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1.
Sci Transl Med ; : eabq3059, 2022 Jun 07.
Article in English | MEDLINE | ID: covidwho-2019709

ABSTRACT

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.

2.
Lancet Digit Health ; 2022 Jul 11.
Article in English | MEDLINE | ID: covidwho-2016308

ABSTRACT

BACKGROUND: COVID-19 is a multi-system disorder with high variability in clinical outcomes among patients who are admitted to hospital. Although some cytokines such as interleukin (IL)-6 are believed to be associated with severity, there are no early biomarkers that can reliably predict patients who are more likely to have adverse outcomes. Thus, it is crucial to discover predictive markers of serious complications. METHODS: In this retrospective cohort study, we analysed samples from 455 participants with COVID-19 who had had a positive SARS-CoV-2 RT-PCR result between April 14, 2020, and Dec 1, 2020 and who had visited one of three Mayo Clinic sites in the USA (Minnesota, Arizona, or Florida) in the same period. These participants were assigned to three subgroups depending on disease severity as defined by the WHO ordinal scale of clinical improvement (outpatient, severe, or critical). Our control cohort comprised of 182 anonymised age-matched and sex-matched plasma samples that were available from the Mayo Clinic Biorepository and banked before the COVID-19 pandemic. We did a deep profiling of circulatory cytokines and other proteins, lipids, and metabolites from both cohorts. Most patient samples were collected before, or around the time of, hospital admission, representing ideal samples for predictive biomarker discovery. We used proximity extension assays to quantify cytokines and circulatory proteins and tandem mass spectrometry to measure lipids and metabolites. Biomarker discovery was done by applying an AutoGluon-tabular classifier to a multiomics dataset, producing a stacked ensemble of cutting-edge machine learning algorithms. Global proteomics and glycoproteomics on a subset of patient samples with matched pre-COVID-19 plasma samples was also done. FINDINGS: We quantified 1463 cytokines and circulatory proteins, along with 902 lipids and 1018 metabolites. By developing a machine-learning-based prediction model, a set of 102 biomarkers, which predicted severe and clinical COVID-19 outcomes better than the traditional set of cytokines, were discovered. These predictive biomarkers included several novel cytokines and other proteins, lipids, and metabolites. For example, altered amounts of C-type lectin domain family 6 member A (CLEC6A), ether phosphatidylethanolamine (P-18:1/18:1), and 2-hydroxydecanoate, as reported here, have not previously been associated with severity in COVID-19. Patient samples with matched pre-COVID-19 plasma samples showed similar trends in muti-omics signatures along with differences in glycoproteomics profile. INTERPRETATION: A multiomic molecular signature in the plasma of patients with COVID-19 before being admitted to hospital can be exploited to predict a more severe course of disease. Machine learning approaches can be applied to highly complex and multidimensional profiling data to reveal novel signatures of clinical use. The absence of validation in an independent cohort remains a major limitation of the study. FUNDING: Eric and Wendy Schmidt.

3.
Eur Respir J ; 2022 May 12.
Article in English | MEDLINE | ID: covidwho-2009349

ABSTRACT

BACKGROUND: There is an emerging understanding that coronavirus disease 2019 (COVID-19) is associated with increased incidence of pneumomediastinum. We aimed to determine its incidence among patients hospitalised with COVID-19 in the United Kingdom and describe factors associated with outcome. METHODS: A structured survey of pneumomediastinum and its incidence was conducted from September 2020 to February 2021. United Kingdom-wide participation was solicited via respiratory research networks. Identified patients had SARS-CoV-2 infection and radiologically proven pneumomediastinum. The primary outcomes were to determine incidence of pneumomediastinum in COVID-19 and to investigate risk factors associated with patient mortality. RESULTS: 377 cases of pneumomediastinum in COVID-19 were identified from 58 484 inpatients with COVID-19 at 53 hospitals during the study period, giving an incidence of 0.64%. Overall 120-day mortality in COVID-19 pneumomediastinum was 195/377 (51.7%). Pneumomediastinum in COVID-19 was associated with high rates of mechanical ventilation. 172/377 patients (45.6%) were mechanically ventilated at the point of diagnosis. Mechanical ventilation was the most important predictor of mortality in COVID-19 pneumomediastinum at the time of diagnosis and thereafter (p<0.001) along with increasing age (p<0.01) and diabetes mellitus (p=0.08). Switching patients from continuous positive airways pressure support to oxygen or high flow nasal oxygen after the diagnosis of pneumomediastinum was not associated with difference in mortality. CONCLUSIONS: Pneumomediastinum appears to be a marker of severe COVID-19 pneumonitis. The majority of patients in whom pneumomediastinum was identified had not been mechanically ventilated at the point of diagnosis.

