Fig 1.
Overview of the dynamic clinical decision support protocol used in managing SARS-CoV-2 patients admitted to a COVID-19-dedicated medical center.
Note that at the time the study was performed, multiple treatments and clinical decision protocols were being developed globally and employed despite the limited data to support improved outcomes and the research use only indications. P/F ratio, ratio of arterial oxygen partial pressure (PaO2) to fractional inspired oxygen (FiO2); US, ultrasound; CT, computed tomography; NICaS, non-invasive cardiac system; NO, nitric oxide; TPA, tissue plasminogen activator; ECMO, extracorporeal membrane oxygenation; CRP, C-reactive protein; IP-10, interferon γ-induced protein 10; Plasm Abs, plasma antibodies; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand.
Table 1.
Characteristics of COVID-19 patients.
Table 2.
Status of the 12 patients admitted to the intensive care unit (ICU).
Fig 2.
IP-10 levels are significantly higher in viral infections associated with pulmonary pathology.
IP-10 levels in the internal medicine ward (non-ICU, n = 40) and ICU (n = 12) COVID-19 patients and in healthy subjects (n = 98) and virally infected patients (n = 182) with polymerase chain reaction-confirmed viral infections such as human rhinovirus (HRV), respiratory syncytial virus (RSV), influenza (Flu), and human coronavirus (HCoV). Each circle represents a patient. The black line denotes the group median and the purple circle corresponds to group mean. The box indicates patients with values between the 25 and 75 percentiles. The whiskers indicate patients with values between the 2.5 and the 97.5 percentiles. For the COVID-19 patients, IP-10 was measured using MeMed Key™ at various time points and the first IP-10 measurement is shown.
Fig 3.
(Left panel) IP-10 levels correlate with COVID-19 severity.
Maximal IP-10 levels in patients classified as non severe or severe according to the NIH COVID-19 severity score (https://www.covid19treatmentguidelines.nih.gov/. Accessed August 2020). The black line denotes the group median and the circle corresponds to group mean. The box indicates patients with values between the 25 and 75 percentiles. The whiskers indicate patients with values between the 2.5 and the 97.5 percentiles. (Right panel) Mortality correlates with the number of days when IP-10 levels exceeded 1,000 pg/mL in SARS-CoV-2-positive patients (n = 52, upper panel) and among the subset of intensive care unit (ICU) patients (n = 12, lower panel). IP-10 was measured at various time points during hospitalization. At least one IP-10 measurement ≥ 1,000 pg/mL in a given day was sufficient to classify the day as exceeding 1,000 pg/mL. Each circle represents a patient; blue dots represent patients who survived and red dots represent patients who died. The cause of death of the ICU patient with a low number of days of IP-10 > 1,000 pg/mL was candidemia and of the non-ICU patient was metastatic breast cancer.
Fig 4.
Initiation of corticosteroid therapy resulted in a decrease in IP-10 levels (ICU patients, n = 12).
IP-10 was measured at the indicated time points during ICU stays. Day 0 indicates initiation of corticosteroid therapy. The pink area indicates IP-10 levels exceeding 1,000 pg/mL. Patients 2, 8, and 11 exhibited subsequent surges in IP-10 levels and are detailed in Fig 5. Of note, at study initiation, some patients were studied who were already hospitalized in the wards and ICU. Corticosteroid treatment was not initiated prior to hospitalization. From the point of patient selection, every measurement taken is included in the graph.
Fig 5.
IP-10 levels reflect personalized corticosteroid dosing.
Three patients exhibited a relapse wherein their IP-10 levels surged to exceed 1,000 pg/mL after an initial treatment with corticosteroids. The right Y axis shows the normalized levels of corticosteroids administered (the hydrocortisone dose was converted to a methylprednisolone dose). The left Y axis shows the levels of IP-10 measured at the indicated time points. The X axis shows the days from the first positive SARS-CoV-2 polymerase chain reaction test. Lines connecting the doses indicate that the dose was given in each of the intervening days. The pink area indicates IP-10 levels exceeding 1,000 pg/mL. Patient 2 survived; Patients 8 and 11 died.
Fig 6.
TRAIL levels correlate with ICU admission (upper panel) and viral positivity (lower panel).
TRAIL was measured at multiple time points during hospitalization. At least one TRAIL measurement exceeding 25 pg/mL in a given day was sufficient to classify the day as exceeding 25 pg/mL. The bottom, middle and top box lines indicate the 25%, 50%, and 75% percentiles, respectively. The whiskers indicate the 25% and 75% quartile plus 1.5 times the interquartile range.