Virome-wide detection of natural infection events and the associated antibody dynamics using longitudinal highly-multiplexed serology.

Current methods for detecting infections either require a sample collected from an actively infected site, are limited in the number of agents they can query, and/or yield no information on the immune response. Here we present an approach that uses temporally coordinated changes in highly-multiplexed antibody measurements from longitudinal blood samples to monitor infection events at sub-species resolution across the human virome. In a longitudinally-sampled cohort of South African adolescents representing >100 person-years, we identify >650 events across 48 virus species and observe strong epidemic effects, including high-incidence waves of Aichivirus A and the D68 subtype of Enterovirus D earlier than their widespread circulation was appreciated. In separate cohorts of adults who were sampled at higher frequency using self-collected dried blood spots, we show that such events temporally correlate with symptoms and transient inflammatory biomarker elevations, and observe the responding antibodies to persist for periods ranging from ≤1 week to >5 years. Our approach generates a rich view of viral/host dynamics, supporting novel studies in immunology and epidemiology.

Enumerating contributions of fentanyls and other factors to the unprecedented 2020 rise in opioid overdose deaths: model-based analysis.

In 2020, the ongoing US opioid overdose crisis collided with the emerging COVID-19 pandemic. Opioid overdose deaths (OODs) rose an unprecedented 38%, due to a combination of COVID-19 disrupting services essential to people who use drugs, continued increases in fentanyls in the illicit drug supply, and other factors. How much did these factors contribute to increased OODs? We used a validated simulation model of the opioid overdose crisis, SOURCE, to estimate excess OODs in 2020 and the distribution of that excess attributable to various factors. Factors affecting OODs that could have been disrupted by COVID-19, and for which data were available, included opioid prescribing, naloxone distribution, and receipt of medications for opioid use disorder. We also accounted for fentanyls' presence in the heroin supply. We estimated a total of 18,276 potential excess OODs, including 1,792 lives saved due to increases in buprenorphine receipt and naloxone distribution and decreases in opioid prescribing. Critically, growth in fentanyls drove 43% (7,879) of the excess OODs. A further 8% is attributable to first-ever declines in methadone maintenance treatment and extended-released injectable naltrexone treatment, most likely due to COVID-19-related disruptions. In all, 49% of potential excess OODs remain unexplained, at least some of which are likely due to additional COVID-19-related disruptions. While the confluence of various COVID-19-related factors could have been responsible for more than half of excess OODs, fentanyls continued to play a singular role in excess OODs, highlighting the urgency of mitigating their effects on overdoses.

Assessing the potential anti-neuroinflammatory effect of minocycline in chronic low back pain: Protocol for a randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Both preclinical studies, and more recent clinical imaging studies, suggest that glia-mediated neuroinflammation may be implicated in chronic pain, and therefore might be a potential treatment target. However, it is currently unknown whether modulating neuroinflammation effectively alleviates pain in humans. This trial tests the hypothesis that minocycline, an FDA-approved tetracycline antibiotic and effective glial cell inhibitor in animals, reduces neuroinflammation and may reduce pain symptoms in humans with chronic low back pain. METHODS AND ANALYSIS: This study is a randomized, double-blind, placebo-controlled clinical trial. Subjects, aged 18-75, with a confirmed diagnosis of chronic (≥ six months) low back pain (cLBP) and a self-reported pain rating of at least four out of ten (for at least half of the days during an average week) are enrolled via written, informed consent. Eligible subjects are randomized to receive a 14-day course of either active drug (minocycline) or placebo. Before and after treatment, subjects are scanned with integrated Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) using [11C]PBR28, a second-generation radiotracer for the 18 kDa translocator protein (TSPO), which is highly expressed in glial cells and thus a putative marker of neuroinflammation. Pain levels are evaluated via daily surveys, collected seven days prior to the start of medication, and throughout the 14 days of treatment. General linear models will be used to assess pain levels and determine the treatment effect on brain (and spinal cord) TSPO signal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT03106740).

Use of provider-to-provider telemedicine in Kenya during the COVID-19 pandemic.

