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1.
Infect Control Hosp Epidemiol ; : 1-6, 2022 Jul 11.
Article in English | MEDLINE | ID: covidwho-1977949

ABSTRACT

BACKGROUND: Air dispersal of respiratory viruses other than SARS-CoV-2 has not been systematically reported. The incidence and factors associated with air dispersal of respiratory viruses are largely unknown. METHODS: We performed air sampling by collecting 72,000 L of air over 6 hours for pediatric and adolescent patients infected with parainfluenza virus 3 (PIF3), respiratory syncytial virus (RSV), rhinovirus, and adenovirus. The patients were singly or 2-patient cohort isolated in airborne infection isolation rooms (AIIRs) from December 3, 2021, to January 26, 2022. The viral load in nasopharyngeal aspirates (NPA) and air samples were measured. Factors associated with air dispersal were investigated and analyzed. RESULTS: Of 20 singly isolated patients with median age of 30 months (range, 3 months-15 years), 7 (35%) had air dispersal of the viruses compatible with their NPA results. These included 4 (40%) of 10 PIF3-infected patients, 2 (66%) of 3 RSV-infected patients, and 1 (50%) of 2 adenovirus-infected patients. The mean viral load in their room air sample was 1.58×103 copies/mL. Compared with 13 patients (65%) without air dispersal, these 7 patients had a significantly higher mean viral load in their NPA specimens (6.15×107 copies/mL vs 1.61×105 copies/mL; P < .001). Another 14 patients were placed in cohorts as 7 pairs infected with the same virus (PIF3, 2 pairs; RSV, 3 pairs; rhinovirus, 1 pair; and adenovirus, 1 pair) in double-bed AIIRs, all of which had air dispersal. The mean room air viral load in 2-patient cohorts was significantly higher than in rooms of singly isolated patients (1.02×104 copies/mL vs 1.58×103 copies/mL; P = .020). CONCLUSION: Air dispersal of common respiratory viruses may have infection prevention and public health implications.

2.
Build Environ ; 221: 109323, 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1906829

ABSTRACT

The phenomenon of vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in high-rise residential buildings (HRRBs) is unique in our densely populated cosmopolitan city. The compulsory testing of a whole building under the scheme of restriction-testing declaration (RTD) during the fourth wave (non-Omicron variant) and fifth wave (mostly Omicron variant) of COVID-19 outbreak in Hong Kong allowed us to study the prevalence of this phenomenon, which may represent a form of airborne transmission. From 23 January 2021 to 24 March 2022, 25,450 (5.8%) of 436,397 residents from 223 (63.0%) of 354 HRRBs under RTD were test-positive for SARS-CoV-2. Using the clustering of cases among vertically aligned flats with shared drainage stack and lightwell as a surrogate marker of vertical transmission, the number of vertically aligned flats with positive COVID-19 cases was significantly higher in the fifth wave compared with the fourth wave (14.2%, 6471/45,531 vs 0.24%, 3/1272; p < 0.001; or 2212 vs 1 per-million-flats; p < 0.001). Excluding 22,801 residents from 38 HRRBs who were tested negative outside the 12-week periods selected in fourth and fifth waves, the positive rate among residents was significantly higher among residents during the fifth wave than the fourth wave (6.5%, 25,434/389,700 vs 0.07%, 16/23,896; p < 0.001). Within the flats with COVID-19 cases, the proportion of vertically aligned flats was also significantly higher in the fifth wave than in the fourth wave (95.6%, 6471/6766 vs 30.0%, 3/10, p < 0.001). The proportion of HRRBs with COVID-19 cases was significantly higher during the corresponding 12-week period chosen for comparison (78.2%, 219/280 vs 11.1%, 4/36; p < 0.001). Whole-genome phylogenetic analysis of 332 viral genomes showed that Omicron BA.2 was the predominant strain, supporting the high transmissibility of BA.2 by airborne excreta-aerosol route in HRRBs of Hong Kong.

