Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 20
Filter
1.
Front Med (Lausanne) ; 10: 1120837, 2023.
Article in English | MEDLINE | ID: covidwho-2301672

ABSTRACT

Background: Previous studies have shown that an awake prone position may be beneficial for the treatment of acute respiratory distress syndrome (ARDS) or acute hypoxic respiratory failure (AHRF) in patients with COVID-19, but the results are not consistent, especially in terms of oxygenation outcomes and intubation rate. This systematic review and meta-analysis assessed the effects of the awake prone position on AHRF in patients with COVID-19 with all randomized controlled trials (RCTs). Methods: An extensive search of online databases, including MEDLINE, Embase, Web of Science, and Cochrane Central Register of Controlled Trials from 1 December 2019 to 30 October 2022, with no language restrictions was performed. This systematic review and meta-analysis are based on the PRISMA statement. We only included RCTs and used the Cochrane risk assessment tool for quality assessment. Results: Fourteen RCTs fulfilled the selection criteria, and 3,290 patients were included. A meta-analysis found that patients in the awake prone position group had more significant improvement in the SpO2/FiO2 ratio [mean difference (MD): 29.76; 95% confidence interval (CI): 1.39-48.13; P = 0.001] compared with the usual care. The prone position also reduced the need for intubation [odd ratio (OR): 0.72; 95% CI: 0.61 to 0.84; P < 0.0001; I 2 = 0%]. There was no significant difference in mortality, hospital length of stay, incidence of intensive care unit (ICU) admission, and adverse events between the two groups. Conclusion: The awake prone position was a promising intervention method, which is beneficial to improve the oxygenation of patients with ARDS or AHRF caused by COVID-19 and reduce the need for intubation. However, the awake prone position showed no obvious advantage in mortality, hospital length of stay, incidence of ICU admission, and adverse events. Systematic review registration: International Prospective Register of Systematic Reviews (PROSPERO), identifier: CRD42022367885.

2.
J Proteome Res ; 22(4): 1009-1023, 2023 04 07.
Article in English | MEDLINE | ID: covidwho-2288822

ABSTRACT

Mass spectrometry (MS)-based blood proteomics is a crucial research focus in identifying disease biomarkers. Blood serum or plasma is the most commonly used sample for such analysis; however, it presents challenges due to the complexity and dynamic range of protein abundance. Despite these difficulties, the development of high-resolution MS instruments has made comprehensive investigation of blood proteomics possible. The evolution of time-of-flight (TOF) or Orbitrap MS instruments has played a significant role in the field of blood proteomics. These instruments are now among the most prominent techniques for blood proteomics due to their sensitivity, selectivity, fast response, and stability. For optimal results, it is necessary to eliminate high-abundance proteins from the blood sample, to maximize the depth coverage of the blood proteomics analysis. This can be achieved through various methods, including commercial kits, chemically synthesized materials, and MS technologies. This paper reviews recent advancements in MS technology and its remarkable applications in biomarker discovery, particularly in the areas of cancer and COVID-19 studies.


Subject(s)
COVID-19 , Proteomics , Humans , Proteomics/methods , Mass Spectrometry/methods , Proteins/chemistry
3.
Nature ; 599(7883): 114-119, 2021 11.
Article in English | MEDLINE | ID: covidwho-2114880

ABSTRACT

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.


Subject(s)
Immune Evasion , SARS-CoV-2/growth & development , SARS-CoV-2/immunology , Virus Replication/immunology , Antibodies, Neutralizing/immunology , COVID-19 Vaccines/immunology , Cell Fusion , Cell Line , Female , Health Personnel , Humans , India , Kinetics , Male , Spike Glycoprotein, Coronavirus/metabolism , Vaccination
4.
Nature ; 593(7857): 136-141, 2021 05.
Article in English | MEDLINE | ID: covidwho-2114170

