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

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

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

Fund

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

Several previous studies investigating the host-pathogen interaction were limited by small sample size and fewer clinical features, whereas a cross-sectional design with laboratory data was typically recorded at a single time.

To address these shortcomings, an effective method was developed that considered the entire course of the disease and the patient’s problems. Longitudinal data integration is an effective method to identify the severity of the disease taking into account the entire course of the disease in terms of patient problems, persistence of symptoms, and use of resources.

Immunophenotyping evaluation in a COVID-19 cohort (IMPACC) considers clinical, laboratory, and radiographic data. It incorporates a longitudinal biological collection of blood and respiratory secretions for in-depth immunological and virological tests, with a follow-up of one year after discharge.

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

The study

IMPACC was a prospective observational cohort study conducted in 1,164 patients from 20 hospitals in the United States. Depending 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 unsupervised grouping of respiratory ordinal score (OS) over time to capture the dynamics of disease progression.

Discoveries

The study identified five course trajectories of the disease: short stay; intermediate stay; intermediate stay with high limitations; prolonged hospitalization; and fatal.

In terms of the symptoms they present, shortness of breath and altered mental status were associated with more severe disease, while gastrointestinal symptoms were correlated with less severe disease progression. The time between the onset of symptoms and hospitalization was not significantly related to a worse prognosis.

In addition, patients were prospectively interviewed quarterly for one year after PASC discharge. For 28 days, demographic data, comorbidities, radiographic observations, clinical laboratory values, polymerase chain reaction (PCR) of SARS-CoV-2, and serology were collected. A multivariable logistic regression analysis was performed.

The results showed that age (65 years or older), Latino ethnicity, specific comorbidities, and the presence of selected chest radiograph infiltrates and biomarkers at baseline were related to a course of the disease more severe and poorer outcomes.

These findings suggested that a higher SARS-CoV-2 viral load on presentation was associated with more severe disease. When calculating the relationship between receptor binding domain (RBD) levels and cycle threshold (Ct) values, it was observed that prolonged hospitalization showed a significantly lower proportion than other trajectories during the first 28 days. after infection. In particular, this study is unique in verifying this observation in a larger sample and demonstrating the connection between longitudinal viral load monitoring and clinical disease progression.

Hispanic / Latino ethnicity was associated with a higher risk of more serious illness; however, neither race nor ethnicity was ultimately related to mortality when analyzing multivariate risk in the most severely ill groups.

The results of this prospective analysis were consistent with previous reports in showing a lack of association between obesity and poor outcome of COVID-19. In addition, this study did not link the use of remdesivir or glucocorticoids to virus clearance.

In addition, 51% of patients had at least one symptom of PASC. Women showed a higher preponderance of PASC, although the study cohort was predominantly male. This finding shows that men had a higher risk of COVID-related hospitalization19.

Conclusion

The initial high viral load and its persistence were related to the severity of COVID-19 disease, according to the present research. While fatal cases of SARS-CoV-2 were related to lower concentrations of anti-RBD and S immunoglobulin (Ig) G.

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

Blood samples from the upper and lower airways collected from this cohort can be immunophenotyped to identify immunological endotypes related to the severity of COVID-19 and / or the persistence of symptoms. This may help to discover the predictive and prognostic features of COVID-19 and to develop theories on the cellular and molecular foundations of disease and recovery.

* Important news

medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guided by clinical practice or health-related behavior, or treated as established information.

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