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1.
Int J Biol Sci ; 18(12): 4744-4755, 2022.
Article in English | MEDLINE | ID: covidwho-1954694

ABSTRACT

Viruses exploit the host lipid metabolism machinery to achieve efficient replication. We herein characterize the lipids profile reprogramming in vitro and in vivo using liquid chromatography-mass spectrometry-based untargeted lipidomics. The lipidome of SARS-CoV-2-infected Caco-2 cells was markedly different from that of mock-infected samples, with most of the changes involving downregulation of ceramides. In COVID-19 patients' plasma samples, a total of 54 lipids belonging to 12 lipid classes that were significantly perturbed compared to non-infected control subjects' plasma samples were identified. Among these 12 lipid classes, ether-linked phosphatidylcholines, ether-linked phosphatidylethanolamines, phosphatidylcholines, and ceramides were the four most perturbed. Pathway analysis revealed that the glycerophospholipid, sphingolipid, and ether lipid metabolisms pathway were the most significantly perturbed host pathways. Phosphatidic acid phosphatases (PAP) were involved in all three pathways and PAP-1 deficiency significantly suppressed SARS-CoV-2 replication. siRNA knockdown of LPIN2 and LPIN3 resulted in significant reduction of SARS-CoV-2 load. In summary, these findings characterized the host lipidomic changes upon SARS-CoV-2 infection and identified PAP-1 as a potential target for intervention for COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Caco-2 Cells , Ceramides , Ethers , Glycerophospholipids , Humans , Lipid Metabolism , Phosphatidate Phosphatase/genetics , Phosphatidate Phosphatase/metabolism , Phosphatidylcholines/metabolism , Phosphatidylethanolamines/metabolism
3.
Vaccines (Basel) ; 10(7)2022 Jul 14.
Article in English | MEDLINE | ID: covidwho-1928706

ABSTRACT

Background: Gut microbiota can be associated with COVID-19 vaccine immunogenicity. We investigated whether recent antibiotic use influences BNT162b2 vaccine immunogenicity. Methods: BNT162b2 recipients from three centers were prospectively recruited. Outcomes of interest were seroconversion of neutralising antibody (NAb) at day 21, 56 and 180 after first dose. We calculated the adjusted odds ratio (aOR) of seroconversion with antibiotic usage (defined as ever use of any antibiotics within six months before first dose of vaccine) by adjusting for covariates including age, sex, smoking, alcohol, and comorbidities. Results: Of 316 BNT162b2 recipients (100 [31.6%] male; median age: 50.1 [IQR: 40.0-57.0] years) recruited, 29 (9.2%) were antibiotic users. There was a trend of lower seroconversion rates in antibiotic users than non-users at day 21 (82.8% vs. 91.3%; p = 0.14) and day 56 (96.6% vs. 99.3%; p = 0.15), but not at day 180 (93.3% vs. 94.1%). A multivariate analysis showed that recent antibiotic usage was associated with a lower seroconversion rate at day 21 (aOR 0.26;95% CI: 0.08-0.96). Other factors associated with a lower seroconversion rate after first dose of the BNT162b2 vaccine included age ≥ 60 years (aOR: 0.34;95% CI: 0.13-0.95) and male sex (aOR: 0.14, 95% CI: 0.05-0.34). There were no significant factors associated with seroconversion after two doses of BNT16b2, including antibiotic use (aOR: 0.03;95% CI: 0.001-1.15). Conclusions: Recent antibiotic use may be associated with a lower seroconversion rate at day 21 (but not day 56 or 180) among BNT162b2 recipients. Further long-term follow-up data with a larger sample size is needed to reach a definite conclusion on how antibiotics influence immunogenicity and the durability of the vaccine response.

