CCR5 inhibition in critical COVID-19 patients decreases inflammatory cytokines, increases CD8 T-cells, and decreases SARS-CoV2 RNA in plasma by day 14

Patterson, Bruce K.; Seethamraju, Harish; Dhody, Kush; Corley, Michael J.; Kazempour, Kazem; Lalezari, J.; Pang, Alina P.S.; Sugai, Christopher; Mahyari, Eisa; Francisco, Edgar B.; Pise, Amruta; Rodrigues, Hallison; Wu, Helen L.; Webb, Gabriela M.; Park, Byung; Kelly, Scott A.; Pourhassan, Nader; Lelic, Alina; Kdouh, Lama; Herrera, Mónica; Hall, Eric W.; Bimber, Benjamin N.; Plassmeyer, Matthew; Gupta, Raavi; Alpan, Oral; O’Halloran, Jane A.; Mudd, Philip A.; Akalin, Enver; Ndhlovu, Lishomwa C.; Sacha, Jonah B.

doi:10.1016/j.ijid.2020.10.101

Cited by 111 publications

(97 citation statements)

References 27 publications

(34 reference statements)

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“…To better estimate the peak severity of the subject’s illness, we measured SARS-CoV-2 viral replication and circulating plasma cytokines as previously described ( 7 , 9 ). Plasma viral load peaked on the third day of study enrollment – the subject’s 15 th day of symptomatic illness ( Figure 2B ).…”

Section: Resultsmentioning

confidence: 99%

“…Plasma viral load measurement was performed as previously described ( 7 ). Briefly, viral RNA was extracted from 100 µL or 200 µL of plasma using the QIAamp Viral Mini Kit (Qiagen) and used immediately in the Bio-Rad SARS-CoV-2 ddPCR kit (Bio-Rad).…”

Section: Methodsmentioning

confidence: 99%

“…Data were analyzed using QuantaSoft 1.7 and QuantaSoft Analysis Pro 1.0 software. The reproducible limit of detection of the assay is 313 viral copies per mL of plasma ( 7 ).…”

Section: Methodsmentioning

confidence: 99%

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SARS-CoV-2 Viral RNA Shedding for More Than 87 Days in an Individual With an Impaired CD8+ T Cell Response

et al. 2021

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Prolonged shedding of viral RNA occurs in some individuals following SARS-CoV-2 infection. We perform comprehensive immunologic evaluation of one individual with prolonged shedding. The case subject recovered from severe COVID-19 and tested positive for SARS-CoV-2 viral RNA repeatedly as many as 87 days after the first positive test, 97 days after symptom onset. The subject did not have any associated rise in anti-Spike protein antibody titers or plasma neutralization activity, arguing against re-infection. This index subject exhibited a profoundly diminished circulating CD8+ T cell population and correspondingly low SARS-CoV-2-specific CD8+ T cell responses when compared with a cohort of other recovering COVID-19 subjects. CD4+ T cell responses and neutralizing antibody responses developed as expected in this individual. Our results demonstrate that detectable viral RNA shedding in the upper airway can occur more than 3 months following infection in some individuals with COVID-19 and suggest that impaired CD8+ T cells may play a role in prolonged viral RNA shedding.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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SARS-CoV-2 Viral RNA Shedding for More Than 87 Days in an Individual With an Impaired CD8+ T Cell Response

et al. 2021

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“…This event, known as cytokine storm, is an immunopathological feature of COVID-19 and it has been associated with the severity of the disease. The increase in blood concentrations of different cytokines and chemokines such as IL-6, IL-8, IL-10, TNF-α, IL-1β, IL-2, IP-10, MCP-1, CCL3, CCL4, and CCL5 has been described for COVID-19 patients (5). Some of these molecules have been proposed as biomarkers to monitor the clinical evolution and to determine treatment selection for COVID-19 patients.…”

Section: Discussionmentioning

confidence: 97%

Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning

Patterson

Guevara-Coto

Yogendra³

et al. 2020

Preprint

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Individuals with systemic symptoms long after COVID-19 has cleared represent approximately ~10% of all COVID-19 infected individuals. Here we present a bioinformatics approach to predict and model the phases of COVID so that effective treatment strategies can be devised and monitored. We investigated 144 individuals including normal individuals and patients spanning the COVID-19 disease continuum. We collected plasma and isolated PBMCs from 29 normal individuals, 26 individuals with mild-moderate COVID-19, 25 individuals with severe COVID-19, and 64 individuals with Chronic COVID-19 symptoms. Immune subset profiling and a 14-plex cytokine panel were run on all patients. Data was analyzed using machine learning methods to predict and distinguish the groups from each other.Using a multi-class deep neural network classifier to better fit our prediction model, we recapitulated a 100% precision, 100% recall and F1 score of 1 on the test set. Moreover, a first score specific for the chronic COVID-19 patients was defined as S1 = (IFN-γ + IL-2)/ CCL4-MIP-1β. Second, a score specific for the severe COVID-19 patients was defined as S2 = (10*IL-10 + IL-6) - (IL-2 + IL-8). Severe cases are characterized by excessive inflammation and dysregulated T cell activation, recruitment, and counteracting activities. While chronic patients are characterized by a profile able to induce the activation of effector T cells with pro-inflammatory properties and the capacity of generating an effective immune response to eliminate the virus but without the proper recruitment signals to attract activated T cells.SummaryImmunologic Modeling of Severity and Chronicity of COVID-19

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“…To better estimate the peak severity of the subject's illness, we measured SARS-CoV-2 viral replication and circulating plasma cytokines as previously described (7,9). Plasma viral load peaked on the third day of study enrollmentthe subject's 15 th day of symptomatic illness ( Figure 2B).…”

Section: Comprehensive Immunologic Evaluationmentioning

confidence: 99%

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CCR5 inhibition in critical COVID-19 patients decreases inflammatory cytokines, increases CD8 T-cells, and decreases SARS-CoV2 RNA in plasma by day 14

Cited by 111 publications

References 27 publications

SARS-CoV-2 Viral RNA Shedding for More Than 87 Days in an Individual With an Impaired CD8+ T Cell Response

SARS-CoV-2 Viral RNA Shedding for More Than 87 Days in an Individual With an Impaired CD8+ T Cell Response

Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning

DataSheet_1.pdf

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