Project Title: „Identification of molecular determinants associated with the risk for various COVID-19 long term effects: a comprehensive cohort-based study in Latvian population. (POST-COVID-TRACK)”
Funding: European Regional Development Fund (ERDF), Measure 1.1.1.1 “Support for applied research”
Project No.: 1.1.1.1/21/A/029
Period: 1 January 2022 – 30 November 2023
Project costs: 500 000,00 EUR
Principle Investigator: Dr. biol. Jānis Kloviņš
Cooperation partner: Pauls Stradiņš Clinical University Hospital
Project summary:
SARS-CoV-2 infection is a pandemic causing serious health and life threats at its acute phase and impacting the long-term health of post-COVID-19 patients, including multiorgan damage and various disease outcomes. It is estimated that around 80% of COVID-19 patients develop at least one of the long-term outcomes, while the detailed understanding of how infection and following recovery process is impacting these effects is not known. The goal of the project is to identify factors predicting and affecting the development of COVID-19 long-term effects by combining the omics-based data and clinical information in various cohorts of Latvian COVID-19 patients by a novel coronavirus with the impact on various concomitant diseases causing multiorgan damage and various disease outcomes. We will explore different omics-based data focusing on longitudinal changes in gene expression, metabolome, and cell-type-specific activity in samples obtained from COVID-19 patients at acute disease state and during the recovery period. We will use the large existing cohort of COVID-19 patients to access the most frequent post-covid symptoms and perform targeted recruitment of patients in specific disease areas to reach out for rare but more severe complications. We aim to increase the knowledge on molecular mechanisms leading to the development of COVID-19 related outcomes and identify new biomarkers that can be used for prevention and therapy optimization.
Information published 03.01.2022.
Progress of the project:
1 January 2022 – 31 March 2022
In collaboration with Latvian Centre for Disease Prevention and Control and Genome State registry responsible for ID decoding, we are collecting the clinical data of COVID-19 patients involved in the Genome Database of Latvian Population during the National Research Program framework to Mitigate Consequences of COVID-19 (July 2020-March 2021) to acquire information about the most frequent post-COVID syndromes and further organize the follow-up procedures. For the establishment of disease targeted post-COVID-19 patient cohorts sample and data collection strategy is being developed considering the specific processing and storage conditions needed for expected downstream analysis (e.g. spatial transcriptomics, single-cell transcriptomics). Meanwhile, the optimal protocol for urine sample pre-treatment for metabolomics analysis is being developed.
Information published 31.03.2022.
Progress of the project
1 April 2022 – 30 June 2022
In collaboration with Pauls Stradiņš Clinical University Hospital we have initiated sample collection from patients with long-term health nephrological, neurological and pulmonary issues associated with COVID-19. For non-standard (bronchoalveolar lavage fluid, cerebrospinal fluid, and kidney biopsy) samples that will be used in further analysis, such as spatial and single-cell transcriptome sequencing, we have established specific protocols for collection, processing, and preservation. We are continuing clinical data acquisition and processing from Latvian Centre for Disease Prevention and Control and Genome State registry, as well as existing patient cohort expansion from Latvian national biobank. Previously and newly obtained omics, metagenome and full genome sequencing data are being gathered and preliminary data analysis has been launched.
Information published 30.06.2022.
Progress of the project
1 July 2022 – 30 September 2022
The clinical, diagnostic and molecular data of long-term COVID-19 patients from the Latvian Center for Disease Prevention and Control have been completely collected. For the time being, these data are being processed, and patients have been approached for repeated sample donations, which would further be included in the project’s patient cohort. In addition, the first kidney biopsy samples have been obtained to undergo spatial transcriptome analysis using the newly developed Stereomics (Spatio-Temporal Enhanced REsolution Omics sequencing). Collection and processing of other patient samples is also continuing, including bronchoalveolar lavage and cerebrospinal fluid samples, which are being specifically prepared for further full genome, single cell and metagenome sequencing.
Information published 30.09.2022.
