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1.
Sci Rep ; 12(1): 1724, 2022 02 02.
Article in English | MEDLINE | ID: covidwho-1663979

ABSTRACT

This study introduces localized surface plasmon resonance (L-SPR) mediated heating filter membrane (HFM) for inactivating universal viral particles by using the photothermal effect of plasmonic metal nanoparticles (NPs). Plasmonic metal NPs were coated onto filter membrane via a conventional spray-coating method. The surface temperature of the HFM could be controlled to approximately 40-60 °C at room temperature, owing to the photothermal effect of the gold (Au) NPs coated on them, under irradiation by visible light-emitting diodes. Due to the photothermal effect of the HFMs, the virus titer of H1Npdm09 was reduced by > 99.9%, the full inactivation time being < 10 min, confirming the 50% tissue culture infective dose (TCID50) assay. Crystal violet staining showed that the infectious samples with photothermal inactivation lost their infectivity against Mardin-Darby Canine Kidney cells. Moreover, photothermal inactivation could also be applied to reduce the infectivity of SARS-CoV-2, showing reduction rate of 99%. We used quantitative reverse transcription polymerase chain reaction (qRT-PCR) techniques to confirm the existence of viral genes on the surface of the HFM. The results of the TCID50 assay, crystal violet staining method, and qRT-PCR showed that the effective and immediate reduction in viral infectivity possibly originated from the denaturation or deformation of membrane proteins and components. This study provides a new, simple, and effective method to inactivate viral infectivity, leading to its potential application in various fields of indoor air quality control and medical science.


Subject(s)
COVID-19/virology , Hot Temperature , Light , Metal Nanoparticles , Micropore Filters , SARS-CoV-2 , Surface Plasmon Resonance/methods , Virion , Virus Inactivation , Air Pollution, Indoor , Animals , Cells, Cultured , Dogs , Gold/chemistry , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity
2.
Front Cell Infect Microbiol ; 12: 967493, 2022.
Article in English | MEDLINE | ID: covidwho-2029957

ABSTRACT

Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has posed a constant threat to human beings and the world economy for more than two years. Vaccination is the first choice to control and prevent the pandemic. However, an effective SARS-CoV-2 vaccine against the virus infection is still needed. This study designed and prepared four kinds of virus-like particles (VLPs) using an insect expression system. Two constructs encoded wild-type SARS-CoV-2 spike (S) fused with or without H5N1 matrix 1 (M1) (S and SM). The other two constructs contained a codon-optimized spike gene and/or M1 gene (mS and mSM) based on protein expression, stability, and ADE avoidance. The results showed that the VLP-based vaccine could induce high SARS-CoV-2 specific antibodies in mice, including specific IgG, IgG1, and IgG2a. Moreover, the mSM group has the most robust ability to stimulate humoral immunity and cellular immunity than the other VLPs, suggesting the mSM is the best immunogen. Further studies showed that the mSM combined with Al/CpG adjuvant could stimulate animals to produce sustained high-level antibodies and establish an effective protective barrier to protect mice from challenges with mouse-adapted strain. The vaccine based on mSM and Al/CpG adjuvant is a promising candidate vaccine to prevent the COVID-19 pandemic.


Subject(s)
COVID-19 , Influenza A Virus, H5N1 Subtype , Viral Vaccines , Adjuvants, Immunologic/pharmacology , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/genetics , Humans , Immunoglobulin G , Mice , Mice, Inbred BALB C , Pandemics/prevention & control , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
3.
Pan Afr Med J ; 41: 55, 2022.
Article in English | MEDLINE | ID: covidwho-2025478

