ABSTRACT
HostSeq was launched in April 2020 as a national initiative to integrate whole genome sequencing data from 10,000 Canadians infected with SARS-CoV-2 with clinical information related to their disease experience. The mandate of HostSeq is to support the Canadian and international research communities in their efforts to understand the risk factors for disease and associated health outcomes and support the development of interventions such as vaccines and therapeutics. HostSeq is a collaboration among 13 independent epidemiological studies of SARS-CoV-2 across five provinces in Canada. Aggregated data collected by HostSeq are made available to the public through two data portals: a phenotype portal showing summaries of major variables and their distributions, and a variant search portal enabling queries in a genomic region. Individual-level data is available to the global research community for health research through a Data Access Agreement and Data Access Compliance Office approval. Here we provide an overview of the collective project design along with summary level information for HostSeq. We highlight several statistical considerations for researchers using the HostSeq platform regarding data aggregation, sampling mechanism, covariate adjustment, and X chromosome analysis. In addition to serving as a rich data source, the diversity of study designs, sample sizes, and research objectives among the participating studies provides unique opportunities for the research community.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/epidemiology , Canada/epidemiology , Genomics , Whole Genome SequencingABSTRACT
Background Real-world data is currently limited on the association between oral antiviral therapy and healthcare system burden in patients with mild-to-moderate COVID-19. This study aims to evaluate the clinical and cost effec-tiveness of Molnupiravir and Nirmatrelvir-ritonavir use in reducing mortality in this population. Methods This is a retrospective cohort study involving 54,355 COVID-19 patients during February 22-March 31,2022 in Hong Kong. Inverse probability of treatment weighting (IPTW) was used to adjust patient characteristics. Our exposure of interest was Molnupiravir/Nirmatrelvir-Ritonavir prescription, with all-cause mortality as the pri-mary outcome. IPTW-adjusted multivariate regressions were used to estimate treatment impact on clinic re -atten-dance and unplanned admissions. Finally, attributed cost and incremental cost-effectiveness ratios (ICER) were estimated. Findings In the outpatient cohort (N = 33,217, 61.1%), 16.1% used Molnupiravir and 13.4% used Nirmatrelvir-Ritona-vir, while in the inpatient cohort (N = 21,138, 38.9%), 3.8% used Molnupiravir and 1.3% used Nirmatrelvir-Ritonavir. IPTW-adjusted Cox model estimated that Molnupiravir (hazard ratio (HR)(95%CI)=0.31 (0.24-0.40), P< 0.0001) and Nirmatrelvir-Ritonavir (HR=0.10 (95%CI 0.05-0.21), P< 0.0001) were significantly associated with a reduced mortality hazard. In the outpatient cohort, both antiviral prescriptions were associated with reduced odds for unplanned hospital admissions (Molnupiravir: odds ratio (OR) =0.72 (0.52-0.98), P=0.039;Nirmatrelvir-Ritonavir: OR=0.37 (0.23-0.60), P<0.0001). Among hospitalised patients, both antiviral prescriptions were associated with sig-nificant reductions in the odds ratios for 28-days readmission (Molnupiravir: OR=0.71 (0.52-0.97), P=0.031;Nirma-trelvir-Ritonavir: OR=0.47 (0.24-0.93), P=0.030). ICERs for death averted for Molnupiravir stood at USD493,345.09 in outpatient settings and USD2,629.08 in inpatient settings. In outpatient settings, Nirmatrelvir-ritonavir cost USD331,105.27 to avert one death, but saved USD5,502.53 to avert one death in comparison with standard care. Interpretation In high-risk patients in Hong Kong with mild-to-moderate COVID-19, Molnupiravir and Nirmatrel-vir-Ritonavir prescriptions were associated with reduced all-cause mortality and significant cost savings.
ABSTRACT
Background: The mechanisms by which COVID-19 results in severe illness in some individuals remains poorly defined. Identification of biomarkers associated with disease severity could be useful in defining the mechanisms of COVID-19 pathology and predicting disease course. Aim(s): Identify trajectories of biomarkers of coagulation, endothelial dysfunction, and fibrinolysis that are associated with COVID-19 severity. Method(s): Longitudinal plasma samples were collected from 99 patients in the Canadian COVID-19 Prospective Cohort Study (CanCOV) (23 outpatients, 31 ward patients, and 45 intensive care unit (ICU) patients). Plasma was quantified using 1) ELISAs for plasminogen, soluble thrombomodulin (sTM), plasminogen activator inhibitor-1 (PAI-1), alpha2-antiplasmin, D-dimer, thrombin-activatable fibrinolysis inhibitor (TAFI), and fibrinogen, and 2) in-house functional assays for clot lysis times and activated TAFI (TAFIa) levels. Biomarker values were log-transformed and linear mixed effects models were used to compare trajectories in ICU and ward patients compared to outpatients from date of symptom onset. Result(s): Among the 45 ICU patients, 24 (53%) died. There were no deaths in the other patient groups. D-dimer (Fig 1A) and sTM (Fig 1B) were significantly elevated for both hospitalized and ICU cohorts when compared with outpatients. PAI-1 (Fig 1C) was significantly elevated only in the ICU group between days 1 and 40. Plasminogen (Fig 1D) significantly decreased only in the ICU group from day 25 onwards. TAFIa (Fig 1E) increased over time only in the ICU cohort, with the levels being significant from day 35. Fibrinogen (Fig 1F) displayed similar trends as plasminogen whereby only the ICU was significantly decreased from day 25. alpha2-antiplasmin, TAFI, and clot lysis times were not significantly different compared to COVID-19 outpatients Conclusion(s): D-dimer and sTM showed the strongest associations with moderate and severe COVID-19 compared to mild disease. PAI-1, plasminogen, TAFIa, and fibrinogen may additionally be useful in identifying patients who become critically ill.
ABSTRACT
Aim: The Anesthesia Patient Safety Foundation and the American Society of Anesthesiologists released a 2022 joint statement suggesting a delay of seven weeks for elective surgeries after a diagnosis of COVID-19 in unvaccinated patients based on data on previous variants of SARS-CoV-2. As Omicron causes less severe disease, we postulate that the delay may be shortened. This study investigates whether the Omicron variant affects perioperative risks and whether surgery can be performed earlier in COVID-19 patients, especially for cancer cases. Method(s): We performed a comparative study on the postoperative outcome of patients undergoing elective cancer surgery with and without COVID-19. We prospectively collected data on COVID-19 patients from March to May, 2022 at North District Hospital, during the Omicron surge and compared with a similar cohort from July to December, 2021, during the quiescence of COVID-19 in Hong Kong. Result(s): 23 COVID-19 positive and 223 COVID-19 negative patients were included in the study. 87% of COVID-19 patients were vaccinated. Patients received surgery from 2 to 11 weeks post- COVID-19 diagnosis. There were no significant differences in preoperative characteristics including age, gender, history of cerebrovascular accident, diabetes mellitus, chronic kidney disease, preoperative pneumonia and American Society of Anesthesiologists classification. Postoperative 30-day mortality, rates of pneumonia, acute respiratory distress syndrome, deep venous thrombosis showed no difference. Conclusion(s): Elective surgery can be safely performed in patients recently diagnosed with COVID-19 Omicron variant with no significant difference in postoperative outcomes compared to patients without COVID-19. With more data, elective surgery may be performed earlier than seven weeks after COVID-19 diagnosis.