An early analysis of circulating monocytes may be critical for predicting COVID-19 course and its sequelae. In 131 untreated, acute COVID-19 patients at emergency room arrival, monocytes showed decreased surface molecule expression, including low HLA-DR, in association with an inflammatory cytokine status and limited anti-SARS-CoV-2-specific T cell response. Most of these alterations had normalized in post-COVID-19 patients 6 months after discharge. Acute COVID-19 monocytes transcriptome showed upregulation of anti-inflammatory tissue repair genes such as BCL6, AREG and IL-10 and increased accessibility of chromatin. Some of these transcriptomic and epigenetic features still remained in post-COVID-19 monocytes. Importantly, a poorer expression of surface molecules and low IRF1 gene transcription in circulating monocytes at admission defined a COVID-19 patient group with impaired SARS-CoV-2-specific T cell response and increased risk of requiring intensive care or dying. An early analysis of monocytes may be useful for COVID-19 patient stratification and for designing innate immunity-focused therapies.

Despite the growing number of patients with persistent symptoms after acute SARS-CoV-2 infection, the pathophysiology underlying long-COVID is not yet well characterized, and there is no established therapy. We performed a deep immune profiling in nine patients with persistent symptoms (PSP), before and after a 4-day prednisone course, and five post-COVID-19 patients without persistent symptoms (NSP). PSP showed a perturbed distribution of circulating mononuclear cell populations. Symptoms in PSP were accompanied by a pro-inflammatory phenotype characterized by increased conventional dendritic cells and augmented expression of antigen presentation, co-stimulation, migration, and activation markers in monocytes. The adaptive immunity compartment in PSP showed a Th1-predominance, decreased naïve and regulatory T cells, and augmentation of the PD-1 exhaustion marker. These immune alterations reverted after the corticosteroid treatment and were maintained during the 4-month follow-up, and their normalization correlated with clinical amelioration. The current work highlights an immunopathogenic basis together with a possible role for steroids in the treatment for long-COVID.

Patients on hemodialysis show dysregulated immunity, basal hyperinflammation and a marked vulnerability to COVID-19. We evaluated the immune profile in COVID-19 hemodialysis patients and the changes associated with clinical deterioration after the hemodialysis session. Recruited patients included eight hemodialysis subjects with active, PCR-confirmed SARS-CoV-2 infection, five uninfected hemodialysis patients and five healthy controls. In SARS-CoV-2-infected hemodialysis patients TNF-α, IL-6 and IL-8 were particularly increased. Lymphopenia was mostly due to reduction in CD4+ T, B and central memory CD8+ T cells. There was a predominance of classical and intermediate monocytes with reduced HLA-DR expression and enhanced production of pro-inflammatory molecules. Immune parameters were analysed pre- and post-hemodialysis in three patients with COVID-19 symptoms worsening after the hemodialysis session. There was a higher than 2.5-fold increase in GM-CSF, IFN-γ, IL-1β, IL-2, IL-6, IL-17A and IL-21 in serum, and augmentation of monocytes-derived TNF-α, IL-1β and IL-8 and CXCL10 (p < 0.05). In conclusion, COVID-19 in hemodialysis patients associates with alteration of lymphocyte subsets, increasing of pro-inflammatory cytokines and monocyte activation. The observed worsening during the hemodialysis session in some patients was accompanied by augmentation of particular inflammatory cytokines, which might suggest biomarkers and therapeutic targets to prevent or mitigate the hemodialysis-related deterioration during SARS-CoV-2 infection.

In patients with hepatocellular carcinoma (HCC), increased myeloid‐derived suppressor cells (MDSC) relate to aggressiveness and poor prognosis. Favorable responses with immune checkpoint inhibitors demonstrate that HCC is susceptible to immune activation, suggesting that the elimination of MDSC would provide therapeutic benefits. However, a global analysis of the different MDSC subsets in HCC is still missing. Here we phenotyped circulating myeloid cell subsets (monocytes, M‐MDSC, PMN‐MDSC and eMDSC) by flow cytometry in HCC and hepatocholangiocarcinoma patients and in healthy donors (HD). Isolated myeloid CD33⁺ cells were analyzed in immunosuppression assays, and cytokines were quantified in the supernatants. Arginase‐1 activity (Arg‐1) was analyzed in serum samples. All three proportions of MDSC, together with the immunosuppressive Arg‐1, were significantly increased in HCC compared with HD. An important proportion of eMDSC expressed CD25, the IL‐2 receptor α chain, and CD25⁺ eMDSC were also significantly expanded in HCC patients. HCC‐CD33⁺ cells, enriched in M‐MDSC and eMDSC, in vitro inhibited both CD4⁺ and CD8⁺ T cell proliferation and IL‐2 production, and augmented IL‐10, IL‐6, and TNF‐α. The correlation between the inhibition of T lymphocyte proliferation and M‐MDSC was the strongest, while eMDSC or CD25⁺ eMDSC did not show antiproliferative capacity. Despite this functional difference, M‐MDSC, CD25⁺ eMDSC, and CD25 expression in eMDSC were more prominent in advanced HCC as defined by a higher number of nodules, TNM stage, and alpha‐fetoprotein level. This better delineation of M‐MDSC and eMDSC phenotype and function in HCC could help to design therapies more likely to succeed in clinical trials.