Recovery of monocyte exhaustion is associated with resolution of lung injury in COVID-19 convalescence

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in the clinical syndrome COVID-19 is associated with an exaggerated immune response and monocyte infiltrates in the lungs and other peripheral tissues. It is now increasingly recognised that chronic morbidity persists in some patients. We recently demonstrated profound alterations of monocytes in hospitalised COVID-19 patients. It is currently unclear whether these abnormalities resolve or progress following patient discharge. We show here that blood monocytes in convalescent patients at their 12 week follow up, have a greater propensity to produce pro-inflammatory cytokines TNFα and IL-6, which was consistently higher in patients with resolution of lung injury as indicated by a normal chest X-ray and no shortness of breath (a key symptom of lung injury). Furthermore, monocytes from convalescent patients also displayed enhanced levels of molecules involved in leucocyte migration, including chemokine receptor CXCR6, adhesion molecule CD31/PECAM and integrins VLA-4 and LFA-1. Expression of migration molecules on monocytes was also consistently higher in convalescent patients with a normal chest X-ray. These data suggest persistent changes in innate immune function following recovery from COVID-19 and indicate that immune modulating therapies targeting monocytes and leucocyte migration may be useful in recovering COVID-19 patients with persistent symptoms.

Immuno-proteomic profiling reveals abundant airway CD8 T cells and ongoing epithelial injury in prolonged post-COVID19 respiratory disease

“…In our post-COVID19 patients, however, the monocyte and myeloid pools in both the airways and peripheral blood appear to have returned to relatively normal numbers and their frequency does not correlate with indicators of ongoing epithelial damage. Likewise, their activation status, as determined by HLA-DR and CD86 expression, is not substantially different between individuals in line with other reports on circulating monocytes from earlier stages of convalescence (Scott et al, 2020).…”

“…The copyright holder for this preprint this version posted August 10, 2021. ; https://doi.org/10.1101/2021.08.10.21261834 doi: medRxiv preprint Immune-proteome landscape post-COVID19 substantially different between individuals in line with other reports on circulating monocytes from earlier stages of convalescence (Scott et al, 2020).…”

“…SARS-CoV-2 infection results in formation of long-lasting systemic immunological memory, with virus-specific antibodies and T cell responses still detectable in the majority of those infected at least 8 months post infection and higher titers seen in previously hospitalized individuals (Dan et al, 2021). Circulating lymphocyte counts and the function and frequency of monocytes are also reduced during acute disease, but they appear to return to normal shortly after resolution of acute disease (Mann et al, 2020;Scott et al, 2020). Likewise, plasma concentrations of inflammatory mediators such as IL-6 and CXCL10, that are highly elevated in acute disease, reduce as individuals recover (Rodriguez et al, 2020).…”

COVID-19 and RA share an SPP1 myeloid pathway that drives PD-L1+ neutrophils and CD14+ monocytes

“…Emerging transcriptomic evidence shows that changes in blood myeloid cells elicited during acute infection can normalize within 14 days of becoming SARS2-CoV-2 negative (56). However, some changes can persist for at least 12 weeks, including high levels of surface molecules that regulate monocyte migration into tissue e.g., CXCR6 and VLA-4 (57). We found that in contrast for example to IL-6, plasma SPP1 and S100A12 remained significantly higher than normal for at least 10 weeks after infection clearance in the post-COVID-19 convalescent phase.…”

Immuno-proteomic profiling reveals aberrant immune cell regulation in the airways of individuals with ongoing post-COVID-19 respiratory disease

“…SARS-CoV-2 infection results in formation of long-lasting systemic immunological memory, with virus-specific antibodies and T cell responses still detectable in the majority of those infected at least 8 months post infection and higher titers seen in previously hospitalized individuals (Dan et al, 2021). Circulating lymphocyte counts and the function and frequency of monocytes are also reduced during acute disease, but they appear to return to normal shortly after resolution of acute disease (Mann et al, 2020;Scott et al, 2020).…”