ABSTRACT
Response to SARS-CoV-2 varies greatly among patients, from no symptoms to mild or severe disease that may end with death. The disease severity differs according to the host immune response and hence treatment plans differ. This review aimed to insight clearly the pathophysiology of the disease and to develop strategies either to enhance the compromised immunity or to modulate the hyperactive immune response in COVID-19. PubMed/MEDLINE, ScienceDirect, Scopus, Research Gate and Google Scholar have been searched and reviewed for the different pathways of COVID-19 pathogenesis. The host immune response against COVID-19 virus ends in one of these three pathways, these are either: (1) With virus clearance that occurs through highly orchestrated dialogue among innate and adaptive immune cells, or (2) Immune hyperactivity that results in cytokine storm through massive production of inflammatory mediators, which makes the cell out of control and ends with acute respiratory distress syndrome or (3) Immune-mediated coagulopathy, which induces disseminated intravascular coagulation which in most patients ultimately ends with death. In conclusion, the state of entanglement between the virus and its host is a struggle that can spin out of immune system control. The precise understanding of the current COVID-19 pathophysiology should direct the treatment strategy in such a way to protect the patient from serious infection complications.
ABSTRACT
Introduction: Coronavirus has caused more than a million deaths as of October 2020. Hospitals consider tracheostomy after the patient is virus negative, usually after 3 weeks. Prevalence and timing of tracheostomy and its impact on survival among COVID patients are unknown. Methods: A retrospective, single-center study of all patients with COVID-19 ARDS who underwent tracheostomy was conducted. Patients with age <18 and patients treated with ECMO were excluded. Duration of ventilation before tracheostomy was recorded. Clinical variables, outcome variables, and confounding variables were recorded and compared between patients with tracheostomy and without tracheostomy. The aim was to determine prevalence and timing of tracheostomy and its impact on clinical outcomes. Results: We found that tracheostomies were performed only in 21 out of 196 patients (10.8%). Tracheostomies were performed after 3 weeks on average (22.1 ± 7.5 days). Survival was significantly higher in patients who underwent tracheostomy (85.7 vs. 42.5%, p = 0.001). LOSICU was longer for tracheostomy patients than patients without tracheostomy (median [IQR]: 35 [23-47] vs. 15 [9-21], p = 0.001). Patients who underwent tracheostomy had a higher proportion of treatment with continuous renal replacement therapy (CRRT) (52 vs. 30%, p = 0.04), more COVID-19 swab testing (6.5 [4.5-8.5] vs. 5 [3-7], p = 0.002), more days on mechanical ventilation (34.5 [24-45] vs. 11 [5.5-16.5], p = 0.001), and more length of stay in the hospital (54 [38-70] vs. 20 [10.5-29.5], p = 0.001). All other factors were not statistically different between the 2 groups. Approximately 29% of patients had possible false-negative testing as their swab became positive after being negative. Conclusion: Tracheostomy was performed only in 10% of our patients with COVID-19 ARDS. Time to tracheostomy was after 3 weeks on average. Survival was better in patients with tracheostomy, but tracheostomized patients stayed longer in the ICU and hospital and utilized more days of mechanical ventilation and CRRT.
ABSTRACT
The recent coronavirus disease 2019 (COVID-19) pandemic is a global threat for healthcare management and the economic system, and effective treatments against the pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus responsible for this disease have not yet progressed beyond the developmental phases. As drug refinement and vaccine progression require enormously broad investments of time, alternative strategies are urgently needed. In this study, we examined phytochemicals extracted from Avicennia officinalis and evaluated their potential effects against the main protease of SARS-CoV-2. The antioxidant activities of A. officinalis leaf and fruit extracts at 150 microg/mL were 95.97% and 92.48%, respectively. Furthermore, both extracts displayed low cytotoxicity levels against Artemia salina. The gas chromatography-mass spectroscopy analysis confirmed the identifies of 75 phytochemicals from both extracts, and four potent compounds, triacontane, hexacosane, methyl linoleate, and methyl palminoleate, had binding free energy values of -6.75, -6.7, -6.3, and -6.3 Kcal/mol, respectively, in complexes with the SARS-CoV-2 main protease. The active residues Cys145, Met165, Glu166, Gln189, and Arg188 in the main protease formed non-bonded interactions with the screened compounds. The root-mean-square difference (RMSD), root-mean-square fluctuations (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), and hydrogen bond data from a molecular dynamics simulation study confirmed the docked complexes' binding rigidity in the atomistic simulated environment. However, this study's findings require in vitro and in vivo validation to ensure the possible inhibitory effects and pharmacological efficacy of the identified compounds.