Many long-COVID patients report symptoms 2 years later

Fatigued older man sitting on couch
Fatigued older man sitting on couch

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A pair of new studies describe the effects of long COVID, with one estimating that half of hospitalized patients have at least one persistent symptom 2 years after infection, and the other revealing a fourfold higher risk of abnormal blood clotting in survivors struggling with basic physical activity more than 12 weeks after diagnosis.

68% had symptoms at 6 months, 55% at 2 years

Researchers at Capital Medical University in Beijing led a team studying the long-term outcomes of 1,192 patients hospitalized for COVID-19 at a single center in Wuhan, China, from Jan 7 to May 29, 2020, the first pandemic wave.

The results were published yesterday in The Lancet Respiratory Medicine. The study is the longest-term follow-up of hospitalized COVID-19 survivors yet, the authors said.

Follow-up at 6 and 12 months and 2 years after symptom onset consisted of a 6-minute walking distance (6MWD) test, lab tests, and questionnaires on symptoms, mental health, health-related quality of life (HRQoL), return to work, and healthcare use. Overall, 94% of participants completed a face-to-face interview at 2 years.

A subgroup of patients underwent lung-function tests and chest imaging at each follow-up visit, and matched, uninfected patients served as controls. Median age at hospital release was 57 years, and 46% were women.

The proportion of COVID-19 survivors with 1 or more symptoms fell from 777 of 1,149 (68%) at 6 months to 650 of 1,190 (55%) at 2 years. The most common symptoms were fatigue and muscle weakness (31%) and sleep difficulties (31%).

The share of survivors with a modified British Medical Research Council (mMRC) dyspnea scale score of at least 1 (indicating shortness of breath when hurrying on even ground or walking slightly uphill) dropped from 288 of 1,104 (26%) at 6 months to 168 of 1,191 (14%) at 2 years.

There was continued improvement in HRQoL in nearly all domains, particularly in anxiety and depression, with anxiety symptoms declining from 256 of 1,105 (23%) at 6 months to 143 of 1,191 (12%) at 2 years.

Among all COVID-19 survivors, the proportion with a lower-than-normal 6MWD fell continuously, and 438 of 494 (89%) had returned to their original work by 2 years. Relative to participants without long COVID, those who still had COVID-19 symptoms at 2 years reported lower HRQoL, worse exercise capacity, more mental health issues, and more healthcare use.

Compared with controls, COVID-19 survivors had more symptoms and pain and discomfort and anxiety and depression at 2 years. A significantly higher share of survivors who received higher-level respiratory support in the hospital had impaired lung diffusion (43 of 55 [65%]) vs 24 of 66 [36%]), lower residual lung volume (62% vs 20%), and total lung capacity (39% to 6%) than controls.

In a Lancet news release, senior author Bin Cao, MD, of the National Clinical Research Center for Respiratory Diseases, said that the results show that some COVID-19 survivors may still need medical attention 2 years or more after infection.

"There is a clear need to provide continued support to a significant proportion of people who've had COVID-19, and to understand how vaccines, emerging treatments, and variants affect long-term health outcomes," he said.

Decline in oxygen saturation, exercise capacity

In the second study, published yesterday in Blood Advances, a team led by University College London researchers assessed 330 patients seen in a long COVID clinic with an elevated (1.5-fold) Von Willebrand Factor (VWF)(Ag):ADAMSTS13 ratio 3 months after infection, indicating a pro–blood-clotting state, from July 2020 to May 2021.

The ratio was also calculated in 50 healthy volunteer controls. VWF is a blood-clotting protein, while ADAMSTS13 is a protein that splices VWF to prevent it from clogging blood vessels. The study was the first to report a link between abnormal blood-clotting tests and lower exercise capacity in long COVID patients, the researchers said.

An elevated VWF(Ag):ADAMSTS13 ratio was four times more likely in long COVID patients with impaired exercise capacity, as shown by a 3% or greater decline in blood oxygen concentration or an increase in lactate level of more than 1 from baseline on a 1-minute sit-to-stand test and/or 6-minute walking test. Lactate is a substance made by muscle tissue and red blood cells to try to compensate for low oxygen saturation.

Fifty-six of 276 patients (20%) had reduced exercise capacity, and 31 of those 56 (55%) had a VWF(Ag):ADAMSTS13 ratio at least 1.5 times higher than that of controls.

Factor VIII (FVIII) and VWF(Ag) were higher than normal in 26% and 18% of long COVID patients, respectively, supplying evidence of a pro–blood-clotting state. "These findings suggest possible ongoing microvascular/endothelial dysfunction in the pathogenesis of PCS [post-COVID syndrome] and highlight a potential role for antithrombotic therapy in the management of these patients," the researchers wrote.

In an American Society of Hematology news release, lead author Nithya Prasannan of University College London and the National Health Service Department of Haematology, said she hopes the findings will advance the understanding of long COVID's mechanisms and help guide future treatment options. "I encourage people experiencing long COVID to participate in clinical trials when available because the more data we have, the better we can understand this condition," she said.

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