ABSTRACT
Background. Anti-SARS-CoV-2 monoclonal antibodies afford prompt immunity, have demonstrated reduction in severe COVID-19 in high risk ambulatory patients, and are available through Emergency Use Authorization. Challenges exist, however, to widespread utilization. Methods. This operations study 11/23/20-4/30/21 identified patients meeting monoclonal AB EUA criteria by test results or referral. Outreach to harder-hit neighborhoods included connecting with primary care teams and testing sites. Infusion centers with staff trained in infection control, rapid response and drug preparation were utilized. The primary study outcome was treatment of qualifying patients. Secondary outcomes included infusion complications, hospitalization/ death, and symptom resolution. Investigational review board approval was obtained. Results. 367 patients were treated: mean age of 63, 201(55%) male, 276(75%) white, 54(15%) black. All patients had a first positive direct SARS-CoV-2 test within 10 days, 232(63%) had > 1 high-risk qualification, 32(9%) were vaccinated for SARSCoV-2. Of patients with available zipcodes, 135(38%) had a Community Need Index >3.5 and 157(45%) a Social Vulnerability Index >0.5. 190(52%) received bamlanivimab, 93(25%) casirivimab/imdevimab, 84(23%) bamlanivimab/etesevimab. Four patients experienced infusion reaction, 1 with anaphylaxis. 172(73%) of 236 patients were symptom free at day 5. 20 patients (5%) were hospitalized for COVID-19 within 30 days with a median time from symptom onset to infusion of 7 days, 11(55%) were admitted within 24 hours, 1 died. Conclusion. Our study demonstrates that treatment with anti-SARS-CoV-2 monoclonal antibodies is feasible in a high resource setting. There were no related SARS-CoV-2 exposures and therapy was well tolerated. Trials of anti-SARS-CoV-2 monoclonal antibodies have reported lower rates of hospitalizations in treated patients than we found. This may reflect the expanded time frame for EUA therapy as compared to clinical trials, differences in real world patients or viral variants. Given potential benefit in unvaccinated patients or those at risk for poor vaccine response, the equitable utilization of anti-SARS-CoV-2 monoclonal antibody therapy in early COVID-19 should remain a focus for researchers and clinicians.
ABSTRACT
Background: Tocilizumab (TCZ) is a monoclonal antibody against the interleuikin- 6 receptor which is potentially beneficial in COVID-19 induced cytokine release syndrome (CRS). However, there are limited studies showing anti-inflammatory effect and clinical benefit of TCZ in COVID-19 patients. This retrospective study examines treatment responses of criteria based TCZ therapy for SARS-CoV-2 respiratory infection for ICU vs. non-ICU patients. Methods: We established institutional criteria to identify patients at risk of CRS from COVID-19. Patients were included if they received at least 1 dose of TCZ and were admitted for at least 72 hours. Primary endpoint was to assess clinical improvement (CI) at the end of admission. CI was defined by extubation, downgrade from ICU, discharged or improvement in Clinical Ordinal Scale by 2. Secondary endpoint of the study was to assess inpatient mortality (IM) and risk factors associated with IM. Subgroup analysis included impact of early (< 96 hours) vs late (≥ 96 hours) TCZ therapy on IM. Results: Between March 25 to May 6, 2020, 170 patients met criteria and received TCZ. There were 83 non-ICU patients and 87 in the ICU. Forty five patients needed invasive mechanical ventilation (IMV). ICU patients tended to be obese, receive 2 doses of TCZ and have longer length of stay. Overall CI was seen in 71% of patients. CI was higher in non-ICU vs ICU patients (85.5% vs 57.5%, P=0.002). Overall IM was 18.8%;however, IM was lower in non-ICU vs ICU patients (8.4% vs 28.7%, P=0.0014). IM was higher in patients on IMV vs. non-IMV (30% vs 15.4%, P=0.03). Risk factors of ICU admission, BMI ≥ 30 kg/m2 and AKI were associated with higher risk of IM. Many IM patients were made comfort care. No differences were observed in early vs late TCZ therapy on inpatient mortality, but there was a trend toward lower mortality with early TCZ. COS Review of Tocilizumab Patients Conclusion: TCZ is an effective treatment option in patients with SARS-CoV-2 patients at risk of CRS. Patients receiving TCZ in non-ICU setting had a better response to treatment compared to ICU patients. Obesity and AKI were associated with higher risk of mortality, but there was no statistical difference in early vs late therapy. Further studies with control group and larger sample size are warranted.