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1.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22269243

RESUMO

SARS-CoV-2 Delta and Omicron strains are the most globally relevant variants of concern (VOCs). While individuals infected with Delta are at risk to develop severe lung disease1, Omicron infection causes less severe disease, mostly upper respiratory symptoms2,3. The question arises whether rampant spread of Omicron could lead to mass immunization, accelerating the end of the pandemic. Here we show that infection with Delta, but not Omicron, induces broad immunity in mice. While sera from Omicron-infected mice only neutralize Omicron, sera from Delta-infected mice are broadly effective against Delta and other VOCs, including Omicron. This is not observed with the WA1 ancestral strain, although both WA1 and Delta elicited a highly pro-inflammatory cytokine response and replicated to similar titers in the respiratory tracts and lungs of infected mice as well as in human airway organoids. Pulmonary viral replication, pro-inflammatory cytokine expression, and overall disease progression are markedly reduced with Omicron infection. Analysis of human sera from Omicron and Delta breakthrough cases reveals effective cross-variant neutralization induced by both viruses in vaccinated individuals. Together, our results indicate that Omicron infection enhances preexisting immunity elicited by vaccines, but on its own may not induce broad, cross-neutralizing humoral immunity in unvaccinated individuals.

2.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21268048

RESUMO

The Omicron SARS-CoV-2 virus contains extensive sequence changes relative to the earlier arising B.1, B.1.1 and Delta SARS-CoV-2 variants that have unknown effects on viral infectivity and response to existing vaccines. Using SARS-CoV-2 virus-like particles (SC2-VLPs), we examined mutations in all four structural proteins and found that Omicron showed 3-fold higher capsid assembly and cell entry relative to Delta, a property conferred by S and N protein mutations. Thirty-eight antisera samples from individuals vaccinated with Pfizer/BioNTech, Moderna, Johnson & Johnson vaccines and convalescent sera from unvaccinated COVID-19 survivors had 15-fold lower efficacy to prevent cell transduction by VLPs containing the Omicron mutations relative to the ancestral B.1 spike protein. A third dose of Pfizer vaccine elicited substantially higher neutralization titers against Omicron, resulting in detectable neutralizing antibodies in 8 out of 8 subjects compared to 1 out of 8 pre-boost. Furthermore, the monoclonal antibody therapeutics Casirivimab and Imdevimab had robust neutralization activity against B.1, B.1.1 or Delta VLPs but no detectable neutralization of Omicron VLPs. Our results suggest that Omicron is more efficient at assembly and cell entry compared to Delta, and the antibody response triggered by existing vaccines or previous infection, at least prior to boost, will have limited ability to neutralize Omicron. In addition, some currently available monoclonal antibodies will not be useful in treating Omicron-infected patients. One-Sentence SummaryOmicron SARS-CoV-2 virus-like particles have enhanced infectivity that is only weakly neutralized by vaccination without boost or prior infection, or antibody therapeutics.