4.
Clin Infect Dis ; 2022 Jun 28.
Article in English | MEDLINE | ID: covidwho-1908778

ABSTRACT

BACKGROUND: Early antiviral therapy was effective in the treatment of COVID-19. We assessed the efficacy and safety of combined interferon beta-1b and remdesivir treatment in hospitalized COVID-19 patients. METHODS: We conducted a multicentre, prospective open-label, randomized-controlled trial involving high-risk adults hospitalized for COVID-19. Patients were randomly assigned to a 5-day interferon beta-1b 16 million units daily and remdesivir 200mg loading on day 1 followed by 100mg daily on day 2 to 5 (combination-group), or to remdesivir only of similar regimen (control-group) (1:1). The primary end-point was the time to complete alleviation of symptoms (NEWS2 = 0). RESULTS: Two-hundred and twelve patients were enrolled. The median days of starting treatment from symptom-onset was 3 days. The median age was 65 years and 159 patients (75%) had chronic disease. The baseline demographics were similar. There was no mortality. For the primary-endpoint, the combination-group was significantly quicker to NEWS2 = 0 (4 versus 6.5 days; hazard-ratio [HR],6.59; 95% confidence-interval [CI],6.1-7.09; p < 0.0001) when compared to the control-group. For the secondary endpoints, the combination-group was quicker to negative NPS VL (6 versus 8 days; HR,8.16; 95% CI,7.79-8.52; p < 0.0001) and develop seropositive IgG (8 versus 10 days; HR,10.78; 95% CI,9.98-11.58; p < 0.0001). All adverse events resolved upon follow-up. Combination group (HR,4.1 95%CI,1.9-8.6, p < 0.0001), was the most significant independent factor associated with NEWS2 = 0 on day 4. CONCLUSIONS: Early treatment with interferon beta-1b and remdesivir was safe and better than remdesivir only in alleviating symptoms, shorten viral shedding and hospitalization with earlier seropositivity in high-risk COVID-19 patients.

5.
Nat Commun ; 13(1): 3618, 2022 06 24.
Article in English | MEDLINE | ID: covidwho-1908176

ABSTRACT

Monitoring population protective immunity against SARS-CoV-2 variants is critical for risk assessment. We hypothesize that Hong Kong's explosive Omicron BA.2 outbreak in early 2022 could be explained by low herd immunity. Our seroprevalence study using sera collected from January to December 2021 shows a very low prevalence of neutralizing antibodies (NAb) against ancestral virus among older adults. The age group-specific prevalence of NAb generally correlates with the vaccination uptake rate, but older adults have a much lower NAb seropositive rate than vaccination uptake rate. For all age groups, the seroprevalence of NAb against Omicron variant is much lower than that against the ancestral virus. Our study suggests that this BA.2 outbreak and the exceptionally high case-fatality rate in the ≥80 year-old age group (9.2%) could be attributed to the lack of protective immunity in the population, especially among the vulnerable older adults, and that ongoing sero-surveillance is essential.


Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Aged, 80 and over , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/epidemiology , Disease Outbreaks , Hong Kong/epidemiology , Humans , Seroepidemiologic Studies
6.
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.

7.
Clin Infect Dis ; 2021 Dec 16.
Article in English | MEDLINE | ID: covidwho-1852987

ABSTRACT

BACKGROUND: The SARS-CoV-2 Omicron variant, designated as a Variant of Concern(VOC) by the World Health Organization, carries numerous spike mutations which have are known to evade neutralizing antibodies elicited by COVID-19 vaccines. A deeper understanding of the susceptibility of Omicron variant to vaccine-induced neutralizing antibodies is urgently needed for risk assessment. METHODS: Omicron variant strains HKU691 and HKU344-R346K were isolated from patients using TMPRSS2-overexpressing VeroE6 cells. Whole genome sequence was determined using nanopore sequencing. Neutralization susceptibility of ancestral lineage A virus and the Omicron, Delta and Beta variants to sera from 25 BNT162b2 and 25 Coronavac vaccine recipients was determined using a live virus microneutralization assay. RESULTS: The Omicron variant strain HKU344-R346K has an additional spike R346K mutation, which is present in 8.5% of strains deposited in GISAID database. Only 20% and 24% of BNT162b2 recipients had detectable neutralizing antibody against the Omicron variant HKU691 and HKU344-R346K, respectively, while none of the Coronavac recipients had detectable neutralizing antibody titer against either Omicron isolate. For BNT162b2 recipients, the geometric mean neutralization antibody titers(GMT) of the Omicron variant isolates(5.43 and 6.42) were 35.7-39.9-fold lower than that of the ancestral virus(229.4), and the GMT of both Omicron variant isolates were significantly lower than those of the Beta and Delta variants. There was no significant difference in the GMT between HKU691 and HKU344-R346K. CONCLUSIONS: Omicron variant escapes neutralizing antibodies elicited by BNT162b2 or Coronavac. The additional R346K mutation did not affect the neutralization susceptibility. Our data suggest that the Omicron variant may be associated with lower COVID-19 vaccine effectiveness.