ABSTRACT

Introduction: the limited number of equipped laboratories and the lack of expertise left Africa lagging behind in terms of contribution in genomic data generation. The COVID-19 pandemic has drawn the attention of all public health stakeholders so that it can be used as a marker of the efforts that public health systems can produced. The main purpose of the present analytical study was to evaluate the contribution of the African continent in the genomic surveillance of SARS-CoV-2. Methods: data from the two most popular genomic databases on SARS-CoV-2 (GISAID EpiCov and NCBI Virus) were extracted and analyzed. Comparisons were made using the sequencing ratio which represents the number of genomic sequence published over one thousands confirmed cases. Results: considering continental blocks, the Africa occupied the fourth place after Oceania, Europe and North America based on sequencing ratios. However, when the considered comparison parameter is the number of sequences, the African continent was the fifth contributor after Europe, North America, Asia and South America. Conclusion: the study showed that African countries have effectively integrated the genomic data generation in the public health response strategies but the effective use of these data for a perfect surveillance is not clearly established. There is a need for capacity building in genomic data analyses for a better response to public health threats in Africa.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Decision Making , Genome, Viral , Genomics , Humans , Pandemics , Public Health , SARS-CoV-2/genetics
4.
PLoS One ; 17(6): e0270060, 2022.
Article in English | MEDLINE | ID: covidwho-2021817

ABSTRACT

BACKGROUND: An ideal test for COVID-19 would combine the sensitivity of laboratory-based PCR with the speed and ease of use of point-of-care (POC) or home-based rapid antigen testing. We evaluated clinical performance of the Diagnostic Analyzer for Selective Hybridization (DASH) SARS-CoV-2 POC rapid PCR test. METHODS: We conducted a cross-sectional study of adults with and without symptoms of COVID-19 at four clinical sites where we collected two bilateral anterior nasal swabs and information on COVID-19 symptoms, vaccination, and exposure. One swab was tested with the DASH SARS-CoV-2 POC PCR and the second in a central laboratory using Cepheid Xpert Xpress SARS-CoV-2 PCR. We assessed test concordance and calculated sensitivity, specificity, negative and positive predictive values using Xpert as the "gold standard". RESULTS: We enrolled 315 and analyzed 313 participants with median age 42 years; 65% were female, 62% symptomatic, 75% had received ≥2 doses of mRNA COVID-19 vaccine, and 16% currently SARS-CoV-2 positive. There were concordant results for 307 tests indicating an overall agreement for DASH of 0.98 [95% CI 0.96, 0.99] compared to Xpert. DASH performed at 0.96 [95% CI 0.86, 1.00] sensitivity and 0.98 [95% CI 0.96, 1.00] specificity, with a positive predictive value of 0.85 [95% CI 0.73, 0.96] and negative predictive value of 0.996 [95% CI 0.99, 1.00]. The six discordant tests between DASH and Xpert all had high Ct values (>30) on the respective positive assay. DASH and Xpert Ct values were highly correlated (R = 0.89 [95% CI 0.81, 0.94]). CONCLUSIONS: DASH POC SARS-CoV-2 PCR was accurate, easy to use, and provided fast results (approximately 15 minutes) in real-life clinical settings with an overall performance similar to an EUA-approved laboratory-based PCR.


Subject(s)
COVID-19 , Adult , COVID-19/diagnosis , COVID-19 Testing , COVID-19 Vaccines , Clinical Laboratory Techniques/methods , Cross-Sectional Studies , Female , Humans , Male , Point-of-Care Systems , Polymerase Chain Reaction , SARS-CoV-2/genetics , Sensitivity and Specificity
5.
PLoS One ; 17(6): e0269798, 2022.
Article in English | MEDLINE | ID: covidwho-2021801

