Study documents devastating effects of Long COVID two years after infection

A study recently published in Nature Medicine comprehensively assessed for the first time a broad range of impacts of COVID-19 up to two years after SARS-CoV-2 infection. It found that of 80 long-term consequences or sequelae of the disease, individuals with past infection remained at risk for 48 or 60 percent of them at two years post-infection. This compared to an elevated risk at one year post-infection for 69 or 86 percent of sequelae.

The implications of this fundamental result are staggering. It means that long past infection, people remain at risk for a broad array of serious, life-threatening health events impacting over half their body systems.

These events include hospitalization, stroke, chest pain, development of a variety of heart arrhythmias, heart failure, blood clots, dizziness, diarrhea, vomiting, kidney failure, loss of hearing, and loss of smell. They also include the onset of a variety of disorders including diabetes, inflammation of the pancreas, irritable bowel syndrome, liver abnormalities, mental disorders, opioid use disorder, joint pain, muscle pain, arthritis, headache disorders, memory disorders, and shortness of breath.

Relative risks by days after infection plotted for time periods of 30–90, 91–180, 181–360, 361–540 and 541–720 days after infection, labeled by the last day of the corresponding time period. Heatmaps include (top row) nonhospitalized for COVID-19 during the acute phase of the disease (n = 118,238) corresponding to each sequela and (bottom row) COVID-19 hospitalization during the acute phase of the disease (n = 20,580). Relative risks were estimated in comparison to a noninfected control (n = 5,985,227). Sequelae are grouped by organ system. ACD, acute coronary disease; AIM, abnormal involuntary movements; AKI, acute kidney injury; CKD, chronic kidney disease; DVT, deep vein thrombosis; ESKD, end-stage kidney disease; GAD, general anxiety disorder; GERD, gastroesophageal reflux disease; IBS, irritable bowel syndrome; ICM, ischemic cardiomyopathy; ILD, interstitial lung disease; MI, myocardial infarction; NCD, neurocognitive decline; NICM, nonischemic cardiomyopathy; PTSD, post-traumatic stress disorder; PUD, peptic ulcer disease; TIA, transient ischemic attack; VTE, venous thromboembolism. NS, non-significant. [Photo by Bowe, B., Xie, Y. & Al-Aly, Z / CC BY 4.0]

If there is any good news in the study, it is that the risks nearly all declined over time, including a return to baseline risk relative to the control group for some of the most serious events such as heart attack, pericarditis and myocarditis, cardiac arrest and death.

However, the risk did increase over two years for some events such as the development of inflammation of the bile ducts, called cholangitis. Furthermore, for the 60 percent of sequelae where the risk remains elevated, the rate of reduction of risk is considerably flattened over time, suggesting these risks could remain elevated above normal for a long time to come.

The study, conducted by noted Long COVID researcher Dr. Ziyad Al-Aly and his team at the Washington University in St. Louis, examined the differential risks for COVID-19 patients who had been hospitalized with the disease vs. those who had not. It found that individuals who had been hospitalized with COVID-19 had significantly higher risks over time for all sequelae, including at two years post-infection, than those who had not been hospitalized.

Notably, hospitalized individuals remained at significantly increased risk of death at two years post-infection, whereas individuals not hospitalized for COVID-19 had a risk of death similar to the control group after two years. The hospitalized cohort remained at elevated risk for 65 percent of COVID-19 sequelae at two years versus 60 percent for the overall COVID-19 population.

Individuals infected but not hospitalized for COVID-19 remained at elevated risk for 31 percent of sequelae at two years, including cardiovascular, coagulation, endocrine, gastrointestinal, kidney, mental health, musculoskeletal and neurologic sequelae.

Looking at changes in risk over time, these non-hospitalized individuals’ risk of death returned to baseline after 6 months post-infection. Their risk of hospitalization only returned to baseline in the final three months of the two-year period, meaning they were at increased risk of hospitalization for approximately 1.75 years post-infection. This was also the case for another 20 sequelae for which non-hospitalized patients returned to a baseline risk at two years, meaning that non-hospitalized patients are at risk for 57 percent of sequelae for 1.75 years.

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