Evaluation of Reliability and Validity of the RALE and BRIXIA Chest-X Ray Scores in Patients Hospitalized with COVID-19 Pneumonia.

INTRODUCTION: Chest X-rays are commonly used to assess the severity in patients that present in the emergency department with suspected COVID-19 pneumonia, but in clinical practice quantitative scales are rarely employed. AIMS: To evaluate the reliability and validity of two semi-quantitative radiological scales in patients hospitalized for COVID-19 pneumonia (BRIXIA score and RALE score). METHODS: Patients hospitalized between October 2021 and March 2022 with confirmed COVID-19 pneumonia diagnosis were eligible for inclusion. All included patients had a chest X-ray taken in the ED before admission. Three raters that participated in the treatment and management of patients with COVID-19 during the pandemic independently assessed chest X-rays. RESULTS: Intraclass coefficients for BRIXΙA and RALES was 0.781 (0.729-0.826) and 0.825 (0.781-0.862) respectively, showing good to excellent reliability overall. Pairwise analysis was performed using quadratic weighted kappa showing significant variability in the inter-rater agreement. The prognostic accuracy of the two scores for in-hospital mortality for all raters was between 0.753 and 0.763 for BRIXIA and 0.737 and 0.790 for RALES, demonstrating good to excellent prognostic value. Both radiological scores were significantly associated with inhospital mortality after adjustment for 4C Mortality score. We found a consistent upwards trend with significant differences between severity groups in both radiological scores. CONCLUSION: Our findings suggest that BRIXIA and RALES are reliable and can be used to assess the prognosis of patients with COVID-19 requiring hospitalization. However, the inherent subjectivity of radiological scores might make it difficult to set a cut-off value suitable for all assessors.

A Literature Review of Pathophysiology, Clinical Manifestations, Medications and Optimal Dosage, Outpatient, and Post-hospitalization Use of Anticoagulation in COVID-19 Patients.

Since severe acute respiratory syndrome coronavirus 2 led to a world pandemic, extensive research has been conducted to identify its characteristics and form an appropriate management plan. One recognized complication of COVID-19 is coagulation defects that can lead to thromboembolic events. We have reviewed the literature to summarize and present the latest research about the pathophysiology, clinical manifestations, anticoagulation use and appropriate dose in COVID-19 patients, as well as the effect of anticoagulation in outpatient and post-hospital settings. The pathophysiology of coagulation abnormalities in COVID-19 is not fully understood yet, but multiple mechanisms appear to be involved, such as a direct viral attack, hyperinflammation, increased immune response, blood stasis, and endothelial injury. Clinical manifestations are mainly venous thromboembolism (deep vein thrombosis and pulmonary embolism), arterial thromboembolism, ischemic stroke, central venous sinus thrombosis, and central retinal vein occlusion. Anticoagulation is widely used in hospitalized patients with COVID-19, unless it is contraindicated. Heparinoid is the main anticoagulant used. However, the appropriate dosage is still debated as research is trying to find a balance between benefits and risks. In outpatients, it appears that anticoagulation has no benefit in contrast to post-hospitalization use, where benefit could be observed in severely affected patients. We concluded that thromboprophylaxis should be used in treating hospitalized COVID-19 patients, but the dosage is still a matter of debate. More research needs to be done on outpatient and post-hospitalized patients to derive accurate conclusions.

Effects of COVID-19 Infection and Vaccination on the Female Reproductive System: A Narrative Review

Several studies and research papers have been published to elucidate and understand the mechanism of the coronavirus disease 2019 (COVID-19) pandemic and its long-term effects on the human body. COVID-19 affects a number of organs, including the female reproductive system. However, less attention has been given to the effects of COVID-19 on the female reproductive system due to their low morbidity. The results of studies investigating the relationship between COVID-19 infection and ovarian function in women of reproductive age have shown the harmless involvement of COVID-19 infection. Several studies have reported the involvement of COVID-19 infection in oocyte quality, ovarian function, and dysfunctions in the uterine endometrium and the menstrual cycle. The findings of these studies indicate that COVID-19 infection negatively affects the follicular microenvironment and dysregulate ovarian function. Although the COVID-19 pandemic and female reproductive health have been studied in humans and animals, very few studies have examined how COVID-19 affects the female reproductive system. The objective of this review is to summarize the current literature and categorize the effects of COVID-19 on the female reproductive system, including the ovaries, uterus, and hormonal profiles. The effects on oocyte maturation, oxidative stress, which causes chromosomal instability and apoptosis in ovaries, in vitro fertilization cycle, high-quality embryos, premature ovarian insufficiency, ovarian vein thrombosis, hypercoagulable state, women's menstrual cycle, the hypothalamus-pituitary-ovary axis, and sex hormones, including estrogen, progesterone, and the anti-Müllerian hormone, are discussed in particular.

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.

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.

N-acetylcysteine efficacy in patients hospitalized with COVID-19 pneumonia: a systematic review and meta-analysis.

