Clinical presentation and outcomes of COVID‐19 following hematopoietic cell transplantation and cellular therapy

Abstract

Background: One year into the pandemic, published data on hematopoietic cell transplantation (HCT) recipients with coronavirus disease 2019 (COVID-19) remain limited. Methods: Single-center retrospective cohort study of adult HCT recipients with polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Results: Twenty-eight consecutive transplantation and cellular therapy patients (autologous, n = 12; allogeneic, n = 15; chimeric antigen receptor T-cell therapy [CAR-T], n = 1) with COVID-19 were identified. The median age was 57 years. The median time from HCT to COVID-19 diagnosis was 656 days (interquartile range [IQR], 33-1274). Patients were followed for a median of 59 days (IQR, 40-88).Among assessable patients (n = 19), 10 (53%) had documented virological clearance; median time to clearance was 34 days (range, 21-56). Out of 28, 12 (43%), 6 (21%), and 10 (36%) patients had mild, moderate, and severe/critical disease, respectively.Overall mortality was 25%, nearly identical for autologous and allogeneic HCT, and exclusively seen in hospitalized patients, older than 50 years of age with severe COVID-19. None of the patients with mild (n = 12) or moderate (n = 6) COVID-19 died whereas 7/10 patients (70%) with severe/critical COVID-19 died (P = .0001). Patients diagnosed with COVID-19 within 12 months of HCT exhibited higher mortality (57% vs 14%; P = .04). All-cause 30-day mortality (n = 4) was 14%. A higher proportion of patients who died within 30 days of COVID-19 diagnosis (3/4) were receiving ≥2 immunosuppressants, compared with patients who survived beyond 30 days after COVID-19 diagnosis (2/24; 75% vs. 8%; P = .01). Conclusions:Mortality in COVID-19 HCT patients is higher than that of the agecomparable general population and largely dependent on age, disease severity, timing from HCT, and intensity of immunosuppression.

Severe acute respiratory syndrome coronavirus 2 infection in the stem cell transplant recipient − clinical spectrum and outcome

“…The clinical manifestations of COVID-19 in the HSCT setting seem not to meaningfully differ from those reported for other immunocompromised hosts such as solid organ transplant (SOT) recipients, as confirmed by a recent meta-analysis [ 16 ]. Most commonly observed symptoms at presentation included fever (62.9% [ 17 ▪ ] to 78.5% [ 10 ▪▪ ] of patients), cough (48.1% [ 17 ▪ ] to 70.5% [ 14 ]), upper respiratory tract symptoms (27.7% [ 10 ▪▪ ] to 44.4% [ 12 ▪ ]), diarrhea and vomiting (7.4% [ 17 ▪ ] to 21.9% [ 11 ▪▪ ]), myalgia or arthralgia (15.2% [ 10 ▪▪ ] to 17.8% [ 11 ▪▪ ]), and anosmia (14.8% [ 17 ▪ ] to 42.4% [ 18 ]). Most patients (64–82%) showed pneumonia on the initial chest radiography [ 11 ▪▪ , 14 , 17 ▪ , 19 ].…”

“…Presentation was similar between allo-HSCT and auto-HSCT recipients in some [ 10 ▪▪ ] but not all series providing separate data, with higher rates of pneumonia and oxygen support requirement in the former group [ 11 ▪▪ , 15 ]. The proportion of asymptomatic patients in these cohorts largely varied from 8.9% [ 10 ▪▪ ] to 14.8% [ 17 ▪ ] depending on the study period (first vs. second pandemic waves) and design (retrospective vs. prospective). Nevertheless, it cannot be ruled out the existence of some degree of reporting bias in studies performed during the first wave, which would have skewed the sample towards the more severe cases because of limited diagnostic capabilities in many countries.…”

“…Only a few studies have provided detailed information on serum IL-6 kinetics in HSCT recipients with COVID-19 [ 11 ▪▪ , 17 ▪ , 19 ]. Piñana et al [ 11 ▪▪ ] found that IL-6 levels >50 pg/ml – present in 42.5% of evaluable patients – was associated with increased infection severity and mortality at the univariate (but not multivariate) analysis.…”

“…Piñana et al [ 11 ▪▪ ] found that IL-6 levels >50 pg/ml – present in 42.5% of evaluable patients – was associated with increased infection severity and mortality at the univariate (but not multivariate) analysis. Peak median IL-6 level in seven patients in which this cytokine was measured was 147.4 pg/ml in other cohort [ 17 ▪ ]. Shah et al [ 19 ] reported peak values of 108.5 and 49.5 pg/ml for 15 allo-HSCT and 13 auto-HSCT recipients, respectively.…”

“…The combined effect of ongoing immunosuppression, SARS-CoV-2-induced immune dysregulation, prolonged hospital and intensive care unit (ICU) stay and immunomodulatory therapies – such as dexamethasone or anti-IL-6 agents – may contribute to the development of infectious complications, either as co-infection at presentation or most commonly during the disease course. The incidence rates of microbiologically confirmed superimposed infections range from 13% to 25% [ 15 , 17 ▪ , 19 ]. Most reported episodes were bacterial, with predominance of hospital-acquired pathogens such as methicillin-resistant Staphylococcus aureus or nonfermenting Gram-negative bacilli.…”