4.
Molecular Therapy - Nucleic Acids ; 2022.
Article in English | ScienceDirect | ID: covidwho-1996465

ABSTRACT

The current COVID-19 pandemic highlights the need for broad-spectrum antiviral therapeutics. Here we describe a new class of self-assembling immunostimulatory short duplex RNAs that potently induce production of type I and type III interferon (IFN-I and IFN-III). These RNAs require a minimum of 20 base pairs, lack any sequence or structural characteristics of known immunostimulatory RNAs, and instead require a unique sequence motif (sense strand: 5’-C, antisense strand: 3’-GGG) that mediates end-to-end dimer self-assembly. The presence of terminal hydroxyl or monophosphate groups, blunt or overhanging ends, or terminal RNA or DNA bases did not affect their ability to induce IFN. Unlike previously described immunostimulatory siRNAs, their activity is independent of TLR7/8, but requires the RIG-I/IRF3 pathway that induces a more restricted antiviral response with a lower proinflammatory signature compared with immunostimulant poly(I:C). Immune stimulation mediated by these duplex RNAs results in broad spectrum inhibition of infections by many respiratory viruses with pandemic potential, including SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-NL63, and influenza A virus in cell lines, human Lung Chips that mimic organ-level lung pathophysiology, and a mouse SARS-CoV-2 infection model. These short dsRNAs can be manufactured easily, and thus potentially could be harnessed to produce broad-spectrum antiviral therapeutics.

5.
J Virol ; 96(15): e0076522, 2022 08 10.
Article in English | MEDLINE | ID: covidwho-1992938

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) represent two highly transmissible airborne pathogens with pandemic capabilities. Although these viruses belong to separate virus families-SARS-CoV-2 is a member of the family Coronaviridae, while IAV is a member of the family Orthomyxoviridae-both have shown zoonotic potential, with significant animal reservoirs in species in close contact with humans. The two viruses are similar in their capacity to infect human airways, and coinfections resulting in significant morbidity and mortality have been documented. Here, we investigate the interaction between SARS-CoV-2 USA-WA1/2020 and influenza H1N1 A/California/04/2009 virus during coinfection. Competition assays in vitro were performed in susceptible cells that were either interferon type I/III (IFN-I/-III) nonresponsive or IFN-I/-III responsive, in addition to an in vivo golden hamster model. We find that SARS-CoV-2 infection does not interfere with IAV biology in vivo, regardless of timing between the infections. In contrast, we observe a significant loss of SARS-CoV-2 replication following IAV infection. The latter phenotype correlates with increased levels of IFN-I/-III and immune priming that interferes with the kinetics of SARS-CoV-2 replication. Together, these data suggest that cocirculation of SARS-CoV-2 and IAV is unlikely to result in increased severity of disease. IMPORTANCE The human population now has two circulating respiratory RNA viruses with high pandemic potential, namely, SARS-CoV-2 and influenza A virus. As both viruses infect the airways and can result in significant morbidity and mortality, it is imperative that we also understand the consequences of getting coinfected. Here, we demonstrate that the host response to influenza A virus uniquely interferes with SARS-CoV-2 biology although the inverse relationship is not evident. Overall, we find that the host response to both viruses is comparable to that to SARS-CoV-2 infection alone.