Introduction: According to the World Health Organization (WHO), about 90 percent of countries continue to report COVID-related disruptions to their health systems. The use of telemedicine has been especially common among high-income countries to safely deliver and access health services where enabling infrastructure like broadband connectivity is more widely available than low- and middle-income countries (LMICs). The Addis Clinic implements a provider-to-provider (P2P) asynchronous telemedicine model in Kenya. We sought to examine the use of the P2P telemedicine platform during the second year of COVID-19. Methods: To assess sustainability, we compared the data for two 12-month calendar periods (period A = year 2020, and period B = year 2021). To examine performance, we compared the data for two different 12-month periods (period C = pandemic period of February 2021 to January 2022, and period D = baseline period of February 2019 to January 2020). Results: Sustainability of the P2P telemedicine platform was maintained during the pandemic with increased activity levels from 2,604 cases in 2020 to 3,525 cases in 2021. There was an average of 82 specialists and 5.9 coordinators during 2020, and an average of 81 specialists and 6.0 coordinators during 2021. During 2020, there were 444 cases per coordinator, and 587 cases per coordinator in 2021(P = 0.078). During 2020, there were 32 cases per specialist, and 43 cases per specialist in 2021(P = 0.068). Performance decreased with 99 percent of cases flagged as "answered" during the baseline period (period D), and 75 percent of cases flagged as "answered" during the pandemic period (period C). Conclusion: Results suggest that despite a decline in certain sustainability and performance indicators, The Addis Clinic was able to sustain a very high level of activity during the second year of the pandemic, as shown by the continued use of the system. Furthermore, despite some of the infrastructure challenges present in LMICs, the P2P telemedicine platform was a viable option for receiving clinical recommendations from medical experts located remotely. As health systems in LMICs grapple with the effects of the pandemic, it is worthwhile to consider the use of telemedicine to deliver essential health services.

The COVID-19 pandemic behind bars: Experimental evidence showing higher support for decarceration when framed as risk to correctional staff.

This study examined the effect of framing COVID-19 spread in correctional facilities as impacting imprisoned individuals or impacting correctional staff on public support for decarceration. I employed an experiment in the 2021 Empire State Poll (n = 765) in which participants were randomly assigned to a treatment condition, which highlighted information about the number of COVID-19 cases among imprisoned individuals, or a control condition, which highlighted correctional staff instead. Participants reported how supportive or unsupportive they are of releasing imprisoned individuals to curb the spread of COVID-19. Overall, 35% of New Yorkers supported decarceration. A higher percentage of respondents supported decarceration when the impact on correctional staff was highlighted (40%) relative to imprisoned individuals (31%). There was also higher support among non-Hispanic Black (54%) and Hispanic (51%) participants relative to non-Hispanic White (28%) participants. Within racial/ethnic groups support for decarceration was higher when the impact on correctional staff was highlighted among non-Hispanic Whites, Hispanics, and those of another race, but not among non-Hispanic Blacks where support for decarceration was higher when the impact on imprisoned individuals was highlighted. Inferential analysis using log binomial regression found that the association between treatment condition assignment and support for decarceration was not significant. Public health practitioners and policy makers should consider leveraging the higher support associated with concerns over the health and wellbeing of correction staff found among some racial/ethnic groups to fight the COVID-19 pandemic.

A Comparison of Distance and On-Campus Learning Models to Prepare Teachers of Students With Visual Impairments

Introduction Since the 1970s, many universities and agencies have prepared professionals in visual impairment through distance educational approaches, including concentrated off-campus courses, video and telephone connections, and synchronous or asynchronous online methods. Although online professional preparation in visual impairment has become common, there is little data that compares outcomes of on-campus instruction with distance education methods. This article reports follow-up data from a federally funded graduate university program that prepares teachers of students with visual impairments: It compares results from a survey that describes how on-campus and distance education students perceived the quality of their preparation. Methods An online survey was sent to 37 bachelor's degree students who had earned certification as teachers of students with visual impairments. 27 students returned usable surveys, in which they reported relevant demographic information and current job roles. The survey included 13 demographic questions about employment and setting. Eight questions related to general evaluation of their preparation program, and 22 questions related to perceived competence in skills needed to prepare teachers of students with visual impairments. Results There were few differences between perceptions of students who were prepared in the full-time on-campus model and those who were prepared through distance education. Most respondents were graduates working as itinerant teachers in public schools or specialized school settings. With regard to perceptions of their own skills related to visual impairment, only the item on assistive technology showed a significant difference between the two models. Students in distance education perceived themselves as less well prepared in that area. Discussion Given the increased shift toward distance learning caused by the COVID-19 virus, the authors suggest that a broad-based national study of outcomes related to distance learning in visual impairment might offer more detailed insights into the quality of teaching produced through distance learning.

