OBJECTIVES: Four peer-reviewed publications have reported results from randomized controlled trials of convalescent plasma for coronavirus disease 2019 infection; none were conducted in the United States nor used standard plasma as a comparator. To determine if administration of convalescent plasma to patients with coronavirus disease 2019 increases antibodies to severe acute respiratory syndrome coronavirus 2 and improves outcome. DESIGN: Double-blind randomized controlled trial. SETTING: Hospital in New York. PATIENTS: Patients with polymerase chain reaction documented coronavirus disease 2019 infection. INTERVENTIONS: Patients were randomized (4:1) to receive 2 U of convalescent plasma versus standard plasma. Antibodies to severe acute respiratory syndrome coronavirus 2 were measured in plasma units and in trial recipients. MEASUREMENTS AND MAIN RESULTS: Enrollment was terminated after emergency use authorization was granted for convalescent plasma. Seventy-four patients were randomized. At baseline, mean (sd) Acute Physiology and Chronic Health Evaluation II score (23.4 [5.6] and 22.5 [6.6]), percent of patients intubated (19% and 20%), and median (interquartile range) days from symptom onset to randomization of 9 (6–18) and 9 (6–15), were similar in the convalescent plasma versus standard plasma arms, respectively. Convalescent plasma had high neutralizing activity (median [interquartile range] titer 1:526 [1:359–1:786]) and its administration increased antibodies to severe acute respiratory syndrome coronavirus 2 by 14.4%, whereas standard plasma administration led to an 8.6% decrease (p = 0.005). No difference was observed for ventilator-free days through 28 days (primary study endpoint): median (interquartile range) of 28 (2–28) versus 28 (0–28; p = 0.86) for the convalescent plasma and standard plasma groups, respectively. A greater than or equal to 2 point improvement in the World Health Organization scale was achieved by 20% of subjects in both arms (p = 0.99). All-cause mortality through 90 days was numerically lower in the convalescent plasma versus standard plasma groups (27% vs 33%; p = 0.63) but did not achieve statistical significance. A key prespecified subgroup analysis of time to death in patients who were intubated at baseline was statistically significant; however, sample size numbers were small. CONCLUSIONS: Administration of convalescent plasma to hospitalized patients with coronavirus disease 2019 infection increased antibodies to severe acute respiratory syndrome coronavirus disease 2 but was not associated with improved outcome.

Janus kinase (JAK) inhibitors have achieved positive responses in myeloproliferative neoplasms, but at the expense of decreased natural killer (NK) cell numbers and compromised function. Selective JAK2 inhibition may also have a role in preventing and treating graft-vs-host disease after allogeneic hematopoietic stem cell transplantation. Although JAK inhibitors can impair monocyte-derived dendritic cell (moDC) activation and function and suppress effector T-cell responses, the effects on NK cells and the relevant mechanisms remain undefined. Using common γc cytokines and distinct human dendritic cell (DC) subtypes, we compared the effects of a JAK2-specific (TG101348) with a less selective JAK1/2 (ruxolitinib) inhibitor on NK-cell activation and function. Ruxolitinib treatment completely blocked IL2, IL15, and DC-mediated STAT5 phosphorylation, along with the capacity of NK cells to secrete IFNγ or lyse NK cell– sensitive targets. Only NK-cell proliferation stimulated by monocyte-derived DCs (moDCs) resisted ruxolitinib treatment. In contrast, TG101348 treatment of stimulated NK cells resulted in far less functional compromise. TG101348 completely inhibited only soluble IL15-mediated STAT5 phosphorylation, which Langerhans-type DCs (LCs), presenting membrane-bound IL15 in trans, could salvage. These results demonstrate that ruxolitinib's nonselective inhibition of JAK1/2 results in profound NK-cell dysfunction by blocking downstream pSTAT5,hence providing a persuasive rationale for the development of selective JAK2 inhibitors for immunotherapeutic applications.

BackgroundMechanically ventilated patients in the intensive care unit (ICU) are unable to communicate verbally. We sought to evaluate their needs via a communication board (CB) and a novel eye tracking device (ETD) that verbalizes selections made by gazing.MethodsThis was a pilot prospective study conducted in a tertiary care surgical ICU. Continuously mechanically ventilated adult surgical ICU patients with a Richmond Agitation-Sedation Scale score of −1 to +1, without cognitive impairment, were eligible. We asked patients four yes-or-no questions to assess basic needs regarding presence of pain, need for endotracheal suction, satisfactory room temperature, and position comfort. Patients were then asked if there was anything else that they wanted to communicate. All responses were confirmed by head nodding.ResultsThe median accuracy of the CB (100% (IQR 100%–100%)) for basic needs communication (yes/no questions) was comparable with that of the ETD (100% (IQR 68.8%–100%); p=0.14) in the 12 enrolled patients. Notably, 83% of patients desired to communicate additional information, ranging from spiritual (eg, desire for prayer/chaplain), emotional (eg, frustration, desire for comfort), physical/environmental (eg, television), to physiological (eg, thirst/hunger) needs.DiscussionThe majority of patients desired to communicate something other than basic needs. Unless specifically assessed via an assistive communication device (eg, CB or ETD), some of these other needs would have been difficult to discern.Level of evidenceIV therapeutic care/management.

It has become increasingly clear that retrotransposons (RTEs) are more widely expressed in somatic tissues than previously appreciated. RTE expression has been implicated in a myriad of biological processes ranging from normal development and aging, to age related diseases such as cancer and neurodegeneration. Long Terminal Repeat (LTR)-RTEs are evolutionary ancestors to, and share many features with, exogenous retroviruses. In fact, many organisms contain endogenous retroviruses (ERVs) derived from exogenous retroviruses that integrated into the germ line. These ERVs are inherited in Mendelian fashion like RTEs, and some retain the ability to transmit between cells like viruses, while others develop the ability to act as RTEs. The process of evolutionary transition between LTR-RTE and retroviruses is thought to involve multiple steps by which the element loses or gains the ability to transmit copies between cells versus the ability to replicate intracellularly. But, typically, these two modes of transmission are incompatible because they require assembly in different sub-cellular compartments. Like murine IAP/IAP-E elements, the gypsy family of retroelements in arthropods appear to sit along this evolutionary transition. Indeed, there is some evidence that gypsy may exhibit retroviral properties. Given that gypsy elements have been found to actively mobilize in neurons and glial cells during normal aging and in models of neurodegeneration, this raises the question of whether gypsy replication in somatic cells occurs via intracellular retrotransposition, intercellular viral spread, or some combination of the two. These modes of replication in somatic tissues would have quite different biological implications. Here, we demonstrate that Drosophila gypsy is capable of both cell-associated and cell-free viral transmission between cultured S2 cells of somatic origin. Further, we demonstrate that the ability of gypsy to move between cells is dependent upon a functional copy of its viral envelope protein. This argues that the gypsy element has transitioned from an RTE into a functional endogenous retrovirus with the acquisition of its envelope gene. On the other hand, we also find that intracellular retrotransposition of the same genomic copy of gypsy can occur in the absence of the Env protein. Thus, gypsy exhibits both intracellular retrotransposition and intercellular viral transmission as modes of replicating its genome.