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1.
Leukemia ; 35(12): 3444-3454, 2021 12.
Article in English | MEDLINE | ID: covidwho-1493064

ABSTRACT

Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41-0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02-1.04; HR = 1.79, 95% CI:1.04-3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated.

2.
Roeker, Lindsey E.; Scarfo, Lydia, Chatzikonstantinou, Thomas, Abrisqueta, Pau, Eyre, Toby A.; Cordoba, Raul, Muntañola Prat, Ana, Villacampa, Guillermo, Leslie, Lori A.; Koropsak, Michael, Quaresmini, Giulia, Allan, John N.; Furman, Richard R.; Bhavsar, Erica B.; Pagel, John M.; Hernandez-Rivas, Jose Angel, Patel, Krish, Motta, Marina, Bailey, Neil, Miras, Fatima, Lamanna, Nicole, Alonso, Rosalia, Osorio-Prendes, Santiago, Vitale, Candida, Kamdar, Manali, Baltasar, Patricia, Österborg, Anders, Hanson, Lotta, Baile, Mónica, Rodríguez-Hernández, Ines, Valenciano, Susana, Popov, Viola Maria, Barez Garcia, Abelardo, Alfayate, Ana, Oliveira, Ana C.; Eichhorst, Barbara, Quaglia, Francesca M.; Reda, Gianluigi, Lopez Jimenez, Javier, Varettoni, Marzia, Marchetti, Monia, Romero, Pilar, Riaza Grau, Rosalía, Munir, Talha, Zabalza, Amaya, Janssens, Ann, Niemann, Carsten U.; Perini, Guilherme Fleury, Delgado, Julio, Yanez San Segundo, Lucrecia, Gómez Roncero, Ma Isabel, Wilson, Matthew, Patten, Piers, Marasca, Roberto, Iyengar, Sunil, Seddon, Amanda, Torres, Ana, Ferrari, Angela, Cuéllar-García, Carolina, Wojenski, Daniel, El-Sharkawi, Dima, Itchaki, Gilad, Parry, Helen, Mateos-Mazón, Juan José, Martinez-Calle, Nicolas, Ma, Shuo, Naya, Daniel, Van Der Spek, Ellen, Seymour, Erlene K.; Gimeno Vázquez, Eva, Rigolin, Gian Matteo, Mauro, Francesca Romana, Walter, Harriet S.; Labrador, Jorge, De Paoli, Lorenzo, Laurenti, Luca, Ruiz, Elena, Levin, Mark-David, Šimkovič, Martin, Špaček, Martin, Andreu, Rafa, Walewska, Renata, Perez-Gonzalez, Sonia, Sundaram, Suchitra, Wiestner, Adrian, Cuesta, Amalia, Broom, Angus, Kater, Arnon P.; Muiña, Begoña, Velasquez, César A.; Ujjani, Chaitra S.; Seri, Cristina, Antic, Darko, Bron, Dominique, Vandenberghe, Elisabeth, Chong, Elise A.; Lista, Enrico, García, Fiz Campoy, Del Poeta, Giovanni, Ahn, Inhye, Pu, Jeffrey J.; Brown, Jennifer R.; Soler Campos, Juan Alfonso, Malerba, Lara, Trentin, Livio, Orsucci, Lorella, Farina, Lucia, Villalon, Lucia, Vidal, Maria Jesus, Sanchez, Maria Jose, Terol, Maria Jose, De Paolis, Maria Rosaria, Gentile, Massimo, Davids, Matthew S.; Shadman, Mazyar, Yassin, Mohamed A.; Foglietta, Myriam, Jaksic, Ozren, Sportoletti, Paolo, Barr, Paul M.; Ramos, Rafael, Santiago, Raquel, Ruchlemer, Rosa, Kersting, Sabina, Huntington, Scott F.; Herold, Tobias, Herishanu, Yair, Thompson, Meghan C.; Lebowitz, Sonia, Ryan, Christine, Jacobs, Ryan W.; Portell, Craig A.; Isaac, Krista, Rambaldi, Alessandro, Nabhan, Chadi, Brander, Danielle M.; Montserrat, Emili, Rossi, Giuseppe, Garcia-Marco, Jose A.; Coscia, Marta, Malakhov, Nikita, Fernandez-Escalada, Noemi, Skånland, Sigrid Strand, Coombs, Callie C.; Ghione, Paola, Schuster, Stephen J.; Foà, Robin, Cuneo, Antonio, Bosch, Francesc, Stamatopoulos, Kostas, Ghia, Paolo, Mato, Anthony R.; Patel, Meera.
Blood ; 136(Supplement 1):45-49, 2020.
Article in English | PMC | ID: covidwho-1338959

