Limited data are available on the clinical presentation and outcomes of coronavirus disease (COVID-19) patients in the United States hospitalized under normal-caseload or nonsurge conditions. We retrospectively studied 72 consecutive adult patients hospitalized with COVID-19 in 2 hospitals in the San Francisco Bay area, California, USA, during March 13–April 11, 2020. The death rate for all hospitalized COVID-19 patients was 8.3%, and median length of hospitalization was 7.5 days. Of the 21 (29% of total) intensive care unit patients, 3 (14.3% died); median length of intensive care unit stay was 12 days. Of the 72 patients, 43 (59.7%) had underlying cardiovascular disease and 19 (26.4%) had underlying pulmonary disease. In this study, death rates were lower than those reported from regions of the United States experiencing a high volume of COVID-19 patients.

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We studied the potential role of the human placenta as a hematopoietic organ during embryonic and fetal development. Placental samples contained two cell populations—CD34++CD45low and CD34+CD45low—that were found in chorionic villi and in the chorioamniotic membrane. CD34++CD45low cells express many cell surface antigens found on multipotent primitive hematopoietic progenitors and hematopoietic stem cells. CD34++CD45low cells contained colony-forming units culture (CFU-C) with myeloid and erythroid potential in clonogenic in vitro assays, and they generated CD56+ natural killer cells and CD19+CD20+sIgM+ B cells in polyclonal liquid cultures. CD34+CD45low cells mostly comprised erythroid- and myeloid-committed progenitors, while CD34− cells lacked CFU-C. The placenta-derived precursors were fetal in origin, as demonstrated by FISH using repeat-sequence chromosome-specific probes for X and Y. The number of CD34++CD45low cells increased with gestational age, but their density (cells per gram of tissue) peaked at 5–8 wk, decreasing more than sevenfold at the onset of the fetal phase (9 wk of gestation). In addition to multipotent progenitors, the placenta contained myeloid- and erythroid-committed progenitors indicative of active in situ hematopoiesis. These data suggest that the human placenta is an important hematopoietic organ, raising the possibility of banking placental hematopoietic stem cells along with cord blood for transplantation.

The case for universal boosters is weak, and the benefits are unclear

BackgroundDespite striking successes, immunotherapies aimed at increasing cancer-specific T cell responses are unsuccessful in most patients with cancer. Inactivating regulatory T cells (Treg) by inhibiting the PI3Kδ signaling enzyme has shown promise in preclinical models of tumor immunity and is currently being tested in early phase clinical trials in solid tumors.MethodsMice bearing 4T1 mammary tumors were orally administered a PI3Kδ inhibitor (PI-3065) daily and tumor growth, survival and T cell infiltrate were analyzed in the tumor microenvironment. A second treatment schedule comprised PI3Kδ inhibitor with anti-LAG3 antibodies administered sequentially 10 days later.ResultsAs observed in human immunotherapy trials with other agents, immunomodulation by PI3Kδ-blockade led to 4T1 tumor regressor and non-regressor mice. Tumor infiltrating T cells in regressors were metabolically fitter than those in non-regressors, with significant enrichments of antigen-specific CD8+ T cells, T cell factor 1 (TCF1)+ T cells and CD69− T cells, compatible with induction of a sustained tumor-specific T cell response. Treg numbers were significantly reduced in both regressor and non-regressor tumors compared with untreated tumors. The remaining Treg in non-regressor tumors were however significantly enriched with cells expressing the coinhibitory receptor LAG3, compared with Treg in regressor and untreated tumors. This striking difference prompted us to sequentially block PI3Kδ and LAG3. This combination enabled successful therapy of all mice, demonstrating the functional importance of LAG3 in non-regression of tumors on PI3Kδ inhibition therapy. Follow-up studies, performed using additional cancer cell lines, namely MC38 and CT26, indicated that a partial initial response to PI3Kδ inhibition is an essential prerequisite to a sequential therapeutic benefit of anti-LAG3 antibodies.ConclusionsThese data indicate that LAG3 is a key bottleneck to successful PI3Kδ-targeted immunotherapy and provide a rationale for combining PI3Kδ/LAG3 blockade in future clinical studies.

a growing body of evidence about covid-19 vaccine effectiveness, including that of third and booster doses, has been published, and several countries have authorized boosters for general adult populations. 2 Well conducted real world studies of vaccine effectiveness are an important complement to randomized controlled trials. For example, two linked studies use test negative designs to analyze rich datasets from large health systems. Firstly, Israel and colleagues (

Epidemiology of HIV/hepatitis C co-infection Of the approximately 35 million people living with human immunodeficiency virus (HIV) worldwide, an estimated 4-7 million are coinfected with chronic hepatitis C virus (HCV), based on the most recent reports [Soriano et al. 2010; Alter, 2006]. The actual number of coinfected patients is likely significantly higher, given that half of patients with chronic HCV in the United States and in Europe are unaware that they are infected [Denniston et al. 2012; Wiessing et al. 2014], and approximately 14% of HIV-infected individuals living in the United States and 47-85% in Europe are undiagnosed [Centers for Disease Control and Prevention, 2014; Ferrer et al. 2015]. Identification of those with infection is urgently needed in order to improve health outcomes and prevent further transmission of both viruses. In Europe and the United States, it is estimated that 20-30% of HIV-infected persons are co-infected with HCV, yet the prevalence varies widely among subpopulations as the efficiency of viral transmission depends upon the route [Sulkowski et al. 2000; Strader, 2005]. Rates of co-infection are highest in individuals with a history of injection drug use (IDU); an estimated 75-90% of HIV-infected patients with a reported history of IDU are coinfected with HCV. Although the majority of HCV is transmitted via percutaneous exposure, sexual transmission of HCV also occurs in individuals without reported histories of IDU, primarily among HIV-positive men who have sex with men [Hagan et al. 2015]. Outcomes with HIV/HCV co-infection HIV and HCV co-infection is associated with an increased risk of adverse health outcomes, largely due to the effects of HIV infection on the natural history of HCV. HIV infection is associated with higher rates of HCV replication and therefore

Although metastatic disease is responsible for the majority of cancer deaths, tests of novel immunotherapies in mouse tumour models often focus on primary tumours without determining whether these therapies also target metastatic disease. This study examined the impact of depleting Foxp3+ regulatory T cells (Treg), on lung metastases, using a mouse model of breast cancer. After Treg-depletion, generation of an immune response to the primary tumour was a critical determinant for limiting development of metastasis. Indeed, resection of the primary tumour abrogated any effect of Treg-depletion on metastases. In addition, whilst the immune response, generated by the primary tumour, prevented metastases development, it had little impact on controlling established disease. Collectively, the data indicate that metastatic cells in the lung are not controlled by immune responses induced by the primary tumour. These findings indicate that targeting Tregs alone will not suffice for treating lung metastases.