SARS CoV-2 detected in neonatal stool remote from maternal COVID-19 during pregnancy.

BACKGROUND: In utero transmission of SARS coronavirus 2 (SARS-CoV-2) has not been fully investigated. We investigated whether newborns of mothers with COVID-19 during pregnancy might harbor SARS-CoV-2 in the gastrointestinal tract. METHODS: This cohort study investigated stool from 14 newborns born at 25-41 weeks admitted at delivery to our urban academic hospital whose mothers had COVID-19 during pregnancy. Eleven mothers had COVID-19 resolved more than 10 weeks before delivery. Newborn stool was evaluated for SARS-CoV-2 RNA, Spike protein, and induction of inflammatory cytokines interleukin-6 (IL-6) and interferon-γ (IFN-γ) in macrophages. RESULTS: Despite negative SARS CoV-2 nasal PCRs from all newborns, viral RNAs and Spike protein were detected in the stool of 11 out of 14 newborns as early as the first day of life and increased over time in 6. Stool homogenates from all 14 newborns elicited elevated inflammatory IL-6 and IFN-γ from macrophages. Most newborns were clinically well except for one death from gestational autoimmune liver disease and another who developed necrotizing enterocolitis. CONCLUSIONS: These findings suggest in utero transmission of SARS-CoV-2 and possible persistent intestinal viral reservoirs in the newborns. Further investigation is required to understand the mechanisms and their clinical implications. IMPACT: SARS-CoV-2 RNAs or Spike protein was detected in the stool of 11 out of 14 preterm newborns born to mothers with resolved COVID-19 weeks prior to delivery despite negative newborn nasal PCR swabs. These novel findings suggest risk of in utero SARS-CoV-2 transmission to the fetal intestine during gestation. The presence of SARS-CoV-2 RNAs and Spike protein in the intestines of newborns may potentially impact the development of the gut microbiome and the immune system; the long-term health impact on the preterm infants should be further investigated.

Levamisole-induced and COVID-19-induced retiform purpura: two overlapping, emerging clinical syndromes.

Levamisole exposure in cocaine users is a well-recognized cause of retiform purpura, a distinctive net-like maculopapular patch. Prolonged exposure to levamisole can lead to a serious systemic syndrome known as levamisole-induced vasculitis, most commonly involving the kidneys and lungs. More recently, retiform purpura has been observed in patients with the novel coronavirus disease of 2019 (COVID-19). Due to their overlapping dermatologic and systemic manifestations, levamisole-induced and COVID-19-induced retiform purpura may mimic one another in clinical presentation. The possibility that patients may present with one or both syndromes creates a diagnostic challenge. This review of levamisole-induced and COVID-19-induced retiform purpura highlights their corresponding and distinctive features. Additionally, we propose a unique staging system for levamisole-induced retiform purpura that may be valid for future classification of COVID-19-induced retiform purpura.

A Small Molecule That In Vitro Neutralizes Infection of SARS-CoV-2 and Its Most Infectious Variants, Delta, and Omicron.

The COVID-19 pandemic has underscored the urgent need to develop highly potent and safe medications that are complementary to the role of vaccines. Specifically, it has exhibited the need for orally bioavailable broad-spectrum antivirals that are able to be quickly deployed against newly emerging viral pathogens. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and its variants Delta and Omicron are still a major threat to patients of all ages. In this brief report, we describe that the small molecule CD04872SC was able to neutralize SARS-CoV2 infection with a half-maximal effective concentration (EC50) = 248 µM. Serendipitously, we also were able to observe that CD04872SC inhibited the infection of the SARS-CoV-2 variants; Delta (EC50 = 152 µM) and Omicron (EC50 = 308 µM). These properties may define CD04872SC as a potential broad-spectrum candidate lead for the development of treatments for COVID-19.

A multi-organoid platform identifies CIART as a key factor for SARS-CoV-2 infection.

