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2.
Clin Infect Dis ; 2021 Aug 23.
Article in English | MEDLINE | ID: covidwho-1702780

ABSTRACT

BACKGROUND: he impact of SARS-CoV-2 variants of concern (VOCs) on disease severity is unclear. In this retrospective study, we compared outcomes of patients infected with B.1.1.7, B.1.351, and B.1.617.2 with those with wild-type strains from early 2020. METHODS: National surveillance data from 1-January-2021 to 22-May-2021 were obtained from the Ministry of Health, and outcomes in relation to VOC were explored. Detailed patient level data from all patients with VOC infection admitted to our center between 20-December-2020 and 12-May-2021 were analyzed. Clinical outcomes were compared with a cohort of 846 patients admitted from January-April 2020. RESULTS: 829 patients in Singapore in the study period were infected with these 3 VOCs. After adjusting for age and sex, B.1.617.2 was associated with higher odds of oxygen requirement, ICU admission, or death (adjusted odds ratio (aOR) 4.90, [95% CI 1.43-30.78]). 157 of these patients were admitted to our center. After adjusting for age, sex, comorbidities, and vaccination, aOR for pneumonia with B.1.617.2 was 1.88 [95% CI 0.95-3.76]) compared with wild-type. These differences were not seen with B.1.1.7 and B.1.351. Vaccination status was associated with decreased severity. B.1.617.2 was associated with significantly lower PCR Ct values and longer duration of Ct value ≤30 (median duration 18 days for B.1.617.2, 13 days for wild-type). CONCLUSIONS: There was a signal toward increased severity associated with B.1.617.2. The association of B.1.617.2 with lower Ct value and longer viral shedding provides a potential mechanism for increased transmissibility. These findings provide an impetus for the rapid implementation of vaccination programs.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-324729

ABSTRACT

Background: Host determinants of severe coronavirus disease 2019 include advanced age, comorbidities and male sex. Virologic factors may also be important in determining clinical outcome and transmission rates, but limited patient-level data is available. Methods: We conducted an observational cohort study at seven public hospitals in Singapore. Clinical and laboratory data were collected and compared between individuals infected with different SARS-CoV-2 clades. Firth’s logistic regression was used to examine the association between SARS-CoV-2 clade and development of hypoxia, and quasi-Poisson regression to compare transmission rates. Plasma samples were tested for immune mediator levels and the kinetics of viral replication in cell culture were compared. Findings: 319 patients with PCR-confirmed SARS-CoV-2 infection had clinical and virologic data available for analysis. 29 (9%) were infected with clade S, 90 (28%) with clade L/V, 96 (30%) with clade G (containing D614G variant), and 104 (33%) with other clades ‘O’ were assigned to lineage B.6. After adjusting for age and other covariates, infections with clade S (adjusted odds ratio (aOR) 0·030 (95% confidence intervals (CI): 0·0002-0·29)) or clade O (B·6) (aOR 0·26 (95% CI 0·064-0·93)) were associated with lower odds of developing hypoxia requiring supplemental oxygen compared with clade L/V. Patients infected with clade L/V had more pronounced systemic inflammation with higher concentrations of pro-inflammatory cytokines, chemokines and growth factors. No significant difference in the severity of clade G infections was observed (aOR 0·95 (95% CI: 0·35-2·52). Though viral loads were significantly higher, there was no evidence of increased transmissibility of clade G, and replicative fitness in cell culture was similar for all clades. Interpretation: Infection with clades L/V was associated with increased severity and more systemic release of pro-inflammatory cytokines. Infection with clade G was not associated with changes in severity, and despite higher viral loads there was no evidence of increased transmissibility.Funding Statement: This study was funded by grants from the Singapore National Medical Research Council (COVID19RF- 001, COVID19RF2-0001, COVID19RF-007, and COVID19RF-60) and Biomedical Research Council (project number H20/04/g1/006).Declaration of Interests: No conflicts of interest declared.Ethics Approval Statement: The epidemiological investigation was conducted under the Infectious Diseases Act (Singapore). Study protocols were approved by ethics committees of the National Healthcare Group and SingHealth. Written informed consent was obtained from participants for clinical data and biological sample collection as part of the PROTECT study (2012/00917;2018/3045). A waiver of informed consent for retrospective data collection only was granted for individuals admitted to the National Centre of Infectious Diseases (2020/01122). Healthy donor samples were collected under study numbers 2017/2806 and NUS IRB 04-140.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319425

