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ABSTRACT
Background
Quite a few publications describe the scientific manifestations of post-acute sequelae of SARS-CoV-2 (PASC or “lengthy COVID”), however they’re troublesome to combine due to heterogeneous strategies and the shortage of a typical for denoting the various phenotypic manifestations. Affected person-led research are of explicit significance for understanding the pure historical past of COVID-19, however integration is hampered as a result of they usually use completely different phrases to explain the identical symptom or situation. This important disparity in affected person versus scientific characterization motivated the proposed ontological method to specifying manifestations, which can enhance seize and integration of future lengthy COVID research.
Strategies
The Human Phenotype Ontology (HPO) is a extensively used customary for alternate and evaluation of phenotypic abnormalities in human illness however has not but been utilized to the evaluation of COVID-19.
Findings
We recognized 303 articles printed earlier than April 29, 2021, curated 59 related manuscripts that described scientific manifestations in 81 cohorts three weeks or extra following acute COVID-19, and mapped 287 distinctive scientific findings to HPO phrases. We current layperson synonyms and definitions that can be utilized to hyperlink affected person self-report questionnaires to straightforward medical terminology. Lengthy COVID scientific manifestations aren’t assessed constantly throughout research, and most manifestations have been reported with a variety of synonyms by completely different authors. Throughout a minimum of 10 cohorts, authors reported 31 distinctive scientific options akin to HPO phrases; essentially the most generally reported function was Fatigue (median 45.1%) and the least generally reported was Nausea (median 3.9%), however the reported percentages diversified extensively between research.
Interpretation
Translating lengthy COVID manifestations into computable HPO phrases will enhance evaluation, knowledge seize, and classification of lengthy COVID sufferers. If researchers, clinicians, and sufferers share a standard language, then research might be in contrast/pooled extra successfully. Moreover, mapping lay terminology to HPO will assist sufferers help clinicians and researchers in creating phenotypic characterizations which are computationally accessible, thereby enhancing the stratification, prognosis, and remedy of lengthy COVID.
Funding
U24TR002306; UL1TR001439; P30AG024832; GBMF4552; R01HG010067; UL1TR002535; K23HL128909; UL1TR002389; K99GM145411.
Key phrases
Proof earlier than this research
A majority of survivors of COVID-19 report manifestations that persist past the acute sickness, so-called Publish-Acute Sequelae of SARS-CoV-2 (PASC, or “lengthy COVID”). Lengthy COVID can have an effect on even those that have been initially mildly symptomatic or asymptomatic, could embrace a constellation of neurological, respiratory, cardiovascular, and gastrointestinal signs, and is debilitating in some affected people. Analysis on lengthy COVID has been difficult as a result of heterogeneous research strategies and lack of a typical for denoting the various phenotypic manifestations (completely different phrases to explain the identical symptom or situation).
Added worth of this research
We reviewed 303 manuscripts flagged as related to lengthy COVID by CoronaCentral. From these, we recognized 59 manuscripts with 81 cohorts that described 287 scientific manifestations of lengthy COVID. Descriptions (signs, laboratory findings, imaging outcomes) have been mapped to Human Phenotype Ontology (HPO) phrases. We have now developed layperson synonyms and definitions for every of the 287 HPO phrases, which considerably improves affected person and clinician accessibility.
Implications of all of the accessible proof
One of many challenges in characterizing lengthy COVID is the truth that patient-reported signs are sometimes not captured by scientific analysis or in surveys. To actually characterise lengthy COVID and due to this fact stratify sufferers into subtypes for care selections, it’s needed to make use of shared terminology. This widespread set of HPO definitions will promote integration of analysis by translating between affected person and clinician descriptions of signs. We anticipate that this can be a important useful resource to be used in survey devices and affected person apps for standardizing patient-reporting sooner or later research of lengthy COVID.
1. Introduction
- Puelles VG
- Lütgehetmann M
- Lindenmeyer MT
- Sperhake JP
- Wong MN
- Allweiss L
- et al.
,
- Gavriatopoulou M
- Korompoki E
- Fotiou D
- Ntanasis-Stathopoulos I
- Psaltopoulou T
- Kastritis E
- et al.