8.
Clin Mol Hepatol ; 28(3): 553-564, 2022 07.
Article in English | MEDLINE | ID: covidwho-1841298

ABSTRACT

BACKGROUND/AIMS: Studies of hepatic steatosis (HS) effect on COVID-19 vaccine immunogenicity are lacking. We aimed to compare immunogenicity of BNT162b2 and CoronaVac among moderate/severe HS and control subjects. METHODS: Two hundred ninety-five subjects who received BNT162b2 or CoronaVac vaccines from five vaccination centers were categorized into moderate/severe HS (controlled attenuation parameter ≥268 dB/m on transient elastography) (n=74) or control (n=221) groups. Primary outcomes were seroconversion rates of neutralising antibody by live virus Microneutralization (vMN) assay (titer ≥10) at day21 (BNT162b2) or day28 (CoronaVac) and day56 (both). Secondary outcome was highest-tier titer response (top 25% of vMN titer; cutoff: 160 [BNT162b2] and 20 [CoronaVac]) at day 56. RESULTS: For BNT162b2 (n=228, 77.3%), there was no statistical differences in seroconversion rates (day21: 71.7% vs. 76.6%; day56: 100% vs. 100%) or vMN geometric mean titer (GMT) (day21: 13.2 vs. 13.3; day56: 91.9 vs. 101.4) among moderate/severe HS and control groups respectively. However, lower proportion of moderate/severe HS patients had highest-tier response (day56: 5.0% vs. 15.5%; P=0.037). For CoronaVac (n=67, 22.7%), there was no statistical differences in seroconversion rates (day21: 7.1% vs. 15.1%; day56: 64.3% vs. 83.0%) or vMN GMT (5.3 vs. 5.8,) at day28. However, moderate/severe HS patients had lower vMN GMT (9.1 vs. 14.8, P=0.021) at day 56 with lower proportion having highest-tier response (21.4% vs. 52.8%, P=0.036). CONCLUSION: While there was no difference in seroconversion rate between moderate/severe HS and control groups after two doses of vaccine, a lower proportion of moderate/severe HS patients achieved highest-tier response for either BNT162b2 or CoronaVac.


Subject(s)
COVID-19 , Fatty Liver , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , COVID-19 Vaccines , Humans
9.
Pediatr Res ; 2022 Apr 13.
Article in English | MEDLINE | ID: covidwho-1788275

ABSTRACT

BACKGROUND: The P.1 variant is a Variant of Concern announced by the WHO. The present work aimed to characterize the clinical features of pediatric patients with SARS-CoV-2 before and after the emergence of P.1. METHODS: This is a cohort study. Data of symptomatic patients younger than 18 years diagnosed with COVID-19 by PCR tests registered in Painel COVID-19 Amazonas were analyzed. RESULTS: A total of 4080 symptomatic pediatric patients were identified in the database between March 2020 and July 2021, of which 1654 were categorized as pre-P.1 and 978 as P.1-dominant cases, based on the prevalence of P.1 of >90% in the North Region, Brazil. Lower case-fatality rate was observed in non-infants infected during the P.1-dominant period (0.9% vs. 2.2%). In general, patients infected during the P.1-dominant period had less fever (70.8% vs. 74.2%) and less lower respiratory tract symptoms (respiratory distress: 11.8% vs. 18.9%, dyspnea: 27.9% vs. 34.5%) yet higher prevalence of neurological symptoms, headache for example (42.8% vs. 5.9%). CONCLUSIONS: The prevalence of symptoms of COVID-19 can differ across different periods of variant dominance. Lower prevalence of fever during the P.1-dominant period may reduce the effectiveness of symptom-based screening in public premises where laboratory diagnostic tests are not available. IMPACT: The prevalence rate of symptoms of SARS-CoV-2 infection can differ among different variants. The present work documents the difference in the clinical features of SARS-CoV-2 in patients aged below 18 years before and after the emergence of P.1, the first study of its kind. Unlike previous studies that focus solely on hospitalized cases, the present work considers both mild and severe cases. While non-infants had a lower fatality rate, lower prevalence of fever associated with the emergence of P.1 may reduce the effectiveness of symptom-based screening in public premises where laboratory diagnostic tests are not available.

