Coma, Delirium, and Mortality Risk Among Patients Hospitalized With COVID-19

Researchers sought to retrospectively assess persistent viral shedding among NMHC patients who were hospitalized with COVID-19 between March and August 2020.

In patients who have been hospitalized with COVID-19, persistent viral shedding occurs often, which is associated with in-hospital coma, delirium, and increased 6-month mortality, according to a retrospective study published in the journal GeroScience.

A retrospective assessment for persistent viral shedding was conducted with the use of Northwestern Medicine Healthcare (NMHC) electronic medical records (EMRs) to identify all patients admitted to an NMHC hospital for a COVID-19 diagnosis between March 5 and August 9, 2020. NMHC comprises a Chicago, Illinois network of 10 hospitals, including an academic medical center, and affiliated outpatient facilities that are managed by a central EMR system. Further, all acute-care hospital reencounters that occurred within 4 months of discharge from the initial COVID-19 hospitalization in any of the 20 hospital systems that participated in the EPIC Care Everywhere Network were identified as well.

A diagnosis of COVID-19 was confirmed by a documented positive SARS-CoV-2 real-time reverse transcription polymerase chain reaction (RT-PCR) of nasopharyngeal swab or bronchoalveolar lavage fluid. To evaluate a patient for evidence of persistent viral shedding, inclusion in the study cohort required the availability of a repeat RT-PCR assay at 14 days or later after the initial test.

Patients were also evaluated for predictors of persistent viral shedding, the presence of in-hospital delirium, acute brain dysfunction, or coma, and 6-month mortality, via binary logistic regression. Over time, the Confusion Assessment Method (CAM) was performed to monitor the presence of delirium and was documented by a nurse. The Richmond Agitation and Sedation Score (RASS) was used to measure acute brain dysfunction; a score of -4 (no response to voice but movement or eye opening to physical stimulation) on the RASS or -5 (no response to voice or physical stimulation) would indicate acute brain dysfunction.

Among a total of 2518 patients admitted to an NMHC hospital during the study period, 959 underwent a repeat SARS-CoV-2 RT-PCR at 14 days or later from receiving an initial positive test result. Overall, 42.2% (405 of 959) of these individuals were shown to have persistent viral shedding. Based on these results, patients were divided into 2 groups: Persistent Viral Shedding group (n=405) and Negative Shedding group (n=554).

The presence of persistent viral shedding was associated with male sex, increased body mass index, chronic kidney disease, diabetes mellitus, and exposure to corticosteroids during the initial COVID-19 hospitalization.

Persistent viral shedding was independently associated with incidence of in-hospital delirium after adjustments for such factors as severity of respiratory dysfunction (adjusted odds ratio [aOR], 2.45; 95% CI, 1.75-3.45; P <.001). After adjusting for age, severity of respiratory dysfunction, and occurrence of in-hospital delirium, persistent viral shedding continued to be statistically significantly associated with increased 6-month mortality rates (aOR, 2.43; 95% CI, 1.42-4.29; P =.002).

Coma, or acute brain dysfunction was also associated with persistent viral shedding (aOR, 2.40; 95% CI, 1.71-3.38; P <.001) during COVID-19 hospitalization.

A major limitation of the current study is its retrospective design. Further, the incomplete capture of patients returning to the hospital may have inadvertently biased results of the analysis in a conservative manner, since patients who presented to a hospital outside the NMHC and EPIC Care Everywhere systems would not have been recognized through the methods used in the current study.

The researchers concluded that “as novel variants of SARS-CoV-2 emerge, a deeper immunologic understanding of host response and association with outcomes with specific variants may help identify ‘at-risk’ hospitalized patients and better inform clinicians on management and treatment.”

Disclosure: None of the study authors has declared affiliations with biotech, pharmaceutical, and/or device companies.  


Batra A, Clark JR, Kang AK, et al. Persistent viral RNA shedding of SARS-CoV-2 is associated with delirium incidence and six-month mortality in hospitalized COVID-19 patients. GeroScience. Published online May 11, 2022. doi:10.1007/s11357-022-00561-z