Scientists in Australia have published a multi-omics analysis of immune responses in blood at a transcriptional, cellular, and serological level at 12, 16, and 24 weeks post-infection (wpi) in 69 patients recovering from mild, moderate, severe, or critical COVID-19 in comparison to healthy uninfected controls.
Using bulk total RNA sequencing they identified significant perturbations to gene expression in COVID-19 convalescents until at least 6 months post-infection. Differential gene expression analysis identified > 950 genes that were significantly (FDR < 0.05, fold change > 1.25) differentially expressed (738 upregulated genes; 230 downregulated) in convalescent individuals.
Many of the most strongly upregulated genes in COVID-19 convalescents encoded known biomarkers of inflammation and innate immunity including S100 calcium-binding protein A8 (S100A8), and high-mobility group protein 1 (HMGB1), 5-azacytidine induced 2 (AZI2), and granzyme A (GZMA). They also identified many differentially expressed long non-coding RNAs including metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) which has been found upregulated in response to flavivirus and SARS-CoV-2 infection and is an important regulator of immunity and the cell cycle.
By comparing convalescent patients which developed long COVID to those who did not, the authors discovered that the purturbations in the blood transcriptome persist in individuals referred to a long COVID clinic, whereas they tend to resolve in convalescent individuals not suffering from long COVID symptoms. Interestingly the main trasncriptional signature they detected in long COVID was related to thrombocytopenia, which is marked by fatigue the primary symptom of long COVID.
Finally the authors used gene set variation analysis together with pre-defined blood transcriptional modules to reduce the dimensions of their RNASeq dataset and perform a correlation analysis with flow cytometry and serology data. Through this they validated signatures in the blood transcriptome were associated with frequency of certain immune cells and identified transcriptional modules associated with anti-Spike and anti-RBD responses.