3.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21250523

RESUMO

BackgroundPatients have been shown to shed SARS-CoV-2 viral RNA in nasopharyngeal (NP) specimens for over 100 days after resolution of clinical disease (1, 2). How this relates to anterior nares and oral fluid specimens has not previously been investigated. MethodsWe prospectively collected oral fluid, anterior nares, NP swab and serum specimens from 1,326 individuals at 2 "drive-through" testing locations. The Curative SARS-CoV-2 Assay (Curative Assay)(3) on oral fluid and anterior nares specimens was compared to the EURORealTime SARS-CoV-2 Assay (EuroRT Assay)(4) on anterior nares and NP specimens. Viral culture and IgG serology were used to assess infectious potential and stage of disease. Additionally we investigated differences in viral RNA detection between specimen types, both early (< 21 days) and late (> 21 days) in SARS-CoV-2 infection, by using an employee surveillance program with daily SARS-CoV-2 testing to precisely determine infection date, even without symptoms. We prospectively collected oral fluid, anterior nares and NP swab specimens from 165 subjects with early infections and 22 subjects with late infections. Specimens were tested using the Curative Assay with the "high-sensitivity" Hologic Aptima SARS-CoV-2 Assay (Hologic Assay)(5) on an NP swab used as the comparator. Late infection specimens were also tested with EuroRT and Zymo Quick SARS-CoV-2 rRT-PCR Kit (Zymo) (6) Assays. ResultsThe "drive-through" study showed similar sensitivities of oral fluid and anterior nares specimens on the Curative Assay to anterior nares specimens tested with the EuroRT Assay. However NP specimens tested with the same EuroRT assay produced 20-30% more positives. Incorporating viral culture and serology data to exclude NP RT-PCR positives that are not infectious or late in the course of disease showed a Positive Percent Agreement (PPA) for of 98.2% and 96.2% and Negative Percent Agreement (NPA) of 97.6% and 98.1% for anterior nares and oral fluid specimens, respectively. Within 21 days of infection, the Curative Assay showed a PPA and NPA of 100% and 100%, respectively for oral fluid; of 100% and 99% respectively for anterior nares; and of 98.2% and 99.0%, respectively in nasopharyngeal specimens compared to an NP specimen on the Hologic Assay. 29 positives were asymptomatic and showed 100% PPA and 100% NPA for all specimen types. After 21 days from infection onset, significant divergence between NP and other specimen types occurred on all 4 assays. Out of 22 paired sample sets, 18, 13, 8 and 4 NP specimens were positive on the Curative, Zymo, Hologic and EuroRT assays, respectively, compared to only 3, 2, 0 and 1 positive anterior nares specimens. Only one oral fluid sample was positive in both the Curative and Zymo assays. ConclusionsWe used a unique population to show significant divergence between NP specimens and anterior nares or oral fluid specimens >21 days from SARS-CoV-2 infection, which appears to be biological variation and is independent of assay used. This has significant public health implications for the use of NP specimens in community testing programs and policy implications for evaluation of novel specimen types and tests where the use of NP swabs as a comparator may say more about the study population than the assay or specimen type to be evaluated and may unnecessarily limit access to testing.

4.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20210609

RESUMO

Current commercially available methods for reliably detecting antibodies against SARS-CoV-2 remain expensive and inaccessible due to the need for whole blood collection by highly trained phlebotomists using personal protective equipment (PPE). We evaluated an antibody detection approach utilizing the OraSure(R) Technologies Oral Antibody Collection Device (OACD) and their proprietary SARS-CoV-2 total antibody detection enzyme-linked immunosorbent assay (ELISA). We found that the OraSure(R) test for total antibody detection in oral fluid had comparable sensitivity and specificity to serum-based ELISAs while presenting a more affordable and accessible system with the potential for self-collection.

5.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20062372

RESUMO

BackgroundCurrently, there is a pandemic caused by the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes Covid-19. We wanted to compare specimen types and collection methods to explore if a simpler to collect specimen type could expand access to testing. MethodsWe recruited individuals recently tested for SARS-CoV-2 infection through a "drive-through" testing program. In participants homes, we assessed the performance of self-collected oral fluid swab specimens with and without clinician supervision, clinician-supervised self-collected mid-turbinate (nasal) swab specimens, and clinician-collected nasopharyngeal swab specimens. We tested specimens with a validated reverse transcription-quantitative polymerase chain reaction assay for the detection of SARS-CoV-2 and measured cycle threshold values. Symptom status and date of onset of symptoms was also recorded for each participant. ResultsWe recruited 45 participants. The median age of study participant was 42 years old (Interquartile range, 31 to 52 years). Of the participants, 29 had at least one specimen test positive for SARS-CoV-2. Of those, 21 (73%) of 29 reported active symptoms. By specimen type and home-based collection method, clinician-supervised self-collected oral fluid swab specimens detected 26 (90%) of 29 infected individuals, clinician-supervised self-collected nasal swab specimens detected 23 (85%) of 27, clinician-collected posterior nasopharyngeal swab specimens detected 23 (79%) of 29, and unmonitored self-collected oral fluid swab specimens detected 19 (66%) of 29. Despite nasopharyngeal swabs being considered the gold standard, 4 participants tested negative by clinician-collected nasopharyngeal swab and positive by the 3 other specimen types. Additionally, false negative results by each sample type were seen to generally not overlap. ConclusionsSupervised self-collected oral fluid and nasal swab specimens performed similarly to, if not better than clinician-collected nasopharyngeal swab specimens for the detection of SARS-CoV-2 infection. No sample type captured all SARS-CoV-2 infections, suggesting potential heterogeneity in the distribution of viral load in different parts of the respiratory tract between individuals. Supervised self-collection performed comparably to clinician collection and would allow for rapid expansion of testing capacity in the United States by reducing the need for trained healthcare workers, reducing exposure of healthcare workers, and reducing the amount of PPE (personal protective equipment) being used for testing during a critical shortage.

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