3.
Clin Infect Dis ; 2022 Feb 18.
Article in English | MEDLINE | ID: covidwho-1886373

ABSTRACT

BACKGROUND: The role of SARS-CoV-2 in the pathogenesis of testicular damage is uncertain. METHODS: We investigated the virological, pathological, and immunological changes in testes of hamsters challenged by SARS-CoV-2 wild-type and its variants by intranasal or direct testicular inoculation using influenza virus A(H1N1)pdm09 as control. RESULTS: Besides self-limiting respiratory tract infection, intranasal SARS-CoV-2 challenge caused acute decrease in sperm count, and serum testosterone and inhibin B at 4 to 7 days post-infection (dpi), and subsequently reduced testicular size and weight, and serum sex hormone level at 42 to 120 dpi. Acute histopathological damage with varying degree of testicular inflammation, haemorrhage, and necrosis, degeneration of seminiferous tubules and disruption of orderly spermatogenesis were seen with increasing virus inoculum. Degeneration and necrosis of Sertoli and Leydig cells were found. Though viral loads and SARS-CoV-2 nucleocapid (N) protein expression were markedly lower in testicular than lung tissues, direct intra-testicular injection showed N expressing interstitial cells and epididymal epithelial cells. Control intranasal or intra-testicular challenge by A(H1N1)pdm09 showed no testicular infection or damage. From 7 to 120 dpi, degeneration and apoptosis of seminiferous tubules, immune complex deposition and depletion of spermatogenic cell and spermatozoa persisted. Intranasal challenge with Omicron and Delta variants could also induce similar testicular changes. These testicular damages can be prevented by vaccination. CONCLUSIONS: SARS-CoV-2 can cause acute testicular damage with subsequent chronic asymmetric testicular atrophy and associated hormonal changes despite a self-limiting pneumonia in hamsters. Awareness of possible hypogonadism and subfertility is important in managing convalescent COVID-19 males.

4.
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.

5.
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.

6.
Clin Infect Dis ; 2022 Jan 04.
Article in English | MEDLINE | ID: covidwho-1852988

ABSTRACT

This retrospective study of incoming travelers with COVID-19 showed that individuals immunized by mRNA vaccines had significantly longer post-vaccination interval (median: 30.5 days) to breakthrough infection, lower WBC and LDH on admission, and less radiographic abnormalities than those immunized by inactivated virus vaccine who paradoxically had lower respiratory viral load.

7.
Clin Infect Dis ; 74(8): 1485-1488, 2022 04 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
8.
Interface Focus ; 12(2): 20210063, 2022 Apr 06.
Article in English | MEDLINE | ID: covidwho-1713822

ABSTRACT

Poor housing conditions are known to be associated with infectious diseases such as high Coronavirus disease 2019 (COVID-19) incidences. Transmission causes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in poor housing conditions can be complex. An understanding of the exact mechanism of transmission can help to pinpoint contributing environmental issues. Here, we investigated a Hong Kong COVID-19 outbreak in early 2021 in four traditional Tong Lau houses with subdivided units. There are more than 80 subdivided units of less than 20 m2 floor area each on average. With a total of 34 confirmed COVID-19 cases, the outbreak had an attack rate of 25.4%, being one of the highest attack rates observed in Hong Kong, and ranked among the highest attack rates in reported outbreaks internationally. Tracer gas leakage and decay measurements were performed in the drainage system and in the subdivided units to determine the transport of infectious aerosols by the owner-modified sophisticated wastewater drainage pipe networks and the poor ventilation conditions in some subdivided units. The results show that the outbreak was probably due to multiple transmission routes, i.e. by the drainage pipe spread of stack aerosols, which is enhanced by poor ventilation in the subdivided units.

9.
Emerg Microbes Infect ; 11(1): 689-698, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1713523

ABSTRACT

During the investigation of a pet shop outbreak of severe acute respiratory coronavirus 2 (SARS-CoV-2) with probable hamster-to-human transmission, the environmental and hamster samples in epidemiologically linked pet shops were found positive for SARS-CoV-2 Delta variant AY.127 strains which are phylogenetically closely related to patients and reported European strains. This interspecies' spill-over has triggered transmission in 58 patients epidemiologically linked to three pet shops. Incidentally, three dwarf hamsters imported from the Netherlands and centralized in a warehouse distributing animals to pet shops were positive for SARS-CoV-2 spike variant phylogenetically related to European B.1.258 strains from March 2020. This B.1.258 strain almost disappeared in July 2021. While no hamster-to-human transmission of B.1.258-like strain was found in this outbreak, molecular docking showed that its spike receptor-binding domain (RBD) has a similar binding energy to human ACE2 compared to that of Delta variant AY.127. Therefore, the potential of this B.1.258-related spike variant for interspecies jumping cannot be ignored. The co-circulation of B.1.258-related spike variants with Delta AY.127, which originated in Europe and was not previously found in Hong Kong, suggested that hamsters in our wholesale warehouse and retail pet shops more likely have acquired these viruses in the Netherlands or stopovers during delivery by aviation than locally. The risk of human-to-hamster reverse zoonosis by multiple SARS-CoV-2 variants leading to further adaptive spike mutations with subsequent transmission back to humans cannot be underestimated as an outbreak source of COVID-19. Testing imported pet animals susceptible to SARS-CoV-2 is warranted to prevent future outbreaks.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Cricetinae , Hong Kong , Humans , Molecular Docking Simulation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry
11.
Clin Infect Dis ; 74(11): 1933-1950, 2022 06 10.
Article in English | MEDLINE | ID: covidwho-1704370