ABSTRACT

Introduction: Patients (pts) with CLL may be at particular risk of severe COVID-19 given advanced age and immune dysregulation. Two large series with limited follow-up have reported outcomes for pts with CLL and COVID-19 (Scarfò, et al. Leukemia 2020;Mato, et al. Blood 2020). To provide maximal clarity on outcomes for pts with CLL and COVID-19, we partnered in a worldwide effort to describe the clinical experience and validate predictors of survival, including potential treatment effects.Methods: This international collaboration represents a partnership between investigators at 141 centers. Data are presented in two cohorts. Cohort 1 (Co1) includes pts captured through efforts by European Research Initiative on CLL (ERIC), Italian CAMPUS CLL Program, and Grupo Español de Leucemia Linfática Crónica. The validation cohort, Cohort 2 (Co2), includes pts from US (66%), UK (23%), EU (7%), and other countries (4%). There is no overlap in cases between cohorts.CLL pts were included if COVID-19 was diagnosed by PCR detection of SARS-CoV-2 and they required inpatient hospitalization. Data were collected retrospectively 2/2020 - 5/2020 using standardized case report forms. Baseline characteristics, preexisting comorbidities (including cumulative illness rating scale (CIRS) score ≥6 vs. <6), CLL treatment history, details regarding COVID-19 course, management, and therapy, and vital status were collected.The primary endpoint of this study was to estimate the case fatality rate (CFR), defined as the proportion of pts who died among all pts hospitalized with COVID-19. Chi-squared test was used to compare frequencies;univariable and multivariable analyses utilized Cox regression. Predictors of inferior OS in both Co1 and Co2 were included in multivariable analyses. Kaplan-Meier method was used to estimate overall survival (OS) from time of COVID-19 diagnosis (dx).Results: 411 hospitalized, COVID-19 positive CLL pts were analyzed (Co1 n=281, Co2 n=130). Table 1 describes baseline characteristics. At COVID-19 dx, median age was 72 in Co1 (range 37-94) and 68 in Co2 (range 41-98);31% (Co1) and 45% (Co2) had CIRS ≥6. In Co1, 48% were treatment-naïve and 26% were receiving CLL-directed therapy at COVID-19 dx (66% BTKi ± anti-CD20, 19% Venetoclax ± anti-CD20, 9.6% chemo/chemoimmunotherapy (CIT), 1.4% PI3Ki, 4% other). In Co2, 36% were never treated and 49% were receiving CLL-directed therapy (65% BTKi ± anti-CD20, 19% Venetoclax ± anti-CD20, 9.4% multi-novel agent combinations, 1.6% CIT, 1.6% PI3Ki, 1.6% anti-CD20 monotherapy, 1.6% other). Most pts receiving CLL-directed therapy had it held at COVID-19 diagnosis (93% in Co1 and 81% in Co2).Frequency of most COVID-19 symptoms/laboratory abnormalities were similar in the two cohorts including fever (88% in both), lymphocytosis (ALC ≥30 x 109/L;27% vs. 21%), and lymphocytopenia (ALC <1.0 x 109/L;18% vs. 28%), while others varied between Co1 and Co2 (p<0.0001), including cough (61% vs. 93%), dyspnea (60% vs. 84%), fatigue (13% vs. 77%).Median follow-up was 24 days (range 2-86) in Co1 and 17 days (1-43) in Co2. CFRs were similar in Co1 and Co2, 30% and 34% (p=0.45). 54% and 43% were discharged while 16% and 23% remained admitted at last follow-up in Co1 and Co2, respectively. The proportion of pts requiring supplemental oxygen was similar (89% vs. 92%) while rate of ICU admission was higher in Co2 (20% vs. 48%, p<0.0001). Figure 1 depicts OS in each cohort. Univariable analyses demonstrated that age and CIRS ≥6 significantly predicted inferior OS in both cohorts, while only age remained an independent predictor of inferior OS in multivariable analyses (Table 2). Prior treatment for CLL (vs. observation) predicted inferior OS in Co1 but not Co2.Conclusions : In the largest cancer dx-specific cohort reported, pts with CLL hospitalized for COVID-19 had a CFR of 30-34%. Advanced patient age at COVID-19 diagnosis was an independent predictor of OS in two large cohorts. This CFR will serve as a benchmark for mortality for future outcomes studies, including thera eutic interventions for COVID-19 in this population. The effect of CLL treatment on OS was inconsistent across cohorts;COVID-19 may be severe regardless of treatment status. While there were no significant differences in distribution of current lines of therapy between cohorts, prior chemo exposure was more common in Co1 vs. Co2, which may account for difference in OS. Extended follow-up will be presented.

