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LONG-COVID may be permanent in 1 in 200 of people infected – July 2022


Profiling post-COVID syndrome across different variants of SARS-CoV-2 (preptint)

Liane S. Canas PhD1 liane.dos_santos_canas at kcl.ac.uk), Erika Molteni PhD1, Jie Deng PhD1, Carole H. Sudre PhD2,3, Benjamin Murray MSc1, Eric Kerfoot PhD1, Michela Antonelli PhD1, Liyuan Chen MSc1, Khaled Rjoob PhD2, Joan Capdevila Pujol PhD4, Lorenzo Polidori MSc4, Anna May MSc4, Marc F. Osterdahl PhD5, Ronan Whiston PhD5, Nathan J. Cheetham PhD5, Vicky Bowyer MSc5, Prof Tim D. Spector PhD5, Prof Alexander Hammers PhD1, Prof Emma L. Duncan PhD5,6, Prof Sebastien Ourselin PhD1, Claire J. Steves PhD5, Marc Modat PhD1

  1. School of Biomedical Engineering & Imaging Sciences, King’s College London, London, UK.
  2. MRC Unit for Lifelong Health and Ageing, Department of Population Health Sciences, University College London, London, UK
  3. Centre for Medical Image Computing, Department of Computer Science, University College London, London, UK
  4. ZOE Limited London, UK
  5. Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK.
  6. Department of Endocrinology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK

Abstract

Background
Self-reported symptom studies rapidly increased our understanding of SARS-CoV-2 during the pandemic and enabled the monitoring of long-term effects of COVID-19 outside the hospital setting. It is now evident that post-COVID syndrome presents with heterogeneous profiles, which need characterisation to enable personalised care among the most affected survivors. This study describes post-COVID profiles, and how they relate to different viral variants and vaccination status.

Methods
In this prospective longitudinal cohort study, we analysed data from 336,652 subjects, with regular health reports through the Covid Symptom Study (CSS) smartphone application. These subjects had reported feeling physically normal for at least 30 days before testing positive for SARS-CoV-2. 9,323 individuals subsequently developed Long-COVID, defined as symptoms lasting longer than 28 days. 1,459 had post-COVID syndrome, defined as more than 12 weeks of symptoms. Clustering analysis of the time-series data was performed to identify distinct symptom profiles for post-COVID patients, across variants of SARS-CoV-2 and vaccination status at the time of infection. Clusters were then characterised based on symptom prevalence, duration, demography, and prior conditions (comorbidities). Using an independent testing sample with additional data (n=140), we investigated the impact of post-COVID symptom clusters on the lives of affected individuals.

Findings
We identified distinct profiles of symptoms for post-COVID syndrome within and across variants: four endotypes were identified for infections due to the wild-type variant; seven for the alpha variant; and five for delta. Across all variants, a cardiorespiratory cluster of symptoms was identified. A second cluster related to central neurological, and a third to cases with the most severe and debilitating multiorgan symptoms. Gastrointestinal symptoms clustered in no more than two specific phenotypes per viral variant. The three main clusters were confirmed in an independent testing sample, and their functional impact was assessed.

Interpretation
Unsupervised analysis identified different post-COVID profiles, characterised by differing symptom combinations, durations, and functional outcomes. Phenotypes were at least partially concordant with individuals’ reported experiences. Our classification may be useful to understand distinct mechanisms of the post-COVID syndrome, as well as subgroups of individuals at risk of prolonged debilitation.

Conclusion

We identified distinct self-reported symptom evolutions, or clusters, in individuals with more than 12 weeks of persisting symptoms after SARS CoV-2 infection, using a data-driven approach. Although multiple clusters were found across the three variants assessed, common features emerged for three clusters dominated by certain symptom groups: central neurological, cardiorespiratory, and systemic/inflammatory (Supplementary Table 1). Our findings may have relevance to individuals living with PCS, their health practitioners, and healthcare services, providing data to validate their illness and manage their expectations during its course. This work adds to the emerging evidence that PCS may have sub-types, possibly with differing pathophysiology. For any given individual, their condition may relate to a specific central/neurological process, to respiratory damage, or to a systemic inflammatory cause. Our study suggests that further investigation into mechanisms underlying PCS should consider subdividing affected individuals into different subgroups, which may increase the ability to identify distinct processes underlying these symptom clusters.

