiologists and Infectiologists as of February 23, 2022.

The first Polish recommendations regarding the management of patients with COVID-19 were published by the Polish Society of Epidemiologists and Infectiologists (PTEiLChZ) on March 31, 2020, and the last annex was dated November 12, 2021. The ongoing state of pandemic, the emergence of new variants of the virus, and the availability of new drugs necessitate their updating. Changes introduced in the current version of recommendations for the management of COVID-19 comprised the possibility of using remedesivir in an outpatient setting, previously reserved for inpatient treatment, as well as other antiviral drugs-molnupiravir and nirmatrelvir / ritonavir. We revised the possibility of using monoclonal antibodies due to the resistance of the currently dominant Omicron variant. Anakinra, an antagonist of interleukin 1 receptors, has been added as a treatment option in advanced stages of the disease, and the recommended daily dose of glucocorticosteroids used in the most severe forms of COVID-19 has been increased. Information on vaccination and pre-exposure prophylaxis in specific populations has also been updated.

COVID-19-Associated Encephalopathy-Case Series and Clinical Considerations.

Neurological manifestations of the SARS-CoV-2 infection are present in up to 80% of the affected patients. While the majority of them is benign, in certain patients, viral replication in the central nervous system results in a severe disruption in cognitive function as well as basic life functions. In this case series, the authors present a detailed description of the three SARS-CoV-2 infection cases, which were all complicated by severe encephalopathy. Consecutive neurological status changes were described for each patient with detailed imaging and clinical sequelae. In the discussion, the authors highlight similarities in the course of the disease in presented patients, as well as common features in test results. An effective causal treatment could not be introduced in any of the patients, nor could the progression of the central nervous system (CNS) damage be stopped. The authors hope that the experiences they gathered will help to accelerate the diagnostic and therapeutic process in other patients with COVID-19-associated encephalopathy and result in introducing an effective treatment.