COVID-19 long-term sequelae and complications

Long COVID, sometimes referred to as post-acute sequelae of COVID-19, is still highly prevalent despite improved acute treatments, the emergence of newer variants, and wider vaccination coverage, says an expert at ECCMID 2023.

“Long COVID means having symptoms beyond 4 weeks after a COVID-19 infection,” said Dr Rachael Evans, associate professor and respiratory physician, Department of Respiratory Sciences, University of Leicester, UK at ECCMID 2023.

Long COVID, according to the WHO definition, is the continuation or development of symptoms 3 months after the initial SARS-CoV-2 infection, and lasting for at least 2 months with no other explanation. [https://www.who.int/europe/news-room/fact-sheets/item/post-covid-19-condition#]

The NICE meanwhile defined long COVID as signs and symptoms that develop during or after an infection consistent with COVID-19 and lasting for >12 weeks, that are not explained by an alternative diagnosis. [https://www.nice.org.uk/guidance/ng188 ] “It usually presents with a cluster of symptoms, often overlapping, which can fluctuate and change over time and can affect body systems,” explained Evans.

About 10–20 percent of people infected by SARS-CoV-2 may go on to develop long COVID. It is estimated that  >17 million people had experienced long COVID during the first two years of the pandemic across the WHO European region. “The prevalence is about 5 percent in adults who were triply vaccinated against Omicron in the UK,” she added.

Impact of long COVID

The impact of COVID-19 on physical and mental health and employment after hospitalization has been the subject of many studies. In the multicentre PHOSP-COVID study of 1,077 adults hospitalized for COVID-19 in the UK, where Evans herself was a principal investigator, one in five was no longer working 6 months after discharge. [Lancet Respir Med 2021;9:1275-1287] “In a national survey of UK adults, three out of 10 people said long COVID had negatively affected their work,” Evans continued.

Looking at recovery 1 year after hospital discharge for COVID-19, 7 in 10 patients did not feel fully recovered at 1 year. [Lancet Respir Med 2022 10:761-775] “Patients had a median number of nine symptoms even after a year, which included muscle pain (54.6 percent), fatigue (60.1 percent), breathlessness (51.4 percent), brain fog (46.7 percent), and pain (46.6 percent),” she added.

There was no or minimal improvement in patient-reported outcome measures, physical function, cognitive impairment, or organ function at 1 year vs 5 months after discharge. “At 1 year, 22 percent of patients had clinically relevant symptoms of anxiety, 25 percent had significant symptoms of depression, and 10 percent had significant cognitive impairment. On top of that, 14 percent had chronic kidney disease, 33 percent had HbA_1c of ≥6 percent, 9 percent had cardiac dysfunction (with elevated natriuretic peptides), and in patients with available CT scans (n=209), 1 in 10 had residual lung abnormalities,” Evans reported.

“The takeaway is we really need to stop people from getting long-COVID,” she emphasized. “We desperately need treatments and support to help people with this awful condition.”

Who is at risk and what causes long COVID?

Anyone is, said Evans. There are a number of risk factors that predispose an individual to long COVID. The reality is, anyone with a lung disease is at risk, she added.

“Being female, obese, with comorbidities, and receiving invasive mechanical ventilation were also independent risk factors associated with being less likely to recover from COVID at 1 year.” [Lancet Respir Med 2022 10:761-775]

Several mechanisms have been hypothesized for long COVID pathogenesis, including immune dysregulation, microbiota disruption, autoimmunity, microvascular blood clotting, and dysfunctional neurological signalling. 

 

Effects of multiple interventions and vaccinations on long COVID

When researchers assessed the effect of treatment in critically ill patients with COVID-19 on longer-term mortality, there was a high likelihood of improvement in 180-day mortality among patients treated with IL-6 receptor antagonists and antiplatelet agents. [JAMA 2023;329:39-51]

As for vaccination, at least one dose of a SARS-CoV-2 vaccine was associated with a protective effect against long COVID (odds ratio, 0.539;p= 0.045) in breakthrough infection. In most cases, vaccination did not affect the symptom trajectory of pre-existing long COVID, and a greater number of individuals had improvement in post-COVID-19 symptoms after vaccination. [Brain Behav Immun 2023:S0889-1591(23)00079-X]

“This supports SARS-CoV-2 vaccination for the prevention of long COVID, and recommends that long COVID patients adhere to standard SARS-CoV-2 vaccination schedules,” said Evans.

Key takeaways

The spectrum of COVID-19 severity can be devastating.  It poses a burden to healthcare systems already overwhelmed by long-term conditions, she pointed out.

“Moving forward, we need to further understand the mechanisms driving long COVID. The priority should be on prevention and finding treatment, with further potential for vaccinations,” she concluded.