A patient-centric modeling framework captures recovery from SARS-CoV-2 infection, 2023, Ruffieux et al

Abstract

The biology driving individual patient responses to severe acute respiratory syndrome coronavirus 2 infection remains ill understood. Here, we developed a patient-centric framework leveraging detailed longitudinal phenotyping data and covering a year after disease onset, from 215 infected individuals with differing disease severities.

Our analyses revealed distinct ‘systemic recovery’ profiles, with specific progression and resolution of the inflammatory, immune cell, metabolic and clinical responses. In particular, we found a strong inter-patient and intra-patient temporal covariation of innate immune cell numbers, kynurenine metabolites and lipid metabolites, which highlighted candidate immunologic and metabolic pathways influencing the restoration of homeostasis, the risk of death and that of long COVID. Based on these data, we identified a composite signature predictive of systemic recovery, using a joint model on cellular and molecular parameters measured soon after disease onset. New predictions can be generated using the online tool http://shiny.mrc-bsu.cam.ac.uk/apps/covid-19-systemic-recovery-prediction-app, designed to test our findings prospectively.

Open access, https://www.nature.com/articles/s41590-022-01380-2

 

Immunologic prediction of long COVID

In addition to the acute phase of SARS-CoV-2 infection, a significant percentage of patients experience a prolonged illness with varying symptomatology. Longitudinal SARS-CoV-2 patient-centric immunologic, inflammatory and metabolic data collection has allowed the generation of a composite signature to predict recovery.
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Symptoms of PASC comprise cough, fatigue, brain fog, myalgias and arthralgias, chest pain and many others, including disruption of smell and taste2. Many of these somatic complaints are relatively nonspecific and have been noted with other viral infections, including Epstein–Barr virus (EBV)4. The anosmia (loss of smell) and aguesia (loss of taste) may be fairly COVID-19 specific, with SARS-CoV-2 infecting the support cells for the olfactory nerves5. However, much of what is experienced during long-term post-SARS-CoV-2 infection overlaps with chronic fatigue syndrome/myalgic encephalitis, and it has been hypothesized to result from EBV reactivation6. Similarly, multiple sclerosis has been linked with EBV infection7. Nonetheless, the biology and immunology of PASC remain unclear, with commonly suggested hypotheses ranging from effects of pathogen remnants to autoimmunity to microbiome dysbiosis to direct tissue damage4. Multiple reports have explored risk definition for PASC development8, but the study by Ruffieux et al. explores patient-centric clinical, inflammatory, immunologic and metabolic parameters longitudinally to predict outcomes3.

https://www.nature.com/articles/s41590-022-01396-8

 

The methodology/analysis is complex but some summary quotes from the discussion —

 

For reference, the condition they refer to, HLH, is a cytokine release ("storm") syndrome and can be primary/familial or secondary, eg with infection, autoimmune/inflammatory conditions and malignancy, esp. in children. I note that Jo and SnowLeopard have previously commented that there isn't good evidence for cytokine storm itself in COVID but am assuming the authors here are more interested in shared mechanisms, esp relating to NK cells.

Some recent references —

Traffic jam within lymphocytes: A clinician's perspective (2023)
Cytokine Storm Syndrome (2023)
Malignancy-associated haemophagocytic lymphohistiocytosis (2022, paywall)
Recent advances in the treatment of hemophagocytic lymphohistiocytosis and macrophage activation syndrome (2022, paywall)
A Review of Current and Emerging Therapeutic Options for Hemophagocytic Lymphohistiocytosis (2022, paywall)

 

This seems a pretty amazing approach...