Immune Determinants of Viral Clearance in Hospitalised COVID-19 Patients: Reduced Circulating Naïve CD4+ T Cell Counts Correspond with Delayed Viral Clearance

Abstract

Virus-specific cellular and humoral responses are major determinants for protection from critical illness after SARS-CoV-2 infection. However, the magnitude of the contribution of each of the components to viral clearance remains unclear. Here, we studied the timing of viral clearance in relation to 122 immune parameters in 102 hospitalised patients with moderate and severe COVID-19 in a longitudinal design. Delayed viral clearance was associated with more severe disease and was associated with higher levels of SARS-CoV-2-specific (neutralising) antibodies over time, increased numbers of neutrophils, monocytes, basophils, and a range of pro-inflammatory cyto-/chemokines illustrating ongoing, partially Th2 dominating, immune activation. In contrast, early viral clearance and less critical illness correlated with the peak of neutralising antibodies, higher levels of CD4 T cells, and in particular naïve CD4+ T cells, suggesting their role in early control of SARS-CoV-2 possibly by proving appropriate B cell help. Higher counts of naïve CD4+ T cells also correlated with lower levels of MIF, IL-9, and TNF-beta, suggesting an indirect role in averting prolonged virus-induced tissue damage. Collectively, our data show that naïve CD4+ T cell play a critical role in rapid viral T cell control, obviating aberrant antibody and cytokine profiles and disease deterioration. These data may help in guiding risk stratification for severe COVID-19.

Innate and adaptive immune response in SARS-CoV-2 infection-Current perspectives

“…SARS-CoV-2-specific CD4 + T cells were associated with ameliorated COVID-19 disease severity, and the induction of SARS-CoV-2-specific CD4 + T cells was correlated with rapid decrease of viral load ( 62 , 63 ). Another study also confirmed that early viral clearance and less critical illness were correlated with the higher counts of CD4 + T cells, particularly naïve CD4 + T cells ( 64 ).…”

A comparison of five Illumina, Ion Torrent, and nanopore sequencing technology-based approaches for whole genome sequencing of SARS-CoV-2

“…Samples were retrospectively included to be tested with five WGS protocols. Samples were previously sent to the Clinical Microbiological Laboratory of the Leiden University Medical Center (LUMC, The Netherlands) for nucleotide extraction and SARS-CoV-2 E-gene PCR testing [ 23 ] in the period March–October 2020 (Wuhan-like viruses circulating). After nucleotide extraction and PCR, samples were stored at ° C until further distribution between different centers for WGS analysis.…”

Causal association of the brain structure with the susceptibility, hospitalization, and severity of COVID‐19: A large‐scale genetic correlation study

“…Early SARS‐CoV‐2‐specific CD4+ T cells in the blood were associated with relatively milder disease 37 . Additionally, higher levels of CD4 T cells were associated with early viral clearance and milder COVID‐19 symptoms 38 . We presumed that increased CSF volume was positively correlated with the number of immune cells, which prevents the occurrence of more severe respiratory symptoms.…”

“…37 Additionally, higher levels of CD4 T cells were associated with early viral clearance and milder COVID-19 symptoms. 38 We presumed that increased CSF volume was positively correlated with the number of immune cells, which prevents the occurrence of more severe respiratory symptoms. Several retrospective studies have also found an association between the inferior temporal area and COVID-19.…”