ABSTRACT

Clinical evidence for asymptomatic cases of coronavirus disease (COVID-19) has reinforced the significance of effective surveillance testing programs. Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) assays are considered the 'gold standard' for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. However, the labor and resource requirements can be prohibitive with respect to large testing volumes associated with the pandemic. Pooled testing algorithms may serve to increase testing capacity with more efficient resource utilization. Due to the lack of carefully curated cohorts, there is limited evidence for the applicability of RT-PCR pooling in asymptomatic COVID-19 cases. In this study, we compared the analytical sensitivity of the TaqMan™ SARS-CoV-2 Pooling Assay to detect one positive sample in a pool of five anterior nares swabs in symptomatic and asymptomatic cohorts at an institute of higher education. Positive pools were deconvoluted and each individual sample was retested using the TaqPath™ COVID-19 Combo Kit. Both assays target the open reading frame (ORF) 1ab, nucleocapsid (N), and spike (S) gene of the strain that originated in Wuhan, Hubei, China. Qualitative results demonstrated absolute agreement between pooled and deconvoluted samples in both cohorts. Independent t-test performed on Ct shifts supported an insignificant difference between cohorts with p-values of 0.306 (Orf1ab), 0.147 (N), and 0.052 (S). All negative pools were correctly reported as negative. Pooled PCR testing up to five samples is a valid method for surveillance testing of students and staff in a university setting, especially when the prevalence is expected to be low.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , COVID-19 Testing , Clinical Laboratory Techniques/methods , Humans , Pandemics , SARS-CoV-2/genetics , Sensitivity and Specificity
6.
Enferm Infecc Microbiol Clin (Engl Ed) ; 40(5): 262-265, 2022 May.
Article in English | MEDLINE | ID: covidwho-2015163

ABSTRACT

INTRODUCTION: SARS-CoV-2variants of concern (VOC) have been described in the UK (B.1.1.7), South Africa (B.1.351) and Brazil (P.1). Among them, the most scarce information has been obtained from the P.1 variant and more data on its global presence and about its spreading dynamics are needed. METHODS: Whole genome sequencing was performed prospectively on travellers arriving from Brazil and on a random selection of SARS-CoV-2 positive cases from our population. RESULTS: In this study we report the first SARS-CoV-2 P.1 and P.2 variants exported from Brazil to Spain. The case infected with the P.1 variant, who had only stayed in Rio de Janeiro, required hospitalisation. The two P.2 cases remained asymptomatic. A wider distribution for P.1 variant beyond the Brazilian Amazonia should be considered. The exportation of the P.2 variant, carrying the E484K mutation, deserves attention. One month after the first description of P.1 and P.2 importations from Brazil to Madrid, these variants were identified circulating in the community, in cases without a travel history, and involved in household transmissions CONCLUSION: Whole genome sequencing of SARS-CoV-2 positive travellers arriving from Brazil allowed us to identify the first importations of P.1 and P.2 variants to Spain and their early community transmission.


Subject(s)
COVID-19 , SARS-CoV-2 , Brazil/epidemiology , COVID-19/epidemiology , Humans , SARS-CoV-2/genetics , Spain/epidemiology
7.
Ann Intern Med ; 175(8): JC94, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-2006466

ABSTRACT

SOURCE CITATION: Karlstad Ø, Hovi P, Husby A, et al. SARS-CoV-2 vaccination and myocarditis in a Nordic cohort study of 23 million residents. JAMA Cardiol. 2022;7:600-12. 35442390.


Subject(s)
COVID-19 , Myocarditis , Viral Vaccines , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Cohort Studies , Humans , RNA, Messenger , SARS-CoV-2/genetics , Vaccination/adverse effects
8.
Cell Rep Med ; 3(4): 100603, 2022 04 19.
Article in English | MEDLINE | ID: covidwho-2004611

ABSTRACT

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic highlights the importance of determining the breadth and durability of humoral immunity to SARS-CoV-2 mRNA vaccination. Herein, we characterize the humoral response in 27 naive and 40 recovered vaccinees. SARS-CoV-2-specific antibody and memory B cell (MBC) responses are durable up to 6 months, although antibody half-lives are shorter for naive recipients. The magnitude of the humoral responses to vaccination strongly correlates with responses to initial SARS-CoV-2 infection. Neutralization titers are lower against SARS-CoV-2 variants in both recovered and naive vaccinees, with titers more reduced in naive recipients. While the receptor-binding domain (RBD) is the main neutralizing target of circulating antibodies, Moderna-vaccinated naives show a lesser reliance on RBDs, with >25% neutralization remaining after depletion of RBD-binding antibodies. Overall, we observe that vaccination induces higher peak titers and improves durability in recovered compared with naive vaccinees. These findings have broad implications for current vaccine strategies deployed against the SARS-CoV-2 pandemic.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , SARS-CoV-2/genetics , Vaccination
9.
Diagn Microbiol Infect Dis ; 103(3): 115718, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-2000368

