Public Health England initiated longitudinal surveillance of clinical and non-clinical healthcare workers for monthly assessment and blood sampling for SARS-CoV-2 antibodies in March 2020. Eight months after enrolment, participants completed an online questionnaire including 72 symptoms in the preceding month. Symptomatic mild-to-moderate cases with confirmed COVID-19 were compared with asymptomatic, seronegative controls. We identified three clusters of symptoms associated with long COVID, those affecting the sensory, neurological and cardiorespiratory systems.
BackgroundMost individuals with COVID-19 will recover without sequelae, but some will develop long-term multi-system impairments. The definition, duration, prevalence and symptoms associated with long COVID, however, have not been established. MethodsPublic Health England (PHE) initiated longitudinal surveillance of clinical and non-clinical healthcare workers for monthly assessment and blood sampling for SARS-CoV-2 antibodies in March 2020. Eight months after enrolment, participants completed an online questionnaire including 72 symptoms in the preceding month. Symptomatic mild-to-moderate cases with confirmed COVID-19 were compared with asymptomatic, seronegative controls. Multivariable logistic regression was used to identify independent symptoms associated with long COVID. FindingsAll 2,147 participants were contacted and 1,671 (77.8%) completed the questionnaire, including 140 (8.4%) cases and 1,160 controls. At a median of 7.5 (IQR 7.1-7.8) months after infection, 20 cases (14.3%) had ongoing (4/140, 2.9%) or episodic (16/140, 11.4%) symptoms. We identified three clusters of symptoms associated with long COVID, those affecting the sensory (ageusia, anosmia, loss of appetite and blurred vision), neurological (forgetfulness, short-term memory loss and confusion/brain fog) and cardiorespiratory (chest tightness/pain, unusual fatigue, breathlessness after minimal exertion/at rest, palpitations) systems. The sensory cluster had the highest association with being a case (aOR 5.25, 95% CI 3.45-8.01). Dermatological, gynaecological, gastrointestinal or mental health symptoms were not significantly different between cases and controls. InterpretationMost persistent symptoms reported following mild COVID-19 were equally common in cases and controls. While all three clusters identified had a strong association with cases, the sensory cluster had the highest specificity and strength of association, and therefore, most likely to be characteristic of long COVID. FundingPHE. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed using search terms "long covid*" OR "post COVID*" in adults for studies including cohort, case reports, randomised control trials, cross-sectional and systematic reviews published up to 12 March 2020 without any language restrictions. Most reports included a small number of cases. Larger studies included very specific cohorts, including hospitalised cases and self-selected participants with COVID-19. A systematic review identified 15 studies and, using a broad case definition, concluded that 80% (95% CI 65-92) of patients with SARS-CoV-2 developed one or more long-term symptoms. The five most common symptoms were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%), but no assessment was made of these symptoms in uninfected adults. Added value of this studyIn a prospective, longitudinal cohort of clinical and non-clinical healthcare workers recruited at the start of the pandemic, we found that most self-reported symptoms were as common in 140 adults who developed mild-to-moderate COVID-19 more than 6 months previously compared to 1,160 controls who were asymptomatic and SARS-CoV-2 antibody negative throughout the surveillance period. Compared to controls, we identified three clusters of symptoms affecting the sensory, neurological and cardiorespiratory systems that were more prevalent among cases. Notably, symptoms affecting other organ systems were as prevalent among cases as controls. The high proportion of cases and controls reporting mental health symptoms highlights the toll that the pandemic has had on healthcare workers Implications of all the available evidenceOur findings highlight the importance of including a representative cohort of cases to assess long-term outcomes of COVID-19 as well as appropriate controls to estimate the relative prevalence of self-reported symptoms to accurately define this new syndrome. Our study adds to the evidence-base for long COVID in adults with mild-to-moderate COVID-19 who contribute to the vast majority of 120+ million infections worldwide. This information is not only important for clinicians, patients and the public, but also for policy makers and healthcare providers who are investing heavily in long-term provisions for COVID-19 survivors.