Subject(s)
COVID-19 , Coinfection , Influenza A Virus, H1N1 Subtype , Influenza A virus , Influenza, Human , Interferon Type I , Animals , Humans , Influenza A Virus, H1N1 Subtype/genetics , SARS-CoV-2 , Virus Replication/genetics
6.
Respir Care ; 67(7): 781-788, 2022 07.
Article in English | MEDLINE | ID: covidwho-1988238

ABSTRACT

BACKGROUND: High-frequency percussive ventilation (HFPV) is an alternative mode of mechanical ventilation that has been shown to improve gas exchange in subjects with severe respiratory failure. We hypothesized that HFPV use would improve ventilation and oxygenation in intubated children with acute bronchiolitis. METHODS: In this single-center prospective cohort study we included mechanically ventilated children in the pediatric ICU with bronchiolitis 1-24 months old who were transitioned to HFPV from conventional invasive mechanical ventilation from November 2018-April 2020. Patients with congenital heart disease, on extracorporeal membrane oxygenation (ECMO), and with HFPV duration < 12 h were excluded. Subject gas exchange metrics and ventilator parameters were compared before and after HFPV initiation. RESULTS: Forty-one of 192 (21%) patients intubated with bronchiolitis underwent HFPV, and 35 met inclusion criteria. Median age of cohort was 4 months, and 60% were previously healthy. All subjects with available oxygenation saturation index (OSI) measurements pre-HFPV met pediatric ARDS criteria (31/35, 89%). Mean CO2 decreased from 65.4 in the 24 h pre-HFPV to 51 (P < .001) in the 24 h post initiation. SpO2 /FIO2 was significantly improved at 24 h post-HFPV (153.3 to 209.7, P = .001), whereas the decrease in mean OSI at 24 h did not meet statistical significance (11.9 to 10.2, P = .15). The mean peak inspiratory pressure (PIP) decreased post-HFPV from 29.7 to 25.0 at 24 h (P < .001). No subjects developed an air leak or hemodynamic instability secondary to HFPV. Two subjects required ECMO, and of these, one subject died. CONCLUSIONS: HFPV was associated with significant improvement in ventilation and decreased exposure to high PIPs for mechanically ventilated children with bronchiolitis in our cohort and had a potential association with improved oxygenation. Our study shows that HFPV may be an effective alternative mode of ventilation in patients with bronchiolitis who have poor gas exchange on conventional invasive mechanical ventilation.


Subject(s)
Bronchiolitis, Viral , High-Frequency Ventilation , Respiratory Distress Syndrome , Bronchiolitis, Viral/complications , Bronchiolitis, Viral/therapy , Child , Child, Preschool , Humans , Infant , Prospective Studies , Respiration, Artificial
8.
Hormone Research in Paediatrics ; 95(SUPPL 1):67-68, 2022.
Article in English | Web of Science | ID: covidwho-1980874
9.
Child Obes ; 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1967828

ABSTRACT

Pediatric obesity is a significant public health concern, and the COVID-19 pandemic altered many of its risk factors. Understanding this impact can help pediatricians and public health officials prioritize initiatives and identify high-risk subgroups. We performed a retrospective longitudinal cohort study of 596 children and adolescents in a primary care clinic to determine changes in weight gain during the pandemic. A significant rise in normalized BMI was found during the prepandemic period across all age groups and initial BMI classification groups. This rate of change increased during the pandemic for those with pre-existing overweight or obesity status who were ≥10 years of age. Children with regular clinic visits in the prepandemic study period, but without a clinic visit during the pandemic, had significantly higher baseline normalized BMI and were older. These changes in the rate of weight gain during the COVID-19 pandemic period raise the possibility that pandemic influences may have exacerbated the rate of weight gain in children and adolescents with pre-existing obese or overweight range BMI. The difference in composition of the cohort without a pandemic time-period visit highlights the need for future studies in this area, especially those focused on adolescents.

11.
Clin Chim Acta ; 532: 181-187, 2022 Jul 01.
Article in English | MEDLINE | ID: covidwho-1966413

ABSTRACT

BACKGROUND: SARS-CoV-2 is an RNA virus that primarily causes respiratory disease; however, infection of other tissue has been reported. Evaluation of SARS-CoV-2 in tissue specimens may increase understanding of SARS-CoV-2 pathobiology. MATERIALS AND METHODS: A qualitative test for detection of SARS-CoV-2 in formalin-fixed paraffin-embedded (FFPE) tissues was developed and validated using droplet digital PCR (ddPCR), which has a lower limit of detection than reverse transcription (RT)-qPCR. After extraction of total RNA from unstained FFPE tissue, SARS-CoV-2 nucleocapsid (N1, N2) target sequences were amplified and quantified, along with human RPP30 as a control using the Bio-Rad SARS-CoV-2 ddPCR kit. RESULTS: SARS-CoV-2 was detected in all 21 known positive samples and none of the 16 negative samples. As few as approximately 5 viral copies were reliably detected. Since January 2021, many tissue types have been clinically tested. Of the 195 clinical specimens, the positivity rate was 35% with placenta and fetal tissue showing the highest percentage of positive cases. CONCLUSION: This sensitive FFPE-based assay has broad clinical utility with applications as diverse as pregnancy loss and evaluation of liver transplant rejection. This assay will aid in understanding atypical presentations of COVID-19 as well as long-term sequelae.