Research in context

__Evidence before this study:))
We conducted a search in the PubMed Central database, with keywords: ("Long-COVID*" OR "post?covid*" OR "post?COVID*" OR postCOVID* OR postCovid*) AND (cluster* OR endotype* OR phenotype* OR sub?type* OR subtype).
On 15 June 2022, 161 documents were identified, of which 24 either provided descriptions of sub-types or proposed phenotypes of Long-COVID or post-COVID syndrome(s). These included 16 studies attempting manual sub-grouping of phenotypes, 6 deployments of unsupervised methods for patient clustering and automatic semantic phenotyping (unsupervised k-means=2; random forest classification; other=2), and two reports of uncommon presentations of Long-COVID/post-COVID syndrome. Overall, two to eight symptom profiles (clusters) were identified, with three recurring clusters. A cardiopulmonary syndrome was the predominant observation, manifesting with exertional intolerance and dyspnoea (n=10), fatigue (n=8), autonomic dysfunction, tachycardia or palpitations (n=5), lung radiological abnormalities including fibrosis (n=2), and.chest pain (n=1). A second common presentation consisted in persistent general autoimmune activation and proinflammatory state (n=2), comprising multi-organ mild sequelae (n=2), gastrointestinal symptoms (n=2), dermatological symptoms (n=2), and/or fever (n=1). A third syndrome was reported, with neurological or neuropsychiatric symptoms: brain fog or dizziness (n=2), poor memory or cognition (n=2), and other mental health issues including mood disorders (n=5), headache (n=2), central sensitization (n=1), paresthesia (n=1), autonomic dysfunction (n=1), fibromyalgia (n=2), and chronic pain or myalgias (n=6). Unsupervised clustering methods identified two to six different post-COVID phenotypes, mapping to the ones described above.
14 further documents focused on possible causes and/or mechanisms of disease underlying one or more manifestations of Long-COVID or post-COVID and identifying immune response dysregulation as a potential common element. All the other documents were beyond the scope of this work.
To our knowledge, there are no studies examining the symptom profile of post-COVID syndrome between different variants and vaccination status. Also, no studies reported the modelling of longitudinally collected symptoms, as time-series data, aiming at the characterisation of post-COVID syndrome.
Added-value of this study:
Our study aimed to identify symptom profiles for post-COVID syndrome across the dominant variants in 2020 and 2021, and across vaccination status at the time of infection, using a large sample with prospectively collected longitudinal self-reports of symptoms. For individuals developing 12 weeks or more of symptoms, we identified three main symptom profiles which were consistent across variants and by vaccination status, differing only in the ratio of individuals affected by each profile and symptom duration overall.
Implications of all the available evidence:
We demonstrate the existence of different post-COVID syndromes, which share commonalities across SARS-CoV-2 variant types in both symptoms themselves and how they evolved through the illness. We describe subgroups of patients with specific post-COVID presentations which might reflect different underlying pathophysiological mechanisms. Given the time-series component, our study is relevant for post-COVID prognostication, indicating how long certain symptoms last. These insights could aid in the development of personalised diagnosis and treatment, as well as helping policymakers plan for the delivery of care for people living with post-COVID syndrome.


Video review of pre-print by Dr. Campbell - Aug 4, 2022

YouTube


See also VitaminDwiki

Half as much Long-Haul with Omicron - June 2022
Long-COVID is now the biggest COVID concern - many studies
Long-Haul more prevalent among seniors - June - 2022
Long-haul fatigue, etc. common after viral infections (SARS1,2, MERS, Swine, 1918,...) even a decade later
Probably fewer long-haul COVID-19 problems when rejuvenated immune system (Vitamin D, etc.)– Dec 2020


VitaminDWiki Virus pages with LONG-HAUL or LONG-COVID in the title (46 as of Aug 2022)