10.
Chemical science ; 13(11):3216-3226, 2022.
Article in English | EuropePMC | ID: covidwho-1782305

ABSTRACT

The ongoing COVID-19 pandemic caused by SARS-CoV-2 highlights the urgent need to develop sensitive methods for diagnosis and prognosis. To achieve this, multidimensional detection of SARS-CoV-2 related parameters including virus loads, immune response, and inflammation factors is crucial. Herein, by using metal-tagged antibodies as reporting probes, we developed a multiplex metal-detection based assay (MMDA) method as a general multiplex assay strategy for biofluids. This strategy provides extremely high multiplexing capability (theoretically over 100) compared with other reported biofluid assay methods. As a proof-of-concept, MMDA was used for serologic profiling of anti-SARS-CoV-2 antibodies. The MMDA exhibits significantly higher sensitivity and specificity than ELISA for the detection of anti-SARS-CoV-2 antibodies. By integrating the high dimensional data exploration/visualization tool (tSNE) and machine learning algorithms with in-depth analysis of multiplex data, we classified COVID-19 patients into different subgroups based on their distinct antibody landscape. We unbiasedly identified anti-SARS-CoV-2-nucleocapsid IgG and IgA as the most potently induced types of antibodies for COVID-19 diagnosis, and anti-SARS-CoV-2-spike IgA as a biomarker for disease severity stratification. MMDA represents a more accurate method for the diagnosis and disease severity stratification of the ongoing COVID-19 pandemic, as well as for biomarker discovery of other diseases. A MMDA platform is developed by using metal-tagged antibodies as reporting probes combined with machine learning algorithms, as a general strategy for highly multiplexed biofluid assay.

11.
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
12.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-332139

ABSTRACT

Monitoring population protective immunity against SARS-CoV-2 variants is critical for risk assessment. In this serosurveillance study, older adults show much lower seropositive rates of neutralizing antibody (NAb) against ancestral virus than the younger population. The increase in NAb seopositive rate generally follows the population vaccination uptake rate, but older adults have a much lower NAb seropositive rate than vaccination uptake rate. For all age groups, the seropositive rates of NAb against Omicron variant are much lower than those against the ancestral virus. During the fifth wave of COVID-19 in Hong Kong which is dominated by Omicron sublineage BA.2, the case-fatality rate is exceptionally high in the ≥80 year-old age group (9.2%). Our study suggests that the severe BA.2 outbreak in Hong Kong can be attributed by the lack of protective immunity in the population, especially among the vulnerable older adults, and highlights the importance of continual surveillance of protective immunity against emerging variants of SARS-CoV-2.

13.
Chem Sci ; 13(11): 3216-3226, 2022 Mar 16.
Article in English | MEDLINE | ID: covidwho-1764224

ABSTRACT

The ongoing COVID-19 pandemic caused by SARS-CoV-2 highlights the urgent need to develop sensitive methods for diagnosis and prognosis. To achieve this, multidimensional detection of SARS-CoV-2 related parameters including virus loads, immune response, and inflammation factors is crucial. Herein, by using metal-tagged antibodies as reporting probes, we developed a multiplex metal-detection based assay (MMDA) method as a general multiplex assay strategy for biofluids. This strategy provides extremely high multiplexing capability (theoretically over 100) compared with other reported biofluid assay methods. As a proof-of-concept, MMDA was used for serologic profiling of anti-SARS-CoV-2 antibodies. The MMDA exhibits significantly higher sensitivity and specificity than ELISA for the detection of anti-SARS-CoV-2 antibodies. By integrating the high dimensional data exploration/visualization tool (tSNE) and machine learning algorithms with in-depth analysis of multiplex data, we classified COVID-19 patients into different subgroups based on their distinct antibody landscape. We unbiasedly identified anti-SARS-CoV-2-nucleocapsid IgG and IgA as the most potently induced types of antibodies for COVID-19 diagnosis, and anti-SARS-CoV-2-spike IgA as a biomarker for disease severity stratification. MMDA represents a more accurate method for the diagnosis and disease severity stratification of the ongoing COVID-19 pandemic, as well as for biomarker discovery of other diseases.

