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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-313315

ABSTRACT

Coronavirus disease (COVID-19), caused by SARS-CoV-2, has a higher case fatality rate (CFR) in European ethnic groups than in others, especially East Asians. One explanation to this phenomenon might be TMPRSS2, a key processing enzyme essential for viral infection. Here, we analyzed the allele frequencies of two nonsynonymous variants rs12329760 (V197M) and rs75603675 (G8V) in the TMPRSS2 gene using over 200,000 present-day and ancient genomic samples. We found a significant association between the CFR of COVID-19 and the allele frequencies of the two variants. Interestingly, they had opposing effects on the CFR: inverse correlation by V197, proportional correlation by G8V. East Asians have higher V197M and lower G8V allele frequencies than Europeans, possibly endowing resistance against SARS-CoV-2. Structural and energy calculation analysis of the V197M amino acid change showed that it destabilizes the TMPRSS2 protein, possibly affecting its ACE2 and viral spike protein processing negatively, ultimately resulting in reduced SARS-CoV-2 infection efficiency and CFR in East Asian ethnic groups.

2.
Clin Exp Pediatr ; 64(12): 652-660, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1555275

ABSTRACT

BACKGROUND: Viral load and shedding duration are highly associated with the transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, limited studies have reported on viral load or shedding in children and adolescents infected with sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PURPOSE: This study aimed to investigate the natural course of viral load in asymptomatic or mild pediatric cases. METHODS: Thirty-one children (<18 years) with confirmed SARS-CoV-2 infection were hospitalized and enrolled in this study. Viral loads were evaluated in nasopharyngeal swab samples using real-time reverse transcription polymerase chain reaction (E, RdRp, N genes). cycle threshold (Ct) values were measured when patients met the clinical criteria to be released from quarantine. RESULTS: The mean age of the patients was 9.8 years, 18 (58%) had mild disease, and 13 (42%) were asymptomatic. Most children were infected by adult family members, most commonly by their mothers. The most common symptoms were fever and sputum (26%), followed by cough and runny nose. Nine patients (29%) had a high or intermediate viral load (Ct value≤30) when they had no clinical symptoms. Viral load showed no difference between symptomatic and asymptomatic patients. Viral rebounds were found in 15 cases (48%), which contributed to prolonged viral detection. The mean duration of viral detection was 25.6 days. Viral loads were significantly lower in patients with viral rebounds than in those with no rebound (E, P=0.003; RdRp, P=0.01; N, P=0.02). CONCLUSION: Our study showed that many pediatric patients with coronavirus disease 2019 (COVID-19) experienced viral rebound and showed viral detection for more than 3 weeks. Further studies are needed to investigate the relationship between viral rebound and infectiousness in COVID-19.

3.
Mol Cells ; 44(9): 680-687, 2021 Sep 30.
Article in English | MEDLINE | ID: covidwho-1444539

ABSTRACT

Coronavirus disease, COVID-19 (coronavirus disease 2019), caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has a higher case fatality rate in European countries than in others, especially East Asian ones. One potential explanation for this regional difference is the diversity of the viral infection efficiency. Here, we analyzed the allele frequencies of a nonsynonymous variant rs12329760 (V197M) in the TMPRSS2 gene, a key enzyme essential for viral infection and found a significant association between the COVID-19 case fatality rate and the V197M allele frequencies, using over 200,000 present-day and ancient genomic samples. East Asian countries have higher V197M allele frequencies than other regions, including European countries which correlates to their lower case fatality rates. Structural and energy calculation analysis of the V197M amino acid change showed that it destabilizes the TMPRSS2 protein, possibly negatively affecting its ACE2 and viral spike protein processing.


