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1.
J Hum Genet ; 67(5): 295-301, 2022 May.
Article in English | MEDLINE | ID: covidwho-1616968

ABSTRACT

Host genetic factors have been shown to play a role in SARs-CoV-2 infection in diverse populations. However, the genetic landscape differs among various ethnicities; therefore, we explored the host genetic factors associated with COVID-19 disease susceptivity and disease severity in a Thai population. We recruited and genotyped 212 unrelated COVID-19 Thai patients and 36 controls using AxiomTM Human Genotyping SARs-COV-2 array, including 847,384 single nucleotide polymorphisms related to SARs-COV-2 pathogenesis, immune response, and related comorbidity No SNPs passed the genome-wide significance threshold of p value <1 × 10-8. However, with a threshold of p value <1 × 10-5, a locus on chromosome 5q32 was found to have a suggestive association with COVID-19 disease susceptibility (p value 6.9 × 10-6; Q-Q plot λ = 0.805, odds ratio 0.02). Notably, IL17B is a gene located in this linkage disequilibrium block and is previously shown to play a part in inflammation and pneumonia. Additionally, a suggestive locus on chromosome 12q22, harboring EEA1 and LOC643339, was associated with COVID-19 disease severity (p value 1.3 × 10-6 - 4.4 × 10-6, Q-Q plot λ = 0.997, odds ratio 0.28-0.31). EEA1 is involved in viral entry into cells, while LOC643339 is a long non-coding RNA. In summary, our study suggested loci on chromosomes 5q32 and 12q22 to be linked to COVID-19 disease susceptibility and disease severity, respectively. The small sample size of this study may lessen the likelihood that the association found is real, but it could still be true. Further study with a larger cohort is required to confirm these findings.


Subject(s)
COVID-19 , COVID-19/epidemiology , COVID-19/genetics , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Polymorphism, Single Nucleotide , SARS-CoV-2 , Severity of Illness Index , Thailand/epidemiology
2.
PLoS One ; 16(2): e0246864, 2021.
Article in English | MEDLINE | ID: covidwho-1083475

ABSTRACT

BACKGROUND: The presence of neutralizing antibodies (NAbs) is an indicator of protective immunity for most viral infections. A newly developed surrogate viral neutralization assay (sVNT) offers the ability to detect total receptor binding domain-targeting NAbs in an isotype-independent manner, increasing the test sensitivity. Thus, specimens with low IgM/ IgG antibody levels showed strong neutralization activity in sVNT. METHODS: This study aimed to measure the %inhibition of NAbs measured by sVNT in PCR-confirmed COVID-19 patients. The sensitivity of sVNT for the diagnosis of SARS-CoV-2 infection and its kinetics were determined. RESULTS: Ninety-seven patients with PCR-confirmed SARS-CoV-2 infection were included in this study. Majority of the patients were 21-40 years old (67%) and 63% had mild symptoms. The sensitivity of sVNT for the diagnosis of SARS-CoV-2 infection was 99% (95% confidence interval (CI) 94.4-100%) and the specificity was 100% (95% CI 98.3-100%). The negative predictive value of sVNT from the samples collected before and after 7 days of symptom onset was 99.5% (95% CI 97.4-100%) and 100% (95% CI 93.8-100%), respectively. The level of inhibition at days 8-14 were significantly higher than days 0-7 (p<0.001). The median %inhibition values by severity of COVID-19 symptoms were 79.9% (interquartile range (IQR) 49.7-91.8%); 89.0% (IQR 71.2-92.4%); and 86.6% (IQR 69.5-92.8%), for mild, moderate and severe/critical symptoms respectively. The median level of sVNT %inhibition of severe was significantly higher than the mild group (p = 0.05). CONCLUSION: The sVNT is a practical and robust serological test for SARS-CoV-2 infection and does not require specialized biosafety containment. It can be used clinically to aid diagnosis in both early and late infection especially in cases when the real-time RT-PCR results in weakly negative or weakly positive, and to determine the protective immune response from SARS-CoV-2 infection in patients.


Subject(s)
Antibodies, Neutralizing/isolation & purification , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Neutralization Tests/methods , SARS-CoV-2/physiology , Adult , Antibodies, Neutralizing/analysis , Antibodies, Viral/isolation & purification , COVID-19/immunology , COVID-19 Nucleic Acid Testing , Female , Humans , Male , Middle Aged , Sensitivity and Specificity , Serologic Tests , Spike Glycoprotein, Coronavirus/chemistry , Thailand , Young Adult
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