Items found: 47
Title Modified
Chronic Fatigue Syndrome and long-haul COVID-19 26 Sep, 2022
Long-COVID is now the biggest COVID concern - many studies 13 Sep, 2022
Some Long-COVID may be adrenal insufficiency – May 2022 27 Aug, 2022
Over Two Million Americans Aren’t Working Due to Long-COVID - Aug 2022 27 Aug, 2022
Long-COVID: often had not been hospitalized - May 2022 25 Aug, 2022
COVID virus persists in most body tissues (Long-COVID) - 2022 23 Aug, 2022
Long COVID Persists in Almost All Tissues of The Body 23 Aug, 2022
Long-COVID in VitaminDWiki 16 Aug, 2022
LONG-COVID may be permanent in 1 in 200 of people infected – July 2022 06 Aug, 2022
LONG-COVID may be permanent in 1 in 200 of people infected – July 2022 06 Aug, 2022
Long-Haul more prevalent among seniors - June - 2022 26 Jun, 2022
Long-Haul can now be claimed a work disability in the UK – June 2022 24 Jun, 2022
Half as much Long-Haul with Omicron - June 2022 19 Jun, 2022
Half as much Long-Haul with Omicron - June 2022 19 Jun, 2022
COVID Spike persists in Long Haul - June 2022 18 Jun, 2022
COVID Long-Haul prevalence increases with time: 50% at 4 months - meta June 2022 17 Jun, 2022
COVID and Magnesium - hypothesis, clinical trials, Long-Haul - Oct 2021 10 Jun, 2022
Mass disabling events: Polio, WWII, HIV, and COVID Long-Haul - June 2022 06 Jun, 2022
1 in 5 Americans who got COVID had Long-Haul for a while - CDC May 2022 27 May, 2022
Long-Haul COVID after 3 months – only 5 percent had even 30 ng of Vitamin D – April 2022 04 May, 2022
Long Covid, Short Magnesium - April 2022 22 Apr, 2022
Hypothesis: 2 long-haul COVIDs: had mild symptoms and had needed ICU - April 2022 15 Apr, 2022
COVID Long-Haul at 49 weeks: overactive immune system, type O blood - March 2022 07 Apr, 2022
Children have less severe COVID, but just as much long-haul as adults - April 2022 06 Apr, 2022
Dietary Recommendations for COVID Long-Haul – March 2022 20 Mar, 2022
Mild Long-Haul 4.2 X more likely if type O blood - preprint March 16, 2022 20 Mar, 2022
Long-Haul COVID is somewhat less of a problem if vaccinated – Nov 2021 18 Mar, 2022
COVID Long-Haul NYT - Feb 2022 19 Feb, 2022
COVID Long-Haul fought by probiotics - Jan 2022 29 Jan, 2022
COVID Long-Haul predicted by 4 factors (Epstein-Barr virus, etc) – Jan 24, 2022 26 Jan, 2022
COVID Long-Haul predicted by 4 factors (Epstein-Barr virus, etc) – Jan 24, 2022 26 Jan, 2022
Some COVID-19 infection become COVID Long-Haul - Nov 2020 15 Dec, 2021
Epstein-Barr Virus may cause Long-Haul, CFS, and MS (Vitamin D should help) 11 Dec, 2021
Epstein-Barr virus appears to cause Long-Haul and Chronic fatiure Syndrome (Vitamin D might help) 11 Dec, 2021
Long-haul after breakthrough COVID – Nov 2021 11 Dec, 2021
Long-haul, VAERS, Ivermectin, vaccines, etc. Drs. Seheult, Patrick: Video with table of contents - Sept 17, 2021 21 Sep, 2021
Your Brain on Covid-19 Long-Haul, Dr. Galland video and transcript - Aug 1, 2021 07 Aug, 2021
Long-haul COVID-19 blood tests at Mayo include vitamin D (but no results published) – July 2021 20 Jul, 2021
Most people with Long-Haul COVID-19 have low Vitamin D – July 2021 15 Jul, 2021
‘Long haul’ COVID rehab worse than cancer rehab, CDC – July 2021 13 Jul, 2021
Long-Haul COVID-19 occurred to 1 in 20 who had been asymptomatic (a study of 2 million with COVID-19) – June 2021 15 Jun, 2021
COVID-19 Long haul - excellent graph - systematic review May 26, 2021 26 May, 2021
COVID-19 vaccines look good in the short term, but probably not good for the long term 29 Apr, 2021
Long-haul COVID-19 - another hint that Vitamin D should help - Dec 2020 16 Apr, 2021
Probably fewer long-haul COVID-19 problems when rejuvenated immune system (Vitamin D, etc.)– Dec 2020 21 Feb, 2021
Long-haul fatigue, etc. common after viral infections (SARS1,2, MERS, Swine, 1918,...) 21 Feb, 2021
Long-distance truck drivers more likely to get COVID-19 (perhaps UVA)- July 2020 12 Aug, 2020


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