Low baseline pulmonary levels of cytotoxic lymphocytes as a predisposing risk factor for severe COVID-19

Abstract

Coronavirus disease 19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and currently has detrimental human health, community and economic impacts around the world. In SARS-CoV-2-infected lung, induction of immune cell-recruiting cytokines is initially poor.When induction does occur, this may in fact exacerbate infection. These observations suggest that baseline levels of leukocytes, already residing in the lung prior to infection, may be important for orchestrating an effective early immune response. Hence, we performed "in silico flow cytometry" on 1,927 human lung tissues to deconvolute the levels of seven leukocyte types involved in triggering an acute anti-viral cellular immune response. Baseline levels of CD8+ T cells, resting natural killer (NK) cells and activated NK cells are significantly lower in lung tissues with high expression of the SARS-CoV-2 host cell entry receptor ACE2. We observe this in univariate analyses, in multivariate analyses that include sex, age, race, body mass index and smoking history, and in two independent datasets. Elevated ACE2 expression increases sensitivity to coronavirus infection. Thus, our results suggest that a subgroup of individuals may be exceedingly susceptible to COVID-19 due to concomitant high preexisting ACE2 expression and low baseline cytotoxic lymphocyte levels in the lung.

High altitude reduces infection rate of COVID-19 but not case-fatality rate

“…Elevated ACE2 expression increases sensitivity to coronavirus infection. Individuals may be exceedingly susceptible to COVID-19 due to concomitant high preexisting ACE2 expression and low baseline cytotoxic lymphocyte levels in the lung (Duijf, 2020). This may occur at older than in younger ages and in males than in females, and at low than at high altitudes.…”

SARS‐CoV‐2, COVID‐19, skin and immunology – What do we know so far?

“…Drug hypersensitivity reactions with changes of the vasculature or vascular pathways such as vasculitis, livedo racemosa, or purpura represent a proportion of 10%-20% of cutaneous reactions to drugs and can occur relatively late [7][8][9][10][11][12][13][14] during or even after drug exposure, but the time of onset to the related drug varies and depending on the causative drug. 93 Numerous drugs can induce vasculitis, which manifests primarily as cutaneous vasculitis, mediated as III hypersensitivity reactions (Table 3), that is, immune complex deposits with antigen excess in arteries, arterioles, venules, or capillaries (Figure 8).…”

“…Importantly, as the efficiency of ACE2-S interaction largely determines SARS-CoV transmissibility, [11][12][13] the expression of ACE2 receptors represents a major risk factor for the vulnerability to SARS-CoV-2 infection. In humans, the ACE2 receptors are expressed by CD8 + T cells, 14 resting and activated natural killer (NK) cells, 14 alveolar epithelial cells of type II, 15 vascular endothelial cells, macrophages, monocytes, and adipocytes. 16 The nose and the nasal epithelium play an important role for infection and viral spreading.…”

NK cells at the crossroads in COVID-19: a question of timing

“…It is possible that IL-22 produced by Th17 cells is protective in COVID-19, as was seen in influenza infections (Ivanov et al, 2013). Another interesting hypothesis is that a subset of patients may be predisposed to severe COVID-19 due to preexisting high ACE2 expression and low baseline cytotoxic NK and T cell populations in the lung (Duijf, 2020).…”