COVID-19 is a systemic disease involving multiple organs. We previously established a platform to derive organoids and cells from human pluripotent stem cells to model SARS-CoV-2 infection and perform drug screens1,2. This provided insight into cellular tropism and the host response, yet the molecular mechanisms regulating SARS-CoV-2 infection remain poorly defined. Here we systematically examined changes in transcript profiles caused by SARS-CoV-2 infection at different multiplicities of infection for lung airway organoids, lung alveolar organoids and cardiomyocytes, and identified several genes that are generally implicated in controlling SARS-CoV-2 infection, including CIART, the circadian-associated repressor of transcription. Lung airway organoids, lung alveolar organoids and cardiomyocytes derived from isogenic CIART-/- human pluripotent stem cells were significantly resistant to SARS-CoV-2 infection, independently of viral entry. Single-cell RNA-sequencing analysis further validated the decreased levels of SARS-CoV-2 infection in ciliated-like cells of lung airway organoids. CUT&RUN, ATAC-seq and RNA-sequencing analyses showed that CIART controls SARS-CoV-2 infection at least in part through the regulation of NR4A1, a gene also identified from the multi-organoid analysis. Finally, transcriptional profiling and pharmacological inhibition led to the discovery that the Retinoid X Receptor pathway regulates SARS-CoV-2 infection downstream of CIART and NR4A1. The multi-organoid platform identified the role of circadian-clock regulation in SARS-CoV-2 infection, which provides potential therapeutic targets for protection against COVID-19 across organ systems.

Generalized Pustular Figurate Erythema in Patients with COVID-19 Treated with Hydroxychloroquine: A Systematic Review.

severe distinctive cutaneous drug reaction, generalized pustular figurate erythema, closely linked with hydroxychloroquine (HCQ), has been documented. It is distinguishable from AGEP by its longer incubation, more varied morphology (initially urticarial and later targetoid, arcuate plaques), recalcitrance to therapy and longer disease course. Aim of the article is to review the recognized entity associated with ingestion of hydroxychloroquine in patients infected with COVID-19. A systematic review using electronic search was performed. Inclusion criteria: n patients with COVID-19 demonstrated by PCR, with typical clinical features of AGEP/GPFE or atypical features associated with typical histopathology. We used the (JBI) Critical Appraisal Checklist for Case Reports for the qualitive assessment. We included 13 publications. Their overall quality was good to moderate. Only 27.3% of the patients had a severe COVID-19 course. The mean lag time between trigger exposure and rash development was 24 days. Only 15.38% of the reported AGEP were clinically typical, while the remaining 69.23 % were suggestive of GPFE. Unfortunately, 2 patients died secondary to massive pulmonary embolism. In COVID-19 infection, we suggest reconsidering treating established COVID-19 empirically with HCQ, as both triggers can augment the subsequent cytokine storm, inducing a severe drug reaction and possibly increasing the risk of thrombo-embolic events.

Characteristics and correlates of fentanyl preferences among people with opioid use disorder.

OBJECTIVES: Fentanyl has come to dominate the U.S. illicit opioid supply. We aimed to characterize and examine correlates of preferences for fentanyl vs. other opioids among individuals starting OUD treatment. METHODS: We interviewed 250 adults initiating buprenorphine treatment with positive fentanyl toxicology at intake. We characterized opioid preferences and examined bivariate associations between opioid preference (preference for heroin, fentanyl, heroin-fentanyl mix, or other opioid) and sociodemographic characteristics, psychosocial factors, and substance use behaviors. We then used multinomial logistic regression to examine factors independently associated with fentanyl preferences. RESULTS: Over half (52.0 %) of participants preferred fentanyl (21.2 % fentanyl alone, 30.8 % heroin-fentanyl mix). In bivariate comparisons, participants who preferred fentanyl were a higher acuity group with respect to risks and problems in general. In the multinomial logistic regression, people who preferred fentanyl, either alone or mixed with heroin, used non-prescribed buprenorphine less in the 30 days preceding treatment entry compared to people who preferred heroin or other opioids (RRRalone= 0.88 [0.78, 0.99]; P = 0.037 and RRRmixed= 0.91 [0.84, 0.99]; P = 0.046). People who preferred fentanyl alone were also younger (RRR= 0.93 [0.90, 0.97]; P < 0.001) and more likely to have severe mental illness (RRR= 2.5 [1.1, 5.6]; P = 0.027) than people who prefer heroin or other opioids. CONCLUSIONS: Many people with OUD report preferring fentanyl. People who express preference for fentanyl differ substantively from those with other opioid preferences, and may be at elevated risk for poor health outcomes. Understanding preferences surrounding fentanyl could inform treatment and harm reduction interventions.

