Research Spotlights April 2020

Research Spotlights April 2020

Controlling people’s movement altered the spread of COVID-19 in China

Worldwide, countries have enacted significant behavioral, clinical, and state interventions slow the COVID-19 epidemic. However, it remains unclear how interventions, such as restrictions on travel, affected COVID-19 spread in China. A global consortium of researchers supported by grants from the NIGMS, the Oxford Martin School, and the Republic of Ecuador conducted an epidemiological study to assess the impact of travel restrictions on the epidemic in China.

The researchers analyzed epidemiological data from China from December 1st, 2019 - February 10th, 2020, that was extracted individual level data from primarily official reports from provincial, municipal or national health governments. Data included basic demographics (age, sex), travel histories and key dates (dates of onset of symptoms, hospitalization). Total numbers of cases were matched with officially reported data from China and other government reports. Using a subset of these data they also assessed the proportion of symptomatic travelers, incubation period, and age and sex distributions. Real-time human mobility data was extracted from the Baidu Qianxi web platform, which presents daily population travels between cities or provinces tracked through the Baidu Huiyan system. Modeling was used to evaluate the effect of mobility and testing on COVID-19 epidemic dynamics.

The data indicated that local person-to-person transmission happened extensively early in the coronavirus outbreak and was mitigated by mobility control measures. However, due to an incubation period ranging from 5 to 14 days, the effects of the mobility restrictions on new cases was not apparent for over a week, with cases increasing in the 5-7 days immediately after the lockdown. Among cases reported outside Hubei, 515 cases had a known travel history to Wuhan and a symptom onset date before 31st January 2020, compared with only 39 after 31st January, illustrating the effect of travel restrictions in decreasing the spread to other Chinese provinces. Provinces outside Hubei that acted early to test, track and contain imported COVID-19 cases fared the best at preventing or containing local outbreaks. However, the benefits from both approaches took time to be seen due to asymptomatic transmission. These findings show that early in the COVID-19 outbreak travel restrictions were effective in preventing the import of infections from a known source. However, once the COVID-19 outbreak began to spread locally, a full package of measures including mobility restrictions, testing, tracing, and physical distancing need to work together to mitigate local spread.

Kraemer MUG, Yang C-H, Gutierrez B, Wu C-H, Klein B, Pigott DM, Open COVID-19 Data Working Group, Plessis L, Faria NR, Li R, Hanage WP, Brownstein JS, Layan M, Vespignani A, Tian H, Dye C, Pybus OG, Scarpino SV. 2020. The effect of human mobility and control measures on the COVID-19 epidemic in China. Science, DOI: 10.1126/science.abb4218,

New links between vaping, oral microbes, and infection

With the increased use of electronic cigarettes (e-cigarettes), understanding the potential health impacts of vaping has become a critical issue. Researchers supported by grants from the NIDCR, NCI, NIEHS, and New York University show that vaping changes the oral microbiome. Previous research has shown that changes in the oral microbiome due to environmental and host factors can contribute several health issues, including cavities, gum disease, halitosis, and medical conditions such as diabetes, cardiovascular disease, and some cancers. It has been established that smoking traditional cigarettes raises the risk of gum disease and infection by altering the oral cavity, leading to an environment which is favorable to infection-causing bacteria, however little is known how vaping e-cigarettes effect the oral microbiome and oral health.

In this study, the researchers examined e-cigarette vapor and its influence on the oral microbiome and immune health. To determine how vaping influences infection efficiency of oral pathogens they used a novel e-cigarette aerosol generating machine and measured pro-inflammatory immune mediators in pre-cancerous and cancer cell lines. Saliva samples and oral exams were obtained from study participants (n=119) that were in three groups (n=40 per group): e-cigarette users, regular cigarette smokers, and those who had never smoked. The e-cigarette and regular cigarette cohorts were 77-80% male, while the non-smoker cohort was 43.6% female. The microbial communities were profiled from the saliva samples using 16S rRNA high throughput sequencing.

