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Background: Post-acute sequelae of COVID-19, or long COVID, is a condition characterized by persistent COVID-19 symptoms. As long COVID is defined by clinical criteria after an elapsed period, an opportunity for early intervention may aid in future prophylactic approaches; however, at present, the pathobiological mechanisms are multifactorial. By analyzing early virally infected upper respiratory tract tissue prior to eventual clinical diagnosis, it may be possible to identify biomarkers of altered immune response to facilitate future studies and interventions. Methods: This is a sub-group analysis of samples collected from those with confirmed COVID-19. RNA extraction from nasopharyngeal/mid-turbinate samples, sequencing, and bioinformatic analysis were performed to analyze long COVID and non-long COVID cohorts at day 14 post infection. Differences in mean viral load at various timepoints were analyzed as well as serological data. Results: We identified 26 upregulated genes in patients experiencing long COVID. Dysregulated pathways including complement and fibrinolysis pathways and IL-7 upregulation. Additionally, genes involved in neurotransmission were dysregulated, and the long COVID group had a significantly higher viral load and slower viral clearance. Conclusions: Uncovering early gene pathway abnormalities associated with eventual long COVID diagnosis may aid in early identification. We show that, post acute infection, in situ pathogenic deviations in viral response are associated with patients destined to meet consensus long COVID diagnosis that is entirely dependent on clinical factors. These results identify an important biological temporal window in the natural history of COVID-19 infection and long COVID pathogenesis amenable to testing from standard-of-care upper respiratory tract specimens.
RESUMO
INTRODUCTION: The on-going substance use crisis has led to unprecedented rates of hepatitis C virus (HCV) in Canada, with increasing positivity among women who use drugs (WWUD). Despite efforts to reduce barriers to HCV testing and treatment, follow-up remains a major issue. METHODS: In this quality improvement project (QIP), we partnered with a short-stay trauma-informed residential drug treatment facility specifically for WWUD, to provide an engaging peer-led HCV education session, followed by low-barrier nurse and peer-led testing and treatment. We sought to evaluate these interventions, as well as determine what factors could improve engagement after women leave. RESULTS: The session was attended by 217 participants, 130 completed the survey and 153 opted into testing. Survey results indicated that participants were highly motivated to access general care as well as HCV testing and treatment. The most frequently reported barriers to testing and treatment were a previous negative test and being asymptomatic, respectively. Follow-up facilitators included a non-judgmental provider (88%), monetary incentives (67%), follow-up phone calls (77%), e-mails (66%) and text messages (58%). Of those who were RNA positive, 5 of 13 initiated treatment on-site. By using the results of the QIP in real-time, 6 of 13 were started after leaving the centre (one pending and one lost to follow-up). DISCUSSION AND CONCLUSIONS: The implementation of co-localised peer-led testing and treatment for HCV, along with persistent follow-up efforts, led to increases in linkage to care and treatment. Co-localisation of testing and care with substance-use services, especially if residential, is a viable, low-barrier strategy for increasing linkage to care among WWUD.