ABSTRACT

BACKGROUND: Post-vaccination myopericarditis is reported after immunization with coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines. The effect of inadvertent intravenous injection of this vaccine on the heart is unknown. METHODS: We compared the clinical manifestations, histopathological changes, tissue mRNA expression, and serum levels of cytokine/chemokine and troponin in Balb/c mice at different time points after intravenous (IV) or intramuscular (IM) vaccine injection with normal saline (NS) control. RESULTS: Although significant weight loss and higher serum cytokine/chemokine levels were found in IM group at 1-2 days post-injection (dpi), only IV group developed histopathological changes of myopericarditis as evidenced by cardiomyocyte degeneration, apoptosis, and necrosis with adjacent inflammatory cell infiltration and calcific deposits on visceral pericardium, although evidence of coronary artery or other cardiac pathologies was absent. Serum troponin level was significantly higher in IV group. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antigen expression by immunostaining was occasionally found in infiltrating immune cells of the heart or injection site, in cardiomyocytes and intracardiac vascular endothelial cells, but not skeletal myocytes. The histological changes of myopericarditis after the first IV-priming dose persisted for 2 weeks and were markedly aggravated by a second IM- or IV-booster dose. Cardiac tissue mRNA expression of interleukin (IL)-1ß, interferon (IFN)-ß, IL-6, and tumor necrosis factor (TNF)-α increased significantly from 1 dpi to 2 dpi in the IV group but not the IM group, compatible with presence of myopericarditis in the IV group. Ballooning degeneration of hepatocytes was consistently found in the IV group. All other organs appeared normal. CONCLUSIONS: This study provided in vivo evidence that inadvertent intravenous injection of COVID-19 mRNA vaccines may induce myopericarditis. Brief withdrawal of syringe plunger to exclude blood aspiration may be one possible way to reduce such risk.


Subject(s)
COVID-19 Vaccines , COVID-19 , Animals , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Chemokines , Cytokines , Endothelial Cells , Humans , Injections, Intravenous , Mice , RNA, Messenger , SARS-CoV-2 , Troponin , Vaccines, Synthetic , mRNA Vaccines
12.
J Hazard Mater ; 430: 128504, 2022 05 15.
Article in English | MEDLINE | ID: covidwho-1693278

ABSTRACT

Airborne transmission of SARS-CoV-2 has been increasingly recognized in the outbreak of COVID-19, especially with the Omicron variant. We investigated an outbreak due to Omicron variant in a restaurant. Besides epidemiological and phylogenetic analyses, the secondary attack rates of customers of restaurant-related COVID-19 outbreak before (Outbreak R1) and after enhancement of indoor air dilution (Outbreak R2) were compared. On 27th December 2021, an index case stayed in restaurant R2 for 98 min. Except for 1 sitting in the same table, six other secondary cases sat in 3 corners at 3 different zones, which were served by different staff. The median exposure time was 34 min (range: 19-98 min). All 7 secondary cases were phylogenetically related to the index. Smoke test demonstrated that the airflow direction may explain the distribution of secondary cases. Compared with an earlier COVID-19 outbreak in another restaurant R1 (19th February 2021), which occurred prior to the mandatory enhancement of indoor air dilution, the secondary attack rate among customers in R2 was significantly lower than that in R1 (3.4%, 7/207 vs 28.9%, 22/76, p<0.001). Enhancement of indoor air dilution through ventilation and installation of air purifier could minimize the risk of SARS-CoV-2 transmission in the restaurants.