]. As of mid-2021, the complete spectrum of the scientific penalties of COVID-19 is just not utterly understood. Particular person signs and illness severity differ extensively amongst sufferers through the acute an infection, with some sufferers growing solely delicate signs and even remaining asymptomatic. In distinction, others expertise acute respiratory misery syndrome (ARDS), sepsis, and different life-threatening situations [
,
- Gao Z
- Xu Y
- Solar C
- Wang X
- Guo Y
- Qiu S
- et al.
]. As extra details about affected person restoration has been collected, it has change into clear that a variety of outcomes can even emerge following the acute part of the sickness, with some sufferers experiencing residual signs or growing new signs lengthy after the preliminary an infection. This post-acute an infection, known as lengthy COVID, post-acute sequelae of COVID (PASC), or post-acute COVID-19 syndrome (PACS), represents a big problem for sufferers, physicians, and society as a result of the causes, affected person profile, and even symptom patterns stay troublesome to characterise [
- Rando HM
- Bennett TD
- Byrd JB
- Bramante C
- Callahan TJ
- Chute CG
- et al.
]. These substantial challenges in describing lengthy COVID have led sufferers to self-organise and carry out analysis to attempt to expedite the characterization of this illness and due to this fact the best way to greatest ameliorate the substantial influence that lengthy COVID has had on their lives [
- Davis HE
- Assaf GS
- McCorkell L
- Wei H
- Low RJ
- Re’em Y
- et al.
].
- Greenhalgh T
- Knight M
- A’Court docket C
- Buxton M
- Husain L
]. There’s at the moment no accepted definition of lengthy COVID; nonetheless, it may be broadly outlined as delayed restoration from an infection with SARS-CoV-2. Lengthy COVID can happen following circumstances of COVID-19 that have been managed in both inpatient or outpatient settings. It’s characterised by lasting results of the an infection, unexplained persistence of signs, or onset of latest persistent illnesses, for a lot longer than can be anticipated primarily based on typical charges of viral clearance [
].
- Rando HM
- Bennett TD
- Byrd JB
- Bramante C
- Callahan TJ
- Chute CG
- et al.
](preprint). None of the commonest signs have been assessed by all 15 research. The authors concluded that the signs of lengthy COVID are extraordinarily heterogeneous and that the evaluation of those signs varies extensively amongst research. One other latest systematic overview concluded that 73% of people who had acute COVID-19 skilled a minimum of one persistent symptom [
- Nasserie T
- Hittle M
- Goodman SN.
]. Nonetheless, the authors of the overview concluded that the broad variation in design and high quality of the research restricted the direct comparability and combinability of the information [
- Nasserie T
- Hittle M
- Goodman SN.
]. The wide selection of signs attributed to lengthy COVID are highlighted by an in depth patient-led survey (Affected person-Led Analysis Collaborative). This research performed deep longitudinal characterization of the lengthy COVID signs and trajectories in suspected and confirmed COVID-19 sufferers who reported sickness lasting greater than 28 days [
]
- Davis HE
- Assaf GS
- McCorkell L
- Wei H
- Low RJ
- Re’em Y
- et al.
]. Evaluating knowledge from 3,762 respondents to 257 survey questions, this evaluation documented 205 phenotypic options related to lengthy COVID. The truth that this patient-led research characterised 205 phenotypic options, whereas the research cited within the aforementioned systematic overview reported solely 84 indicators or signs and 19 laboratory or imaging measurements [
- Nasserie T
- Hittle M
- Goodman SN.
], means that the analysis group has not but characterised the complete spectrum of scientific manifestations of lengthy COVID. This important disparity in affected person versus scientific characterization motivates the proposed ontological method to specifying manifestations, which can enhance seize and integration of future lengthy COVID research.
- Köhler S
- Gargano M
- Matentzoglu N
- Carmody LC
- Lewis-Smith D
- Vasilevsky NA
- et al.
