Complications in various organ systems develop in half of adults admitted to the hospital with COVID-19, even in young, previously healthy individuals, a new study finds.

Of 73,197 patients aged 19 years or older admitted to UK hospitals with severe COVID-19 from January 17 to August 4, 2020, 49.7% experienced 1 or more in-hospital complications within 28 days, particularly those requiring critical care (82.4%) or mechanical ventilation (91.7%), Ewen M. Harrison, MBChB, PhD, MSc, of the University of Edinburgh, Scotland, and colleagues reported in The Lancet. Overall, 31.5% of patients died, including 40.1% with any complication.

Complications in Every Age Group

The incidence of in-hospital complications increased with age, from 39% of those aged 19-49 years to 51% of those aged 50 years and older, the investigators reported. Specifically, a complication developed in 27%, 37%, and 43% of patients aged 19-29, 30-39, and 40-49 years hospitalized with COVID-19, respectively. By comparison, a complication developed in 49%, 54%, 52%, 51%, and 50% of older patients aged 50-59, 60-69, 70-79, 80-89, and 90 years or more, respectively.

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Men, who comprised 56% of the cohort, were more likely than women to experience a complication, particularly older men: 49% vs 37% of those younger than 60 years and 55% vs 48% of those aged 60 years or older.

White, South Asian, and East Asian ethnic groups had similar rates of complications, but rates were highest among Black adults: 58% Black vs 49% White patients.

Various Organ Systems Affected

According to Dr Harrison’s team, in-hospital complication rates with COVID-19 seem the same or higher than with influenza, and appear to be driven by noninfectious complications.

The most common complications included renal (24.3%), complex respiratory (18.4%), and systemic complications (16.3%), but cardiovascular (12.3%), gastrointestinal (GI) and liver (10.8%), and neurological (4.3%) complications were also reported. Acute kidney injury (AKI; 15.6%), probable acute respiratory distress syndrome (15.6%), liver injury (11.3%), anemia (9.0%), and cardiac arrhythmia (4.8%) were the most prevalent conditions (data reflect patients with no pre-existing illnesses).

The investigators found that increasing age and male sex predicted the development of any and all organ-specific complications, except for GI and liver complications, which were more likely to affect younger patients.

The presence of any and multiple complications increased the odds of poor survival. For example, more patients with than without cardiovascular or respiratory complications died. The predefined categories used in the study limited capture of some important complications, such as pulmonary embolism and deep vein thrombosis.  

Comorbidities Play a Role

Among the hospitalized patients, 81% had an underlying health condition. Chronic cardiac disease, chronic pulmonary disease, and chronic kidney disease (CKD) were the most common. Complication rates increased with the number of comorbidities from 38% to 47% to 55% in patients with 0, 1, and 2 or more comorbidities, respectively.

The investigators found that patients with a preexisting condition affecting a specific organ had a higher risk of having a complication involving that same organ. A cardiac complication, for example, more frequently developed in patients with than without preexisting cardiac disease (19.9% vs 8.9%). AKI developed in more patients with than without CKD (39.8% vs 21.6%). Liver injury was more common in patients with preexisting moderate to severe liver disease compared with those without liver problems (22.4% vs 6.2%). Patients who were obese were 1.6 times more likely to have respiratory complications and 1.3 times more likely to have renal complications compared with non-obese patients.

Complications Hinder Self-Care

Among survivors, having an acute complication was associated with 2.4-fold increased odds of worse self-care ability after hospital discharge. Even 13% of patients aged 19-29 years and 16% of those aged 30-39 years were less able to perform self-care at discharge, the investigators reported.

In descending order, neurological, respiratory, cardiovascular, renal, and GI complications were associated with significant 4.4-, 3.6-, 2.2-, 2.1-, and 2.0-fold increased odds of worse self-care ability. 

“We found respiratory and cardiovascular complications were associated with greatest [COVID-19] severity and acute kidney injury was one of the most common,” Dr Harrison’s team stated. “Treatments such as enhanced monitoring and early treatment for patients for cardiac arrhythmias that might lead to further problems such as stroke or cardiac arrest might, therefore, be useful. Similarly, for acute kidney injury, optimising fluid balance to ensure adequate renal perfusion in patients with less severe respiratory disease might lessen the impact of acute kidney injury.”

Whether the effects of in-hospital complications are transient or long-term requires further study.

In an accompanying editorial, Xiaoying Gu, MD, and Bin Cao, MD, of the National Clinical Research Center for Respiratory Diseases in Beijing, China, commented, “Comprehensively understanding the health effects of COVID-19 from its acute to chronic stages is important, not only for the preparation of further waves of the pandemic, but also for assessing the burden on health-care systems due to COVID-19 consequences.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Drake TM, Riad AM, Fairfield CJ, et al; on behalf of the ISARIC4C investigators. Characterisation of in-hospital complications associated with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol UK: a prospective, multicenter cohort study. Lancet 398:223-37. Published online July 15, 2021. doi:10.1016/S0140-6736(21)00799-6

Gu X, Cao B. In-hospital complications associated with COVID-19. Lancet 398:188-190. Published online July 15, 2021. doi:10.1016/S0140-6736(21)00983-1