Subject(s)
Air Pollution, Indoor , COVID-19 , COVID-19/epidemiology , Disease Outbreaks , Humans , Phylogeny , Restaurants , SARS-CoV-2/genetics
13.
J Hazard Mater ; 430: 128475, 2022 05 15.
Article in English | MEDLINE | ID: covidwho-1676810

ABSTRACT

Vertical transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) along a vertical column of flats has been documented in several outbreaks of coronavirus disease 2019 (COVID-19) in Guangdong and Hong Kong. We describe an outbreak in Luk Chuen House, involving two vertical columns of flats associated with an unusually connected two-stack drainage system, in which nine individuals from seven households were infected. The index case resided in Flat 812 (8th floor, Unit 12), two flats (813, 817) on its opposite side reported one case each (i.e., a horizontal sub-cluster). All other flats with infected residents were vertically associated, forming a vertical sub-cluster. We injected tracer gas (SF6) into drainage stacks via toilet or balcony of Flat 812, monitored gas concentrations in roof vent, toilet, façade, and living room in four of the seven flats with infected residents and four flats with no infected residents. The measured gas concentration distributions agreed with the observed distribution of affected flats. Aerosols leaking into drainage stacks may generate the vertical sub-cluster, whereas airflow across the corridor probably caused the horizontal sub-cluster. Sequencing and phylogenetic analyses also revealed a common point-source. The findings provided additional evidence of probable roles of drainage systems in SARS-CoV-2 transmission.


Subject(s)
COVID-19 , Aerosols , COVID-19/epidemiology , Disease Outbreaks , Housing , Humans , Phylogeny , SARS-CoV-2
16.
Microbiol Resour Announc ; 10(15)2021 Apr 15.
Article in English | MEDLINE | ID: covidwho-1522915

ABSTRACT

We report the genome sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains from the clinical samples of three coronavirus disease 2019 (COVID-19) patients in Hong Kong. All the genome sequences showed a 370-nucleotide deletion resulting in the complete loss of ORF7a.

17.
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).

18.
Clin Infect Dis ; 73(6): e1356-e1364, 2021 09 15.
Article in English | MEDLINE | ID: covidwho-1412019

ABSTRACT

BACKGROUND: Nosocomial outbreaks with superspreading of coronavirus disease 2019 due to a possible airborne transmission have not been reported. METHODS: Epidemiological analysis, environmental samplings, and whole-genome sequencing (WGS) were performed for a hospital outbreak. RESULTS: A superspreading event that involved 12 patients and 9 healthcare workers (HCWs) occurred within 9 days in 3 of 6 cubicles at an old-fashioned general ward with no air exhaust built within the cubicles. The environmental contamination by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was significantly higher in air grilles (>2 m from patients' heads and not within reach) than on high-touch clinical surfaces (36.4%, 8 of 22 vs 3.4%, 1 of 29, P = .003). Six (66.7%) of 9 contaminated air exhaust grilles were located outside patient cubicles. The clinical attack rate of patients was significantly higher than of HCWs (15.4%, 12 of 78 exposed patients vs 4.6%, 9 of 195 exposed HCWs, P = .005). Moreover, the clinical attack rate of ward-based HCWs was significantly higher than of nonward-based HCWs (8.1%, 7 of 68 vs 1.8%, 2 of 109, P = .045). The episodes (mean ±â€…standard deviation) of patient-care duty assignment in the cubicles was significantly higher among infected ward-based HCWs than among noninfected ward-based HCWs (6.0 ±â€…2.4 vs 3.0 ±â€…2.9, P = .012) during the outbreak period. The outbreak strains belong to SARS-CoV-2 lineage B.1.36.27 (GISAID clade GH) with the unique S-T470N mutation on WGS. CONCLUSIONS: This nosocomial point source superspreading event due to possible airborne transmission demonstrates the need for stringent SARS-CoV-2 screening at admission to healthcare facilities and better architectural design of ventilation systems to prevent such outbreaks. Portable high-efficiency particulate filters were installed in each cubicle to improve ventilation before resumption of clinical service.


Subject(s)
COVID-19 , Cross Infection , Cross Infection/epidemiology , Disease Outbreaks , Health Personnel , Hospitals , Humans , SARS-CoV-2
19.
Clin Infect Dis ; 74(8): 1485-1488, 2022 04 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
20.
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
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