Prolonged presence of replication‐competent SARS‐CoV‐2 in mildly symptomatic individuals: A report of two cases

Corrêa, Maria Cássia Mendes; Leal, Fábio E.; Boas, Lucy S. Vilas; A, de Paula; Tozetto‐Mendoza, Tânia Regina; Ferreira, Noely Evangelista; Curty, Gislaine; Carvalho, Pedro S. de; Buss, Lewis; Costa, Sílvia Figueiredo; Carvalho, Flávia Mendes da Cunha; Kawakami, Joyce T.; Taniwaki, Noemi Nosomi; Paião, Heuder Gustavo Oliveira; Bizário, João Carlos da Silva; Jesus, Jaqueline Góes de; Sabino, Éster Cerdeira; Romano, Camila Malta; Grepan, Regina Maura Zetone; Sesso, Antônio

doi:10.1002/jmv.27021

Cited by 7 publications

(4 citation statements)

References 23 publications

(47 reference statements)

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“…Viral reservoirs are cells or anatomical sites where a replication-competent form of the virus can persist and accumulate with higher kinetic stability than the main pool of actively replicating viruses [ 11 ]. The prolonged presence of replication-competent SARS-CoV-2 viral ribonucleic acid (RNA) in mildly symptomatic or clinically recovered individuals is extensively documented [ 12 , 13 , 14 ]. Even in asymptomatic individuals, 50% of intestinal biopsies obtained at 4 months after COVID-19 infection displayed a lingering presence of SARS-CoV-2 nucleic acids and immunoreactivity [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19

Loh¹,

Reíter

2022

IJMS

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The relentless, protracted evolution of the SARS-CoV-2 virus imposes tremendous pressure on herd immunity and demands versatile adaptations by the human host genome to counter transcriptomic and epitranscriptomic alterations associated with a wide range of short- and long-term manifestations during acute infection and post-acute recovery, respectively. To promote viral replication during active infection and viral persistence, the SARS-CoV-2 envelope protein regulates host cell microenvironment including pH and ion concentrations to maintain a high oxidative environment that supports template switching, causing extensive mitochondrial damage and activation of pro-inflammatory cytokine signaling cascades. Oxidative stress and mitochondrial distress induce dynamic changes to both the host and viral RNA m6A methylome, and can trigger the derepression of long interspersed nuclear element 1 (LINE1), resulting in global hypomethylation, epigenetic changes, and genomic instability. The timely application of melatonin during early infection enhances host innate antiviral immune responses by preventing the formation of “viral factories” by nucleocapsid liquid-liquid phase separation that effectively blockades viral genome transcription and packaging, the disassembly of stress granules, and the sequestration of DEAD-box RNA helicases, including DDX3X, vital to immune signaling. Melatonin prevents membrane depolarization and protects cristae morphology to suppress glycolysis via antioxidant-dependent and -independent mechanisms. By restraining the derepression of LINE1 via multifaceted strategies, and maintaining the balance in m6A RNA modifications, melatonin could be the quintessential ancient molecule that significantly influences the outcome of the constant struggle between virus and host to gain transcriptomic and epitranscriptomic dominance over the host genome during acute infection and PASC.

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Section: Introductionmentioning

confidence: 99%

Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19

Loh¹,

Reíter

2022

IJMS

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“…Effects of PAF Units on Deposition. When considering that viable SARS-CoV-2 is detectable on plastic and stainless steel surfaces for >72 h 27 and that viral shedding of replication-competent SARS-CoV-2 has been noted for greater than a week after initial infection in individuals with COVID-19, 70,71 it follows that studying engineering control measures that can be taken to lessen indirect exposure risk and additional viral load is important. The National Institute for Occupational Safety and Health, within their Hierarchy of Controls, 72 notes that engineering controls are one of the ways in which individuals can be isolated from a hazard in the environment.…”

Section: Discussionmentioning

confidence: 99%

Localized and Whole-Room Effects of Portable Air Filtration Units on Aerosol Particle Deposition and Concentration in a Classroom Environment

Kong

Eilts

et al. 2022

ACS EST Eng.

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In indoor environments with limited ventilation, recirculating portable air filtration (PAF) units may reduce COVID-19 infection risk via not only the direct aerosol route (i.e., inhalation) but also via an indirect aerosol route (i.e., contact with the surface where aerosol particles deposited). We systematically investigated the impact of PAF units in a mock classroom, as a supplement to background ventilation, on localized and whole-room surface deposition and particle concentration. Fluorescently tagged particles with a volumetric mean diameter near 2 μm were continuously introduced into the classroom environment via a breathing simulator with a prescribed inhalation–exhalation waveform. Deposition velocities were inferred on >50 horizontal and vertical surfaces throughout the classroom, while aerosol concentrations were spatially monitored via optical particle spectrometry. Results revealed a particle decay rate consistent with expectations based upon the reported clean air delivery rates of the PAF units. Additionally, the PAF units reduced peak concentrations by a factor of around 2.5 compared to the highest concentrations observed and led to a statistically significant reduction in deposition velocities for horizontal surfaces >2.5 m from the aerosol source. Our results not only confirm that PAF units can reduce particle concentrations but also demonstrate that they may lead to reduced particle deposition throughout an indoor environment when properly positioned with respect to the location of the particle source(s) within the room (e.g., where the largest group of students sit) and the predominant air distribution profile of the room.

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“…COVID status was determined by detection of SARS-CoV-2 on nasal samples or saliva by gene amplification and analysis, as described previously 15 . Health care workers were defined as any worker working within the HCFMUSP, including hospital and auxiliary services.…”

Section: Methodsmentioning

confidence: 99%

Association between development of severe COVID-19 and a polymorphism in the CIAS1 gene that codes for an inflammasome component

Tozetto‐Mendoza

Mendes-Corrêa

Linhares

et al. 2023

Sci Rep

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An elevated pro-inflammatory cytokine response is associated with severe life-threatening symptoms in individuals with Coronavirus Disease-2019 (COVID). The inflammasome is an intracellular structure responsible for generation of interleukin (IL)-1β and IL-18. NALP3, a product of the CIAS1 gene, is the rate-limiting component for inflammasome activity. We evaluated if a CIAS1 42 base pair length polymorphism (rs74163773) was associated with severe COVID. DNA from 93 individuals with severe COVID, 38 with mild COVID, and 98 controls were analyzed for this polymorphism. The 12 unit repeat allele is associated with the highest inflammasome activity. Five alleles, corresponding to 6, 7, 9, 12 or 13 repeat units, divided into 12 genotypes were identified. The frequency of the 12 unit repeat allele was 45.3% in those with severe disease as opposed to 30.0% in those with mild disease and 26.0% in controls (p < 0.0001, severe vs. controls). In contrast, the 7 unit repeat allele frequency was 30.1% in controls as opposed to 14.0% and 12.5% in those with severe or mild disease, respectively (p ≤ 0.0017). We conclude that individuals positive for the CIAS1 12 allele may be at elevated risk for development of severe COVID due to an increased level of induced pro-inflammatory cytokine production.

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Prolonged presence of replication‐competent SARS‐CoV‐2 in mildly symptomatic individuals: A report of two cases

Cited by 7 publications

References 23 publications

Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19

Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19

Localized and Whole-Room Effects of Portable Air Filtration Units on Aerosol Particle Deposition and Concentration in a Classroom Environment

Association between development of severe COVID-19 and a polymorphism in the CIAS1 gene that codes for an inflammasome component

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