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.

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 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.

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.

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.

Continuous positive airway pressure in the treatment of COVID-19 patients with respiratory failure. A report of six cases with excellent outcome.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently considered a significant threat to global health and global economy. This new rapidly spreading virus causes enormous stress to healthcare systems as large number of patients present with respiratory failure, needing intubation and mechanical ventilation. While the industry is racing to meet the rising demand for ventilators, all the alternative respiratory support modalities are employed to save lives in hospitals around the globe. We hereby report 6 patients who were diagnosed with SARS-CoV-2 and treated with continuous positive airway pressure in a negative pressure isolated room in a tertiary center in western Greece. The rapid progression of mild flu-like symptoms to respiratory failure in all patients was controlled with the use of continuous positive airway pressure making this strategy a reasonable alternative to respiratory failure due to SARS-CoV-2 as it may avert intubation and mechanical ventilation.

High flow nasal cannula oxygen therapy in adults with COVID-19 respiratory failure. A case report.

The novel corona virus (SARS-CoV-2) continuous to spread around the globe causing high mortality, tremendous stress on healthcare systems and an unprecedented disruption of everyday life with unpredictable socioeconomic ramifications. The diseaseis typically affecting the respiratory system and some patients will develop refractory hypoxemic respiratory insufficiency requiring mechanical ventilation. The role of non-invasive ventilation (NIV), high flow nasal cannula (HFNC) or continuous positive airway pressure devices (C-PAP) in the treatment of the 2019 corona virus disease (COVID-19) is not yet clear. We hereby report a case of a 44-year-old COVID-19 positive male patient suffering from hypoxic respiratory failure that was successfully treated with high flow nasal cannula oxygen therapy in a negative pressure intensive care room. Although specific criteria for the use of high flow nasal canula devices COVID-19 are not available at this time, clinicians could use this non-invasive modality as analternative method of respiratory support in selected patients presenting with respiratory failure.