Post by Nadica (She/Her) on Oct 29, 2024 at 5:59am
Blood transcriptomic analyses do not support SARS-CoV-2 persistence in patients with post-COVID-19 condition with chronic fatigue syndrome - Published Oct 25, 2024
Post-COVID-19 condition (also known as long COVID) represents a crucial and emerging global public health challenge. Intriguingly, growing claims exist about the persistence of SARS-CoV-2 or viral antigens in the blood and tissues of patients with long COVID for months after the acute infection. This occurrence is not exclusive to SARS-CoV-2 as long-term shedding of influenza A virus in the stool of immunocompromised patients has been reported previously.1 Furthermore, this finding corresponds with that of a previous report that at 2 months following acute COVID-19, viral RNA was detected in various solid tissues and peripheral blood of immunocompromised individuals with post-COVID-19 symptoms, as opposed to that in immunocompetent individuals.2 Further in-depth studies are warranted to investigate the different aspects of a SARS-CoV-2 reservoir or persistent viral presence in long COVID. Viraemia is not a common outcome of COVID-19, occurring in approximately 1% of severe cases. Overall, the majority of studies3 conducted during the acute phase of COVID-19 show the presence of detectable RNA in few blood samples, frequently characterised by low copy numbers and replication-incompetent viruses.
Previous studies2,4 have reported the presence of viral RNA predominantly in the gut and other solid tissues (eg, liver, kidney, and lung); however, a recent study based on transcriptomic analysis has shown the presence of persistent SARS-CoV-2 RNA 2 years post-acute COVID-19 symptoms in the whole blood of a majority of patients with long COVID.5 This intriguing observation encouraged us to evaluate whether a similar occurrence was evident in our cohort of patients with long COVID with myalgic encephalomyelitis or chronic fatigue syndrome at 12 months following acute COVID-19.6 Therefore, we performed digital transcriptomic analysis using the VIRal Usage Sensor 2 pipeline.7 The platform facilitated the isolation of viral components present in the whole blood of some patients admitted in the intensive care unit during the acute phase of COVID-19; however, we could not detect any SARS-CoV-2 viral components in whole blood samples obtained from our long COVID cohort (n=18) and the recovered group (n=17; figure and appendix). Similarly, our transcriptomic analysis did not support the presence of antisense or other viral components in the whole blood of our study participants; however, we were able to detect antisense, ORF1ab, ORF8, and 5’-UTR in patients with acute COVID-19 (appendix).
In conclusion, in contrast to the previous report findings,5 we were unable to detect any SARS-CoV-2 viral components in the whole blood samples obtained from our long COVID cohort with debilitating myalgic encephalomyelitis or chronic fatigue syndrome. Our observation aligns with the low proportion (1%) of detectable viral load during the acute phase of COVID-19. Further in-depth studies involving large, multi-centre long COVID cohorts are required to validate the persistence of SARS-CoV-2 or viral antigens in the blood of patients with long COVID.
Competing Interests
We declare no competing interests. We thank our study volunteers for providing samples and supporting this work. This work was primarily supported by a grant from the Canadian Institutes of Health Research (CIHR #174901) to SE and a grant from the Li Ka Shing Institute of Virology to MO and SE. Further, SS is supported by a CIHR Research Excellence, Diversity, and Independence Early Career Transition Award, and MO is supported by a STAR Arthritis Society/Institute of Musculoskeletal Health and Arthritis Career Development Award (# 00049). The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All data related to this work are included in the main manuscript and appendices, and the RNAseq data are publicly available at the Sequence Read Archive portal of the National Center for Biotechnology Information under the accession number GSE270045.
Supplementary Material (1)
PDF (156.20 KB)
Supplementary appendix
References
1.
Pinsky, BA ∙ Mix, S ∙ Rowe, J ∙ et al.
Long-term shedding of influenza A virus in stool of immunocompromised child
Emerg Infect Dis. 2010; 16:1165-1167
2.
Zuo, W ∙ He, D ∙ Liang, C ∙ et al.
The persistence of SARS-CoV-2 in tissues and its association with long COVID symptoms: a cross-sectional cohort study in China
Lancet Infect Dis. 2024; 24:845-855
3.
Andersson, MI ∙ Arancibia-Carcamo, CV ∙ Auckland, K ∙ et al.
SARS-CoV-2 RNA detected in blood products from patients with COVID-19 is not associated with infectious virus
Wellcome Open Res. 2020; 5:181
4.
Cheung, CCL ∙ Goh, D ∙ Lim, X ∙ et al.
Residual SARS-CoV-2 viral antigens detected in GI and hepatic tissues from five recovered patients with COVID-19
Gut. 2022; 71:226-229
5.
Menezes, SM ∙ Jamoulle, M ∙ Carletto, MP ∙ et al.
Blood transcriptomic analyses reveal persistent SARS-CoV-2 RNA and candidate biomarkers in post-COVID-19 condition
Lancet Microbe. 2024; 5, 100849
6.
Saito, S ∙ Shahbaz, S ∙ Osman, M ∙ et al.
Diverse immunological dysregulation, chronic inflammation, and impaired erythropoiesis in long COVID patients with chronic fatigue syndrome
J Autoimmun. 2024; 147, 103267
7.
Kwan, PKW ∙ Cross, GB ∙ Naftalin, CM ∙ et al.