High-Throughput COVID-19 Testing of Naso-Oropharyngeal Swabs Using a Sensitive Extraction-Free Sample Preparation Method.

High-throughput diagnostic assays are required for large-scale population testing for severe acute respiratory coronavirus 2 (SARS-CoV-2). The gold standard technique for SARS-CoV-2 detection in nasopharyngeal swab specimens is nucleic acid extraction followed by real-time reverse transcription-PCR. Two high-throughput commercial extraction and detection systems are used routinely in our laboratory: the Roche cobas SARS-CoV-2 assay (cobas) and the Roche MagNA Pure 96 system combined with the SpeeDx PlexPCR SARS-CoV-2 assay (Plex). As an alternative to more costly instrumentation, or tedious sample pooling to increase throughput, we developed a high-throughput extraction-free sample preparation method for naso-oropharyngeal swabs using the PlexPCR SARS-CoV-2 assay (Direct). A collection of SARS-CoV-2-positive (n = 185) and -negative (n = 354) naso-oropharyngeal swabs in transport medium were tested in parallel to compare Plex to Direct. The overall agreement comparing the qualitative outcomes was 99.3%. The mean cycle of quantification (Cq) increase and corresponding mean reduction in viral load for Direct ORF1ab and RdRp compared to Plex was 3.11 Cq (-0.91 log10 IU/mL) and 4.78 Cq (-1.35 log10 IU/mL), respectively. We also compared Direct to a four-sample pool by combining each positive sample (n = 185) with three SARS-CoV-2-negative samples extracted with MagNA Pure 96 and tested with the PlexPCR SARS-CoV-2 assay (Pool). Although less sensitive than Plex or Pool, the Direct method is a sufficiently sensitive and viable approach to increase our throughput by 12,032 results per day. Combining cobas, Plex, and Direct, an overall throughput of 19,364 results can be achieved in a 24-h period. IMPORTANCE Laboratories have experienced extraordinary demand globally for reagents, consumables, and instrumentation, while facing unprecedented testing demand needed for the diagnosis of SARS-CoV-2 infection. A major bottleneck in testing throughput is the purification of viral RNA. Extraction-based methods provide the greatest yield and purity of RNA for downstream PCR. However, these techniques are expensive, time-consuming, and depend on commercial availability of consumables. Extraction-free methods offer an accessible and cost-effective alternative for sample preparation. However, extraction-free methods often lack sensitivity compared to extraction-based methods. We describe a sensitive extraction-free protocol based on a simple purification step using a chelating resin, combined with proteinase K and thermal treatment. We compare the sensitivity qualitatively and quantitatively to a well-known commercial extraction-based system, using a PCR assay calibrated to the 1st WHO international standard for SARS-CoV-2 RNA. This method entails high throughput and is suitable for all laboratories, particularly in jurisdictions where access to instrumentation and reagents is problematic.

Modeling the systemic risks of COVID-19 on the wildland firefighting workforce.

Wildfire management in the US relies on a complex nationwide network of shared resources that are allocated based on regional need. While this network bolsters firefighting capacity, it may also provide pathways for transmission of infectious diseases between fire sites. In this manuscript, we review a first attempt at building an epidemiological model adapted to the interconnected fire system, with the aims of supporting prevention and mitigation efforts along with understanding potential impacts to workforce capacity. Specifically, we developed an agent-based model of COVID-19 built on historical wildland fire assignments using detailed dispatch data from 2016-2018, which form a network of firefighters dispersed spatially and temporally across the US. We used this model to simulate SARS-CoV-2 transmission under several intervention scenarios including vaccination and social distancing. We found vaccination and social distancing are effective at reducing transmission at fire incidents. Under a scenario assuming High Compliance with recommended mitigations (including vaccination), infection rates, number of outbreaks, and worker days missed are effectively negligible, suggesting the recommended interventions could successfully mitigate the risk of cascading infections between fires. Under a contrasting Low Compliance scenario, it is possible for cascading outbreaks to emerge leading to relatively high numbers of worker days missed. As the model was built in 2021 before the emergence of the Delta and Omicron variants, the modeled viral parameters and isolation/quarantine policies may have less relevance to 2022, but nevertheless underscore the importance of following basic prevention and mitigation guidance. This work could set the foundation for future modeling efforts focused on mitigating spread of infectious disease at wildland fire incidents to manage both the health of fire personnel and system capacity.

