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1.
J Clin Microbiol ; 60(5): e0006622, 2022 May 18.
Article in English | MEDLINE | ID: covidwho-1779307

ABSTRACT

As the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) begins to overlap with the traditional respiratory season in the Northern Hemisphere, simultaneous testing for SARS-CoV-2 and the other common causes of respiratory infections is imperative. This has led to the development of multiplex respiratory assays that include SARS-CoV-2 as a target. One such assay is the BioFire respiratory panel 2.1 (RP2.1), which is an expansion of the original BioFire FilmArray respiratory panel 2 (RP2) to include SARS-CoV-2. In this multicenter evaluation, we assessed the performance characteristics of the BioFire RP2.1 for the detection of SARS-CoV-2. One or more targets on the panel were detected in 19.3% (101/524) of specimens tested, with SARS-CoV-2 detected in 12.6% (66/524) of specimens. Human rhinovirus/enterovirus was also detected in 32.7% (33/101) and adenovirus in 3.0% (3/101) of positive specimens, with one dual positive for both SARS-CoV-2 and adenovirus being detected. A further breakdown of pathogens by age revealed a 4-fold predominance of human rhinovirus/enterovirus in subjects 0 to 18 years of age, whereas in all other age groups, SARS-CoV-2 was clearly the predominant pathogen. Overall, SARS-CoV-2 results obtained from the BioFire RP2.1 were highly concordant with the composite result, exhibiting 98.4% (61/62) positive percent agreement (95% confidence interval [CI], 91.4 to 99.7%) and 98.9% (457/462) negative percent agreement (95% CI, 97.5 to 99.5%) with further analysis of discordant results suggesting that the concentration of SARS-CoV-2 in the specimens was near the limit of detection (LoD) for both the BioFire RP2.1 and the comparator assays. Overall, the BioFire RP2.1 exhibited excellent performance in the detection of SARS-CoV-2.


Subject(s)
COVID-19 , Respiratory Tract Infections , Viruses , Adolescent , COVID-19/diagnosis , Child , Child, Preschool , GTP-Binding Proteins , Humans , Infant , Infant, Newborn , Membrane Proteins , Nasopharynx , Respiratory Tract Infections/diagnosis , Rhinovirus , SARS-CoV-2 , Sensitivity and Specificity
2.
Lancet Microbe ; 3(3): e193-e202, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1721237