ABSTRACT

Transmission of SARS-CoV-2 is uncontrolled in many parts of the world; control is compounded in some areas by the higher transmission potential of the B.1.1.7 variant1, which has now been reported in 94 countries. It is unclear whether the response of the virus to vaccines against SARS-CoV-2 on the basis of the prototypic strain will be affected by the mutations found in B.1.1.7. Here we assess the immune responses of individuals after vaccination with the mRNA-based vaccine BNT162b22. We measured neutralizing antibody responses after the first and second immunizations using pseudoviruses that expressed the wild-type spike protein or a mutated spike protein that contained the eight amino acid changes found in the B.1.1.7 variant. The sera from individuals who received the vaccine exhibited a broad range of neutralizing titres against the wild-type pseudoviruses that were modestly reduced against the B.1.1.7 variant. This reduction was also evident in sera from some patients who had recovered from COVID-19. Decreased neutralization of the B.1.1.7 variant was also observed for monoclonal antibodies that target the N-terminal domain (9 out of 10) and the receptor-binding motif (5 out of 31), but not for monoclonal antibodies that recognize the receptor-binding domain that bind outside the receptor-binding motif. Introduction of the mutation that encodes the E484K substitution in the B.1.1.7 background to reflect a newly emerged variant of concern (VOC 202102/02) led to a more-substantial loss of neutralizing activity by vaccine-elicited antibodies and monoclonal antibodies (19 out of 31) compared with the loss of neutralizing activity conferred by the mutations in B.1.1.7 alone. The emergence of the E484K substitution in a B.1.1.7 background represents a threat to the efficacy of the BNT162b2 vaccine.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , COVID-19/therapy , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Synthetic/immunology , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/isolation & purification , Antibodies, Neutralizing/isolation & purification , Antibodies, Viral/isolation & purification , COVID-19/metabolism , COVID-19/virology , Female , HEK293 Cells , Humans , Immune Evasion/genetics , Immune Evasion/immunology , Immunization, Passive , Male , Middle Aged , Models, Molecular , Mutation , Neutralization Tests , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Vaccines, Synthetic/administration & dosage , COVID-19 Serotherapy
5.
Cell Host Microbe ; 30(11): 1527-1539.e5, 2022 11 09.
Article in English | MEDLINE | ID: covidwho-2104544

ABSTRACT

Recently emerged SARS-CoV-2 Omicron subvariant, BA.2.75, displayed a growth advantage over circulating BA.2.38, BA.2.76, and BA.5 in India. However, the underlying mechanisms for enhanced infectivity, especially compared with BA.5, remain unclear. Here, we show that BA.2.75 exhibits substantially higher affinity for host receptor angiotensin-converting enzyme 2 (ACE2) than BA.5 and other variants. Structural analyses of BA.2.75 spike shows its decreased thermostability and increased frequency of the receptor binding domain (RBD) in the "up" conformation under acidic conditions, suggesting enhanced low-pH-endosomal cell entry. Relative to BA.4/BA.5, BA.2.75 exhibits reduced evasion of humoral immunity from BA.1/BA.2 breakthrough-infection convalescent plasma but greater evasion of Delta breakthrough-infection convalescent plasma. BA.5 breakthrough-infection plasma also exhibits weaker neutralization against BA.2.75 than BA.5, mainly due to BA.2.75's distinct neutralizing antibody (NAb) escape pattern. Antibody therapeutics Evusheld and Bebtelovimab remain effective against BA.2.75. These results suggest BA.2.75 may prevail after BA.4/BA.5, and its increased receptor-binding capability could support further immune-evasive mutations.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Humans , Spike Glycoprotein, Coronavirus/genetics , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Serotherapy
6.
Nat Commun ; 13(1): 6131, 2022 Oct 17.
Article in English | MEDLINE | ID: covidwho-2077051

