Intestinal barrier dysfunction as a key driver of severe COVID-19.

The intestinal lumen harbors a diverse consortium of microorganisms that participate in reciprocal crosstalk with intestinal immune cells and with epithelial and endothelial cells, forming a multi-layered barrier that enables the efficient absorption of nutrients without an excessive influx of pathogens. Despite being a lung-centered disease, severe coronavirus disease 2019 (COVID-19) affects multiple systems, including the gastrointestinal tract and the pertinent gut barrier function. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can inflict either direct cytopathic injury to intestinal epithelial and endothelial cells or indirect immune-mediated damage. Alternatively, SARS-CoV-2 undermines the structural integrity of the barrier by modifying the expression of tight junction proteins. In addition, SARS-CoV-2 induces profound alterations to the intestinal microflora at phylogenetic and metabolomic levels (dysbiosis) that are accompanied by disruption of local immune responses. The ensuing dysregulation of the gut-lung axis impairs the ability of the respiratory immune system to elicit robust and timely responses to restrict viral infection. The intestinal vasculature is vulnerable to SARS-CoV-2-induced endothelial injury, which simultaneously triggers the activation of the innate immune and coagulation systems, a condition referred to as "immunothrombosis" that drives severe thrombotic complications. Finally, increased intestinal permeability allows an aberrant dissemination of bacteria, fungi, and endotoxin into the systemic circulation and contributes, to a certain degree, to the over-exuberant immune responses and hyper-inflammation that dictate the severe form of COVID-19. In this review, we aim to elucidate SARS-CoV-2-mediated effects on gut barrier homeostasis and their implications on the progression of the disease.

Association of Antiretroviral Therapy with Platelet Function and Systemic Inflammatory Response in People Living with HIV: A Cross-Sectional Study.

People living with HIV (PLWHIV) present an increased risk of adverse cardiovascular events. We aimed to assess whether antiretroviral therapy (ART) pharmacologically enhances platelet reactivity and platelet activation intensity, and explore the potential association with underlying inflammatory status. This was a cross-sectional cohort study carried out among PLWHIV on diverse ART regimens. Platelet reactivity and activation intensity were assessed using the bedside point-of-care VerifyNow assay, in P2Y12 reaction units (PRU), measurements of monocyte-platelet complexes, and P-selectin and GPIIb/IIIa expression increase, following activation with ADP, respectively. Levels of major inflammatory markers and whole blood parameters were also evaluated. In total, 71 PLWHIV, 59 on ART and 22 healthy controls, were included in this study. PRU values were significantly elevated in PLWHIV compared to controls [Mean; 257.85 vs. 196.67, p < 0.0001], but no significant differences were noted between ART-naïve or ART-experienced PLWHIV, or between TAF/TDF and ABC based regimens, similar to systemic inflammatory response. However, within-group analysis showed that PRUs were significantly higher in ABC/PI vs ABC/INSTI or TAF/TDF + PI patients, in line with levels of IL-2. PRU values did not correlate strongly with CD4 counts, viral load, or cytokine values. P-selectin and GPIIb/IIIa expression increased following ADP activation and were significantly more prominent in PLWHIV (p < 0.005). Platelet reactivity and platelet activation intensity were shown to be increased in PLWHIV, but they did not appear to be related to ART initiation, similar to the underlying systemic inflammatory response.

Alterations in gut immunological barrier in SARS-CoV-2 infection and their prognostic potential.

Although coronavirus disease 2019 (COVID-19) is primarily associated with mild respiratory symptoms, a subset of patients may develop more complicated disease with systemic complications and multiple organ injury. The gastrointestinal tract may be directly infected by SARS-CoV-2 or secondarily affected by viremia and the release of inflammatory mediators that cause viral entry from the respiratory epithelium. Impaired intestinal barrier function in SARS-CoV-2 infection is a key factor leading to excessive microbial and endotoxin translocation, which triggers a strong systemic immune response and leads to the development of viral sepsis syndrome with severe sequelae. Multiple components of the gut immune system are affected, resulting in a diminished or dysfunctional gut immunological barrier. Antiviral peptides, inflammatory mediators, immune cell chemotaxis, and secretory immunoglobulins are important parameters that are negatively affected in SARS-CoV-2 infection. Mucosal CD4+ and CD8+ T cells, Th17 cells, neutrophils, dendritic cells, and macrophages are activated, and the number of regulatory T cells decreases, promoting an overactivated immune response with increased expression of type I and III interferons and other proinflammatory cytokines. The changes in the immunologic barrier could be promoted in part by a dysbiotic gut microbiota, through commensal-derived signals and metabolites. On the other hand, the proinflammatory intestinal environment could further compromise the integrity of the intestinal epithelium by promoting enterocyte apoptosis and disruption of tight junctions. This review summarizes the changes in the gut immunological barrier during SARS-CoV-2 infection and their prognostic potential.

Tocilizumab versus baricitinib in hospitalized patients with severe COVID-19: an open label, randomized controlled trial.

OBJECTIVE: Randomized controlled trials comparing tocilizumab and baricitinib in patients with coronavirus disease 2019 (COVID-19) are needed. This was an open-label, randomized controlled trial aiming to address this unmet need. METHODS: To determine whether baricitinib was non-inferior to tocilizumab, we assessed whether the upper boundary of the two-sided 95% CI of the hazard ratio (HR) did not exceed 1.50. The primary outcome was mechanical ventilation or death by day 28. Secondary outcomes included time to hospital discharge by day 28 and change in WHO progression scale at day 10. RESULTS: We assigned 251 patients with COVID-19 and a PaO2/FiO2 ratio of <200 to receive either tocilizumab (n = 126) or baricitinib (n = 125) plus standard of care. Baricitinib was non-inferior to tocilizumab for the primary composite outcome of mechanical ventilation or death by day 28 (mechanical ventilation or death for patients who received baricitinib, 39.2% [n = 49/125]; mechanical ventilation or death for patients who received tocilizumab, 44.4% [n = 56/126]; HR, 0.83; 95% CI, 0.56-1.21; p 0.001 for non-inferiority). Baricitinib was non-inferior to tocilizumab for the time to hospital discharge within 28 days (patients who received baricitinib- discharged alive: 58.4% [n = 73/125] vs. patients who received tocilizumab- discharged alive: 52.4% [n = 66/126]; HR, 0.85; 95% CI, 0.61-1.18; p < 0.001 for non-inferiority). There was no significant difference between the baricitinib and tocilizumab arms in the change in WHO scale at day 10 (0.0 [95% CI, 0.0-0.0] vs. 0.0 [95% CI, 0.0-1.0]; p 0.83). DISCUSSION: In the setting of this trial, baricitinib was non-inferior to tocilizumab with regards to the composite outcome of mechanical ventilation or death by day 28 and the time to discharge by day 28 in patients with severe COVID-19.

Impact of Bacterial Infections on COVID-19 Patients: Is Timing Important?

BACKGROUND: Along with important factors that worsen the clinical outcome of COVID-19, it has been described that bacterial infections among patients positive for a SARS-CoV-2 infection can play a dramatic role in the disease process. Co-infections or community-acquired infections are recognized within the first 48 h after the admission of patients. Superinfections occur at least 48 h after admission and are considered to contribute to a worse prognosis. Microbiologic parameters differentiate infections that happen after the fifth day of hospitalization from those appearing earlier. Specifically, after the fifth day, the detection of resistant bacteria increases and difficult microorganisms emerge. OBJECTIVES: The aim of the study was to evaluate the impact of bacterial infections in patients with COVID-19 on the length of the hospital stay and mortality. METHODS: A total of 177 patients hospitalized due to COVID-19 pneumonia were consecutively sampled during the third and fourth wave of the pandemic at a University Hospital in Greece. A confirmed bacterial infection was defined as positive blood, urinary, bronchoalveolar lavage (BAL) or any other infected body fluid. Patients with confirmed infections were further divided into subgroups according to the time from admission to the positive culture result. RESULTS: When comparing the groups of patients, those with a confirmed infection had increased odds of death (odds ratio: 3.634; CI 95%: 1.795-7.358; p < 0.001) and a longer length of hospital stay (median 13 vs. 7 days). A late onset of infection was the most common finding in our cohort and was an independent risk factor for in-hospital death. Mortality and the length of hospital stay significantly differed between the subgroups. CONCLUSION: In this case series, microbial infections were an independent risk factor for a worse outcome among patients with COVID-19. Further, a correlation between the onset of infection and a negative outcome in terms of non-infected, community-acquired, early hospital-acquired and late hospital-acquired infections was identified. Late hospital-acquired infections increased the mortality of COVID-19 patients whilst superinfections were responsible for an extended length of hospital stay.

Efficacy of Fosfomycin-Containing Regimens for Treatment of Bacteremia Due to Pan-Drug Resistant Acinetobacter baumannii in Critically Ill Patients: A Case Series Study.

Acinetobacter baumannii (AB) has evolved over the last decades as a major problem in carbapenem-resistant gram-negative nosocomial infections, associated with high mortality rates especially in the intensive care unit (ICU). Recent reports highlight the increasing prevalence of resistance to colistin, a last resort therapeutic option for carbapenem-resistant AB. We retrospectively evaluated the characteristics, treatment regimens and outcomes of twenty patients with pan-drug resistant (PDR) AB primary bacteremia hospitalized in the ICU of the University General Hospital of Patras, during a two-year period (October 2020-September 2022). The 28-day mortality reached 50%. Between survivors and non-survivors, no differences were found regarding age, gender, and Charlson comorbidity index (CCI). However, non-survivors had higher APACHE II scores and higher prevalence of septic shock and COVID-19 infection. A significantly higher percentage in the survivor group received Fosfomycin as part of the combination regimen. Inclusion of fosfomycin in the combination therapeutic regimen was associated with significantly better survival as compared to non-fosfomycin-containing regimens. In view of the increasing prevalence of PDR-AB infections in ICUs, its associated high rates of mortality and the lack of effective treatment options, the observed survival benefit with fosfomycin inclusion in the therapeutic regimen merits further validation in larger prospective studies.

Alterations in Laboratory Parameters Related to Disease Severity in Vaccinated Patients Against SARS-CoV-2.

Background: Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide with global financial and health care systems consequences. It is already well recognized that immunization against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a precondition for blocking mutations and prevent the emergence of variants. The aim of the study was to investigate the possible relationship between COVID-19 vaccines and the commonly used disease-related blood biomarkers. Methods: Adult patients with confirmed SARS-CoV-2 infection who were hospitalized from November 8, 2021, to December 31, 2021, were included. The retrospective study was conducted in Patras University Hospital, Greece. Two groups of patients were assessed, the ones who were previously vaccinated against SARS-CoV-2 (group A, n = 21), and those who were not (group B, n = 55). After analysis of peripheral blood, we calculated on admission day for each patient the total white blood cell (WBC), absolute lymphocytes count (ALC), absolute monocyte count, D-dimers, C-reactive protein (CRP) plasma levels, lactate dehydrogenase (LDH), ferritin, high-sensitive troponin, as well as the arterial oxygen partial pressure/fractional inspired oxygen (PO2/FiO2) ratio. Results: The median age of all patients was 65.3 ± 15.2 years old; 68.4% were men and 31.6% were women. Comorbidities were present in 51 patients (67.1%). Hypertension and diabetes were observed as the most common comorbidities (33.3%). About 72.4% of the patients were unvaccinated or have received the first dose of vaccine, and 27.6% were completely vaccinated. No statistical difference was found in the total WBC count and ALC between the two groups (group A vs. group B: 8,168.95 ± 7,584.4 vs. 8,521.9 ± 6,571.3, P = 0.848 and 3,052.1 ± 7,230.7 vs. 1,279.6 ± 1,218.6, P = 0.087). Monocytes count in both groups did not show statistical difference: group A vs. group B: 672.6 ± 384.7 vs. 637.9 ± 477.8 (P = 0.754). Similarly, no difference for D-dimers (1,348.5 ± 1,397.6 vs. 1,850.9 ± 3,877.5, P = 0.575), ferritin (1,082.8 ± 1,399.5 vs. 1,327.4 ± 1,307.8, P = 0.508), high-sensitive troponin (113.6 ± 318.1 vs. 157.5 ± 48.8, P = 0.252), and CRP (6.92 ± 4.9 vs. 7.4 ± 5.9, P = 0.732). For LDH plasma levels, the statistical difference was significant (274.2 ± 85.6 vs. 387.5 ± 223.4, P = 0.003), as well as for the PO2/FiO2 ratio (355.6 ± 129.7 vs. 260.5 ± 123.3, P = 0,006). Conclusions: In a mixed population hospitalized for COVID-19, only LDH plasma levels and the PaO2/FiO2 on admission day showed statistically significant difference between vaccinated and unvaccinated patients. Although unvaccinated patients are more likely to develop severe illness, they did not express significantly higher values of commonly used plasma biomarkers such as ferritin, CRP, and D-dimers which are related to disease severity.

Greek Remdesivir Cohort (GREC) Study: Effectiveness of Antiviral Drug Remdesivir in Hospitalized Patients with COVID-19 Pneumonia.

In several randomized studies, remdesivir (RDV) has been reported to shorten the recovery period and improve clinical outcomes in COVID-19 patients, and thus, it is recommended as a standard of care. Nevertheless, controversial reports have been published. The aim of the present study is to evaluate the effectiveness of remdesivir in hospitalized patients with COVID-19 pneumonia at three Greek University Departments of Infectious Diseases with homogenous treatment protocols. From September 2020 to February 2021, we retrospectively analyzed adults hospitalized with confirmed SARS-CoV-2 infection and radiological findings of pneumonia, who received remdesivir once daily for five days. Exploratory end points were duration of hospitalization, time of intubation, and death. Overall, 551 patients were included in the study. The optimal cutoff point for the number of days needed after symptom initiation for drug administration associated with better clinical outcome was 7 days. Higher odds for discharge and lower for intubation were observed in patients with treatment initiation ≤7 days (p = 0.052 and p = 0.019, retrospectively) regardless of gender (p = 0.537), hypertension (p = 0.096), dyslipidemia (p = 0.221), diabetes mellitus (p = 0.306), and usage of immunomodulators (p = 0.408). Our study has demonstrated beneficial effects of early treatment with remdesivir (≤7 days from symptom onset) on rates of intubation and probability of discharge.

External validation of the 4C Mortality Score and PRIEST COVID-19 Clinical Severity Score in patients hospitalized with COVID-19 pneumonia in Greece.

Background: Prognostic scores can be used to facilitate better management of patients suffering from life-threatening diseases, provided that they have been tested in the population of interest. Aim: To perform external validation of the 4C Mortality Score and PRIEST COVID-19 Clinical Severity Score. Study Design: Prospective observational Study. Methods: Patients hospitalized with COVID-19 pneumonia in a tertiary hospital in Greece were enrolled in the study. The prognostic scores were calculated based on hospital admission data and ROC curve analysis was performed. We assessed a composite outcome of either in-hospital death or need for invasive ventilation. Results: Both 4C and PRIEST scores showed good discriminative ability with an AUC value of 0.826 (CI 95%: 0.765-0.887) and 0.852 (CI 95%: 0.793-0.910) respectively. Based on the Youden Index the optimal cut-off for the 4C score was 11 (Sensitivity 75%, Specificity 75.5%) and 10 for the PRIEST score (Sensitivity 83% and Specificity 69.4%). Calibration was adequate for both scores, except for the low and very high risk groups in the PRIEST score. Conclusion: The 4C Mortality Score and PRIEST COVID-19 Clinical Severity Score can be used for early identification of patients with poor prognosis in a Greek population cohort hospitalized with COVID-19.

SARS CoV-2-Induced Viral Sepsis: The Role of Gut Barrier Dysfunction.

A considerable proportion of patients with severe COVID-19 meet Sepsis-3 criteria and share common pathophysiological mechanisms of multiorgan injury with bacterial sepsis, in absence of secondary bacterial infections, a process characterized as "viral sepsis". The intestinal barrier exerts a central role in the pathophysiological sequence of events that lead from SARS-CoV-2 infection to severe systemic complications. Accumulating evidence suggests that SARS-CoV-2 disrupts the integrity of the biological, mechanical and immunological gut barrier. Specifically, microbiota diversity and beneficial bacteria population are reduced, concurrently with overgrowth of pathogenic bacteria (dysbiosis). Enterocytes' tight junctions (TJs) are disrupted, and the apoptotic death of intestinal epithelial cells is increased leading to increased gut permeability. In addition, mucosal CD4(+) and CD8(+) T cells, Th17 cells, neutrophils, dendritic cells and macrophages are activated, and T-regulatory cells are decreased, thus promoting an overactivated immune response, which further injures the intestinal epithelium. This dysfunctional gut barrier in SARS-CoV-2 infection permits the escape of luminal bacteria, fungi and endotoxin to normally sterile extraintestinal sites and the systemic circulation. Pre-existing gut barrier dysfunction and endotoxemia in patients with comorbidities including cardiovascular disease, obesity, diabetes and immunosuppression predisposes to aggravated endotoxemia. Bacterial and endotoxin translocation promote the systemic inflammation and immune activation, which characterize the SARS-CoV-2 induced "viral sepsis" syndrome associated with multisystemic complications of severe COVID-19.

Factors associated with anti-SARS-CoV-2 antibody titres 3 months post-vaccination with the second dose of BNT162b2 vaccine: a longitudinal observational cohort study in western Greece.

OBJECTIVES: Vaccination against SARS-CoV-2 has been extensively deployed during COVID-19 pandemic. One efficient method to evaluate response to vaccination is the assessment of humoral immunity by measuring SARS-CoV-2 antibody titres. We investigated the association between anthropometric parameters (age, body mass index), smoking, diabetes, statin use, hypertension, levels of 25(OH)D and dehydroepiandrosterone sulfate (DHEAS), and SARS-CoV-2 antibody titres after vaccination. DESIGN: In this longitudinal observational cohort study, 712 subjects were tested for SARS-CoV-2 antibodies 3 months after the second dose of BNT162b2 vaccine. Multiple linear regression analysis was performed to identify which factors are associated with the antibody titres. SETTING: Healthcare units of western Greece (University Hospital of Patras and "St Andrews" State General Hospital of Patras). PARTICIPANTS: All adults receiving their second dose of BNT162b2 vaccine at the participating healthcare units were eligible to participate in the study. Exclusion criteria were SARS-CoV-2 infection or positive SARS-CoV-2 antibody titre at baseline. Patients who did not provide all necessary information were excluded from our analyses. RESULTS: We found age to be negatively associated with antibody titre (-0.005; 95% CI -0.009 to -0.001, p=0.0073), as was male gender (-0.11; 95% CI -0.1738 to -0.04617, p=0.0008). The interaction of age and gender was significant (-0.01090; 95% CI -0.01631 to -0.005490, p<0.0001), highlighting that the rate of decline in antibody titre with increasing age tends to be higher in men rather than in women. No linear trend was found between DHEAS levels and antibody titres when the lower quartile of DHEAS levels was used as reference. Tobacco use was associated with low antibody titre (-0.1097; 95% CI -0.174 to -0.046, p=0.0008) but overweight, obese or underweight subjects had similar antibody responses to normal-weight individuals. Although subjects with diabetes and hypertension had numerically lower antibody titres, this association was not statistically significant. Vitamin D levels showed no clear relationships with antibody titres. CONCLUSIONS: Age, male gender and tobacco use are negatively associated with antibody titres after COVID-19 vaccination, but our data showed no clear correlation with vitamin D levels. TRIAL REGISTRATION NUMBER: NCT04954651; Results.

Increased incidence of candidemia in critically ill patients during the Coronavirus Disease 2019 (COVID-19) pandemic.

BACKGROUND: Patients with severe Coronavirus Disease 2019 (COVID-19) are treated with corticosteroids. AIM: We aimed to evaluate the role of corticosteroid treatment in candidemia development during the COVID-19 pandemic. METHODS: This retrospective study was conducted in a Greek ICU, from 2010 to August 2021, encompassing a pre-pandemic and a pandemic period (pandemic period: April 2020 to August 2021). All adult patients with candidemia were included. RESULTS: During the study period, 3,572 patients were admitted to the ICU, 339 patients during the pandemic period, of whom 196 were SARS-CoV-2-positive. In total, 281 candidemia episodes were observed in 239 patients, 114 in the pandemic period. The majority of candidemias in both periods were catheter-related (161; 50.4%). The incidence of candidemia in the pre-pandemic period was 5.2 episodes per 100 admissions, while in the pandemic period was 33.6 (p < 0.001). In the pandemic period, the incidence among COVID-19 patients was 38.8 episodes per 100 admissions, while in patients without COVID-19 incidence was 26.6 (p = 0.019). Corticosteroid administration in both periods was not associated with increased candidemia incidence. CONCLUSIONS: A significant increase of candidemia incidence was observed during the pandemic period in patients with and without COVID-19. This increase cannot be solely attributed to immunosuppression (corticosteroids, tocilizumab) of severe COVID-19 patients, but also to increased workload of medical and nursing staff.

Tocilizumab improves 28-day survival in hospitalized patients with severe COVID-19: an open label, prospective study.

BACKGROUND: Data on the safety and efficacy profile of tocilizumab in patients with severe COVID-19 needs to be enriched. METHODS: In this open label, prospective study, we evaluated clinical outcomes in consecutive patients with COVID-19 and PaO2/FiO2 < 200 receiving tocilizumab plus usual care versus usual care alone. Tocilizumab was administered at the time point that PaO2/FiO2 < 200 was observed. The primary outcome was 28-day mortality. Secondary outcomes included time to discharge, change in PaO2/FiO2 at day 5 and change in WHO progression scale at day 10. FINDINGS: Overall, 114 patients were included in the analysis (tocilizumab plus usual care: 56, usual care: 58). Allocation to usual care was associated with significant increase in 28-day mortality compared to tocilizumab plus usual care [Cox proportional-hazards model: HR: 3.34, (95% CI: 1.21-9.30), (p = 0.02)]. There was not a statistically significant difference with regards to hospital discharge over the 28 day period for patients receiving tocilizumab compared to usual care [11.0 days (95% CI: 9.0 to 16.0) vs 14.0 days (95% CI: 10.0-24.0), HR: 1.32 (95% CI: 0.84-2.08), p = 0.21]. ΔPaO2/FiO2 at day 5 was significantly higher in the tocilizumab group compared to the usual care group [42.0 (95% CI: 23.0-84.7) vs 15.8 (95% CI: - 19.4-50.3), p = 0.03]. ΔWHO scale at day 10 was significantly lower in the tocilizumab group compared to the usual care group (-0.5 ± 2.1 vs 0.6 ± 2.6, p = 0.005). CONCLUSION: Administration of tocilizumab, at the time point that PaO2/FiO2 < 200 was observed, improved survival and other clinical outcomes in hospitalized patients with severe COVID-19 irrespective of systemic inflammatory markers levels.

Evaluation of Plasma Soluble Urokinase Plasminogen Activator Receptor Levels in Patients With COVID-19 and Non-COVID-19 Pneumonia: An Observational Cohort Study.

BACKGROUND: The respiratory system is the main system affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and a great number of infected people need hospitalization. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker indicative of acute and chronic inflammation. Current literature supports that suPAR has great predictive ability for mortality in patients with coronavirus disease 2019 (COVID-19). The aim of this study was to compare the value of suPAR and other laboratory biomarkers in patients with chest infection and suspected COVID-19. METHODS: A total of 41 consecutive patients with chest infection were enrolled in the study and were assigned into two groups according to the real-time polymerase chain reaction (PCR) result for SARS-CoV-2. The two groups had no significant difference in baseline data (age, sex), arterial oxygen partial pressure (PO2)/fraction of inspired oxygen (FiO2) ratio and mortality. RESULTS: Among patients with chest infection who required hospitalization, suPAR was significantly higher on admission in those with COVID-19 when compared to patients with non-COVID-19. suPAR had a great prognostic ability for in-hospital mortality in the COVID-19 subgroup. CONCLUSIONS: A single measurement of suPAR on admission can provide prognostic information for patients with suspected COVID-19 pneumonia. In the subgroup of patients with positive real-time PCR result for SARS-CoV2, suPAR was significantly higher and had an excellent prognostic value for the in-hospital mortality.