ABSTRACT

BACKGROUND: Safe and effective vaccines are urgently needed to end the COVID-19 pandemic caused by SARS-CoV-2 infection. We aimed to assess the preliminary safety, tolerability, and immunogenicity of an mRNA vaccine ARCoV, which encodes the SARS-CoV-2 spike protein receptor-binding domain (RBD). METHODS: This single centre, double-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial of ARCoV was conducted at Shulan (Hangzhou) hospital in Hangzhou, Zhejiang province, China. Healthy adults aged 18-59 years negative for SARS-CoV-2 infection were enrolled and randomly assigned using block randomisation to receive an intramuscular injection of vaccine or placebo. Vaccine doses were 5 µg, 10 µg, 15 µg, 20 µg, and 25 µg. The first six participants in each block were sentinels and along with the remaining 18 participants, were randomly assigned to groups (5:1). In block 1 sentinels were given the lowest vaccine dose and after a 4-day observation with confirmed safety analyses, the remaining 18 participants in the same dose group proceeded and sentinels in block 2 were given their first administration on a two-dose schedule, 28 days apart. All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation. Humoral responses were assessed by measuring anti-SARS-CoV-2 RBD IgG using a standardised ELISA and neutralising antibodies using pseudovirus-based and live SARS-CoV-2 neutralisation assays. SARS-CoV-2 RBD-specific T-cell responses, including IFN-γ and IL-2 production, were assessed using an enzyme-linked immunospot (ELISpot) assay. The primary outcome for safety was incidence of adverse events or adverse reactions within 60 min, and at days 7, 14, and 28 after each vaccine dose. The secondary safety outcome was abnormal changes detected by laboratory tests at days 1, 4, 7, and 28 after each vaccine dose. For immunogenicity, the secondary outcome was humoral immune responses: titres of neutralising antibodies to live SARS-CoV-2, neutralising antibodies to pseudovirus, and RBD-specific IgG at baseline and 28 days after first vaccination and at days 7, 15, and 28 after second vaccination. The exploratory outcome was SARS-CoV-2-specific T-cell responses at 7 days after the first vaccination and at days 7 and 15 after the second vaccination. This trial is registered with www.chictr.org.cn (ChiCTR2000039212). FINDINGS: Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 µg group, 13 [65%] of 20 in the 10 µg group, 17 [85%] of 20 in the 15 µg group, 19 [95%] of 20 in the 20 µg group, 16 [100%] of 16 in the 25 µg group; p<0·0001). The incidence of grade 3 systemic adverse events were none (0%) of 20 in the 5 µg group, three (15%) of 20 in the 10 µg group, six (30%) of 20 in the 15 µg group, seven (35%) of 20 in the 20 µg group, five (31%) of 16 in the 25 µg group, and none (0%) of 20 in the placebo group (p=0·0013). As expected, the majority of fever resolved in the first 2 days after vaccination for all groups. The incidence of solicited systemic adverse events was similar after administration of ARCoV as a first or second vaccination. Humoral immune responses including anti-RBD IgG and neutralising antibodies increased significantly 7 days after the second dose and peaked between 14 and 28 days thereafter. Specific T-cell response peaked between 7 and 14 days after full vaccination. 15 µg induced the highest titre of neutralising antibodies, which was about twofold more than the antibody titre of convalescent patients with COVID-19. INTERPRETATION: ARCoV was safe and well tolerated at all five doses. The acceptable safety profile, together with the induction of strong humoral and cellular immune responses, support further clinical testing of ARCoV at a large scale. FUNDING: National Key Research and Development Project of China, Academy of Medical Sciences China, National Natural Science Foundation China, and Chinese Academy of Medical Sciences.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , China , Humans , Immunogenicity, Vaccine , Immunoglobulin G , Pandemics/prevention & control , Spike Glycoprotein, Coronavirus , Vaccines, Synthetic
3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329581

ABSTRACT

Emerging in December 2019, coronavirus disease 2019 (COVID-19) eventually became a pandemic and has posed a tremendous threat to global public health. However, the origins of SARS-CoV-2, the causative agent of COVID-19, remain to be determined. It has reported that a certain number of the early case clusters had a contact history with Huanan Seafood Market. Therefore, surveillance of SARS-CoV-2 within the market is of vital importance. Herein, we presented the SARS-CoV-2 detection results of 1380 samples collected from the environment and the animals within the market in early 2020. By SARS-CoV-2-specific RT-qPCR, 73 environmental samples tested positive for SARS-CoV-2 and three live viruses were successfully isolated. The viruses from the market shared nucleotide identity of 99.980% to 99.993% with the human isolate HCoV/Wuhan/IVDC-HB-01. In contrast, no virus was detected in the animal swabs covering 18 species of animals in the market. The SARS-COV-2 nucleic acids in the positive environmental samples showed significant correlation of abundance of Homo sapiens with SARS-CoV-2. In summary, this study provided convincing evidence of the prevalence of SARS-CoV-2 in the Huanan Seafood Market during the early stage of COVID-19 outbreak.

4.
Cell Discov ; 8(1): 17, 2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-1692628

ABSTRACT

The continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structural and computational analyses, we present a mutation-integrated trimeric form of spike receptor-binding domain (mutI-tri-RBD) as a broadly protective vaccine candidate, which combined heterologous RBDs from different representative strains into a hybrid immunogen and integrated immune-escape hotspots into a single antigen. When compared with a homo-tri-RBD vaccine candidate in the stage of phase II trial, of which all three RBDs are derived from the SARS-CoV-2 prototype strain, mutI-tri-RBD induced significantly higher neutralizing antibody titers against the Delta and Beta variants, and maintained a similar immune response against the prototype strain. Pseudo-virus neutralization assay demonstrated that mutI-tri-RBD also induced broadly strong neutralizing activities against all tested 23 SARS-CoV-2 variants. The in vivo protective capability of mutI-tri-RBD was further validated in hACE2-transgenic mice challenged by the live virus, and the results showed that mutI-tri-RBD provided potent protection not only against the SARS-CoV-2 prototype strain but also against the Delta and Beta variants.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325184

