"Long Haul" COVID-19 Associated With More Medication Use, Higher Risk of Death

Doctor and Patient

A new study suggests that many patients with long-term COVID-19 symptoms still experience health issues six months following infection, are survivors with "long haul" disease have a greater risk of dying and use a more significant number of medications than patients who have fully recovered from the virus. 

This new study, which enrolled over 74,000 veterans, represents the largest studies to date that featured "COVID-19 long haulers" – people who still experience symptoms for weeks or months following the onset of initial symptoms. 

Some long haulers feel better after a couple of weeks following the initial infection but then relapse to old or even new disease-related symptoms, such as brain fog and fatigue.

Often called post-COVID-19 syndrome or post-acute sequalae COVID-19, patients with this health issue tend to be at high risk for severe outcomes, but experts say that an increasing proportion of otherwise healthy people may also experience long-lasting symptoms. 

In the new study, published in a recent online edition of the journal Nature, survivors of COVID-19 who are considered long haulers had a 59% increased risk of death within six months following initial infection with the novel coronavirus. The investigators of the study explained that this excess mortality rate translates to approximately eight extra deaths per 1,000 patients. 

Long haulers in this study also had increased risks of blood clots, stroke, diabetes and breathing difficulties. In addition, survivors who developed long-term symptoms showed more signs of heart, liver, kidney damage, and depression, anxiety, and memory problems. 

In line with these findings, long haulers also had higher incident use of pain medications, anti-depressants and anti-anxiety medications, anti-hypertensives and oral hypoglycemics, indicating an association between long haul COVID-19 symptoms and increased healthcare utilization. 

"When we are looking at the acute phase, we're only pretty much looking at the tip of the iceberg," said lead study investigator Ziyad Al-Aly, chief of the research and development service at the St. Louis VA Medical Center in Missouri, in an interview with Bloomberg. "We're starting to see a little bit beneath that iceberg, and it's really alarming." 

Al-Aly and colleagues noted that the researchers worry about possible spikes in opioid overdoses and suicides related to this increased medication usage and the psychological impacts related to the disease. 

"The constellation of evidence suggests that 30-day survivors of COVID-19 exhibited increased risk of death and health resource utilization, and substantial burden of health loss (spanning pulmonary and several extrapulmonary organ systems) and highlights the need for a holistic and integrated multidisciplinary long-term care of COVID-19 survivors," the researchers wrote.

In terms of patient demographics, COVID-19 survivors in this study were enrolled at a mean age of 61 years, and 88% of patients were men. These findings correspond with previous study results showing that older age and male sex are potential risk factors for more severe outcomes related to SARS-CoV-2 infection. 

Overall, the investigators noted that their findings are concerning, giving most patients with long haul COVID-19 symptoms did not initially have severe enough disease to require hospitalization. The researchers suggest "persistent virus in immune-privileged sites, aberrant immune response, hyperactivation of the immune system, or autoimmunity" may partially explain lingering symptoms in these patients. Then effects of the pandemic on social isolation, changes in lifestyle habits, and loneliness were other factors the researchers hypothesized as contributing to long-term COVID-19 symptoms. 

The fact that COVID-19 may be considered a chronic disease in some people has made many biopharmaceutical and biotech companies take note. Many of these companies are starting to work on therapies or harness existing treatments to manage long-term symptoms related to the disease. No such therapy currently exists, making long haul COVID-19 an area of significant unmet need. 

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