Safety and efficacy of prophylactic anticoagulation versus therapeutic anticoagulation in hospital-admitted COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: COVID-19 disease-related coagulopathy and thromboembolic complication, an important aspect of the disease pathophysiology, are frequent and associated with poor outcomes, particularly significant in hospitalized patients. Undoubtedly, anticoagulation forms a cornerstone for the management of hospitalized COVID-19 patients, but the appropriate dosing has been inconclusive and a subject of research. We aim to review existing literature and compare safety and efficacy outcomes of prophylactic and therapeutic dose anticoagulation in such patients. METHODS: We did a systematic review and meta-analysis to compare the efficacy and safety of prophylactic dose anticoagulation when compared with therapeutic dosing in hospitalized COVID-19 patients. We searched PubMed, Google Scholar, EMBASE and COCHRANE databases from 2019 to 2021, without any restriction by language. We screened records, extracted data and assessed the risk of bias in the studies. RCTs that directly compare therapeutic and prophylactic anticoagulants dosing and are not placebo-controlled trials were included. Analyses of data were conducted using the Mantel-Haenszel random-effects model (DerSimonian-Laird analysis). The study is registered with PROSPERO (CRD42021265948). RESULTS: We included three studies in the final quantitative analysis. The incidence of thromboembolic events in therapeutic anticoagulation was lower in comparison with prophylactic anticoagulation in hospitalized COVID-19 patients and reached statistical significance [RR 1·45, 95% CI (1.07, 1.97) I2 -0%], whereas major bleeding as an adverse event was found lower in prophylactic anticoagulation in comparison with therapeutic anticoagulation that was statistically significant [RR 0·42, 95% CI(0.19, 0.93) I2 -0%]. CONCLUSION: Our study shows that therapeutic dose anticoagulation is more effective in preventing thromboembolic events than prophylactic dose but significantly increases the risk of major bleeding as an adverse event. So, the risk-benefit ratio must be considered while using either of them.

Post-COVID-19 Pulmonary Fibrosis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions worldwide with a high mortality rate due to a lack of definitive treatment. Despite having a wide range of clinical features, acute respiratory distress syndrome (ARDS) has emerged as the primary cause of mortality in these patients. Risk factors and comorbidities like advanced age with limited lung function, pre-existing diabetes, hypertension, cardiovascular diseases, and obesity have increased the risk for severe COVID-19 infection. Rise in inflammatory markers like transforming growth factor ß (TGF-ß), interleukin-6 (IL-6), and expression of matrix metalloproteinase 1 and 7 (MMP-1, MMP-7), along with collagen deposition at the site of lung injury, results in extensive lung scarring and fibrosis. Anti-fibrotic drugs, such as Pirfenidone and Nintedanib, have emerged as potential treatment options for post-COVID-19 pulmonary fibrosis. A lung transplant might be the only life-saving treatment. Despite the current advances in the management of COVID-19, there is still a considerable knowledge gap in the management of long-term sequelae in such patients, especially concerning pulmonary fibrosis. Follow up on the current clinical trials and research to test the efficacy of various anti-inflammatory drugs is needed to prevent long-term sequelae early mortality in these patients.

IVIG plus Glucocorticoids versus IVIG Alone in Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19: A Systematic Review and Meta-Analysis.

Background: There is limited information available regarding the management of multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2. We performed a systematic review and meta-analysis to evaluate the optimal treatment using IVIG alone versus IVIG plus glucocorticoids. Methods: PubMed, Google Scholar, EMBASE, and Cochrane databases were searched along with other secondary searches. Studies published within the time frame of January 2020 to August 2021 were included. We screened records, extracted data, and assessed the quality of the studies using NOS. Studies that directly compare the two treatment groups were included. Analyses were conducted using the random-effects model (DerSimonian-Laird analysis) if I 2 > 50% and fixed-effects model was used if I 2 < 50%. Results: We included three studies in the final quantitative analysis. The initial therapy with the IVIG plus glucocorticoids group significantly lowered the risk of treatment failure (OR 0.57, 95% CI (0.42, 0.79), I 2 45.36%) and the need for adjunctive immunomodulatory therapy (OR 0.27, 95% CI (0.20, 0.37), I 2 0.0%). The combination therapy showed no significant reduction in occurrence of left ventricular dysfunction (OR 0.79, 95% CI (0.34, 1.87), I 2 58.44%) and the need for inotropic support (OR 0.83, 95% CI (0.35, 1.99), I 2 75.40%). Conclusion: This study supports the use of IVIG with glucocorticoids compared to IVIG alone, as the combination therapy significantly lowered the risk of treatment failure and the need for adjunctive immunomodulatory therapy.

Oral manifestations associated with COVID-19 disease: An observational cross sectional study.

Objectives: The aim of present study was to investigate oral manifestations associated with COVID-19 disease. Materials and methods: This cross-sectional study comprised 367 suspects with mild/moderate COVID-19 symptoms who reported to a tertiary care hospital's screening OPD. An in-depth case history was taken, and an oral cavity examination was performed to detect any oral findings. All participants were tested for SARS-CoV-2 using a naso-pharyngeal swab and reverse transcription polymerase chain reaction.Oral manifestations and the results of RT-PCR testing were correlated. Statistical analyses were performed using Epi Info and R software. To estimate the prevalence of oral symptoms, the Pearson chi-square test was used. Results: Oral manifestations were found in 58% of the study population. The difference in the prevalence of oral manifestations between RT-PCR positive COVID-19 patients versus RT-PCR negative suspects was statistically significant (p = 0.007) with xerostomia and dysgeusia being significantly higher in positive patients (p = 0.036 and p = 0.044 respectively) while the prevalence of stomatopyrosis and other intraoral signs was insignificant. Conclusion: Xerostomia and dysgeusia are the common oral manifestations of COVID-19.

Cell-free hemoglobin is a marker of systemic inflammation in mouse models of sepsis: a Raman spectroscopic study.

Sepsis is a life-threatening condition caused by heightened host immune responses post infection. Despite intensive research, most of the existing diagnostic methods remain non-specific, labour-intensive, time-consuming or are not sensitive enough for rapid and timely diagnosis of the onset and progression of sepsis. The present work was undertaken to explore the potential of Raman spectroscopy to identify the biomarkers of sepsis in a label-free and minimally invasive manner using different mouse models of inflammation. The sera of BALB/c mice infected with Salmonella Typhimurium reveal extensive hemolysis, as indicated by the Raman bands that are characteristic of the porphyrin ring of hemoglobin (668, 743, 1050, 1253 and 1397 cm-1) which increase in a kinetic manner. These markers are also observed in a lipopolysaccharide-induced endotoxic shock model, but not in a thioglycollate-induced sterile peritonitis model. These data demonstrate that hemolysis is a signature of systemic, but not localised, inflammation. To further validate our observations, sepsis was induced in the nitric oxide synthase 2 (Nos2-/-) deficient strain which is more sensitive to infection. Interestingly, Nos2-/- mice exhibit a higher degree of hemolysis than C57BL/6 mice. Sepsis-induced hemolysis was also confirmed using resonance Raman spectroscopy with 442 nm excitation which demonstrated a pronounced increase in the resonant Raman bands at 670 and 1350 cm-1 in sera of the infected mice. This is the first study to identify inflammation-induced hemolysis in mouse models of sepsis using Raman spectral signatures for hemoglobin. The possible implications of this method in detecting hemolysis in different inflammatory pathologies, such as the ongoing COVID-19 pandemic, are discussed.