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1.
Clin Infect Dis ; 2022 Mar 10.
Article in English | MEDLINE | ID: covidwho-1886378

ABSTRACT

BACKGROUND: The SARS-CoV-2 Omicron variant BA.2 sublineage has increased rapidly in Europe and Asia since January 2022. Here, we report the epidemiological and genomic analysis of a large single source BA.2 outbreak in a housing estate. METHODS: We analyzed the epidemiological information of a community outbreak of BA.2 (STY outbreak). We performed whole viral genome sequencing using the Oxford Nanopore MinION device. We calculated the doubling time of the outbreak within a housing estate. RESULTS: The STY outbreak involved a total of 768 individuals as of 5 th February 2022, including 432 residents, visitors or staff (56.3%) from a single housing estate (KC Estate). The outbreak at the KC Estate has a short doubling time of 1.28 days (95% confidence interval: 0.560-1.935). The outbreak was promptly controlled with the lockdown of 3 buildings within the housing estate. Whole genome sequencing was performed for 133 patients in the STY outbreak, including 106 residents of the KC Estate. All 133 sequences from the STY outbreak belonged to the BA.2 sublineage, and phylogenetic analysis showed that these sequences cluster together. All individuals in the STY cluster had the unique mutation C12525T. CONCLUSIONS: Our study highlights the exceptionally high transmissibility of the Omicron variant BA.2 sublineage in Hong Kong where stringent measures are implemented as part of the elimination strategy. Continual genomic surveillance is crucial in monitoring the emergence of epidemiologically important Omicron sub-variants.

2.
Antibiotics (Basel) ; 11(6)2022 May 31.
Article in English | MEDLINE | ID: covidwho-1869451

ABSTRACT

Nonpharmaceutical interventions implemented during the COVID-19 pandemic (2020-2021) have provided a unique opportunity to understand their impact on the wholesale supply of antibiotics and incidences of infections represented by bacteremia due to common bacterial species in Hong Kong. The wholesale antibiotic supply data (surrogate indicator of antibiotic consumption) and notifications of scarlet fever, chickenpox, and tuberculosis collected by the Centre for Health Protection, and the data of blood cultures of patients admitted to public hospitals in Hong Kong collected by the Hospital Authority for the last 10 years, were tabulated and analyzed. A reduction in the wholesale supply of antibiotics was observed. This decrease coincided with a significant reduction in the incidence of community-onset bacteremia due to Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are encapsulated bacteria with respiratory transmission potential. This reduction was sustained during two pandemic years (period 2: 2020-2021), compared with eight pre-pandemic years (period 1: 2012-2019). Although the mean number of patient admissions per year (1,704,079 vs. 1,702,484, p = 0.985) and blood culture requests per 1000 patient admissions (149.0 vs. 158.3, p = 0.132) were not significantly different between periods 1 and 2, a significant reduction in community-onset bacteremia due to encapsulated bacteria was observed in terms of the mean number of episodes per year (257 vs. 58, p < 0.001), episodes per 100,000 admissions (15.1 vs. 3.4, p < 0.001), and per 10,000 blood culture requests (10.1 vs. 2.1, p < 0.001), out of 17,037,598 episodes of patient admissions with 2,570,164 blood culture requests. Consistent with the findings of bacteremia, a reduction in case notification of scarlet fever and airborne infections, including tuberculosis and chickenpox, was also observed; however, there was no reduction in the incidence of hospital-onset bacteremia due to Staphylococcus aureus or Escherichia coli. Sustained implementation of non-pharmaceutical interventions against respiratory microbes may reduce the overall consumption of antibiotics, which may have a consequential impact on antimicrobial resistance. Rebound of conventional respiratory microbial infections is likely with the relaxation of these interventions.