ABSTRACT

The outbreak of novel coronavirus disease 2019 (COVID-19) has already infected millions of people and is still rapidly spreading all over the globe. Most COVID-19 patients suffer from lung infection, so one important diagnostic method is to screen chest radiography images, e.g., X-Ray or CT images. However, such examinations are time-consuming and labor-intensive, leading to limited diagnostic efficiency. To solve this issue, AI-based technologies, such as deep learning, have been used recently as effective computer-aided means to improve diagnostic efficiency. However, one practical and critical difficulty is the limited availability of annotated COVID-19 data, due to the prohibitive annotation costs and urgent work of doctors to fight against the pandemic. This makes the learning of deep diagnosis models very challenging. To address this, motivated by that typical pneumonia has similar characteristics with COVID-19 and many pneumonia datasets are publicly available, we propose to conduct domain knowledge adaptation from typical pneumonia to COVID-19. There are two main challenges: 1) the discrepancy of data distributions between domains;2) the task difference between the diagnosis of typical pneumonia and COVID-19. To address them, we propose a new deep domain adaptation method for COVID-19 diagnosis, namely COVID-DA. Specifically, we alleviate the domain discrepancy via feature adversarial adaptation and handle the task difference issue via a novel classifier separation scheme. In this way, COVID-DA is able to diagnose COVID-19 effectively with only a small number of COVID-19 annotations. Extensive experiments verify the effectiveness of COVID-DA and its great potential for real-world applications.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-319498

ABSTRACT

The main protease (Mpro or 3CLpro) of SARS-CoV-2 virus is a cysteine enzyme critical for viral replication and transcription, thus indicating a potential target for antiviral therapy. A recent repurposing effort has identified ebselen, a multifunctional drug candidate, as an inhibitor of Mpro. Our docking of ebselen to crystal structure of Mpro catalytic pocket reveals a better fit of “tail-to-head” mode through noncovalent binding, suggesting modification of ebselen for its improvement of potency, antiviral activity and selectivity. To test this hypothesis, we designed and synthesized ebselen derivatives aimed at enhancing their non-covalent bonds within Mpro and reducing steric hindrance. The inhibition of Mpro by ebselen derivatives (0.3 μM) was screened in both HPLC and FRET assays. Nine ebselen derivatives exhibited stronger inhibitory effect on Mpro with IC50 of 0.07 to 0.38 μM. Further evaluation of three derivatives showed the inhibition on SARS-CoV-2 viral replication with their IC50 values from 4.08 to 19.93 µM in HPAepiC cells, as compared to prototype ebselen at 24.61 μM. Taken together, our identification of ebselen derivatives with improved antiviral activity may lead to developmental potential for treatment of COVID-19 and SARS-CoV-2 infection.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315529

