Study: Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: results from the IMPACC study. Image Credit: sfam_photo/Shutterstock

Study examines results from the IMPACC trial to understand clinical phenotypes of disease severity in hospitalized patients with COVID-19

In a recent article published on honeyRxiv*, longitudinal clinical phenotypes were described based on respiratory ordinal scales. According to the study, demographics, clinical features, laboratory tests and radiographic observations were correlated with the trajectory of coronavirus disease 2019 (COVID-19).

Study: Disease Severity Phenotypes in a Cohort of Hospitalized Patients with COVID-19: Results from the IMPACC Study. Image credit: sfam_photo/Shutterstock


Host-pathogen interactions determine the outcome of most diseases caused by microbial infections. In-depth investigation of these interactions may facilitate the identification of promising biomarkers and host-targeted therapeutic approaches against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and post-acute sequelae of COVID-19 (PASC).

The few previous studies that have examined the host-pathogen interaction have been limited by small sample sizes and fewer clinical characteristics, while the cross-sectional design with laboratory data has typically been recorded at a single time point.

To solve these shortcomings, an effective method was developed that took into account the entire course of the disease and the patient’s problems. Longitudinal data integration is an effective method to identify disease severity with respect to the entire disease course in terms of patient problems, symptom persistence, and resource utilization.

The Assessment of Immunophenotyping in the COVID-19 Cohort (IMPACC) considers clinical, laboratory and radiographic data. It includes longitudinal biological sampling of blood and respiratory secretions for in-depth immunological and virological testing – with one-year follow-up after discharge.

This study examined the results of the IMPACC trial to better understand the relationship between the characteristics of patients hospitalized with coronavirus 2019 (COVID-19) and their outcomes, with the aim of improving COVID-19 therapies and disease outcomes – with the aim of improving patient management.


IMPACC was a prospective observational cohort study conducted in 1,164 patients from 20 hospitals across the United States. Based on the severity of the respiratory disease, a seven-point ordinal scale was used to assess the severity of the disease. This study examined patient characteristics using uncontrolled clustering of the respiratory ordinal score (OS) over time to capture the dynamics of disease progression.


The study identified five disease course trajectories – short length of stay; average length of stay; average length of stay with discharge restrictions; prolonged hospitalization; and fatal.

Regarding presenting symptoms, dyspnea and altered mental status were associated with more severe disease, while gastrointestinal symptoms were associated with less severe disease progression. Time between symptom onset and hospitalization was not significantly associated with worse prognosis.

Furthermore, patients were prospectively interviewed quarterly for one year after discharge for PASC. Demographic data, comorbidities, radiographic observations, clinical laboratory values, SARS-CoV-2 polymerase chain reaction (PCR), and serology were collected over 28 days. Multivariate logistic regression analysis was performed.

The results showed that age (65 years or older), Latin American ethnicity, specific comorbidities, and the presence of infiltrate on chest X-ray examination and selected biomarkers at the beginning of the study were related to a more severe course of the disease and worse outcomes.

These findings suggest that a higher SARS-CoV-2 viral load at presentation was associated with more severe disease. When calculating the ratio of anti-receptor-binding domain (RBD) levels to cycle threshold (Ct) values, it was noted that prolonged hospitalization showed a significantly lower ratio than other trajectories during the first 28 days after infection. This study is particularly unique in that it validates this observation in a larger sample and demonstrates an association between longitudinal viral load monitoring and clinical disease progression.

Hispanic/Latino ethnicity was associated with an increased risk of more severe disease; however, in multivariable risk analysis in the most severely ill groups, neither race nor ethnicity was ultimately associated with mortality.

The results of this prospective analysis were consistent with previous reports in showing a lack of association between obesity and poor COVID-19 outcome. Furthermore, this study failed to link the use of remdesivir or glucocorticoids with viral clearance.

Additionally, 51% of patients had at least one symptom of PASC. Females showed a higher prevalence of PASC, despite the study cohort being predominantly male. This finding showed that men were at greater risk of hospitalization related to COVID19.


A high baseline viral load and its persistence were associated with the severity of COVID-19 disease according to the current investigation. While fatal cases of SARS-CoV-2 were associated with the lowest concentrations of anti-RBD and S immunoglobulin (Ig)G.

These results suggest that a deficient antiviral immune response—which is important for virus clearance—may play a key role in short-term mortality. The determined ratio (binding IgG/PCR Ct value) reflected host-pathogen interactions and was a practical method for patient risk classification.

Blood, upper and lower respiratory tract samples collected from this cohort can be immunophenotyped to identify immunological endotypes associated with COVID-19 severity and/or symptom persistence. This may aid in uncovering predictive and prognostic features of COVID-19 and devising theories regarding the cellular and molecular basis of disease and recovery.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guiding clinical practice/health-related behavior, nor should they be treated as verified information.

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