# Heterogeneity of the Immunological and Pathogenic Profiles in Patients Hospitalize Early Versus Late During an Acute Vital Illness as Shown in Native SARS-CoV-2 Infection

## TL;DR

This study examines how the immune response and disease progression differ in patients hospitalized at different times during a severe SARS-CoV-2 infection.

## Contribution

The study identifies distinct immunological and clinical clusters based on symptom onset timing during acute illness.

## Key findings

- Patients with immediate symptoms showed high variability in S-spike protein levels and random immunoglobulin titers.
- Procalcitonin was the only marker distinguishing clusters in nonspecific inflammation.
- Clusters C and D required more ECMO or noninvasive ventilation despite similar SOFA and APACHE II scores.

## Abstract

The immune system’s response to an invading pathogen is the critical determinant in recovery from illness. Here, we hypothesize that the immune response will swiftly follow classical activation and a resolution trajectory in patients with the rapid evolution of symptoms if challenged by a viral pathogen for the first time. Alternatively, a dysregulated response will be signified by a protracted clinical trajectory. Consequently, we enrolled 106 patients during the first wave of COVID-19 and collected their blood within 24 h, 48 h, 7 days, and over 28 days from symptoms onset. The pathogenic burden was measured via serum levels of the S-spike protein and specific immunoglobulin titers against the S and N proteins of SARS-CoV-2. The nonspecific immunological response was gauged using interleukin 6, leukocytosis, and C-reactive protein. Coagulation status was assessed. Several serum biomarkers were used as surrogates of clinical outcomes. We identified four clusters depending on the onset of symptoms (immediate [A], 6 days [B], 12 days [C], and over 21 days [D]). High variability in the S-spike protein in cluster A was present. The corresponding immunoglobulin titer was random. Only procalcitonin differentiated clusters in terms of markers of nonspecific inflammation. Coagulation markers were not significantly different between clusters. Serum surrogates on cardiomyopathy and neuronal pathology exhibited significant variability. Implementation of ECMO or noninvasive ventilation was more prominent in cluster C and D. Interestingly, SOFA or APACHE II scores were not different between nominal (A and B) versus dysregulated clusters (C and D).