Prolonged SARS-CoV-2 Positivity in Immunocompetent Patients: Virus Isolation, Genomic Integrity, and Transmission Risk

Leitão, Isabela de Carvalho; Calil, Pedro Telles; Galliez, Rafael Mello; Moreira, Filipe Romero Rebello; Mariani, Diana; Castiñeiras, Anna Carla Pinto; Silva, Gustavo Peixoto Duarte da; Maia, Richard Araujo; Corrêa, Isadora Alonso; Monteiro, Fábio L.; Souza, Marcos Romário Matos de; Gonçalves, Cássia Cristina Alves; Higa, Luiza M.; Ribeiro, Liane de Jesus; Fonseca, Vinicius Wakoff Pereira; Bastos, Victoria Cortes; Voloch, Carolina M; Faffe, Débora S.; Ferreira, Orlando da Costa; Tanuri, Amílcar; Castiñeiras, Terezinha Marta Pereira Pinto; Costa, Luciana Jesus da

doi:10.1128/spectrum.00855-21

Cited by 11 publications

(13 citation statements)

References 40 publications

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“…Most long-term carriers remained SARS-CoV-2 positive by qRT-PCR despite seroconversion, reinforcing the risk of continuous SARS-CoV-2 transmission 23,27,28 . Defects in antigen-specific cytotoxic T cell responses were found in such patients 29 , but the immune dynamics during the first days of infection remains unclear.…”

Section: (Which Was Not Certified By Peer Review) Preprintmentioning

confidence: 90%

“…Although viral persistence has been more frequently described in immunosuppressed patients, persistent URT infection and long-term virus shedding have been documented in immunocompetent patients with asymptomatic or mild COVID-19 as well 22–26 . Most long-term carriers remained SARS-CoV-2 positive by qRT-PCR despite seroconversion, reinforcing the risk of continuous SARS-CoV-2 transmission 23,27,28 . Defects in antigen-specific cytotoxic T cell responses were found in such patients 29 , but the immune dynamics during the first days of infection remains unclear.…”

Section: Introductionmentioning

confidence: 90%

“…19.22282546 doi: medRxiv preprint Low resistance might impact SARS-CoV-2 clearance in multiple ways, leading to high viral titers in the upper-respiratory tract (URT), dissemination to other tissues, especially the lungs, or longterm virus persistence. Although viral persistence has been more frequently described in immunosuppressed patients, persistent URT infection and long-term virus shedding have been documented in immunocompetent patients with asymptomatic or mild COVID-19 as well [22][23][24][25][26] .…”

Section: (Which Was Not Certified By Peer Review) Preprintmentioning

confidence: 99%

“…In COVID-19 as well as in other viral infections, oligosymptomatic and asymptomatic carriers represent the main vector of viral transmission. Therefore, long-term immunocompetent infected individuals are potential long-term spreaders and may, additionally, facilitate intra-host evolution of SARS-CoV-2 and other viruses 17,22,23 . This reinforces the need for a better understanding of the immune mechanisms of viral control in these patients.…”

Section: (Which Was Not Certified By Peer Review) Preprintmentioning

confidence: 99%

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Oligosymptomatic long-term carriers of SARS-CoV-2 display impaired innate resistance and high Spike-specific neutralizing antibodies

Montes-Cobos

Bastos

Monteiro

et al. 2022

Preprint

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The vast spectrum of clinical features of COVID-19 keeps challenging scientists and clinicians. Control of pathogen load (host resistance) and prevention of tissue damage (disease tolerance) are essential for the outcome of infectious diseases. Both low resistance and high disease tolerance might result in long-term viral persistence, but the underlying mechanisms remain unclear. Here, we studied the immune response of immunocompetent COVID-19 patients with prolonged SARS-CoV-2 infection by immunophenotyping, cytokine and serological analysis. Despite viral loads and symptoms comparable to regular mildly-symptomatic patients, long-term carriers displayed weaker systemic IFN-I responses and fewer circulating pDCs and NK cells at disease onset. Type 1 cytokines remained low, while type-3 cytokines were in turn enhanced. Interestingly, the plasma of these patients showed a higher spike-specific neutralization capacity. The identification of very early distinct immune responses in long-term carriers adds up to our understanding on essential host protective mechanisms to ensure tissue damage control despite prolonged viral infection.

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Section: (Which Was Not Certified By Peer Review) Preprintmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 90%

Section: (Which Was Not Certified By Peer Review) Preprintmentioning

confidence: 99%

Section: (Which Was Not Certified By Peer Review) Preprintmentioning

confidence: 99%

See 2 more Smart Citations

Oligosymptomatic long-term carriers of SARS-CoV-2 display impaired innate resistance and high Spike-specific neutralizing antibodies

Montes-Cobos

Bastos

Monteiro

et al. 2022

Preprint

Self Cite

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“…At the same time, the absence of support from the adaptive immune response could result in persistent infection resulting in a more severe pathological damage in the respiratory and intestinal tissues. Long-term presence of active SARS-CoV-2 in patients is an indication of such a strategy (34). Whether this scenario contributed to higher cases of respiratory sickness associated with Delta infection needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Variant Delta Potently Suppresses Innate Immune Response and Evades Interferon-Activated Antiviral Responses

Tandel

Sah

Singh

et al. 2022

Preprint

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Delta variant of SARS-CoV-2 has caused more severe infections than its previous variants. We studied the host innate immune response to Delta, Alpha and two earlier variants to map the evolution of the recent ones. Our biochemical and transcriptomic studies reveal that Alpha and Delta have progressively evolved over the ancestral variants by silencing innate immune response, thereby limiting cytokine and chemokine production. Though Alpha silenced RLR pathway just as Delta, it failed to persistently silence the innate immune response unlike Delta. Both Alpha and Delta have evolved to resist IFN treatment while they are still susceptible to RLR activation, further highlighting the importance of RLR-mediated, IFN-independent mechanisms in restricting SARS-CoV-2. Our studies reveal that SARS-CoV-2 Delta has integrated multiple mechanisms to silence host innate immune response and evade IFN response. Delta's silent replication and sustained suppression of host innate immune response, possibly resulting in delayed or reduced intervention by the adaptive immune response, could potentially contribute to the severe symptoms and poor recovery index associated with it.

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Oligosymptomatic long-term carriers of SARS-CoV-2 display impaired innate resistance but increased high-affinity anti-spike antibodies

Montes-Cobos¹,

Bastos²,

Monteiro³

et al. 2023

iScience

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Prolonged SARS-CoV-2 Positivity in Immunocompetent Patients: Virus Isolation, Genomic Integrity, and Transmission Risk

Abstract: In this study, we evaluated mildly symptomatic immunocompetent patients with long-lasting positive rRT-PCR results for SARS-CoV-2. Infectious viruses were successfully isolated in cell cultures from nasopharynx samples obtained 14 days or longer after symptom onset.

Cited by 11 publications

References 40 publications

Oligosymptomatic long-term carriers of SARS-CoV-2 display impaired innate resistance and high Spike-specific neutralizing antibodies

Oligosymptomatic long-term carriers of SARS-CoV-2 display impaired innate resistance and high Spike-specific neutralizing antibodies

SARS-CoV-2 Variant Delta Potently Suppresses Innate Immune Response and Evades Interferon-Activated Antiviral Responses

Oligosymptomatic long-term carriers of SARS-CoV-2 display impaired innate resistance but increased high-affinity anti-spike antibodies

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