Persistence of SARS-CoV-2 RNA in lung tissue after mild COVID-19

Ceulemans, Laurens J.; Khan, Mona; Yoo, Sung Jin; Zapiec, Bolek; Gerven, Laura Van; Slambrouck, Jan Van; Vanstapel, Arno; Raemdonck, Dirk Van; Vos, Robin; Wauters, Els; Wauters, Joost; Carmeliet, Peter; Mombaerts, Peter

doi:10.1016/s2213-2600(21)00240-x

Cited by 37 publications

(35 citation statements)

References 6 publications

(5 reference statements)

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“…The presence of persistent viral reservoirs of SARS-CoV-2 has been proposed as a possible explanation of PASC pathophysiology (27). Studies in macaques and humans demonstrated viral replication can persist months after initial infection in multiple organ systems (28)(29)(30)(31) and viral presence in cerebrospinal fluid has been observed in neurological PASC (32). Alternatively, damage resulting from severe disease during acute infection has also been proposed as a cause of PASC (27).…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2-specific T cells associate with reduced lung function and inflammation in pulmonary post-acute sequalae of SARS-CoV-2

Littlefield

Watson

Schneider

et al. 2022

Preprint

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As of January 2022, at least 60 million individuals are estimated to develop post-acute sequelae of SARS-CoV-2 (PASC) after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While elevated levels of SARS-CoV-2-specific T cells have been observed in non-specific PASC, little is known about their impact on pulmonary function which is compromised in the majority of these individuals. This study compares frequencies of SARS-CoV-2-specific T cells and inflammatory markers with lung function in participants with pulmonary PASC and resolved COVID-19 (RC). Compared to RC, participants with respiratory PASC had up to 34-fold higher frequencies of IFN-γ- and TNF-α-producing SARS-CoV-2-specific CD4+ and CD8+ T cells in peripheral blood and elevated levels of plasma CRP and IL-6. Importantly, in PASC participants the frequency of TNF-α-producing SARS-CoV-2-specific CD4+ and CD8+ T cells, which exhibited the highest levels of Ki67 indicating they were activity dividing, correlated positively with plasma IL-6 and negatively with measures of lung function, including forced expiratory volume in one second (FEV1), while increased frequencies of IFN-γ-producing SARS-CoV-2-specific T cells associated with prolonged dyspnea. Statistical analyses stratified by age, number of comorbidities and hospitalization status demonstrated that none of these factors affect differences in the frequency of SARS-CoV-2 T cells and plasma IL-6 levels measured between PASC and RC cohorts. Taken together, these findings demonstrate elevated frequencies of SARS-CoV-2-specific T cells in individuals with pulmonary PASC are associated with increased systemic inflammation and decreased lung function, suggesting that SARS-CoV-2-specific T cells contribute to lingering pulmonary symptoms. These findings also provide mechanistic insight on the pathophysiology of PASC that can inform development of potential treatments to reduce symptom burden.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2-specific T cells associate with reduced lung function and inflammation in pulmonary post-acute sequalae of SARS-CoV-2

Littlefield

Watson

Schneider

et al. 2022

Preprint

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“…RT‐PCR on a biopsy of the donor lung before LTx revealed a low viral load with a Ct value of 35, reflecting persistence of viral RNA. Viral culture on the same sample was negative 4,5 . Interestingly, in samples of the respiratory mucosa of the nasal cavity in the same donor, no persistence of viral RNA was detected 6 …”

Section: Figurementioning

confidence: 90%

“…Viral culture on the same sample was negative. 4,5 Interestingly, in samples of the respiratory mucosa of the nasal cavity in the same donor, no persistence of viral RNA was detected. 6 Several cases of liver, kidney, and heart transplantation with organs from RT-PCR positive donors have been reported but no donor-derived SARS-CoV-2 transmission has occurred.…”

mentioning

confidence: 90%

Lung donation and SARS‐CoV‐2 transmission: Missed detection versus missed opportunity?

Slambrouck

Raemdonck

Wauters

et al. 2022

Immunity Inflam & Disease

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“…It was suggested that patients developing PASC generally had higher pro-inflammatory cytokine levels, among them TNFα [128]. It has been speculated that there may be a hidden reservoir of SARS-CoV-2 and studies have reported the persistence of viral proteins and RNA in intestinal biopsies [129,130]. Slow replication or traces of viral components could provide triggers for the immune system, fueling chronic inflammation and facilitating PASC [95,129].…”

Section: Post-acute Sequelae Of Covid19 (Pasc)mentioning

confidence: 99%

Implications of Innate Immunity in Post-Acute Sequelae of Non-Persistent Viral Infections

Hirschenberger

Hunszinger

Sparrer

2021

Cells

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Non-persistent viruses classically cause transient, acute infections triggering immune responses aimed at the elimination of the pathogen. Successful viruses evolved strategies to manipulate and evade these anti-viral defenses. Symptoms during the acute phase are often linked to dysregulated immune responses that disappear once the patient recovers. In some patients, however, symptoms persist or new symptoms emerge beyond the acute phase. Conditions resulting from previous transient infection are termed post-acute sequelae (PAS) and were reported for a wide range of non-persistent viruses such as rota-, influenza- or polioviruses. Here we provide an overview of non-persistent viral pathogens reported to be associated with diverse PAS, among them chronic fatigue, auto-immune disorders, or neurological complications and highlight known mechanistic details. Recently, the emergence of post-acute sequelae of COVID-19 (PASC) or long COVID highlighted the impact of PAS. Notably, PAS of non-persistent infections often resemble symptoms of persistent viral infections, defined by chronic inflammation. Inflammation maintained after the acute phase may be a key driver of PAS of non-persistent viruses. Therefore, we explore current insights into aberrant activation of innate immune signaling pathways in the post-acute phase of non-persistent viruses. Finally, conclusions are drawn and future perspectives for treatment and prevention of PAS are discussed.

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Persistence of SARS-CoV-2 RNA in lung tissue after mild COVID-19

Cited by 37 publications

References 6 publications

SARS-CoV-2-specific T cells associate with reduced lung function and inflammation in pulmonary post-acute sequalae of SARS-CoV-2

SARS-CoV-2-specific T cells associate with reduced lung function and inflammation in pulmonary post-acute sequalae of SARS-CoV-2

Lung donation and SARS‐CoV‐2 transmission: Missed detection versus missed opportunity?

Implications of Innate Immunity in Post-Acute Sequelae of Non-Persistent Viral Infections

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