Bone Marrow versus Peripheral Blood Grafts for Haploidentical Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide.

In the coronavirus disease 19 (COVID-19) pandemic era, the number of haploidentical hematopoietic cell transplantations (HCTs) with peripheral blood (PB) grafts increased significantly compared with HCTs with bone marrow (BM) grafts, which may be associated with adverse outcomes. We compared outcomes of HCT in BM graft and PB graft recipients age ≥18 years with hematologic malignancies who underwent T cell- replete haploidentical HCT and received graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil. Among the 264 patients, 180 (68%) received a BM graft and 84 (32%) received a PB graft. The median patient age was 50 years in both groups. The majority (n = 199; 75%) received reduced-intensity conditioning. The rate of acute leukemia or myelodysplastic syndrome was higher in the BM graft recipients compared with the PB graft recipients (85% [n = 152] versus 55% [n = 46]; P < .01). The median times to neutrophil and platelet engraftment and the incidence of grade II-IV and grade III-IV acute GVHD (aGVHD) were comparable in the 2 groups. Among the patients with grade II-IV aGVHD, the rate of steroid-refractory aGVHD was 9% (95% confidence interval [CI], 5% to 18%) in the BM group versus 32% (95% CI, 19% to 54%) in the PB group (hazard ratio [HR], 3.7, 95% CI, 1.5 to 9.3; P = .006). At 1 year post-HCT, the rate of chronic GVHD (cGVHD) was 8% (95% CI, 4% to 13%) in the BM group versus 22% (95% CI, 14% to 36%) in the PB group (HR, 3.0; 95% CI, 1.4-6.6; P = .005), and the rate of systemic therapy-requiring cGVHD was 2.5% (95% CI, 1% to 7%) versus 14% (95% CI, 7% to 27%), respectively (HR, 5.6; 95% CI, 1.7 to 18; P = .004). The PB group had a significantly higher risk of bacterial and viral infections, with no appreciable advantage in the duration of hospitalization, immune reconstitution, relapse, nonrelapse mortality, or survival. Our data suggest a benefit of the use of BM grafts over PB grafts for haplo-HCT.

Early and consecutive RT-PCR tests with both oropharyngeal swabs and sputum could improve testing yield for patients with COVID-19: An observation cohort study in China.

OBJECTIVE: The real-time polymerase chain reaction (RT-PCR) test is recommended for the diagnosis of COVID-19 and provides a powerful tool to identify new infections and facilitate contact tracing. In fact, as the prevalence of COVID-19 decreases, this RT-PCR testing remains as the main preventive measure to avoid rebound. However, inconsistent results can lead to misdiagnoses in the clinic. These inconsistencies are due to the variability in (1) the collection times of biological samples post infection, and (2) sampling procedures. METHODS: We applied the Kaplan-Meier method and multivariate logistic regression on RT-PCR results from 258 confirmed patients with COVID-19 to evaluate the factors associated with negative conversion. We also estimated the proportion (%) of negative conversion among patients who had tested twice or more, and compared the proportions arising from oropharyngeal swabs, sputum, and combined double testing, respectively. MAIN RESULTS: The proportion of negative conversion was 6.7% on day 4, 16.4% on day 7, 41.0% at 2 weeks, and 61.0% at 3 weeks post-admission. We also found that 34.1% and 60.3% of subjects had at least one negative RT-PCR result on days 7 and 14 after the onset of symptoms, respectively. The proportion of negative conversions following sputum testing was higher than that from oropharyngeal swabs in the early stages but this declined after the onset of symptoms. CONCLUSION: In the absence of effective treatments or vaccines, efficient testing strategies are critical if we are to control the COVID-19 epidemic. According to this study, early, consecutive and combined double testing, will be the key to identify infected patients, particularly for asymptomatic and mild symptomatic cases. These strategies will minimize misdiagnosis and the ineffective isolation of infected patients.

Early identification of patients with severe COVID-19 at increased risk of in-hospital death: a multicenter case-control study in Wuhan.

