Long Covid Land Toolbox
Justin’s Long Covid Story
One Long Covid sufferer describes his experience of this severely debilitating condition without a cure, and the grief of how it has altered his life.
We’re working to help people like Justin, to protect your health, and to make living in a world with Covid safer.
Why the Patient-Made Term 'Long Covid' is needed
Elisa Perego, Felicity Callard, Laurie Stras, Barbara Melville-Johannesson, Rachel Pope, Nisreen A. Alwan
The patient-made term ‘Long Covid’ is, we argue, a helpful and capacious term that is needed to address key medical, epidemiological and socio-political challenges posed by diverse symptoms persisting beyond four weeks after symptom onset suggestive of coronavirus disease 2019 (COVID-19). An international movement of patients (which includes all six authors) brought the persistence and heterogeneity of long-term symptoms to widespread visibility. The same grassroots movement introduced the term ‘Long Covid’ (and the cognate term ‘long-haulers’) to intervene in relation to widespread assumptions about disease severity and duration. Persistent symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are now one of the most pressing clinical and public health phenomena to address: their cause(s) is/are unknown, their effects can be debilitating, and the percentage of patients affected is unclear, though likely significant. The term ‘Long Covid’ is now used in scientific literature, the media, and in interactions with the WHO. Uncertainty regarding its value and meaning, however, remains. In this Open Letter, we explain the advantages of the term ‘Long Covid’ and bring clarity to some pressing issues of use and definition. We also point to the importance of centring patient experience and expertise in relation to ‘Long Covid’ research, as well as the provision of care and rehabilitation.
Post-COVID-19 condition (also known as long COVID) is generally defined as symptoms persisting for 3 months or more after acute COVID-19. Long COVID can affect multiple organ systems and lead to severe and protracted impairment of function as a result of organ damage. The burden of this disease, both on the individual and on health systems and national economies, is high. In this interdisciplinary Review, with a coauthor with lived experience of severe long COVID, we sought to bring together multiple streams of literature on the epidemiology, pathophysiology (including the hypothesised mechanisms of organ damage), lived experience and clinical manifestations, and clinical investigation and management of long COVID.
Although current approaches to long COVID care are largely symptomatic and supportive, recent advances in clinical phenotyping, deep molecular profiling, and biomarker identification might herald a more mechanism-informed and personally tailored approach to clinical care. We also cover the organisation of services for long COVID, approaches to preventing long COVID, and suggestions for future research.
Three-year outcomes of post-acute sequelae of COVID-19
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to long-term health effects in nearly every organ system, collectively referred to by the patient-coined term Long Covid1,2,3,4,5,6,7,8,9,10,11,12,13,14. Studies following infected individuals for 1 year and 2 years described risk trajectories for many conditions1,3,4,5,6,7,8,9,10,11,12,13,15,16,17,18,19. Risks for some conditions abate after the first year after infection, but risks for many conditions persist at 2 years after initial infection, especially among individuals who were hospitalized for coronavirus disease 2019 (COVID-19) during the acute phase of illness20. About 25% of the burden of the 2-year cumulative burden of disability and disease due to SARS-CoV-2 emanates from the second year after initial infection20. However, studies with longer follow-up times are limited21. It is unclear whether and to what extent risks remain in the third year after infection and whether new latent risks (that have not yet been observed) become apparent in the third year after infection.
Accordingly, we undertook a comprehensive assessment of the risks and burdens of post-acute sequelae of COVID-19 (PASC) across care settings of the acute infection—both non-hospitalized and hospitalized individuals—in the 3 years after infection. Addressing this knowledge gap is important to deepen understanding of the post-acute and long-term health trajectories of people who had SARS-CoV-2 infection and will inform care of people with these conditions.
Plasma-based antigen persistence in the post-acute phase of COVID-19
Persistent symptoms among some individuals who develop COVID-19 have led to the hypothesis that SARS-CoV-2 might, in some form or location, persist for long periods following acute infection.
