ABSTRACT
D-dimer levels, which originate from the lysis of cross-linked fibrin, are serially measured during coronavirus disease 2019 illness to rule out hypercoagulability as well as a septic marker. Methods: This multicenter retrospective study was carried out in two tertiary care hospitals in Karachi, Pakistan. The study included adult patients admitted with a laboratory-confirmed coronavirus disease 2019 infection, with at least one measured d-dimer within 24 h following admission. Discharged patients were compared with the mortality group for survival analysis. Results: The study population of 813 patients had 68.5% males, with a median age of 57.0 years and 14.0 days of illness. The largest d-dimer elevation was between 0.51-2.00 mcg/ml (tertile 2) observed in 332 patients (40.8%), followed by 236 patients (29.2%) having values greater than 5.00 mcg/ml (tertile 4). Within 45 days of hospital stay, 230 patients (28.3%) died, with the majority in the ICU (53.9%). On multivariable logistic regression between d-dimer and mortality, the unadjusted (Model 1) had a higher d-dimer category (tertile 3 and tertile 4) associated with a higher risk of death (OR: 2.15; 95% CI: 1.02-4.54, P=0.044) and (OR: 4.74; 95% CI: 2.38-9.46, P<0.001). Adjustment for age, sex, and BMI (Model 2) yields only tertile 4 being significant (OR: 4.27; 95% CI: 2.06-8.86, P<0.001). Conclusion: Higher d-dimer levels were independently associated with a high risk of mortality. The added value of d-dimer in risk stratifying patients for mortality was not affected by invasive ventilation, ICU stays, length of hospital stays, or comorbidities.
ABSTRACT
Background: Recent studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reveal that Omicron variant BA.1 and sub-lineages have revived the concern over resistance to antiviral drugs and vaccine-induced immunity. The present study aims to analyze the clinical profile and genome characterization of the SARS-CoV-2 variant in eastern Uttar Pradesh (UP), North India. Methods: Whole-genome sequencing (WGS) was conducted for 146 SARS-CoV-2 samples obtained from individuals who tested coronavirus disease 2019 (COVID-19) positive between the period of 1 January 2022 and 24 February 2022, from three districts of eastern UP. The details regarding clinical and hospitalized status were captured through telephonic interviews after obtaining verbal informed consent. A maximum-likelihood phylogenetic tree was created for evolutionary analysis using MEGA7. Results: The mean age of study participants was 33.9 ± 13.1 years, with 73.5% accounting for male patients. Of the 98 cases contacted by telephone, 30 (30.6%) had a travel history (domestic/international), 16 (16.3%) reported having been infected with COVID-19 in past, 79 (80.6%) had symptoms, and seven had at least one comorbidity. Most of the sequences belonged to the Omicron variant, with BA.1 (6.2%), BA.1.1 (2.7%), BA.1.1.1 (0.7%), BA.1.1.7 (5.5%), BA.1.17.2 (0.7%), BA.1.18 (0.7%), BA.2 (30.8%), BA.2.10 (50.7%), BA.2.12 (0.7%), and B.1.617.2 (1.3%) lineages. BA.1 and BA.1.1 strains possess signature spike mutations S:A67V, S:T95I, S:R346K, S:S371L, S:G446S, S:G496S, S:T547K, S:N856K, and S:L981F, and BA.2 contains S:V213G, S:T376A, and S:D405N. Notably, ins214EPE (S1- N-Terminal domain) mutation was found in a significant number of Omicron BA.1 and sub-lineages. The overall Omicron BA.2 lineage was observed in 79.5% of women and 83.2% of men. Conclusion: The current study showed a predominance of the Omicron BA.2 variant outcompeting the BA.1 over a period in eastern UP. Most of the cases had a breakthrough infection following the recommended two doses of vaccine with four in five cases being symptomatic. There is a need to further explore the immune evasion properties of the Omicron variant.
ABSTRACT
Acute renal infarction is a rare and often underdiagnosed condition with estimated incidence of 0.5-1.5%. Coronavirus disease 2019 (COVID-19) has been shown to cause a hypercoagulable state in patients leading to arterial and venous thromboembolism. Renal infarction as a consequence of COVID-associated coagulopathy has been reported, sometimes resulting in acute kidney injury. Most of the patients so far reported had other existing comorbidities and risk factors that compounded the risk of precipitating an infarction. Here, we present a 37-year-old, the youngest patient reported so far, with no pre-existing comorbidities or risk factors, who developed bilateral renal infarction with COVID-19 pneumonia. The patient was treated with anticoagulation for renal infarction and discharged on apixaban. Anticoagulation is an important part of current treatment strategies for COVID-19 pneumonia and should extend beyond the acute phase of the disease to prevent long-term sequelae, especially in young patients.
ABSTRACT
Now a days, more than 200 countries faces the health crisis due to epidemiological disease COVID-19 caused by SARS-CoV-2 virus. It will cause a very high impact on world's economy and global health sector. Earlier the structure of main protease (Mpro) protein was deposited in the RCSB protein repository. Hydroxychloroquine (HCQ) and remdesivir were found to effective in treatment of COVID-19 patients. Here we have performed docking and molecule dynamic (MD) simulation study of HCQ and remdesivir with Mpro protein which gave promising results to inhibit Mpro protein in SARS-CoV-2. On the basis of results obtained we designed structurally modified 18 novel derivatives of HCQ, remdesivir and tetrahydrocannabinol (THC) and carried out docking studies of all the derivatives. From the docking studies six molecules DK4, DK7, DK10, DK16, DK17 and DK19 gave promising results and can be use as inhibitor for Mpro of SARS-CoV-2 to control COVID-19 very effectively. Further, molecular dynamics simulation of one derivative of HCQ and one derivative of tetrahydrocannabinol showing excellent docking score was performed along with the respective parent molecules. The two derivatives gave excellent docking score and higher stability than the parent molecule as validated with molecular dynamics (MD) simulation for the binding affinities towards Mpro of SARS-CoV-2 thus represented as strong inhibitors at very low concentration.