Since December 2019, the novel coronavirus (SARS-CoV-2) and associated COVID-19 illness
has spread worldwide. Globally, there are >86 million infections and over 1.8 million
confirmed deaths, with the pandemic continuing at record levels throughout the USA. While
new data on COVID-19 are emerging daily, several knowledge gaps remain, including
understanding of the adaptive immune response to infection, the propensity for infected
patients to experience thrombotic events, and identification of biomarkers that might
predict clinical deterioration.

The adaptive immune response, consisting of antiviral T and B cells, is critical for
providing protection against viruses such as SARS-CoV-2, both during an active infection
and later following a subsequent exposure. They can both also potentially contribute to
pathogenesis if they are overstimulated. Much has been learned about the T and B cell
responses to SARS-CoV-2 since the beginning of the COVID-19 pandemic. The most
comprehensive study to date shows that most individuals make a balanced T and B cell
response that persists for at least 8 months. Despite these advances in knowledge, there
are still significant gaps in understanding of what constitutes a protective or
immunopathologic immune response and their durability.

Significant knowledge gaps also remain pertaining to the early recognition of COVID
patients with increased risk of clinical deterioration who require continued
hospitalization and the use of more intensive treatments designed to improve outcomes. In
addition, the identification of low risk patients who can be discharged from the hospital
would reduce the use of potentially scarce medical resources, particularly during a
surge. Among patients with thrombosis, 49% required critical care and 43% died. Data from
non-COVID patients with MI show that platelet surface expression of FcγRIIa, the
low-affinity receptor for the Fc fragment of immunoglobulin (Ig) G, identifies patients
at high and low risk of subsequent cardiovascular events. Platelet expression of FcγRIIa
is increased by interferon γ20 that is significantly elevated in severe COVID-19
infections. Because FcγRIIa amplifies platelet activation, greater expression of FcγRIIa
on the surface of the platelet increases platelet reactivity. The high prevalence of
arterial thrombosis among COVID-19 patients and the central role of thrombosis in
respiratory failure support the hypothesis that elevated platelet expression of FcγRIIa
will identify COVID patients at increased risk of thrombotic complications and clinical
deterioration.

In addition to the potential role of platelet activation in thrombosis associated with
COIVD-19, the endothelium may also play a significant role. The endothelium is a key site
of entry for COVID-19 infection and endothelial injury contributes to thrombotic events
that increase morbidity and mortality. Endothelial microparticles (EMPs), submicron
membranous vesicles indicating endothelial activation and injury, are released by the
endothelium into blood and reflect the competency of endothelial function by identifying
endothelial activation and injury, which promote thrombosis. Circulating EMPs can be
quantified with the use of flow cytometry. The investigators hypothesize that elevated
EMPs in plasma will identify patients at high risk of thrombosis and clinical
deterioration.

To begin to address the knowledge gaps above and obtain preliminary data for future large
grant submission, the investigators propose a small, prospective, single-center cohort
study that will enroll patients hospitalized for COVID-19 infection and exhibiting a
range of disease severity. Blood will be obtained on study days 1, 3±1, 7±1 (and every
7±1 days thereafter up to day 28 while hospitalized), and again at 12 months of follow
up. Nasopharyngeal (NP) swabs will be collected on these same study days through day 28,
but not at 12 months. These biosamples will be used to study T and B cells, antibody
repertoire, and durability of protective immunity, and also to quantify platelet
expression of FcγRIIa and circulating EMPs, as described in the protocol.