COVID-19 vaccination elicits an evolving, cross-reactive antibody response to epitopes conserved with endemic coronavirus spike proteins.

The COVID-19 pandemic has triggered the first widespread vaccination campaign against a coronavirus. Many vaccinated subjects are previously naive to SARS-CoV-2; however, almost all have previously encountered other coronaviruses (CoVs), and the role of this immunity in shaping the vaccine response remains uncharacterized. Here, we use longitudinal samples and highly multiplexed serology to identify mRNA-1273 vaccine-induced antibody responses against a range of CoV Spike epitopes, in both phylogenetically conserved and non-conserved regions. Whereas reactivity to SARS-CoV-2 epitopes shows a delayed but progressive increase following vaccination, we observe distinct kinetics for the endemic CoV homologs at conserved sites in Spike S2: these become detectable sooner and decay at later time points. Using homolog-specific antibody depletion and alanine-substitution experiments, we show that these distinct trajectories reflect an evolving cross-reactive response that can distinguish rare, polymorphic residues within these epitopes. Our results reveal mechanisms for the formation of antibodies with broad reactivity against CoVs.

Breast Biopsy Recommendations and Breast Cancers Diagnosed during the COVID-19 Pandemic.

Background The COVID-19 pandemic reduced mammography use, potentially delaying breast cancer diagnoses. Purpose To examine breast biopsy recommendations and breast cancers diagnosed before and during the COVID-19 pandemic by mode of detection (screen detected vs symptomatic) and women's characteristics. Materials and Methods In this secondary analysis of prospectively collected data, monthly breast biopsy recommendations after mammography, US, or both with subsequent biopsy performed were examined from 66 facilities of the Breast Cancer Surveillance Consortium between January 2019 and September 2020. The number of monthly and cumulative biopsies recommended and performed and the number of subsequent cancers diagnosed during the pandemic period (March 2020 to September 2020) were compared with data from the prepandemic period using Wald χ2 tests. Analyses were stratified by mode of detection and race or ethnicity. Results From January 2019 to September 2020, 17 728 biopsies were recommended and performed, with 6009 cancers diagnosed. From March to September 2020, there were substantially fewer breast biopsy recommendations with cancer diagnoses when compared with the same period in 2019 (1650 recommendations in 2020 vs 2171 recommendations in 2019 [24% fewer], P < .001), predominantly due to fewer screen-detected cancers (722 cancers in 2020 vs 1169 cancers in 2019 [38% fewer], P < .001) versus symptomatic cancers (895 cancers in 2020 vs 965 cancers in 2019 [7% fewer], P = .27). The decrease in cancer diagnoses was largest in Asian (67 diagnoses in 2020 vs 142 diagnoses in 2019 [53% fewer], P = .06) and Hispanic (82 diagnoses in 2020 vs 145 diagnoses in 2019 [43% fewer], P = .13) women, followed by Black women (210 diagnoses in 2020 vs 287 diagnoses in 2019 [27% fewer], P = .21). The decrease was smallest in non-Hispanic White women (1128 diagnoses in 2020 vs 1357 diagnoses in 2019 [17% fewer], P = .09). Conclusion There were substantially fewer breast biopsies with cancer diagnoses during the COVID-19 pandemic from March to September 2020 compared with the same period in 2019, with Asian and Hispanic women experiencing the largest declines, followed by Black women. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Heller in this issue.