14.
mSphere ; 7(2): e0091521, 2022 04 27.
Article in English | MEDLINE | ID: covidwho-1741581

ABSTRACT

COVID-19 infection is a global health issue, and vaccination is the main strategy to control this pandemic. In this study, 189 participants received BNT162b2 or CoronaVac vaccine, and 133 of them recorded adverse events (AEs) daily for 4 weeks after vaccination. Their neutralizing antibody against SARS-CoV-2 was determined with live virus microneutralization (vMN) assay. The vMN geometric mean titer (GMT) on day 56 was 129.9 (95% confidence interval [CI],108.6 to 155.2) in the BNT162b2 group and 13.1 (95% CI, 11.2 to 15.3) in the CoronaVac group. Day 56 vMN GMT was 147.9 (95% CI, 118.9 to 184.1) in females and 129.9 (95% CI, 108.6 to 155.2) in males receiving BNT162b2, while it was 14.0 (95% CI, 11.6 to 17.0) in females and 11.4 (95% CI, 8.7 to 15.0) in males receiving CoronaVac. Injection site pain (88.8%) and redness (77.5%) were the most commonly BNT162b2-related AEs, and injection site pain (37.7%) and tiredness (26.4%) were more frequent in the CoronaVac group. Women showed a higher frequency of headache (45.7% versus 29.4%) and joint pain (26.1 versus 14.7%) than men in BTN162b2 group. Headache (26.5% versus 0%) and tiredness (38.2% versus 5.3%) were more common in women than in men vaccinated with CoronaVac. No correlation between any AE and antibody response was observed in BNT162b2 or CoronaVac platforms. After taking the gender factor into account, in the BNT162b2 group, a low correlation between day 21 vMN titer and redness (rho = 0.34) or itching (rho = 0.32) was presented in females, and a low correlation between day 56 vMN titer and fever (rho = 0.35) was presented in males. Taken together, AEs could have a low correlation with BNT162b2 vaccine response. IMPORTANCE Effective vaccines against SARS-CoV-2 are vital tools for containing the COVID-19 pandemic by increasing population immunity. While currently available vaccines can elicit antibody response against SARS-CoV-2 with high efficacy, the associated side effects may cause vaccine hesitancy. Our work is important in that we have thoroughly analyzed the correlation between immunogenicity and reactogenicity of two COVID-19 vaccines (BNT162b2 and CoronaVac) in the study. Our results showed that women had higher levels of neutralizing antibodies than men after receiving BNT162b2 or CoronaVac. Furthermore, a low correlation was observed between day 21 vMN titer and local reactions (redness and itching) in females, as well as between day 56 vMN titer and fever in males receiving BNT162b2. Thus, common side effects are not always a negative impact of vaccination but may serve as an indicator of immunogenicity of vaccines. Our study may help in increasing the public's acceptance and confidence over COVID-19 vaccination and ultimately achieving the goal of containing COVID-19 pandemic.


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Female , Headache , Humans , Male , Pain , Pandemics , Pruritus , SARS-CoV-2
15.
Microbiol Spectr ; 10(2): e0099321, 2022 04 27.
Article in English | MEDLINE | ID: covidwho-1731261

ABSTRACT

Detection and tracking of antibodies play an increasingly prominent role in population surveillance and implementation of public health measures to combat the current coronavirus disease 2019 (COVID-19) pandemic, with much attention placed on developing commercial serological assays as point-of-care diagnostic tools. While many rapid diagnostic tests (RDTs) that detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG and IgM antibodies have been evaluated, there is currently limited insight into detection of neutralizing antibodies (nAbs) by such modalities. Here, we evaluate performance characteristics of an RDT that detects SARS-CoV-2 IgG antibodies and, importantly, nAbs based on both infection- and vaccine-immunized cohorts by direct comparison to known antibody titers obtained from live virus microneutralization (VMN) assays. We further contextualize interpretations of band intensity of the RDT with reference to the World Health Organization (WHO) International Standard. We report a sensitivity of 94.37% and specificity of 92.50% for SARS-CoV-2 IgG detection and a sensitivity of 94.37% and specificity of 92.68% for nAbs. A limit of detection was determined as 3.125 IU/mL and 25.00 IU/mL, respectively, with reference to the WHO International Standard. We confirm that indication of nAb concentration, as elucidated by band intensity on the RDT, correlated with nAb titers defined by VMN assays and surrogate nAb assays. We additionally observe no cross-reactivity of the nAb test line to SARS-CoV-1 but report display of weak seropositivity for one sample on the SARS-CoV-2 IgG test line. Our study reveals promising performance characteristics of the assessed RDT, which implicates its usefulness in a wide range of diagnostic and epidemiological settings. IMPORTANCE In the ongoing coronavirus disease 2019 (COVID-19) pandemic, antibody tests play an increasingly important role in detecting previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and monitoring of response to vaccinations. In particular, neutralizing antibodies have recently been demonstrated to be highly predictive of immune protection against symptomatic infection. Our study is the first to evaluate a rapid diagnostic test based on samples acquired from both recovered COVID-19 patients and individuals vaccinated for SARS-CoV-2, which detects neutralizing antibodies in addition to SARS-CoV-2 IgG. We report promising sensitivity, specificity, and cross-reactivity profiles, which implicate its usefulness in a wide range of settings as a diagnostic point-of-care tool to aid in curbing transmission and reducing mortality caused by COVID-19 symptoms.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/diagnosis , Humans , Immunoglobulin G , Point-of-Care Systems , Point-of-Care Testing
16.
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.