ABSTRACT

Starting with a handful of SARS-CoV-2 infections in dormitory residents in late March 2020, rapid tranmission in their dense living environments ensued and by October 2020, more than 50,000 acute infections were identified across various dormitories. Extensive epidemiological, serological and phylogentic investigations, supported by simulation models, helped to reveal the factors of transmission and impact of control measures in a dormitory. We find that asymptomatic cases and symptomatic cases who did not seek medical attention were major drivers of the outbreak. Furthermore, each resident has about 30 close contacts and each infected resident spread to 4.4 (IQR 3.5–5.3) others at the start of the outbreak. The final attack rate of the current outbreak was 76.2% (IQR 70.6%–98.0%) and could be reduced by further 10% under a modified dormitory housing condition. These findings are important when designing living environments in a post COVID-19 future to reduce disease spread and facilitate rapid implementation of outbreak control measures.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-318655

ABSTRACT

Backgroun:d Residents in nursing homes are at risk of high morbidity and mortality due to coronavirus disease 2019 (COVID-19). We report the first nursing home COVID-19 outbreak in Singapore and its clinical, epidemiological, laboratory and phylogenetic investigations.Methods: Serial point prevalence testing was conducted among the residents and staff following identification of the index case (a symptomatic resident) with SARS-CoV-2 infection. Active contact tracing, screening of close contacts, whole genome sequencing and phylogenetic analysis were conducted to identify the source and extent of the outbreak.Results: Among the 108 residents and 56 healthcare workers (HCW) in the nursing home, 14 (13%) residents and two (3.6%) HCW were diagnosed with COVID-19, with case fatality rate of 28.6% (4/14) among the residents. Five residents were symptomatic (35.7%) and the others were asymptomatic (64.3%) before the point prevalence survey. The genomic virus typing in this nursing home outbreak was lineage B.6 which is rare among other GISAID clades globally but common regionally. Among the family contacts of the two infected healthcare workers, only one member was infected and had recent travel history.Conclusion: The COVID-19 outbreak in a nursing home in Singapore was contained through prompt epidemiological investigations, active case finding and containment, and infection prevention and control measures.Funding Statement: None.Declaration of Interests: The authors declared no conflict of interest.Ethics Approval Statement: Data were collected under the Infectious Disease Act for outbreak investigation and approved by Ministry of Health, Singapore.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-318389

ABSTRACT

This protocol presents the Variant Nucleotide Guard (VaNGuard) assay, which is robust towards viral mutations and can be performed on purified RNA or directly on nasopharyngeal (NP) swab samples. The procedure typically comprises three parts, namely sample preparation, RT-LAMP reaction, and Cas12a-based detection via fluorescence or lateral flow assay. Sample preparation from NP swabs involves Proteinase K digestion followed by heat inactivation. Purified RNA or digested NP swab samples are then added as templates into RT-LAMP reactions and incubated at 65ºC for 22 minutes. Next, enAsCas12a and ssDNA-probes are added and the reactions are incubated at 60ºC for another 5 minutes. End-point fluorescence can be detected by a plate reader or a real-time PCR machine. Alternatively, a lateral flow strip can be inserted into each reaction tube for equipment-free read-out. The VaNGuard assay is a rapid and convenient point-of-care test for SARS-CoV-2 and is applicable to resource poor settings.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-318385