Subject(s)
COVID-19/genetics , COVID-19/mortality , Serine Endopeptidases/genetics , COVID-19/ethnology , Gene Frequency , Humans , Models, Molecular , Mortality , Polymorphism, Single Nucleotide , Republic of Korea , Serine Endopeptidases/chemistry
4.
PLoS One ; 16(3): e0248042, 2021.
Article in English | MEDLINE | ID: covidwho-1115310

ABSTRACT

A newly identified coronavirus, designated as severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), has spread rapidly from its epicenter in China to more than 150 countries across six continents. In this study, we have designed three reverse-transcription loop-mediated isothermal amplification (RT-LAMP) primer sets to detect the RNA-dependent RNA polymerase (RdRP), Envelope (E) and Nucleocapsid protein (N) genes of SARS CoV-2. For one tube reaction, the detection limits for five combination SARS CoV-2 LAMP primer sets (RdRP/E, RdRP/N, E/N, RdRP/E/N and RdRP/N/Internal control (actin beta)) were evaluated with a clinical nasopharyngeal swab sample. Among the five combination, the RdRP/E and RdRP/N/IC multiplex LAMP assays showed low detection limits. The sensitivity and specificity of the RT-LAMP assay were evaluated and compared to that of the widely used Allplex™ 2019-nCoV Assay (Seegene, Inc., Seoul, South Korea) and PowerChek™ 2019-nCoV Real-time PCR kit (Kogenebiotech, Seoul, South Korea) for 130 clinical samples from 91 SARS CoV-2 patients and 162 NP specimens from individuals with (72) and without (90) viral respiratory infections. The multiplex RdRP (FAM)/N (CY5)/IC (Hex) RT-LAMP assay showed comparable sensitivities (RdRP: 93.85%, N: 94.62% and RdRP/N: 96.92%) to that of the Allplex™ 2019-nCoV Assay (100%) and superior to those of PowerChek™ 2019-nCoV Real-time PCR kit (RdRP: 92.31%, E: 93.85% and RdRP/E: 95.38%).


Subject(s)
COVID-19/diagnosis , Molecular Diagnostic Techniques/methods , Nucleic Acid Amplification Techniques/methods , SARS-CoV-2/genetics , COVID-19/genetics , COVID-19 Testing/methods , Clinical Laboratory Techniques/methods , Coronavirus Infections/virology , DNA Primers/genetics , Humans , Nucleocapsid Proteins/genetics , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction/methods , Reverse Transcription/genetics , SARS-CoV-2/pathogenicity , Sensitivity and Specificity
6.
Clin Infect Dis ; 73(9): e3002-e3008, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-939552

ABSTRACT

BACKGROUND: Positive results from real-time reverse-transcription polymerase chain reaction (rRT-PCR) in recovered patients raise concern that patients who recover from coronavirus disease 2019 (COVID-19) may be at risk of reinfection. Currently, however, evidence that supports reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been reported. METHODS: We conducted whole-genome sequencing of the viral RNA from clinical specimens at the initial infection and at the positive retest from 6 patients who recovered from COVID-19 and retested positive for SARS-CoV-2 via rRT-PCR after recovery. A total of 13 viral RNAs from the patients' respiratory specimens were consecutively obtained, which enabled us to characterize the difference in viral genomes between initial infection and positive retest. RESULTS: At the time of the positive retest, we were able to acquire a complete genome sequence from patient 1, a 21-year-old previously healthy woman. In this patient, through the phylogenetic analysis, we confirmed that the viral RNA of positive retest was clustered into a subgroup distinct from that of the initial infection, suggesting that there was a reinfection of SARS-CoV-2 with a subtype that was different from that of the primary strain. The spike protein D614G substitution that defines the clade "G" emerged in reinfection, while mutations that characterize the clade "V" (ie, nsp6 L37F and ORF3a G251V) were present at initial infection. CONCLUSIONS: Reinfection with a genetically distinct SARS-CoV-2 strain may occur in an immunocompetent patient shortly after recovery from mild COVID-19. SARS-CoV-2 infection may not confer immunity against a different SARS-CoV-2 strain.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Female , Humans , Phylogeny , RNA, Viral/genetics , Reinfection , Young Adult
8.
Transbound Emerg Dis ; 68(4): 2059-2065, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-797741

