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.