17.
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.

18.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-316481

ABSTRACT

Coronaviruses have repeatedly crossed species barriers to cause epidemics 1 . “Pan-coronavirus” antivirals targeting conserved viral components involved in coronavirus replication, such as the extensively glycosylated spike protein, can be designed. Here we show that the rationally engineered H84T-banana lectin (H84T-BanLec), which specifically recognizes high-mannose found on viral proteins but seldom on healthy human cells 2 , potently inhibits the highly virulent MERS-CoV, pandemic SARS-CoV-2 and its variants, and other human-pathogenic coronaviruses at nanomolar concentrations. MERS-CoV-infected human DPP4-transgenic mice treated by H84T-BanLec have significantly higher survival, lower viral burden, and reduced pulmonary damage. Similarly, prophylactic or therapeutic H84T-BanLec is effective against SARS-CoV-2 in hamsters. Importantly, intranasally and intraperitoneally administered H84T-BanLec are comparably effective. Time-of-drug-addition assay shows that H84T-BanLec targets virus entry. Real-time structural analysis with high-speed atomic force microscopy depicts multi-molecular associations of H84T-BanLec dimers with the SARS-CoV-2 spike trimer. Single-molecule force spectroscopy demonstrates binding of H84T-BanLec to multiple SARS-CoV-2 spike mannose sites with high affinity, and that H84T-BanLec competes with SARS-CoV-2 spike for binding to cellular ACE2. Modelling experiments identify distinct high-mannose glycans in spike recognized by H84T-BanLec. The multiple H84T-BanLec binding sites on spike likely account for the activity against SARS-CoV-2 variants and the lack of resistant mutants. The broad-spectrum H84T-BanLec should be clinically evaluated in respiratory viral infections including COVID-19.

19.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315123

ABSTRACT

There are few studies describing the presence of respiratory viruses in respiratory droplets and aerosols in the exhaled breath of infected persons, and the efficacy of facemasks as a source control to prevent respiratory virus transmission. Here, we recruited children and adults with acute respiratory illness and collected respiratory droplets and aerosols, with and without surgical facemasks. We identified human coronaviruses, influenza virus and rhinovirus from both respiratory droplets and aerosols. Surgical face masks reduced detection of coronavirus RNA in both respiratory droplets and aerosols, but only respiratory droplets and not aerosols for influenza virus RNA. Our results provide mechanistic evidence that surgical facemasks could prevent transmission of human coronavirus and influenza virus infections if worn by symptomatic individuals.Authors Donald K Milton and Benjamin J Cowling are joint senior authors.

20.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-308551

ABSTRACT

Background: Non-conductive olfactory dysfunction (OD) is an important extra-pulmonary manifestation of coronavirus disease 2019 (COVID-19). Prolonged COVID-19-related OD is a serious neurosensory disability. Treatment for the restoration of smell is urgently needed. Case presentation Two patients presenting with prolonged COVID-19-related OD underwent structural and resting-state functional magnetic resonance imaging (rs-fMRI) brain scans. Two healthy controls were recruited for radiological comparison. One patient received olfactory treatment (OT) by the combination of oral vitamin A and smell training via the novel electronic portable aromatic rehabilitation (EPAR) diffusers. After four-weeks of OT, clinical recuperation of smell was correlated with interval increase of bilateral OB volumes [right: 22.5mm 3 to 49.5mm 3 (120%), left: 37.5mm 3 to 42mm 3 (12%)] and the enhancement of mean olfactory functional connectivity [0.09 to 0.15 (66.6%)]. Conclusions: Olfactory network functional defects and OB volume loss were identified in patients presenting with prolonged COVID-19-related OD. Preliminary evidence demonstrated that the combination of oral vitamin A and smell training may induce neurogenesis at the olfactory apparatus and achieve olfactory neurosensory rehabilitation. This observation should be validated in large scale randomized–controlled trials.

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