C allele of rs479200 of the host EGLN1 gene - a risk factor for severe COVID-19 (pilot study)

BackgroundCoronavirus disease-2019 (COVID-19) symptoms can range from asymptomatic, moderate to severe manifestations that result in an overall global case fatality rate of 2-7 %. While each variant has had it challenges, and some variants are more severe than others, risk factors of severe COVID-19 are still under investigation. In this context, the host genetic predisposition is also a crucial factor to investigate. In the present study, we investigated host genotypes of the SNP rs479200 of the host EGLN1 gene, previously implicated in high altitude pulmonary edema (HAPE), some of whose symptoms such as hypoxia profoundly overlap with severe COVID-19. MethodsAfter informed consent, 158 RT-PCR confirmed COVID-19 patients (March 2020 to June 2021) were enrolled in the study. Based on their clinical manifestations, disease severity was categorized by the clinical team. Blood samples were drawn and DNA was extracted from the clot to infer different genotypes of the SNP rs479200 of the host EGLN1 gene. PCR-RFLP analysis of the SNP rs479200 (C > T) was performed with an amplicon size of 367 bp. Various genotypes (TT, TC and CC) were assigned based on the presence/absence of a restriction site (T/GTACA) for restriction enzyme BsrGI. Allele frequencies, Hardy-Weinberg Equilibrium (HWE) and multinomial logistic regression were performed using statistical tool SPSS version 23 (IBM). FindingsWe observed that the severe COVID-19 category was composed of comparatively younger patients with mean age (34.9{+/-}15.6), compared to asymptomatic and moderate categories whose mean age was 49.7{+/-}17.9 and 54.3{+/-}15.7, respectively. Preponderance of males and high heterozygosity (TC) was observed across the clinical categories. Notably, the frequency of C allele (0.664) was 2-fold higher than the T allele (0.336) in severe COVID-19 patients, whereas the allele frequencies were similar in asymptomatic and moderate category of COVID-19 patients. Multinomial logistic regression showed an association of genotypes with increasing clinical severity; odds ratio (adjusted OR-11.414 (2.564-50.812)) and (unadjusted OR-6.214 (1.84-20.99)) for the genotype CC in severe category of COVID-19. Interestingly, the TC genotype was also found to be positively associated with severe outcome (unadjusted OR-5.816 (1.489-22.709)), indicating association of C allele in imparting the risk of severe outcome. InterpretationThe study provides strong evidence that the presence of C allele of SNP (rs479200) of the EGLN1 gene associates with severity in COVID-19 patients. Thus, the presence of C allele may be a risk factor for COVID-19 severity. This study opens new avenues towards risk assessment that include EGLN1 (rs479200) genotype testing and identifying patients with C allele who might be prioritized for critical care.

Lung Perfusion Scintigraphy Early After COVID-19: A Single-Center Retrospective Study.

The incidence of thromboembolic complications in coronavirus disease 2019 (COVID-19) infection is well recognized. The present study retrospectively evaluated the type and prevalence of lung perfusion defects in early-post-COVID-19 patients with hypoxia and was aimed to identify the risk factors for mismatched perfusion defects. Methods: We analyzed SPECT/CT images of 54 early-post-COVID-19 patients (44 men and 10 women). Logistic regression analysis was used to examine the risk. Results: The mean age of the study population was 55.4 y (range, 34-76 y). All received prophylactic anticoagulation from the day of hospitalization to the date of perfusion scanning. The median interval between COVID-19-positive reports and lung perfusion scanning was 22 d. Lung perfusion defects (of any type) were observed in most (87%). Twenty-three subjects (42.6%) had mismatched perfusion defects. Mismatched perfusion defects were segmental in 14 subjects (25.9%) and subsegmental in 11 (20.4%). Higher age was a risk factor for mismatched perfusion defects (odds ratio, 1.06; 95% CI, 0.99-1.13; P = 0.06). Subjects with a serum D-dimer level of at least 2,500 ng/mL on the day before the scan were not at higher risk for having mismatched perfusion defects (odds ratio, 1.14; 95% CI, 0.34-3.9; P = 0.83). Conclusion: Despite prophylactic anticoagulation, mismatched perfusion defects suggestive of pulmonary thromboembolism were observed. Serum D-dimer level in patients early after COVID-19 is a poor predictor of mismatched perfusion defects. Confirmed evidence of pulmonary embolism by imaging studies should support the decision to extend anticoagulant prophylaxis in post-COVID-19 patients.

An HIV1/2 point of care test on sputum for screening TB/HIV co-infection in Central India - Will it work?

OBJECTIVE@#To determine whether the OraQuick® HIV-1/2 Assay (OraSure Technologies, Inc., Bethlehem, PA, USA) in sputum is a valid tool for HIV surveillance among TB patients.@*METHODS@#A cross sectional study was carried out on sputa of patients diagnosed with tuberculosis. Sputa were tested for antibodies to HIV using OraQuick® HIV-1/2 Assay (OraSure Technologies, Inc., Bethlehem, PA, USA). The results were compared with results of serum ELISA.@*RESULTS@#Compared to serum ELISA, the OraQuick® HIV-1/2 Assay in sputum specimens reported 90% sensitivity (9/10) and 100% specificity (307/307), with a positive predictive value of 100% (95%CI: 66.37%-100.00%) and a negative predictive value of 99.68% (95%CI: 98.20%-99.99%).@*CONCLUSIONS@#This testing method may provide a useful strategy for conducting HIV surveillance in possible co-infected TB patients at peripheral centres. Since there is no investment on infrastructure, it may be possible for paramedical health professionals to carry out the test, particularly in areas with low HIV endemicity.