Dual-Reporter System for Real-Time Monitoring of SARS-CoV-2 Main Protease Activity in Live Cells Enables Identification of an Allosteric Inhibition Path.

The SARS-CoV-2 pandemic is an ongoing threat to global health, and the continuing emergence of contagious variants highlights the urgent need for additional antiviral therapy to attenuate COVID-19 disease. The SARS-CoV-2 main protease (3CLpro) presents an attractive target for such therapy due to its high sequence conservation and key role in the viral life cycle. In this study, we designed a fluorescent-luminescent cell-based reporter for the detection and quantification of 3CLpro intracellular activity. Employing this platform, we examined the efficiency of known protease inhibitors against 3CLpro and further identified potent inhibitors through high-throughput chemical screening. Computational analysis confirmed a direct interaction of the lead compounds with the protease catalytic site and identified a prototype for efficient allosteric inhibition. These developments address a pressing need for a convenient sensor and specific targets for both virus detection and rapid discovery of potential inhibitors.

The impact of COVID-19 on the treatment of opioid use disorder in carceral facilities: a cross-sectional study.

While the COVID-19 pandemic disrupted healthcare delivery everywhere, persons with carceral system involvement and opioid use disorder (OUD) were disproportionately impacted and vulnerable to severe COVID-associated illness. Carceral settings and community treatment programs (CTPs) rapidly developed protocols to sustain healthcare delivery while reducing risk of COVID-19 transmission. This survey study assessed changes to OUD treatment, telemedicine use, and re-entry support services among carceral and CTPs participating in the National Institute on Drug Abuse (NIDA)-funded study, Long-Acting Buprenorphine vs. Naltrexone Opioid Treatments in Criminal Justice System-Involved Adults (EXIT-CJS) study. In December 2020, carceral sites (n = 6; median pre-COVID 2020 monthly census = 3468 people) and CTPs (n = 7; median pre-COVID 2020 monthly census = 550 patients) participating in EXIT-CJS completed a cross-sectional web-based survey. The survey assessed changes pre- (January-March 2020) and post- (April-September 2020) COVID-19 in OUD treatment, telemedicine use, re-entry supports and referral practices. Compared to January-March 2020, half of carceral sites (n = 3) increased the total number of persons initiating medication for opioid use disorder (MOUD) from April-September 2020, while a third (n = 2) decreased the number of persons initiated. Most CTPs (n = 4) reported a decrease in the number of new admissions from April-September 2020, with two programs stopping or pausing MOUD programs due to COVID-19. All carceral sites with pre-COVID telemedicine use (n = 5) increased or maintained telemedicine use, and all CTPs providing MOUD (n = 6) increased telemedicine use. While expansion of telemedicine services supported MOUD service delivery, the majority of sites experienced challenges providing community support post-release, including referrals to housing, employment, and transportation services. During the COVID-19 pandemic, this small sample of carceral and CTP sites innovated to continue delivery of treatment for OUD. Expansion of telemedicine services was critical to support MOUD service delivery. Despite these innovations, sites experienced challenges providing reintegration supports for persons in the community. Pre-COVID strategies for identifying and engaging individuals while incarcerated may be less effective since the pandemic. In addition to expanding research on the most effective telemedicine practices for carceral settings, research exploring strategies to expand housing and employment support during reintegration are critical.

Correlates of wanting to seek help for mental health and substance use concerns by sexual and gender minority young adults during the COVID-19 pandemic: A machine learning analysis.

The COVID-19 pandemic has worsened the mental health and substance use challenges among many people who are Two Spirit, lesbian, gay, bisexual, transgender, queer, questioning, and intersex (2SLGBTQI+). We aimed to identify the important correlates and their effects on the predicted likelihood of wanting to seek help among 2SLGBTQI+ young adults for mental health or substance use concerns during the pandemic. A cross-sectional survey was conducted in 2020-2021 among 2SLGBTQI+ young adults aged 16-29 living in two Canadian provinces (Ontario and Quebec). Among 1414 participants, 77% (n = 1089) wanted to seek help for their mental health or substance use concerns during the pandemic, out of these, 69.8% (n = 760) reported delay in accessing care. We built a random forest (RF) model to predict the status of wanting to seek help, which achieved moderately high performance with an area under the receiver operating characteristic curve (AUC) of 0.85. The top 10 correlates of wanting to seek help were worsening mental health, age, stigma and discrimination, and adverse childhood experiences. The interactions of adequate housing with certain sexual orientations, gender identities and mental health challenges were found to increase the likelihood of wanting to seek help. We built another RF model for predicting risk of delay in accessing care among participants who wanted to seek help (n = 1089). The model identified a similar set of top 10 correlates of delay in accessing care but lacked adequate performance (AUC 0.61). These findings can direct future research and targeted prevention measures to reduce health disparities for 2SLGBTQI+ young adults.