ABSTRACT

Significant efforts are being made worldwide to understand the immune response to SARS-CoV-2, responsible for the COVID-19 pandemic, including the role of pre-existing T cell immunity. Understanding the mechanisms that promote cross-recognition by T cells induced by seasonal coronaviruses will be critical for future predictions on the role of pre-existing immunity in protection against severe disease. We demonstrate that the SARS-CoV-2 nucleocapsid (N) protein induces an immunodominant response in HLA-B7+ COVID-19-recovered individuals that is also readily detectable in unexposed donors. This immunodominant response is driven by a single N-encoded epitope that displays a high degree of conservation with the homologous region in circulating coronaviruses. We show that T cell-mediated cross-reactivity can be detected towards the circulating OC43/HKU-1 coronaviruses, but not the 229E or NL63 coronaviruses, due to different peptide conformations. This cross-reactivity is driven by private T cell receptor repertoires with a bias for TRBV27 and a long CDR3b loop in unexposed and COVID-19-recovered individuals. Together, our findings demonstrate the basis of pre-existing immunity to a conserved and highly immunogenic SARS-CoV-2 epitope driven by cross-reactive memory T cells, suggesting long-lived protective immunity.Funding: This work was supported by generous donations from the QIMR Berghofer COVID 19 appeal, and financial contributions from Monash University, Australian Nuclear Science and Technology Organisation (ANSTO, AISNE ECR grants), Australian Research Council (ARC), National Health and Medical Research Council (NHMRC), and the Medical Research Future Fund (MRFF). H.S. is supported by an Australian Government Research Training Program Scholarship, E.J.G. was supported by an NHMRC CJ Martin Fellowship (#1110429) and is supported by an Australian Research Council DECRA (DE210101479), K.R.S.is supported by an Australian Research Council DECRA (DE180100512), S.G. is supported by and NHMRC SRF (#1159272).Conflict of Interest: The authors declare no competing interests.Ethical Approval: This study was performed according to the principles of the Declaration of Helsinki.Ethics approval to undertake the research was obtained from the QIMR Berghofer Medical Research Institute Human Research Ethics Committee and Monash University Human Research Ethics Committee.

8.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-328894

ABSTRACT

The World Health Organization has defined long COVID-19 (LC) as a condition where patients exhibit persistent symptoms over time after its acute phase, which cannot be explained by alternative diagnosis. Since we have previously reported residual viral antigens in tissues of convalescent patients, we now aim to assess the presence of such antigens in post-convalescent tissues. Here, we established the presence of residual virus within the appendix and breast tissue of 2 patients who exhibited LC symptoms, 175 to 462 days upon positive diagnosis, using immunohistological techniques. We observed positive staining for viral nucleocapsid protein (NP) in the appendix, and tumour-adjacent region of the breast, but not within the tumour via multiplex immunohistochemistry. Notably, with RNAscope, both positive-sense and negative-sense (replicative intermediate) viral RNA were detected. As a single-stranded virus, SARS-CoV-2, have to produce a replicative intermediate as a template to synthesize new genomic RNAs. Thus, the detection of negative-sense viral RNA suggests ongoing viral replication. While viral RNA and antigen from gastrointestinal and stool samples of convalescent patients has been extensively reported, we believe this is the first study to detect viable virus. Furthermore, our positive finding in the breast tissue also corroborated with recent reports that immunocompromised patients had also experienced LC symptoms and persistent viral replication. Overall, our findings, along with emerging LC studies, question the possibility of the gastrointestinal tract functioning as a reservoir.

9.
Microbiol Spectr ; 10(1): e0109021, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1673362

ABSTRACT

The rapid emergence of the coronavirus disease 2019 (COVID-19) pandemic has introduced a new challenge in diagnosing and differentiating respiratory infections. Accurate diagnosis of respiratory infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is complicated by overlapping symptomology, and stepwise approaches to testing for each infection would lead to increased reagent usage and cost, as well as delays in clinical interventions. To avoid these issues, multiplex molecular assays have been developed to differentiate between respiratory viruses in a single test to meet clinical diagnostic needs. To evaluate the analytical performance of the FDA emergency use authorization (EUA)-approved Abbott Alinity m resp-4-plex assay (Alinity m) in testing for SARS-CoV-2, influenza A virus, influenza B virus, and respiratory syncytial virus (RSV), we compared its performance to those of both the EUA-approved Cepheid Xpert Xpress SARS-CoV-2, influenza A/B virus, and RSV assay (Xpert Xpress) and the EUA-approved Roche Cobas SARS-CoV-2 and influenza A/B virus assay (Cobas) in a single-center retrospective analysis. High concordance was observed among all three assays, with kappa statistics showing an almost perfect agreement (>0.90). The limit of detection (LOD) results for SARS-CoV-2 showed the Alinity m exhibiting the lowest LOD at 26 copies/mL, followed by the Cobas at 58 copies/mL and the Xpert Xpress at 83 copies/mL, with LOD results for the influenza A virus, influenza B virus, and RSV viral targets also showing equivalent or better performance on the Alinity m compared to the other two platforms. The Alinity m can be used as a high-volume testing platform for SARS-CoV-2, influenza A virus, influenza B virus, and RSV and exhibits analytical performance comparable to those of both the Xpert Xpress and Cobas assays. IMPORTANCE The rapid emergence of SARS-CoV-2 has introduced a new challenge in diagnosing and differentiating respiratory infections, especially considering the overlapping symptomology of many of these infections and differences in clinical interventions depending on the pathogen identified. To avoid these issues, multiplex molecular assays like the one described in this article need to be developed to differentiate between the most common respiratory pathogens in a single test and most effectively meet clinical diagnostic needs.