BACKGROUND: Most evidence regarding the risk factors for early in-hospital mortality in patients with severe COVID-19 focused on laboratory data at the time of hospital admission without adequate adjustment for confounding variables. A multicenter, age-matched, case-control study was therefore designed to explore the dynamic changes in laboratory parameters during the first 10 days after admission and identify early risk indicators for in-hospital mortality in this patient cohort. METHODS: Demographics and clinical data were extracted from the medical records of 93 pairs of patients who had been admitted to hospital with severe COVID-19. These patients had either been discharged or were deceased by March 3, 2020. Data from days 1, 4, 7, and 10 of hospital admission were compared between survivors and non-survivors. Univariate and multivariate conditional logistic regression analyses were employed to identify early risk indicators of in-hospital death in this cohort. RESULTS: On admission, in-hospital mortality was associated with five risk indicators (ORs in descending order): aspartate aminotransferase (AST, >32 U/L) 43.20 (95% CI: 2.63, 710.04); C-reactive protein (CRP) greater than 100 mg/L 13.61 (1.78, 103.941); lymphocyte count lower than 0.6×109/L 9.95 (1.30, 76.42); oxygen index (OI) less than 200 8.23 (1.04, 65.15); and D-dimer over 1 mg/L 8.16 (1.23, 54.34). Sharp increases in D-dimer at day 4, accompanied by decreasing lymphocyte counts, deteriorating OI, and persistent remarkably high CRP concentration were observed among non-survivors during the early stages of hospital admission. CONCLUSIONS: The potential risk factors of high D-dimer, CRP, AST, low lymphocyte count and OI could help clinicians identify patients at high risk of death early in the hospital admission. This might assist with rationalization of health care resources.

Brief Report: Retrospective Evaluation on the Efficacy of Lopinavir/Ritonavir and Chloroquine to Treat Nonsevere COVID-19 Patients.

BACKGROUND: The effectiveness of lopinavir/ritonavir (LPV/r) and chloroquine treatment for COVID-19 has not been verified. METHODS: We conducted a retrospective study to summarize the clinical practices of nonsevere patients with COVID-19 receiving the standard care, LPV/r or chloroquine in Beijing Ditan Hospital from January 20 to March 26, 2020. The main outcome measurements include the changes of cycle threshold values of open reading frame 1 ab (ORF1ab) and nucleocapsid (N) genes by reverse transcriptase-polymerase chain reaction assay from day 1 to 7 after admission for patients receiving standard care or after treatment being initiated for patients receiving either LPV/r or chloroquine. The proportion of developing severe illness, fever duration and the time from symptom onset to chest computer tomography improvement, and negative conversion of nucleic acid were compared. RESULTS: Of the 129 patients included in the study, 59 received the standard care, 51 received LPV/r, and 19 received chloroquine. The demographics and baseline characteristics were comparable among the 3 groups. The median duration of fever, median time from symptom onset to chest computer tomography improvement, and negative conversion of the nucleic acid were similar among the 3 groups. The median increase in cycle threshold values of N and ORF1ab gene for patients receiving LPV/r or chloroquine or the standard care during the treatment course was 7.0 and 8.5, 8.0, and 7.6, 5.0, and 4.0, respectively. These figures were not found significantly different among the 3 groups. CONCLUSIONS: Antiviral therapy using LPV/r or chloroquine seemed not to improve the prognosis or shorten the clinical course of COVID-19.

Specific dynamic variations in the peripheral blood lymphocyte subsets in COVID-19 and severe influenza A patients: a retrospective observational study.

BACKGROUND: Both COVID-19 and influenza A contribute to increased mortality among the elderly and those with existing comorbidities. Changes in the underlying immune mechanisms determine patient prognosis. This study aimed to analyze the role of lymphocyte subsets in the immunopathogenesisof COVID-19 and severe influenza A, and examined the clinical significance of their alterations in the prognosis and recovery duration. METHODS: By retrospectively reviewing of patients in four groups (healthy controls, severe influenza A, non-severe COVID-19 and severe COVID-19) who were admitted to Ditan hospital between 2018 to 2020, we performed flow cytometric analysis and compared the absolute counts of leukocytes, lymphocytes, and lymphocyte subsets of the patients at different time points (weeks 1-4). RESULTS: We reviewed the patients' data of 94 healthy blood donors, 80 Non-severe-COVID-19, 19 Severe-COVID-19 and 37 severe influenza A. We found total lymphocytes (0.81 × 109/L vs 1.74 × 109/L, P = 0.001; 0.87 × 109/L vs 1.74 × 109/L, P < 0.0001, respectively) and lymphocyte subsets (T cells, CD4+ and CD8+ T cell subsets) of severe COVID-19 and severe influenza A patients to be significantly lower than those of healthy donors at early infection stages. Further, significant dynamic variations were observed at different time points (weeks 1-4). CONCLUSIONS: Our study suggests the plausible role of lymphocyte subsets in disease progression, which in turn affects prognosis and recovery duration in patients with severe COVID-19 and influenza A.