ABSTRACT

To curb the COVID-19 pandemic, isolation measures are required. Shared room occupancy is recommended when isolation rooms are insufficient. However, there is little evidence of the applicability of shared and single room occupancy for patients with COVID-19 to determine whether shared room occupancy is feasible. COVID-19-infected patients admitted to the Daegu Dongsan Hospital of Keimyung University from 21 February 2020 to 20 April 2020 were enrolled in the study and randomly assigned to hospital rooms. Clinical symptoms, underlying diseases and epidemiological data of patients were analysed after dividing participants into a shared room occupancy group (group A) and a single room occupancy group (group B). Outcomes analysed included microbiological cure rates, time to clinical symptom improvement, time to defervescence and negative-to-positive conversion rates of polymerase chain reaction (PCR) results during hospitalization. A total of 666 patients were included in this study, 535 and 131 patients in groups A and B, respectively. Group B included more underlying conditions, such as pregnancy and solid organ transplantation, and was more closely associated with severe pneumonia during hospitalization. Besides, no statistically significant differences between the two groups in terms of negative PCR rates at HD 7 and 14, conversion rates of PCR results from negative-to-positive, as well as time to the improvement of clinical symptoms, and time to defervescence were observed. Our results suggest that the shared room occupancy of patients with mild symptoms could be an alternative to single room occupancy during the COVID-19 pandemic.


Subject(s)
COVID-19 , Pandemics , Animals , Bed Occupancy , COVID-19/veterinary , Female , Male , Pregnancy , SARS-CoV-2
9.
Ann Lab Med ; 40(6): 439-447, 2020 11.
Article in English | MEDLINE | ID: covidwho-599917

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early detection of COVID-19 and immediate isolation of infected patients from the naive population are important to prevent further pandemic spread of the infection. Real-time reverse transcription (RT)-PCR to detect SARS-CoV-2 RNA is currently the most reliable diagnostic method for confirming COVID-19 worldwide. Guidelines for clinical laboratories on the COVID-19 diagnosis have been recently published by Korean Society for Laboratory Medicine and the Korea Centers for Disease Control and Prevention. However, these formal guidelines do not address common practical laboratory issues related to COVID-19 real-time RT-PCR testing and their solutions. Therefore, this guideline is intended as a practical and technical supplement to the "Guidelines for Laboratory Diagnosis of COVID-19 in Korea".


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , COVID-19 , Coronavirus Infections/genetics , Coronavirus Infections/virology , Coronavirus Nucleocapsid Proteins , Guanidines/chemistry , Guidelines as Topic , Humans , Nasopharynx/virology , Nucleocapsid Proteins/genetics , Open Reading Frames/genetics , Oropharynx/virology , Pandemics , Phosphoproteins , Pneumonia, Viral/genetics , Pneumonia, Viral/virology , RNA, Viral/genetics , RNA, Viral/metabolism , Real-Time Polymerase Chain Reaction , Republic of Korea , SARS-CoV-2 , Thiocyanates/chemistry , Viral Envelope Proteins/genetics , Viroporin Proteins
10.
Annals of laboratory medicine ; 2020.
Article | WHO COVID | ID: covidwho-27715

ABSTRACT

The outbreak of coronavirus disease 2019 (COVID-19), which began in December 2019, is still ongoing in Korea, with >9,000 confirmed cases as of March 25, 2020. COVID-19 is a severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection, and real-time reverse transcription-PCR is currently the most reliable diagnostic method for COVID-19 around the world. Korean Society for Laboratory Medicine and the Korea Centers for Disease Prevention and Control propose guidelines for diagnosing COVID-19 in clinical laboratories in Korea. These guidelines are based on other related domestic and international guidelines, as well as expert opinions and include the selection of test subjects, selection of specimens, diagnostic methods, interpretation of test results, and biosafety.

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