3.
Dtsch Med Wochenschr ; 146(13-14): 924-926, 2021 Jul.
Article in German | MEDLINE | ID: covidwho-1324450

ABSTRACT

COVID-19 continues to pose major challenges for GP practice and emergency rooms across Germany. Even if there is now a certain routine, the optimal treatment of patients is still difficult. This article provides an overview of the aspects of caring for COVID-19 patients in GP practice and emergency rooms and the changes since the beginning of the pandemic.


Subject(s)
COVID-19/therapy , Emergency Service, Hospital/statistics & numerical data , General Practice/methods , COVID-19/complications , COVID-19/epidemiology , Emergency Service, Hospital/trends , General Practice/standards , General Practice/trends , Germany/epidemiology , Humans , Risk Factors
4.
Eur Respir J ; 58(1)2021 Jul.
Article in English | MEDLINE | ID: covidwho-1105685

ABSTRACT

A fraction of COVID-19 patients progress to a severe disease manifestation with respiratory failure and the necessity of mechanical ventilation. Identifying patients at risk is critical for optimised care and early therapeutic interventions. We investigated the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding relative to disease severity.We analysed nasopharyngeal and tracheal shedding of SARS-CoV-2 in 92 patients with diagnosed COVID-19. Upon admission, standardised nasopharyngeal swab or sputum samples were collected. If patients were mechanically ventilated, endotracheal aspirate samples were additionally obtained. Viral shedding was quantified by real-time PCR detection of SARS-CoV-2 RNA.45% (41 out of 92) of COVID-19 patients had a severe disease course with the need for mechanical ventilation (severe group). At week 1, the initial viral shedding determined from nasopharyngeal swabs showed no significant difference between nonsevere and severe cases. At week 2, a difference could be observed as the viral shedding remained elevated in severely ill patients. A time-course of C-reactive protein, interleukin-6 and procalcitonin revealed an even more protracted inflammatory response following the delayed drop of virus shedding load in severely ill patients. A significant proportion (47.8%) of patients showed evidence of prolonged viral shedding (>17 days), which was associated with severe disease courses (73.2%).We report that viral shedding does not differ significantly between severe and nonsevere COVID-19 cases upon admission to the hospital. Elevated SARS-CoV-2 shedding in the second week of hospitalisation, a systemic inflammatory reaction peaking between the second and third week, and prolonged viral shedding are associated with a more severe disease course.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , RNA, Viral , Respiratory System , Severity of Illness Index , Virus Shedding
5.
Dtsch Med Wochenschr ; 145(15): 1080-1085, 2020 Jul.
Article in German | MEDLINE | ID: covidwho-705552

ABSTRACT

COVID-19 challenges GP practice and emergency rooms across Germany. In addition to hygiene, the correct assignment of patients to outpatient, inpatient or intensive care management is difficult. This article provides an overview of aspects of initial care, management and risk assessment in COVID-19 patients. The care of corona infected patients can be improved at the interface between outpatient and inpatient care. There can be no "business as usual" after the crisis! Age, male sex and overweight are among the most important risk factors for serious corona disease. Poor oxygen saturation (< 88 %) and increased signs of inflammation (CRP > 97 mg/l and/or IL-6 > 80 pg/ml) indicate a critical course and should be determined in symptomatic patients. Only through regular dialogue between hospital and practice can meaningful decisions be made to slowly move from individual cases to a basic care structure.


