Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Meta-analysis is a method to obtain a weighted average of results from various studies. In addition to pooling effect sizes, meta-analysis can also be used to estimate disease frequencies, such as incidence and prevalence. In this article we present methods for the meta-analysis of prevalence. We discuss the logit and double arcsine transformations to stabilise the variance. We note the special situation of multiple category prevalence, and propose solutions to the problems that arise. We describe the implementation of these methods in the MetaXL software, and present a simulation study and the example of multiple sclerosis from the Global Burden of Disease 2010 project. We conclude that the double arcsine transformation is preferred over the logit, and that the MetaXL implementation of multiple category prevalence is an improvement in the methodology of the meta-analysis of prevalence.

Meta-analysis of prevalence

Summary Background The efficacy and safety profiles of vaccines against SARS-CoV-2 in patients with cancer is unknown. We aimed to assess the safety and immunogenicity of the BNT162b2 (Pfizer–BioNTech) vaccine in patients with cancer. Methods For this prospective observational study, we recruited patients with cancer and healthy controls (mostly health-care workers) from three London hospitals between Dec 8, 2020, and Feb 18, 2021. Participants who were vaccinated between Dec 8 and Dec 29, 2020, received two 30 μg doses of BNT162b2 administered intramuscularly 21 days apart; patients vaccinated after this date received only one 30 μg dose with a planned follow-up boost at 12 weeks. Blood samples were taken before vaccination and at 3 weeks and 5 weeks after the first vaccination. Where possible, serial nasopharyngeal real-time RT-PCR (rRT-PCR) swab tests were done every 10 days or in cases of symptomatic COVID-19. The coprimary endpoints were seroconversion to SARS-CoV-2 spike (S) protein in patients with cancer following the first vaccination with the BNT162b2 vaccine and the effect of vaccine boosting after 21 days on seroconversion. All participants with available data were included in the safety and immunogenicity analyses. Ongoing follow-up is underway for further blood sampling after the delayed (12-week) vaccine boost. This study is registered with the NHS Health Research Authority and Health and Care Research Wales (REC ID 20/HRA/2031). Findings 151 patients with cancer (95 patients with solid cancer and 56 patients with haematological cancer) and 54 healthy controls were enrolled. For this interim data analysis of the safety and immunogenicity of vaccinated patients with cancer, samples and data obtained up to March 19, 2021, were analysed. After exclusion of 17 patients who had been exposed to SARS-CoV-2 (detected by either antibody seroconversion or a positive rRT-PCR COVID-19 swab test) from the immunogenicity analysis, the proportion of positive anti-S IgG titres at approximately 21 days following a single vaccine inoculum across the three cohorts were 32 (94%; 95% CI 81–98) of 34 healthy controls; 21 (38%; 26–51) of 56 patients with solid cancer, and eight (18%; 10–32) of 44 patients with haematological cancer. 16 healthy controls, 25 patients with solid cancer, and six patients with haematological cancer received a second dose on day 21. Of the patients with available blood samples 2 weeks following a 21-day vaccine boost, and excluding 17 participants with evidence of previous natural SARS-CoV-2 exposure, 18 (95%; 95% CI 75–99) of 19 patients with solid cancer, 12 (100%; 76–100) of 12 healthy controls, and three (60%; 23–88) of five patients with haematological cancers were seropositive, compared with ten (30%; 17–47) of 33, 18 (86%; 65–95) of 21, and four (11%; 4–25) of 36, respectively, who did not receive a boost. The vaccine was well tolerated; no toxicities were reported in 75 (54%) of 140 patients with cancer following the first dose of BNT162b2, and in 22 (71%) of 31 patients with cancer following the second dose. Similarly, no toxicities were reported in 15 (38%) of 40 healthy controls after the first dose and in five (31%) of 16 after the second dose. Injection-site pain within 7 days following the first dose was the most commonly reported local reaction (23 [35%] of 65 patients with cancer; 12 [48%] of 25 healthy controls). No vaccine-related deaths were reported. Interpretation In patients with cancer, one dose of the BNT162b2 vaccine yields poor efficacy. Immunogenicity increased significantly in patients with solid cancer within 2 weeks of a vaccine boost at day 21 after the first dose. These data support prioritisation of patients with cancer for an early (day 21) second dose of the BNT162b2 vaccine. Funding King's College London, Cancer Research UK, Wellcome Trust, Rosetrees Trust, and Francis Crick Institute.

Safety and immunogenicity of one versus two doses of the COVID-19 vaccine BNT162b2 for patients with cancer: interim analysis of a prospective observational study.

Outcomes of patients with hematologic malignancies and COVID-19: A systematic review and meta-analysis of 3377 patients.