,
]. The HPO features a standardised vocabulary of over 16,000 phrases with 37,072 synonyms that outline phenotypic abnormalities related to over 7,000 illnesses. This software permits non-exact matching of units of phenotypic options (phenotype profile) towards recognized illnesses, different sufferers, and mannequin organisms. The algorithms have been carried out for computational comparability of abnormalities and to be used in genetic illness diagnostics, and they’re the de facto customary for deep phenotyping within the discipline of uncommon illness. The HPO is utilized in a spread of tasks together with the UK’s Nationwide Institute for Well being Analysis (NIHR) Uncommon Illness initiatives, the 100,000 Genomes undertaking, the NIH Kidney Precision Drugs Venture, and the NIH Undiagnosed Illnesses Venture and Community, RD-CONNECT, SOLVE-RD, and plenty of others [
- Köhler S
- Gargano M
- Matentzoglu N
- Carmody LC
- Lewis-Smith D
- Vasilevsky NA
- et al.
,
- Köhler S
- Carmody L
- Vasilevsky N
- Jacobsen JOB
- Danis D
- Gourdine J-P
- et al.
]. Present publications on the scientific features of lengthy COVID haven’t used a typical vocabulary to report phenotypic abnormalities, impeding the search, evaluation, and integration of data related to lengthy COVID in databases resembling Medline. Ontologies resembling HPO are systematic representations of information that outline terminology in a human-readable format and outline relationships between ideas in a means that enables computational logical reasoning that helps the mixing and evaluation of enormous quantities of information [
- Haendel MA
- Chute CG
- Robinson PN.
]. The numerous disparity in affected person versus scientific characterization motivated the proposed ontological method to specifying manifestations, which can enhance seize and integration of future lengthy COVID research.
2. Strategies
]. We retrieved 303 articles predicted to be related to lengthy COVID on April twenty ninth, 2021. From these, 59 articles described the scientific manifestations in scientific cohorts of people three weeks or extra following acute COVID-19. We outlined three weeks or extra primarily based on the preliminary look of signs for outpatients or on three weeks or extra after discharge for hospitalised sufferers. Descriptions of lengthy COVID manifestations have been mapped to Human Phenotype Ontology (https://hpo.jax.org/app/) phrases. For this research, the HPO launch 2021-06-08 was used. 4 curators, one with
expertise in lengthy COVID and three with in depth expertise in HPO curation, manually reviewed the articles and recognized HPO phrases that corresponded to the outline of scientific abnormalities (signs, indicators, laboratory abnormalities, irregular imaging findings) within the articles (Determine 1) and mapped them in a spreadsheet. Every mapping was reviewed by all 4 curators and discrepancies have been resolved by dialogue till consensus was reached. Some publications described a number of time factors (e.g., early and late), or various severities of acute sickness (e.g., important/extreme, average, delicate), which have been handled as separate cohorts for the needs of the present descriptive evaluation (Supplemental Desk S1). We tabulated the relationships between publications and the signs they reported, the mapped HPO phrases, and physique techniques (Supplemental Desk S2).
Determine 1The HPO is organized in a hierarchy from normal to extra particular. This graph exhibits a consultant hierarchy of a portion of the HPO ‘abnormality of the respiratory system’ department. On this research, observations from 59 publications have been mapped to the corresponding HPO phrases (nodes). A number of the unique terminology used within the manuscripts (in italics) is proven adjoining to the HPO time period to which it was mapped. An in depth record of all mapped phrases is supplied in Supplemental File 2.
The funders had no position in research design, knowledge assortment, knowledge analyses, interpretation, or writing of report.
