The US’s National Institutes of Health’s ‘Researching COVID to Enhance Recovery’ (RECOVER) initiative has released updated research which identifies 5 distinct symptom sub-types which may aid doctors diagnose long COVID.
The National Academies of Sciences, Engineering, and Medicine (NASEM) defines long COVID as a heterogeneous (diverse), infection-associated chronic condition present for at least 3 months after SARS-CoV-2 infection.
Researchers utilised symptom data reported by participants and assigned points to each of the symptoms. Scores were then calculated for participants based on symptom combinations.
Such an index for long COVID is needed both to support rigorous and reproducible research, and also to identify possible biomarkers and treatments. Challenges to the establishment of such a research index include the nonspecific nature of many symptoms; the complex and often fluctuating illness trajectory; uncertainty about SARS-CoV-2 infection history; and shifts in virus, immunity, reinfections, and treatments that may be altering the nature of the condition itself.
Based on analysing an additional 3,883 individuals, and utilising an expanded symptom questionnaire, researchers were able to augment data from an initial 13, 647 adults and update their 2023 findings.
Of the original participants 11, 743 had a known prior SARS-CoV-2 infection and 1,904 had no known prior SARS-CoV-2 infection; median age was 45 years; and 73% were female. Data on symptoms of ME/CFS, dysautonomia, and mast cell activation syndrome were also collected. Overall, categories of symptoms encompassed post-exertional malaise, fatigue, brain fog, dizziness, palpitations, change in smell or taste, thirst, chronic cough, chest pain, shortness of breath, and sleep apnoea within its 44 symptom list.
This new index used an updated point system, where points were allotted to each symptom in the list of 44 most reported symptoms in people with likely long COVID based on how often they occur.
The most common symptoms reported were fatigue (85.8%), post-exertional malaise (87.4%), and post-exertional soreness (75.0%) — where persistent fatigue and discomfort occur after physical or mental exertion — dizziness (65.8%), brain fog (63.8%), gastrointestinal symptoms (59.3%), and palpitations (58%).
Researchers identified five distinct symptom sub-types within the participants:
Sub-type 1
Those grouped into sub-type 1 did not report a high incidence of impact on quality of life, physical health, or daily function. Only 21% of people in sub-type 1 reported a “poor or fair quality of life.”
Everyone placed in sub-type 1 reported a change in smell or taste. The only other symptoms in over 50% of people with sub-type 1— which were 490 of the 2213 with prior COVID infection — were fatigue (66%), post-exertional malaise (53%), and post-exertional soreness (55%).
Sub-type 2
The prevalence of possibly debilitating symptoms like post-exertional malaise (94%), fatigue (81%), and chronic cough (100%) rose dramatically in people grouped into sub-type 2. A quarter of people in sub-type 2 reported a “poor or fair quality of life”.
Sub-type 3
Fatigue symptoms were reported by 92% of participants placed in sub-type 3, whereas 82% reported post-exertional soreness, and 70% reported dizziness. All people in sub-type 3 reported brain fog as a symptom and approximately 37% of people grouped in sub-type 3 reported a “poor or fair quality of life” – a significant rise from sub-types 1 and 2.
Sub-type 4
About 65% reported symptoms of brain fog; 92% reported palpitations; dizziness was given at 71%; whereas 60% reported gastrointestinal issues; and 36% said they experienced fever, sweats, and chills. About 40% of people in the study grouped into sub-type 4 reported a “poor or fair quality of life”.
Sub-type 5
Of the 44 common long COVID symptoms, 99% reported shortness of breath; 98%, post-exertional soreness; 94%, dizziness; 92%, post-exertional malaise; 80%, GI problems; 78% weakness; and 69% chest pain.
66% of people in sub-type 5 reported a “poor or fair quality of life” and also usually multisystem symptoms.
Strengths and limitations of the research
Acknowledged by the authors, strengths of the study included the large sample size and collection of information on symptoms as they happened (prospectively), rather than looking back in time at pre-collected symptom information (retrospective analysis).
Limitations were also recognised — researchers were unable to consider illness trajectory, and whether and how symptoms changed over time. Additionally it is possible that symptoms from other illnesses and medications may have impacted the findings. Systematic differences in characteristics between those who took part in the study and those who did not (selection bias), and between those who remained in the study and those who dropped out (attrition bias) may have had an impact on how representative the study population is, both overall and within the sub-types.
