Background: The ability to predict likely prognosis and infectiousness for patients with COVID-19 would aid patient management decisions. Diagnosis is usually via real-time PCR, and it is unclear whether the semi-quantitative capability of this method, determining viral load through cycle threshold (Ct) values, can be leveraged. Objectives: We aim to review available knowledge on correlations between SARS-COV-2 Ct values and patient-or healthcare-related outcomes to determine whether Ct values provide useful clinical information. Sources: A PubMed search was conducted on 1 June 2020 based on a search strategy of (Ct value OR viral load) AND SARS-CoV-2. Data were extracted from studies reporting on the presence or absence of an association between Ct values, or viral loads determined via Ct value, and clinical outcomes. Content: Data from 18 studies were relevant for inclusion. One study reported on the correlation between Ct values and mortality and one study reported on the correlation between Ct values and progression to severe disease; both reported a significant association (p \ 0.001 and p = 0.008, respectively). Fourteen studies reported on the correlation between Ct value or viral loads determined via Ct value and disease severity, and an association was observed in eight (57%) studies. Studies reporting on the correlation of viral load with biochemical and haematological markers showed an association with at least one marker, including increased lactate dehydrogenase (n = 4), decreased lymphocytes (n = 3) and increased high-sensitivity troponin I (n = 2). Two studies reporting on the correlation with infectivity showed that lower Ct values were associated with higher viral culture positivity. Implications: Data suggest that lower Ct values may be associated with worse outcomes and that Ct values may be useful in predicting the clinical course and prognosis of patients with Digital Features: To view digital features for this article go to
A recent publication by Sun H. and colleagues in the Proceedings of the National Academy of Science (PNAS) has drown global attention to the predominant genotype "G4" Eurasian (EA) avian-like H1N1 In uenza A virus that has been spreading among pigs in China since 2016, which is predicted to have a signi cant pandemic potential. Since pigs are hosts for the generation of pandemic In uenza A viruses (IAVs), surveillance and preparedness are critical to prevent pandemics. In this regards, one distinguishing feature of the QIAstat-Dx ® Respiratory SARS-CoV-2 panel is the double target approach In uenza A detection of seasonal strains affecting humans, by ampli cation of a generic In uenza A assay plus one of the speci c assays discriminating H3, H1 and H1N1pdm09 subtypes. The generic In uenza A assay is designed to amplify any IAV, a key feature for preparedness. Here we report an initial in-silico analysis that predicts that the G4 EA avian-like H1N1 strains tested in the QIAstat-Dx ® Respiratory SARS-CoV-2 Panel would be detected yielding a positive result for the generic In uenza A assay and negative results for the seasonal H3, H1 and H1N1pdm09 assays. This prediction was con rmed in-vitro using dsDNA fragments mixed to mimic the genomes of the different reported G4 EA IAV strains. In conclusion, the QIAstat-Dx ® Respiratory SARS-CoV-2 Panel could be a useful tool to differentially diagnose zoonotic strains from the seasonal In uenza A strains commonly affecting humans.
Introduction There is an increasing body of evidence surrounding the importance of a T cell-mediated response to SARS-CoV-2 infection and after COVID-19 vaccination. In this internal feasibility study, we evaluated both the total antibody (IgA, IgM, and IgG) and T cell responses in a cohort of COVID-19 convalescents and vaccinated individuals. Methods Whole blood specimens were collected weekly from 12 subjects at different time points within/after the COVID-19 mRNA vaccination regimen, and from 4 PCR-confirmed convalescent donors to measure durability of humoral and cell-mediated immune response. T cell and antibody responses were evaluated via the QuantiFERON SARS-CoV-2 research use only (QFN SARS-CoV-2) assay which is an interferon gamma release assay (IGRA) and QIAreach Anti-SARS-CoV-2 total (Anti-CoV-2) test, respectively. Results In a cohort of recently vaccinated individuals, subjects demonstrated robust total antibody and CD4+/CD8+ T cell response to SARS-CoV-2 mRNA vaccines when followed for 2 months post-2nd dose. In most individuals, T cell response declined between the 1st and 2nd doses suggesting a need for a booster or the completion of the 2-dose vaccine series. In a group of convalescent donors tested with QFN SARS-CoV-2 and Anti-CoV-2 tests, all patients had an antibody and T cell response up to 1 year after natural infection. Conclusion This small feasibility study demonstrates that the QFN-SARS-CoV-2 test is able to identify CD4+ and CD8+ T cell-mediated responses in SARS-CoV-2-vaccinated subjects and those recovered from COVID-19, alongside a qualitative antibody response detectable via the QIAreach Anti-CoV2 test.
Despite the rise and impact of methicillin-resistant Staphylococcus aureus, methicillin-susceptible S. aureus (MSSA) continues to contribute to the overall burden of S. aureus infections, representing Ն50% of clinical S. aureus strains (1-3) with known appreciable mortality outcomes (4, 5). Prevailing evidence supports the use of semisynthetic penicillins, such as oxacillin or nafcillin, or the first-generation cephalosporin cefazolin in preference to vancomycin as optimal therapy for MSSA bloodstream infections (BSI) (6-11). Moreover, an early switch from vancomycin to either nafcillin or cefazolin with definitive MSSA identification was associated with a 69% risk reduction in 30-day in-hospital mortality in a recent retrospective cohort study (11).Cefazolin offers a convenient dosing scheme with a favorable adverse event profile, allowing many institutions to consider its use in the management of MSSA infections (12). However, deepseated infections with a high burden of S. aureus have been shown to overproduce certain types of -lactamases, rendering cefazolin inactive and thus resulting in possible treatment failure (13-15). Furthermore, current practice guidelines, such as those for infective endocarditis, suggest reserving the use of cefazolin for patients with nonanaphylactoid-type penicillin allergies (7). As a result, clinician preference for either nafcillin or oxacillin for more severe or deep-seated MSSA infection has evolved in practice, while the use of cefazolin in this setting remains controversial (12,16,17). The purpose of this study was to evaluate and compare treatment outcomes using cefazolin or oxacillin for MSSA BSI, including deep-seated sources of infection.(Portions of this paper were presented as a poster at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy, 5 to 9 September 2014, Washington, DC.) MATERIALS AND METHODS Study design.From January 2010 to April 2013, a retrospective cohort study was conducted at Rush University Medical Center (RUMC) and Northwestern Memorial Hospital (NMH), two tertiary care academic medical centers in Chicago, IL. The study methods were reviewed and approved by the institutional review boards at RUMC, NMH, and Midwestern University. Adult patients who received in-hospital definitive treatment with cefazolin or oxacillin within 48 h of finalized blood cultures with MSSA were eligible for inclusion in the study. Patients were included only once, and only the first (index) in-hospital admission during the study period was evaluated. The index blood culture was the first blood culture growing MSSA during the index admission. Patients were excluded if they (i) were Ͻ18 years of age, (ii) received antibiotics other than cefazolin or oxacillin for definitive treatment of an MSSA BSI, (iii) received Ն5 days of an empirical antibiotic agent active against MSSA prior to definitive treatment with cefazolin or oxacillin, (iv) had a docu-
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