A Historical Perspective to Inform Strategic Planning for 2020 End-of-Year Wildland Fire Response Efforts

A severe outbreak of wildfire across the US Pacific Coast during August 2020 led to persistent fire activity through the end of summer. In late September, Fire Weather Outlooks predicted higher than usual fire activity into the winter in parts of California, with concomitant elevated fire danger in the Southeastern US. To help inform the regional and national allocation of firefighting personnel and equipment, we developed visualizations of resource use during recent late season, high-demand analogs. Our visualizations provided an overview of the crew, engine, dozer, aerial resource, and incident management team usage by geographic area. While these visualizations afforded information that managers needed to support their decisions regarding resource allocation, they also revealed a potentially significant gap between resource demand and late-season availability that is only likely to increase over time due to lengthening fire seasons. This gap highlights the need for the increased assessment of suppression resource acquisition and allocation systems that, to date, have been poorly studied.

Opioid overdose decedent characteristics during COVID-19.

INTRODUCTION: Alongside the emergence of COVID-19 in the United States, several reports highlighted increasing rates of opioid overdose from preliminary data. Yet, little is known about how state-level opioid overdose death trends and decedent characteristics have evolved using official death records. METHODS: We requested vital statistics data from 2018-2020 from all 50 states and the District of Columbia, receiving data from 14 states. Accounting for COVID-19, we excluded states without data past March 2020, leaving 11 states for analysis. We defined state-specific analysis periods from March 13 until the latest reliable date in each state's data, then conducted retrospective year-over-year analyses comparing opioid-related overdose death rates, the presence of specific opioids and other psychoactive substances, and decedents' sex, race, and age from 2020 to 2019 and 2019 to 2018 within each state's analysis period. We assessed whether significant changes in 2020 vs. 2019 in opioid overdose deaths were new or continuing trends using joinpoint regression. RESULTS: We found significant increases in opioid-related overdose death rates in Alaska (55.3%), Colorado (80.2%), Indiana (40.1%), Nevada (50.0%), North Carolina (30.5%), Rhode Island (29.6%), and Virginia (66.4%) - all continuing previous trends. Increases in synthetic opioid-involved overdose deaths were new in Alaska (136.5%), Indiana (27.6%), and Virginia (16.5%), whilst continuing in Colorado (44.4%), Connecticut (3.6%), Nevada (75.0%), and North Carolina (14.6%). We found new increases in male decedents in Indiana (12.0%), and continuing increases in Colorado (15.2%). We also found continuing increases in Black non-Hispanic decedents in Massachusetts (43.9%) and Virginia (33.7%). CONCLUSION: This research analyzes vital statistics data from 11 states, highlighting new trends in opioid overdose deaths and decedent characteristics across 10 of these states. These findings can inform state-specific public health interventions and highlight the need for timely and comprehensive fatal opioid overdose data, especially amidst concurrent crises such as COVID-19. Key messages:Our results highlight shifts in opioid overdose trends during the COVID-19 pandemic that cannot otherwise be extracted from aggregated or provisional opioid overdose death data such as those published by the Centres for Disease Control and Prevention.Fentanyl and other synthetic opioids continue to drive increases in fatal overdoses, making it difficult to separate these trends from any possible COVID-19-related factors.Black non-Hispanic people are making up an increasing proportion of opioid overdose deaths in some states.State-specific limitations and variations in data-reporting for vital statistics make it challenging to acquire and analyse up-to-date data on opioid-related overdose deaths. More timely and comprehensive data are needed to generate broader insights on the nature of the intersecting opioid and COVID-19 crises.

The pandemic brain: Neuroinflammation in non-infected individuals during the COVID-19 pandemic.

