Longitudinal immune dynamics of mild COVID-19 define signatures of recovery and persistence
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Abstract
SARS-CoV-2 has infected over 200 million and caused more than 4 million deaths to date. Most individuals (>80%) have mild symptoms and recover in the outpatient setting, but detailed studies of immune responses have focused primarily on moderate to severe COVID-19. We deeply profiled the longitudinal immune response in individuals with mild COVID-19 beginning with early time points post-infection (1-15 days) and proceeding through convalescence to >100 days after symptom onset. We correlated data from single cell analyses of peripheral blood cells, serum proteomics, virus-specific cellular and humoral immune responses, and clinical metadata. Acute infection was characterized by vigorous coordinated innate and adaptive immune activation that differed in character by age (young vs. old). We then characterized signals associated with recovery and convalescence to define and validate a new signature of inflammatory cytokines, gene expression, and chromatin accessibility that persists in individuals with post-acute sequelae of SARS-CoV-2 infection (PASC).
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SciScore for 10.1101/2021.05.26.442666: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:There are several key limitations to our study, including 1) a small sample size especially for PASC participants, 2) lack of geographic and racial diversity, 3) asynchronous sampling due to outpatient status, and 4) gaps in sampling during early infection (first ∼7 days PSO) for some participants. Natural history studies are intrinsically …
SciScore for 10.1101/2021.05.26.442666: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:There are several key limitations to our study, including 1) a small sample size especially for PASC participants, 2) lack of geographic and racial diversity, 3) asynchronous sampling due to outpatient status, and 4) gaps in sampling during early infection (first ∼7 days PSO) for some participants. Natural history studies are intrinsically limited to correlative associations. Confirming causality from our findings to mechanistically link early infection immune responses to convalescent CoV-2-specific immune responses will require preclinical models. Multi-omic assays were conducted on parallel samples and independently from CoV-2-specific assays, so relationships between different -omics and CoV-2 responses were inferred. Direct multiplexed analysis, particularly adding TCR and BCR clonality, will better enable dissection of virus-specific vs. non-specific immune mechanisms. Despite these weaknesses, our study provides insightful data that advance our understanding of SARS-CoV-2 infection, mild COVID-19, convalescence, and PASC. Overall, our study results provide a comprehensive longitudinal roadmap of immune activation and resolution in mild COVID-19, including a potential mechanism for an age-dependent effect on immune responses. We observed a robust plasmablast response that may be tightly regulated by early IFN responses, and identified key early correlates of antibody and B cell responses, both findings which should be broadly tested as potential shared features in diver...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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