ABSTRACT

Real-world data on vaccine-elicited neutralising antibody responses for two-dose AZD1222 in African populations are limited. We assessed baseline SARS-CoV-2 seroprevalence and levels of protective neutralizing antibodies prior to vaccination rollout using binding antibodies analysis coupled with pseudotyped virus neutralisation assays in two cohorts from West Africa: Nigerian healthcare workers (n = 140) and a Ghanaian community cohort (n = 527) pre and post vaccination. We found 44 and 28% of pre-vaccination participants showed IgG anti-N positivity, increasing to 59 and 39% respectively with anti-receptor binding domain (RBD) IgG-specific antibodies. Previous IgG anti-N positivity significantly increased post two-dose neutralizing antibody titres in both populations. Serological evidence of breakthrough infection was observed in 8/49 (16%). Neutralising antibodies were observed to wane in both populations, especially in anti-N negative participants with an observed waning rate of 20% highlighting the need for a combination of additional markers to characterise previous infection. We conclude that AZD1222 is immunogenic in two independent West African cohorts with high background seroprevalence and incidence of breakthrough infection in 2021. Waning titres post second dose indicates the need for booster dosing after AZD1222 in the African setting despite hybrid immunity from previous infection.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Neutralizing , Antibodies, Viral , Antibody Formation , COVID-19/epidemiology , COVID-19/prevention & control , ChAdOx1 nCoV-19 , Ghana , Humans , Immunoglobulin G , SARS-CoV-2 , Seroepidemiologic Studies , Vaccination
8.
Cell host & microbe ; 2022.
Article in English | EuropePMC | ID: covidwho-2045135

ABSTRACT

Recently emerged SARS-CoV-2 Omicron subvariant, BA.2.75, displayed a growth advantage over circulating BA.2.38, BA.2.76 and BA.5 in India. However, the underlying mechanisms for enhanced infectivity, especially compared to BA.5, remain unclear. Here we show BA.2.75 exhibits substantially higher affinity for host receptor ACE2 than BA.5 and other variants. Structural analyses of BA.2.75 Spike shows its decreased thermostability and increased frequency of the receptor binding domain (RBD) in the “up” conformation under acidic conditions, suggesting enhanced low-pH-endosomal cell entry. Relative to BA.4/BA.5, BA.2.75 exhibits reduced evasion of humoral immunity from BA.1/BA.2 breakthrough-infection convalescent plasma, but greater evasion of Delta breakthrough-infection convalescent plasma. BA.5 breakthrough infection plasma also exhibits weaker neutralization against BA.2.75 than BA.5, mainly due to BA.2.75’s distinct neutralizing antibody escape pattern. Antibody therapeutics Evusheld and Bebtelovimab remain effective against BA.2.75. These results suggest BA.2.75 may prevail after BA.4/BA.5, and its increased receptor-binding capability could support further immune-evasive mutations. Graphical SARS-CoV-2 BA.2.75 is growing rapidly and globally. Cao et al. solved the structure of BA.2.75 spike and show it has stronger binding to human ACE2 than previous variants. BA.2.75 also exhibited distinct antigenicity compared to BA.5, escaping neutralizing antibodies targeting various epitopes and evading convalescent plasma from BA.5 breakthrough infections.

9.
Int J Mol Sci ; 23(17)2022 Sep 01.
Article in English | MEDLINE | ID: covidwho-2023754

ABSTRACT

Carbohydrate antigen 199 (CA199) is a serum biomarker which has certain value and significance in the diagnosis, prognosis, treatment, and postoperative monitoring of cancer. In this study, a lateral flow immunoassay based on europium (III) polystyrene time-resolved fluorescence microspheres (TRFM-based LFIA), integrated with a portable fluorescence reader, has been successfully establish for rapid and quantitative analysis of CA199 in human serum. Briefly, time-resolved fluorescence microspheres (TRFMs) were conjugated with antibody I (Ab1) against CA199 as detection probes, and antibody II (Ab2) was coated as capture element, and a "TRFMs-Ab1-CA199-Ab2" sandwich format would form when CA199 was detected by the TRFM-based LFIA. Under the optimal parameters, the detection limit of the TRFM-based LFIA for visible quantitation with the help of an ultraviolet light was 4.125 U/mL, which was four times lower than that of LFIA based on gold nanoparticles. Additionally, the fluorescence ratio is well linearly correlated with the CA199 concentration (0.00-66.0 U/mL) and logarithmic concentration (66.0-264.0 U/mL) for quantitative detection. Serum samples from 10 healthy people and 10 liver cancer patients were tested to confirm the performances of the point-of-care application of the TRFM-based LFIA, 20.0 U/mL of CA199 in human serum was defined as the threshold for distinguishing healthy people from liver cancer patients with an accuracy of about 60%. The establishment of TRFM-based LFIA will provide a sensitive, convenient, and efficient technical support for rapid screening of CA199 in cancer diagnosis and prognosis.


