Published in Cell : Immune Monitoring and Early Factors of Long Covid

As we continue to face the pandemic, more information has emerged about post-acute sequelae of COVID-19 (PASC), also referred to as long COVID. The CDC has defined PASC as the occurrence of new, returning, or ongoing health problems that people can experience four or more weeks following a SARS-CoV-2 infection.1

It’s estimated that 31-69% of COVID-19 patients suffer from PASC – with symptoms ranging from memory loss, gastrointestinal distress and fatigue to anosmia and shortness of breath. It has also been associated with acute disease severity and there’s speculation that PASC could be related to autoimmune factors as well as unresolved viral fragments. Due to the heterogeneity of PASC and the wide variety of factors that may be associated with it, there is a critical need to characterize its biological and immunological foundations as well as the evolution of these mechanisms throughout infection and recovery. 1

To gain a better understanding of PASC and how it is caused, researchers performed a multi-omic study of COVID-19 patients from initial diagnosis to early recovery. 1 The study results were recently published in Cell, in an article titled, “Multiple Early Factors Anticipate Post-Acute COVID-19 Sequelae.”

IsoPlexis’ Single-cell Secretome Identifies Supervillain Cell Types in Development of Long COVID

By correlating patient symptoms with in-depth profiling of blood cells and plasma components throughout COVID-19 infection, this study identified factors that may predict sustained disease or PASC.

The authors conducted a longitudinal multi-omic study of 309 COVID-19 patients from initial clinical diagnosis to early-stage recovery from acute disease compared to 457 controls. Patients were split into three stages: clinical diagnosis (T1), acute disease (acute, T2), and 2-3 months post onset of initial symptoms (convalescent, T3).

Blood draws, supplemented with nasal swabs and plasma measurements, were analyzed for autoantibodies, COVID-specific antibodies, global plasma proteomic and metabolomic profiles, as well as single-cell multi-omic characterizations of the blood. The team used IsoPlexis’ 32-plex single-cell functional secretome analysis to detect enhanced polyfunctional cell subsets with cytokine signatures across CD4+ and CD8+ T cells, monocytes and NK cells among various patient PASC endotypes two to three months post COVID-19 infection.

Single-Cell Functional Proteomics Reveals Potential Impact of Supervillain Cells on Sustained Inflammation

IsoPlexis’ single-cell proteomics revealed a correlation between the increased frequency of “supervillain” T cell subsets, “supervillain” monocytes or “resting” NK cells and PASC endotypes as well as their associations with disease severity in convalescent patients, indicating the impact of T cells and monocytes on a sustained inflammation at convalescence. Functional proteomics at a single-cell level was able to provide a unique assessment to dissect the functional impacts of different cell types across multiple timepoints and the interplay between innate and adaptive immune responses that contributed to effector functions or inflammation in Long Covid.


  1. Su, Y., et al. “Multiple Early Factors Anticipate Post-Acute COVID-19 Sequelae.” Cell (2022), doi:
  2. Belluck, Pam. “New Research Hints at 4 Factors That May Increase Chances of Long Covid”. New York Times. New Research Hints at 4 Factors That May Increase Chances of Long Covid – The New York Times (
Share This Article
Subscribe to Follow the Data

Weekly email to keep you at the forefront of single-cell & multiplexed proteomics.