The Yield and Consistency of the Detection of SARS-CoV-2 in Multiple Respiratory Specimens.

BACKGROUND: Few studies have compared the yield of reverse transcription polymerase chain reaction (RT-PCR) assays in nasopharyngeal swabs, oropharyngeal swabs, and sputum for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection. METHODS: We conducted an observational study in Beijing Ditan Hospital, China. Specimens including nasopharyngeal swabs, oropharyngeal swabs, and sputum from confirmed coronavirus 2019 patients were collected for RT-PCR testing. Disease duration was calculated from the date of symptom onset to the date of specimen collection and divided into 3 groups: ≤14 days, 14-21 days, and >21 days. We compared positive rates across the 3 specimens collected. The kappa coefficient was used to evaluate the consistency of RT-PCR results between different specimens. RESULTS: A total of 291 specimens were collected and tested from 43 confirmed patients. Among specimens collected with a disease duration of ≤14 days, the positive rate was highest in sputum (79.2%); this rate was significantly higher than that in nasopharyngeal swabs (37.5%; P = .003) and oropharyngeal swabs (20.8%; P < .001). Similar findings were observed with the disease durations of 14-21 days and >21 days. The consistency of testing results between nasopharyngeal swabs and oropharyngeal swabs was low with the disease durations of ≤14 days and >21 days. The consistency between the sputum and oropharyngeal swabs and between the sputum and nasopharyngeal swabs was very low across all 3 disease durations, with statistical significance. CONCLUSIONS: Compared with nasopharyngeal swabs and oropharyngeal swabs, sputum had the highest yield of SARS-CoV-2 detection. Nasopharyngeal swabs and oropharyngeal swabs had a similar yield. If sputum is not feasible, a nasopharyngeal swab can be recommended for the detection of SARS-CoV-2, and early testing is needed.

Next-Generation Scholarship: Rebranding Hematopathology Using Twitter: The MD Anderson Experience.

Hematopathologists are witnessing very exciting times, as a new era of unsurpassed technological advances is unfolding exponentially, enhancing our understanding of diseases at the genomic and molecular levels. In the evolving field of precision medicine, our contributions as hematopathologists to medical practice are of paramount importance. Social media platforms such as Twitter have helped facilitate and enrich our professional  interactions and collaborations with others in our field and in other medical disciplines leading to a more holistic approach to patient care. These platforms also have created a novel means for instantaneous dissemination of new findings and recent publications, and are proving to be increasingly useful tools that can be harnessed to expand our knowledge and amplify our presence in the medical community. In this Editorial, we share our experience as hematopathologists with Twitter, and how we leveraged this platform to boost scholarly activities within and beyond our subspecialty, and as a powerful medium for worldwide dissemination of educational material and to promote our remote teaching activities during the COVID-19 pandemic.

Genomic surveillance of COVID-19 cases in Beijing.

The spread of SARS-CoV-2 in Beijing before May, 2020 resulted from transmission following both domestic and global importation of cases. Here we present genomic surveillance data on 102 imported cases, which account for 17.2% of the total cases in Beijing. Our data suggest that all of the cases in Beijing can be broadly classified into one of three groups: Wuhan exposure, local transmission and overseas imports. We classify all sequenced genomes into seven clusters based on representative high-frequency single nucleotide polymorphisms (SNPs). Genomic comparisons reveal higher genomic diversity in the imported group compared to both the Wuhan exposure and local transmission groups, indicating continuous genomic evolution during global transmission. The imported group show region-specific SNPs, while the intra-host single nucleotide variations present as random features, and show no significant differences among groups. Epidemiological data suggest that detection of cases at immigration with mandatory quarantine may be an effective way to prevent recurring outbreaks triggered by imported cases. Notably, we also identify a set of novel indels. Our data imply that SARS-CoV-2 genomes may have high mutational tolerance.

Clinical Characteristics and Risk Factors of Acute Respiratory Distress Syndrome (ARDS) in COVID-19 Patients in Beijing, China: A Retrospective Study.