Subject(s)
Liver Neoplasms , Metal Nanoparticles , Biomarkers, Tumor , Gold , Humans , Immunoassay , Limit of Detection , Microspheres
10.
Cell Rep ; 40(7): 111220, 2022 08 16.
Article in English | MEDLINE | ID: covidwho-1966425

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike N-terminal domain (NTD) remains poorly characterized despite enrichment of mutations in this region across variants of concern (VOCs). Here, we examine the contribution of the NTD to infection and cell-cell fusion by constructing chimeric spikes bearing B.1.617 lineage (Delta and Kappa variants) NTDs and generating spike pseudotyped lentivirus. We find that the Delta NTD on a Kappa or wild-type (WT) background increases S1/S2 cleavage efficiency and virus entry, specifically in lung cells and airway organoids, through use of TMPRSS2. Delta exhibits increased cell-cell fusogenicity that could be conferred to WT and Kappa spikes by Delta NTD transfer. However, chimeras of Omicron BA.1 and BA.2 spikes with a Delta NTD do not show more efficient TMPRSS2 use or fusogenicity. We conclude that the NTD allosterically modulates S1/S2 cleavage and spike-mediated functions in a spike context-dependent manner, and allosteric interactions may be lost when combining regions from more distantly related VOCs.


Subject(s)
COVID-19 , Virus Internalization , Humans , SARS-CoV-2 , Serine Endopeptidases/genetics , Spike Glycoprotein, Coronavirus/genetics
11.
Front Public Health ; 10: 855633, 2022.
Article in English | MEDLINE | ID: covidwho-1847239

ABSTRACT

COVID-19, which occurred at the end of December 2019, has evolved into a global public health threat and affects every aspect of human life. COVID-19's high infectivity and mortality prompted governments and the scientific community to respond quickly to the pandemic outbreak. The application of personal protective equipment (PPE) is of great significance in overcoming the epidemic situation. Since the discovery of severe acute respiratory coronavirus 2 (SARS-CoV-2), bibliometric analysis has been widely used in many aspects of the COVID-19 epidemic. Although there are many reported studies about PPE and COVID-19, there is no study on the bibliometric analysis of these studies. The citation can be used as an indicator of the scientific influence of an article in its field. The aim of this study was to track the research trends and latest hotspots of COVID-19 in PPE by means of bibliometrics and visualization maps.


Subject(s)
COVID-19 , Bibliometrics , COVID-19/prevention & control , Humans , Pandemics/prevention & control , Personal Protective Equipment , SARS-CoV-2
12.
Nature ; 603(7902): 706-714, 2022 03.
Article in English | MEDLINE | ID: covidwho-1764186

ABSTRACT

The SARS-CoV-2 Omicron BA.1 variant emerged in 20211 and has multiple mutations in its spike protein2. Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron's evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways3 demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis.


Subject(s)
COVID-19/pathology , COVID-19/virology , Membrane Fusion , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Serine Endopeptidases/metabolism , Virus Internalization , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19 Vaccines/immunology , Cell Line , Cell Membrane/metabolism , Cell Membrane/virology , Chlorocebus aethiops , Convalescence , Female , Humans , Immune Sera/immunology , Intestines/pathology , Intestines/virology , Lung/pathology , Lung/virology , Male , Middle Aged , Mutation , Nasal Mucosa/pathology , Nasal Mucosa/virology , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Tissue Culture Techniques , Virulence , Virus Replication
13.
Biosensors (Basel) ; 12(2)2022 Feb 07.
Article in English | MEDLINE | ID: covidwho-1674496

