Persistent SARS-CoV-2 Nucleocapsid Protein Presence in the Intestinal Epithelium of a Pediatric Patient 3 Months After Acute Infection

Arostegui, Dalia; Castro, Kenny; Schwarz, Steven M.; Vaidy, Katherine; Rabinowitz, Simon S.; Wallach, Thomas

doi:10.1097/pg9.0000000000000152

Cited by 35 publications

(46 citation statements)

References 31 publications

(31 reference statements)

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“…Based on machine learning, cortisol levels alone were the most significant predictor for Long COVID classification, as well as for estimation of Long COVID Propensity Score. Multiple hypotheses have been proposed for Long COVID pathogenesis, including persistent virus/virus remnants, autoimmunity, dysbiosis, latent viral reactivation and unrepaired tissue damage 18,[32][33][34][35][36][37][38] . Our data suggest the involvement of persistent antigen, reactivation of latent herpesviruses, and chronic inflammation, and are less consistent with the autoantibodies to extracellular antigens.…”

Section: Discussionmentioning

confidence: 99%

Distinguishing features of Long COVID identified through immune profiling

Klein

Wood

Jaycox

et al. 2022

Preprint

206

220

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SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease called post-acute sequelae of COVID-19 (PASC) or Long COVID. Individuals diagnosed with Long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions; however, the basic biological mechanisms responsible for these debilitating symptoms are unclear. Here, 215 individuals were included in an exploratory, cross-sectional study to perform multi-dimensional immune phenotyping in conjunction with machine learning methods to identify key immunological features distinguishing Long COVID. Marked differences were noted in specific circulating myeloid and lymphocyte populations relative to matched control groups, as well as evidence of elevated humoral responses directed against SARS-CoV-2 among participants with Long COVID. Further, unexpected increases were observed in antibody responses directed against non-SARS-CoV-2 viral pathogens, particularly Epstein-Barr virus. Analysis of circulating immune mediators and various hormones also revealed pronounced differences, with levels of cortisol being uniformly lower among participants with Long COVID relative to matched control groups. Integration of immune phenotyping data into unbiased machine learning models identified significant distinguishing features critical in accurate classification of Long COVID, with decreased levels of cortisol being the most significant individual predictor. These findings will help guide additional studies into the pathobiology of Long COVID and may aid in the future development of objective biomarkers for Long COVID.

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Section: Discussionmentioning

confidence: 99%

Distinguishing features of Long COVID identified through immune profiling

Klein

Wood

Jaycox

et al. 2022

Preprint

206

220

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“…Gastrointestinal involvement is a frequent feature of long COVID-19 syndrome, 32 furthermore long-term presence of SARS-CoV-2 nucleocapsid protein was found in the gut mucosa of patients suffering from long COVID-19. 33 Our finding that intestinal bacteria may support SARS-CoV-2 replication therefore is likely to have important bearing on explaining the pathophysiology of the gastrointestinal symptoms during long COVID-19. On a separate note, the evidence we provide here that SARS-CoV-2 is capable of replicating in F.prausnitzii gives new significance to earlier evidence of inverse correlation between abundance of this anti-inflammatory bacterium in the intestines and COVID-19 severity, 17 suggesting indirectly that infection of symbiotic gut bacteria may correlate positively with disease severity.…”