3. Outcomes
We reviewed 303 articles that have been predicted to be related to lengthy COVID. We excluded articles that have been evaluations, associated solely to acute-COVID timepoints, or didn’t present adequate particulars to extract percentages for the signs (i.e., solely supplied averages however not the variety of sufferers affected in a cohort). Evaluation of the remaining 59 articles revealed a wide range of standards have been used to determine and consider sufferers with lengthy COVID. The research included 11 cohorts of sufferers who had been handled within the intensive care unit (ICU) throughout acute COVID-19, 36 cohorts of sufferers who have been hospitalised however not admitted to an ICU through the acute part, 16 cohorts of sufferers who weren’t hospitalised through the acute part, and 19 combined cohorts. Some articles pulled knowledge from digital well being data (EHRs), whereas others strictly relied on patient-reported signs from surveys. Research additionally diversified within the technique of assortment and devices used. Strategies of gathering knowledge got here from telephone or digital surveys, in individual overview, or pull from digital medical data. For 26 cohorts, info was collected by in-person, phone, electronic mail, or different on-line questionnaire. For 51 cohorts, info was collected by scientific examination, and for five cohorts, info was collected by questionnaire and scientific examination (Supplemental Desk S1). The timeframe for knowledge assortment and follow-up additionally differed throughout research. Some used a comparatively exact window for affected person evaluation (e.g., 21 days after symptom onset), whereas others included individuals at varied distances from acute SARS-COV-2 an infection. Some research aimed to gather info solely on sufferers affected by lengthy COVID, whereas others collected follow-up info on all sufferers that had beforehand had COVID-19 no matter whether or not they at the moment or ever skilled lengthy COVID. Research differed in how they referred to the phenomenon studied. Some referred to it as lengthy COVID or utilizing an analogous time period resembling post-acute COVID-19 syndrome, whereas others mentioned the scientific course or affected person restoration with out mentioning lengthy COVID particularly. Lastly, research diversified extensively within the terminology used to explain patient-reported signs.
Determine 2Reported frequencies for the 25 phenotypic options recognized in 12 or extra cohorts. Field plots are proven for every merchandise, displaying the minimal (1.5 occasions the interquartile vary beneath the decrease quartile), first quartile, median, third quartile, and most (1.5 occasions the interquartile vary above the higher quartile). Outliers are proven as dots. DLCO: diffusing capability of the lungs for carbon monoxide, FEV1: compelled expiratory quantity in a single second; TLC: whole lung capability.
ad of organ techniques.
Desk 1Overview of irregular phenotypic findings by class. Probably the most generally reported findings are proven for every class. The entire variety of options reported in every organ system is proven within the second column. Classes with a minimum of 7 options are proven. The median % column exhibits the median for the share of sufferers with the function indicated within the earlier column, along with the variety of cohorts reporting the function. Supplemental File S2 supplies particulars.
In our research, we curated 287 HPO phrases representing scientific abnormalities noticed in people following COVID-19. Extra analysis can be wanted to find out which of the phrases, and probably which extra phrases, are particularly and causally associated to SARS-CoV-2 an infection. As an illustration, 10 phenotypic abnormalities in our research have additionally been reported to happen in Publish-Intensive Care Syndrome (PICS). Whereas a lot of the manifestations have been reported to happen at related frequencies, Dyspnea was extra generally reported in sufferers following COVID-19 (Supplemental Determine S26). Extra feedback are supplied in Supplemental Be aware 2. It’s conceivable that in some circumstances, the incidence of those ten manifestations in COVID-19 sufferers is expounded to care within the ICU. Nonetheless, all ten signs have additionally been reported in cohorts of people handled for COVID-19 as outpatients (Supplemental File 2).
4. Dialogue
- White PD
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,
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,
- Hickie I
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]. Power fatigue syndrome (CFS) is incessantly preceded by a viral an infection [
- Bansal AS
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]. Nonetheless, though these sequelae are nicely documented, they’re nonetheless not nicely understood, and the molecular mechanisms underlying these post-acute shows have but to be elucidated.
], following restoration from the acute an infection [
,
- Lam MH-B
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- Yu MW-M
- Leung C-M
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- et al.
,
- Lee SH
- Shin H-S
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- Lee JJ
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- et al.
]. For SARS, follow-up has been performed as much as 15 years post-infection. Along with fatigue, research rep
orted results on lung well being and capability [
- Ong K-C
- Ng AW-K
- Lee LS-U
- Kaw G
- Kwek S-K
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- et al.
,
- Ngai JC
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,
- Hui DS
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- To KW
- et al.
,
- Zhang P
- Li J
- Liu H
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- Ju J
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- et al.
], psychological well being [
], bone well being [
- Zhang P
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- Liu H
- Han N
- Ju J
- Kou Y
- et al.
