Long COVID: what it is, impacts, and treatments

“Long COVID refers to a variety of symptoms affecting different organs reported by people following Coronavirus Disease 2019 (COVID-19) infection” (Taquet, 2021). “The symptoms of Long Covid include fatigue, dyspnea, cardiac abnormalities, cognitive impairment, sleep disturbances, symptoms of post-traumatic stress disorder, muscle pain, concentration problems, and headache” (Crook, 2021).

Long Covid can be terribly debilitating and have profound effects on the people it impacts. See this article for background: Long covid is destroying careers, leaving economic distress in its wake (Rowland, Christopher. 2021, December 9. The Washington Post).

What does the research say?

**created December 2021**

Featured articles:

*Alwan, N. A. (2021). The road to addressing Long Covid. Science, 373(6554), 491-493. [PDF] [Cited by]

“The risk of COVID-19 has been largely communicated only in terms of deaths and hospital capacity, with recovery and survival conflated with each other. Around one in three people with symptomatic COVID-19 still experience symptoms 12 weeks after onset. Long Covid can be experienced by all age groups and not only those with acute severe disease. The debilitating symptoms are wide-ranging, multisystemic, and predominantly fluctuating or relapsing. There is still much to understand about Long Covid, but what is not well understood should not be ignored.”

*Baig, A. M. (2021). Chronic long‐COVID syndrome: A protracted COVID‐19 illness with neurological dysfunctions. CNS Neuroscience & Therapeutics, 27(12), 1433-1436. [PDF] [Cited by]

“After almost a year of COVID-19, the chronic long-COVID syndrome has been recognized as an entity in 2021. The patients with the long-COVID are presenting with ominous neurological deficits that with time are becoming persistent and are causing disabilities in the affected individuals. The mechanisms underlying the neurological syndrome in long-COVID have remained obscure and need to be actively researched to find a resolution for the patients with long-COVID. Here, the factors like site of viral load, the differential immune response, neurodegenerative changes, and inflammation as possible causative factors are debated to understand and investigate the pathogenesis of neuro-COVID in long-COVID syndrome.”

*Crook, H., Raza, S., Nowell, J., Young, M., & Edison, P. (2021). Long covid—mechanisms, risk factors, and management. BMJ: British Medical Journal (Online), 374. [PDF] [Cited by]

“Since its emergence in Wuhan, China, covid-19 has spread and had a profound effect on the lives and health of people around the globe … Recent evidence has shown that a range of persistent symptoms can remain long after the acute SARS-CoV-2 infection, and this condition is now coined long covid by recognized research institutes. Studies have shown that long covid can affect the whole spectrum of people with covid-19, from those with very mild acute disease to the most severe forms. Like acute covid-19, long covid can involve multiple organs and can affect many systems including, but not limited to, the respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems. The symptoms of long covid include fatigue, dyspnea, cardiac abnormalities, cognitive impairment, sleep disturbances, symptoms of post-traumatic stress disorder, muscle pain, concentration problems, and headache. This review summarizes studies of the long-term effects of covid-19 in hospitalized and non-hospitalized patients and describes the persistent symptoms they endure. Risk factors for acute covid-19 and long covid and possible therapeutic options are also discussed.”

*Deer, R. R., Rock, M. A., Vasilevsky, N., Carmody, L., Rando, H., Anzalone, A. J., Basson, M. D., Bennett, T. D., Bergquist, T., Boudreau, E. A., Bramante, C. T., Byrd, J. B., Callahan, T. J., Chan, L. E., Chu, H., Chute, C. G., Coleman, B. D., Davis, H. E., Gagnier, J., . . . Robinson, P. N. (2021). Characterizing Long COVID: Deep Phenotype of a Complex Condition. EBioMedicine, 74, 103722. [PDF] [Cited by]

A majority of survivors of COVID-19 report manifestations that persist beyond the acute illness, so-called Post-Acute Sequelae of SARS-CoV-2 (PASC, or “long COVID”). Long COVID can affect even those who were initially mildly symptomatic or asymptomatic, may include a constellation of neurological, respiratory, cardiovascular, and gastrointestinal symptoms, and is debilitating in some affected individuals. Research on long COVID has been complicated due to heterogeneous study methods and lack of a standard for denoting the many phenotypic manifestations (different terms to describe the same symptom or condition).

We reviewed 303 manuscripts flagged as relevant to long COVID by CoronaCentral. From these, we identified 59 manuscripts with 81 cohorts that described 287 clinical manifestations of long COVID. Descriptions (symptoms, laboratory findings, imaging results) were mapped to Human Phenotype Ontology (HPO) terms. We have developed layperson synonyms and definitions for each of the 287 HPO terms, which significantly improves patient and clinician accessibility.

