ABSTRACT
Introduction: Severe COVID-19 has been associated with aberrant coagulation factor activities, particularly in patients with a thrombotic event (TE). Management of anticoagulant is critical in the care of hospitalized patients with COVID-19.Hypothesis: Evaluation of a point-of-care (POC), functional, clot-time-based coagulation test to detect the anticoagulant effect of therapeutic unfractionated heparin (UFH) in hospitalized SARS-CoV-2-positive patients who developed a TE. Methods: An IRB-approved analysis of 36 citrated plasma specimens from 26 SARS-CoV-2-positive patients and 10 matched negative controls was performed. A Clotting Time Score (CTS), a measure of factor-specific inhibition (i.e. anticoagulant activity), was derived for each patient. CTS results were compared with traditional coagulation tests. Five UFH COVID-19 samples with low CTS scores (<10) were spiked with uniform dosing of UFH, low molecular weight heparin (LMWH), apixaban, or argatroban and retested to assess anticoagulation response. Results: The CTS detected subtherapeutic UFH anticoagulation levels more frequently in COVID-19 cases compared with controls (76% vs. 17%). Prothrombin Times, activated Partial Thromboplastin Times, anti-Xa levels, and antithrombin activity did not correlate with each other or with the CTS in the COVID-19 samples. CTS correlated with both FV and Factor X activity (R =0.49, Spearman R=-0.68), which form the prothrombinase complex. The CTS was 94% sensitive and 67% specific for the occurrence of TEs in patients on UFH. CTS demonstrated a consistent anticoagulant response only to argatroban (100%) compared with other anticoagulants (60%). Conclusions: The CTS, generated using a novel, low-volume, rapid POC coagulation test is a strong indicator of the therapeutic effect of UFH anticoagulation in COVID-19 patients and may provide a predictive measure of TEs potentially occurring from anticoagulation resistance.
ABSTRACT
Background: As secondary bacterial infections have been associated with increased mortality in respiratory virus pandemics, we sought to determine if prior pneumococcal vaccination improves clinical outcomes in COVID-19 patients. Methods: We analyzed an observational registry of patients tested for COVID-19 at the Cleveland Clinic because of symptoms or other qualifying criteria from 3/8/2020-5/8/2020. Overlap propensity-score weighted logistic/linear regressions investigated associations between pneumococcal vaccination status and COVID-19- related clinical outcomes. Results: 18,197 patients (median age 50.2 yrs [IQR 30.4], 40% male, 67% white) were included. 2785 (15.3%) tested SARS-CoV-2-positive and 738(26.5%) were hospitalized. Prior pneumococcal vaccination in SARS-CoV-2 positive patients did not reduce ICU admission, oxygen usage, radiographic infiltrates, or need for mechanical ventilation. Pneumococcal vaccine recipients were less likely to test positive for SARSCoV- 2 (OR 0.77, 95% CI [0.68,0.87]). Pneumococcal vaccine recipients aged 15-65 years testing positive for SARS-CoV-2 had increased risk of hospitalization (OR 1.54 [1.001, 2.38] and death (OR 12.51 [1.92,81.36]) compared to non-recipients, and those >65 years were more likely to develop pneumonia (OR 8.45, 95% CI [1.77,40.42]). Conclusions: Pneumococcal vaccination status serves as a marker of underlying co-morbidities with greater risk of hospitalization and death from COVID-19 for those age 15-65 and of pneumonia for those >65, with no impact on other important adverse outcomes. The reduced prevalence of SARS-CoV-2 among pneumococcal vaccine recipients could reflect off-target vaccine effects or patterns of health behavior that persist despite propensity score adjustments. Our study supports evaluation of vaccination status, and vaccination of those at risk.