Validation of dried blood spot sampling for detecting SARS-CoV-2 antibodies and total immunoglobulins in a large cohort of asymptomatic young adults.

BACKGROUND: Detecting antibody responses following infection with SARS-CoV-2 is necessary for sero-epidemiological studies and assessing the role of specific antibodies in disease, but serum or plasma sampling is not always viable due to logistical challenges. Dried blood spot sampling (DBS) is a cheaper, simpler alternative and samples can be self-collected and returned by post, reducing risk for SARS-CoV-2 exposure from direct patient contact. The value of large-scale DBS sampling for the assessment of serological responses to SARS-CoV-2 has not been assessed in depth and provides a model for examining the logistics of using this approach to other infectious diseases. The ability to measure specific antigens is attractive for remote outbreak situations where testing may be limited or for patients who require sampling after remote consultation. METHODS: We compared the performance of SARS-CoV-2 anti-spike and anti-nucleocapsid antibody detection from DBS samples with matched serum collected by venepuncture in a large population of asymptomatic young adults (N = 1070) living and working in congregate settings (military recruits, N = 625); university students, N = 445). We also compared the effect of self-sampling (ssDBS) with investigator-collected samples (labDBS) on assay performance, and the quantitative measurement of total IgA, IgG and IgM between DBS eluates and serum. RESULTS: Baseline seropositivity for anti-spike IgGAM antibody was significantly higher among university students than military recruits. Strong correlations were observed between matched DBS and serum samples in both university students and recruits for the anti-spike IgGAM assay. Minimal differences were found in results by ssDBS and labDBS and serum by Bland Altman and Cohen kappa analyses. LabDBS achieved 82.0% sensitivity and 98.2% specificity and ssDBS samples 86.1% sensitivity and 96.7% specificity for detecting anti-spike IgGAM antibodies relative to serum samples. For anti-SARS-CoV-2 nucleocapsid IgG there was qualitatively 100% agreement between serum and DBS samples and weak correlation in ratio measurements. Strong correlations were observed between serum and DBS-derived total IgG, IgA, and IgM. CONCLUSIONS: This is the largest validation of DBS against paired serum for SARS-CoV-2 specific antibody measurement and we have shown that DBS retains performance from prior smaller studies. There were no significant differences regarding DBS collection methods, suggesting that self-collected samples are a viable sampling collection method. These data offer confidence that DBS can be employed more widely as an alternative to classical serology.

EFFECTS OF LOW MOLECULAR WEIGHT HEPARIN AND FONDAPARINUX ON MORTALITY, HEMORRHAGIC AND THROMBOTIC COMPLICATIONS IN COVID-19 PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Background and aims: Coronavirus disease 2019 (COVID-19) is associated with increased thrombosis prevalence. However, there are insufficient data supporting the appropriate anticoagulation (AC) dose in COVID-19. Methods: We conducted a living systematic review and meta-analysis on the effects of different low molecular weight heparin (LMWH) and/ or fondaparinux doses on mortality, thrombotic and hemorrhagic events in COVID-19 patients. MEDLINE, Scopus, Embase, Cochrane Library, Cochrane COVID-19 study register, European Union Drug Regulating Authorities Clinical Trials Database and ClinicalTrials.gov were searched to detect observational cohort studies and randomized-controlled clinical trials (RCTs) comparing difference doses of LMWH or fondaparinux among confirmed COVID-19 cases. Results: Thirty-one eligible studies (6 RCTs and 25 cohort studies) with 11,430 hospitalized patients were included. No association was found between AC and mortality during the following comparisons: a) no AC versus any AC;b) prophylactic versus higher than prophylactic AC;c) prophylactic versus therapeutic AC;d) intermediate versus therapeutic AC;and e) lower than therapeutic versus therapeutic AC. However, the risk for all-cause mortality was higher in patients receiving prophylactic versus intermediate AC (OR=2.01;95%CI: 1.19-3.39). No associations were detected between the intensity of AC and the risk of thrombotic and hemorrhagic events, except the significantly lower risk for hemorrhage in patients on prophylactic compared to higher AC doses. Conclusions: The risk for all-cause mortality was significantly higher in patients receiving prophylactic AC compared to those on an intermediate dose of AC. These results should be interpreted in light of the moderate quality and heterogeneity of the included studies.