Therapeutic plasma exchange decreases plasma anti-SARS-CoV-2 spike IgG without increasing the proximate incidence of COVID-19.

BACKGROUND: Therapeutic plasma exchange (TPE) removes both pathologic and protective immunoglobulins (Ig). SARS-CoV-2 immunity is partially mediated by anti-SARS-CoV-2 spike antibodies (SAb), which impair viral host-cell invasion. Nonetheless, the systematic effect of TPE on SAb concentration and SARS-CoV-2 immunity is unknown. METHODS: Paired plasma waste specimens from the first (first-TPE) and last (last-TPE) TPE treatment were collected from 9 patients between July 21, 2021 and March 1, 2022. The effects of TPE on Ig levels were assessed by quantitatively comparing the SAb, total IgG, and total IgM levels first-/last-TPE treatment. Complementary qualitative assessment for these changes was achieved via protein electrophoresis (PEP) and immunofixation (IFE). A retrospective review was performed to investigate the incidence of new SARS-CoV-2 infections following TPE v. other treatment at the same outpatient apheresis/infusion center during the same time frame. RESULTS: Median SAb levels between the first- and last-TPE waste specimens decreased significantly from 424.6 AU/mL to 17.0 AU/mL (P = 0.004). Concordantly, PEP and IFE analysis demonstrated broad Ig decreases. Cumulative incidence of subsequent COVID-19 diagnosis at 30, 90, and 180 days post-procedure did not differ between the TPE v. other treatment groups (n = 709 total patients). CONCLUSIONS: TPE significantly reduced SAb levels, a marker of SARS-CoV-2 immunity, but did not appear to provoke increased incidence of COVID-19 infections. Further investigation of the kinetics of TPE-mediated SAb decrease and post-TPE recovery are warranted.

Marked factor V activity elevation in severe COVID-19 is associated with venous thromboembolism.

Coagulopathy causes morbidity and mortality in patients with coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Yet, the mechanisms are unclear and biomarkers are limited. Early in the pandemic, we observed markedly elevated factor V activity in a patient with COVID-19, which led us to measure factor V, VIII, and X activity in a cohort of 102 consecutive inpatients with COVID-19. Contemporaneous SARS-CoV-2-negative controls (n = 17) and historical pre-pandemic controls (n = 260-478) were also analyzed. This cohort represents severe COVID-19 with high rates of ventilator use (92%), line clots (47%), deep vein thrombosis or pulmonary embolism (DVT/PE) (23%), and mortality (22%). Factor V activity was significantly elevated in COVID-19 (median 150 IU/dL, range 34-248 IU/dL) compared to contemporaneous controls (median 105 IU/dL, range 22-161 IU/dL) (P < .001)-the strongest association with COVID-19 of any parameter studied, including factor VIII, fibrinogen, and D-dimer. Patients with COVID-19 and factor V activity >150 IU/dL exhibited significantly higher rates of DVT/PE (16/49, 33%) compared to those with factor V activity ≤150 IU/dL (7/53, 13%) (P = .03). Within this severe COVID-19 cohort, factor V activity associated with SARS-CoV-2 load in a sex-dependent manner. Subsequent decreases in factor V were linked to progression toward DIC and mortality. Together, these data reveal marked perturbations of factor V activity in severe COVID-19, provide links to SARS-CoV-2 disease biology and clinical outcomes, and nominate a candidate biomarker to investigate for guiding anticoagulation therapy in COVID-19.