Dödligt virus från Kina orsakar panik (SARS-CoV-2, COVID-19)

Introduction:

Most patients infected by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) suffer no or
only mild symptoms. A small minority of patients develop severe Coronavirus Disease 2019 (COVID-19),
and these patients account for almost all of the morbidity and mortality associated with the infection [1].
Reported rates of mortality in patients with severe disease range between 20–40% [3–5]. The relatively
high mortality among patients with severe SARS-CoV-2 pneumonia reported in some centers, combined
with a systemic inflammatory response that is severe in some patients, have led to speculation that the
pathobiology of SARS-CoV-2 pneumonia is distinct from other respiratory viral and bacterial pathogens [2].

In the alveolar space, we
confirm that SARS-CoV-2 infects alveolar epithelial cells and alveolar macrophages [27]. Alveolar
macrophages might be infected with SARS-CoV-2 by 1) phagocytosis of infected epithelial cells, 2) via direct
infection, as was shown for SARS-CoV and MERS-CoV [15,16] or 3) through other mechanisms, such as
antibody mediated enhancement as was shown for SARS-CoV [17,29]. Indeed, it is estimated that ~90% of
adults have antibodies against one of four major seasonal coronaviruses [30], and antibodies cross-reacting
with SARS-CoV-2 might facilitate viral entry into alveolar macrophages.

While tissue-resident alveolar macrophages are poor antigen-presenting cells and do not migrate to lymph
nodes to participate in conversion of naive T cells into effector T cells [31], a low level of antigen presentation
by alveolar macrophages in the alveolar space might be sufficient to drive activation of pre-existing memory
T cells that target endemic seasonal coronaviruses, but cross-react with SARS-CoV-2. Existence of such
cross-reactive memory T cells has been reported for SARS-CoV [32] and, recently, SARS-CoV-2 [33–36].
This mechanism might explain the epidemiology of SARS-CoV-2, which disproportionately affects elderly
individuals, while children and young adults often have only mild symptoms, despite having viral load in
upper airways compatible to adults [37,38]. Children and young individuals have fewer encounters with
seasonal coronaviruses during their lifetime than elderly individuals and therefore would have fewer crossreactive antibodies or memory T cells.