ABSTRACT

Faced with the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), high-throughput respiratory tests are in high demand. We evaluated the clinical performance of the GSD NovaPrime® SARS-CoV-2 RTq-PCR assay, a new assay that detects 2 specific RNA sequences of the nucleocapsid (N) gene. It was assessed using 99 nasopharyngeal samples and compared in parallel with the Allplex® assay. Among those samples, 72 and 27 were included in the positive (PPA) and negative (NPA) percent agreement analyses, respectively. In case of discordance, samples were reanalyzed with another amplification technique, the Aptima® SARS-CoV-2 assay. Cross-reactivity, including specimens positive for another respiratory virus and collected before the COVID-19 outbreak, was also evaluated (n = 32). Based on the patients' clinical history, the Ct (cycle threshold) values obtained, and the results of the Aptima® assay, the clinical performances were deemed satisfactory, with the PPA reaching a minimum percentage of 87.5% and the NPA reaching 100%. No cross-reactivity with other respiratory viruses was observed.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , COVID-19 Testing , Humans , Nasopharynx , Polymerase Chain Reaction , SARS-CoV-2/genetics , Sensitivity and Specificity
10.
Orv Hetil ; 163(33): 1295-1302, 2022 Aug 14.
Article in English | MEDLINE | ID: covidwho-1993571

ABSTRACT

INTRODUCTION: BioFire FilmArray Pneumonia plus Panel (bioMérieux) is a PCR method for microbiological diagnostics of lower respiratory infections. It can detect 18 bacteria, 9 viruses and 7 antibiotic resistance genes in real time. It can help the differential diagnosis and the choice of therapy of pneumonia, by giving results in two hours. OBJECTIVE: Reviewing the results of pneumonia PCR tests performed in our laboratory, and comparing them with the results of conventional culturing. METHOD: From October 2020 to September 2021, 820 lower respiratory tract samples were analyzed from inpatients with suspected pneumonia. Beside the PCR test, culturing was also performed. Oropharyngeal swabs were used for supplementary SARS-CoV-2 PCR. RESULTS: 40% of samples were collected from SARS-CoV-2-positive patients. In 60% of the samples, the PCR test detected pathogens or resistance genes. The most commonly detected pathogens were Pseudomonas aeruginosa, Staphylococcus aureus and Acinetobacter baumannii. 44% of the bacteria detected by PCR were not verified by culturing, whereas by culturing, several other bacteria, fungi and antibiotic resistance mechanisms were detected, which were not shown in the results of the multiplex PCR tests. In SARS-CoV-2-positive inpatients, 25.8% of the detected bacteria was S. aureus. The most common resistance gene was mecA/C (MRSA). In this group, other respiratory virus genes were detected in 2% of SARS-CoV-2-positive patients, whereas in 13% in samples of SARS-CoV-2-negative patients. CONCLUSIONS: Because of the importance of pathogens excluded from the PCR targets and multifactorial mechanisms of antibiotic resistance, culturing is recommended to perform beside pneumonia-specific multiplex PCR tests. Orv Hetil. 2022; 163(33): 1295-1302.


Subject(s)
COVID-19 , Pneumonia , Bacteria , COVID-19/diagnosis , Humans , Multiplex Polymerase Chain Reaction , SARS-CoV-2/genetics , Staphylococcus aureus
11.
Genome Med ; 14(1): 90, 2022 Aug 12.
Article in English | MEDLINE | ID: covidwho-1993379

