Tens of millions of Americans have been infected with the virus thus far. But although the vast majority have recovered, long-term complications related to COVID-19 may continue to put their lives at risk. A new study that examined over 87,000 patients found that COVID-19 survivors had an almost 60% increased risk of death over the following six months compared with the general population.

“Our study demonstrates that up to six months after diagnosis, the risk of death following even a mild case of COVID-19 is not trivial and increases with disease severity,” said senior author Ziyad Al-Aly, MD, an assistant professor at the Washington University School of Medicine. “It is not an exaggeration to say that long COVID-19 — the long-term health consequences of COVID-19 — is America’s next big health crisis. Given that more than 30 million Americans have been infected with this virus, and given that the burden of long COVID-19 is substantial, the lingering effects of this disease will reverberate for many years and even decades. Physicians must be vigilant in evaluating people who have had COVID-19. These patients will need integrated, multidisciplinary care.”

Al-Aly and colleagues combed through a massive dataset from Veterans Health Administration (VHA) to comprehensively catalog all diseases that may be attributable to COVID-19. The dataset included 73,435 VHA patients with confirmed COVID-19 but who were not hospitalized and, for comparison, almost 5 million VHA patients who did not have a COVID-19 diagnosis and were not hospitalized during this time frame. Most of the veterans included in the study were men, but 12% were women so the results may still be relevant to both sexes.

In order to paint a more complete picture of the potential long-term effects of more severe COVID-19, the researchers also conducted a separate analysis involving 13,654 patients hospitalized with COVID-19 compared with 13i997 patients hospitalized with seasonal flu. Both analyses included six months of follow-up data.

According to the results, at the sixth-month mark, excess deaths among all COVID-19 survivors numbered 8 people per 1,000 patients. Among COVID-19 patients who were ill enough to be hospitalized and survived the first 30 days of illness, there 29 excess deaths per 1,000 patients.

“These later deaths due to long-term complications of the infection are not necessarily recorded as deaths due to COVID-19,” Al-Aly said. “As far as the total pandemic death toll, these numbers suggest that the deaths we’re counting due to the immediate viral infection are only the tip of the iceberg.”

Compared to the risk of death for flu survivors, the risk of death was 50% greater among COVID-19 survivors.

“Compared with flu, COVID-19 showed remarkably higher burden of disease, both in the magnitude of risk and the breadth of organ system involvement,” Al-Aly said. “Long COVID-19 is more than a typical postviral syndrome. The size of the risk of disease and death and the extent of organ system involvement is far higher than what we see with other respiratory viruses, such as influenza.”

Although COVID-19 is technically a respiratory illness, the virus can actually affect virtually every organ in the body. The researchers identified a number of persisting health issues associated with COVID-19. These include:

• Respiratory system: persistent cough, shortness of breath, and low oxygen levels in the blood.
• Nervous system: stroke, headaches, memory problems, and problems with senses of taste and smell.
• Mental health: anxiety, depression, sleep problems, and substance abuse.
• Metabolism: new onset of diabetes, obesity, and high cholesterol.
• Cardiovascular system: acute coronary disease, heart failure, heart palpitations, and irregular heart rhythms.
• Gastrointestinal system: constipation, diarrhea, and acid reflux.
• Kidney: acute kidney injury and chronic kidney disease that can, in severe cases, require dialysis.
• Coagulation regulation: blood clots in the legs and lungs.
• Skin: rash and hair loss.
• Musculoskeletal system: joint pain and muscle weakness.

Not all COVID-19 survivors will suffer from all of these health issues following their recovery. However, those who do have post-recovery health problems tend to develop a cluster of several issues.

“Some of these problems may improve with time — for example, shortness of breath and cough may get better — and some problems may get worse,” Al-Aly added. “We will continue following these patients to help us understand the ongoing impacts of the virus beyond the first six months after infection. We’re only a little over a year into this pandemic, so there may be consequences of long COVID-19 that are not yet visible.”

The findings appeared in the journal Nature.