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.

Analytic Sensitivity of 3 Nucleic Acid Detection Assays in Diagnosis of SARS-CoV-2 Infection.

BACKGROUND: Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcription PCR is the primary method to diagnose coronavirus disease 2019 (COVID-19). However, the analytic sensitivity required is not well defined and it is unclear how available assays compare. METHODS: For the Abbott RealTime SARS-CoV-2 assay (m2000; Abbott Molecular), we determined that it could detect viral concentrations as low as 26 copies/mL, we defined the relationship between cycle number and viral concentrations, and we tested naso- and oropharyngeal swab specimens from 8538 consecutive individuals. Using the m2000 as a reference assay method, we described the distribution of viral concentrations in these patients. We then used selected clinical specimens to determine the positive percent agreement of 2 other assays with more rapid turnaround times [Cepheid Xpert Xpress (GeneXpert; Cepheid); n = 27] and a laboratory developed test on the Luminex ARIES system [ARIES LDT (Luminex); n = 50] as a function of virus concentrations, from which we projected their false-negative rates in our patient population. RESULTS: SARS-CoV-2 was detected in 27% (95% CI: 26%-28%) of all specimens. Estimated viral concentrations were widely distributed, and 17% (95% CI: 16%-19%) of positive individuals had viral concentrations <845 copies/mL. Positive percent agreement was strongly related to viral concentration, and reliable detection (i.e., ≥95%) was observed at concentrations >100 copies/mL for the GeneXpert but not the ARIES LDT, corresponding to projected false-negative rates of 4% (95% CI: 0%-21%) and 27% (95% CI: 11%-46%), respectively. CONCLUSIONS: Substantial proportions of clinical specimens have low to moderate viral concentrations and may be missed by methods with less analytic sensitivity.