Outcomes in Patients with Hematologic Disease and COVID-19 in Russia: Interim Analysis of CHRONOS19 Registry
Authors: Gavrilina Olga A. , Zakurdaeva Kristina , Vorobyev Vladimir I. , Vasileva Anastasia N. , Butaev Lev S. , Sukhareva Alena , Gavrilova Lubov , Samoylova Olga , Grishunina Maria , Ochirova Ochsana , Karpova Alina , Panteleeva Olga , Kunst Mikhail A. , Shuvaev Vasily , Rakhmani Anzhelika , Gaponova Tatiana V. , Galstyan Gennadiy M. , Troitskaya Vera V. , Luchkin Anton V. , Parovichnikova Elena N. , Savchenko Valery 
Published: November 2020

Background: Patients (pts) with hematologic disease are at increased risk of severe SARS-CoV-2 infection. Recent observations reported poor outcomes of COVID-19 in pts with various cancer types and higher mortality rates compared with the general population. However, currently available data on COVID-19 in pts with hematologic disease are limited.
Methods: CHRONOS19 registry is an observational prospective cohort study with the primary objective to evaluate the treatment outcomes in adult pts (age 18 or older) with hematologic disease and COVID-19. Secondary objectives are to describe severity and complications of COVID-19 and course of hematologic disease in SARS-CoV-2 infected pts, and to explore importance of various factors for disease severity and mortality. Pts with laboratory-confirmed or suspected (based on clinical symptoms and/or CT) COVID-19 were eligible for enrollment. Data were collected on a web platform and managed in a de-identified manner. Physicians from 8 hematology clinical centers and hospitals from all over Russia (Moscow, Ulan-Ude, Saransk, Vladimir, Nizhniy Novgorod, Kazan) participate in this study. Pts are followed for 30 days (ds) after COVID-19 diagnosis and up to 6 months (mos) for hematologic disease outcomes and overall survival assessment. The results of the first follow-up are presented in this interim analysis.
Results: As of July 30, 2020, 184 pts were enrolled (females/males [n(%)]: 80(44%)/104 (56%); median [range] age: 55 [18-83] years. Disease type (malignant/non-malignant [n(%)]): 164(89%)/20(11%), including AML 36(20%), ALL 16(9%), MDS 5(2%), APL 5(2%), MM 38(21%), HL 4(2%), NHL 38(21%), MPN 9(5%), CLL 13(7%), others 20(11%). Concomitant diseases were in 95(52%) pts: cardiovascular 56(59%), pulmonary 6(6%), hepatic 6(6%) or renal 5(5%), diabetes 17(18%), obesity 4(4%), other 16(17%). 176 patients were evaluable for the primary outcome assessment with a median follow-up of 41(1-125) ds. Thirty-day all-cause mortality was 23% (41 pts died). Death due to COVID-19 complications occurred in 34 (83%) pts, 7(17%) pts died due to progression of hematologic disease. Fifty (28%) pts experienced COVID-19 complications, the most common were pneumonia in 125 (71%) pts, respiratory failure in 82(47%) pts, ARDS in 11(6%) pts, cytokine release syndrome in 15(9%) pts, multiple organ failure in 10(6%) pts, sepsis in 6(3%) pts, and pulmonary bleeding in 1(0,6%). Specific anti-COVID-19 treatment was given to 117 pts(67%) pts: most common first-line treatment was hydroxichloroquine+azithromycin in 84(72%) pts, azithromycin monotherapy in 27(23%) pts, other drugs in 6(5%) pts; second-line treatment comprised lopinavir+ritonavir in 38 pts, tocilizumab in 29 pts, umifenovir in 5 pts, baricitinib in 5 pts, canakinumab in 1pt, sarilumab in 1 pt. The rate of ICU admissions was 27%(47 pts), among them only 11(23%) pts survived, 36(20%) pts required mechanical ventilation, only 2(5.5%) pts survived. Eighty-eight(50%) pts received anticoagulants. With regard to the blood disease, treatment delays occurred in 101(57%) pts with a median 4 weeks, 6(3%) pts required change of treatment. At the first follow-up (30 ds) the rate of relapse / progression of hematologic disease was 16 of 151 evaluable pts (10.6%). Thirty-day overall survival was 75%. At the data cutoff, median overall survival was not reached. Antibody detection was performed in 70 pts: 53(76%) pts had IgG SARS-CoV-2 antibodies. Among factors possibly associated with poor survival were: stage of COVID-19 1(n=41) - 91,8%/ 2(n=75) - 90%/ 3(n=36) - 56,5%/ 4(n=22) - 13,6% (p&lt;0,0001), concomitant diseases (n=93/81): 59,5% vs. 87% (p=0,0001), transfusion dependence (n=65/104): 58,1% vs. 81,8% (p=0,0007), prior steroid therapy (n=73/90): 64,6% vs. 82% (p=0,019), older age (&lt;60 (n=108)/≥60 (n=68) years): 80% vs. 60% (p=0,048). Sex, disease type, myelotoxic agranulocytosis, and prior hematopoietic stem cell transplantation were not associated with worse outcomes. Data on the longer follow-up (90 and 180 ds) will be presented.
Conclusions: Patients with hematologic disease and SARS-CoV-2 infection have high 30-day all-cause mortality predominantly due to COVID-19 complications. Stage of COVID-19, concomitant diseases, transfusion dependence, prior steroid therapy, and older age were associated with poor outcomes.

Disclosures
Shuvaev: Novartis: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau.

OffLabel Disclosure:
hydroxichloroquine, azithromycin, lopinavir+ritonavir, tocilizumab, umifenovir, baricitinib, canakinumab, sarilumab for COVID-19 treatment