Dual-Reporter System for Real-Time Monitoring of SARS-CoV-2 Main Protease Activity in Live Cells Enables Identification of an Allosteric Inhibition Path

The SARS-CoV-2 pandemic is an ongoing threat to global health, and the continuing emergence of contagious variants highlights the urgent need for additional antiviral therapy to attenuate COVID-19 disease. The SARS-CoV-2 main protease (3CLpro) presents an attractive target for such therapy due to its high sequence conservation and key role in the viral life cycle. In this study, we designed a fluorescent–luminescent cell-based reporter for the detection and quantification of 3CLpro intracellular activity. Employing this platform, we examined the efficiency of known protease inhibitors against 3CLpro and further identified potent inhibitors through high-throughput chemical screening. Computational analysis confirmed a direct interaction of the lead compounds with the protease catalytic site and identified a prototype for efficient allosteric inhibition. These developments address a pressing need for a convenient sensor and specific targets for both virus detection and rapid discovery of potential inhibitors.

SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations after recovery.

The host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in prolonged pathologies collectively referred to as post-acute sequalae of COVID-19 (PASC) or long COVID. To better understand the mechanism underlying long COVID biology, we compared the short- and long-term systemic responses in the golden hamster after either SARS-CoV-2 or influenza A virus (IAV) infection. Results demonstrated that SARS-CoV-2 exceeded IAV in its capacity to cause permanent injury to the lung and kidney and uniquely affected the olfactory bulb (OB) and olfactory epithelium (OE). Despite a lack of detectable infectious virus, the OB and OE demonstrated myeloid and T cell activation, proinflammatory cytokine production, and an interferon response that correlated with behavioral changes extending a month after viral clearance. These sustained transcriptional changes could also be corroborated from tissue isolated from individuals who recovered from COVID-19. These data highlight a molecular mechanism for persistent COVID-19 symptomology and provide a small animal model to explore future therapeutics.

Host protein kinases required for SARS-CoV-2 nucleocapsid phosphorylation and viral replication.

Multiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccinated or who experience breakthrough infections. Understanding the common host factors necessary for the life cycles of coronaviruses may reveal conserved therapeutic targets. Here, we used the known substrate specificities of mammalian protein kinases to deconvolute the sequence of phosphorylation events mediated by three host protein kinase families (SRPK, GSK-3, and CK1) that coordinately phosphorylate a cluster of serine and threonine residues in the viral N protein, which is required for viral replication. We also showed that loss or inhibition of SRPK1/2, which we propose initiates the N protein phosphorylation cascade, compromised the viral replication cycle. Because these phosphorylation sites are highly conserved across coronaviruses, inhibitors of these protein kinases not only may have therapeutic potential against COVID-19 but also may be broadly useful against coronavirus-mediated diseases.

A human iPSC-array-based GWAS identifies a virus susceptibility locus in the NDUFA4 gene and functional variants.

Population-based studies to identify disease-associated risk alleles typically require samples from a large number of individuals. Here, we report a human-induced pluripotent stem cell (hiPSC)-based screening strategy to link human genetics with viral infectivity. A genome-wide association study (GWAS) identified a cluster of single-nucleotide polymorphisms (SNPs) in a cis-regulatory region of the NDUFA4 gene, which was associated with susceptibility to Zika virus (ZIKV) infection. Loss of NDUFA4 led to decreased sensitivity to ZIKV, dengue virus, and SARS-CoV-2 infection. Isogenic hiPSC lines carrying non-risk alleles of SNPs or deletion of the cis-regulatory region lower sensitivity to viral infection. Mechanistic studies indicated that loss/reduction of NDUFA4 causes mitochondrial stress, which leads to the leakage of mtDNA and thereby upregulation of type I interferon signaling. This study provides proof-of-principle for the application of iPSC arrays in GWAS and identifies NDUFA4 as a previously unknown susceptibility locus for viral infection.

