Veterans Affairs study explores long COVID

Although many people hospitalized with acute COVID-19 have died, many have also survived. After their recovery from acute COVID-19, some people have persistent symptoms. Researchers have recently begun to study these survivors.

Veterans Affairs

A team of researchers in the U.S. has investigated databases that collect health-related information on veterans. The researchers focused on people who survived 30 days after their initial diagnosis of COVID-19. Specifically, they assessed subsequent diagnoses of complications, laboratory tests and medicines that were initiated and other measures.

The researchers compared information from different groups of people. First, they compared more than 73,000 people who survived at least 30 days after a diagnosis of acute COVID-19 and who were not hospitalized with nearly 5 million other people who did not have COVID-19 and who were also not hospitalized. They also used data from about 26,000 hospitalized people with and without COVID-19.

The researchers found that survivors of COVID-19 had health issues that affected different organ systems for up to six months after recovery from acute COVID. (Note that other, longer studies have found longer durations of long COVID.) Affected organs and systems in the present study included the following:

  • brain and nerves
  • bone marrow
  • gastrointestinal system
  • lungs
  • metabolism

Common issues included the following:

  • fatigue
  • anemia
  • bone and muscle pain

Researchers noted that after people recovered from acute COVID-19 some received certain categories of prescription medicines for the first time, as follows:

  • anti-anxiety drugs
  • antidepressants
  • drugs to treat high blood pressure
  • drugs to treat diabetes
  • drugs to ease breathing

Research is urgently needed to find out why some people who develop acute COVID-19 subsequently develop persistent, late-stage complications.

Study details

The researchers analyzed data from two main groups of people, as follows:

  • non-hospitalized people – 73,435 people diagnosed with COVID-19 who survived at least 30 days after their diagnosis and 4,990,835 people who did not have COVID-19
  • hospitalized people – 13,654 people diagnosed with COVID-19 who survived for at least 30 days after being admitted to hospital and 13,997 people who were also hospitalized but who did not have COVID-19

Participants were already part of the Veterans Affairs database for at least a year before December 31, 2019. People who tested positive for SARS-CoV-2 had their tests done between March 1, 2020 and November 30, 2020. Participants were monitored until January 31, 2021.

The researchers assessed data for up to six months after participants left the hospital.


Among people who recovered from acute COVID-19, whether or not they had been hospitalized, the researchers found that they developed a “broad array” of conditions affecting many organ systems.

Researchers grouped categories of illnesses that appeared in long COVID as follows:


  • problems breathing, coughing

Brain and nervous system

  • The researchers found that there was an increase in diagnoses of headache, problems with memory and thinking clearly, loss of sense of smell and an increased risk for stroke.

Mental health

  • problems with sleep, anxiety and depression


  • high cholesterol, high blood sugar


  • fatigue, muscle pain and weakness, anemia

Heart and circulatory system

  • high blood pressure, abnormal heart rhythm, chest pain

Gastrointestinal system

  • problems swallowing, abdominal pain, nausea, excess stomach acid, constipation in some people and diarrhea in others

Other issues

  • The researchers found that there was an increased risk for blood clots in the lungs, and additional problems unrelated to clots: skin disorders, bone and joint pain and infections (including urinary tract infections).


The researchers found an increased risk of death among people who survived the first 30 days after a diagnosis of acute COVID-19. This elevated risk was highest among participants who were previously hospitalized for COVID-19. Also, among people who had been diagnosed with COVID-19 but who were not hospitalized, there was also an increased risk of death even if they survived the first 30 days of their illness.

Bear in mind

The present analysis, which found an increased risk for a wide range of persistent complications one month or more after a diagnosis of acute COVID-19, is sobering. This problem of long COVID occurred whether or not participants were initially hospitalized for COVID-19. Among participants who survived their first 30 days after a diagnosis of acute COVID-19, whether or not they were hospitalized within those first 30 days, there was a remarkably increased risk of death over the next six months.

The researchers stated that, overall, their findings about the long-term consequences of COVID-19 “highlight the need for holistic and integrated multidisciplinary long-term care for patients with COVID-19.”

Many potential causes

As explained earlier in this issue of TreatmentUpdate, scientists are exploring several leads as they seek to uncover the causes of long COVID. The present team is not certain why long COVID occurs, but due to the broad nature of long COVID, they suggested the following possibilities:

  • fragments of SARS-CoV-2 persist deep inside the body, such as in the central nervous system (the brain and spinal cord)
  • the immune system remains highly activated and inflamed
  • the immune system attacks parts of the body

In addition to the biological issues mentioned above, the researchers suggested that social factors and other issues may indirectly contribute to the poor health of some people with long COVID:

  • reduced social contact and loneliness
  • loss of employment
  • changes to diet and reduced exercise

Notes about the study

Although the present study is an important step forward, it does have some limitations:

  • Due to the study’s design, it is not clear which manifestations of long COVID are direct or indirect consequences of SARS-CoV-2.
  • Participants in the study were overwhelmingly male, while other studies suggest that long COVID may be common among women.
  • As SARS-CoV-2 mutates and more people become vaccinated, it is possible that the manifestations of long COVID may change over time.

—Sean R. Hosein


Al-Aly Z, Xie Y, Bowe B. High-dimensional characterization of post-acute sequelae of COVID-19. Nature. 2021 Jun;594(7862):259-264.