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1.
EBioMedicine ; 79: 103986, 2022 May.
Article in English | MEDLINE | ID: covidwho-1778094

ABSTRACT

BACKGROUND: SARS-CoV-2 Omicron variant evades immunity from past infection or vaccination and is associated with a greater risk of reinfection among recovered COVID-19 patients. We assessed the serum neutralizing antibody (NAb) activity against Omicron variant (Omicron NAb) among recovered COVID-19 patients with or without vaccination. METHODS: In this prospective cohort study with 135 recovered COVID-19 patients, we determined the serum NAb titers against ancestral virus or variants using a live virus NAb assay. We used the receiver operating characteristic analysis to determine the optimal cutoff for a commercially-available surrogate NAb assay. FINDINGS: Among recovered COVID-19 patients, the serum live virus geometric mean Omicron NAb titer was statistically significantly higher among BNT162b2 recipients compared to non-vaccinated individuals (85.4 vs 5.6,P < 0.0001). The Omicron seropositive rates in live virus NAb test (NAb titer ≥10) were statistically significantly higher among BNT162b2 (90.6% [29/32];P < 0.0001) or CoronaVac (36.7% [11/30]; P = 0.0115) recipients when compared with non-vaccinated individuals (12.3% [9/73]). Subgroup analysis of CoronaVac recipients showed that the Omicron seropositive rates were higher among individuals with two doses than those with one dose (85.7% vs 21.7%; P = 0.0045). For the surrogate NAb assay, a cutoff of 109.1 AU/ml, which is 7.3-fold higher than the manufacturer's recommended cutoff, could achieve a sensitivity and specificity of 89.5% and 89.8%, respectively, in detecting Omicron NAb. INTERPRETATION: Among individuals with prior COVID-19, one dose of BNT162b2 or two doses of CoronaVac could induce detectable serum Omicron NAb. Our result would be particularly important for guiding vaccine policies in countries with COVID-19 vaccine shortage. FUNDING: Health and Medical Research Fund, Richard and Carol Yu, Michael Tong (see acknowledgments for full list).


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Blocking , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , Humans , Prospective Studies , SARS-CoV-2
2.
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.

3.
SSRN;
Preprint in English | SSRN | ID: ppcovidwho-326165

ABSTRACT

Background: SARS-CoV-2 Omicron variant evades immunity from past infection or vaccination and is associated with a greater risk of reinfection among recovered COVID-19 patients. We assessed the serum neutralizing antibody (NAb) activity against Omicron variant (Omicron NAb) among recovered COVID-19 patients with or without vaccination. Methods: In this prospective cohort study with 135 recovered COVID-19 patients, we determined the serum NAb titers against ancestral virus or variants using a live virus NAb assay. We used the receiver operating characteristic analysis to determine the optimal cutoff for a commercially-available surrogate NAb assay. Findings: Among recovered COVID-19 patients, the serum live virus geometric mean Omicron NAb titer was statistically significantly higher among BNT162b2 recipients compared to non-vaccinated individuals (85.4 vs 5.6, P<0.0001). The Omicron seropositive rates in live virus NAb test (NAb titer ≥10) were statistically significantly higher among BNT162b2 (93.5% [29/32];P<0.0001) or CoronaVac (36.7% [11/30];P=0.0115) recipients when compared with non-vaccinated individuals (12.3% [9/73]). Subgroup analysis of CoronaVac recipients showed that the Omicron seropositive rates were higher among individuals with two doses than those with one dose (85.7% vs 21.7%;P=0.0045). For the surrogate NAb assay, a cutoff of 109.1 AU/ml, which is 7.3-fold higher than the manufacturer’s recommended cutoff, could achieve a sensitivity and specificity of 89.5% and 89.8%, respectively, in detecting Omicron NAb. Interpretation: Among individuals with prior COVID-19, one dose of BNT162b2 and two doses of CoronaVac could induce detectable serum Omicron NAb. Our result would be particularly important for guiding vaccine policies in countries with COVID-19 vaccine shortage. Funding Information: This work was supported by Health and Medical Research Fund, the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region (Ref no.: COVID190124 and COVID1903010 [Project 1]), and donations of Richard Yu and Carol Yu, Shaw Foundation Hong Kong, Michael Seak-Kan Tong, May Tam Mak Mei Yin, Lee Wan Keung Charity Foundation Limited, Hong Kong Sanatorium & Hospital, Respiratory Viral Research Foundation Limited, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Chan Yin Chuen Memorial Charitable Foundation, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, the Jessie & George Ho Charitable Foundation, Kai Chong Tong, Tse Kam Ming Laurence, Foo Oi Foundation Limited, Betty Hing-Chu Lee, and Ping Cham So. Declaration of Interests: KYY and KKWT report collaboration with SinoVac and Sinopharm. Other authors declare no conflict of interest.