ABSTRACT

Background: The impact of SARS-CoV-2 variants of concern (VOCs) on disease severity is unclear. In this retrospective cohort study, we compared outcomes of patients infected with B.1.1.7, B.1.351, and B.1.617.2 with those with wild-type strains from early 2020.Methods: National surveillance data from 1-January-2021 to 22-May-2021 were obtained from the Ministry of Health, and outcomes in relation to VOC were explored. Detailed patient level data from all SARS-CoV-2 patients with VOC infection admitted to our centre between 20-December-2020 and 12-May-2021 were analysed. Outcomes were compared with a cohort of 846 patients admitted January-April 2020.Findings: There were 838 VOC infections in Singapore in the study period. After adjusting for age and gender, B.1.617.2 infection was associated with higher odds of oxygen requirement, ICU admission, or death (adjusted odds ratio (aOR) 4·90, [95% CI 1·43-30·78]. 157 patients with VOCs were admitted to our centre. After adjusting for age, gender, comorbidities, and vaccination, aOR for pneumonia with B.1.617.2 was 1·88 [95% CI 0·95-3·76]) compared with wild-type. B.1.617.2 was associated with significantly lower PCR Ct values and significantly longer duration of Ct value ≤30 (estimated median duration 18 days for B.1.617.2, 13 days for wild-type). Vaccine breakthrough cases were less severe.Interpretation: There was a signal toward increased severity associated with B.1.617.2. The association of B.1.617.2 with lower Ct value and longer viral shedding provides a potential mechanism for increased transmissibility. These findings provide a strong impetus for the rapid implementation of vaccination programmes.Funding Information: National Medical Research Council grants COVID19RF-001 and COVID19RF-008.Declaration of Interests: BEY reports personal fees from Roche and Sanofi, outside the submitted work. All other authors declare no competing interests.Ethics Approval Statement: Informed consent for retrospective data collection was waived as approved by the institutional review board (NHG-DSRB reference number 2020/01122).

8.
Front Med (Lausanne) ; 8: 790177, 2021.
Article in English | MEDLINE | ID: covidwho-1686494

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has resulted in a significant burden among nursing home facilities globally. This prospective observational cohort study aims to define the potential sources of introduction and characteristics of SARS-CoV-2 transmission of the first nursing home facility in Singapore. An epidemiological serial point-prevalence survey of SARS-CoV-2 was conducted among 108 residents and 56 healthcare staff (HCS). In the current study, 14 (13%) residents and two (3.6%) HCS were diagnosed with coronavirus disease 2019 (COVID-19), with a case fatality rate (CFR) of 28.6% (4/14) among the residents. The median age of the infected residents was 86.5 [interquartile range (IQR) 78.5-88] and 85.7% were women. Five residents were symptomatic (35.7%) and the others were asymptomatic (64.3%). A higher proportion of residents who succumbed to COVID-19 had hypertension than those who recovered. The SARS-CoV-2 whole-genome sequencing showed lineage B.6 which is rare globally but common regionally during the early phase of the pandemic. Household transmission is a potential source of introduction into the nursing home, with at least six epidemiologically linked secondary cases. Male residents were less implicated due to the staff segregation plan by block. Among residents, a higher proportion of the non-survivors were asymptomatic and had hypertension compared with survivors.

9.
EMBO Mol Med ; 14(3): e15227, 2022 03 07.
Article in English | MEDLINE | ID: covidwho-1643965

ABSTRACT

The SARS-CoV-2 Delta (B.1.617.2) variant is capable of infecting vaccinated persons. An open question remains as to whether deficiencies in specific vaccine-elicited immune responses result in susceptibility to vaccine breakthrough infection. We investigated 55 vaccine breakthrough infection cases (mostly Delta) in Singapore, comparing them against 86 vaccinated close contacts who did not contract infection. Vaccine breakthrough cases showed lower memory B cell frequencies against SARS-CoV-2 receptor-binding domain (RBD). Compared to plasma antibodies, antibodies secreted by memory B cells retained a higher fraction of neutralizing properties against the Delta variant. Inflammatory cytokines including IL-1ß and TNF were lower in vaccine breakthrough infections than primary infection of similar disease severity, underscoring the usefulness of vaccination in preventing inflammation. This report highlights the importance of memory B cells against vaccine breakthrough and suggests that lower memory B cell levels may be a correlate of risk for Delta vaccine breakthrough infection.


