Data-driven identification of post-acute SARS-CoV-2 infection subphenotypes

Zhang, Hao; Zang, Chengxi; Xu, Zhenxing; Zhang, Yongkang; Xu, Jie; Bian, Jiang; Morozyuk, Dmitry; Khullar, Dhruv; Zhang, Yiye; Nordvig, Anna S.; Schenck, Edward J.; Shenkman, Louis; Rothman, Russell L.; Block, Jason P.; Lyman, Kristin; Weiner, Mark G.; Carton, Thomas; Wang, Fei; Kaushal, Rainu

doi:10.1038/s41591-022-02116-3

Cited by 129 publications

(105 citation statements)

References 37 publications

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“…Critical: cases who develop respiratory failure and need mechanical ventilation; or cases who develop shock; or cases with other organ failures who need intensive care unit. The occurrence of COVID-19 sequelae was evaluated in the 2nd month after discharge according to symptoms and RT-qPCR results [ 32 ]. To reduce the possibility of an association with possible previous infection, reinfection is defined as a positive RT-qPCR result at least 90 days after the end of the latest infection course.…”

Section: Methodsmentioning

confidence: 99%

SARS-CoV-2 BA.2 (Omicron) variant infection in pediatric liver transplanted recipients and cohabitants during 2022 Shanghai outbreak: a prospective cohort

Zhu

Xue

et al. 2023

Virol J

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Background The Omicron variant BA.2 was the dominant variant in the COVID-19 outbreak in Shanghai since March 2022. We aim to investigate the characteristics of SARS-CoV-2 Omicron variant infection in pediatric liver-transplanted recipients. Methods We conducted a single-center, prospective, observational, single-arm study. We enrolled pediatric liver-transplanted patients infected with the Omicron variant BA.2 from March 19th to October 1st, 2022 and analyzed their demographic, clinical, laboratory, and outcome data. The management of COVID-19 was conducted according to the 9th trial edition of the Chinese guideline. The immunosuppressive therapy was tailored considering the patients’ infection developments and liver functions. Results Five children were included. The primary diseases included Niemann-Pick disease, propionic acidemia, decompensated cirrhosis, biliary atresia, and Crigler-Najjar syndrome type I. All of the patients were onset with fever before or when getting RNA-positive results at the age of 3 (Range: 1–13) years. The infection duration was 29 (Range: 18–40) days. Three and two children were diagnosed with mild and moderate COVID-19 respectively. Two patients were tested RNA-positive within 14 days after having been tested negative. The immunosuppressants were paused or extenuated in four patients. Eight of all nine cohabitants were injected with at least two doses of inactivated SARS-CoV-2 vaccine. The disease courses were significantly longer than the patients (P < 0.05). Conclusions Post-transplant immunosuppression slows down the virus clearance and increases the risk of relapse but does not affect symptom duration or infection severity in pediatric patients. Patients can usually gain a favorable outcome and prognosis by extenuating immunosuppressants.

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Section: Methodsmentioning

confidence: 99%

SARS-CoV-2 BA.2 (Omicron) variant infection in pediatric liver transplanted recipients and cohabitants during 2022 Shanghai outbreak: a prospective cohort

Zhu

Xue

et al. 2023

Virol J

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“…Future directions for this model involve utilizing five-digit zip codes combined with non-shifted COVID diagnosis dates to further investigate the link between climate/sunlight and long COVID and incorporating data on the likely SAR2-COV strains for given dates and locations. Future work will also involve subdividing the Long COVID patients into phenotypic clusters as has been recently reported/suggested by other investigators [12,13]; this will potentially provide insight into whether there are specific features or trajectories that can be correlated to clinical phenotypes.…”

Section: Discussionmentioning

confidence: 99%

Prediction of Long COVID Based on Severity of Initial COVID-19 Infection: Differences in predictive feature sets between hospitalized versus non-hospitalized index infections