3.
Clin Infect Dis ; 2022 Mar 02.
Article in English | MEDLINE | ID: covidwho-1852993

ABSTRACT

BACKGROUND: SARS-CoV-2 can infect human and other mammals, including hamsters. Syrian (Mesocricetus auratus) and dwarf (Phodopus sp.) hamsters are susceptible to SARS-CoV-2 infection in the laboratory setting. However, pet shop-related COVID-19 outbreaks have not been reported. METHODS: We conducted an investigation of a pet shop-related COVID-19 outbreak due to Delta variant AY.127 involving at least three patients in Hong Kong. We tested samples collected from the patients, environment, and hamsters linked to this outbreak and performed whole genome sequencing analysis of the RT-PCR-positive samples. RESULTS: The patients included a pet shop keeper (Patient 1), a female customer of the pet shop (Patient 2), and the husband of Patient 2 (Patient 3). Investigation showed that 17.2% (5/29) and 25.5% (13/51) environmental specimens collected from the pet shop and its related warehouse, respectively, tested positive for SARS-CoV-2 RNA by RT-PCR. Among euthanized hamsters randomly collected from the storehouse, 3% (3/100) tested positive for SARS-CoV-2 RNA by RT-PCR and seropositive for anti-SARS-CoV-2 antibody by ELISA. Whole genome analysis showed that although all genomes from the outbreak belonged to the Delta variant AY.127, there were at least 3 nucleotide differences among the genomes from different patients and the hamster cages. Genomic analysis suggests that multiple strains have emerged within the hamster population, and these different strains have likely transmitted to human either via direct contact or via the environment. CONCLUSIONS: Our study demonstrated probable hamster-to-human transmission of SARS-CoV-2. As pet trading is common around the world, this can represent a route of international spread of this pandemic virus.

4.
Clin Infect Dis ; 74(8): 1485-1488, 2022 Apr 28.
Article in English | MEDLINE | ID: covidwho-1816023

ABSTRACT

A false-positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction result can lead to unnecessary public health measures. We report 2 individuals whose respiratory specimens were contaminated by an inactivated SARS-CoV-2 vaccine strain (CoronaVac), likely at vaccination premises. Incidentally, whole genome sequencing of CoronaVac showed adaptive deletions on the spike protein, which do not result in observable changes of antigenicity.


Subject(s)
COVID-19 Vaccines , COVID-19 , COVID-19/prevention & control , Humans , SARS-CoV-2/genetics , Vaccination
5.
Clin Infect Dis ; 2021 Jul 26.
Article in English | MEDLINE | ID: covidwho-1707925

ABSTRACT

BACKGROUND: Several SARS-CoV-2 lineages with mutations at the spike protein receptor binding domain (RBD) have reduced susceptibility to antibody neutralization, and have been classified as Variants of Concern (VOCs) or Variants of Interest (VOIs). Here, we systematically compared the neutralization susceptibility and RBD binding of different VOCs/VOIs, including B.1.617.1 (kappa variant) and P.3 (theta variant) which were first detected in India and the Philippines, respectively. METHODS: The neutralization susceptibility of the VOCs/VOIs (B.1.351, B.1.617.1 and P.3) and a non-VOC/VOI without RBD mutations (B.1.36.27) to convalescent sera from COVID-19 patients or BNT162b2 vaccinees was determined using a live virus microneutralization (MN) assay. Serum IgG binding to wild type and mutant RBDs were determined using an enzyme immunoassay. RESULTS: The geometric mean neutralization titers (GMT) of B.1.351, P.3, and B.1.617.1 were significantly lower than that of B.1.36.27 for COVID-19 patients infected with non-VOCs/VOIs (3.4-5.7-fold lower) or individuals who have received 2 doses of BNT162b2 vaccine (4.4-7.3-fold lower). The GMT of B.1.351 or P.3 were lower than that of B.1.671.1. For the 4 patients infected with B.1.351 or B.1.617.1, the MN titer was highest for their respective lineage. RBD with E484K or E484Q mutation, either alone or in combination with other mutations, showed greatest reduction in serum IgG binding. CONCLUSION: P.3 and B.1.617.1 escape serum neutralization induced by natural infection or vaccine. Infection with one variant do not confer cross protection for heterologous lineages. Immunogenicity testing for second generation COVID-19 vaccines should include multiple variant and "non-variant" strains.