Gum disease or infection was significantly higher among cigarette smokers (72.5%), followed by e-cigarette users (42.5%) and non-smokers (28.2%). There were also significant differences the microbial composition between the three cohorts. A complex cytokine network regulates the cross talk between periodontal pathogens and immune mediators. The altered microbiome in e-cigarette users influenced the local host immune environment, with e-cigarette users having elevated levels of the pro-inflammatory cytokines, Interleukin (IL)-6 and IL-1β, when compared with non-users. Additionally, the cell culture studies showed an upregulation of IL-6 after exposure to e-cigarette aerosols, that resulted in an elevated inflammatory response. The aerosols from e-cigarettes made the cells more susceptible to bacterial infection, indicating that e-cigarette may alter the user’s immune function. Together, these results indicate that vaping e-cigarettes alters the oral environment and raises the risk for oral inflammation and infection.

Pushalkar S, Paul B, Li Q, Yang J, Vasconcelos R, Makwana S, González JM, Shah S, Xie C, Janal MN, Queiroz E, Bederoff M, Leinwand J, Solarewicz J, Xu F, Aboseria E, Guo Y, Aguallo D, Gomez C, Kamer A, Shelley D, Aphinyanaphongs Y, Barber C, Gordon T, Corby P, Li X, Saxena D. 2020. Electronic Cigarette Aerosol Modulates the Oral Microbiome and Increases Risk of Infection, iScience, 27;23(3):100884. doi: 10.1016/j.isci.2020.100884

Researchers identify a consciousness “switch” in the brain

Consciousness is the capacity to experience your own environment and internal states, however minimal mechanisms that are needed for consciousness are unclear. Researchers supported by grants from the NIMH, ORIP, the U.S.-Israel Binational Science Foundation, and the Wisconsin National Primate Research Center have discovered an area deep in the brain that is sensitive to consciousness levels. Theories of consciousness emphasize the importance of recurrent activity and interaction between neurons. These interactions can take the form of communication between brain areas along feedforward and feedback pathways and intracolumnar (vertical circuits) communication within a cortical area. Feedforward pathways carry sensory information from superficial layers to superficial and middle layers of higher-order cortical areas, whereas feedback pathways carry priorities and predictions from deep layers to either superficial or deep layers of lower-order cortical areas. Previous studies have suggested that consciousness depends on large-scale thalamocortical and corticocortical interactions. In particular, the central lateral thalamus (CL) has been implicated in consciousness, since lesions of this area in humans has been associated with severe disruptions in consciousness, such as coma. The researchers hypothesized that CL, based on its location and connectivity in the brain, influences feedforward, feedback, and intracolumnar cortical processes to regulate information and as a result, consciousness.

The researchers simultaneously recorded electrophysiological activity from the CL and across layers of the frontoparietal cortex in macaques during three states of conscientiousness (Macaca mulatta, 4.3-5.5 years old males, n=2). To compare the different states of consciousness, they acquired electrophysiological data from both awake and anesthetized monkeys during a passive auditory oddball paradigm as well as during a “resting state” which had no sensory stimuli. The passive auditory oddball paradigm is an auditory stimulation which consists of a series of beeps interspersed with other random sounds. As a control, recordings were collected in awake monkeys during a visual fixation task and during the passive auditory oddball paradigm while the monkey also maintained fixation. To manipulate consciousness and show causality they stimulated the CL in anesthetized macaques. The activity in the CL was coupled with brain activity recordings in the cortex.

They found that neurons in thalamus and deep cortical layers are most sensitive to changes in consciousness level, this was similar across different types of anesthetics and sleep. Deep-layer activity is sustained by interactions with the CL. Consciousness also depends on deep-layer neurons providing feedback to superficial layers indicating that long-range feedback and intracolumnar signaling are important. When anesthetized macaques received stimulation to the CL it restored arousal and wake-like neural processing. These findings suggest layer-specific thalamocortical correlates of consciousness. These results may help to inform how targeted deep brain stimulation can alleviate disorders of consciousness.

Redinbaugh MJ, Phillips JM, Kambi NA, Mohanta S, Andryk S, Dooley GL, Afrasiabi M, Raz A, Saalmann YB. 2020 Thalamus Modulates Consciousness via Layer-Specific Control of Cortex, Neuron, 106:1, 66-75.e12

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