], and lipid metabolism [
- Wu Q
- Zhou L
- Solar X
- Yan Z
- Hu C
- Wu J
- et al.
], with the latter two attributed to remedies involving massive doses of steroids [
- Zhang P
- Li J
- Liu H
- Han N
- Ju J
- Kou Y
- et al.
,
- Wu Q
- Zhou L
- Solar X
- Yan Z
- Hu C
- Wu J
- et al.
]. Many of the enchancment amongst SARS sufferers occurred throughout the first one to 2 years following an infection [
- Zhang P
- Li J
- Liu H
- Han N
- Ju J
- Kou Y
- et al.
,
Yin C-H, Wang C, Wen Y, Jiang L, Lu Q, Li J-L, et al. [Prospective 2-year clinical study of patients with positive IgG-antibodies after recovering from severe acute respiratory syndrome]. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2005 Dec;17(12):740–2.
,
- Liu Y-X
- Ye Y-P
- Zhang P
- Chen J
- Ye H
- He Y-H
- et al.
]. Some sufferers continued to expertise decreased high quality o
f life for greater than a decade following the acute sickness [
- Wu Q
- Zhou L
- Solar X
- Yan Z
- Hu C
- Wu J
- et al.
]. Although follow-up research in MERS sufferers are sparse, results on pulmonary operate have been noticed at one 12 months post-infection, with sufferers who skilled extra extreme illness at better threat for long-term results [
- Il Jun Ok
- Park WB
- Kim G
- Choi J-P
- Rhee J-Y
- Cheon S
- et al.
].
- Giordo R
- Paliogiannis P
- Mangoni AA
- Pintus G.
]. A variety of outcomes following acute COVID-19 have emerged as extra details about affected person restoration has been collected and pathophysiologic mechanisms are revealed. Some sufferers expertise residual signs and others develop new signs lengthy after the preliminary an infection. Given the timeline of SARS-CoV-2’s emergence, research up to now have tracked sufferers’ scientific course as much as six months post-infection [
- Sykes DL
- Holdsworth L
- Jawad N
- Gunasekera P
- Morice AH
- Crooks MG.
,
- Zhang J
- Xu J
- Zhou S
- Wang C
- Wang X
- Zhang W
- et al.
,
- Huang C
- Huang L
- Wang Y
- Li X
- Ren L
- Gu X
- et al.
], however anecdotal studies can be found describing sufferers with ongoing signs so long as one 12 months post-infection [
]. Signs skilled after the acute sickness signify a big problem for sufferers, physicians, and society as a complete. The causes, affected person profile, and even symptom patterns related to lengthy COVID stay troublesome to isolate, and the pure historical past of this situation stays uncharacterised. Targets of analysis on lengthy COVID embrace understanding the pure historical past of the illness together with the prognosis of the various particular person manifestations of illness, whether or not there are nicely delineated subtypes, whether or not particular traits of the acute part of COVID-19 predispose to lengthy COVID, and what remedies could greatest speed up restoration. Right here, now we have reported 287 HPO phrases representing scientific anomalies reported as lengthy COVID in individuals following acute COVID-19. For a number of the phrases, resembling these reported solely as soon as up to now, additional analysis can be required to find out if the abnormalities are particularly associated to COVID-19 and their frequency. We have now introduced plain-language ‘translations’ of all phrases that can be utilized to create affected person questionnaires.
4.1 Linking layperson and health-professional analysis
- Davis HE
- Assaf GS
- McCorkell L
- Wei H
- Low RJ
- Re’em Y
- et al.
]. Sufferers and clinicians use completely different phrases to explain the identical signs or situations. In lots of circumstances, the scientific time period is an actual match to the layperson synonym; nonetheless, different occasions the layperson terminology is much less exact. HPO permits layperson synonyms to be mapped to an ontology, with extra particular phrases being outlined as subtypes of extra normal phrases. Mapping lay terminology to HPO for lengthy COVID signs will assist sufferers help clinicians and researchers in creating strong computational phenotype profiles, which can enhance the prognosis and remedy of lengthy COVID. Right here, we systematically abstracted 287 lengthy COVID manifestations together with indicators, signs, and laboratory in addition to imaging abnormalities, added layperson synonyms the place lacking, and mapped layperson to HPO terminology. We wrote plain-language definitions for these phrases to complement the prevailing definitions which are geared toward healthcare professionals and researchers. [
- Vasilevsky NA
- Foster ED
- Engelstad ME
- Carmody L
- May M
- Chambers C
- et al.
