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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.
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.

3.
Science ; 369(6508): 1210-1220, 2020 09 04.
Article in English | MEDLINE | ID: covidwho-704393

ABSTRACT

Coronavirus disease 2019 (COVID-19) represents a global crisis, yet major knowledge gaps remain about human immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed immune responses in 76 COVID-19 patients and 69 healthy individuals from Hong Kong and Atlanta, Georgia, United States. In the peripheral blood mononuclear cells (PBMCs) of COVID-19 patients, we observed reduced expression of human leukocyte antigen class DR (HLA-DR) and proinflammatory cytokines by myeloid cells as well as impaired mammalian target of rapamycin (mTOR) signaling and interferon-α (IFN-α) production by plasmacytoid dendritic cells. By contrast, we detected enhanced plasma levels of inflammatory mediators-including EN-RAGE, TNFSF14, and oncostatin M-which correlated with disease severity and increased bacterial products in plasma. Single-cell transcriptomics revealed a lack of type I IFNs, reduced HLA-DR in the myeloid cells of patients with severe COVID-19, and transient expression of IFN-stimulated genes. This was consistent with bulk PBMC transcriptomics and transient, low IFN-α levels in plasma during infection. These results reveal mechanisms and potential therapeutic targets for COVID-19.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , COVID-19 , Cytokines/blood , DNA, Bacterial/blood , Dendritic Cells/immunology , Dendritic Cells/metabolism , Female , Flow Cytometry , HLA-DR Antigens/analysis , Humans , Immunity , Immunity, Innate , Immunoglobulins/blood , Immunoglobulins/immunology , Inflammation Mediators/blood , Interferon Type I/metabolism , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Lipopolysaccharides/blood , Male , Myeloid Cells/immunology , Myeloid Cells/metabolism , Pandemics , SARS-CoV-2 , Signal Transduction , Single-Cell Analysis , Systems Biology , TOR Serine-Threonine Kinases/metabolism , Transcription, Genetic , Transcriptome
4.
Cell Rep ; 31(9): 107725, 2020 06 02.
Article in English | MEDLINE | ID: covidwho-276452

ABSTRACT

The World Health Organization has declared the ongoing outbreak of COVID-19, which is caused by a novel coronavirus SARS-CoV-2, a pandemic. There is currently a lack of knowledge about the antibody response elicited from SARS-CoV-2 infection. One major immunological question concerns antigenic differences between SARS-CoV-2 and SARS-CoV. We address this question by analyzing plasma from patients infected by SARS-CoV-2 or SARS-CoV and from infected or immunized mice. Our results show that, although cross-reactivity in antibody binding to the spike protein is common, cross-neutralization of the live viruses may be rare, indicating the presence of a non-neutralizing antibody response to conserved epitopes in the spike. Whether such low or non-neutralizing antibody response leads to antibody-dependent disease enhancement needs to be addressed in the future. Overall, this study not only addresses a fundamental question regarding antigenicity differences between SARS-CoV-2 and SARS-CoV but also has implications for immunogen design and vaccine development.


Subject(s)
Antibodies, Viral/immunology , Antigens, Viral/immunology , Betacoronavirus/immunology , SARS Virus/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/immunology , COVID-19 , Chlorocebus aethiops , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Cross Reactions/immunology , Enzyme-Linked Immunosorbent Assay , Humans , Male , Mice , Mice, Inbred BALB C , Neutralization Tests , Pandemics/prevention & control , Pneumonia, Viral/immunology , Pneumonia, Viral/prevention & control , Receptors, Virus/metabolism , SARS-CoV-2 , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/prevention & control , Sf9 Cells , Vero Cells , Viral Vaccines/immunology
6.
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
7.
Clin Infect Dis ; 71(15): 841-843, 2020 07 28.
Article in English | MEDLINE | ID: covidwho-724

ABSTRACT

The 2019 novel coronavirus (2019-nCoV) was detected in the self-collected saliva of 91.7% (11/12) of patients. Serial saliva viral load monitoring generally showed a declining trend. Live virus was detected in saliva by viral culture. Saliva is a promising noninvasive specimen for diagnosis, monitoring, and infection control in patients with 2019-nCoV infection.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Saliva/virology , Adult , Aged , Animals , COVID-19 , Cell Line , Chlorocebus aethiops , Female , Hong Kong , Humans , Infection Control/methods , Male , Middle Aged , Pandemics , SARS-CoV-2 , Vero Cells , Viral Load/methods
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