A blood RNA transcriptome signature for COVID-19
BMC Med Genomics. 2021; 14:155
Post-COVID-19 condition (also known as long COVID) represents a crucial and emerging global public health challenge. Intriguingly, growing claims exist about the persistence of SARS-CoV-2 or viral antigens in the blood and tissues of patients with long COVID for months after the acute infection. This occurrence is not exclusive to SARS-CoV-2 as long-term shedding of influenza A virus in the stool of immunocompromised patients has been reported previously.1 Furthermore, this finding corresponds with that of a previous report that at 2 months following acute COVID-19, viral RNA was detected in various solid tissues and peripheral blood of immunocompromised individuals with post-COVID-19 symptoms, as opposed to that in immunocompetent individuals.2 Further in-depth studies are warranted to investigate the different aspects of a SARS-CoV-2 reservoir or persistent viral presence in long COVID. Viraemia is not a common outcome of COVID-19, occurring in approximately 1% of severe cases. Overall, the majority of studies3 conducted during the acute phase of COVID-19 show the presence of detectable RNA in few blood samples, frequently characterised by low copy numbers and replication-incompetent viruses.
Previous studies2,4 have reported the presence of viral RNA predominantly in the gut and other solid tissues (eg, liver, kidney, and lung); however, a recent study based on transcriptomic analysis has shown the presence of persistent SARS-CoV-2 RNA 2 years post-acute COVID-19 symptoms in the whole blood of a majority of patients with long COVID.5 This intriguing observation encouraged us to evaluate whether a similar occurrence was evident in our cohort of patients with long COVID with myalgic encephalomyelitis or chronic fatigue syndrome at 12 months following acute COVID-19.6 Therefore, we performed digital transcriptomic analysis using the VIRal Usage Sensor 2 pipeline.7 The platform facilitated the isolation of viral components present in the whole blood of some patients admitted in the intensive care unit during the acute phase of COVID-19; however, we could not detect any SARS-CoV-2 viral components in whole blood samples obtained from our long COVID cohort (n=18) and the recovered group (n=17; figure and appendix). Similarly, our transcriptomic analysis did not support the presence of antisense or other viral components in the whole blood of our study participants; however, we were able to detect antisense, ORF1ab, ORF8, and 5’-UTR in patients with acute COVID-19 (appendix).
In conclusion, in contrast to the previous report findings,5 we were unable to detect any SARS-CoV-2 viral components in the whole blood samples obtained from our long COVID cohort with debilitating myalgic encephalomyelitis or chronic fatigue syndrome. Our observation aligns with the low proportion (1%) of detectable viral load during the acute phase of COVID-19. Further in-depth studies involving large, multi-centre long COVID cohorts are required to validate the persistence of SARS-CoV-2 or viral antigens in the blood of patients with long COVID.
Competing Interests
We declare no competing interests. We thank our study volunteers for providing samples and supporting this work. This work was primarily supported by a grant from the Canadian Institutes of Health Research (CIHR #174901) to SE and a grant from the Li Ka Shing Institute of Virology to MO and SE. Further, SS is supported by a CIHR Research Excellence, Diversity, and Independence Early Career Transition Award, and MO is supported by a STAR Arthritis Society/Institute of Musculoskeletal Health and Arthritis Career Development Award (# 00049). The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All data related to this work are included in the main manuscript and appendices, and the RNAseq data are publicly available at the Sequence Read Archive portal of the National Center for Biotechnology Information under the accession number GSE270045.
Supplementary Material (1)
PDF (156.20 KB)
Supplementary appendix
References
1.
Pinsky, BA ∙ Mix, S ∙ Rowe, J ∙ et al.
Long-term shedding of influenza A virus in stool of immunocompromised child
Emerg Infect Dis. 2010; 16:1165-1167
2.
Zuo, W ∙ He, D ∙ Liang, C ∙ et al.
The persistence of SARS-CoV-2 in tissues and its association with long COVID symptoms: a cross-sectional cohort study in China
Lancet Infect Dis. 2024; 24:845-855
3.
Andersson, MI ∙ Arancibia-Carcamo, CV ∙ Auckland, K ∙ et al.
SARS-CoV-2 RNA detected in blood products from patients with COVID-19 is not associated with infectious virus
Wellcome Open Res. 2020; 5:181
4.
Cheung, CCL ∙ Goh, D ∙ Lim, X ∙ et al.
Residual SARS-CoV-2 viral antigens detected in GI and hepatic tissues from five recovered patients with COVID-19
Gut. 2022; 71:226-229
5.
Menezes, SM ∙ Jamoulle, M ∙ Carletto, MP ∙ et al.
Blood transcriptomic analyses reveal persistent SARS-CoV-2 RNA and candidate biomarkers in post-COVID-19 condition
Lancet Microbe. 2024; 5, 100849
6.
Saito, S ∙ Shahbaz, S ∙ Osman, M ∙ et al.
Diverse immunological dysregulation, chronic inflammation, and impaired erythropoiesis in long COVID patients with chronic fatigue syndrome
J Autoimmun. 2024; 147, 103267
7.
Kwan, PKW ∙ Cross, GB ∙ Naftalin, CM ∙ et al.
A blood RNA transcriptome signature for COVID-19
BMC Med Genomics. 2021; 14:155