Subject(s)
Coronavirus Infections , Emergency Service, Hospital , General Practice , Pandemics , Pneumonia, Viral , Betacoronavirus , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Coronavirus Infections/transmission , Female , Germany , Humans , Male , Oxygen/blood , Pandemics/prevention & control , Pneumonia, Viral/diagnosis , Pneumonia, Viral/prevention & control , Pneumonia, Viral/therapy , Pneumonia, Viral/transmission , Risk Assessment , Risk Factors , SARS-CoV-2
6.
Leukemia ; 34(9): 2354-2363, 2020 09.
Article in English | MEDLINE | ID: covidwho-638239

ABSTRACT

Chronic lymphocytic leukemia (CLL) is a disease of the elderly, characterized by immunodeficiency. Hence, patients with CLL might be considered more susceptible to severe complications from COVID-19. We undertook this retrospective international multicenter study to characterize the course of COVID-19 in patients with CLL and identify potential predictors of outcome. Of 190 patients with CLL and confirmed COVID-19 diagnosed between 28/03/2020 and 22/05/2020, 151 (79%) presented with severe COVID-19 (need of oxygen and/or intensive care admission). Severe COVID-19 was associated with more advanced age (≥65 years) (odds ratio 3.72 [95% CI 1.79-7.71]). Only 60 patients (39.7%) with severe COVID-19 were receiving or had recent (≤12 months) treatment for CLL at the time of COVID-19 versus 30/39 (76.9%) patients with mild disease. Hospitalization rate for severe COVID-19 was lower (p < 0.05) for patients on ibrutinib versus those on other regimens or off treatment. Of 151 patients with severe disease, 55 (36.4%) succumbed versus only 1/38 (2.6%) with mild disease; age and comorbidities did not impact on mortality. In CLL, (1) COVID-19 severity increases with age; (2) antileukemic treatment (particularly BTK inhibitors) appears to exert a protective effect; (3) age and comorbidities did not impact on mortality, alluding to a relevant role of CLL and immunodeficiency.


Subject(s)
Betacoronavirus , Coronavirus Infections/pathology , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Pneumonia, Viral/pathology , Adenine/analogs & derivatives , Age Factors , Aged , Aged, 80 and over , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , COVID-19 , Comorbidity , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Female , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Male , Middle Aged , Pandemics , Piperidines , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Prognosis , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , Pyrimidines/pharmacology , Pyrimidines/therapeutic use , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Surveys and Questionnaires
7.
J Allergy Clin Immunol ; 146(1): 128-136.e4, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-526034

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) can manifest as a viral-induced hyperinflammation with multiorgan involvement. Such patients often experience rapid deterioration and need for mechanical ventilation. Currently, no prospectively validated biomarker of impending respiratory failure is available. OBJECTIVE: We aimed to identify and prospectively validate biomarkers that allow the identification of patients in need of impending mechanical ventilation. METHODS: Patients with COVID-19 who were hospitalized from February 29 to April 9, 2020, were analyzed for baseline clinical and laboratory findings at admission and during the disease. Data from 89 evaluable patients were available for the purpose of analysis comprising an initial evaluation cohort (n = 40) followed by a temporally separated validation cohort (n = 49). RESULTS: We identified markers of inflammation, lactate dehydrogenase, and creatinine as the variables most predictive of respiratory failure in the evaluation cohort. Maximal IL-6 level before intubation showed the strongest association with the need for mechanical ventilation, followed by maximal CRP level. The respective AUC values for IL-6 and CRP levels in the evaluation cohort were 0.97 and 0.86, and they were similar in the validation cohort (0.90 and 0.83, respectively). The calculated optimal cutoff values during the course of disease from the evaluation cohort (IL-6 level > 80 pg/mL and CRP level > 97 mg/L) both correctly classified 80% of patients in the validation cohort regarding their risk of respiratory failure. CONCLUSION: The maximal level of IL-6, followed by CRP level, was highly predictive of the need for mechanical ventilation. This suggests the possibility of using IL-6 or CRP level to guide escalation of treatment in patients with COVID-19-related hyperinflammatory syndrome.


Subject(s)
Biomarkers/blood , C-Reactive Protein/metabolism , Coronavirus Infections/blood , Interleukin-6/blood , Pneumonia, Viral/blood , Respiration, Artificial , Adolescent , Adult , Aged , Betacoronavirus , C-Reactive Protein/analysis , COVID-19 , Coronavirus Infections/therapy , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/therapy , Respiratory Insufficiency/blood , Respiratory Insufficiency/therapy , Respiratory Insufficiency/virology , SARS-CoV-2 , Young Adult
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