Subject(s)
Influenza A virus/isolation & purification , Influenza B virus/isolation & purification , Respiratory Syncytial Viruses/isolation & purification , Respiratory Tract Infections/diagnosis , SARS-CoV-2/isolation & purification , Diagnosis, Differential , Humans , Respiratory Tract Infections/virology , Sensitivity and Specificity , Time Factors
10.
Preprint in English | bioRxiv | ID: ppbiorxiv-473243

ABSTRACT

The >30 mutated residues in the Omicron spike protein have led to its rapid classification as a new SARS-CoV-2 variant of concern. As a result, Omicron may escape from the immune system, decreasing the protection provided by COVID-19 vaccines. Preliminary data shows a weaker neutralizing antibody response to Omicron compared to the ancestral SARS-CoV-2 virus, which can be increased after a booster vaccine. Here, we report that CD8+ T cells can recognize Omicron variant epitopes presented by HLA-A*02:01 in both COVID-19 recovered and vaccinated individuals, even 6 months after infection or vaccination. Additionally, the T cell response was stronger for Omicron variant epitopes after the vaccine booster. Altogether, T cells can recognize Omicron variants, especially in vaccinated individuals after the vaccine booster. One-Sentence SummaryCD8+ T cells response against Omicron variant epitopes is stronger after the vaccine booster.

11.
J Appl Lab Med ; 6(5): 1213-1220, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1387918

ABSTRACT

INTRODUCTION: The ePlex® SARS-CoV-2 emergency use authorization (EUA) test is a cartridge-based assay for the detection of SARS-CoV-2 in nasopharyngeal specimens. Since performance data has been previously published on this platform, the manufacturer has modified the workflow design in order to improve assay performance. Evaluation of the new workflow, which eliminated the sample delivery device (SDD), led to a dramatic improvement of assay performance while saving time and making cartridge loading more convenient. METHODS: 145 confirmed positive nasopharyngeal swab specimens were used to evaluate the assay analytical sensitivity, accuracy, and overall time-saving for the 2 workflows that is with and without the use of SDD on the ePlex SARS-CoV-2 test. RESULTS: Elimination of the SDD step led to a dramatic increase in accuracy and the overall limit of detection when using 145 previously defined and valid SARS-CoV-2 positive specimens with relatively low, medium, and high cycle thresholds (CT). This simple workflow change led to an overall detection from 94/145 (64.8%) to 131/145 (90.3%), with an additional 37 specimens being detected. CT value ranges revealed that 90% of the specimens in the 33 ≤ CT < 35.3 CT range were detected, whereas with the SDD workflow, only 30% of positive specimens were detected in this same range. Hands-on time for each specimen also improved and showed overall time savings. CONCLUSION: The simple workflow modification eliminating the SDD led to an overall improvement in the detection of positive specimens and also simplified workflow and reduced hands-on time.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19 Testing , Humans , Nasopharynx , Specimen Handling
12.
J Clin Virol ; 143: 104945, 2021 10.
Article in English | MEDLINE | ID: covidwho-1364216