4.
Front Immunol ; 12: 799896, 2021.
Article in English | MEDLINE | ID: covidwho-1662583

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in rapid T lymphocytopenia and functional impairment of T cells. The underlying mechanism, however, remains incompletely understood. In this study, we focused on characterizing the phenotype and kinetics of T-cell subsets with mitochondrial dysfunction (MD) by multicolor flow cytometry and investigating the association between MD and T-cell functionality. While 73.9% of study subjects displayed clinical lymphocytopenia upon hospital admission, a significant reduction of CD4 or CD8 T-cell frequency was found in all asymptomatic, symptomatic, and convalescent cases. CD4 and CD8 T cells with increased MD were found in both asymptomatic and symptomatic patients within the first week of symptom onset. Lower proportion of memory CD8 T cell with MD was found in severe patients than in mild ones at the stage of disease progression. Critically, the frequency of T cells with MD in symptomatic patients was preferentially associated with CD4 T-cell loss and CD8 T-cell hyperactivation, respectively. Patients bearing effector memory CD4 and CD8 T cells with the phenotype of high MD exhibited poorer T-cell responses upon either phorbol 12-myristate-13-acetate (PMA)/ionomycin or SARS-CoV-2 peptide stimulation than those with low MD. Our findings demonstrated an MD-associated mechanism underlying SARS-CoV-2-induced T lymphocytopenia and functional impairment during the acute phase of infection.


Subject(s)
COVID-19/complications , Lymphopenia/complications , Lymphopenia/etiology , Mitochondrial Diseases/etiology , Adult , Aged , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/drug therapy , COVID-19/immunology , Female , Humans , Immunologic Memory/immunology , Ionomycin/therapeutic use , Lymphopenia/immunology , Male , Middle Aged , Mitochondria/immunology , Mitochondrial Diseases/immunology , Phosphorylcholine/analogs & derivatives , Phosphorylcholine/therapeutic use , Polymethacrylic Acids/therapeutic use
5.
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.

6.
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
8.
Lancet Infect Dis ; 20(5): 565-574, 2020 05.
Article in English | MEDLINE | ID: covidwho-14173

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) causes severe community and nosocomial outbreaks. Comprehensive data for serial respiratory viral load and serum antibody responses from patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not yet available. Nasopharyngeal and throat swabs are usually obtained for serial viral load monitoring of respiratory infections but gathering these specimens can cause discomfort for patients and put health-care workers at risk. We aimed to ascertain the serial respiratory viral load of SARS-CoV-2 in posterior oropharyngeal (deep throat) saliva samples from patients with COVID-19, and serum antibody responses. METHODS: We did a cohort study at two hospitals in Hong Kong. We included patients with laboratory-confirmed COVID-19. We obtained samples of blood, urine, posterior oropharyngeal saliva, and rectal swabs. Serial viral load was ascertained by reverse transcriptase quantitative PCR (RT-qPCR). Antibody levels against the SARS-CoV-2 internal nucleoprotein (NP) and surface spike protein receptor binding domain (RBD) were measured using EIA. Whole-genome sequencing was done to identify possible mutations arising during infection. FINDINGS: Between Jan 22, 2020, and Feb 12, 2020, 30 patients were screened for inclusion, of whom 23 were included (median age 62 years [range 37-75]). The median viral load in posterior oropharyngeal saliva or other respiratory specimens at presentation was 5·2 log10 copies per mL (IQR 4·1-7·0). Salivary viral load was highest during the first week after symptom onset and subsequently declined with time (slope -0·15, 95% CI -0·19 to -0·11; R2=0·71). In one patient, viral RNA was detected 25 days after symptom onset. Older age was correlated with higher viral load (Spearman's ρ=0·48, 95% CI 0·074-0·75; p=0·020). For 16 patients with serum samples available 14 days or longer after symptom onset, rates of seropositivity were 94% for anti-NP IgG (n=15), 88% for anti-NP IgM (n=14), 100% for anti-RBD IgG (n=16), and 94% for anti-RBD IgM (n=15). Anti-SARS-CoV-2-NP or anti-SARS-CoV-2-RBD IgG levels correlated with virus neutralisation titre (R2>0·9). No genome mutations were detected on serial samples. INTERPRETATION: Posterior oropharyngeal saliva samples are a non-invasive specimen more acceptable to patients and health-care workers. Unlike severe acute respiratory syndrome, patients with COVID-19 had the highest viral load near presentation, which could account for the fast-spreading nature of this epidemic. This finding emphasises the importance of stringent infection control and early use of potent antiviral agents, alone or in combination, for high-risk individuals. Serological assay can complement RT-qPCR for diagnosis. FUNDING: Richard and Carol Yu, May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Michael Tong, Marina Lee, Government Consultancy Service, and Sanming Project of Medicine.


Subject(s)
Antibodies, Viral/blood , Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Saliva/virology , Adult , Aged , Betacoronavirus/genetics , Betacoronavirus/immunology , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/immunology , Coronavirus Infections/virology , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2 , Severity of Illness Index , Viral Load
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