One of the challenges in characterizing long COVID is the fact that patient-reported symptoms are often not captured by clinical evaluation or in surveys. To truly characterize long COVID and therefore stratify patients into subtypes for care decisions, it is necessary to use shared terminology. This common set of HPO definitions will promote integration of research by translating between patient and clinician descriptions of symptoms. We anticipate that this will be a critical resource for use in survey instruments and patient apps for standardizing patient-reporting in the future study of long COVID.”

*Sudre, C. H., Murray, B., Varsavsky, T., Graham, M. S., Penfold, R. S., Bowyer, R. C., Pujol, J. C., Kerstin, K., Michela, A., Canas, L. S., Molteni, E., Marc, M., Jorge Cardoso, M., May, A., Sajaysurya, G., Davies, R., Nguyen, L. H., Drew, D. A., Astley, C. M., . . . Steves, C. J. (2021). Attributes and predictors of long COVID. Nature Medicine, 27(4), 626-631. [PDF] [Cited by]

“Reports of long-lasting coronavirus disease 2019 (COVID-19) symptoms, the so-called ‘long COVID’, are rising but little is known about prevalence, risk factors or whether it is possible to predict a protracted course early in the disease. We analyzed data from 4,182 incident cases of COVID-19 in which individuals self-reported their symptoms prospectively in the COVID Symptom Study app. A total of 558 (13.3%) participants reported symptoms lasting ≥28 days, 189 (4.5%) for ≥8 weeks and 95 (2.3%) for ≥12 weeks. Long COVID was characterized by symptoms of fatigue, headache, dyspnea and anosmia and was more likely with increasing age and body mass index and female sex. Experiencing more than five symptoms during the first week of illness was associated with long COVID (odds ratio = 3.53 (2.76–4.50)). A simple model to distinguish between short COVID and long COVID at 7 days (total sample size, n = 2,149) showed an area under the curve of the receiver operating characteristic curve of 76%, with replication in an independent sample of 2,472 individuals who were positive for severe acute respiratory syndrome coronavirus 2. This model could be used to identify individuals at risk of long COVID for trials of prevention or treatment and to plan education and rehabilitation services.”

*Taquet, M., Dercon, Q., Sierra, L., Geddes, J. R., Husain, M., & Harrison, P. J. (2021). Incidence, co-occurrence, and evolution of long-COVID features: A 6-month retrospective cohort study of 273,618 survivors of COVID-19. PLoS Medicine, 18(9). [PDF] [Cited by]

“Background: Long-COVID refers to a variety of symptoms affecting different organs reported by people following Coronavirus Disease 2019 (COVID-19) infection. To date, there have been no robust estimates of the incidence and co-occurrence of long-COVID features, their relationship to age, sex, or severity of infection, and the extent to which they are specific to COVID-19. The aim of this study is to address these issues.

Methods and findings: We conducted a retrospective cohort study based on linked electronic health records (EHRs) data from 81 million patients including 273,618 COVID-19 survivors. The incidence and co-occurrence within 6 months and in the 3 to 6 months after COVID-19 diagnosis were calculated for 9 core features of long-COVID (breathing difficulties/breathlessness, fatigue/malaise, chest/throat pain, headache, abdominal symptoms, myalgia, other pain, cognitive symptoms, and anxiety/depression). Their co-occurrence network was also analyzed. Comparison with a propensity score–matched cohort of patients diagnosed with influenza during the same time period was achieved using Kaplan–Meier analysis and the Cox proportional hazard model. The incidence of atopic dermatitis was used as a negative control.

Among COVID-19 survivors (mean [SD] age: 46.3 [19.8], 55.6% female), 57.00% had one or more long-COVID feature recorded during the whole 6-month period (i.e., including the acute phase), and 36.55% between 3 and 6 months. The incidence of each feature was: abnormal breathing (18.71% in the 1- to 180-day period; 7.94% in the 90- to180-day period), fatigue/malaise (12.82%; 5.87%), chest/throat pain (12.60%; 5.71%), headache (8.67%; 4.63%), other pain (11.60%; 7.19%), abdominal symptoms (15.58%; 8.29%), myalgia (3.24%; 1.54%), cognitive symptoms (7.88%; 3.95%), and anxiety/depression (22.82%; 15.49%). All 9 features were more frequently reported after COVID-19 than after influenza (with an overall excess incidence of 16.60% and hazard ratios between 1.44 and 2.04, all p < 0.001), co-occurred more commonly, and formed a more interconnected network. Significant differences in incidence and co-occurrence were associated with sex, age, and illness severity. Besides the limitations inherent to EHR data, limitations of this study include that (i) the findings do not generalize to patients who have had COVID-19 but were not diagnosed, nor to patients who do not seek or receive medical attention when experiencing symptoms of long-COVID; (ii) the findings say nothing about the persistence of the clinical features; and (iii) the difference between cohorts might be affected by one cohort seeking or receiving more medical attention for their symptoms.

Conclusions: Long-COVID clinical features occurred and co-occurred frequently and showed some specificity to COVID-19, though they were also observed after influenza. Different long-COVID clinical profiles were observed based on demographics and illness severity.”

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