Subject(s)
COVID-19 , RNA, Viral , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , COVID-19/diagnosis , Formaldehyde , Humans , Paraffin Embedding , RNA, Viral/isolation & purification , SARS-CoV-2/genetics
12.
AIDS Behav ; 2022 Jul 27.
Article in English | MEDLINE | ID: covidwho-1959018

ABSTRACT

COVID-19 has disrupted sexual behaviour and access to health systems. We adapted regular HIV behavioural surveillance of gay and bisexual men (GBM) in Australia in response to COVID-19, assessed the impact on the profile of the sample, the participants' HIV-related behaviour, and whether COVID-19 may have accentuated existing disparities in the Australian HIV epidemic. Data collected from five states during July 2017-June 2021 were included (N = 31,460). The emphasis on online recruitment after COVID-19 led to smaller sample sizes, greater geographic reach, and a higher proportion of bisexual-identifying participants. Most participants (88.1%) reported physical distancing and 52.1% had fewer sex partners due to COVID-19. In the COVID-19-affected rounds (July 2020-June 2021), the number of male partners, recent HIV testing and pre-exposure prophylaxis (PrEP) use all fell, and HIV risk among the smaller group of participants who reported casual sex increased. COVID-related changes were generally more pronounced among GBM aged under 25 years, participants from suburbs with fewer gay residents, and bisexual men. These groups should be prioritised when encouraging GBM to reengage with HIV testing services and effective prevention methods, like condoms and PrEP.


RESUMEN: COVID-19 ha interrumpido el comportamiento sexual y el acceso a los sistemas de salud. Adaptamos la vigilancia regular del comportamiento de hombres homosexuales y bisexuales (GBM) hacia el VIH en Australia en respuesta a COVID-19, evaluamos el impacto en el perfil de la muestra, el comportamiento relacionado con el VIH de los participantes y si COVID-19 puede haber acentuado las existentes disparidades en la epidemia australiana de VIH. Se incluyeron los datos recopilados de cinco estados entre julio de 2017 y junio de 2021 (N = 31 460). El énfasis en el reclutamiento en línea después de COVID-19 resulto en tamaños de muestra más pequeños, mayor alcance geográfico y una mayor proporción de participantes que se identifican como bisexuales. La mayoría de los participantes (88,1%) describieron participando en el distanciamiento físico y el 52,1% tuvo menos parejas sexuales debido a la COVID-19. En las rondas afectadas por COVID-19 (julio de 2020 a junio de 2021), disminuyó la cantidad de parejas masculinas, el uso reciente de pruebas de VIH y de la profilaxis previa a la exposición (PrEP), y el riesgo de VIH entre el grupo más pequeño de participantes que participaron en sexo casual aumentó. Los cambios relacionados con COVID fueron generalmente más pronunciados entre GBM menores de 25 años, participantes de suburbios con menos residentes homosexuales y hombres bisexuales. Se debe priorizar a estos grupos al alentar a GBM a volver a comprometerse con los servicios de pruebas de VIH y métodos de prevención efectivos, como condones y PrEP.