6.
Clin Infect Dis ; 73(9): e2946-e2951, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1500988

ABSTRACT

BACKGROUND: Waning immunity occurs in patients who have recovered from Coronavirus Disease 2019 (COVID-19). However, it remains unclear whether true re-infection occurs. METHODS: Whole genome sequencing was performed directly on respiratory specimens collected during 2 episodes of COVID-19 in a patient. Comparative genome analysis was conducted to differentiate re-infection from persistent viral shedding. Laboratory results, including RT-PCR Ct values and serum Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) IgG, were analyzed. RESULTS: The second episode of asymptomatic infection occurred 142 days after the first symptomatic episode in an apparently immunocompetent patient. During the second episode, there was evidence of acute infection including elevated C-reactive protein and SARS-CoV-2 IgG seroconversion. Viral genomes from first and second episodes belong to different clades/lineages. The virus genome from the first episode contained a a stop codon at position 64 of ORF8, leading to a truncation of 58 amino acids. Another 23 nucleotide and 13 amino acid differences located in 9 different proteins, including positions of B and T cell epitopes, were found between viruses from the first and second episodes. Compared to viral genomes in GISAID, the first virus genome was phylogenetically closely related to strains collected in March/April 2020, while the second virus genome was closely related to strains collected in July/August 2020. CONCLUSIONS: Epidemiological, clinical, serological, and genomic analyses confirmed that the patient had re-infection instead of persistent viral shedding from first infection. Our results suggest SARS-CoV-2 may continue to circulate among humans despite herd immunity due to natural infection. Further studies of patients with re-infection will shed light on protective immunological correlates for guiding vaccine design.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Genome, Viral , Humans , Reinfection , Whole Genome Sequencing
7.
Lancet Reg Health West Pac ; 17: 100281, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1446927

ABSTRACT

BACKGROUND: Global dissemination of SARS-CoV-2 Variants of Concern (VOCs) remains a concern. The aim of this study is to describe how mass testing and phylogenetic analysis successfully prevented local transmission of SARS-CoV-2 VOC in a densely populated city with low herd immunity for COVID-19. METHODS: In this descriptive study, we conducted contact tracing, quarantine, and mass testing of the potentially exposed contacts with the index case. Epidemiological investigation and phylogeographic analysis were performed. FINDINGS: Among 11,818 laboratory confirmed cases of COVID-19 diagnosed till 13th May 2021 in Hong Kong, SARS-CoV-2 VOCs were found in 271 (2.3%) cases. Except for 10 locally acquired secondary cases, all SARS-CoV-2 VOCs were imported or acquired in quarantine hotels. The index case of this SARS-CoV-2 VOC B.1.351 epidemic, an inbound traveler with asymptomatic infection, was diagnosed 9 days after completing 21 days of quarantine. Contact tracing of 163 contacts in household, hotel, and residential building only revealed 1 (0.6%) secondary case. A symptomatic foreign domestic helper (FDH) without apparent epidemiological link but infected by virus with identical genome sequence was subsequently confirmed. Mass testing of 0.34 million FDHs identified two more cases which were phylogenetically linked. A total of 10 secondary cases were identified that were related to two household gatherings. The clinical attack rate of household close contact was significantly higher than non-household exposure during quarantine (7/25, 28% vs 0/2051, 0%; p<0.001). INTERPRETATION: The rising epidemic of SARS-CoV-2 VOC transmission could be successfully controlled by contact tracing, quarantine, and rapid genome sequencing complemented by mass testing. FUNDING: Health and Medical Research Fund Commissioned Research on Control of Infectious Disease (see acknowledgments for full list).

8.
Clin Infect Dis ; 74(8): 1485-1488, 2022 Apr 28.
Article in English | MEDLINE | ID: covidwho-1402369

ABSTRACT

A false-positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction result can lead to unnecessary public health measures. We report 2 individuals whose respiratory specimens were contaminated by an inactivated SARS-CoV-2 vaccine strain (CoronaVac), likely at vaccination premises. Incidentally, whole genome sequencing of CoronaVac showed adaptive deletions on the spike protein, which do not result in observable changes of antigenicity.


Subject(s)
COVID-19 Vaccines , COVID-19 , COVID-19/prevention & control , Humans , SARS-CoV-2/genetics , Vaccination
9.
EBioMedicine ; 71: 103544, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1363987

ABSTRACT

BACKGROUND: Several SARS-CoV-2 lineages with spike receptor binding domain (RBD) N501Y mutation have spread globally. We evaluated the impact of N501Y on neutralizing activity of COVID-19 convalescent sera and on anti-RBD IgG assays. METHODS: The susceptibility to neutralization by COVID-19 patients' convalescent sera from Hong Kong were compared between two SARS-CoV-2 isolates (B117-1/B117-2) from the α variant with N501Y and 4 non-N501Y isolates. The effect of N501Y on antibody binding was assessed. The performance of commercially-available IgG assays was determined for patients infected with N501Y variants. FINDINGS: The microneutralization antibody (MN) titers of convalescent sera from 9 recovered COVID-19 patients against B117-1 (geometric mean titer[GMT],80; 95% CI, 47-136) were similar to those against the non-N501Y viruses. However, MN titer of these serum against B117-2 (GMT, 20; 95% CI, 11-36) was statistically significantly reduced when compared with non-N501Y viruses (P < 0.01; one-way ANOVA). The difference between B117-1 and B117-2 was confirmed by testing 60 additional convalescent sera. B117-1 and B117-2 differ by only 3 amino acids (nsp2-S512Y, nsp13-K460R, spike-A1056V). Enzyme immunoassay using 272 convalescent sera showed reduced binding of anti-RBD IgG to N501Y or N501Y-E484K-K417N when compared with that of wild-type RBD (mean difference: 0.1116 and 0.5613, respectively; one-way ANOVA). Of 7 anti-N-IgG positive sera from patients infected with N501Y variants (collected 9-14 days post symptom onset), 6 (85.7%) tested negative for a commercially-available anti-S1-IgG assay. FUNDING: Richard and Carol Yu, Michael Tong, and the Government Consultancy Service (see acknowledgments for full list). INTERPRETATION: We highlighted the importance of using a panel of viruses within the same lineage to determine the impact of virus variants on neutralization. Furthermore, clinicians should be aware of the potential reduced sensitivity of anti-RBD IgG assays.


