Background Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness.Methods In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing. FindingsOf 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57-76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1•84, 95% CI 1•53-2•21), male sex (1•63, 1•07-2•48), smoking status (former smoker vs never smoked: 1•60, 1•03-2•47), number of comorbidities (two vs none: 4•50, 1•33-15•28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3•89, 2•11-7•18), active cancer (progressing vs remission: 5•20, 2•77-9•77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2•93, 1•79-4•79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0•24, 0•07-0•84) or the US-Midwest (0•50, 0•28-0•90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality. Interpretation Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments.

Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.

Purpose: Recently, the majority of protein coding genes were sequenced in a collection of pancreatic cancers, providing an unprecedented opportunity to identify genetic markers of prognosis for patients with adenocarcinoma of the pancreas. Experimental Design: We previously sequenced more than 750 million base pairs of DNA from 23,219 transcripts in a series of 24 adenocarcinomas of the pancreas. In addition, 39 genes that were mutated in more than one of these 24 cancers were sequenced in a separate panel of 90 well-characterized adenocarcinomas of the pancreas. Of these 114 patients, 89 underwent pancreaticoduodenectomy, and the somatic mutations in these cancers were correlated with patient outcome. Results: When adjusted for age, lymph node status, margin status, and tumor size, SMAD4 gene inactivation was significantly associated with shorter overall survival (hazard ratio, 1.92; 95% confidence interval, 1.20-3.05; P = 0.006). Patients with SMAD4 gene inactivation survived a median of 11.5 months, compared with 14.2 months for patients without SMAD4 inactivation. By contrast, mutations in CDKN2A or TP53 or the presence of multiple (z4) mutations or homozygous deletions among the 39 most frequently mutated genes were not associated with survival. Conclusions: SMAD4 gene inactivation is associated with poorer prognosis in patients with surgically resected adenocarcinoma of the pancreas.Pancreatic cancer is the fourth leading cause of cancer death in the United States (1). Worldwide pancreatic cancer is responsible for more than 213,000 deaths each year (2). The 5-year overall survival rate for all patients diagnosed with pancreatic cancer is less than 4% (3). Surgical resection offers the best hope for long-term survival, with a 17% 5-year survival rate in most surgical series (4 -10). A number of pathologic features have been shown to correlate with outcome following surgery (4,(11)(12)(13)(14). For example, the completeness of resection (margin status), size of the cancer, degree of differentiation, vascular invasion, lymph node status, and tumor stage are all independent prognostic indicators following pancreaticoduodenectomy for pancreatic cancer (4, 11 -16). These factors have been useful guides in the clinical management of patients with pancreatic cancer. Genetic markers that could be used as prognostic indicators of outcome would be useful in establishing an individualized treatment plan for a patient. For example, a more aggressive surgical approach, such as vascular resection and reconstruction, may be considered for a patient with a reduced risk of systemic recurrence.In an attempt to establish such genetic makers, we took advantage of the recently completed mutational analysis of the pancreatic cancer coding genome (17). The results of this ''pancreatic cancer genome project'' provide a unique opportunity to determine if any genes with somatic changes correlate with patient outcome following surgical resection (17). This previous study included the sequencing of the protein-coding exons f...

IMPORTANCE COVID-19 is a life-threatening illness for many patients. Prior studies have established hematologic cancers as a risk factor associated with particularly poor outcomes from COVID-19. To our knowledge, no studies have established a beneficial role for anti-COVID-19 interventions in this at-risk population. Convalescent plasma therapy may benefit immunocompromised individuals with COVID-19, including those with hematologic cancers.OBJECTIVE To evaluate the association of convalescent plasma treatment with 30-day mortality in hospitalized adults with hematologic cancers and COVID-19 from a multi-institutional cohort. DESIGN, SETTING, AND PARTICIPANTSThis retrospective cohort study using data from the COVID-19 and Cancer Consortium registry with propensity score matching evaluated patients with hematologic cancers who were hospitalized for COVID-19. Data were collected between

Varicella-zoster virus (VZV) open reading frame 63 (ORF63), located between nucleotides 110581 and 111417 in the internal repeat region, encodes a nuclear phosphoprotein which is homologous to herpes simplex virus type 1 (HSV-1) ICP22 and is duplicated in the terminal repeat region as ORF70 (nucleotides 118480 to 119316). We evaluated the role of ORFs 63 and 70 in VZV replication, using recombinant VZV cosmids and PCR-based mutagenesis to make single and dual deletions of these ORFs. VZV was recovered within 8 to 10 days when cosmids with single deletions were transfected into melanoma cells along with the three intact VZV cosmids. In contrast, VZV was not detected in transfections carried out with a dual deletion cosmid. Infectious virus was recovered when ORF63 was cloned into a nonnative AvrII site in this cosmid, confirming that failure to generate virus was due to the dual ORF63/70 deletion and that replication required at least one gene copy. This requirement may be related to our observation that ORF63 interacts directly with ORF62, the major immediate-early transactivating protein of VZV. ORF64 is located within the inverted repeat region between nucleotides 111565 and 112107; it has some homology to the HSV-1 Us10 gene and is duplicated as ORF69 (nucleotides 117790 to 118332). ORF64 and ORF69 were deleted individually or simultaneously using the VZV cosmid system. Single deletions of ORF64 or ORF69 yielded viral plaques with the same kinetics and morphology as viruses generated with the parental cosmids. The dual deletion of ORF64 and ORF69 was associated with an abnormal plaque phenotype characterized by very large, multinucleated syncytia. Finally, all of the deletion mutants that yielded recombinants retained infectivity for human T cells in vitro and replicated efficiently in human skin in the SCIDhu mouse model of VZV pathogenesis.Varicella-zoster virus (VZV) is a ubiquitous human herpesvirus that causes varicella during primary infection of susceptible individuals (2). VZV is a lymphotropic virus, with the capacity to infect CD4 and CD8 T cells, permitting its spread to mucocutaneous sites and producing the vesicular rash commonly referred to as chicken pox. VZV is a member of the alphaherpesvirus group and also exhibits the neurotropism characteristic of these viruses; it establishes latency in sensory nerve ganglia, and its reactivation results in herpes zoster, a localized dermatomal exanthem.The VZV genome is a double-stranded DNA molecule with open reading frames (ORFs) that are known or predicted to encode at least 69 distinct gene products. The genome consists of two main coding regions, the unique long (U L ) and unique short (U S ) segments, each of which is flanked by internal repeat (IR) and terminal repeat (TR) sequences. Functions have been assigned to only about half of the VZV gene products, and many of these are presumed because of their partial sequence homologies with herpes simplex virus type 1 (HSV-1), which is the prototype of the alphaherpesviruses. Whereas generating mutant ...