Discussion
bleeding, pneumonia, inflammation, ARDS, lymphopenia, empyema
BLEEDING, PNEUMONIA, SARS-COV-2 INFECTION, INFLAMMATORY RESPONSE, ADVERSE EVENTS, INFLAMMATION, CYTOKINE RELEASE SYNDROME, INFECTIONS, DISORDERS, LYMPHOPENIA, SECONDARY, SYNDROME, EMPYEMA, ARDS, PULMONARY FAILURE
In our study, plasmapheresis (PLEX) showed to improve survival from patients with severe COVID-19, as compared with control group. Consistently, several case-series have reported a reduction of 28-days mortality associated with PLEX, which ranges between 10% and 28% in patients with SARS-Cov2, ARDS and cytokine release syndromeIndeed, one study achieved zero mortality in patients with severe COVID that received 5 sessions of PLEX (0% vs 35%, PLEX vs not PLEX), without adverse events reportedIt is possible that the effect of PLEX be mediated by the clearance of pro-inflammatory mediators and toxic biological substances with molecular weights bigger than 15,000 daltons, representing a therapeutic option in patients with hyperinflammatory state secondary to SARS-CoV-2 infection. In our study PLEX was effective to clear pro-inflammatory mediators and to reduce mortality; however, it did not prevent mechanical ventilation, suggesting that additional disorders may underlie pulmonary failure.A point to highlight is the selectivity of patients with potential benefit from PLEX therapy, which include particular features like severe course of COVID and evidence of cytokine storm syndrome. Similarly, several trials using such indications for PLEX were registered during the present pandemicInterestingly, there is not a current accepted definition for cytokine release syndrome, and whether this syndrome represents an appropriate inflammatory response is still controversialIn the present study, cytokine release syndrome was considered as IL-6 cutoff value higher than 40 pg/mL, accompanied by elevation of other markers of inflammation and lymphopenia. Previously, Guiaro et al, found that an IL-6 cut-off value higher than 35 pg/mL was associated with increased mortality and higher risk for ICU admissionAlong clearance of pro-inflammatory mediators, PLEX showed to improve lymphopenia in our study, potentially representing a prognosis modification, since severe lymphopenia (< 500/mmRegarding adverse events, potential mechanisms related to PLEX has been described to clearance of procoagulant factors, immunoglobulins and cytokines, leading to risk of bleeding and/or immunosuppression. In our study only 4 patients developed hospital-acquired infections like pneumonia and one subject developed empyema. Finally, the length of hospital stay was significantly longer in the group with PLEX. Comparatively, PLEX therapy during Faqihi’s trial significantly reduced length of ICU stay. This difference may be explained because institutional CT scan programming was performed at day 10 after the first session of PLEX, independently from severity scoresLimitations of the present study include a single-center design with a limited sample size that may have caused a statistical overestimation of effect size. In addition, control-case match was uncomplete, which may be explained by the reduced number of candidates for PLEX, who also had incomplete information for adequate analysis. Likewise, the heterogeneity of pharmacologic therapy, which was inherent to the available scientific evidence during the course of pandemia. For example, PLEX and control group received the same non-specific therapy, which included immunoglobulin; but we cannot rule out potential effect of PLEX on immunoglobulin clearance.