Sensing of SARS-CoV-2 by pDCs and their subsequent production of IFN-I contribute to macrophage-induced cytokine storm during COVID-19.

Lung-infiltrating macrophages create a marked inflammatory milieu in a subset of patients with COVID-19 by producing a cytokine storm, which correlates with increased lethality. However, these macrophages are largely not infected by SARS-CoV-2, so the mechanism underlying their activation in the lung is unclear. Type I interferons (IFN-I) contribute to protecting the host against SARS-CoV-2 but may also have some deleterious effect, and the source of IFN-I in the lungs of infected patients is not well defined. Plasmacytoid dendritic cells (pDCs), a key cell type involved in antiviral responses, can produce IFN-I in response to SARS-CoV-2. We observed the infiltration of pDCs in the lungs of SARS-CoV-2-infected patients, which correlated with strong IFN-I signaling in lung macrophages. In patients with severe COVID-19, lung macrophages expressed a robust inflammatory signature, which correlated with persistent IFN-I signaling at the single-cell level. Hence, we observed the uncoupling in the kinetics of the infiltration of pDCs in the lungs and the associated IFN-I signature, with the cytokine storm in macrophages. We observed that pDCs were the dominant IFN-α-producing cells in response to the virus in the blood, whereas macrophages produced IFN-α only when in physical contact with infected epithelial cells. We also showed that IFN-α produced by pDCs, after the sensing of SARS-CoV-2 by TLR7, mediated changes in macrophages at both transcriptional and epigenetic levels, which favored their hyperactivation by environmental stimuli. Together, these data indicate that the priming of macrophages can result from the response by pDCs to SARS-CoV-2, leading to macrophage activation in patients with severe COVID-19.

Early Impacts of the COVID-19 Pandemic on Public Health Systems and Practice in 3 Canadian Provinces From the Perspective of Public Health Leaders: A Qualitative Study.

CONTEXT: The COVID-19 pandemic has impacted health systems worldwide. Studies to date have largely focused on the health care system with less attention to the impact on public health systems and practice. OBJECTIVE: To describe the early impacts of COVID-19 on public health systems and practice in 3 Canadian provinces from the perspective of public health system leaders and synthesize lessons learned. DESIGN: A qualitative study using semistructured virtual interviews with public health leaders between October 2020 and April 2021. The World Health Organization's essential public health operations framework guided data collection and analysis. SETTING: This study involved the Canadian provinces of Alberta, Ontario, and Québec. These provinces were chosen for their large populations, relatively high COVID-19 burden, and variation in public health systems. PARTICIPANTS: Public health leaders from Alberta (n = 21), Ontario (n = 18), and Québec (n = 19) in organizations with a primary mandate of stewardship and/or administration of essential public health operations (total n = 58). RESULTS: We found that the COVID-19 pandemic led to intensified collaboration in public health systems and a change in workforce capacity to respond to the pandemic. This came with opportunities but also challenges of burnout and disruption of non-COVID-19 services. Information systems and digital technologies were increasingly used and there was greater proximity between public health leaders and other health system leaders. A renewed recognition for public health work was also highlighted. CONCLUSIONS: The COVID-19 pandemic impacted several aspects of public health systems in the provinces studied. Our findings can help public health leaders and policy makers identify areas for further investment (eg, intersectoral collaboration, information systems) and develop plans to address challenges (eg, disrupted services, workforce burnout) that have surfaced.

Pathobiology of Cutaneous Manifestations Associated with COVID-19 and Their Management.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has been a rising concern since its declaration as a pandemic by the World Health Organization on 11 March 2020. Recently, its association with multiple underlying organs has been identified that includes cardiac, renal, gastrointestinal, nervous systems, and cutaneous manifestations. Cutaneous COVID-19 findings have been supposedly classified into the following categories: vesicular (varicella-like), papulo-vesiculsar, chilblains-like ("COVID toes") maculopapular, and urticarial morphologies. In this review, we aim to focus on the proposed pathophysiology behind the various dermatological manifestations associated with COVID-19 and their associated management. We also included prevalence and clinical features of the different COVID-19-related skin lesions in our review. A comprehensive narrative review of the literature was performed in PubMed databases. Data from case reports, observational studies, case series, and reviews till June 2022 were all screened and included in the review.