BACKGROUND Coronavirus disease 2019 (COVID-19) is a new infectious disease, and acute respiratory syndrome (ARDS) plays an important role in the process of disease aggravation. The detailed clinical course and risk factors of ARDS have not been well described. MATERIAL AND METHODS We retrospectively investigated the demographic, clinical, and laboratory data of adult confirmed cases of COVID-19 in Beijing Ditan Hospital from Jan 20 to Feb 29, 2020 and compared the differences between ARDS cases and non-ARDS cases. Univariate and multivariate logistic regression methods were employed to explore the risk factors associated with ARDS. RESULTS Of the 130 adult patients enrolled in this study, the median age was 46.5 (34-62) years and 76 (58.5%) were male. ARDS developed in 26 (20.0%) and 1 (0.8%) death occurred. Fever occurred in 114 patients, with a median highest temperature of 38.5 (38-39)°C and median fever duration of 8 (3-11) days. The median time from illness onset to ARDS was 10 (6-13) days, the median time to chest CT improvement was 17 (14-21) days, and median time to negative nucleic acid test result was 27 (17-33) days. Multivariate regression analysis showed increasing odds of ARDS associated with age older than 65 years (OR=4.75, 95% CL1.26-17.89, P=0.021), lymphocyte counts [0.5-1×109/L (OR=8.80, 95% CL 2.22-34.99, P=0.002); <0.5×109/L(OR=36.23, 95% CL 4.63-2083.48, P=0.001)], and temperature peak ≥39.1°C (OR=5.35, 95% CL 1.38-20.76, P=0.015). CONCLUSIONS ARDS tended to occur in the second week of the disease course. Potential risk factors for ARDS were older age (>65 years), lymphopenia (≤1.0×109/L), and temperature peak (≥39.1°C). These findings could help clinicians to predict which patients will have a poor prognosis at an early stage.

First Case of Coronavirus Disease 2019 in Childhood Leukemia in China.

We report the first case of coronavirus disease 2019 (COVID-19) comorbid with leukemia in a patient hospitalized in Beijing, China. The patient showed a prolonged manifestation of symptoms and a protracted diagnosis period of COVID-19. It is necessary to extend isolation time, increase the number of nucleic acid detections and conduct early symptomatic treatment for children with both COVID-19 and additional health problems.

Evaluating a Nurse Training Program in the Emergency Surgery Department Based on the Kirkpatrick's Model and Clinical Demand During the COVID-19 Pandemic.

Objective:To analyze the application of Kirkpatrick's model in the nurse training program among the emergency surgery department based on clinical demand during the COVID-19 (coronavirus disease-2019). To provide reference for the training of emergency surgical nurses during the outbreak of COVID-19.Design:Guided by Kirkpatrick's model, 35 nurses in the emergency surgery department were trained according to a program that resulted from the clinical demand during the pandemic. The trainees were observed in terms of their performance at reaction level and learning level.Results:At reaction level, the degree of satisfaction scored by nurses was relatively high, with its total score achieving (18.77 ± 3.09). At learning level, the differences between theoretical and operational scores of tested nurses before and after training proved to be statistically significant (p < 0.001).Conclusion:The application of Kirkpatrick's model based on clinical demand during the COVID-19 confirms to be effective for the training program of nurses in the emergency surgery department. It is also beneficial to improve nurses' knowledge and skills during the pandemic, which serves as a positive influence for clinical reference.

Quantitative Detection and Viral Load Analysis of SARS-CoV-2 in Infected Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a public health emergency. The widely used reverse transcription-polymerase chain reaction (RT-PCR) method has limitations for clinical diagnosis and treatment. METHODS: A total of 323 samples from 76 COVID-19-confirmed patients were analyzed by droplet digital PCR (ddPCR) and RT-PCR based 2 target genes (ORF1ab and N). Nasal swabs, throat swabs, sputum, blood, and urine were collected. Clinical and imaging data were obtained for clinical staging. RESULTS: In 95 samples that tested positive by both methods, the cycle threshold (Ct) of RT-PCR was highly correlated with the copy number of ddPCR (ORF1ab gene, R2 = 0.83; N gene, R2 = 0.87). Four (4/161) negative and 41 (41/67) single-gene positive samples tested by RT-PCR were positive according to ddPCR with viral loads ranging from 11.1 to 123.2 copies/test. The viral load of respiratory samples was then compared and the average viral load in sputum (17 429 ±â€…6920 copies/test) was found to be significantly higher than in throat swabs (2552 ±â€…1965 copies/test, P < .001) and nasal swabs (651 ±â€…501 copies/test, P < .001). Furthermore, the viral loads in the early and progressive stages were significantly higher than that in the recovery stage (46 800 ±â€…17 272 vs 1252 ±â€…1027, P < .001) analyzed by sputum samples. CONCLUSIONS: Quantitative monitoring of viral load in lower respiratory tract samples helps to evaluate disease progression, especially in cases of low viral load.