14.
Sex Res Social Policy ; : 1-12, 2022 May 28.
Article in English | MEDLINE | ID: covidwho-1943344

ABSTRACT

Introduction: COVID-19 related lockdowns have impacted the sexual activity of gay and bisexual men (GBM). We investigated trends in sexual behaviors and the COVID-19 context in which they occurred (COVID-notification rates and jurisdictional restrictions) to understand changes in the duration and severity of periods of lockdown on the sexual behavior of Australian GBM. Methods: In an online, prospective observational study of 831 GBM from May 2020 to May 2021, we investigated associations between changes in sexual behavior among Australian GBM, lockdowns, and COVID-19 notification rates through weekly surveys from May 2020 to May 2021. Results: The mean age was 45.71 years (SD: 13.93). Most identified as gay (89.0%) and 10.2% were living with HIV. There was an overall increase in the mean weekly number of non-committed relationship partners (0.53-0.90, p < 0.001). The state of Victoria experienced a significant extended COVID-19 outbreak, accompanied by severe lockdown restrictions. In response, Victorian men's partner numbers shifted three times, while elsewhere there was an overall gradually increasing trend. Conclusions: Less severe outbreaks with shorter lockdown periods, involving fewer and geographically contained, COVID-19 notifications were accompanied by non-significant changes in sex with non-relationship partners than more severe outbreaks over extended periods and larger geographical areas. Supplementary Information: The online version contains supplementary material available at 10.1007/s13178-022-00733-8.

15.
iScience ; 25(8): 104798, 2022 Aug 19.
Article in English | MEDLINE | ID: covidwho-1936592

ABSTRACT

The emergence of SARS-CoV-2 variants of concern (VOCs) requires the development of next-generation biologics with high neutralization breadth. Here, we characterized a human VH domain, F6, which we generated by sequentially panning large phage-displayed VH libraries against receptor binding domains (RBDs) containing VOC mutations. Cryo-EM analyses reveal that F6 has a unique binding mode that spans a broad surface of the RBD and involves the antibody framework region. Attachment of an Fc region to a fusion of F6 and ab8, a previously characterized VH domain, resulted in a construct (F6-ab8-Fc) that broadly and potently neutralized VOCs including Omicron. Additionally, prophylactic treatment using F6-ab8-Fc reduced live Beta (B.1.351) variant viral titers in the lungs of a mouse model. Our results provide a new potential therapeutic against SARS-CoV-2 variants including Omicron and highlight a vulnerable epitope within the spike that may be exploited to achieve broad protection against circulating variants.

16.
Microsurgery ; 2022 Jul 15.
Article in English | MEDLINE | ID: covidwho-1935713

ABSTRACT

BACKGROUND: The healthcare industry's efforts to immunize the global community against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been unprecedented. Given the fast-tracking of the novel vaccine, its short- and long-term medical implications remain largely to-be-determined in most patient populations. This study aims to analyze 90-day post-operative outcomes in microsurgical patients, who have received or not received SARS-CoV-2-vaccination, using a continuously updated federated electronic medical record network (TriNetX Inc, Cambridge, MA). METHODS: After screening 70 million de-identified records, 16,799 microsurgery patients aged 18-99 meeting medical coding criteria were allocated into two cohorts. Cohort One received SARS-CoV-2-vaccination prior to undergoing microsurgery whereas Cohort Two did not. Two equally sized cohorts, totaling 818 patients were created after propensity score matching for characteristics including: age, race, ethnicity, smoking, hypertension, heart disease, diabetes, obesity, chronic obstructive pulmonary disease, and history of SARS-CoV-2 exposure. Postoperative outcomes within 30-, 60-, and 90-days of microsurgery were analyzed. RESULTS: Patients who were SARS-CoV-2-immunized experienced significantly lower (p < .01) surgical site infections (Absolute Risk Reduction (ARR)[95%CI]) = (3.79%-5.36% [0.84-8.54]) ICU admission (9.47%-9.82%[5.45-13.88]), generalized infections (7.68%-9.92%[3.15-14.64]), and hospitalizations (28.48%-32.57%[20.99-40.13]) within 30-, 60-, and 90-days of microsurgery. Additionally, SARS-CoV-2-vaccinated patients also experienced significantly less flap failure (2.49%[0.97-4.02]) and death (2.46%[0.96-3.97]) within 30- and 60-days post-operatively. CONCLUSION: Our analysis examines the potential protective effect of SARS-CoV-2-vaccination in microsurgical patients. Limitations include the retrospective nature of this analysis and the inherent reliance on medical coding. Future prospective studies are warranted to better understand if in fact pre-operative SARS-CoV-2-vaccination has the potential to protect against post-operative microsurgery outcomes.