“We cobble together a storyline of system performance using a diversity of things”: a qualitative study of perspectives on public health performance measurement in Canada

There have been longstanding calls for public health systems transformations in many countries, including Canada. Core to these calls has been strengthening performance measurement. While advancements have been made in performance measurement for certain sectors of the health care system (primarily focused on acute and primary health care), effective use of indicators for measuring public health systems performance are lacking. This study describes the current state, anticipated challenges, and future directions in the development and implementation of a public health performance measurement system for Canada. We conducted a qualitative study using semi-structured interviews with public health leaders (n = 9) between July and August 2021. Public health leaders included researchers, government staff, and former medical officers of health who were purposively selected due to their expertise and experience with performance measurement with relevance to public health systems in Canada. Thematic analysis included both a deductive approach for themes consistent with the conceptual framework and an inductive approach to allow new themes to emerge from the data. Conceptual, methodological, contextual, and infrastructure challenges were highlighted by participants in designing a performance measurement system for public health. Specifically, six major themes evolved that encompass 1) the mission and purpose of public health systems, including challenges inherent in measuring the functions and services of public health;2) the macro context, including the impacts of chronic underinvestment and one-time funding injections on the ability to sustain a measurement system;3) the organizational structure/governance of public health systems including multiple forms across Canada and underdevelopment of information technology systems;4) accountability approaches to performance measurement and management;and 5) timing and unobservability in public health indicators. These challenges require dedicated investment, strong leadership, and political will from the federal and provincial/territorial governments. Unprecedented attention on public health due to the coronavirus disease 2019 pandemic has highlighted opportunities for system improvements, such as addressing the lack of a performance measurement system. This study provides actionable knowledge on conceptual, methodological, contextual, and infrastructure challenges needed to design and build a pan-Canadian performance measurement system for public health.

The Evolution of Vigilance and Its Atrophy Preceding the COVID-19 Global Pandemic.

Introduction: Recent infectious outbreaks preceding the COVID-19 crisis resulted in the evolution of vigilance for preparedness against the next pandemic. This vigilance was maintained to varying degrees in different jurisdictions. Objective: To evaluate the evolution of vigilance following previous epidemics and pandemics and the subsequent atrophy of vigilance prior to the COVID-19 global pandemic. Methods: We evaluated documentation discussing US, Canada, and South Korea from March 2002 to October 2021. Our policy search strategy was rooted in academic literature, government documents and media reports. Results: In the US, there were examples of atrophy of vigilance; however, there was clear understanding of pandemic readiness actions that were simply not executed amongst political chaos. In Canada, political mishaps were less evident at the time the pandemic unfolded. Nevertheless, atrophy was evident with erosion in preparedness programs following SARS. South Korea appeared least subjected to atrophy of vigilance. The more recent MERS outbreak prompted evolution of sustained vigilance and compliance with basic public health measures such as mask wearing. Recommendations: Policy options need to be explored and instituted that increase protection of preparedness programs through institutional safeguards and accountability measure.

SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations post recovery

The host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in prolonged pathologies collectively referred to as post-acute sequalae of COVID-19 (PASC) or long COVID. To better understand the mechanism underlying long COVID biology, we compared the short- and long-term systemic responses in the golden hamster following either SARS-CoV-2 or influenza A virus (IAV) infection. Results demonstrated that SARS-CoV-2 exceeded IAV in its capacity to cause permanent injury to the lung and kidney and uniquely impacted the olfactory bulb (OB) and epithelium (OE). Despite a lack of detectable infectious virus, the OB and OE demonstrated myeloid and T cell activation, proinflammatory cytokine production, and an interferon response that correlated with behavioral changes extending a month post viral clearance. These sustained transcriptional changes could also be corroborated from tissue isolated from individuals who recovered from COVID-19. These data highlight a molecular mechanism for persistent COVID-19 symptomology and provide a small animal model to explore future therapeutics. SARS-CoV-2 infection results in sustained inflammation in the nervous system and is a driver of long COVID. Description