Knowing Comorbidities, Medication Use May Save Lives in COVID-19

Almost one in every five patients hospitalized with COVID-19 in the United States was admitted to the ICU and nearly one-sixth required mechanical ventilation, but the risk of severe illness varied according to a range of underlying comorbidities and medication use, a nationwide study hints.

For hospitalized patients, 20.3% died from the virus, with men and patients 80 years and older at a significantly higher risk of death compared with women and younger patients, respectively. The new findings published December 10, 2020, in JAMA Network Open capture some of the earliest epidemiologic data, risk factors, clinical outcomes, and treatment patterns of patients infected with COVID-19 that were included in a national, administrative database.

Lead investigator Ning Rosenthal, MD, PhD (Premier Inc, Charlotte, NC), said it’s upsetting to hear talk, particularly from politicians, undermining the severity of COVID-19. “We talk with data, and this data is from 592 hospitals across the nation,” she said. “This is a severe, severe disease.”

Of the 35,302 patients hospitalized with COVID-19, 19.4% were admitted to the ICU. The in-hospital mortality rate of hospitalized COVID-19 patients, including those with no ICU stay, was 20.3% in this study, higher than the 9.25% in-hospital mortality rate among all ICU patients treated in hospitals participating the Premier Health Database (PHD) during 2016-2019, Rosenthal pointed out.

The PHD is a large geographically diverse all-payer hospital administrative database from Premier Inc, a healthcare consulting firm that includes a large network of member hospitals focusing on improving quality of care while reducing costs. It represents approximately 20% of all inpatient admissions in the US since 2000. “It’s a really robust database for researching COVID-19 patients,” said Rosenthal. “We captured both hospital-based outpatient and inpatient visits, including their [emergency department] visits.”  

Between April 1 and May 31, 2020, the researchers identified 64,781 patients with COVID-19, including 29,479 who were treated as outpatients and the remainder treated in the inpatient setting. Outpatients were, on average, 19 years younger than those hospitalized (46 vs 65 years), and there was a nearly equal split between men and women in the overall cohort. Roughly 40% of all patients were white US residents, while 22.1% were Black, 21.3% Hispanic, 55.2% non-Hispanic, and the rest other/unknown. Nearly 80% of all patients arrived at the hospital from a non-healthcare facility, while 9.4% came from a clinic and 3.7% from a long-term care facility.

In terms of comorbidities at baseline, the Charlson Comorbidity Index (CCI) score was 1.3, with 40.7% of patients having CCI score between one and four. In total, 9.3% of those with COVID-19 had congestive heart failure, while 16.1% had chronic pulmonary disease.

Regarding acute complications, more than half (55.8%) of hospitalized patients developed respiratory failure, 33.7% developed sepsis, 33.9% went into acute kidney failure, and 12.2% developed hyperkalemia. Venous thromboembolism occurred in 4.1% of inpatients, 2.3% had a cerebrovascular event, and 8.1% had acute ischemic cardiovascular event.

In multivariable regression analysis that controlled for baseline comorbidities including cardiovascular diseases, statin use was associated with a significantly lower risk of in-hospital mortality (adjusted OR 0.60; 95% CI 0.56-0.63). Additionally, patients taking an ACE inhibitor or calcium channel blocker also had 47% and 27% lower risks of death, respectively, when compared with nonusers.

“We can’t draw any conclusions on [a] causal relationship,” said Rosenthal. Nonetheless, it’s reassuring, she said, especially given the some of the early concerns about renin-angiotensin-aldosterone system (RAAS) inhibitors in patients with COVID-19. There was some initial worry that RAAS antagonists could increase susceptibility of infection and also the severity of disease, but those concerns have largely been assuaged.    

In contrast, hydroxychloroquine or azithromycin use individually did not have any impact on in-hospital mortality, while their use in combination was associated with an increased risk of death (adjusted OR 1.21; 95% CI 1.11-1.31). Developing sepsis, acute kidney failure, and hyperkalemia were also associated with significantly higher risk of death.

Rosenthal said the findings underscore the importance of being mindful about acute complications associated with increased risks of mortality such as hyperkalemia, sepsis, and acute kidney failure when assessing a patient’s risk. “Everyone is overwhelmed, and it’s hard to ask the physicians to closely monitor these conditions, but they do need to pay attention to the early signs of these complications,” she said. “Identifying and treating them early may save lives.”