Subject(s)
COVID-19 , COVID-19/prevention & control , COVID-19 Vaccines , Humans , SARS-CoV-2
11.
Lancet Reg Health West Pac ; 17: 100299, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1506512

ABSTRACT

BACKGROUND: Impact of the Delta variant and vaccination on SARS-CoV-2 transmission remains unclear. In Singapore, quarantine of all close contacts, including entry and exit PCR testing, provided the opportunity to determine risk of infection by the Delta variant compared to other variants, vaccine efficacy against SARS-CoV-2 acquisition, symptomatic or severe COVID-19, and risk factors associated with SARS-CoV-2 acquisition and symptomatic disease. METHODS: This retrospective cohort study included all close contacts between September 1, 2020 and May 31, 2021. Regardless of symptoms, all were quarantined for 14 days with entry and exit PCR testing. Household contacts were defined as individuals who shared a residence with a Covid-19 index case. Secondary attack rates among household close contacts of Delta variant-infected indexes and other variant-infected indexes were derived from prevalence of diagnosed cases among contacts. Relative risk ratios and bootstrapping at the cluster level was used to determine risk of infection by the Delta variant compared to other variants and vaccine efficacy against SARS-CoV-2 acquisition, symptomatic or severe COVID-19. Logistic regression using generalized estimating equations was used to determine risk factors associated with SARS-CoV-2 acquisition and symptomatic disease. FINDINGS: Of 1024 household contacts linked to 301 PCR-confirmed index cases, 753 (73.5%) were linked to Delta-infected indexes and 248 (24.2%) were exposed to indexes with other variants. Household secondary attack rate among unvaccinated Delta-exposed contacts was 25.8% (95% boostrap confidence interval [BCI] 20.6-31.5%) compared with 12.9% (95%BCI 7.0-20.0%) among other variant-exposed contacts. Unvaccinated Delta-exposed contacts were more likely to be infected than those exposed to other variants (Relative risk 2.01, 95%CI 1.24-3.84). Among Delta-exposed contacts, complete vaccination had a vaccine effectiveness of 56.4% (95%BCI 32.6-75.8%) against acquisition, 64.1% (95%BCI 37.8-85.4%) against symptomatic disease and 100% against severe disease. Among Delta-exposed contacts, vaccination status (adjusted odds ratio [aOR] 0.33, 95% robust confidence interval [RCI] 0.17-0.63) and older age of the index (aOR 1.20 per decade, 95%RCI 1.03-1.39) was associated with increased risk of SARS-CoV-2 acquisition by the contact. Vaccination status of the index was not associated with a statistically-significant difference for contact SARS-CoV-2 acquisition (aOR 0.73, 95%RCI 0.38-1.40). INTERPRETATION: Increased risk of SARS-CoV-2 Delta acquisition compared with other variants was reduced with vaccination. Close-contacts of vaccinated Delta-infected indexes did not have statistically significant reduced risk of acquisition compared with unvaccinated Delta-infected indexes.

12.
NPJ Vaccines ; 6(1): 125, 2021 Oct 25.
Article in English | MEDLINE | ID: covidwho-1483131

ABSTRACT

The rapid spreading of SARS-CoV-2 variants B.1.1.7 originated from the United Kingdom and B.1.351 from South Africa has contributed to the second wave of COVID-19 cases in the respective countries and also around the world. In this study, we employed advanced biochemical and virological methodologies to evaluate the impact of Spike mutations of these strains on the degree of protection afforded by humoral immune responses following natural infection of the ancestral SARS-CoV-2 strain during the early stages of the outbreak. We found that antibody-mediated neutralization activity was partially reduced for B.1.1.7 variant and significantly attenuated for the B.1.351 strain. We also found that mutations outside the receptor-binding domain (RBD) can strongly influence antibody binding and neutralization, cautioning the use of solely RBD mutations in evaluating vaccine efficacy. These findings highlight an urgent need to develop new SARS-CoV-2 vaccines that are not based exclusively on the ancestral SARS-CoV-2 Spike gene sequence.

