Early immune responses have long-term associations with clinical, virologic, and immunologic outcomes in patients with COVID-19

Abstract

The great majority of SARS-CoV-2 infections are mild and uncomplicated, but some individuals with initially mild COVID-19 progressively develop more severe symptoms. Furthermore, there is substantial heterogeneity in SARS-CoV-2-specific memory immune responses following infection. There remains a critical need to identify host immune biomarkers predictive of clinical and immunologic outcomes in SARS-CoV-2-infected patients. Leveraging longitudinal samples and data from a clinical trial in SARS-CoV-2 infected outpatients, we used host proteomics and transcriptomics to characterize the trajectory of the immune response in COVID-19 patients within the first 2 weeks of symptom onset. We identify early immune signatures, including plasma RIG-I levels, early interferon signaling, and related cytokines (CXCL10, MCP1, MCP-2 and MCP-3) associated with subsequent disease progression, control of viral shedding, and the SARS-CoV-2 specific T cell and antibody response measured up to 7 months after enrollment. We found that several biomarkers for immunological outcomes are shared between individuals receiving BNT162b2 (Pfizer–BioNTech) vaccine and COVID-19 patients. Finally, we demonstrate that machine learning models using 7-10 plasma protein markers measured early within the course of infection are able to accurately predict disease progression, T cell memory, and the antibody response post-infection in a second, independent dataset.

The Frequency and Patterns of Post-COVID-19 Vaccination Syndrome Reveal Initially Mild and Potentially Immunocytopenic Signs in Primarily Young Saudi Women

“…The finding that respondents were primarily young (19–29 years old 53.1%, n = 530), educated (71%, n = 711), Saudi (95%, n = 953), female (78.7%, n = 785) is a significant criterion indicating age- and sex-specific factors in susceptibility to post-COVID vaccine reactions. Our results are consistent with recent studies on similar sample sizes of studies in different continents including Germany, Israel, and Africa [ 38 , 39 , 40 ]. This implies that being female at a young age is a major global risk factor that is constant across different nations with mosaic as well as homogenous population genetic structures.…”

Antibody therapy reverses biological signatures of COVID-19 progression

“…Finally, to independently validate the 10-gene panel, we examined gene-expression profiles reported by Hu et al. 16 We chose this study because it had similar enrollment criteria, time points, sample handling, and sequencing and it had over 100 patients. Compared with Hu et al., 16 we find that, with the exception of MYO18A , the trends in expression that we observe for low- versus high-risk participant clusters closely match the trends by disease severity in this external cohort ( Figure S5 ).…”

“…The transcriptomic data to validate the 10-gene signature were obtained from the GEO under the accession number GSE178967 . 16 The data were processed through the same analytical pipeline as described above.…”

Prior Vaccination Exceeds Prior Infection in Eliciting Innate and Humoral Immune Responses in Omicron Infected Outpatients

“…It is possible this is due to a difference in disease severity or the timing of the vaccination prior to infection or a variant-specific because breakthrough Omicron infection has been reported to be less immunogenic than infection with other variants ( 15 , 18 , 19 ). Other groups as well as we have examined the immune transcriptional response post vaccination ( 10 , 20 – 22 ) and document that, like acute SARS-CoV-2 infection, innate immunity pathways are activated.…”

“…Identification of biomarkers predictive of disease progression has the possibility of contributing positively to clinical management of patients. Type I Interferon response, RIG-I signaling, and multiple proteins known to be induced by interferon signaling including CXCL10 (also known as Interferon Gamma-induced protein, IP-10), MCP-1, MCP-2 and CXCL11 have been reported in a recent preprint to be associated with COVID-19 disease progression in a study of eight patients ( 22 ). As discussed above, in the cohort study here we had insufficient numbers of patients with progressive severe disease to test for biomarkers of progression.…”