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About this publication
This rapid review is a first look at possible long-term effects of COVID-19 (>28 days), including long COVID. We performed a systematic literature search on January 26th for studies with more than 100 participants. One researcher screened the search results. Two researchers selected studies for inclusion and summarised study findings. Experts in the field assisted with study inclusion and provided input during the review process. In the current situation, there remains an urgent need for identifying the most important evidence quickly. Hence, we opted for this semi rapid approach despite an inherent risk of overlooking key evidence or making misguided judgements.
We included 43 studies stratified by length of follow-up, 1-3 months, 3-6 months, and longer than six months follow-up. For six months of follow-up, we have included studies without peer-review. Our approach reflects the early stage of research and emphasises that current findings need to be considered critically. Meta-analysis was not feasible, and the main results of this rapid review are therefore presented tabular and narratively.
Studies with 6 months of follow-up
We identified 11 studies with six months follow-up, of which only four studies are peer reviewed. We identified seven European, two Chinese, one Israeli study and one international survey. Only four studies performed clinical follow-ups, and seven studies used a PCR test to diagnose COVID-19. Included participants were mostly middle-aged. Loss to follow up was generally high. The majority of the studies focused on prevalence of symptoms. These studies showed that at least any one symptom remained at six months of follow-up for many patients. Most commonly reported symptoms were dyspnoea, fatigue and smell and taste abnormalities. Fewer studies included analysis for correlating factors between initially registered clinical information and measured outcomes, findings remain heterogeneous, whilst indicating that severity of initial COVID-19 illness is associated with prolonged symptoms. Echoing this, one study assessing healthcare utilisation found that patients with severe COVID-19 probably consumed more healthcare due to their initial illness, not seen in patients with initial mild COVID-19. Similarly, one study found that among non-hospitalised COVID patients quality of life scores were similar to the population norms, at 1.5-6 months post infection.
Studies with 3-6 months of follow-up
We identified six peer-reviewed studies with 3-6 months follow up of COVID-19 patients. Five studies came from Europe, and one from China. All but one study included PCR confirmed hospitalised COVID-19 patients. There is high heterogeneity across the studies. Four studies conducted clinical follow-ups, in addition to self-reported symptoms. One study only looked at the pulmonary function. Two studies compared COVID-19 intensive care unit vs. non-intensive care unit patients concluding that there were few differences in the symptoms at follow-up. All studies reported lasting symptoms in some of the included patients on follow-up. Most commonly reported symptoms were dyspnoea, fatigue, anosmia and sleeping problems. Most consistent predicting factors for symptom duration were age and severity of COVID-19 illness.
The included studies were heterogeneous in terms of statistical methods and procedures. Most studies suffered from large loss to follow up, and were prone to recall bias. The majority of studies did not include matched controls, which is a strong limitation in evaluating COVID-19 specific effects. Due to lack of controls, it remains uncertain how far prevailing symptoms are specific to COVID-19 or more generally attributable to a period of illness. Equally, pandemic related infringements on personal liberty, lockdowns and changes to pre-pandemic lifestyle might also be factors underlying reporting of some symptoms. These factors are not limited to patients who have had COVID-19, but apply to the whole population. The long-termed effects of COVID-19 and long-termed effect of the pandemic situation are difficult to single out in un-controlled studies.
Patients who have been admitted to intensive care unit with COVID-19 seem to be at greatest risk for developing long COVID, but without controlled studies it remains unclear to what extent their symptoms are COVID-19 specific or reflects more general consequences of intensive care. It is well-known that many patients who are admitted to intensive care units after invasive medical treatment experience post-intensive care syndrome (PICS). PICS shares many similarities with long COVID-19. In line with some studies on long COVID, typical risk factor for PICS are older age, female sex and disease severity. Furthermore, the majority of studies focused on the prevalence of symptoms, but it remains unclear to what extent these symptoms affect activities of daily living and quality of life.
Only one study assessed changes in healthcare utilisation for patients before and after COVID-19. The large prevalence of symptoms in mild COVID-19 patients over time is not reflected in respective changes of healthcare utilisation. Interestingly, for more severe COVID-19 patients this inconsistency is not apparent. This might indicate that patients with mild COVID-19 continue to experience symptoms, but not to the extent that they consider medical help as necessary. It could also be that there is an over-reporting of symptoms, possibly due to loss to follow up and recall bias. With the currently available data, still too much uncertainty remains to reach a clear conclusion.
Based on 43 studies of mixed quality and limited representativeness we have found that; Hospitalised COVID-19 patients report prevailing symptoms long after infection, with a large proportion continuing to experience one or more symptoms at six months of follow-up. Severe COVID-19 illness, requiring intensive treatment, correlates with longer and more functional limitations on follow up. It appears that patients with more severe COVID-19 require more healthcare services and are more affected by adverse effects over time. Due to an over representation of hospitalised patients with severe COVID-19 in the reviewed studies, the findings are not considered representative for those with milder symptoms. The long-term impact of COVID-19 on the quality of life in the general population remains unclear.