While COVID-19 research has seen an explosion in the literature, the impact of pandemic-related societal and lifestyle disruptions on brain health among the uninfected remains underexplored. However, a global increase in the prevalence of fatigue, brain fog, depression and other "sickness behavior"-like symptoms implicates a possible dysregulation in neuroimmune mechanisms even among those never infected by the virus. We compared fifty-seven 'Pre-Pandemic' and fifteen 'Pandemic' datasets from individuals originally enrolled as control subjects for various completed, or ongoing, research studies available in our records, with a confirmed negative test for SARS-CoV-2 antibodies. We used a combination of multimodal molecular brain imaging (simultaneous positron emission tomography / magnetic resonance spectroscopy), behavioral measurements, imaging transcriptomics and serum testing to uncover links between pandemic-related stressors and neuroinflammation. Healthy individuals examined after the enforcement of 2020 lockdown/stay-at-home measures demonstrated elevated brain levels of two independent neuroinflammatory markers (the 18 kDa translocator protein, TSPO, and myoinositol) compared to pre-lockdown subjects. The serum levels of two inflammatory markers (interleukin-16 and monocyte chemoattractant protein-1) were also elevated, although these effects did not reach statistical significance after correcting for multiple comparisons. Subjects endorsing higher symptom burden showed higher TSPO signal in the hippocampus (mood alteration, mental fatigue), intraparietal sulcus and precuneus (physical fatigue), compared to those reporting little/no symptoms. Post-lockdown TSPO signal changes were spatially aligned with the constitutive expression of several genes involved in immune/neuroimmune functions. This work implicates neuroimmune activation as a possible mechanism underlying the non-virally-mediated symptoms experienced by many during the COVID-19 pandemic. Future studies will be needed to corroborate and further interpret these preliminary findings.

COVID-19 vaccination recruits and matures cross-reactive antibodies to conserved epitopes in endemic coronavirus Spike proteins (preprint)

The COVID-19 pandemic has triggered the first widespread vaccination campaign against a coronavirus. Most vaccinated subjects are na ve to SARS-CoV-2, however almost all have previously encountered other coronaviruses (CoVs) and the role of this immunity in shaping the vaccine response remains uncharacterized. Here we use longitudinal samples and highly-multiplexed serology to identify mRNA-1273 vaccine-induced antibody responses against a range of CoV Spike epitopes and in both phylogenetically conserved and non-conserved regions. Whereas reactivity to SARS-CoV-2 epitopes showed a delayed but progressive increase following vaccination, we observed distinct kinetics for the endemic CoV homologs at two conserved sites in Spike S2: these became detectable sooner, and decayed at later timepoints. Using homolog-specific depletion and alanine-substitution experiments, we show that these distinctly-evolving specificities result from cross-reactive antibodies as they mature against rare, polymorphic residues within these epitopes. Our results reveal mechanisms for the formation of antibodies with broad reactivity against CoVs.

Telehealth is here to stay but not without challenges: a consultation of cardiac rehabilitation clinicians during COVID-19 in Victoria, Australia.

AIMS: Delivery of cardiac rehabilitation (CR) was challenged during the pandemic caused by the Coronavirus disease (COVID-19), due to government stay-at-home directives which restricted in-person programmes. The Australian state of Victoria experienced the longest and most severe COVID-19 restrictions and was in lockdown for ∼6 months of 2020. We aimed to explore (i) clinicians' experiences and perceptions and (ii) identify barriers and enablers, for delivering CR during the COVID-19 pandemic. METHODS AND RESULTS: Victorian members of the Australian Cardiovascular Health and Rehabilitation Association (ACRA) were invited to attend an exploratory qualitative online consultation in November 2020. An inductive thematic analysis was undertaken, before deductively applying the Non-adoption, Abandonment, Scale-up, Spread, and Sustainability (NASSS) framework to identify barriers and enablers for technology adoption in CR. Thirty members participated in a 106-min consultation. Seventeen members who provided demographics represented multiple disciplines (nursing n = 13, exercise physiology n = 3, and physiotherapy n = 1) and geographical settings (metropolitan n = 10, regional n = 4, and rural n = 3). Four main themes were inductively identified: consequences of change; use of technology; capacity; and the way forward. The deductive NASSS analysis demonstrated the main challenges of continuing remotely delivered CR lie with adopters (staff, patients, and carers) and with organizations. CONCLUSION: The COVID-19 pandemic expedited significant changes to CR delivery models. While clinicians are eager to retain technology-enabled delivery in addition to resuming in-person CR, it is now timely to review remote models of care, tools used and plan how they will be integrated with traditional in-person programmes.

Normalization of SARS-CoV-2 viral load via RT-qPCR provides higher-resolution data for comparison across time and between patients.