Subject(s)
COVID-19/therapy , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Adult , Aged , Antibodies, Neutralizing/administration & dosage , Antibodies, Neutralizing/immunology , Antibodies, Viral/administration & dosage , Antibodies, Viral/ultrastructure , COVID-19/genetics , COVID-19/immunology , COVID-19/virology , Female , Humans , Immunization, Passive , Male , Middle Aged , Mutation/genetics , Neutralization Tests , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/immunology
10.
Clin Infect Dis ; 2021 Jul 26.
Article in English | MEDLINE | ID: covidwho-1324612

ABSTRACT

BACKGROUND: Several SARS-CoV-2 lineages with mutations at the spike protein receptor binding domain (RBD) have reduced susceptibility to antibody neutralization, and have been classified as Variants of Concern (VOCs) or Variants of Interest (VOIs). Here, we systematically compared the neutralization susceptibility and RBD binding of different VOCs/VOIs, including B.1.617.1 (kappa variant) and P.3 (theta variant) which were first detected in India and the Philippines, respectively. METHODS: The neutralization susceptibility of the VOCs/VOIs (B.1.351, B.1.617.1 and P.3) and a non-VOC/VOI without RBD mutations (B.1.36.27) to convalescent sera from COVID-19 patients or BNT162b2 vaccinees was determined using a live virus microneutralization (MN) assay. Serum IgG binding to wild type and mutant RBDs were determined using an enzyme immunoassay. RESULTS: The geometric mean neutralization titers (GMT) of B.1.351, P.3, and B.1.617.1 were significantly lower than that of B.1.36.27 for COVID-19 patients infected with non-VOCs/VOIs (3.4-5.7-fold lower) or individuals who have received 2 doses of BNT162b2 vaccine (4.4-7.3-fold lower). The GMT of B.1.351 or P.3 were lower than that of B.1.671.1. For the 4 patients infected with B.1.351 or B.1.617.1, the MN titer was highest for their respective lineage. RBD with E484K or E484Q mutation, either alone or in combination with other mutations, showed greatest reduction in serum IgG binding. CONCLUSION: P.3 and B.1.617.1 escape serum neutralization induced by natural infection or vaccine. Infection with one variant do not confer cross protection for heterologous lineages. Immunogenicity testing for second generation COVID-19 vaccines should include multiple variant and "non-variant" strains.

11.
Clin Infect Dis ; 73(1): 137-142, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1291923

ABSTRACT

After 2 months of relative quiescence, a large coronavirus disease 2019 outbreak occurred in Hong Kong in July 2020 after gradual relaxation of social distancing policy. Unique severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) phylogenetic clusters have been identified among locally acquired cases, with most genomes belonging to cluster HK1, which is phylogenetically related to SARS-CoV-2 reported overseas.


Subject(s)
COVID-19 , SARS-CoV-2 , Disease Outbreaks , Hong Kong , Humans , Phylogeny
12.
Clin Infect Dis ; 72(10): e659-e662, 2021 05 18.
Article in English | MEDLINE | ID: covidwho-1232198

ABSTRACT

We recently reported a patient with coronavirus disease 2019 reinfection. Here, we show that serum neutralizing antibodies could be detected during the first episode but not at the presentation of the second episode. During reinfection, neutralizing antibodies and high avidity immunoglobulin G were found within 8 days after hospitalization, whereas immunoglobulin M response was absent.