14.
Clin Infect Dis ; 2021 Aug 23.
Article in English | MEDLINE | ID: covidwho-1369072

ABSTRACT

BACKGROUND: he impact of SARS-CoV-2 variants of concern (VOCs) on disease severity is unclear. In this retrospective study, we compared outcomes of patients infected with B.1.1.7, B.1.351, and B.1.617.2 with those with wild-type strains from early 2020. METHODS: National surveillance data from 1-January-2021 to 22-May-2021 were obtained from the Ministry of Health, and outcomes in relation to VOC were explored. Detailed patient level data from all patients with VOC infection admitted to our center between 20-December-2020 and 12-May-2021 were analyzed. Clinical outcomes were compared with a cohort of 846 patients admitted from January-April 2020. RESULTS: 829 patients in Singapore in the study period were infected with these 3 VOCs. After adjusting for age and sex, B.1.617.2 was associated with higher odds of oxygen requirement, ICU admission, or death (adjusted odds ratio (aOR) 4.90, [95% CI 1.43-30.78]). 157 of these patients were admitted to our center. After adjusting for age, sex, comorbidities, and vaccination, aOR for pneumonia with B.1.617.2 was 1.88 [95% CI 0.95-3.76]) compared with wild-type. These differences were not seen with B.1.1.7 and B.1.351. Vaccination status was associated with decreased severity. B.1.617.2 was associated with significantly lower PCR Ct values and longer duration of Ct value ≤30 (median duration 18 days for B.1.617.2, 13 days for wild-type). CONCLUSIONS: There was a signal toward increased severity associated with B.1.617.2. The association of B.1.617.2 with lower Ct value and longer viral shedding provides a potential mechanism for increased transmissibility. These findings provide an impetus for the rapid implementation of vaccination programs.

15.
Sci Rep ; 11(1): 15297, 2021 07 27.
Article in English | MEDLINE | ID: covidwho-1328854

ABSTRACT

Starting with a handful of SARS-CoV-2 infections in dormitory residents in late March 2020, rapid transmission in their dense living environments ensued and by October 2020, more than 50,000 acute infections were identified across various dormitories in Singapore. The aim of the study is to identify combination of factors facilitating SARS-CoV-2 transmission and the impact of control measures in a dormitory through extensive epidemiological, serological and phylogenetic investigations, supported by simulation models. Our findings showed that asymptomatic cases and symptomatic cases who did not seek medical attention were major drivers of the outbreak. Furthermore, each resident had about 30 close contacts and each infected resident spread to 4.4 (IQR 3.5-5.3) others at the start of the outbreak. The final attack rate of the current outbreak was 76.2% (IQR 70.6-98.0%) and could be reduced by further 10% under a modified dormitory housing condition. These findings are important when designing living environments in a post COVID-19 future to reduce disease spread and facilitate rapid implementation of outbreak control measures.


Subject(s)
COVID-19/prevention & control , COVID-19/transmission , Disease Outbreaks/prevention & control , Population Density , SARS-CoV-2/physiology , COVID-19/epidemiology , Disease Outbreaks/statistics & numerical data , Humans , Phylogeny
17.
Cell ; 184(12): 3192-3204.e16, 2021 06 10.
Article in English | MEDLINE | ID: covidwho-1222850

ABSTRACT

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is initiated by binding of the viral Spike protein to host receptor angiotensin-converting enzyme 2 (ACE2), followed by fusion of viral and host membranes. Although antibodies that block this interaction are in emergency use as early coronavirus disease 2019 (COVID-19) therapies, the precise determinants of neutralization potency remain unknown. We discovered a series of antibodies that potently block ACE2 binding but exhibit divergent neutralization efficacy against the live virus. Strikingly, these neutralizing antibodies can inhibit or enhance Spike-mediated membrane fusion and formation of syncytia, which are associated with chronic tissue damage in individuals with COVID-19. As revealed by cryoelectron microscopy, multiple structures of Spike-antibody complexes have distinct binding modes that not only block ACE2 binding but also alter the Spike protein conformational cycle triggered by ACE2 binding. We show that stabilization of different Spike conformations leads to modulation of Spike-mediated membrane fusion with profound implications for COVID-19 pathology and immunity.