Progress of the project
1 October 2022 – 31 December 2022
Currently, the collected data of COVID-19 patients from the National state register are linked with the data of the National population genome database. For this purpose, specific COVID-19 illness questionnaires have been created, which will facilitate patient surveying and further data analysis. The collection, preparation and processing of blood and non-standard samples of neurological, nephrological and lung patients has also been actively initiated. In addition, this project recently became part of the International Common Disease Alliance (ICDA), which means that it is now directly involved in the long-term research of COVID-19 not only in Latvia, but also internationally.
Information published 30.12.2022.
Progress of the project
1 January 2023 – 31 March 2023
In total, we have involved 602 COVID-19 patients (SARS-CoV-2 positive at the time of involvement), including 191 hospitalized subjects. An extensive set of biological samples and data have been collected, and for the majority of these patients, we have completed the follow-up collection. We have also created an extensive online survey for the 602 COVID-19 patients regarding symptoms associated with long-COVID-19. Out of all the patients questioned, 40 were distinguished as long-COVID-19 sufferers (disease symptoms longer than 12 weeks) and determined as particularly interesting for further detailed analysis. Another source for cohorts’ medical information was the National Health registry, from the gathered data we know that 114 cohort participants had U09 or U09.9 (ICD 10 codes for Post COVID-19 condition) at some point, and the registry data also provide additional details regarding their overall health. We are currently also compiling their biochemical analysis results and their cytokine and chemokine profiles. The aforementioned selected 40 patients who are phenotypically best described were invited for a follow-up visit (1.5 – 2 years after initial samples were taken) with a request to submit additional blood samples (for clinical biochemistry analysis, blood transcriptome and single-seq analysis). These patients are compared to matched controls by age, gender and BMI that have had the SARS-CoV-2 infection, but have not developed long COVID symptoms.
Information published 31.03.2023.
Progress of the project
1 April 2022 – 30 June 2022
We have completed sampling and data collection from long-COVID-19 patients with cardiovascular and pulmonary symptoms who will undergo single-cell sequencing – longitudinal samples have been collected during the acute phase of COVID-19 disease, 1-3 months and 1.5-2 years’ post-infection. The first single-cell RNA samples have been successfully sequenced and data analysis has been initiated. In addition, the first data for spatial transcriptome analysis from kidney biopsies of long-term COVID-19 patients with nephrological complications have also been obtained. Microbiome, metagenome and biochemistry data from the total patient cohort are also being collected and analysed in parallel. Currently, the collection of existing data and literature for publications has been actively started.
Information published 30.06.2023.
Progress of the project
1 July 2023 – 30 September 2023
Sample collection and data collection in long-term COVID-19 patients with cardiovascular and pulmonary symptoms for whom single-cell sequencing has been completed has been fully completed. Data analysis has also been completed and the results are currently being prepared for publication in the MDPI journal. Blood plasma metabolome data of COVID-19 patients at three time points (acute phase, after one month and 3-6 months) have also been analyzed, metabolome data of COVID-19 patients have been compared with population controls and correlations of metabolites with clinical analyzes have been carried out, and work is currently underway on a manuscript. In addition, blood transcriptome sequencing of 76 COVID-19 patients at several time points, urine metabolome analysis and measurements of potentially important proteins associated with kidney damage in urine have been performed. The results of this data are also being prepared for publication.
Information published 02.10.2023.
Progress of the project
1 October 2023 – 30 November 2023
Prepared and submitted for publication a manuscript on the diversity and taxonomic composition of the gut microbiome in COVID-19 patients, describing the association of the gut microbiome with antibiotic use and differences in different subgroups of disease severity and in recovered patients and patients with long-term complications. Prepared and submitted for publication a manuscript on changes in blood metabolite profiles during recovery in severe COVID-19 patients, also describing differences between patients with long-term complications and patients who have recovered. Sequencing of the blood transcriptome of COVID-19 (245 samples in total) and bioinformatic analysis were completed, and preliminary statistical analysis was performed. Instrumental analysis of urine metabolite profile of COVID-19 patients, quantification of metabolites (63 patients), and initial statistical analysis completed. Preparation of the final report is underway.
Information published 30.11.2023.