ABSTRACT
Background. Tocilizumab (TCZ) was approved by the Food and Drug Administration under emergency use authorization for treatment of COVID-19 in patients requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation. Despite multiple clinical trials, there remain unanswered questions surrounding TCZ use. Methods. This multi-hospital retrospective cohort study included patients who received TCZ for COVID-19 between January 29th, 2021 and June 30th, 2021 at five University of Pennsylvania Health System (UPHS) hospitals. Patients were eligible for TCZ per UPHS criteria if they scored >= 5 on the World Health Organization (WHO) ordinal scale for <= 24 hours and experienced < 14 days of acute COVID-19 symptoms. Descriptive statistics were performed to characterize usage within the health system. Results. This study evaluated 134 patients who received TCZ for the treatment of COVID-19. TCZ was ordered a median of 22 hours (interquartile range [IQR], 13.2 - 41.5) after hospital admission. A majority of patients (76.1%) were admitted to the intensive care unit and a small portion (12.7%) had a WHO ordinal scale that was >5 at time of TCZ order entry. All patients received concomitant dexamethasone therapy at a total prednisone equivalent of 400 mg (IQR, 335.6 - 480). Overall 33.6% of patients experienced an adverse event (ADE) within 30 days of TCZ administration (Table 1). Most common ADEs included bacterial infection (29.9%), hepatitis (6.7%), and fungal infection (3%);other etiologies of ADEs were not accounted for. All-cause mortality (Table 2) at day 30 occurred in 20.9% of patients and median time from TCZ administration to mortality was 12.5 days (IQR 5 - 18.3). Ninety-six patients in the cohort (71.6%) were discharged by day 30. Of the subgroup discharged by day 30, the majority (70.8%) were discharged to home. Conclusion. Patients who received TCZ for severe COVID-19 experienced 20.9% mortality;mortality was higher among those with higher ordinal scale at the time of TCZ dosing. A large portion of patients (70.8%) were discharged to home within 30 days. One third of patients experienced an adverse event, primarily bacterial or fungal infection. Our experience may be useful in counseling patients about anticipated effects of TCZ.
ABSTRACT
Introduction: B cell depleting therapies have been successfully utilized over the past decade to treat neuroimmune diseases. However, during the COVID-19 pandemic, these therapies pose a clinical concern, as patients may not be able to mount a sufficient antibody-mediated immune response to SARS-CoV-2 infection and vaccinations. Objective(s): Studies to-date have reported conflicting results on the degree of antibody production post-SARS-CoV-2 infection and vaccinations and have focused primarily on short-term follow up immune profiling. Our objective was to perform a longitudinal follow up of immune responses post-SARS-CoV-2 infection and vaccination in a cohort of COVID-19 B cell depleted autoimmune patients (n=5), COVID-19 non-B cell depleted autoimmune patients (n=15), COVID-19 immunocompetent patients (n=117), and healthy controls (n=6) for a total of 259 samples in 137 participants. Aim(s): B cell depleted patients and controls were followed prospectively for 12 months and were evaluated at multiple time points for spike antibody titers, B and T cell composition, and frequency of T cells specific for SARS-CoV-2 spike, nucleocapsid, membrane, and envelope antigens. Result(s): Four out of five B cell-depleted patients developed detectable anti-spike SARS-CoV-2 antibodies, which were boosted by vaccinations in two out of four patients. While SARSCoV- 2 spike antibodies were associated with presence of CD20+B cells, very few B cells were required. In contrast, patients who primarily had CD19+CD20-B cells during acute COVID-19 disease or vaccination did not seroconvert. Interestingly, circulating B cells in B cell depleted patients were significantly CD38highwith co-expression of CD24 and CD27, indicating that B cell depletion may directly impact B cell-signatures and activation patterns. Additionally, all patients post COVID-19 mounted a sustained T-cell response to SARS-CoV-2 antigens, regardless of B cell depletion status and seroconversion. Specifically, all patients had responding naive, central memory, effector memory, and effector memory RA+ T-cells, suggesting intact T-cell memory conversion in B cell depleted patients compared to COVID-19 controls. Conclusion(s): We present the longest COVID-19 immune profiling analysis to date in B cell depleted patients, demonstrating that both humoral and cellular immune responses can be generated and sustained in this patient population for up to 12 months in response to SARS-CoV-2 infection and vaccination.