ABSTRACT
Background Post-acute sequelae of COVID-19 (PASC) is characterized by having 1 + persistent, recurrent, or emergent symptoms post the infection’s acute phase. The duration and symptom manifestation of PASC remain understudied in nonhospitalized patients. Literature on PASC is primarily based on data from hospitalized patients where clinical indicators such as respiratory rate, heart rate, and oxygen saturation have been predictive of disease trajectories. Digital wearables allow for a continuous collection of such physiological parameters. This protocol outlines the design, aim, and procedures of a natural history study of PASC using digital wearables.Methods This is a single-arm, prospective, natural history study of a cohort of 550 patients, ages 18 to 65 years old, males or females who own a smartphone and/or a tablet that meets pre-determined Bluetooth version and operating system requirements, speak English, and provide documentation of a positive COVID-19 test issued by a healthcare professional or organization within 5 days before enrollment. The study aims to identify wearables collected physiological parameters that are associated with PASC in patients with a positive diagnosis. The primary endpoint is long COVID-19, defined as ≥ 1 symptom at 3 weeks beyond first symptom onset or positive diagnosis, whichever comes first. The secondary endpoint is chronic COVID-19, defined as ≥ 1 symptom at 12 weeks beyond first symptom onset or positive diagnosis. We hypothesize that physiological parameters collected via wearables are associated with self-reported PASC. Participants must be willing and able to consent to participate in the study and adhere to study procedures for six months.Discussion This is a fully decentralized study investigating PASC using wearable devices to collect physiological parameters and patient-reported outcomes. Given evidence on key demographics and risk profiles associated with PASC, the study will shed light on the duration and symptom manifestation of PASC in nonhospitalized patient subgroups and is an exemplar of use of wearables as population-level monitoring health tools for communicable diseases.Trial registration: ClinicalTrials.gov NCT04927442, Submitted: 6/15/2021, First posted: 6/16/2021.
Subject(s)
COVID-19ABSTRACT
The entry of the severe acute respiratory syndrome coronavirus 2 virus in human cells is mediated by the binding of its surface spike protein to the human angiotensin-converting enzyme 2 (ACE2) receptor. A 23-residue long helical segment (SBP1) at the binding interface of human ACE2 interacts with viral spike protein and therefore has generated considerable interest as a recognition element for virus detection. Unfortunately, emerging reports indicate that the affinity of SBP1 to the receptor-binding domain of the spike protein is much lower than that of the ACE2 receptor itself. Here, we examine the biophysical properties of SBP1 to reveal factors leading to its low affinity for the spike protein. Whereas SBP1 shows good solubility (solubility > 0.8 mM), circular dichroism spectroscopy shows that it is mostly disordered with some antiparallel ß-sheet content and no helicity. The helicity is substantial (>20%) only upon adding high concentrations (≥20% v/v) of 2,2,2-trifluoroethanol, a helix promoter. Fluorescence correlation spectroscopy and single-molecule photobleaching studies show that the peptide oligomerizes at concentrations >50 nM. We hypothesized that mutating the hydrophobic residues (F28, F32, and F40) of SBP1, which do not directly interact with the spike protein, to alanine would reduce peptide oligomerization without affecting its spike binding affinity. Whereas the mutant peptide (SBP1mod) shows substantially reduced oligomerization propensity, it does not show improved helicity. Our study shows that the failure of efforts, so far, to produce a short SBP1 mimic with a high affinity for the spike protein is not only due to the lack of helicity but is also due to the heretofore unrecognized problem of oligomerization.