Key Points Question Does COVID-19 convalescent plasma (CCP), compared with placebo, improve the clinical status of hospitalized patients with COVID-19 requiring noninvasive supplemental oxygen? Findings In this randomized clinical trial including 941 patients, based on the World Health Organization 11-point Ordinal Scale for Clinical Improvement, CCP did not benefit 468 participants randomized to CCP compared with 473 randomized to placebo from April 2020 to March 2021. However, in exploratory analyses, CCP appeared to benefit those enrolled from April to June 2020, the period when most participants received high-titer CCP and were not receiving remdesivir and corticosteroids at randomization. Meaning In this trial, CCP did not meet prespecified outcomes for efficacy, but high-titer CCP may have benefited hospitalized patients with COVID-19 early in the pandemic when other treatments were not in use, suggesting a heterogenous treatment effect over time.

In human immunodeficiency virus-1 (HIV) infected individuals, substance abuse may accelerate the development and/or increase the severity of HIV associated neurocognitive disorders (HAND). It is proposed that CD14+CD16+ monocytes mediate HIV entry into the central nervous system (CNS) and that uninfected and infected CD14+CD16+ monocyte transmigration across the blood brain barrier (BBB) contributes to the establishment and propagation of CNS HIV viral reservoirs and chronic neuroinflammation, important factors in the development of HAND. The effects of substance abuse on the frequency of CD14+CD16+ monocytes in the peripheral circulation and on the entry of these cells into the CNS during HIV neuropathogenesis are not known. PBMC from HIV infected individuals were analyzed by flow cytometry and we demonstrate that the frequency of peripheral blood CD14+CD16+ monocytes in HIV infected substance abusers is increased when compared to those without active substance use. Since drug use elevates extracellular dopamine concentrations in the CNS, we examined the effects of dopamine on CD14+CD16+ monocyte transmigration across our in vitro model of the human BBB. The transmigration of this monocyte subpopulation is increased by dopamine and the dopamine receptor agonist, SKF 38393, implicating D1-like dopamine receptors in the increase in transmigration elicited by this neurotransmitter. Thus, elevated extracellular CNS dopamine may be a novel common mechanism by which active substance use increases uninfected and HIV infected CD14+CD16+ monocyte transmigration across the BBB. The influx of these cells into the CNS may increase viral seeding and neuroinflammation, contributing to the development of HIV associated neurocognitive impairments.

The blacklegged tick (Ixodes scapularis) is an important vector of emerging human pathogens. It has three blood-feeding stages, as follows: larva, nymph, and adult. Owing to inefficient transovarial transmission, at least for the Lyme disease agent (Borrelia burgdorferi), larval ticks rarely hatch infected, but they can acquire infection during their larval blood meal. Nymphal ticks are primarily responsible for transmitting pathogens to hosts, including humans. The transition from uninfected host-seeking larva to infectious host-seeking nymph is therefore a key aspect of human risk of infection. It can be divided into a series of steps, as follows: finding a host, taking a blood meal, becoming infected, molting, and overwintering. The chance of succeeding in each of these steps may depend on the species identity of the blood meal host. We used a Bayesian method to estimate the molting success of larval I. scapularis collected from four commonly parasitized species of birds and eight commonly parasitized small and mid-sized mammals found in the forests of Dutchess County, New York. We show that molting success varies substantially among host species; white-footed mice, veeries, and gray catbirds support particularly high molting success, whereas ticks feeding on short-tailed shrews, robins, and wood thrushes were less successful. We also show that larval molting success varies substantially between individual blood meal hosts, and that this intraspecific variability is much higher in some species than in others. The causes of both inter- and intraspecific variation in molting success remain to be determined.

Antiretroviral drugs have dramatically improved the morbidity and mortality of people living with HIV (PLWH). While current antiretroviral therapy (ART) regimens are generally well-tolerated, risks for side effects and toxicity remain as PLWH must take life-long medications. Antiretroviral drugs impact autophagy, an intracellular proteolytic process that eliminates debris and foreign material, provides nutrients for metabolism, and performs quality control to maintain cell homeostasis. Toxicity and adverse events associated with antiretrovirals may be due, in part, to their impacts on autophagy. A more complete understanding of the effects on autophagy is essential for developing antiretroviral drugs with decreased off target effects, meaning those unrelated to viral suppression, to minimize toxicity for PLWH. This review summarizes the findings and highlights the gaps in our knowledge of the impacts of antiretroviral drugs on autophagy.