Final Results of CHRONOS19 Observational Study in Patients with Hematologic Disease and COVID-19 in Russia
Authors: Gavrilina Olga A. , Zakurdaeva Kristina A. , Vasileva Anastasia N. , Dubov Sergei , Dubov Vitaly S. , Vorobyev Vladimir I. , Butaev Lev S. , Gavrilova Lubov , Toropova Inessa Yu. , Popova Marina O. , Siniaev Aleksander A. , Kaplanov Kamil , Petrenko Andrei , Ochirova Oksana , Chelysheva Ekaterina Yu. , Sveshnikova Yulia , Shuvaev Vasily , Grishunina Maria E. , Chabaeva Julia A. , Karpova Alina , Sukhareva Alena , Baryshnikova Dasha , Gaponova Tatiana V. , Troitskaya Vera V. , Savchenko Valery G. 
Published: November 2021

Abstract
Background: Research on the impact of COVID-19 on different patient populations has been of great value for the optimization of patient care since the start of the SARS-CoV-2 pandemic. Earlier, we reported the interim analysis of the immediate outcomes in patients (pts) with hematologic (hem) disease and COVID-19. Long-term results of the CHRONOS19 registry are now available.
Methods: CHRONOS19 is an observational prospective cohort study among adult pts ((≥18 years) with hem diseases (malignant or non-malignant) and laboratory-confirmed or suspected (based on clinical symptoms and/or CT) COVID-19 in Russia. Data from 15 centers all over the country were collected on a web-based platform in a de-identified manner at 30, 90, and 180 days after COVID-19 was diagnosed. The primary endpoint was 30-day all-cause mortality. Secondary outcomes included COVID-19 complications, rate of ICU admission and mechanical ventilation, outcomes of hem disease in SARS-CoV-2 infected pts, overall survival, and risk factors for disease severity and mortality.
Results: As of July 30, 2021, 666 pts were enrolled (females / males [n (%)]: 317 (48%) / 349 (52%); median [range] age: 56 [18-90] years. Disease types (malignant/non-malignant [n (%)]): 618 (93%) / 48 (7%), including AML 115 (17%), MM 113 (17%), NHL 106 (16%), CML / CMPD 92 (14%), ALL 52 (8%), CLL 50 (8%), MDS 25 (4%), HCL 23 (3%), HL 21 (3%), AA 16 (2%), APL 11 (2%), others 42 (6%); among them induction phase / remission / relapse or refractory / NA in 237 (35%) / 231 (35%) / 152 (23%) / 46 (7%) pts. Concomitant conditions were reported in 385 (58%) pts: cardiovascular 254 (66%), diabetes 76 (20%), obesity 57 (15%), pulmonary 41 (11%), chronic renal 44 (11%) or hepatic 33 (9%) disease, other 90 (23%).
At a median follow-up of 7,5(1-19) months, 618 pts were evaluable for the primary outcome. Thirty-day all-cause mortality was 16% (100 pts died). Death due to COVID-19 complications occurred in 82 pts, 14 pts died due to progression of hem disease. Overall, 217 (33%) pts had severe disease, COVID-19 complications were detected in 458 (70%) pts, the most common were pneumonia in 425 (93%) pts, respiratory failure in 252 (55%) pts, multiple organ failure in 56 (12%) pts, cytokine storm in 52 (11%) pts, ARDS in 47 (10%) pts, and sepsis in 44 (10%) pts. The rate of ICU admission was 23% (145 pts) with high mortality in this group of pts (77%), 111 (17%) pts required mechanical ventilation, among them only 5 (4.5%) pts survived.
Treatment of hem disease was changed, interrupted, or discontinued in 395 (60%) pts with a median delay of 4 weeks. At 30 days, the rate of relapse / progression of hem disease was 5% / 8% (24 / 40 of 517 evaluable pts). At the longer follow-up (90 and 180 days), relapse / progression occurred in another 9 / 23 pts. At the data cutoff, the median overall survival was not reached. Antibody detection was performed in 253 pts: 211 (84%) pts had IgG to SARS-CoV-2.
In a univariate analysis, older age (&gt; 60 years), myelotoxic agranulocytosis, transfusion dependence, diabetes among comorbidities, ARDS and other complications, except CRS, ICU and mechanical ventilation (Fig. 1) were associated with higher risks of mortality (p&lt;0.05). The final results of the CHRONOS19 study will be presented.
Conclusions: Patients with hem disease and COVID-19 have higher mortality than a general population with SARS-CoV-2 infection, predominantly due to COVID-19 complications. The longer-term follow-up did not reveal any concerns in terms of hem disease outcomes.
Figure 1 Figure 1.

Disclosures
Vorobyev: Janssen, Roche, Sanofi, Takeda, Biocad, Abbvie: Other: Advisory Boards, Speakers Bureau; Astellas, Novartis, AstraZeneca: Speakers Bureau. Chelysheva: Pharmstandart: Speakers Bureau; Pfizer: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; Novartis Pharma: Speakers Bureau.