ABSTRACT

Neutralizing antibody (NAb) is a family of antibodies with special functions, which afford a degree of protection against infection and/or reduce the risk of clinically severe infection. Receptor binding domain (RBD) in the spike protein of SARS-CoV-2, a portion of the S1 subunit, can stimulate the immune system to produce NAb after infection and vaccination. The detection of NAb against SARS-CoV-2 is a simple and direct approach for evaluating a vaccine's effectiveness. In this study, a direct, rapid, and point-of-care bicolor lateral flow immunoassay (LFIA) was developed for NAb against SARS-CoV-2 detection without sample pretreatment, and which was based on the principle of NAb-mediated blockage of the interaction between RBD and angiotensin-converting enzyme 2. In the bicolor LFIA, red and blue latex microspheres (LMs) were used to locate the test and control lines, leading to avoidance of erroneous interpretations of one-colored line results. Under the optimal conditions, NAb against SARS-CoV-2 detection carried out using the bicolor LFIA could be completed within 9 min, and the visible limit of detection was about 48 ng/mL. Thirteen serum samples were analyzed, and the results showed that the NAb levels in three positive serum samples were equal to, or higher than, 736 ng/mL. The LM-based bicolor LFIA allows one-step, rapid, convenient, inexpensive, and user-friendly determination of NAb against SARS-CoV-2 in serum.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , Antibodies, Neutralizing/isolation & purification , Antibodies, Viral/isolation & purification , COVID-19/diagnosis , Chromatography, Affinity , Humans , Latex , Microspheres , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology
14.
Sustainability ; 13(22):12386, 2021.
Article in English | MDPI | ID: covidwho-1512647

ABSTRACT

Since the COVID-19 pandemic, airlines worldwide have enforced strict travel restrictions, driving passengers to seek alternative transportations such as High-Speed Railway (HSR). Nevertheless, the current understanding of HSR travelers’ behavior is scarce. Moreover, despite the extensive application of the Theory of Planned Behavior (TPB) to explain and predict patrons and tourists’ behavior in the tourism and hospitality context, little research has employed this theory to examine HSR travelers’ processes in making travelling decisions. This study developed a research model by integrating perceived quality into the TPB and examined the relation between HSR passengers’ service quality and intention to travel in the future and the mediating effect of TPB attributes. It is found that perceived train service quality and perceived travel quality have a significant influence on the TPB attributes, which further influence HSR travelers’ travel intention. This study contributes practical implications to destinations and the travel industry that they might attract visitors by marketing the corresponding HSR train service quality and travel experience quality. This also provides recovery guidelines for the transportation and travel industry after the COVID-19 pandemic.

15.
Sustainability ; 13(19):10819, 2021.
Article in English | MDPI | ID: covidwho-1444310

ABSTRACT

The outbreak of the coronavirus disease in 2019 (COVID-19) has greatly impacted the life and mental health of many people globally. The objective of this study was to investigate the factors associated with preventive behaviors and mental health among Chinese adults during their home quarantine in the COVID-19 period. An online questionnaire survey was administered in March 2020. The study participants were adults aged between 18 and 70 years old from 31 provinces in China. Of the 3878 participants, 1314 reported moderate levels of anxiety, and the remaining participants reported moderate to severe levels of anxiety. Findings revealed that females aged between 18 and 30 years old who had higher educational qualifications, greater levels of preventive knowledge, trust in the government, and resided in urban and medium-risk areas (R2 = 0.100, F = 27.97, p <0.001) were more likely to exhibit preventive behaviors. In contrast, a higher negative emotional response was generally seen in males who had low levels of preventive knowledge and behaviors, higher risk perception of infection, lower trust in the government, and unhealthy lifestyles (R2 = 0.127, F = 32.33, p <0.001). In addition, the high-risk perception of infection was positively associated with high odds of anxiety (AOR = 1.17, 95% CI: 1.10–1.24), whereas a greater level of preventive knowledge (AOR = 0.36, 95% CI: 0.19–0.70) and behaviors (AOR = 0.69, 95% CI: 0.57–0.84), higher trust in the government’s COVID-19 pandemic mitigation measures (AOR = 0.77, 95% CI: 0.71–0.83), and a healthier lifestyle (AOR = 0.89, 95% CI: 0.79–0.99) were negatively associated with high odds of anxiety. Results showed that a lower level of anxiety and negative emotional response were associated with better preventive behaviors against COVID-19, which were influenced by preventive knowledge, risk perception, trust in the government’s COVID-19 pandemic mitigation measures, and healthy lifestyle. Findings in this study could help formulate health interventions for vulnerable groups related to gendered vulnerabilities in the COVID-19 environment to improve their mental health and preventive behaviors, especially during the period of a pandemic.