Studies on SARS-CoV-2 persistence to date, however, have been limited by small and non-representative study populations, short durations since acute infection, unclear documentation of vaccination and reinfection histories, and the absence of a true negative comparator group to assess assay specificity (appendix p 2). To address these limitations, we evaluated the presence of SARS-CoV-2 antigens in once-thawed plasma from a well characterised group of 171 adults (appendix pp 3, 9) at several timepoints in the 14 months following RNA-confirmed SARS-CoV-2 infection, most of whom were studied before vaccination or reinfection (so-called pandemic-era participants).
To understand the specificity of our findings, we compared them to 250 adults (appendix pp 3, 9) whose plasma was collected before 2020, who, by definition, were not infected with SARS-CoV-2 (pre-pandemic era). We used the Simoa (Quanterix) single molecule array detection platform to measure SARS-CoV-2 spike, S1, and nucleocapsid antigens (appendix p 4).
Blood transcriptomic analyses reveal persistent SARS-CoV-2 RNA and candidate biomarkers in post-COVID-19 condition
With an estimated 65 million individuals affected by post-COVID-19 conditions (also known as long COVID), non-invasive biomarkers are direly needed to guide clinical management. To address this pressing need, we used blood transcriptomics in a general practice-based case-control study. Individuals with long COVID were diagnosed according to WHO criteria, and validated clinical scales were used to quantify patient-reported outcomes.
Whole blood samples were collected from 48 individuals with long COVID and 12 control individuals matched for age, sex, time since acute COVID-19, severity, vaccination status, and comorbidities (appendix 1 p 2). Digital transcriptomic analysis was performed using the nCounter (Nanostring Technologies, Seattle, WA, USA) platform, as described for critical COVID-19.
Consequently, 212 genes were identified to be differentially expressed between individuals with long COVID and controls (figure A), of which 70 remained significant after adjustment for false discovery rate correction (appendix 1). Several viral RNAs were upregulated: nucleocapsid, ORF7a, ORF3a, Mpro (a nirmatrelvir plus ritonavir [Paxlovid] target), and antisense ORF1ab RNA. Specifically, the upregulation of antisense ORF1ab RNA suggests ongoing viral replication. SARS-CoV-2-related host RNAs (ACE2/TMPRSS2 receptors, DPP4/FURIN proteases) and RNAs prototypical for memory B-cells and platelets
were also upregulated (figure A). Multivariable logistic regression identified antisense SARS-CoV-2 and FYN RNA concentrations as independent predictors of long COVID (corrected for age and sex; appendix 1 p 2). Receiver operating characteristic curve analysis showed significant discrimination (area under curve [AUC] 0·94, 95% CI 0·86–1·00) between individuals with long COVID (n=48) and controls (n=12), with 93·8% sensitivity and 91·7% specificity (figure B).
Solving the Puzzle of Long Covid
Long Covid provides an opportunity to understand
how acute infections cause chronic disease
Postacute Sequelae of SARS-CoV-2 in Children
STATE-OF-THE-ART REVIEW | FEBRUARY 07, 2024
The coronavirus disease 2019 (COVID-19) pandemic has caused significant medical, social, and economic impacts globally, both in the short and long term. Although most individuals recover within a few days or weeks from an acute infection, some experience longer lasting effects. Data regarding the postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) in children, or long COVID, are only just emerging in the literature. These symptoms and conditions may reflect persistent symptoms from acute infection (eg, cough, headaches, fatigue, and loss of taste and smell), new symptoms like dizziness, or exacerbation of underlying conditions. Children may develop conditions de novo, including postural orthostatic tachycardia syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, autoimmune conditions and multisystem inflammatory syndrome in children. This state-of-the-art narrative review provides a summary of our current knowledge about PASC in children, including prevalence, epidemiology, risk factors, clinical characteristics, underlying mechanisms, and functional outcomes, as well as a conceptual framework for PASC based on the current National Institutes of Health definition.