Persistent SARS-CoV-2 infection: significance and implications

Machkovech, Heather M; Hahn, Anne M; Garonzik Wang, Jacqueline; Grubaugh, Nathan D; Halfmann, Peter J; Johnson, Marc C; Lemieux, Jacob E; O'Connor, David H; Piantadosi, Anne; Wei, Wanting; Friedrich, Thomas C

doi:10.1016/s1473-3099(23)00815-0

Cited by 39 publications

(8 citation statements)

References 60 publications

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“…The results presented above add to an accumulating body of evidence suggesting that in a small number of cases SARS-CoV-2 can form a reservoir in different anatomical compartments [48][49][50] and that in many cases this reservoir is not always detectable via conventional SARS-CoV-2 testing [48] . This highlights that further investigation on how these tissue reservoirs contribute to SARS-CoV-2 persistence is needed.…”

Section: Discussionsupporting

confidence: 55%

“…These observations also have implications for the care of immunocompromised individuals as a negative SARS-CoV-2 test is not a guarantee that an infection has cleared. Alternative specimen types, such as stool should be considered [50] and any SARS-CoV-2 positive samples from immunocompromised patients should be sequenced to distinguish between acute and long-term SARS-CoV-2 infections.…”

Section: Discussionmentioning

confidence: 99%

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Intrahost evolution leading to distinct lineages in the upper and lower respiratory tracts during SARS-CoV-2 prolonged infection

El Moussaoui,

Bontems,

Meex

et al. 2024

Preprint

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Accumulating evidence points to persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunocompromised individuals as a source of genetically divergent, novel lineages, generally characterised by increased transmissibility and immune escape. While intrahost evolutionary dynamics of the virus in chronically infected patients have been previously reported, existing knowledge is primarily based on samples obtained from the nasopharyngeal compartment. In this study, we investigate the intrahost evolution and genetic diversity that accumulated during a prolonged SARS-CoV-2 infection with the Omicron sublineage BF.7, estimated to have persisted for over one year in an immunosuppressed patient. Based on the sequencing of eight viral genomes collected from the patient at six time points, we identified 86 intrahost single-nucleotide variants (iSNVs), two indels, and a 362 bp deletion. Our analysis revealed distinct viral genotypes in the nasopharyngeal (NP), endotracheal aspirate (ETA), and bronchoalveolar (BAL) samples. Notably, while significant divergence was observed between NP and BAL samples, most of the iSNVs found in ETA samples were also detected in NP or BAL samples. This suggests that NP samples may not offer a comprehensive representation of the overall intrahost viral diversity. Nonsynonymous mutations were most frequent in the spike and envelope genes, along with loss-of-function mutations in ORF8, generated by a frameshift mutation and a large deletion detected in the BAL and NP samples, respectively. Using long-range PCR on SARS-CoV-2 samples sequenced as part of routine surveillance, we validated that similar deletions causing ORF8 loss of function can be carried by SARS-CoV-2 during acute infection. Our findings not only demonstrate that the Omicron sublineage BF.7 can further diverge from its already exceptionally mutated state but also highlight that patients chronically infected with SARS-CoV-2 can develop genetically specific viral populations across distinct anatomical compartments. This provides novel insights into the intricate nature of viral diversity and evolution dynamics in persistent infections.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Intrahost evolution leading to distinct lineages in the upper and lower respiratory tracts during SARS-CoV-2 prolonged infection

El Moussaoui,

Bontems,

Meex

et al. 2024

Preprint

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“…We and others have reported such clinical cases -patients who have received B-cell targeting therapies and were currently on extended cortical steroids treatment (affecting also the T cell activity) would experience prolonged respiratory symptoms following SARS-CoV-2 infection. 4 Clinical observations underscore the lingering respiratory symptoms following SARS-CoV-2 infection in patients subjected to such therapies, further emphasizing the urgent need for clinical research and therapeutic interventions tailored to this demographic.…”

Section: Commentarymentioning

confidence: 99%

“…In these patients, the limited inflammatory response against viral infection leads to persisting symptoms such as fever and shortness of breath; on the other hand, the immune response is not strong enough to clear the virus, leading to the lesions being migratory in radiological examinations. 4 We propose to describe this scenario as chronic active SARS-CoV-2 infection, particularly in B-cell immunodeficiency (CASBI). The chronic here describes the persistent detection of SARS-CoV-2 in the respiratory tract samples and prolonged viral shedding, usually for more than 30-60 days.…”

Section: Commentarymentioning

confidence: 99%

Chronic active SARS-CoV-2 in B-cell immunodeficiency

Xu,

Zhang,

Wang

et al. 2024

TIME

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“…Over the past three years, the spread and severity of coronavirus disease 19 (COVID-19) have declined. However, a rare and intriguing manifestation of SARS-CoV-2 infection, known as ‘prolonged SARS-CoV-2 infection’ is garnering attention [ 1 ]. This condition encompasses cases of SARS-CoV-2 infection that extend beyond the typical duration of viral shedding in the respiratory tract, which is usually 17–21 days, along with persistent clinical symptoms [ 2 3 4 5 ].…”

Section: Introductionmentioning

confidence: 99%

Radiologic Abnormalities in Prolonged SARS-CoV-2 Infection: A Systematic Review

Beck,

Yoon,

Yoon

2024

Korean J Radiol

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We systematically reviewed radiological abnormalities in patients with prolonged SARS-CoV-2 infection, defined as persistently positive polymerase chain reaction (PCR) results for SARS-CoV-2 for > 21 days, with either persistent or relapsed symptoms. We extracted data from 24 patients (median age, 54.5 [interquartile range, 44–64 years]) reported in the literature and analyzed their representative CT images based on the timing of the CT scan relative to the initial PCR positivity. Our analysis focused on the patterns and distribution of CT findings, severity scores of lung involvement on a scale of 0–4, and the presence of migration. All patients were immunocompromised, including 62.5% (15/24) with underlying lymphoma and 83.3% (20/24) who had received anti-CD20 therapy within one year. Median duration of infection was 90 days. Most patients exhibited typical CT appearance of coronavirus disease 19 (COVID-19), including ground-glass opacities with or without consolidation, throughout the follow-up period. Notably, CT severity scores were significantly lower during ≤ 21 days than during > 21 days ( P < 0.001). Migration was observed on CT in 22.7% (5/22) of patients at ≤ 21 days and in 68.2% (15/22) to 87.5% (14/16) of patients at > 21 days, with rare instances of parenchymal bands in previously affected areas. Prolonged SARS-CoV-2 infection usually presents as migrating typical COVID-19 pneumonia in immunocompromised patients, especially those with impaired B-cell immunity.

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Persistent SARS-CoV-2 infection: significance and implications

Cited by 39 publications

References 60 publications

Intrahost evolution leading to distinct lineages in the upper and lower respiratory tracts during SARS-CoV-2 prolonged infection

Intrahost evolution leading to distinct lineages in the upper and lower respiratory tracts during SARS-CoV-2 prolonged infection

Chronic active SARS-CoV-2 in B-cell immunodeficiency

Radiologic Abnormalities in Prolonged SARS-CoV-2 Infection: A Systematic Review

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