ABSTRACT
SARS-CoV-2 and its emerging variants of concern remain a major threat for global health. Here we introduce a novel infection model based upon polarized human Alveolar Epithelial Lentivirus immortalized (hAELVi) cells grown at the air-liquid interface to estimate replication and epidemic potential of respiratory viruses in the human lower respiratory tract. hAELVI cultures are highly permissive for different human coronaviruses and seasonal influenza A virus and upregulate various mediators following virus infection. Our analysis revealed a significantly reduced capacity of SARS-CoV-2 Omicron variant to propagate in this human model compared to earlier D614G and Delta variants, which extends early risk assessments from epidemiological and animal studies suggesting a reduced pathogenicity of Omicron.
ABSTRACT
The reliable detection of SARS-CoV-2 genomic RNA and infectious virus particles from patient samples requires a good sample quality. This is especially critical when the sample has to be transported to the analysing laboratory which can take several days. To determine optimal transport conditions, we simulated oropharyngeal swab samples using defined virus amounts and stored the samples at 4 °C or at room temperature for up to four days. Moreover, we analysed the influence of dry swabs in comparison to swabs stored in transport medium. Our results show that care should be taken when analysing samples for infectious SARS-CoV-2 particles since infectivity is strongly influenced by sample storage.
ABSTRACT
Background The detection of SARS-CoV-2 with rapid diagnostic tests has become an important tool to identify infected people and break infection chains. These rapid diagnostic tests are usually based on antigen detection in a lateral flow approach. Aims & Methods While for PCR diagnostics the validation of a PCR assay is well established, for antigen tests e.g. rapid diagnostic tests there is no common validation strategy. Here we present the establishment of a panel of 50 pooled clinical specimens that cover a SARS-CoV-2 concentration range from approximately 1.1 × 10 9 to 420 genome copies per mL of specimen. The panel was used to evaluate 31 rapid diagnostic tests in up to 6 laboratories. Results Our results show that there is significant variation in the detection limits and the clinical sensitivity of different rapid diagnostic tests. We conclude that the best rapid diagnostic tests can be applied to reliably identify infectious individuals who are presenting with SARS-CoV-2 loads correlated to 10 6 genome copies per mL of specimen. Infected individuals displaying SARS-CoV-2 genome loads corresponding to less than 10 6 genome copies per mL will be identified by only some rapid diagnostics tests, while many tests miss these viral loads to a large extent. Conclusions Sensitive RDTs can be applied to identify infectious individuals with high viral loads, but not to identify infected individuals.
ABSTRACT
SARS-CoV and SARS-CoV-2 infections are characterized by remarkable differences, including contagiosity and case fatality rate. The underlying mechanisms are not well understood, illustrating major knowledge gaps of coronavirus biology. In this study, protein expression of SARS-CoV- and SARS-CoV-2-infected human lung epithelial cell line Calu-3 was analysed using data-independent acquisition mass spectrometry (DIA-MS). This resulted in the so far most comprehensive map of infection-related proteome-wide expression changes in human cells covering the quantification of 7478 proteins across 4 time points. Most notably, the activation of interferon type-I response was observed, which surprisingly is absent in other recent proteome studies, but is known to occur in SARS-CoV-2-infected patients. The data reveal that SARS-CoV-2 triggers interferon-stimulated gene (ISG) expression much stronger than SARS-CoV, which reflects the already described differences in interferon sensitivity. Potentially, this may be caused by the enhanced expression of viral M protein of SARS-CoV in comparison to SARS-CoV-2, which is a known inhibitor of type I interferon expression. This study expands the knowledge on the host response to SARS-CoV-2 infections on a global scale using an infection model, which seems to be well suited to analyse innate immunity.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
Point of care detection of SARS-CoV-2 is one pillar in a containment strategy and important to break infection chains. Here we report the sensitive, specific and robust detection of SARS-CoV-2 and respective variants of concern by the ID NOW COVID-19 device.
Subject(s)
COVID-19ABSTRACT
In early 2020 COVID-19 turned into a global pandemic. Non-pharmaceutical interventions (NPIs), including the isolation of infected individuals, tracing and quarantine of exposed individuals are decisive tools to prevent onwards transmission and curb fatalities. Strategies that combine NPIs with SARS-CoV-2 testing may help to shorten quarantine durations while being non-inferior with respect to infection prevention. Thus, combined strategies can help reducing the socio-economic burden of SARS-CoV2 and generate greater public acceptance. We developed a software that enables policy makers to calculate the reduction in transmissibility through quarantine or isolation in combination with arbitrary testing strategies. The user chooses between three different modi [(i) isolation of infected individuals, (ii) management of potentially infected contacts and (iii) quarantine of incoming travelers], while having total flexibility in customizing testing strategies, as well as setting model parameters. The software enables decision makers to tailor calculations specifically to their questions and perform an assessment on the fly, based on current evidence on infection dynamics. Underneath, we analytically solve a stochastic transit compartment model of the infection time course, which captures temporal changes in test sensitivities, incubation- and infectious periods, as well as times to symptom onset using its default parameters. Using default parameters, we estimated that testing travelers at the point of entry reduces the risk about 4.69 (4.19,4.83) fold for PCR vs. 3.59 (3.22, 3.69) fold for based rapid diagnostic tests (RDT, 87% relative sensitivity) when combined with symptom screening. In comparison to 14 days of pure quarantine, 8 (PCR) vs. 10 (RDT) days of pre-test quarantine would be noninferior for incoming travelers as well as for contact person management. De-isolation of infected individuals 11 days after symptom onset reduces the risk by >99fold (7.68,>1012). This tool is freely available from: https://github.com/CovidStrategyCalculator/CovidStrategyCalculator