](35). A full record is obtainable within the supplemental materials in human and laptop readable kind. This widespread set of definitions can promote integration of analysis by translating between affected person and clinician descriptions of signs. We anticipate that these phrases, synonyms and definitions can be a important useful resource to be used in survey devices and affected person apps for standardizing patient-reporting sooner or later research of lengthy COVID.
]. Parosmia in COVID-19 has been reported as an disagreeable notion of odorants (troposmia) that follows anosmia and will persist for a number of months [
- Chary E
- Carsuzaa F
- Trijolet J-P
- Capitaine A-L
- Roncato-Saberan M
- Fouet Ok
- et al.
]. Publish-viral parosmia has been advised to develop within the olfactory neuron regeneration part as a result of a preponderance of immature neurons throughout re-innervation [
- Cavazzana A
- Larsson M
- Münch M
- Hähner A
- Hummel T.
]. This idea has been proposed for COVID-19 associated parosmia as nicely as a result of an analogous sample of succession [
- Mastrangelo A
- Bonato M
- Cinque P.
]. Parosmia was not particularly famous within the research reviewed for this work, however has been proven to have a excessive prevalence in acute and post-acute COVID-19 related parosmia [
- Hopkins C
- Surda P
- Vaira LA
- Lechien JR
- Safarian M
- Saussez S
- et al.
].
- Sheehan J
- Hirschfeld S
- Foster E
- Ghitza U
- Goetz Ok
- Karpinski J
- et al.
]. Creating a standardised vocabulary with HPO mapped to layperson phrases to characterise lengthy COVID signs and findings will present useful steerage in constructing widespread knowledge components for textual and imaging annotation schema in addition to creating patient-centered measurement devices and scientific surveys.
esult of many suppliers are unfamiliar with the huge array of lengthy COVID signs, many aren’t recorded in these narratives. The layperson definitions and related synonym mapping would enormously speed up the event and analysis of NLP algorithms for extracting lengthy COVID indicators and signs from EHRs. Baseline NLP algorithms primarily based on HPO might be carried out. Particularly, a quick trie primarily based string matching method can spot lengthy COVID phrases on the fly in huge scientific corpora for close to real-time interactive analyses of lengthy COVID phenomena from EHR knowledge. A many-to-one mapping from synonyms to HPO phrases recognized on this effort will then facilitate extra fast lengthy COVID analytics. Moreover, this effort would allow the fast growth of an annotation guideline for producing benchmarking knowledge, a important part in growing and evaluating NLP algorithms. If this annotation consists of notes from a number of websites, even spelling errors (that however consult with lengthy COVID phrases) might be noticed by first constructing a named entity recognition (NER) software after which mapping mentions to lengthy COVID HPO phrases by approximate matching through neural phrase embeddings constructed from character-based neural language fashions. One other essential affordance of this effort is to have the ability to mine social media posts for lengthy COVID disclosures from sufferers and healthcare customers to enrich EHR-derived surveillance [
- Banda JM
- Singh GV S.
- Alser OH
- Prieto-Alhambra D.
](preprint).
Because the Nationwide COVID Cohort Collaborative (N3C) established a collaboration amongst a number of organizations by pandemic knowledge sharing, i.e., Widespread Knowledge Mannequin (CDM), the lengthy COVID idea standardization enabled by this research will play an indispensable position in attaining the semantic interoperability for the secondary use of EHR amongst a number of websites.
4.2 Bettering future analysis on the pure historical past of lengthy COVID
]. Though no agency standards have been established to outline the post-acute interval or sub-categories inside lengthy COVID, a number of units of pointers have been proposed for the classification of COVID-19-related illness phenotypes, and these standards have been in comparison with the definitions used within the literature. For instance, a just lately proposed public well being framework classifies SARS-CoV-2-related illness into three classes [
- Datta SD
- Talwar A
- Lee JT.