ABSTRACT

While diagnosis of COVID-19 relies on qualitative molecular testing for the absence or presence of SARS-CoV-2 RNA, quantitative viral load determination for SARS-CoV-2 has many potential applications in antiviral therapy and vaccine trials as well as implications for public health and quarantine guidance. To date, no quantitative SARS-CoV-2 viral load tests have been authorized for clinical use by the FDA. In this study, we modified the FDA emergency use authorized qualitative RealTime SARS-CoV-2 assay into a quantitative SARS-CoV-2 Laboratory Developed Test (LDT) using newly developed Abbott SARS-CoV-2 calibration standards. Both analytical and clinical performance of this SARS-CoV-2 quantitative LDT was evaluated using nasopharyngeal swabs (NPS). We further assessed the correlation between Ct and the ability to culture virus on Vero CCL81 cells. The SARS-CoV-2 quantitative LDT demonstrated high linearity with R2 value of 0.992, high inter- and intra-assay reproducibility across the dynamic range (SDs ± 0.08-0.14 log10 copies/mL for inter-assay reproducibility and ± 0.09 to 0.19 log10 copies/mL for intra-assay reproducibility). Lower limit of detection was determined as 1.90 log10 copies/mL. The highest Ct at which CPE was detected ranged between 28.21-28.49, corresponding to approximately 4.2 log10 copies/mL. Quantitative tests, validated against viral culture capacity, may allow more accurate identification of individuals with and without infectious viral shedding from the respiratory tract.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19 Testing , Clinical Laboratory Techniques , Humans , Laboratories , RNA, Viral/genetics , Reproducibility of Results , Sensitivity and Specificity
13.
Build Environ ; 205: 108239, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1347510

ABSTRACT

Airborne transmission of respiratory diseases has been under intense spotlight in the context of coronavirus disease 2019 (COVID-19) where continued resurgence is linked to the relaxation of social interaction measures. To understand the role of speech aerosols in the spread of COVID-19 globally, the lifetime and size distribution of the aerosols are studied through a combination of light scattering observation and aerosol sampling. It was found that aerosols from speaking suspended in stagnant air for up to 9 h with a half-life of 87.2 min. The half-life of the aerosols declined with the increase in air change per hour from 28 to 40 min (1 h-1), 10-14 min (4 h-1), to 4-6 min (9 h-1). The speech aerosols in the size range of about 0.3-2 µm (after dehydration) witnessed the longest lifetime compared to larger aerosols (2-10 µm). These results suggest that speech aerosols have the potential to transmit respiratory viruses across long duration (hours), and long-distance (over social distance) through the airborne route. These findings are important for researchers and engineers to simulate the airborne dispersion of viruses in indoor environments and to design new ventilation systems in the future.

14.
FEBS J ; 288(17): 5042-5054, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1295003

ABSTRACT

The COVID-19 pandemic has highlighted the vulnerability of people with diabetes mellitus (DM) to respiratory viral infections. Despite the short history of COVID-19, various studies have shown that patients with DM are more likely to have increased hospitalisation and mortality rates as compared to patients without. At present, the mechanisms underlying this susceptibility are unclear. However, prior studies show that the course of COVID-19 disease is linked to the efficacy of the host's T-cell responses. Healthy individuals who can elicit a robust T-cell response are more likely to limit the severity of COVID-19. Here, we investigate the hypothesis that an impaired T-cell response in patients with type 2 diabetes mellitus (T2DM) drives the severity of COVID-19 in this patient population. While there is currently a limited amount of information that specifically addresses T-cell responses in COVID-19 patients with T2DM, there is a wealth of evidence from other infectious diseases that T-cell immunity is impaired in patients with T2DM. The reasons for this are likely multifactorial, including the presence of hyperglycaemia, glycaemic variability and metformin use. This review emphasises the need for further research into T-cell responses of COVID-19 patients with T2DM in order to better inform our response to COVID-19 and future disease outbreaks.


