The pandemic has claimed over seven million lives officially, but the actual death toll is believed to be much higher. Among COVID-19 survivors, a significant number develop long-term health problems. The World Health Organization uses the term Long COVID for individuals experiencing such symptoms for over three months without another explanation.
Unfortunately, measuring chronic illness and disability resulting from COVID-19 has been challenging due to various factors. While binary outcomes like deaths and ICU admissions are easily counted, tracking slow-onset health issues is more difficult. This is further complicated by the fact that new health problems can arise even without SARS-CoV-2 infection. Consequently, studies utilising different methodologies have reported a wide range of Long COVID incidence rates. A recent study in JAMA Network Open has aimed to address this issue by comparing people who had COVID-19 with those who did not.
The researchers utilised the U.S. blood donor data from 2,38,828 individuals, leveraging antibody test results from the pre-Omicron era to identify individuals who had COVID-19. Specifically, they looked for the presence of anti-nucleocapsid (anti-N) antibodies, which indicates past natural infection. The advantage is that it also identifies people who had asymptomatic infection and those who were infected but did not get tested. The two COVID-19 vaccines used in the U.S. do not elicit the anti-N antibody, thus distinguishing natural infection from COVID-19 vaccination.
Participants were categorised into those who tested positive for the anti-N antibody and those who did not. A diagnosis of COVID-19 by a healthcare professional or a positive COVID-19 test were also accepted as evidence of infection. Essentially, the researchers were able to distinguish individuals who genuinely had COVID-19 from those who did not, using robust parameters. This differs from other studies that may have relied on self-reported COVID-19 diagnoses, which tend to be less reliable. Having a dependable control group for comparison is crucial for accurately estimating the impact of the pandemic.
The researchers discovered that 43.3% of individuals with confirmed SARS-CoV-2 infections experienced new symptoms lasting four weeks or longer, after recovering from COVID. Among those without infection, 22.1% reported new-onset symptoms, as might be expected in the general population. This indicated that 21.2%, or the difference between 43.3% and 22.1%, had long-term health problems genuinely resulting from SARS-CoV-2 infection. Among them, 84.5% were still experiencing symptoms, while 15.5% said that their symptoms had resolved. Long-term physical symptoms were less common following mild or asymptomatic infection.
Neurological symptoms were reported by 23.6%, while 23.1% experienced other problems such as changes in taste or smell, and 15.8% had cardiac or respiratory symptoms. The two most common individual long-term symptoms were difficulty thinking or concentrating (12.7%) and fatigue (11.1%).
Surprisingly, the picture of mental health was different. Among those without infection, as many as 9.8% developed mental health problems such as anxiety and depression. The incidence was only slightly higher at 11.9% among those with prior infection. This is attributed to loneliness, fear of infection or death of oneself or loved ones, bereavement and financial worries that affected people regardless of their infection status. The World Health Organization (WHO) had noted a 25% increase in anxiety and depression in 2022 due to these factors. Therefore, a key takeaway from the study is that a pandemic impacts the mental well-being of the entire population – not just those who got COVID.
Among those who had prior infection in the study, one out of six people (16.5%) said that their current physical health was worse than before the pandemic. For those without prior infection, the corresponding percentage was 10.9%.
Although symptoms lasting over a year are common, the study also reveals that Long COVID resolves in a significant number of cases. Accordingly, household pulse surveys in the U.S. indicate that the percentage of people currently experiencing Long COVID has remained steady, with 10% of adults with prior COVID-19 (equivalent to 7% of all adults) still affected by it.
Studies from India show that Long COVID is less common following Omicron infection compared to previous variants. A study from AIIMS Bhubaneswar found that 8.2% of individuals developed long-term symptoms following Omicron infection, compared to 29.2% with the Delta variant. They found that the risk of Long COVID is heightened with repeated infections.
A limitation of the current study is that it did not measure antibodies at subsequent time points, potentially missing individuals who were infected afterward. They could have incorrectly classified people as uninfected controls. The study also excluded people who were not healthy enough to donate blood, focusing on those with relatively mild outcomes.
(Rajeev Jayadevan is co-chairman of the National IMA COVID task Force)