]. The primary is acute COVID-19, or the illness mostly related to acute SARS-CoV-2 an infection. The second class consists of Multisystem Inflammatory Syndrome in Kids (MIS-C) and in adults (MIS-A), a much less widespread presentation of SARS-CoV-2 an infection characterised by hyperinflammation that may seem 4-6 weeks after viral an infection [
- Vogel TP
- Prime KA
- Karatzios C
- Hilmers DC
- Tapia LI
- Moceri P
- et al.
]. The third class describes late sequelae [
- Datta SD
- Talwar A
- Lee JT.
]. By way of defining research cohorts, adherence with this definition would require a scientific prognosis, fairly than a SARS-CoV-2 take a look at alone, to differentiate MIS-C/A and COVID-19. Whereas it seems too early to suggest a set of computable definitions for the varied sorts of illness related to SARS-CoV-2 (as a result of we’re nonetheless studying concerning the pure historical past), it will be advantageous for research to use a at the moment accepted definition of lengthy COVID and to explain particulars within the strat
egies. Research ought to denote comorbidities utilizing a typical ontology of illnesses resembling Mondo [
- Shefchek KA
- Harris NL
- Gargano M
- Matentzoglu N
- Unni D
- Brush M
- et al.
].
- Dennis A
- Wamil M
- Alberts J
- Oben J
- Cuthbertson DJ
- Wootton D
- et al.
]. Nonetheless, it is a widespread discovering within the normal inhabitants and extra analysis can be required to characterise its exact relation to lengthy COVID.
- Garrigues E
- Janvier P
- Kherabi Y
- Le Bot A
- Hamon A
- Gouze H
- et al.
,
- Goërtz YMJ
- Van Herck M
- Delbressine JM
- Vaes AW
- Meys R
- Machado FVC
- et al.
], anosmia [
- Garrigues E
- Janvier P
- Kherabi Y
- Le Bot A
- Hamon A
- Gouze H
- et al.
,
- Goërtz YMJ
- Van Herck M
- Delbressine JM
- Vaes AW
- Meys R
- Machado FVC
- et al.
], anosmia/ageusia [
- Carvalho-Schneider C
- Laurent E
- Lemaignen A
- Beaufils E
- Bourbao-Tournois C
- Laribi S
- et al.
], lack of scent [
- Tenforde MW
- Kim SS
- Lindsell CJ
- Rose EB
- Shapiro NI
- Clark Information D
- et al.
,
- Sudre CH
- Murray B
- Varsavsky T
- Graham MS
- Penfold RS
- Bowyer RC
- et al.
], lack of style [
- Tenforde MW
- Kim SS
- Lindsell CJ
- Rose EB
- Shapiro NI
- Clark Information D
- et al.
], lack of scent and style [
- Petersen MS
- Kristiansen MF
- Hanusson KD
- Danielsen ME
- Á Steig B
- Gaini S
- et al.
], lack of scent or style [
- Nehme M
- Braillard O
- Alcoba G
- Aebischer Perone S
- Courvoisier D
- Chappuis F
- et al.
], and lack of scent and/or style [
- Chopra V
- Flanders SA
- O’Malley M
- Malani AN
- Prescott HC
]. Whereas in lots of circumstances there are parallels amongst research (e.g., research reporting anosmia and lack of scent are prone to be asking the identical or related questions of sufferers), the shortage of a strict definition prevents straight-forward symptom matching throughout a number of printed analyses. Totally different research measure scientific manifestations in several methods. As an illustration, the presence of fatigue might be measured by a sure/no query in a web based questionnaire or might be inferred from the outcomes of a multidimensional research instrument such because the Brief Kind-36 Vitality scale [
]. In such circumstances, customary use of a full terminology resembling HPO can be helpful to create expressive and constant which means throughout research. Future research ought to make knowledge accessible utilizing both the HPO phrases supplied right here or different phrases from the complete assortment of over 16,000 HPO phrases.