Subject(s)
COVID-19/immunology , Diabetes Mellitus, Type 2/immunology , Hyperglycemia/immunology , T-Lymphocytes/immunology , COVID-19/complications , COVID-19/pathology , COVID-19/virology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/pathology , Diabetes Mellitus, Type 2/virology , Humans , Hyperglycemia/complications , Hyperglycemia/pathology , Hyperglycemia/virology , Pandemics , SARS-CoV-2/pathogenicity , T-Lymphocytes/virology
15.
Clin Infect Dis ; 72(12): e1146-e1153, 2021 06 15.
Article in English | MEDLINE | ID: covidwho-1269565

ABSTRACT

The role of children in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains highly controversial. To address this issue, we performed a meta-analysis of the published literature on household SARS-CoV-2 transmission clusters (n = 213 from 12 countries). Only 8 (3.8%) transmission clusters were identified as having a pediatric index case. Asymptomatic index cases were associated with a lower secondary attack in contacts than symptomatic index cases (estimate risk ratio [RR], 0.17; 95% confidence interval [CI], 0.09-0.29). To determine the susceptibility of children to household infections the secondary attack rate in pediatric household contacts was assessed. The secondary attack rate in pediatric household contacts was lower than in adult household contacts (RR, 0.62; 95% CI, 0.42-0.91). These data have important implications for the ongoing management of the COVID-19 pandemic, including potential vaccine prioritization strategies.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Child , Family Characteristics , Humans , Incidence , Pandemics
16.
J Mol Diagn ; 23(6): 778-779, 2021 06.
Article in English | MEDLINE | ID: covidwho-1187797
17.
Chin J Nat Med ; 19(6): 473-480, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1258508

ABSTRACT

Huashi Baidu prescription (HSBDF), recommended in the Guideline for the Diagnosis and Treatment of Novel Coronavirus (2019-nCoV) Pneumonia (On Trials, the Seventh Edition), was clinically used to treat severe corona virus disease 2019 (COVID-19) with cough, blood-stained sputum, inhibited defecation, red tongue etc. symptoms. This study was aimed to elucidate and profile the knowledge on its chemical constituents and the potential anti-inflammatory effect in vitro. In the study, the chemical constituents in extract of HSBDF were characterized by UPLC-Q-TOF/MS in both negative and positive modes, and the pro-inflammatory cytokines were measured by enzyme-linked immunosorbent assays (ELISA) to determine the effects of HSBDF in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The results showed that a total of 217 chemical constituents were tentativedly characterized in HSBDF. Moreover, HSBDF could alleviate the expression levels of IL-6 and TNF-α in the cell models, indicating that the antiviral effects of HSBDF might be associated with regulation of the inflammatory cytokines production in RAW264.7 cells. We hope that the results could be served as the basic data for further study of HSBDF on anti-COVID-19 effect.


Subject(s)
Anti-Inflammatory Agents/chemistry , Antiviral Agents/chemistry , COVID-19/drug therapy , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/therapeutic use , Plant Extracts/chemistry , SARS-CoV-2/drug effects , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , Humans , Plant Extracts/therapeutic use
18.
J Appl Lab Med ; 6(5): 1213-1220, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1203710

ABSTRACT

INTRODUCTION: The ePlex® SARS-CoV-2 emergency use authorization (EUA) test is a cartridge-based assay for the detection of SARS-CoV-2 in nasopharyngeal specimens. Since performance data has been previously published on this platform, the manufacturer has modified the workflow design in order to improve assay performance. Evaluation of the new workflow, which eliminated the sample delivery device (SDD), led to a dramatic improvement of assay performance while saving time and making cartridge loading more convenient. METHODS: 145 confirmed positive nasopharyngeal swab specimens were used to evaluate the assay analytical sensitivity, accuracy, and overall time-saving for the 2 workflows that is with and without the use of SDD on the ePlex SARS-CoV-2 test. RESULTS: Elimination of the SDD step led to a dramatic increase in accuracy and the overall limit of detection when using 145 previously defined and valid SARS-CoV-2 positive specimens with relatively low, medium, and high cycle thresholds (CT). This simple workflow change led to an overall detection from 94/145 (64.8%) to 131/145 (90.3%), with an additional 37 specimens being detected. CT value ranges revealed that 90% of the specimens in the 33 ≤ CT < 35.3 CT range were detected, whereas with the SDD workflow, only 30% of positive specimens were detected in this same range. Hands-on time for each specimen also improved and showed overall time savings. CONCLUSION: The simple workflow modification eliminating the SDD led to an overall improvement in the detection of positive specimens and also simplified workflow and reduced hands-on time.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19 Testing , Humans , Nasopharynx , Specimen Handling
19.
Immunity ; 54(5): 1055-1065.e5, 2021 05 11.
Article in English | MEDLINE | ID: covidwho-1179683