Subject(s)
COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , Humans , Immunoglobulin M , Reinfection , SARS-CoV-2
13.
Lancet Reg Health West Pac ; 10: 100130, 2021 May.
Article in English | MEDLINE | ID: covidwho-1144861

ABSTRACT

BACKGROUND: Viral genomic surveillance is vital for understanding the transmission of COVID-19. In Hong Kong, breakthrough outbreaks have occurred in July (third wave) and November (fourth wave) 2020. We used whole viral genome analysis to study the characteristics of these waves. METHODS: We analyzed 509 SARS-CoV-2 genomes collected from Hong Kong patients between 22nd January and 29th November, 2020. Phylogenetic and phylodynamic analyses were performed, and were interpreted with epidemiological information. FINDINGS: During the third and fourth waves, diverse SARS-CoV-2 genomes were identified among imported infections. Conversely, local infections were dominated by a single lineage during each wave, with 96.6% (259/268) in the third wave and 100% (73/73) in the fourth wave belonging to B.1.1.63 and B.1.36.27 lineages, respectively. While B.1.1.63 lineage was imported 2 weeks before the beginning of the third wave, B.1.36.27 lineage has circulated in Hong Kong for 2 months prior to the fourth wave. During the fourth wave, 50.7% (37/73) of local infections in November was identical to the viral genome from an imported case in September. Within B.1.1.63 or B.1.36.27 lineage in our cohort, the most common non-synonymous mutations occurred at the helicase (nsp13) gene. INTERPRETATION: Although stringent measures have prevented most imported cases from spreading in Hong Kong, a single lineage with low-level local transmission in October and early November was responsible for the fourth wave. A superspreading event or lower temperature in November may have facilitated the spread of the B.1.36.27 lineage.

14.
Emerg Infect Dis ; 27(1): 196-204, 2021 01.
Article in English | MEDLINE | ID: covidwho-993249

ABSTRACT

Initial cases of coronavirus disease in Hong Kong were imported from mainland China. A dramatic increase in case numbers was seen in February 2020. Most case-patients had no recent travel history, suggesting the presence of transmission chains in the local community. We collected demographic, clinical, and epidemiologic data from 50 patients, who accounted for 53.8% of total reported case-patients as of February 28, 2020. We performed whole-genome sequencing to determine phylogenetic relationship and transmission dynamics of severe acute respiratory syndrome coronavirus 2 infections. By using phylogenetic analysis, we attributed the community outbreak to 2 lineages; 1 harbored a common mutation, Orf3a-G251V, and accounted for 88.0% of the cases in our study. The estimated time to the most recent common ancestor of local coronavirus disease outbreak was December 24, 2019, with an evolutionary rate of 3.04 × 10-3 substitutions/site/year. The reproduction number was 1.84, indicating ongoing community spread.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , Disease Outbreaks , Adult , Aged , Aged, 80 and over , COVID-19/transmission , Cluster Analysis , Disease Hotspot , Evolution, Molecular , Female , Hong Kong/epidemiology , Humans , Male , Middle Aged , Mutation , Phylogeny , Phylogeography , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Viroporin Proteins/genetics , Whole Genome Sequencing , Young Adult
15.
Clin Microbiol Infect ; 27(9): 1350.e1-1350.e5, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-938847

ABSTRACT

OBJECTIVES: SARS-CoV-2 has evolved rapidly into several genetic clusters. However, data on mutations during the course of infection are scarce. This study aims to determine viral genome diversity in serial samples of COVID-19 patients. METHODS: Targeted deep sequencing of the spike gene was performed on serial respiratory specimens from COVID-19 patients using nanopore and Illumina sequencing. Sanger sequencing was then performed to confirm the single nucleotide polymorphisms. RESULTS: A total of 28 serial respiratory specimens from 12 patients were successfully sequenced using nanopore and Illumina sequencing. A 75-year-old patient with severe disease had a mutation, G22017T, identified in the second specimen. The frequency of G22017T increased from ≤5% (nanopore: 3.8%; Illumina: 5%) from the first respiratory tract specimen (sputum) to ≥60% (nanopore: 67.7%; Illumina: 60.4%) in the second specimen (saliva; collected 2 days after the first specimen). The difference in G22017T frequency was also confirmed by Sanger sequencing. G22017T corresponds to W152L amino acid mutation in the spike protein which was only found in <0.03% of the sequences deposited into a public database. Spike amino acid residue 152 is located within the N-terminal domain, which mediates the binding of a neutralizing antibody. DISCUSSION: A spike protein amino acid mutation W152L located within a neutralizing epitope has appeared naturally in a patient. Our study demonstrated that monitoring of serial specimens is important in identifying hotspots of mutations, especially those occurring at neutralizing epitopes which may affect the therapeutic efficacy of monoclonal antibodies.