17.
Cureus ; 14(6): e25765, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1928852

ABSTRACT

The limited psychiatric bedspace due to the COVID-19 pandemic and the lack of access to an up-to-date medication regimen delayed the recognition of the diagnosis and treatment for a 40-year-old man with schizoaffective disorder, bipolar type, who traveled from his home city and abruptly discontinued his prescription of clozapine. He developed a cholinergic rebound syndrome including delirium and extrapyramidal symptoms (EPS). The delay included time spent in two different medical hospitals: one awaiting psychiatric bedspace, and secondly, when the patient's cholinergic rebound syndrome was misdiagnosed as acute alcohol withdrawal. Once the etiology was recognized, he was promptly treated with anticholinergic medication (benztropine) and retitrated to his outpatient dose of clozapine leading to the resolution of symptoms including delirium and EPS. This case will discuss the challenges of continuity of care in delirious, psychotic, or otherwise confused patients, including contributions from the COVID-19 pandemic. A medication card or other improvements in medication databases that may reduce delays in treatment are discussed.

18.
Br J Gen Pract ; 72(720): e446-e455, 2022 07.
Article in English | MEDLINE | ID: covidwho-1924323

ABSTRACT

BACKGROUND: Colchicine has been proposed as a COVID-19 treatment. AIM: To determine whether colchicine reduces time to recovery and COVID-19-related admissions to hospital and/or deaths among people in the community. DESIGN AND SETTING: Prospective, multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial (PRINCIPLE). METHOD: Adults aged ≥65 years or ≥18 years with comorbidities or shortness of breath, and unwell for ≤14 days with suspected COVID-19 in the community, were randomised to usual care, usual care plus colchicine (500 µg daily for 14 days), or usual care plus other interventions. The co-primary endpoints were time to first self-reported recovery and admission to hospital/death related to COVID-19, within 28 days, analysed using Bayesian models. RESULTS: The trial opened on 2 April 2020. Randomisation to colchicine started on 4 March 2021 and stopped on 26 May 2021 because the prespecified time to recovery futility criterion was met. The primary analysis model included 2755 participants who were SARS-CoV-2 positive, randomised to colchicine (n = 156), usual care (n = 1145), and other treatments (n = 1454). Time to first self-reported recovery was similar in the colchicine group compared with usual care with an estimated hazard ratio of 0.92 (95% credible interval (CrI) = 0.72 to 1.16) and an estimated increase of 1.4 days in median time to self-reported recovery for colchicine versus usual care. The probability of meaningful benefit in time to recovery was very low at 1.8%. COVID-19-related admissions to hospital/deaths were similar in the colchicine group versus usual care, with an estimated odds ratio of 0.76 (95% CrI = 0.28 to 1.89) and an estimated difference of -0.4% (95% CrI = -2.7 to 2.4). CONCLUSION: Colchicine did not improve time to recovery in people at higher risk of complications with COVID-19 in the community.


Subject(s)
COVID-19 , Adult , Bayes Theorem , COVID-19/drug therapy , Colchicine/therapeutic use , Humans , Prospective Studies , SARS-CoV-2 , Treatment Outcome
19.
Science translational medicine ; 2022.
Article in English | EuropePMC | ID: covidwho-1918644

ABSTRACT

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

20.
Health Commun ; 37(9): 1192-1203, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1908537

ABSTRACT

It is important to evaluate the media's health coverage of Indigenous communities both because these communities have been hit very hard by health inequities, and because misinformation can negatively affect the future health of Indian Country. This study takes the unique angle of examining both Indigenous and non-Indigenous ("mainstream") news publications to evaluate information gaps in health, health policy, and health efficacy coverage. The Indigenous media examined, which covered 14 times more health stories than mainstream media, highlighted health issues in Indian Country through the lens of resilience by using framing to emphasize unequal power, while at the same time providing depth and specificity. Instead of putting Indigenous health stories into historical and cultural context, mainstream media focused on the lack of resources and the chronic struggle of Indigenous communities. Mainstream media often only covered the topic once per outlet; however, those outlets with connections to Indigenous communities did provide more balanced coverage. Instead of promoting change, most mainstream media stories blamed Indigenous people for their situation and offered a doom trajectory for tribes hit hardest by health disparities. This study reveals how embedded framing and mediatization direct non-Native readers' attention away from the systemic deprivation of support to U.S. Indigenous tribes that was guaranteed to them by the U.S. government in tribal agreements. The implications for journalism and policy are discussed.


Subject(s)
Communication , Health Policy , Humans , Mass Media
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