16.
J Infect Dis ; 224(6): 989-994, 2021 09 17.
Article in English | MEDLINE | ID: covidwho-1429251

ABSTRACT

The SARS-CoV-2 B.1.617 variant emerged in the Indian state of Maharashtra in late 2020. There have been fears that 2 key mutations seen in the receptor-binding domain, L452R and E484Q, would have additive effects on evasion of neutralizing antibodies. We report that spike bearing L452R and E484Q confers modestly reduced sensitivity to BNT162b2 mRNA vaccine-elicited antibodies following either first or second dose. The effect is similar in magnitude to the loss of sensitivity conferred by L452R or E484Q alone. These data demonstrate reduced sensitivity to vaccine-elicited neutralizing antibodies by L452R and E484Q but lack of synergistic loss of sensitivity.


Subject(s)
COVID-19/immunology , COVID-19/virology , Immune Evasion , Mutation , SARS-CoV-2/genetics , Angiotensin-Converting Enzyme 2 , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , BNT162 Vaccine , COVID-19 Vaccines/immunology , Chlorocebus aethiops , HEK293 Cells , Humans , India , Protein Binding , SARS-CoV-2/immunology , Serine Endopeptidases , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vero Cells
17.
Nature ; 596(7872): 417-422, 2021 08.
Article in English | MEDLINE | ID: covidwho-1287811

ABSTRACT

Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating.


Subject(s)
Aging/immunology , COVID-19 Vaccines/immunology , Immunity , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , Aging/blood , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Autoantibodies/immunology , B-Lymphocytes/cytology , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , BNT162 Vaccine , COVID-19 Vaccines/administration & dosage , Female , Health Personnel , Humans , Immunity/genetics , Immunization, Secondary , Immunoglobulin A/immunology , Immunoglobulin Class Switching , Immunoglobulin G/genetics , Immunoglobulin G/immunology , Immunologic Memory/immunology , Inflammation/blood , Inflammation/immunology , Interferon-gamma/immunology , Interleukin-2/immunology , Male , Middle Aged , Somatic Hypermutation, Immunoglobulin , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology , Vaccination , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunology
18.
Cell Rep ; 35(13): 109292, 2021 06 29.
Article in English | MEDLINE | ID: covidwho-1281394

ABSTRACT

We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike ΔH69/V70 in multiple independent lineages, often occurring after acquisition of receptor binding motif replacements such as N439K and Y453F, known to increase binding affinity to the ACE2 receptor and confer antibody escape. In vitro, we show that, although ΔH69/V70 itself is not an antibody evasion mechanism, it increases infectivity associated with enhanced incorporation of cleaved spike into virions. ΔH69/V70 is able to partially rescue infectivity of spike proteins that have acquired N439K and Y453F escape mutations by increased spike incorporation. In addition, replacement of the H69 and V70 residues in the Alpha variant B.1.1.7 spike (where ΔH69/V70 occurs naturally) impairs spike incorporation and entry efficiency of the B.1.1.7 spike pseudotyped virus. Alpha variant B.1.1.7 spike mediates faster kinetics of cell-cell fusion than wild-type Wuhan-1 D614G, dependent on ΔH69/V70. Therefore, as ΔH69/V70 compensates for immune escape mutations that impair infectivity, continued surveillance for deletions with functional effects is warranted.