Evaluation of Admission Chest X-Ray Findings in Patients With Respiratory Infection During the COVID-19 Pandemic

Aims: To evaluate the prevalence of X-ray findings in hospitalized patients requiring hospitalization with suspected Coronavirus disease 2019 (COVID-19) infection and potential differences in the laboratory values and clinical outcomes related to the presence of abnormal chest X-ray (CXR) findings. Methods: A total of 117 patients suspected of COVID-19 pneumonia and hospitalized with symptoms of lower respiratory tract disease were included in this study. Patients were divided into subgroups according to COVID-19 diagnosis and statistical comparisons were made according to CXR findings. Results: In our cohort, CXR abnormalities were more common in patients with confirmed COVID-19 diagnosis and were associated with increased mortality. Patients with abnormal chest X-rays had a significantly lower PaO2/FiO2 ratio both in the COVID-19 and non-COVID-19 groups. Conclusion: CXR is a routine examination in all patients with symptoms of lower respiratory tract disease and its findings relate to in-hospital mortality and PaO2/FiO2 ratio. Thus, it can be a significant measure of disease severity, especially in resource restrained settings and emergency situations such as the COVID-19 pandemic.

Red Blood Cell Distribution Width: Another Prognostic Factor for COVID-19?

The coronavirus disease 2019 (COVID-19) is a pandemic with a high rate of hospitalization, admission to intensive care units, and mortality. Identifying patients at the highest risk for severe disease is important to facilitate early, aggressive intervention. High red blood cell distribution width (RDW) values are associated with increased mortality in the general population in patients suffering from several conditions, including cardiovascular disease, sepsis, acute kidney injury, chronic obstructive pulmonary disease, and hepatitis B. Our study aimed to determine whether RDW levels in all COVID-19 confirmed cases admitted to the Patras University Hospital, Greece, was an independent prognostic factor of hospitalization and disease outcome.

Elements of Th1/Th2 response and disease severity in COVID-19 patients: A short report.

The presence of a complex immune dysregulation syndrome has been established in COVID-19 patients. We aimed to assess Th1/Th2 response in COVID-19 patients and its association with disease severity by performing a prospective cohort study in a tertiary hospital COVID-19 referral center. We report no difference between Th1/Th2 responses between patients with severe and mild disease, except for levels of interleukin-6 (IL-6) and IL-10. Future larger studies should examine lung-specific versus systemic inflammatory responses, as well as, diverse immunotypes driving poor clinical outcomes.

Evaluation of four novel prognostic scores on admission for COVID-19 mortality. An experience from a Mediterranean tertiary center.

AIM: To assess the performance of four novel prognostic scores on admission in predicting in-hospital mortality in patients with confirmed SARS-CoV-2 infection and compare it to NEWS2 and respiratory SOFA score. METHODS: A total of 85 adult patients admitted to a tertiary hospital in Western Greece with positive SARS-CoV-2 PCR test, were enrolled and divided into the non-survivor (n = 10) and survivor (n = 75) groups. Receiver Operating Characteristic (ROC) analysis was conducted to determine the predictive effect of the COVID-19 Mortality Score, COVID-19 Severity Index, 4 C Mortality Score and COVID-IRS NLR. Subsequently, they were compared to the respiratory component of the SOFA score and NEWS2. RESULTS: ROC curve analysis showed that the COVID-19 Mortality Score (score ≥4) had the highest combination of sensitivity and specificity values for predicting in-hospital mortality (Sensitivity = 0.8, Specificity = 0.853). The Area Under Curve (AUC) for predicting in hospital mortality for the COVID-19 Mortality Score, COVID-19 Severity Index, 4 C Mortality Score and COVID-IRS NLR were 0.846, 0.815, 0.789 and 0.787, respectively. Comparison between the AUC of the four novel COVID-19 scores, respiratory SOFA and NEWS2 showed no significant differences. CONCLUSION: All four novel prognostic scores had acceptable to excellent AUC values for predicting in hospital mortality. Out of the four novel prognostic scores for patients with COVID-19, the COVID-19 mortality score showed the best results in our cohort. Its prognostic ability was superior to that of the NEWS2 and respiratory SOFA score.