ABSTRACT
Genetically distinct variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged since the start of the COVID-19 pandemic. Over this period, we developed a rapid platform (R-20) for viral isolation and characterization using primary remnant diagnostic swabs. This, combined with quarantine testing and genomics surveillance, enabled the rapid isolation and characterization of all major SARS-CoV-2 variants circulating in Australia in 2021. Our platform facilitated viral variant isolation, rapid resolution of variant fitness using nasopharyngeal swabs and ranking of evasion of neutralizing antibodies. In late 2021, variant of concern Omicron (B1.1.529) emerged. Using our platform, we detected and characterized SARS-CoV-2 VOC Omicron. We show that Omicron effectively evades neutralization antibodies and has a different entry route that is TMPRSS2-independent. Our low-cost platform is available to all and can detect all variants of SARS-CoV-2 studied so far, with the main limitation being that our platform still requires appropriate biocontainment.
Subject(s)
COVID-19 , SARS-CoV-2 , Australia , COVID-19/diagnosis , Humans , Pandemics , SARS-CoV-2/geneticsABSTRACT
A proportion of patients surviving acute coronavirus disease 2019 (COVID-19) infection develop post-acute COVID syndrome (long COVID (LC)) lasting longer than 12 weeks. Here, we studied individuals with LC compared to age- and gender-matched recovered individuals without LC, unexposed donors and individuals infected with other coronaviruses. Patients with LC had highly activated innate immune cells, lacked naive T and B cells and showed elevated expression of type I IFN (IFN-ß) and type III IFN (IFN-λ1) that remained persistently high at 8 months after infection. Using a log-linear classification model, we defined an optimal set of analytes that had the strongest association with LC among the 28 analytes measured. Combinations of the inflammatory mediators IFN-ß, PTX3, IFN-γ, IFN-λ2/3 and IL-6 associated with LC with 78.5-81.6% accuracy. This work defines immunological parameters associated with LC and suggests future opportunities for prevention and treatment.
Subject(s)
B-Lymphocytes/immunology , COVID-19/complications , Immunity, Innate , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Adult , Aged , B-Lymphocytes/metabolism , B-Lymphocytes/virology , Biomarkers/blood , COVID-19/blood , COVID-19/immunology , COVID-19/virology , Case-Control Studies , Cytokines/blood , Female , Host-Pathogen Interactions , Humans , Inflammation Mediators/blood , Male , Middle Aged , Prognosis , SARS-CoV-2/pathogenicity , Severity of Illness Index , T-Lymphocytes/metabolism , T-Lymphocytes/virology , Time Factors , Post-Acute COVID-19 SyndromeABSTRACT
ObjectivesTo characterise cognitive performance and olfaction in recovered COVID-19 patients.MethodsPatients underwent cognitive, olfaction and mental health assessments 2 months after initial SARS-CoV-2 infection as part of the Sydney St. Vincent’s Hospital ADAPT study, a prospective cohort study. Cognition was assessed with the Cogstate computerised battery and expressed as a demographically-corrected composite z-score and clinically classified as impaired/borderline/unimpaired. Anxio-depressive symptoms were assessed with the Depression in the Medical ill scale-10 (DMI-10), the Somatic and Psychological HEalth Report-34 (SPHERE) Psych sub-scale, and the Impact of Events Scale-Revised (IESR) and reduced into single Principal Component explaining 80% of the variance. Olfaction was assessed with the NIH Toolbox Odor Identification test and expressed as demographically-corrected T-scores, and impaired/unimpaired. Disease severity was classified as mild (40%), moderate (50%) or hospitalised (10%).Results132 patients (mean age=46±15;40% women, median education=16 years, 10% Non-English-Speaking Background-NESB) were included. 17% had impaired cognition, 10% had borderline deficits, 25% has impaired olfaction. 25% had clinically elevated symptoms on the DMI-10, 13% on the IESR, and 35% on the SPHERE. Regression analyses showed that anxio-depression was not associated with cognitive performance (unadjusted p=.43;adjusted for sex & NESB p=.98) nor impaired/unimpaired status (unadjusted p=.50;adjusted for sex & NESB p=.78). Cognitively impaired patients were more likely to have impaired olfaction (p<.009). Results were independent of disease severity.ConclusionsCognitive impairment is common and not related to psychological factors, may occur independent of disease severity and is associated with anosmia. These point to direct brain effects of COVID-19.