ABSTRACT

BACKGROUND: Genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the only approach to rapidly monitor and tackle emerging variants of concern (VOC) of the COVID-19 pandemic. Such scrutiny is crucial to limit the spread of VOC that might escape the immune protection conferred by vaccination strategies or previous virus exposure. It is also becoming clear now that efficient genomic surveillance would require monitoring of the host gene expression to identify prognostic biomarkers of treatment efficacy and disease progression. Here we propose an integrative workflow to both generate thousands of SARS-CoV-2 genome sequences per week and analyze host gene expression upon infection. METHODS: In this study we applied an integrated workflow for RNA extracted from nasal swabs to obtain in parallel the full genome of SARS-CoV-2 and transcriptome of host respiratory epithelium. The RNA extracted from each sample was reverse transcribed and the viral genome was specifically enriched through an amplicon-based approach. The very same RNA was then used for patient transcriptome analysis. Samples were collected in the Campania region, Italy, for viral genome sequencing. Patient transcriptome analysis was performed on about 700 samples divided into two cohorts of patients, depending on the viral variant detected (B.1 or delta). RESULTS: We sequenced over 20,000 viral genomes since the beginning of the pandemic, producing the highest number of sequences in Italy. We thus reconstructed the pandemic dynamics in the regional territory from March 2020 to December 2021. In addition, we have matured and applied novel proof-of-principle approaches to prioritize possible gain-of-function mutations by leveraging patients' metadata and isolated patient-specific signatures of SARS-CoV-2 infection. This allowed us to (i) identify three new viral variants that specifically originated in the Campania region, (ii) map SARS-CoV-2 intrahost variability during long-term infections and in one case identify an increase in the number of mutations in the viral genome, and (iii) identify host gene expression signatures correlated with viral load in upper respiratory ways. CONCLUSION: In conclusion, we have successfully generated an optimized and cost-effective strategy to monitor SARS-CoV-2 genetic variability, without the need of automation. Thus, our approach is suitable for any lab with a benchtop sequencer and a limited budget, allowing an integrated genomic surveillance on premises. Finally, we have also identified a gene expression signature defining SARS-CoV-2 infection in real-world patients' upper respiratory ways.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/genetics , Genome, Viral , Humans , Pandemics , RNA , SARS-CoV-2/genetics
12.
J Nanobiotechnology ; 20(1): 269, 2022 Jun 11.
Article in English | MEDLINE | ID: covidwho-1993364

ABSTRACT

BACKGROUND: RNA viruses periodically trigger pandemics of severe human diseases, frequently causing enormous economic losses. Here, a nucleic acid extraction-free and amplification-free RNA virus testing probe was proposed for the sensitive and simple detection of classical swine fever virus (CSFV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), based on a double-stranded molecular beacon method. This RNA virus probe contains two base sequences-a recognition strand that binds to the specific domain of CSFV N2 or SARS-CoV-2 N, with a fluorophore (FAM) labeled at the 5' end, and a complementary strand (CSFV-Probe B or SARS-CoV-2-Probe B), combined with a quencher (BHQ2) labeled at the 3' end. RESULTS: Using linear molecular beacon probe technology, the detection limit of the RNA virus probe corresponding to CSFV and SARS-CoV-2 were as low as 0.28 nM and 0.24 nM, respectively. After CSFV E2 and SARS-CoV-2 N genes were transfected into corresponding host cells, the monitoring of RNA virus probes showed that fluorescence signals were dramatically enhanced in a concentration- and time-dependent manner. These results were supported by those of quantitative (qRT-PCR) and visualization (confocal microscopy) analyses. Furthermore, CSF-positive swine samples and simulated SARS-CoV-2 infected mouse samples were used to demonstrate their applicability for different distributions of viral nucleic acids in series tissues. CONCLUSIONS: The proposed RNA virus probe could be used as a PCR-free, cost-effective, and rapid point-of-care (POC) diagnostic platform for target RNA virus detection, holding great potential for the convenient monitoring of different RNA viruses for early mass virus screening.


Subject(s)
COVID-19 , Classical Swine Fever Virus , Nucleic Acids , Animals , COVID-19/diagnosis , Classical Swine Fever Virus/genetics , Mice , Molecular Probes , Polymerase Chain Reaction , SARS-CoV-2/genetics , Sensitivity and Specificity , Swine
15.
Philos Trans A Math Phys Eng Sci ; 380(2233): 20210315, 2022 Oct 03.
Article in English | MEDLINE | ID: covidwho-1992467