The 2020 pandemic has transformed the world and elicited thousands of studies to better understand the SARS-CoV-2 virus. Viral load has been a common measure to monitor treatment therapies and associate viral dynamics with patient outcomes; however, methods associated with viral load have varied across studies. These variations have the potential to sacrifice the accuracy of findings as they often do not account for inter-assay variation or variation across samples. In a retrospective study of nasopharyngeal samples, we found a significant amount of variation within the DNA and RNA targets; for example, across time within a single patient, there was an average of a 32-fold change. Further, we explore the impacts of host normalization on 94 clinical samples using the TGen Quantitative SARS-CoV-2 assay, finding that without host normalization samples with the same viral concentration can have up to 100-fold variation in the viral load.

Paranoia and belief updating during a crisis.

The 2019 coronavirus (COVID-19) pandemic has made the world seem unpredictable. During such crises we can experience concerns that others might be against us, culminating perhaps in paranoid conspiracy theories. Here, we investigate paranoia and belief updating in an online sample (N=1,010) in the United States of America (U.S.A). We demonstrate the pandemic increased individuals' self-rated paranoia and rendered their task-based belief updating more erratic. Local lockdown and reopening policies, as well as culture more broadly, markedly influenced participants' belief-updating: an early and sustained lockdown rendered people's belief updating less capricious. Masks are clearly an effective public health measure against COVID-19. However, state-mandated mask wearing increased paranoia and induced more erratic behaviour. Remarkably, this was most evident in those states where adherence to mask wearing rules was poor but where rule following is typically more common. This paranoia may explain the lack of compliance with this simple and effective countermeasure. Computational analyses of participant behaviour suggested that people with higher paranoia expected the task to be more unstable, but at the same time predicted more rewards. In a follow-up study we found people who were more paranoid endorsed conspiracies about mask-wearing and potential vaccines - again, mask attitude and conspiratorial beliefs were associated with erratic task behaviour and changed priors. Future public health responses to the pandemic might leverage these observations, mollifying paranoia and increasing adherence by tempering people's expectations of other's behaviour, and the environment more broadly, and reinforcing compliance.

The Pandemic Brain: neuroinflammation in healthy, non-infected individuals during the COVID-19 pandemic (preprint)

SummaryO_ST_ABSBackgroundC_ST_ABSThe impact of COVID-19 on human health extends beyond the morbidity and death toll directly caused by the SARS-CoV-2 virus. In fact, accumulating evidence indicates a global increase in the incidence of fatigue, brain fog and depression, including among non-infected, since the pandemic onset. Motivated by previous evidence linking those symptoms to neuroimmune activation in other pathological contexts, we hypothesized that subjects examined after the enforcement of lockdown/stay-at-home measures would demonstrate increased neuroinflammation. MethodsWe performed simultaneous brain Positron Emission Tomography / Magnetic Resonance Imaging in healthy volunteers either before (n=57) or after (n=15) the 2020 Massachusetts lockdown, using [11C]PBR28, a radioligand for the glial marker 18 kDa translocator protein (TSPO). First, we compared [11C]PBR28 signal across pre- and post-lockdown cohorts. Then, we evaluated the link between neuroinflammatory signals and scores on a questionnaire assessing mental and physical impacts of the pandemic. Further, we investigated multivariate associations between the spatial pattern of [11C]PBR28 post-lockdown changes and constitutive brain gene expression in post-mortem brains (Allen Human Brain Atlas). Finally, in a subset (n=13 pre-lockdown; n=11 post-lockdown), we also used magnetic resonance spectroscopy to quantify brain (thalamic) levels of myoinositol (mIns), another neuroinflammatory marker. FindingsBoth [11C]PBR28 and mIns signals were overall stable pre-lockdown, but markedly elevated after lockdown, including within brain regions previously implicated in stress, depression and "sickness behaviors". Moreover, amongst the post-lockdown cohort, subjects endorsing higher symptom burden showed higher [11C]PBR28 PET signal compared to those reporting little/no symptoms. Finally, the post-lockdown [11C]PBR28 signal changes were spatially aligned with the constitutive expression of several genes highly expressed in glial/immune cells and/or involved in neuroimmune signaling. InterpretationOur results suggest that pandemic-related stressors may have induced sterile neuroinflammation in healthy individuals that were not infected with SARS-CoV-2. This work highlights the possible impact of the COVID-19 pandemic-related lifestyle disruptions on human brain health. FundingR01-NS094306-01A1, R01-NS095937-01A1, R01-DA047088-01, The Landreth Family Foundation.