Ruxolitinib on acute graft-versus-host disease prophylaxis after modified donor lymphocyte infusion.

OBJECTIVE: To evaluate the effectiveness of ruxolitinib on acute graft-versus-host disease (aGVHD) prophylaxis and its impact on graft-versus-leukemia (GVL) effect in patients after modified donor lymphocyte infusion (mDLI). METHODS: We retrospectively included patients with relapsed leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT) who received ruxolitinib prophylaxis between October 2018 and April 2020. The incidence of aGVHD, disease-free survival (DFS), overall survival (OS), and treatment safety were evaluated. RESULTS: Seventeen patients were followed up for a median time of 8 months (range: 1-26 months). The incidence of aGVHD on Day 30 after mDLI was 41.2% and ranged from Grade 1 to 4; ten of 17 patients (58.8%) achieved a complete response (CR), and two (11.8%) had a partial response (PR). Cytomegalovirus (CMV) reactivation rate was 23.5%, and the median time from mDLI to CMV reactivation was 48.5 days. The mean DFS and OS after mDLI were 1.0 (95% CI 0.0-3.5) and 9.0 (95% CI 1.2-16.8) months, respectively. The causes of death for 10 patients were leukemia relapse (n = 5), aGVHD and septic shock (n = 3), intracranial lesion (n = 1), and COVID-19 (n = 1). CONCLUSIONS: We reported encouraging results of ruxolitinib monotherapy in the prevention of aGVHD and maintenance of GVL for post-transplantation relapsed patients, even though being at high risk with poor initial prognosis.

Meplazumab in hospitalized adults with severe COVID-19 (DEFLECT): a multicenter, seamless phase 2/3, randomized, third-party double-blind clinical trial.

Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile.

Changes in the medical-seeking pattern and daily behavior of hematopoietic stem-cell transplant recipients during the COVID-19 epidemic: An online survey in Hubei Province, China

Background To curb the spread of the coronavirus disease 2019 (COVID-19) epidemic, the Chinese government shut down Wuhan city from January 23rd to April 8th, 2020. The COVID-19 epidemic not only leads to widespread illness but also affects the diagnosis and treatment of hematopoietic stem-cell transplant (HSCT) recipients. Objective To investigate the medical-seeking pattern and daily behavior changes in Hubei Province during the COVID-19 epidemic in Hubei Province during the lockdown. Methods We conducted a multicenter, cross-sectional, web-based investigation among 325 HSCT recipients by online questionnaires in Hubei Province during the COVID-19 epidemic. Results A total of 145 complete responses were collected both before and during the epidemic questionnaires. The participants from pre-epidemic group preferred to go to hospital (68.29%) when they experienced influenza-like symptoms. The majority of the patients elected to take oral drugs by themselves (40%) or consulted their attending physicians online or by telephone during the lockdown (23.33%). 64.83% had difficulties in purchasing drugs during the lockdown, which was significantly higher than the proportion of the pre-epidemic group (24.83%) (P < 0.05). The participants preferred to purchase drugs online (23.40%) and decrease or withdraw drugs (18.09%) during the epidemic. The number of participants received regular re-examinations during the epidemic decreased sharply. The proportion of wearing masks and isolating themselves at home increased significantly during the epidemic. No statistic difference was observed in the incidence of graft-versus-host disease (GVHD)complications in participants between the during the epidemic group and the pre-epidemic group. In our study, six patients were confirmed to have COVID-19, and half of them died due to COVID-19-related complications. Conclusion The medical-seeking pattern and daily behavior of HSCT recipients changed during the lockdown;the methods of self-protection, online consultation and drug delivery can help patients receive necessary follow-up and reduce the occurrence of COVID-19.

A Chinese host genetic study discovered IFNs and causality of laboratory traits on COVID-19 severity.

The COVID-19 pandemic has caused over 220 million infections and 4.5 million deaths worldwide. Current risk factor cannot fully explain the diversity in disease severity. Here, we present a comprehensive analysis of a broad range of patients' laboratory and clinical assessments to investigate the genetic contributions to COVID-19 severity. By performing GWAS analysis, we discovered several concrete associations for laboratory traits and used Mendelian randomization (MR) analysis to further investigate the causality of traits on disease severity. Two causal traits, WBC counts and cholesterol levels, were identified based on MR study, and their functional genes are located at genes MHC complex and ApoE, respectively. Our gene-based analysis and GSEA revealed four interferon pathways, including type I interferon receptor binding and SARS coronavirus and innate immunity. We hope that our work will contribute to studying the genetic mechanisms of disease and serve as a useful reference for COVID-19 diagnosis and treatment.

Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial.

Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.

A Case of Severe COVID-19 in a Patient with Acute Graft-versus-Host Disease after Haploidentical Transplantation.