ABSTRACT

Efforts are being made worldwide to understand the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, including the impact of T cell immunity and cross-recognition with seasonal coronaviruses. Screening of SARS-CoV-2 peptide pools revealed that the nucleocapsid (N) protein induced an immunodominant response in HLA-B7+ COVID-19-recovered individuals that was also detectable in unexposed donors. A single N-encoded epitope that was highly conserved across circulating coronaviruses drove this immunodominant response. In vitro peptide stimulation and crystal structure analyses revealed T cell-mediated cross-reactivity toward circulating OC43 and HKU-1 betacoronaviruses but not 229E or NL63 alphacoronaviruses because of different peptide conformations. T cell receptor (TCR) sequencing indicated that cross-reactivity was driven by private TCR repertoires with a bias for TRBV27 and a long CDR3ß loop. Our findings demonstrate the basis of selective T cell cross-reactivity for an immunodominant SARS-CoV-2 epitope and its homologs from seasonal coronaviruses, suggesting long-lasting protective immunity.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Coronavirus Nucleocapsid Proteins/immunology , Immunodominant Epitopes/immunology , SARS-CoV-2/immunology , Amino Acid Sequence , Coronavirus/classification , Coronavirus/immunology , Coronavirus Nucleocapsid Proteins/chemistry , Cross Reactions , Epitopes, T-Lymphocyte/chemistry , Epitopes, T-Lymphocyte/immunology , HLA-B7 Antigen/chemistry , HLA-B7 Antigen/genetics , HLA-B7 Antigen/immunology , Humans , Immunodominant Epitopes/chemistry , Immunologic Memory , Models, Molecular , Peptides/chemistry , Peptides/immunology , Receptors, Antigen, T-Cell/chemistry , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/immunology
20.
J Glob Health ; 10(2): 020513, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1106360

ABSTRACT

BACKGROUND: The COVID-19 pandemic is challenging the public health response system worldwide, especially in poverty-stricken, war-torn, and least developed countries (LDCs). METHODS: We characterized the epidemiological features and spread dynamics of COVID-19 in Niger, quantified the effective reproduction number (Rt ), evaluated the impact of public health control measures, and estimated the disease burden. RESULTS: As of 4 July 2020, COVID-19 has affected 29 communes of Niger with 1093 confirmed cases, among whom 741 (67.8%) were males. Of them 89 cases died, resulting in a case fatality rate (CFR) of 8.1%. Both attack rates and CFRs were increased with age (P < 0.0001). Health care workers accounted for 12.8% cases. Among the reported cases, 39.3% were isolated and treated at home, and 42.3% were asymptomatic. 74.6% cases were clustered in Niamey, the capital of Niger. The Rt fluctuated in correlation to control measures at different outbreak stages. After the authorities initiated the national response and implemented the strictest control measures, Rt quickly dropped to below the epidemic threshold (<1), and maintained low level afterward. The national disability-adjusted life years attributable to COVID-19 was 1267.38 years in total, of which years of life lost accounted for over 99.1%. CONCLUSIONS: Classic public health control measures such as prohibition of public gatherings, travelling ban, contact tracing, and isolation and quarantine at home, are proved to be effective to contain the outbreak in Niger, and provide guidance for controlling the ongoing COVID-19 pandemic in LDCs.


Subject(s)
COVID-19/epidemiology , COVID-19/prevention & control , Communicable Disease Control/organization & administration , Adult , Developing Countries , Female , Health Personnel , Humans , Male , Middle Aged , Niger/epidemiology , Pandemics , SARS-CoV-2 , Socioeconomic Factors
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