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1.
Emerg Microbes Infect ; 11(1): 1024-1036, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1740712

ABSTRACT

SARS-CoV-2 has caused the COVID-19 pandemic. B.1.617 variants (including Kappa and Delta) have been transmitted rapidly in India. The transmissibility, pathogenicity, and neutralization characteristics of these variants have received considerable interest. In this study, 22 pseudotyped viruses were constructed for B.1.617 variants and their corresponding single amino acid mutations. B.1.617 variants did not exhibit significant enhanced infectivity in human cells, but mutations T478K and E484Q in the receptor binding domain led to enhanced infectivity in mouse ACE2-overexpressing cells. Furin activities were slightly increased against B.1.617 variants and cell-cell fusion after infection of B.1.617 variants were enhanced. Furthermore, B.1.617 variants escaped neutralization by several mAbs, mainly because of mutations L452R, T478K, and E484Q in the receptor binding domain. The neutralization activities of sera from convalescent patients, inactivated vaccine-immunized volunteers, adenovirus vaccine-immunized volunteers, and SARS-CoV-2 immunized animals against pseudotyped B.1.617 variants were reduced by approximately twofold, compared with the D614G variant.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Neutralizing , Cell Fusion , Humans , Mice , Mutation , Pandemics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus , Viral Tropism
2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323773

ABSTRACT

SARS-CoV-2 has caused the COVID-19 pandemic. Recently, B.1.617 variants have been transmitted rapidly in India. The transmissibility, pathogenicity, and neutralization characteristics of these variants have received considerable interest. In this study, 22 pseudotyped viruses were constructed for B.1.617 variants and their corresponding single amino acid mutations. B.1.617 variants did not exhibit significant enhanced infectivity in human cells, but mutations T478K and E484Q in the receptor binding domain led to enhanced infectivity in mouse ACE2-overexpressing cells. Furin activities were slightly increased against B.1.617 variants and cell–cell fusion after infection of B.1.617 variants was enhanced. Furthermore, B.1.617 variants escaped neutralization by several mAbs, mainly because of mutations L452R, T478K, and E484Q in the receptor binding domain. The neutralization activities of sera from convalescent patients, inactivated vaccine-immunized volunteers, adenovirus vaccine-immunized volunteers, and SARS-CoV-2 immunized animals against pseudotyped B.1.617 variants were reduced by approximately twofold, compared with the D614G variant.

3.
Nature ; 603(7903): 919-925, 2022 03.
Article in English | MEDLINE | ID: covidwho-1655591

ABSTRACT

Omicron (B.1.1.529), the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising concerns about the effectiveness of antibody therapies and vaccines1,2. Here we examined whether sera from individuals who received two or three doses of inactivated SARS-CoV-2 vaccine could neutralize authentic Omicron. The seroconversion rates of neutralizing antibodies were 3.3% (2 out of 60) and 95% (57 out of 60) for individuals who had received 2 and 3 doses of vaccine, respectively. For recipients of three vaccine doses, the geometric mean neutralization antibody titre for Omicron was 16.5-fold lower than for the ancestral virus (254). We isolated 323 human monoclonal antibodies derived from memory B cells in triple vaccinees, half of which recognized the receptor-binding domain, and showed that a subset (24 out of 163) potently neutralized all SARS-CoV-2 variants of concern, including Omicron. Therapeutic treatments with representative broadly neutralizing monoclonal antibodies were highly protective against infection of mice with SARS-CoV-2 Beta (B.1.351) and Omicron. Atomic structures of the Omicron spike protein in complex with three classes of antibodies that were active against all five variants of concern defined the binding and neutralizing determinants and revealed a key antibody escape site, G446S, that confers greater resistance to a class of antibodies that bind on the right shoulder of the receptor-binding domain by altering local conformation at the binding interface. Our results rationalize the use of three-dose immunization regimens and suggest that the fundamental epitopes revealed by these broadly ultrapotent antibodies are rational targets for a universal sarbecovirus vaccine.


Subject(s)
COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Animals , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/isolation & purification , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/isolation & purification , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/immunology , Antibodies, Viral/isolation & purification , Antibodies, Viral/therapeutic use , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Disease Models, Animal , Humans , Mice , Neutralization Tests , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology
4.
BJPsych Open ; 7(3): e76, 2021 Apr 05.
Article in English | MEDLINE | ID: covidwho-1166953

ABSTRACT

BACKGROUND: It is important to maintain the psychological well-being of front-line healthcare staff during the coronavirus disease 2019 (COVID-19) pandemic. AIMS: To examine COVID-19-related stress and its immediate psychological impact on healthcare staff. METHOD: All healthcare staff working in the fever clinic, from 20 January 2020 to 26 March 2020, of a tertiary general hospital were enrolled. Stress management procedures were in place to alleviate concerns about the respondents' own health and the health of their families, to help them adjust their work and to provide psychological support via a hotline. Qualitative interviews were undertaken and the Sources of Distress and the Impact of Event Scale-Revised (IES-R) were administered. RESULTS: Among the 102 participants (25 males; median age 30 years, interquartile range (IQR) = 27-36), the median IES-R total score was 3 (IQR = 0-8), and 6 participants (6.0%) scored above the cut-off on the IES-R (≥20). Safety and security were acceptable or better for 92 (90.2%) participants. The top four sources of distress were worry about the health of one's family/others at 0.88 (IQR = 0.25-1.25), worry about the virus spread at 0.50 (IQR = 0.00-1.00), worry about changes in work at 0.50 (IQR = 0.00-1.00) and worry about one's own health at 0.25 (IQR = 0.25-0.75). There was a moderate correlation between the IES-R score and the Sources of Distress score (rho = 0.501, P = 0.001). CONCLUSIONS: The stress levels of healthcare staff in the fever clinic during the COVID-19 epidemic were not elevated. Physio-psychosocial interventions, including fulfilment of basic needs, activation of self-efficacy and psychological support, are helpful and worth recommending in fighting COVID-19.

5.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-815

ABSTRACT

Background: The outbreak of COVID-19 puts major psychological pressure on medical workers exposed to patients. We examined COVID-19-related stress and its immed

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