Editors' ChoiceQUARTERLY PICKS

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Science Translational Medicine  16 Dec 2020:
Vol. 12, Issue 574, eabg0485
DOI: 10.1126/scitranslmed.abg0485

Abstract

Four times a year, the Science Translational Medicine editors select recently published articles across the Science family of journals and highlight interesting translational ties. These short write-ups identify common links between disparate diseases; technologies and research approaches that could prove complementary; and biomedical insights that may inform therapies or treatments. This quarter’s articles cover flexible biosensors, SARS-CoV-2 transmission from a genomics perspective, advances in CAR T cell engineering, the intestinal microbiome, the host immune response to SARS-CoV-2, and strategies for treating infectious diseases.

CORONAVIRUS

SARS-CoV-2 and the host antibody response

The robustness and the types of antibodies involved in host antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes coronavirus disease 2019 (COVID-19), remain unclear. Wajnberg et al. report in Science their analysis of more than 30,000 individuals infected with SARS-CoV-2. Individuals with mild or moderate COVID-19 disease showed a robust IgG response against the viral spike protein and neutralizing antibody titers could be detected for up to 5 months. Delving into the antibody types involved, Sterlin et al. and Wang et al. reveal in Science Translational Medicine a key role for secretory IgA antibody. Examining serum, saliva and bronchoalveolar fluid samples from 159 patients with COVID-19, Sterlin et al. found that IgA predominated during the early humoral response, peaking 3 weeks after infection. Meanwhile, analyzing a cohort of 149 patients convalescing from COVID-19, Wang et al. observed that IgA dimers were 15 times more potent than IgA monomers at neutralizing SARS-CoV-2. Together these three studies confirm the importance of antibody responses to SARS-CoV-2 infection and suggest that they are more robust and persist for longer than previously appreciated. —OS

INFECTIOUS DISEASE

Antimicrobials in action

Microorganism resistance to existing treatments is an increasing problem worldwide. In three recent articles, authors have repurposed or re-dosed existing drugs to improve the sensitivity of difficult-to-treat microbes to therapy. Vinayak et al. successfully applied bicyclic azetidines, which have been shown to be effective against the malaria parasite, for the treatment of Cryptosporidium infection in mice, while De Oliveira et al. repurposed the neurodegenerative disease drug PBT2 to sensitize resistant Gram-negative bacteria to polymyxin antibiotics for the treatment of sepsis. Lastly Bustamante and colleagues showed that a higher dose of benznidazole, given weekly rather than daily over a much longer time period, could kill both active and dormant Trypanosoma cruzi, the parasite that causes Chagas disease, in several mouse models. These articles highlight the gains being made in the fight against resistant infectious organisms. —MN

BIOSENSORS

Flexible under pressure

Soft, thin electronic sensors that can conform to the skin are demonstrating increasing utility in biomedical applications. Toward improving fit of prosthetic sockets, Kwak et al. developed wireless sensors to measure pressure and temperature at the interface between residual limb and prosthesis for lower-limb amputees. Two other recent studies used biosensors to focus on touch: Lee et al. electrospun polymer-gold nanomesh sensors that measured the force participants used to grasp objects without interfering with fingertip sensation of the objects, while Cai and colleagues fabricated a stretchable electronic skin sensor system from nanoparticle-polymer hydrogel, nanosheets, and nanowires that detected tactile pressure and stretching. These three examples highlight the versatility of flexible electronics for human-device interfaces. —CC

CANCER

Pressing the CAR T cell accelerator

Chimeric antigen receptor (CAR) T cells have revolutionized treatment of hematological cancer. However, traditional CAR T cells have not been nearly as successful at treating solid tumors. To address this problem, Ding et al. and Hao et al. further modified CAR T cells to improve their functionality. Ding et al. included a constitutively active version of STAT5 in their CAR T cell construct, which enhanced CAR T cell killing of lymphoma tumors. Using another strategy, Hao et al. anchored a metabolism-modulating drug, avasimibe, to CAR T cells to increase cholesterol in the T cell membrane. This led to sustained activation of CAR T cells and control of melanoma and glioma tumors. Together, these studies demonstrate that the next advance in CAR T cell engineering might be achieved by giving the cells a tune-up. —CM

INTESTINAL MICROBIOME

Selecting intestinal guests

Commensal bacteria living in our gut form what’s called the intestinal microbiome. Three studies published recently investigated endogenous and external factors affecting the intestinal microbiome and how this might impact general health. Roslund et al. showed that changing surface soil in a daycare yard altered intestinal and skin microbiome, and consequently immune responses, in children. Bergstrom et al. reported that production of mucus in the colon is critical for regulating host-microbiota symbiosis, whereas Khan et al. revealed that simple sugar-enriched diet promoted formation of mucus-degrading bacteria and development of colitis in mice. These studies highlight how endogenous mechanisms, environment and lifestyle contribute to determining gut health by modulating our intestinal guests. —MM

CORONAVIRUS

Genomic SARS-CoV-2 sleuthing

The early spread of SARS-CoV-2 was elusive in real time. However, genome sequence analysis of collected viral samples coupled with clinical or contact tracing data has allowed reconstruction of essential features of the virus’s initial spread after the fact. From similarities in viral mutational profiles, Bedford et al. determined that a single event introduced SARS-CoV-2 into Washington state from China. Popa et al. analyzed SARS-CoV-2 mutations to track the tourism-driven spread of the virus within and beyond Austria, finding genetic evidence of ongoing allele fixation and the viral transmission bottleneck size. Worobey et al. report that initial introductions of SARS-CoV-2 to Germany and the United States were halted by successful public health interventions that were unappreciated at the time, before eventual viral reintroduction and spread. These studies show how viral genomic epidemiology can aid understanding of SARS-CoV-2 transmission and may have public health control ramifications. —CAC

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