Patients who were discharged following a Covid-19 hospital admission were more than twice as likely to experience subsequent hospitalization or death within 6 months and had nearly five times the risk of all-cause mortality compared to the general population, researchers found.

As the Covid-19 pandemic persists into another year, there is an ever growing population of individuals who have survived Covid-19 hospitalization. However, little is currently known about long-term health outcomes in this population. “Given high rates of current and past SARS-CoV-2 infection in many countries, understanding risks to health beyond acute infection is vital to support resource planning and inform measures to mitigate and reduce risks,” Krishnan Bhaskaran, PhD, of the London School of Hygiene and Tropical Medicine in London, U.K., and colleagues wrote in PLOS Medicine.

Bhaskaran and colleagues conducted a cohort study using primary care and hospital data from OpenSAFELY—a health analytics platform with patient data from England—to compare the risk of re-hospital admission and/or death, both overall and by specific cause, among patients discharged from Covid-19 hospitalization from February-December 2020, against both demographically matched controls from 2019 and individuals discharged from influenza hospitalization prior to the pandemic (2017-2019).

“Patients discharged from a Covid-19 hospitalization and surviving at least a week had more than double the risk of subsequent hospitalization or death and a 4.8-fold higher risk of all-cause mortality than controls from the general population, after adjusting for baseline personal and clinical characteristics,” the study authors wrote. “Risks were higher for all categories of disease-specific hospital admissions/deaths after a Covid-19 hospitalization than in general population controls, with excess risks more pronounced earlier in follow-up for several outcomes.”

Notably, the risks for most outcomes were similar or lower for patients post-Covid-19 discharge compared with patients discharged following flu hospitalizations; however, “the Covid-19 group had higher subsequent all-cause mortality, higher rates of respiratory infection admissions and deaths (predominantly Covid-19), and more adverse mental health and cognitive outcomes (particularly deaths attributed to dementia among people with preexisting dementia) compared with the influenza group.”

Bhaskaran and colleagues concluded that their findings “suggest a need for services to support and closely monitor people following discharge from hospital with Covid-19, for example, through more frequent/active follow-up in primary care in the weeks and months following a hospitalization. Our results can be used to help inform healthcare providers and raise awareness of potential complications during this period. Our findings will also help with public health resource planning in the context of high rates of SARS-CoV-2 infection in many countries. Ongoing monitoring will be important to investigate whether these patterns persist in the light of new variants and increasing levels of vaccination.”

For their analysis, Bhaskaran pulled data for all patients discharged from the hospital from Feb. 1-Dec. 30, 2020, following Covid-19–related hospitalization lasting more than one day. In order to avoid data on hospital transfers and immediate readmissions/deaths, they limited their analysis to patients who were alive and had follow-up in a TPP-affiliated practice one week post-discharge.

For the comparison groups, the study authors identified patients from the general population who were under follow-up in 2019 and individually matched them 5:1 to the Covid-19 group based on age, sex, geographical area, and calendar month. Next, they identified all individuals discharged from the hospital from 2017-2019 with influenza coded as the primary reason for hospitalization and who were alive and under follow-up one week post-discharge.

The primary study outcomes were time to first hospitalization or death, all-cause mortality, and time to first cause-specific hospitalization or death.

The final analysis included 24,673 post-discharge Covid-19 patients, 123,362 general population controls, and 16,058 influenza controls, all of whom were followed for ≤315 days. The Covid-19 group had similar age and sex distribution to the general population (median age 66 years for both; 55.7% male for both), but differed from the influenza group (median age 69 years, 44.2% male). Patients in the Covid-19 group were also more likely to be obese, non-White, and less likely to be current smokers compared to the two control groups, and they were more likely to have received critical care during hospital admission and had a longer median duration of hospital stay.

“Overall risk of hospitalization or death (30,968 events) was higher in the Covid-19 group than general population controls (fully adjusted hazard ratio [aHR] 2.22, 2.14 to 2.30, P<0.001) but slightly lower than the influenza group (aHR 0.95, 0.91 to 0.98, P=0.004),” the study authors found. “All-cause mortality (7,439 events) was highest in the Covid-19 group (aHR 4.82, 4.48 to 5.19 versus general population controls [P<0.001] and 1.74, 1.61 to 1.88 versus influenza controls [P<0.001]). Risks for cause-specific outcomes were higher in Covid-19 survivors than in general population controls and largely similar or lower in Covid-19 compared with influenza patients. However, Covid-19 patients were more likely than influenza patients to be readmitted or die due to their initial infection or other lower respiratory tract infection (aHR 1.37, 1.22 to 1.54, P<0.001) and to experience mental health or cognitive-related admission or death (aHR 1.37, 1.02 to 1.84, P=0.039); in particular, Covid-19 survivors with preexisting dementia had higher risk of dementia hospitalization or death (age- and sex-adjusted HR 2.47, 1.37 to 4.44, P=0.002).”

Bhaskaran and colleagues noted that their data showing that patients hospitalized with Covid-19 were more likely to have baseline comorbidities jibe with known associations between comorbidities and severe Covid-19 outcomes, and the different outcomes identified in this study “might therefore reflect baseline differences not fully captured in our adjustment models and might also reflect a generic adverse effect of hospitalization.”

Their findings also suggested a disproportionate rate of dementia deaths following Covid-19 hospital discharge, and the study authors noted it is possible that hospital admission, social isolation, and medications may have accelerated dementia progression in these patients. However, “it is possible that deaths where the underlying cause was recorded as dementia may have been due to progression of underlying health problems following an acute illness as well as difficulty in managing these due to dementia,” they added. “Covid-19–related delirium may have also triggered or worsened emerging dementia in some patients, or even driven a degree of misclassification given the potential clinical challenge in distinguishing between subacute or chronic delirium and progressive dementia… It will be important to continue to monitor these outcomes as more follow-up accumulates.”

Study limitations included possible misclassification of the reasons for hospitalization or death due to inconsistent code use and a lack of data distinguishing cases attributable to Covid-19 variants.


Bhaskaran had no relevant relationships to disclose.



John McKenna, Associate Editor, BreakingMED™

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