Socia

Larie

Feuerwerker

et al. 2023

Preprint

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Long COVID is recognized as a significant consequence of SARS-COV2 infection. While the pathogenesis of Long COVID is still a subject of extensive investigation, there is considerable potential benefit in being able to predict which patients will develop Long COVID. We hypothesize that there would be distinct differences in the prediction of Long COVID based on the severity of the index infection, and use whether the index infection required hospitalization or not as a proxy for developing predictive models. We divide a large population of COVID patients drawn from the United States National Institutes of Health (NIH) National COVID Cohort Collaborative (N3C) Data Enclave Repository into two cohorts based on the severity of their initial COVID-19 illness and correspondingly trained two machine learning models: the Long COVID after Severe Disease Model (LCaSDM) and the Long COVID after Mild Disease Model (LCaMDM). The resulting models performed well on internal validation/testing, with a F1 score of 0.94 for the LCaSDM and 0.82 for the LCaMDM. There were distinct differences in the top 10 features used by each model, possibly reflecting the differences in type and amount of pathophysiological data between the hospitalized and non-hospitalized patients and/or reflecting different pathophysiological trajectories in the development of Long COVID. Of particular interest was the importance of Plant Hardiness Zone in the feature set for the LCaMDM, which may point to a role of climate and/or sunlight in the progression to Long COVID. Future work will involve a more detailed investigation of the potential role of climate and sunlight, as well as refinement of the predictive models as Long COVID becomes increasingly parsed into distinct clinical phenotypes.

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“…However, most of the many symptoms ascribed to ME/CFS have also been associated with Long COVID (and are also found in only a proportion of the cases in this cohort). This would indicate there are multiple phenotypes among Long COVID patients as well, and indeed analysis of health record data from two large patient cohorts has identified four subtypes [ 32 ].…”

Section: What Is the Significance Of ‘Subtypes/phenotypes’ In Me/cfs?mentioning

confidence: 99%

Towards a Better Understanding of the Complexities of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID

Tate

Walker

Peppercorn

et al. 2023

IJMS

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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex condition arising in susceptible people, predominantly following viral infection, but also other stressful events. The susceptibility factors discussed here are both genetic and environmental although not well understood. While the dysfunctional physiology in ME/CFS is becoming clearer, understanding has been hampered by different combinations of symptoms in each affected person. A common core set of mainly neurological symptoms forms the modern clinical case definition, in the absence of an accessible molecular diagnostic test. This landscape has prompted interest in whether ME/CFS patients can be classified into a particular phenotype/subtype that might assist better management of their illness and suggest preferred therapeutic options. Currently, the same promising drugs, nutraceuticals, or behavioral therapies available can be beneficial, have no effect, or be detrimental to each individual patient. We have shown that individuals with the same disease profile exhibit unique molecular changes and physiological responses to stress, exercise and even vaccination. Key features of ME/CFS discussed here are the possible mechanisms determining the shift of an immune/inflammatory response from transient to chronic in ME/CFS, and how the brain and CNS manifests the neurological symptoms, likely with activation of its specific immune system and resulting neuroinflammation. The many cases of the post viral ME/CFS-like condition, Long COVID, following SARS-CoV-2 infection, and the intense research interest and investment in understanding this condition, provide exciting opportunities for the development of new therapeutics that will benefit ME/CFS patients.

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Data-driven identification of post-acute SARS-CoV-2 infection subphenotypes

Cited by 129 publications

References 37 publications

SARS-CoV-2 BA.2 (Omicron) variant infection in pediatric liver transplanted recipients and cohabitants during 2022 Shanghai outbreak: a prospective cohort

SARS-CoV-2 BA.2 (Omicron) variant infection in pediatric liver transplanted recipients and cohabitants during 2022 Shanghai outbreak: a prospective cohort

Prediction of Long COVID Based on Severity of Initial COVID-19 Infection: Differences in predictive feature sets between hospitalized versus non-hospitalized index infections

Towards a Better Understanding of the Complexities of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID

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