ABSTRACT

The English SARS-CoV-2 epidemic has been affected by the emergence of new viral variants such as B.1.177, Alpha and Delta, and changing restrictions. We used statistical models and the agent-based model Covasim, in June 2021, to estimate B.1.177 to be 20% more transmissible than the wild type, Alpha to be 50-80% more transmissible than B.1.177 and Delta to be 65-90% more transmissible than Alpha. Using these estimates in Covasim (calibrated 1 September 2020 to 20 June 2021), in June 2021, we found that due to the high transmissibility of Delta, resurgence in infections driven by the Delta variant would not be prevented, but would be strongly reduced by delaying the relaxation of restrictions by one month and with continued vaccination. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Models, Statistical , SARS-CoV-2/genetics , Systems Analysis
16.
Philos Trans A Math Phys Eng Sci ; 380(2233): 20210304, 2022 Oct 03.
Article in English | MEDLINE | ID: covidwho-1992462

ABSTRACT

The SARS-CoV-2 epidemic has been extended by the evolution of more transmissible viral variants. In autumn 2020, the B.1.177 lineage became the dominant variant in England, before being replaced by the B.1.1.7 (Alpha) lineage in late 2020, with the sweep occurring at different times in each region. This period coincided with a large number of non-pharmaceutical interventions (e.g. lockdowns) to control the epidemic, making it difficult to estimate the relative transmissibility of variants. In this paper, we model the spatial spread of these variants in England using a meta-population agent-based model which correctly characterizes the regional variation in cases and distribution of variants. As a test of robustness, we additionally estimated the relative transmissibility of multiple variants using a statistical model based on the renewal equation, which simultaneously estimates the effective reproduction number R. Relative to earlier variants, the transmissibility of B.1.177 is estimated to have increased by 1.14 (1.12-1.16) and that of Alpha by 1.71 (1.65-1.77). The vaccination programme starting in December 2020 is also modelled. Counterfactual simulations demonstrate that the vaccination programme was essential for reopening in March 2021, and that if the January lockdown had started one month earlier, up to 30 k (24 k-38 k) deaths could have been prevented. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Communicable Disease Control , Humans , SARS-CoV-2/genetics , Seasons
17.
J Infect Dis ; 226(1): 23-31, 2022 Aug 12.
Article in English | MEDLINE | ID: covidwho-1992205

ABSTRACT

The durability of protective humoral immunity after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and infection is largely dependent on the generation and persistence of antigen-specific isotype-switched memory B cells (MBCs) and long-lived plasma cells that reside in the bone marrow and secrete high-affinity neutralizing antibodies. The reactivity of vaccine-induced MBCs to emerging clinically significant SARS-CoV-2 variants of concern (VoCs) is largely unknown. In a longitudinal cohort study (up to 6 months following coronavirus disease 2019 messenger RNA vaccination), we measured MBCs in concert with other functional antibody measures. We found statistically significant differences between the frequencies of MBCs responding to homologous and VoC (Beta, Gamma, and Delta) receptor-binding domains after vaccination that persisted over time. In concert with a waning antibody response, the reduced MBC response to VoCs could translate to a weaker subsequent recall immune response and increased susceptibility to the emerging SARS-CoV-2 variant strains after vaccination.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , Antibody Formation , COVID-19/prevention & control , Humans , Longitudinal Studies , RNA, Messenger , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Vaccination
18.
Clin Infect Dis ; 75(Supplement_1): S110-S120, 2022 Aug 15.
Article in English | MEDLINE | ID: covidwho-1992148