Subject(s)
Antibodies, Viral/immunology , COVID-19/virology , Epitopes/genetics , Genetic Variation , Genome, Viral/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Adult , Aged , Antibodies, Neutralizing/immunology , Epitopes/immunology , Female , High-Throughput Nucleotide Sequencing , Humans , Immunoglobulin G/immunology , Male , Middle Aged , Mutation , Nanopore Sequencing , Respiratory System/virology , SARS-CoV-2/genetics , Saliva/virology , Sequence Analysis, RNA , Spike Glycoprotein, Coronavirus/immunology
17.
Emerg Microbes Infect ; 9(1): 1664-1670, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-630769

ABSTRACT

Coronavirus disease 2019 (COVID-19) has a wide spectrum of disease severity from mild upper respiratory symptoms to respiratory failure. The role of neutralizing antibody (NAb) response in disease progression remains elusive. This study determined the seroprevalence of 733 non-COVID-19 individuals from April 2018 to February 2020 in the Hong Kong Special Administrative Region and compared the neutralizing antibody (NAb) responses of eight COVID-19 patients admitted to the intensive care unit (ICU) with those of 42 patients not admitted to the ICU. We found that NAb against SARS-CoV-2 was not detectable in any of the anonymous serum specimens from the 733 non-COVID-19 individuals. The peak serum geometric mean NAb titer was significantly higher among the eight ICU patients than the 42 non-ICU patients (7280 [95% confidence interval (CI) 1468-36099]) vs (671 [95% CI, 368-1223]). Furthermore, NAb titer increased significantly at earlier infection stages among ICU patients than among non-ICU patients. The median number of days to reach the peak Nab titers after symptoms onset was shorter among the ICU patients (17.6) than that of the non-ICU patients (20.1). Multivariate analysis showed that oxygen requirement and fever during admission were the only clinical factors independently associated with higher NAb titers. Our data suggested that SARS-CoV-2 was unlikely to have silently spread before the COVID-19 emergence in Hong Kong. ICU patients had an accelerated and augmented NAb response compared to non-ICU patients, which was associated with disease severity. Further studies are required to understand the relationship between high NAb response and disease severity.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Betacoronavirus/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , Adult , Aged , COVID-19 , Cells, Cultured , Female , Humans , Intensive Care Units , Male , Middle Aged , Pandemics , SARS-CoV-2
18.
J Med Virol ; 92(11): 2725-2734, 2020 11.
Article in English | MEDLINE | ID: covidwho-530466

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19) pandemic. Accurate detection of SARS-CoV-2 using molecular assays is critical for patient management and the control of the COVID-19 pandemic. However, there is an increasing number of SARS-CoV-2 viruses with mutations at the primer or probe binding sites, and these mutations may affect the sensitivity of currently available real-time reverse transcription-polymerase chain reaction (RT-PCR) assays targeting the nucleocapsid (N), envelope (E), and open reading frame 1a or 1b genes. Using sequence-independent single-primer amplification and nanopore whole-genome sequencing, we have found that the nonstructural protein 1 (nsp1) gene, located at the 5' end of the SARS-CoV-2 genome, was highly expressed in the nasopharyngeal or saliva specimens of 9 COVID-19 patients of different clinical severity. Based on this finding, we have developed a novel nsp1 real-time RT-PCR assay. The primers and probes are highly specific for SARS-CoV-2. Validation with 101 clinical specimens showed that our nsp1 RT-PCR assay has a sensitivity of 93.1% (95% confidence interval [CI]: 86.2%-97.2%), which was similar to those of N and E gene RT-PCR assays. The diagnostic specificity was 100% (95% CI: 92.9%-100%). The addition of nsp1 for multitarget detection of SARS-CoV-2 can avoid false-negative results due to mutations at the primers/probes binding sites of currently available RT-PCR assays.


Subject(s)
COVID-19/diagnosis , Nanopore Sequencing/methods , RNA-Dependent RNA Polymerase/genetics , SARS-CoV-2/genetics , Viral Nonstructural Proteins/genetics , Whole Genome Sequencing/methods , COVID-19/virology , COVID-19 Nucleic Acid Testing , Female , Humans , Male , Middle Aged , Mutation , Nasopharynx/virology , Open Reading Frames , RNA, Viral/genetics , Saliva/virology , Sensitivity and Specificity
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