Acute HIV-1 and SARS-CoV-2 Infections Share Slan+ Monocyte Depletion—Evidence from an Hyperacute HIV-1 Case Report

Abstract

Monocytes are key modulators in acute viral infections, determining both inflammation and development of specific B- and T-cell responses. Recently, these cells were shown to be associated to different SARS-CoV-2 infection outcome. However, their role in acute HIV-1 infection remains unclear. We had the opportunity to evaluate the mononuclear cell compartment in an early hyper-acute HIV-1 patient in comparison with an untreated chronic HIV-1 and a cohort of SARS-CoV-2 infected patients, by high dimensional flow cytometry using an unsupervised approach. A distinct polarization of the monocyte phenotype was observed in the two viral infections, with maintenance of pro-inflammatory M1-like profile in HIV-1, in contrast to the M2-like immunosuppressive shift in SARS-CoV-2. Noticeably, both acute infections had reduced CD14low/-CD16+ non-classical monocytes, with depletion of the population expressing Slan (6-sulfo LacNac), which is thought to contribute to immune surveillance through pro-inflammatory properties. This depletion indicates a potential role of these cells in acute viral infection, which has not previously been explored. The inflammatory state accompanied by the depletion of Slan+ monocytes may provide new insights on the critical events that determine the rate of viral set-point in acute HIV-1 infection and subsequent impact on transmission and reservoir establishment.

Phenotype of BTK‐lacking myeloid cells during prolonged COVID‐19 and upon convalescent plasma

“…We evaluated longitudinally the myeloid compartment by flow cytometry, as illustrated in Figure S1A, and found lower expression of several activation markers like HLA‐DR, PD‐L1, CD86, and CD80 as compared with patients with moderate to severe COVID‐19 and healthy individuals, in both the unsupervised approach to total monocytes (Figure 1B), and the manual analysis of monocyte subsets (Figure 1C). Additionally, there was marked reduction in Slan+ non‐classical monocytes (Figure 1C), a sub‐population involved in inflammatory conditions but shown to be reduced in COVID‐19 3,5 . The levels of HLA‐DR were also reduced in plasmacytoid dendritic cells (DCs), as well as in CD141+ and CD1c+ DCs (Figure S1B).…”

“…The levels of HLA‐DR were also reduced in plasmacytoid dendritic cells (DCs), as well as in CD141+ and CD1c+ DCs (Figure S1B). These findings contrasted with the progressive increase observed in serum IL‐6 levels and CRP (Table 1), as well as the increase in neutrophils and decline in lymphocyte counts, which have been associated with adverse prognosis of COVID‐19 3,5 . Regarding T cells, the flow cytometry analysis revealed the expected expansion of memory‐effector CD4 and CD8 T‐cell subsets (Figure S2).…”

“…All samples were processed immediately after collection, and the staining performed in whole blood allowed the analysis of a large number of cells by flow cytometry using both unsupervised and manual approaches, as previously described. 3 , 5 …”

“…Additionally, there was marked reduction in Slan+ nonclassical monocytes (Figure 1C), a sub-population involved in inflammatory conditions but shown to be reduced in COVID-19. 3,5 The levels of HLA-DR were also reduced in plasmacytoid dendritic cells T A B L E 1 Clinical and epidemiological data from patients and healthy controls (DCs), as well as in CD141+ and CD1c+ DCs (Figure S1B). These findings contrasted with the progressive increase observed in serum IL-6 levels and CRP (Table 1), as well as the increase in neutrophils and decline in lymphocyte counts, which have been associated with adverse prognosis of COVID-19.…”

“…All samples were processed immediately after collection, and the staining performed in whole blood allowed the analysis of a large number of cells by flow cytometry using both unsupervised and manual approaches, as previously described. 3,5 The XLA patient features a c.1559G>A mutation in the exon 15 of the BTK gene. Intravenous IgG (IVIG) replacement therapy was started at the age of 4 after septic hip and recurrent respiratory infections, maintaining IgG serum level above 800 mg/dl, without major infections besides occasional sinusitis.…”