ABSTRACT

BACKGROUND: Comprehensive pathogen genomic surveillance represents a powerful tool to complement and advance precision vaccinology. The emergence of the Alpha variant in December 2020 and the resulting efforts to track the spread of this and other severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern led to an expansion of genomic sequencing activities in Germany. METHODS: At Robert Koch Institute (RKI), the German National Institute of Public Health, we established the Integrated Molecular Surveillance for SARS-CoV-2 (IMS-SC2) network to perform SARS-CoV-2 genomic surveillance at the national scale, SARS-CoV-2-positive samples from laboratories distributed across Germany regularly undergo whole-genome sequencing at RKI. RESULTS: We report analyses of 3623 SARS-CoV-2 genomes collected between December 2020 and December 2021, of which 3282 were randomly sampled. All variants of concern were identified in the sequenced sample set, at ratios equivalent to those in the 100-fold larger German GISAID sequence dataset from the same time period. Phylogenetic analysis confirmed variant assignments. Multiple mutations of concern emerged during the observation period. To model vaccine effectiveness in vitro, we employed authentic-virus neutralization assays, confirming that both the Beta and Zeta variants are capable of immune evasion. The IMS-SC2 sequence dataset facilitated an estimate of the SARS-CoV-2 incidence based on genetic evolution rates. Together with modeled vaccine efficacies, Delta-specific incidence estimation indicated that the German vaccination campaign contributed substantially to a deceleration of the nascent German Delta wave. CONCLUSIONS: SARS-CoV-2 molecular and genomic surveillance may inform public health policies including vaccination strategies and enable a proactive approach to controlling coronavirus disease 2019 spread as the virus evolves.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/prevention & control , Genome, Viral , Genomics , Humans , Phylogeny , SARS-CoV-2/genetics , Vaccinology
19.
Clin Infect Dis ; 75(Supplement_1): S61-S71, 2022 Aug 15.
Article in English | MEDLINE | ID: covidwho-1992145

ABSTRACT

BACKGROUND: Male sex and old age are risk factors for severe coronavirus disease 2019, but the intersection of sex and aging on antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has not been characterized. METHODS: Plasma samples were collected from older adults (aged 75-98 years) before and after 3 doses of SARS-CoV-2 mRNA vaccination, and from younger adults (aged 18-74 years) post-dose 2, for comparison. Antibody binding to SARS-CoV-2 antigens (spike protein [S], S receptor-binding domain, and nucleocapsid), functional activity against S, and live-virus neutralization were measured against the vaccine virus and the Alpha, Delta, and Omicron variants of concern (VOCs). RESULTS: Vaccination induced greater antibody titers in older females than in older males, with both age and frailty associated with reduced antibody responses in males but not females. Responses declined significantly in the 6 months after the second dose. The third dose restored functional antibody responses and eliminated disparities caused by sex, age, and frailty in older adults. Responses to the VOCs, particularly the Omicron variant, were significantly reduced relative to the vaccine virus, with older males having lower titers to the VOCs than older females. Older adults had lower responses to the vaccine and VOC viruses than younger adults, with greater disparities in males than in females. CONCLUSIONS: Older and frail males may be more vulnerable to breakthrough infections owing to low antibody responses before receipt of a third vaccine dose. Promoting third dose coverage in older adults, especially males, is crucial to protecting this vulnerable population.


Subject(s)
COVID-19 , Frailty , Viral Vaccines , Aged , COVID-19/prevention & control , Humans , Male , SARS-CoV-2/genetics , Vaccines, Synthetic , mRNA Vaccines
20.
Proc Natl Acad Sci U S A ; 119(34): e2204256119, 2022 Aug 23.
Article in English | MEDLINE | ID: covidwho-1991767

ABSTRACT

Antibody therapeutics for the treatment of COVID-19 have been highly successful. However, the recent emergence of the Omicron variant has posed a challenge, as it evades detection by most existing SARS-CoV-2 neutralizing antibodies (nAbs). Here, we successfully generated a panel of SARS-CoV-2/SARS-CoV cross-neutralizing antibodies by sequential immunization of the two pseudoviruses. Of the potential candidates, we found that nAbs X01, X10, and X17 offer broad neutralizing potential against most variants of concern, with X17 further identified as a Class 5 nAb with undiminished neutralization against the Omicron variant. Cryo-electron microscopy structures of the three antibodies together in complex with each of the spike proteins of the prototypical SARS-CoV, SARS-CoV-2, and Delta and Omicron variants of SARS-CoV-2 defined three nonoverlapping conserved epitopes on the receptor-binding domain. The triple-antibody mixture exhibited enhanced resistance to viral evasion and effective protection against infection of the Beta variant in hamsters. Our findings will aid the development of antibody therapeutics and broad vaccines against SARS-CoV-2 and its emerging variants.


Subject(s)
COVID-19 , SARS Virus , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , Cryoelectron Microscopy , Epitopes , Humans , Neutralization Tests , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
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