Subject(s)
Antibodies, Neutralizing/chemistry , Giant Cells/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/immunology , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/metabolism , Antigen-Antibody Complex/chemistry , Antigen-Antibody Complex/metabolism , Binding Sites , CHO Cells , COVID-19/pathology , COVID-19/virology , Cricetinae , Cricetulus , Cryoelectron Microscopy , Giant Cells/cytology , Humans , Membrane Fusion , Peptide Library , Protein Binding , Protein Domains , Protein Structure, Quaternary , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism
18.
EBioMedicine ; 66: 103319, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1174196

ABSTRACT

BACKGROUND: Host determinants of severe coronavirus disease 2019 include advanced age, comorbidities and male sex. Virologic factors may also be important in determining clinical outcome and transmission rates, but limited patient-level data is available. METHODS: We conducted an observational cohort study at seven public hospitals in Singapore. Clinical and laboratory data were collected and compared between individuals infected with different SARS-CoV-2 clades. Firth's logistic regression was used to examine the association between SARS-CoV-2 clade and development of hypoxia, and quasi-Poisson regression to compare transmission rates. Plasma samples were tested for immune mediator levels and the kinetics of viral replication in cell culture were compared. FINDINGS: 319 patients with PCR-confirmed SARS-CoV-2 infection had clinical and virologic data available for analysis. 29 (9%) were infected with clade S, 90 (28%) with clade L/V, 96 (30%) with clade G (containing D614G variant), and 104 (33%) with other clades 'O' were assigned to lineage B.6. After adjusting for age and other covariates, infections with clade S (adjusted odds ratio (aOR) 0·030 (95% confidence intervals (CI): 0·0002-0·29)) or clade O (B·6) (aOR 0·26 (95% CI 0·064-0·93)) were associated with lower odds of developing hypoxia requiring supplemental oxygen compared with clade L/V. Patients infected with clade L/V had more pronounced systemic inflammation with higher concentrations of pro-inflammatory cytokines, chemokines and growth factors. No significant difference in the severity of clade G infections was observed (aOR 0·95 (95% CI: 0·35-2·52). Though viral loads were significantly higher, there was no evidence of increased transmissibility of clade G, and replicative fitness in cell culture was similar for all clades. INTERPRETATION: Infection with clades L/V was associated with increased severity and more systemic release of pro-inflammatory cytokines. Infection with clade G was not associated with changes in severity, and despite higher viral loads there was no evidence of increased transmissibility.


Subject(s)
COVID-19/etiology , COVID-19/transmission , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Adult , Age Factors , Aged , COVID-19/epidemiology , COVID-19/immunology , Comorbidity , Female , Humans , Hypoxia/therapy , Hypoxia/virology , Male , Middle Aged , Singapore/epidemiology , Viral Load
19.
Nat Commun ; 12(1): 1739, 2021 03 19.
Article in English | MEDLINE | ID: covidwho-1142438

ABSTRACT

Extensive testing is essential to break the transmission of SARS-CoV-2, which causes the ongoing COVID-19 pandemic. Here, we present a CRISPR-based diagnostic assay that is robust to viral genome mutations and temperature, produces results fast, can be applied directly on nasopharyngeal (NP) specimens without RNA purification, and incorporates a human internal control within the same reaction. Specifically, we show that the use of an engineered AsCas12a enzyme enables detection of wildtype and mutated SARS-CoV-2 and allows us to perform the detection step with loop-mediated isothermal amplification (LAMP) at 60-65 °C. We also find that the use of hybrid DNA-RNA guides increases the rate of reaction, enabling our test to be completed within 30 minutes. Utilizing clinical samples from 72 patients with COVID-19 infection and 57 healthy individuals, we demonstrate that our test exhibits a specificity and positive predictive value of 100% with a sensitivity of 50 and 1000 copies per reaction (or 2 and 40 copies per microliter) for purified RNA samples and unpurified NP specimens respectively.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , RNA, Guide , SARS-CoV-2/genetics , Bacterial Proteins/genetics , COVID-19/virology , CRISPR-Associated Proteins/genetics , CRISPR-Cas Systems , Clustered Regularly Interspaced Short Palindromic Repeats , Endodeoxyribonucleases/genetics , Humans , Molecular Diagnostic Techniques/methods , Mutation , Nasopharynx/virology , Nucleic Acid Amplification Techniques/methods , RNA, Viral/genetics , Sensitivity and Specificity
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