How well do patients who had coronavirus disease 2019 (COVID-19) recover after the virus is cleared from their systems? A new preprint reports on symptom profiles over the first nine months of the illness.
The study, which appeared on the medRxiv* server, examined 301 participants, from May 2020 to the end of January 2021. About half had moderate COVID-19, a third had a mild illness, while about one in five had severe/critical disease, respectively. The median age was higher in the latter groups, while these patients were also heavier.
Other risk factors such as cardiovascular disease, chronic lung disease, immunosuppression and diabetes were all more common among those with severe or critical COVID-19 as well. Most of the patients were followed up prospectively, with 42 being lost to follow-up.
What were the findings?
The findings show that during acute infection, COVID-19 patients most frequently cited fatigue and cough, followed by loss of appetite, fever and body aches, diarrhea and nausea. In the first week, more mild and moderate patients said they had lost their sense of smell or taste, had a headache or a running nose, or sore throat.
This remained consistent at one month, at which point two out of three patients with moderate to critical COVID-19 were likely to report being short of breath, vs. 43% of mild patients.
Anosmia and dysgeusia (loss of smell and taste) were reported as severe at the onset of illness for mild COVID-19 patients, but rapidly improved within a week. In fact, most patients reported decreasingly severe symptoms over time for most major symptoms.
As expected, mildly ill patients recovered the fastest, with a median of 57 days to full recovery. At three months, one or more symptom was reported to be consistent by a third of these patients, compared to double this figure with moderate illness, and over 80% of patients with severe/critical disease.
About a fifth of patients with mild illness, but half of those with higher grades, reported one or more ongoing symptoms at nine months.
The greatest risk for delayed recovery was a high body mass index. The time to complete recovery was increased by half in obese patients and a quarter in overweight patients, compared to those with normal weight.
With regard to individual symptoms, cough persisted longer with obese patients, who had a 44% increase in recovery time. These patients also had more than double the recovery time from smell/taste alterations.
Older patients recovered less rapidly from cough, taking 20% longer to recover than younger patients, as did those with shortness of breath. Patients with muscle pain also took 25% more time to recover from this symptom.
The number of coexisting illnesses affected the duration of tiredness, with one such illness more than doubling the time to recovery compared to those without any. Individual specific illnesses such as those mentioned earlier failed to affect the period taken to recover.
Reassuringly, most symptoms, even those which persisted at one month, were decreased in severity at this point. However, persistent symptoms which met the NICE criteria for post-COVID syndrome were reported by a third of patients with only mild illness and twice this number in those with moderate illness.
Concerning those with severe/critical disease, four out of five patients had prolonged symptoms. This pattern continued to manifest itself at nine months, with one-fifth and half of the patients with mild and moderate-to-critical disease, respectively, being affected by one or more symptoms at this point in time. The greatest risk was seen in obese patients.
What are the implications?
This study is pioneering in its follow-up of COVID-19 symptoms over a long period of nine months in patients with all grades of illness. The findings show, first of all, that the classic symptoms of COVID-19 affect patients with all levels of severity to a comparable extent.
These findings are crucial in view of the need to limit the long-term sequelae of COVID-19 by appropriate follow-up and care. While high numbers of hospitalizations and deaths have rightly been the focus of healthcare, in the exponential growth phases of the pandemic, the future sequelae are also a matter of concern.
This study shows that almost 60% of patients, overall, met the NICE definition of post-COVID syndrome, which agrees with earlier studies. However, it exceeds the estimates of the UK Office for National Statistics as well as those reported among healthcare workers.
One reason could be that the current study included only symptomatic patients. Even so, considering the immense number of symptomatic individuals worldwide, the potential burden of post-COVID syndrome is staggering. Moreover, as new immune-evading and more virulent variants of the virus continue to emerge and spread rapidly, this is only likely to go up to higher levels.
The wide range of symptoms reported as part of this syndrome makes it difficult to evaluate with any consistency, and to evolve a uniform management protocol. The first step would be to develop a “universally accepted and evidence-based definition of post-COVID syndrome” to facilitate the comparability of research findings.
Other measures include coming up with a risk score to promote the early identification of those who could benefit from specific interventions, such as reducing obesity. It is important to understand that not only is obesity a chronic inflammatory condition, but it also dogs the lower strata of society, who are generally poor, excluded from mainstream healthcare, and thus already prone to adverse outcomes. Thus, it is necessary to evaluate how these related factors affect recovery time, besides taking steps to reduce the prevalence of obesity.
The chronic fatigue reported by many patients during acute illness and at three months is also a drain on the individual and the society, both in terms of healthcare costs and reduced productivity at the workplace. Since this occurs mostly in those recovering from mild COVID-19, the numbers are likely to be large, and it is urgent to find effective ways of managing this symptom.
Other studies have already shown the persistence of breathing difficulty and myalgia even after three months in many patients who had moderate to critical disease, especially in the elderly. This requires further work to elucidate the mechanism.
While these results require validation in a larger cohort and with patients treated by different management strategies or with those infected by more recent variants, the principles will hold good.
Next steps in post-COVID syndrome research must include assessing the public health and socioeconomic impact, identifying further predictive and prognostic characteristics, and exploring the underlying biological mechanisms of disease in order to identify and develop effective interventions.”
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.