BACKGROUND: N-acetylcysteine (NAC) is a mucolytic agents with anti-inflammatory properties that has been suggested as an adjunctive therapy in patients with COVID-19 pneumonia. OBJECTIVES: We conducted a systematic review and meta-analysis to evaluate available evidence on the possible beneficial effects of NAC on SARS-CoV-2 infection. METHODS: In September 2022, we conducted a comprehensive search on Pubmed/Medline and Embase on randomized controlled trials (RCTs) and observational studies on NAC in patients with COVID-19 pneumonia. Study selection, data extraction and risk of bias assessment was performed by two independent authors. RCTs and observational studies were analyzed separately. RESULTS: We included 3 RCTs and 5 non-randomized studies on the efficacy of NAC in patients with COVID-19, enrolling 315 and 20826 patients respectively. Regarding in-hospital mortality, the summary effect of all RCTs was OR: 0.85 (95% CI: 0.43 to 1.67, I2=0%) and for non-randomized studies OR: 1.02 (95% CI: 0.47 to 2.23, I2=91%). Need for ICU admission was only reported by 1 RCT (OR: 0.86, 95% CI:0.44-1.69, p=0.66), while all included RCTs reported need for invasive ventilation (OR:0.91, 95% CI:0.54 to 1.53, I2=0). Risk of bias was low for all included RCTs, but certainty of evidence was very low for all outcomes due to serious imprecision and indirectness. CONCLUSION: The certainty of evidence in the included studies was very low, thus recommendations for clinical practice cannot be yet made. For all hard clinical outcomes point estimates in RCTs are close to the line of no effect, while observational studies have a high degree of heterogeneity with some of them suggesting favorable results in patients receiving NAC. More research is warranted to insure that NAC is both effective and safe in patients with COVID-19 pneumonia.

The Effect of Long COVID-19 Infection and Vaccination on Male Fertility; A Narrative Review.

Earlier research has suggested that the male reproductive system could be particularly vulnerable to SARS-CoV-2 (COVID-19) infection, and infections involving this novel disease not only pose serious health threats but could also cause male infertility. Data from multi-organ research during the recent outbreak indicate that male infertility might not be diagnosed as a possible consequence of COVID-19 infection. Several review papers have summarized the etiology factors on male fertility, but to date no review paper has been published defining the effect of COVID-19 infection on male fertility. Therefore, the aim of this study is to review the published scientific evidence regarding male fertility potential, the risk of infertility during the COVID-19 pandemic, and the impact of COVID-19 vaccination on the male reproductive system. The effects of COVID-19 infection and the subsequent vaccination on seminal fluid, sperm count, sperm motility, sperm morphology, sperm viability, testes and sex hormones are particularly reviewed.

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.

The Role of High Flow Nasal Oxygen in the Management of Severe COVID-19: A Systematic Review.

INTRODUCTION: Oxygen therapy remains the cornerstone for managing patients with severe SARS-CoV-2 infection and several modalities of non-invasive ventilation are used worldwide. High-flow oxygen via nasal canula is one therapeutic option which may in certain cases prevent the need of mechanical ventilation. The aim of this review is to summarize the current evidence on the use of high-flow nasal oxygen in patients with severe SARS-CoV-2 infection. MATERIAL AND METHODS: We conducted a systematic literature search of the databases PubMed and Cochrane Library until April 2021 using the following search terms: "high flow oxygen and COVID-19" and "high flow nasal and COVID-19". RESULTS: Twenty-three articles were included in this review, in four of which prone positioning was used as an adjunctive measure. Most of the articles were cohort studies or case series. High-flow nasal oxygen therapy was associated with a reduced need for invasive ventilation compared to conventional oxygen therapy and led to an improvement in secondary clinical outcomes such as length of stay. The efficacy of high-flow nasal oxygen therapy was comparable to that of other non-invasive ventilation options, but its tolerability is likely higher. Failure of this modality was associated with increased mortality. CONCLUSION: High flow nasal oxygen is an established option for respiratory support in COVID-19 patients. Further investigation is required to quantify its efficacy and utility in preventing the requirement of invasive ventilation.

Introdução: A oxigenoterapia continua a ser o pilar do tratamento de doentes com infecção grave por SARS-CoV-2 e várias modalidades de ventilação não invasiva são usadas em todo o mundo. O oxigénio de alto fluxo via cânula nasal é uma opção terapêutica que pode, em certos casos, evitar a necessidade de ventilação mecânica. Material e Métodos: Realizámos uma pesquisa sistemática da literatura nas bases de dados PubMed e Cochrane Library até abril de 2021 usando os seguintes termos de pesquisa: "oxigénio de alto fluxo e COVID-19" e "alto fluxo nasal e COVID-19". Resultados: Vinte e três artigos foram incluídos nesta revisão, em quatro dos quais a posição de decúbito ventral foi usada como medida adjuvante. A maioria dos artigos eram estudos de coorte ou séries de casos. A oxigenoterapia nasal de alto fluxo pode reduzir a necessidade de ventilação invasiva em comparação com a oxigenoterapia convencional e pode melhorar os resultados clínicos. A eficácia da oxigenoterapia nasal de alto fluxo é comparável à de outras opções de ventilação não invasiva, embora a sua tolerabilidade seja provavelmente superior. O insucesso dessa modalidade está associado ao aumento da mortalidade. Conclusão: O oxigénio nasal de alto fluxo é uma opção estabelecida para suporte respiratório em doentescom COVID-19. É necessária investigação adicional para medir a sua eficácia e utilidade na prevenção da necessidade de ventilação invasiva.

SARS-CoV-2 infection in adults and HIV: an update.

Aim COVID-19 pandemic caused by SARS-CoV-2 is spreading throughout the world affecting both healthy individuals and people with underlying immune-deficiencies. People living with human immunodeficiency virus (HIV) consist a group multiply affected by this universal crisis. Methods Literature search aiming to identify relevant publications referring to the consequences of the COVID-19 pandemic in HIV infected population. Results A body of literature is rapidly growing in regard to epidemiological data, the interaction between HIV and SARS-CoV-2, and clinical outcome in people living with HIV. Intensive research is warranted to identify any interactions of the co-existence of the two viruses in the immune system of HIV infected patients as common pathophysiology and molecular aspects are recognized. Human relations are diminished as a result of the social measures, and detailed recording of the consequences in this population is needed. Conclusion Further research could shed light on the common underlying molecular mechanisms of both conditions in an attempt to discover treatment regimens for SARS-CoV-2 infection.

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.