Subject(s)
COVID-19/immunology , COVID-19/virology , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Cell Line , Chlorocebus aethiops , HEK293 Cells , Humans , Immune Evasion , Mutation , Pandemics , Phylogeny , Protein Binding , Recurrence , SARS-CoV-2/immunology , Vero Cells
19.
Cell Rep Med ; 1(6): 100099, 2020 09 22.
Article in English | MEDLINE | ID: covidwho-738567

ABSTRACT

Rapid COVID-19 diagnosis in the hospital is essential, although this is complicated by 30%-50% of nose/throat swabs being negative by SARS-CoV-2 nucleic acid amplification testing (NAAT). Furthermore, the D614G spike mutant dominates the pandemic and it is unclear how serological tests designed to detect anti-spike antibodies perform against this variant. We assess the diagnostic accuracy of combined rapid antibody point of care (POC) and nucleic acid assays for suspected COVID-19 disease due to either wild-type or the D614G spike mutant SARS-CoV-2. The overall detection rate for COVID-19 is 79.2% (95% CI 57.8-92.9) by rapid NAAT alone. The combined point of care antibody test and rapid NAAT is not affected by D614G and results in very high sensitivity for COVID-19 diagnosis with very high specificity.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Point-of-Care Testing , SARS-CoV-2/isolation & purification , Aged , Aged, 80 and over , Antibodies, Viral/blood , COVID-19 Testing/standards , Female , Humans , Immunoassay , Male , Middle Aged , Neutralization Tests , Nucleic Acid Amplification Techniques , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
20.
Indian J Med Microbiol ; 38(1): 87-93, 2020.
Article in English | MEDLINE | ID: covidwho-688925

ABSTRACT

Objective: This study aims to provide scientific basis for rapid screening and early diagnosis of the coronavirus disease 2019 (COVID-19) through analysing the clinical characteristics and early imaging/laboratory findings of the inpatients. Methods: Three hundred and three patients with laboratory-confirmed COVID-19 from the East Hospital of People's Hospital of Wuhan University (Wuhan, China) were selected and divided into four groups: youth (20-40 years, n = 64), middle-aged (41-60 years, n = 89), older (61-80 years, n = 118) and elderly (81-100 years, n = 32). The clinical characteristics and imaging/laboratory findings including chest computed tomography (CT), initial blood count, C-reactive protein [CRP]), procalcitonin (PCT) and serum total IgE were captured and analysed. Results: (1) The first symptoms of all age groups were primarily fever (76%), followed by cough (12%) and dyspnoea (5%). Beside fever, the most common initial symptom of elderly patients was fatigue (13%). (2) Fever was the most common clinical manifestation (80%), with moderate fever being the most common (40%), followed by low fever in patients above 40 years old and high fever in those under 40 years (35%). Cough was the second most common clinical manifestation and was most common (80%) in the middle-aged. Diarrhoea was more common in the middle-aged (21%) and the older (19%). Muscle ache was more common in the middle-aged (15%). Chest pain was more common in the youth (13%), and 13% of the youth had no symptoms. (3) The proportion of patients with comorbidities increased with age. (4) Seventy-one per cent of the patients had positive reverse transcription-polymerase chain reaction results and 29% had positive chest CT scans before admission to the hospital. (5) Lesions in all lobes of the lung were observed as the main chest CT findings (76%). (6) Decrease in lymphocytes and increase in monocytes were common in the patients over 40 years old but rare in the youth. Eosinophils (50%), red blood cells (39%) and haemoglobin (40%) decreased in all age groups. (7) The proportion of patients with CRP and PCT elevation increased with age. (8) Thirty-nine per cent of the patients had elevated IgE, with the highest proportion in the old (49%). Conclusion: The clinical characteristics and imaging/laboratory findings of COVID-19 patients vary in different age groups. Personalised criteria should be formulated according to different age groups in the early screening and diagnosis stage.


Subject(s)
Betacoronavirus/growth & development , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Coronavirus Infections/pathology , Diagnostic Tests, Routine/methods , Pneumonia, Viral/diagnosis , Pneumonia, Viral/pathology , Tomography, X-Ray Computed/methods , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19 , China , Coronavirus Infections/diagnostic imaging , Early Diagnosis , Female , Hospitals, University , Humans , Male , Mass Screening/methods , Middle Aged , Pandemics , Pneumonia, Viral/diagnostic imaging , SARS-CoV-2 , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL