Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Pérez-Gómez, Alberto; Vitallé, Joana; Gasca-Capote, Carmen; Gutiérrez‐Valencia, Alicia; Trujillo‐Rodríguez, María; Serna-Gallego, Ana; Muñoz-Muela, Esperanza; Jiménez-Leon, María de los Reyes; Benhnia, Mohammed Rafii‐El‐Idrissi; Rivas‐Jeremías, Inmaculada; Fernández-Villar, Alberto; Pérez-González, Alexandre; Poveda, Eva; Ruiz‐Mateos, Ezequiel; Cisneros, José Miguel; Salto‐Alejandre, Sonsoles; Berastegui‐Cabrera, Judith; Camacho‐Martínez, Pedro; Infante-Domínguez, Carmen; Carretero-Ledesma, Marta; Crespo‐Rivas, Juan Carlos; Márquez, Eduardo; Lomas, José Manuel; Bueno, C Villanueva; Amaya, Rosario; Lepe, José Antonio Suárez; Pachón, Jerónimo; Cordero, Elisa; Sánchez‐Céspedes, Javier; Aguilar‐Guisado, Manuela; Aguilera, Almudena; Aguilera, Clara; Aldabó-Pallás, Teresa; Alfaro-Lara, Verónica; Amodeo, Cristina; Ampuero, Javier; Avilés, María-Dolores; Asensio, Maribel; Barón‐Franco, Bosco; Barrera-Pulido, L.; Bellido-Alba, Rafael; Bernabéu-Wittel, Máximo; Caballero-Eraso, Candela; Cabrera, Macarena; Calderón, Enrique; Carbajal-Guerrero, J.; Cid-Cumplido, Manuela; Corcia-Palomo, Y.; Delgado, Juan; Domínguez-Petit, Antonio; Deniz, Alejandro; Dusseck-Brutus, Reginal; Escoresca‐Ortega, Ana; Espinosa, Fátima; Espinosa, Núria; Espinoza, Michelle; Ferrándiz-Millón, Carmen; Ferrer, Marta; Ferrer, Teresa; Gallego-Texeira, Ignacio; Gámez-Mancera, Rosa; García, Eva Alarcón; García-Delgado, Horacio; García-Gutiérrez, Manuel; Gascón-Castillo, María Luisa; González-Estrada, Aurora; González, Demetrio; Gómez-González, Carmen; González-León, Rocío; Grande-Cabrerizo, Carmen; Gutiérrez, Sonia; Hernández-Quiles, Carlos; Herrera-Melero, Inmaculada Concepción; Herrero-Romero, Marta; Jara, Luis; Jiménez-Juan, Carlos; Jiménez-Jorge, Silvia; Jiménez-Sánchez, Mercedes; Lanseros-Tenllado, Julia; López, Carmina; López, Isabel; López-Barrios, Álvaro; López‐Cortés, Luis F.; Luque‐Márquez, Rafael; Macías‐García, Daniel; Martín-Gutiérrez, Guillermo; Martín-Villén, Luis; Molina, J M; Morillo, Aurora Fernández‐Cañadas; Navarro-Amuedo, María Dolores; Nieto-Martín, Dolores; Ortega, Francisco J.; Paniagua-García, María; Peña-Rodríguez, Amelia; Pérez, Eduardo; Poyato, Manuel; Praena-Segovia, Julia; Ríos, Rafaela; Roca-Oporto, Cristina; Rodrı́guez, J.; Rodríguez-Hernández, María Jesús; Rodríguez-Suárez, Santiago; Rodríguez-Villodres, Ángel; Romero-Rodríguez, Nieves; Ruiz, Ricardo; Azua, Zida Ruiz de; Salamanca, Celia; Sánchez, Sònia; Sánchez-Montagut, Víctor Manuel; Sotomayor, César; Benjumea, Alejandro Suárez; Toral, Javier

doi:10.1038/s41423-021-00728-2

Cited by 92 publications

(51 citation statements)

References 40 publications

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“…Deep CD19 depletion has been unveiled in some patients with long-term and prolonged shedding of SARS-CoV-2 [24]. In addition, COVID-19 is associated with a deficit in plasmacytoid dendritic cells (pDCs) and their capacity to IFN-α production, which has been associated with disease severity and SARS-CoV-2 persistence [41,42]. Unexpectedly, in our patient, a severe CD4+ T-cell depletion, non-suppressed HIV viremia and an accumulation of life-threatening opportunistic infections, did not lead to a poorer COVID-19 course.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Evolution and Spike-Specific CD4+ T-Cell Response in Persistent COVID-19 with Severe HIV Immune Suppression

et al. 2022

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Intra-host evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported in cases with persistent coronavirus disease 2019 (COVID-19). In this study, we describe a severely immunosuppressed individual with HIV-1/SARS-CoV-2 coinfection with a long-term course of SARS-CoV-2 infection. A 28-year-old man was diagnosed with HIV-1 infection (CD4+ count: 3 cells/µL nd 563000 HIV-1 RNA copies/mL) and simultaneous Pneumocystis jirovecii pneumonia, disseminated Mycobacterium avium complex infection and SARS-CoV-2 infection. SARS-CoV-2 real-time reverse transcription polymerase chain reaction positivity from nasopharyngeal samples was prolonged for 15 weeks. SARS-CoV-2 was identified as variant Alpha (PANGO lineage B.1.1.7) with mutation S:E484K. Spike-specific T-cell response was similar to HIV-negative controls although enriched in IL-2, and showed disproportionately increased immunological exhaustion marker levels. Despite persistent SARS-CoV-2 infection, adaptive intra-host SARS-CoV-2 evolution, was not identified. Spike-specific T-cell response protected against a severe COVID-19 outcome and the increased immunological exhaustion marker levels might have favoured SARS-CoV-2 persistence.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Evolution and Spike-Specific CD4+ T-Cell Response in Persistent COVID-19 with Severe HIV Immune Suppression

et al. 2022

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“…Severe COVID-19 infections are associated with a dysregulation of myelopoiesis that is so extreme that monocytes and neutrophils are unrecognizable by blood smear [39], and have dramatic changes in granularity, size, and surface marker expression [40]. Both mild and severe COVID-19 are associated with changes in the number and migratory potential of dendritic cells for at least 7 months post-infection [41]. We do not know if the transient changes in expression of CCR2 and CX 3 CR 1 on circulating monocytes 1-3 months after infection are due to emigration of cells with the highest expression of those markers to inflamed or damaged tissues; however, CCL2 has been implicated in recruitment of monocyte to the lungs during infection [42].…”

Section: Discussionmentioning

confidence: 99%

Lasting Changes to Circulating Leukocytes in People with Mild SARS-CoV-2 Infections

Kennedy

Cook

Breznik

et al. 2021

Viruses

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Survivors of severe SARS-CoV-2 infections frequently suffer from a range of post-infection sequelae. Whether survivors of mild or asymptomatic infections can expect any long-term health consequences is not yet known. Herein we investigated lasting changes to soluble inflammatory factors and cellular immune phenotype and function in individuals who had recovered from mild SARS-CoV-2 infections (n = 22), compared to those that had recovered from other mild respiratory infections (n = 11). Individuals who had experienced mild SARS-CoV-2 infections had elevated levels of C-reactive protein 1–3 months after symptom onset, and changes in phenotype and function of circulating T-cells that were not apparent in individuals 6–9 months post-symptom onset. Markers of monocyte activation, and expression of adherence and chemokine receptors indicative of altered migratory capacity, were also higher at 1–3 months post-infection in individuals who had mild SARS-CoV-2, but these were no longer elevated by 6–9 months post-infection. Perhaps most surprisingly, significantly more T-cells could be activated by polyclonal stimulation in individuals who had recently experienced a mild SARS-CoV-2, infection compared to individuals with other recent respiratory infections. These data are indicative of prolonged immune activation and systemic inflammation that persists for at least three months after mild or asymptomatic SARS-CoV-2 infections.

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“…The role of NK cell subtypes and the killer immunoglobulin-like receptors (KIRs) that regulate their function during SARS-CoV-2 infection is still under investigation, since research has been mainly focused on the adaptive immune responses. Impaired NK cell counts and functionality [18], as well as deficits in other members of the innate immunity such as dendritic cells that include alterations in their homing and activation markers in SARS-COV-2-infected patients [19], have been reported. In the present study, we aimed to characterize the phenotypic and KIR expression changes in NK cells during COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Expansion of CD56dimCD16neg NK Cell Subset and Increased Inhibitory KIRs in Hospitalized COVID-19 Patients

Casado

Moraga

Vizcarra

et al. 2021

Viruses

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Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection induces elevated levels of inflammatory cytokines, which are mainly produced by the innate response to the virus. The role of NK cells, which are potent producers of IFN-γ and cytotoxicity, has not been sufficiently studied in the setting of SARS-CoV-2 infection. We confirmed a different distribution of NK cell subsets in hospitalized COVID-19 patients despite their NK cell deficiency. The impairment of this innate defense is mainly focused on the cytotoxic capacity of the CD56dim NK cells. On the one hand, we found an expansion of the CD56dimCD16neg NK subset, lower cytotoxic capacities, and high frequencies of inhibitory 2DL1 and 2DL1/S1 KIR receptors in COVID-19 patients. On the other hand, the depletion of CD56dimCD16dim/bright NK cell subsets, high cytotoxic capacities, and high frequencies of inhibitory 2DL1 KIR receptors were found in COVID-19 patients. In contrast, no differences in the distribution of CD56bright NK cell subsets were found in this study. These alterations in the distribution and phenotype of NK cells might enhance the impairment of this crucial innate line of defense during COVID-19 infection.

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Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Cited by 92 publications

References 40 publications

SARS-CoV-2 Evolution and Spike-Specific CD4+ T-Cell Response in Persistent COVID-19 with Severe HIV Immune Suppression

SARS-CoV-2 Evolution and Spike-Specific CD4+ T-Cell Response in Persistent COVID-19 with Severe HIV Immune Suppression

Lasting Changes to Circulating Leukocytes in People with Mild SARS-CoV-2 Infections

Expansion of CD56dimCD16neg NK Cell Subset and Increased Inhibitory KIRs in Hospitalized COVID-19 Patients

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