We report a case of coronavirus disease 2019 (COVID-19) after haploidentical transplantation with acute graft-versus-host disease (aGVHD). COVID-19 and aGVHD were improved under treatment with arbidol, remdesivir, methylprednisolone, and ruxolitinib. However, eventually, the patient died of septic shock and multiple organ failure. It was concluded that the disease condition of this COVID-19 patient after transplantation was serious, complex, and variable, with poor prognosis.

Prognostic Accuracy of Early Warning Scores for Clinical Deterioration in Patients With COVID-19.

Background: Early Warning Scores (EWS), including the National Early Warning Score 2 (NEWS2) and Modified NEWS (NEWS-C), have been recommended for triage decision in patients with COVID-19. However, the effectiveness of these EWS in COVID-19 has not been fully validated. The study aimed to investigate the predictive value of EWS to detect clinical deterioration in patients with COVID-19. Methods: Between February 7, 2020 and February 17, 2020, patients confirmed with COVID-19 were screened for this study. The outcomes were early deterioration of respiratory function (EDRF) and need for intensive respiratory support (IRS) during the treatment process. The EDRF was defined as changes in the respiratory component of the sequential organ failure assessment (SOFA) score at day 3 (ΔSOFAresp = SOFA resp at day 3-SOFAresp on admission), in which the positive value reflects clinical deterioration. The IRS was defined as the use of high flow nasal cannula oxygen therapy, noninvasive or invasive mechanical ventilation. The performances of EWS including NEWS, NEWS 2, NEWS-C, Modified Early Warning Scores (MEWS), Hamilton Early Warning Scores (HEWS), and quick sepsis-related organ failure assessment (qSOFA) for predicting EDRF and IRS were compared using the area under the receiver operating characteristic curve (AUROC). Results: A total of 116 patients were included in this study. Of them, 27 patients (23.3%) developed EDRF and 24 patients (20.7%) required IRS. Among these EWS, NEWS-C was the most accurate scoring system for predicting EDRF [AUROC 0.79 (95% CI, 0.69-0.89)] and IRS [AUROC 0.89 (95% CI, 0.82-0.96)], while NEWS 2 had the lowest accuracy in predicting EDRF [AUROC 0.59 (95% CI, 0.46-0.720)] and IRS [AUROC 0.69 (95% CI, 0.57-0.81)]. A NEWS-C ≥ 9 had a sensitivity of 59.3% and a specificity of 85.4% for predicting EDRF. For predicting IRS, a NEWS-C ≥ 9 had a sensitivity of 75% and a specificity of 88%. Conclusions: The NEWS-C was the most accurate scoring system among common EWS to identify patients with COVID-19 at risk for EDRF and need for IRS. The NEWS-C could be recommended as an early triage tool for patients with COVID-19.

Characteristics and Outcomes of 35 Breast Cancer Patients Infected With COVID-19.

Since December 2019, a novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly engulfed the world. Cancer patients infected with COVID-19 are considered to carry higher severity of the disease and higher mortality rate than common COVID-19 patients in previous studies. However, due to the poor clinical information on COVID-19 patients with cancer, the evidences that supported this conclusion are insufficient. At present, rather limited reports have analyzed the clinical data of breast cancer patients infected with COVID-19. Therefore, in this retrospective study, we described the clinical characteristics and the outcomes of 35 COVID-19 patients with breast cancer and compared 55 COVID-19 patients without cancer and 81 COVID-19 patients with other types of cancer as controls. Our data showed that there were no differences in disease severity and outcomes between the COVID-19 patients with breast cancer and the common COVID-19 patients, which was in contrast to previous studies. In addition, compared with other types of cancer patients, asymptomatic infections and mild cases among breast cancer patients made up a substantially larger proportion. Our results indicated that the clinical characteristics of breast cancer patients were milder than those of other types of cancer patients, but there were no significant differences in outcomes between the two groups.

Clinical and Epidemiological Features of 46 Children <1 Year Old With Coronavirus Disease 2019 in Wuhan, China: A Descriptive Study.

The number of coronavirus disease 2019 (COVID-19) cases has exceeded 10 million. However, little is known about the epidemiology and clinical characteristics of COVID-19 infants. We collected medical information of 46 confirmed patients (<1 year old) and retrospectively analyzed epidemiological history, clinical symptoms, and laboratory test results. The median age was 5 (interquartile range, 2-7) months. Sixteen cases had fever and 27 cases had cough. Moderate disease was present in 40 cases and cardiac injury occurred in 38 cases, following by liver dysfunction in 20 cases and lymphocytosis in no cases. Of all infant patients, 2 received invasive mechanical ventilation and 1 died with multiple organ dysfunction syndrome.