mentioning

confidence: 83%

Evidence of SARS-CoV-2 bacteriophage potential in human gut microbiota

Petrillo¹,

Querci

Brogna³

et al. 2022

F1000Res

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Background: In previous studies we have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates in vitro in bacterial growth medium, that the viral replication follows bacterial growth, and it is influenced by the administration of specific antibiotics. These observations are compatible with a ‘bacteriophage-like’ behaviour of SARS-CoV-2. Methods: We have further elaborated on these unusual findings and here we present the results of three different supplementary experiments: (1) an electron-microscope analysis of samples of bacteria obtained from a faecal sample of a subject positive to SARS-CoV-2; (2) mass spectrometric analysis of these cultures to assess the eventual de novo synthesis of SARS-CoV-2 spike protein; (3) sequencing of SARS-CoV-2 collected from plaques obtained from two different gut microbial bacteria inoculated with supernatant from faecal microbiota of an individual positive to SARS-CoV-2. Results: Immuno-labelling with Anti-SARS-CoV-2 nucleocapsid protein antibody confirmed presence of SARS-CoV-2 both outside and inside bacteria. De novo synthesis of SARS-CoV-2 spike protein was observed, as evidence that SARS-CoV-2 RNA is translated in the bacterial cultures. In addition, phage-like plaques were spotted on faecal bacteria cultures after inoculation with supernatant from faecal microbiota of an individual positive to SARS-CoV-2. Bioinformatic analyses on the reads obtained by sequencing RNA extracted from the plaques revealed nucleic acid polymorphisms, suggesting different replication environment in the two bacterial cultures. Conclusions: Based on these results we conclude that, in addition to its well-documented interactions with eukaryotic cells, SARS-CoV-2 may act as a bacteriophage when interacting with at least two bacterial species known to be present in the human microbiota. If the hypothesis proposed, i.e., that under certain conditions SARS-CoV-2 may multiply at the expense of human gut bacteria, is further substantiated, it would drastically change the model of acting and infecting of SARS-CoV-2, and most likely that of other human pathogenic viruses.

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“…This adaptation is a marked advantage for SARS‐CoV‐2 since it allows for increased transmissibility prior to more invasive infection of the lower airway and arguably could contribute to more asymptomatic spread. Interestingly, with the emergence of SARS‐CoV‐2 variants throughout the pandemic, fluctuations in viral replication levels across different mucosal surfaces of the airway have also been noted, 13 as well as evidence of lingering viral antigen in the intestinal mucosa 14,15 . A significant gap in our knowledge exists regarding the interaction between host immunity and SARS‐CoV‐2 along the mucosal tract, in addition to compartmental variations.…”

Section: Location Location Locationmentioning

confidence: 99%

Guardians of the oral and nasopharyngeal galaxy: IgA and protection against SARS‐CoV‐2 infection*

Sheikh-Mohamed

Sanders

Gommerman

et al. 2022

Immunological Reviews

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In early 2020, a global emergency was upon us in the form of the coronavirus disease 2019 (COVID-19) pandemic. While horrific in its health, social and economic devastation, one silver lining to this crisis has been a rapid mobilization of cross-institute, and even cross-country teams that shared common goals of learning as much as we could as quickly as possible about the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and how the immune system would respond to both the virus and COVID-19 vaccines. Many of these teams were formed by women who quickly realized that the classical model of "publish first at all costs" was maladaptive for the circumstances and needed to be supplanted by a more collaborative solution-focused approach. This review is an example of a collaboration that unfolded in separate countries, first Canada and the United States, and then also Israel. Not only did the collaboration allow us to cross-validate our results using different hands/techniques/ samples, but it also took advantage of different vaccine types and schedules that were rolled out in our respective home countries. The result of this collaboration was a new understanding of how mucosal immunity to SARS-CoV-2 infection vs COVID-19 vaccination can be measured using saliva as a biofluid, what types of vaccines are best able to induce (limited) mucosal immunity, and what are potential correlates of protection against breakthrough infection. In this review, we will share what we have learned about the mucosal immune response to SARS-CoV-2 and to COVID-19 vaccines and provide a perspective on what may be required for next-generation pansarbecoronavirus vaccine approaches.

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Persistent SARS-CoV-2 Nucleocapsid Protein Presence in the Intestinal Epithelium of a Pediatric Patient 3 Months After Acute Infection

Cited by 35 publications

References 31 publications

Distinguishing features of Long COVID identified through immune profiling

Distinguishing features of Long COVID identified through immune profiling

Evidence of SARS-CoV-2 bacteriophage potential in human gut microbiota

Guardians of the oral and nasopharyngeal galaxy: IgA and protection against SARS‐CoV‐2 infection*

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