From a scientific standpoint our work demonstrates that managing lengthy COVID sufferers would require a multidisciplinary effort. On condition that respiratory system findings and fatigue have been the commonest, a pulmonologist with a pulmonary rehabilitation program can be one of many cornerstones of any lengthy COVID administration program. On the identical time contemplating the excessive frequency of psychiatric and neurological signs, psychiatrists and neurologists with specialization in neurocognitive testing and remedy can be needed. Moreover given the acute variation in signs and presentation, a main care internist must be answerable for coordinating the care of lengthy COVID sufferers with acceptable referrals when required. Taking into consideration the excessive frequency of lengthy COVID in survivors main care physicians must be made conscious of the myriad shows of lengthy COVID with lively screening for lengthy COVID. Major care physicians might want to refer lengthy COVID sufferers to devoted lengthy COVID administration applications.
Working towards computable lengthy COVID phenotypes on this means will enhance our skill to grasp the pure historical past of lengthy COVID. Such phenotypes may even permit observational analyses of things which will cut back lengthy COVID signs. The standardised phenotypic options and synonyms bundled within the HPO phrases introduced listed here are a basis for pure language processing of EHR knowledge, scientific determination help instruments, and analytic approaches resembling machine studying.
5. Contributors
Creator contributions are as follows: MAH, PNR, RRD conceptualised and designed the research. RRD, MAR, NV, LC, HR, PNR carried out the information abstraction and curation. RRD, PNR validated the information. PNR carried out the information evaluation. RRD, MAR, HR, PNR, MAH drafted the manuscript. RRD, MAR, NV, LC, JR, AJA, MDB, TDB, TB, EAB, CTB, JBB, TJC, LEC, HC, CGC, BDC, HED, JG, CSG, WBH, RK, WDK, FMK, SK, CL, FL, HL, VM, CRM, NM, DRM, JAM, DSM, RAM, TSM, AMP, MAP, EP, JTR, JS, RS, AES, JS, HE, GSS, AAS, UT, GDV, LW, MAH, and PNR interpreted the information and critically revised the manuscript for essential mental content material associated to their space of experience. JAM, PNR assisted with knowledge visualization. All authors learn and permitted the ultimate model to be printed.
Declaration of Competing Curiosity
RRD, TDB, JBB, CGC, WBH, JAM, AMP, ERP, HMR, JS, RAS, AES, JS, GS, MAH, PNR report funding from NIH. MAH and JAM are co-founders of Pryzm Well being.
Acknowledgements
This work was supported by NCATS U24 TR002306. Rachel R. Deer supported by UTMB CTSA UL1TR001439 and NIA P30AG024832; Halie M. Rando was supported by The Gordon and Betty Moore Basis (GBMF 4552) and the Nationwide Human Genome Analysis Institute (R01 HG010067); Tellen D. Bennett supported by NIH UL1TR002535 03S2 and NIH UL1TR002535; James Brian Byrd supported by NIH grant K23HL128909; Christopher G. Chute supported by U24 TR002306. Julian Solway supported by UL1TR002389. Mallory A. Perry supported by K99GM145411.
Knowledge Sharing Assertion
The info used to help the findings of this research are supplied in the primary textual content and supplemental information.
[Appendix. Supplementary materials
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1. Supplemental File 1
Contains Figure S1 (Number of HPO terms per cohort); Figures S2-S25 (Reported frequencies of 287 HPO terms arranged according to categories). Table S1. Summary of papers reviewed for inclusion in this work. Table S2 (post-acute COVID-19 studies curated in this work, including cohort characteristics and PubMed identifiers). Table S3 (HPO terms used to annotated PICU cohorts).
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2. Supplemental File 2
Excel file with detailed curations (HPO label, id, original description, PubMed identifier, first author, year, as well as the counts and percentages in the original study).
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3. Supplemental File 3
Word file with tables that contain HPO ids, labels, definitions, synonyms, and plain-language labels and definitions for the 287 HPO terms used in this work.
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Article Data
Publication Historical past
Revealed: November 25, 2021
Accepted:
November 15,
2021
Obtained in revised kind:
October 22,
2021
Obtained:
September 10,
2021
Identification
DOI: https://doi.org/10.1016/j.ebiom.2021.103722
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