Patients with cancer have high mortality from coronavirus disease 2019 (COVID-19), and the immune parameters that dictate clinical outcomes remain unknown. In a cohort of 100 patients with cancer who were hospitalized for COVID-19, patients with hematologic cancer had higher mortality relative to patients with solid cancer. In two additional cohorts, flow cytometric and serologic analyses demonstrated that patients with solid cancer and patients without cancer had a similar immune phenotype during acute COVID-19, whereas patients with hematologic cancer had impairment of B cells and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody responses. Despite the impaired humoral immunity and high mortality in patients with hematologic cancer who also have COVID-19, those with a greater number of CD8 T cells had improved survival, including those treated with anti-CD20 therapy. Furthermore, 77% of patients with hematologic cancer had detectable SARS-CoV-2-specific T cell responses. Thus, CD8 T cells might influence recovery from COVID-19 when humoral immunity is deficient. These observations suggest that CD8 T cell responses to vaccination might provide protection in patients with hematologic cancer even in the setting of limited humoral responses.

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CD8 + T cells contribute to survival in patients with COVID-19 and hematologic cancer.

Cancer has been shown to be associated with higher risk of COVID-19 complications [1]. However, data on patients with COVID-19 and an underlying hematological disease as well as on specific risks factors in this particularly immunocompromised population are scarce [2–5]. We conducted a retrospective study in a tertiary center of 1000 beds with a hematology reference center. Our ethics committee approved the study (N CEHF 2020/06AVR/ 201). Between March 13 and May 15, 2020 a total of 375 consecutive patients were hospitalized with COVID-19 and among them 13 (3.4%) met the inclusion criteria of having an underlying hematological disease. Demographics, clinical characteristics and laboratory findings are summarized in Table 1. The median age was 70 years (IQR 59–79) and 77% of patients were male. COVID-19 pneumonia was the admitting diagnosis for the majority of patients (n = 10, 77%) and a delayed secondary diagnosis in 3 patients (23%) with one of them being highly suspect for nosocomial infection. Diagnosis was based on the association of positive RT-PCR and CT-scan in 11 patients (85%) and on compatible CT-scan only in the two remaining. Median duration of symptoms (after exclusion of patients presenting with symptom-overlapping acute conditions) was 8 days (IQR 3–10). The most common reported symptoms were fever (n = 12, 92%), shortness of breath (n = 8, 62%) and cough (n = 5, 39%). Lymphopenia was present in 5 patients (39%) and neutropenia (grade 3 or more) in 2 patients. Therapy directed against COVID-19 included hydroxychloroquine for 10 patients (77%) with addition of methylprednisolone in 2 patients, azithromycin in 1 patient, and lopinavir/ritonavir in 1 patient. The underlying hematological diseases (Table 1) were distributed as following: 4 chronic lymphocytic leukemia’s (31%), 4 plasma cell dyscrasia’s (31%), 2 acute myeloid leukemia’s (15%) with one of them being secondary to primary myelofibrosis and the other one being a phenotype shift from early T cell precursor acute lymphoblastic leukemia, 2 non-Hodgkin lymphoma’s (15%) and 1 non-malignant condition which was a chronic hypogammaglobinemia of unknown origin. Two patients were stem cell transplant receptors (1 autologous and 1 allogeneic). Four malignant hematological diseases (33%) were newly diagnosed or in first line treatment, 3 were in remission or in a watch and wait strategy without ever having had any treatment, 2 were stable without remission and 3 were relapsed or refractory. Patients received a median of 1 (range 0–5) treatment lines. Two patients were admitted to the intensive care unit (ICU) at presentation: one received high flow oxygen therapy and the other one invasive mechanical ventilation. Five more patients (39%) presented worsening respiratory state later during hospitalization and were medically eligible for an admission to the ICU but, owing to age and comorbidities, palliative care was provided instead. Four patients (31%) had a documented bacterial co-infection (Three urinary tract infections caused by Escherichia coli [2],and Enterococcus faecalis [1] and one septicemia R. Lattenist and H. Yildiz have contributed equally as first authors.

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COVID-19 in Adult Patients with Hematological Disease: Analysis of Clinical Characteristics and Outcomes.

Julien De Greef* (1,2), Lucie Pothen * (1,2), Halil Yildiz (1),William Poncin (2,3), Gregory Reychler (2,3), Sarah Brilot (1), Sophie Demartin (1), Eugénie Lagneaux (1), Raphaël Lattenist (1), Jeanne Lux (1),Guillaume Pierman (1), Geoffroy Vandercam (1), Silvio Wallemacq (1), Anaïs Scohy (4) , Alexia Verroken (4), Benny Mwenge (2,5), Giuseppe Liistro (2,5), Antoine Froidure (2,5), Charles Pilette (2,5), Leïla Belkhir **(1,2), Jean-Cyr Yombi**(1,2)

Raphaël Lattenist

Papers

Outcomes of patients with hematologic malignancies and COVID-19: A systematic review and meta-analysis of 3377 patients.

COVID-19 in Adult Patients with Hematological Disease: Analysis of Clinical Characteristics and Outcomes.

COVID-19 : infection par le virus SARS-CoV-2

P-040: Unusual presentation of multiple myeloma with rapidly progressing lesions of the distal bones: about a case report