Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection
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Abstract
Fatigue is a common symptom in those presenting with symptomatic COVID-19 infection. However, it is unknown if COVID-19 results in persistent fatigue in those recovered from acute infection. We examined the prevalence of fatigue in individuals recovered from the acute phase of COVID-19 illness using the Chalder Fatigue Score (CFQ-11). We further examined potential predictors of fatigue following COVID-19 infection, evaluating indicators of COVID-19 severity, markers of peripheral immune activation and circulating pro-inflammatory cytokines. Of 128 participants (49.5 ± 15 years; 54% female), more than half reported persistent fatigue (67/128; 52.3%) at median of 10 weeks after initial COVID-19 symptoms. There was no association between COVID-19 severity (need for inpatient admission, supplemental oxygen or critical care) and fatigue following COVID-19. Additionally, there was no association between routine laboratory markers of inflammation and cell turnover (leukocyte, neutrophil or lymphocyte counts, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, C-reactive protein) or pro-inflammatory molecules (IL-6 or sCD25) and fatigue post COVID-19. Female gender and those with a pre-existing diagnosis of depression/anxiety were over-represented in those with fatigue. Our findings demonstrate a significant burden of post-viral fatigue in individuals with previous SARS-CoV-2 infection after the acute phase of COVID-19 illness. This study highlights the importance of assessing those recovering from COVID-19 for symptoms of severe fatigue, irrespective of severity of initial illness, and may identify a group worthy of further study and early intervention.
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SciScore for 10.1101/2020.07.29.20164293: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: Ethical Approval: Informed consent was obtained from all participants in the current study in accordance with the Declaration of Helsinki (37).
IRB: Ethical approval for the current study was obtained from the Tallaght University Hospital (TUH)/St James’s Hospital (SJH) Joint Research Ethics Committee (reference REC 2020-04 (01)).Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Statistics: All statistical analysis was carried out using STATA v15.0 (Texas, USA) and statistical significance considered p<0.05. STATAsuggested: (Stata, …SciScore for 10.1101/2020.07.29.20164293: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: Ethical Approval: Informed consent was obtained from all participants in the current study in accordance with the Declaration of Helsinki (37).
IRB: Ethical approval for the current study was obtained from the Tallaght University Hospital (TUH)/St James’s Hospital (SJH) Joint Research Ethics Committee (reference REC 2020-04 (01)).Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Statistics: All statistical analysis was carried out using STATA v15.0 (Texas, USA) and statistical significance considered p<0.05. STATAsuggested: (Stata, RRID:SCR_012763)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:Our single centre study in a predominantly Caucasian Irish population has several limitations worthy of discussion. Our study is cross-sectional in nature and only assessed participants at a single timepoint. As previously mentioned, we are also reporting at a medium time point. As such, we would recommend that longitudinal studies are designed to assess patients at multiple time points and to examine the changes in immune markers and immune cell populations over time. It will also be illustrative to describe the persistence of fatigue at six months and beyond. It is important to note that there is no consensus on the nature of fatigue and its evaluation. However, the use of the widely applied Chalder Fatigue Scale is appropriate in this context. Further studies in large cohorts will be required to tease out fatigue subgroups and the potential complex factors at play. We also suggest that it is now time to consider the management of this post-COVID syndrome and advocate early analysis of multidisciplinary fatigue management strategies.
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.
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SciScore for 10.1101/2020.07.29.20164293: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Ethical Approval Informed consent was obtained from all participants in the current study in accordance with the Declaration of Helsinki (37). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable These were consecutively enrolled (mean age: 49.5 15 years; 52.3% female) (See Table 1). Table 2: Resources
Software and Algorithms Sentences Resources Statistics All statistical analysis was carried out using STATA v15.0 (Texas, USA) and statistical significance considered p<0.05. …STATAsuggested: (Stata, RRID:SCR_012763)SciScore for 10.1101/2020.07.29.20164293: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Ethical Approval Informed consent was obtained from all participants in the current study in accordance with the Declaration of Helsinki (37). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable These were consecutively enrolled (mean age: 49.5 15 years; 52.3% female) (See Table 1). Table 2: Resources
Software and Algorithms Sentences Resources Statistics All statistical analysis was carried out using STATA v15.0 (Texas, USA) and statistical significance considered p<0.05. STATAsuggested: (Stata, RRID:SCR_012763)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:
Our single centre study in a predominantly Caucasian Irish population has several limitations worthy of discussion. Our study is cross-sectional in nature and only assessed participants at a single timepoint. As previously mentioned, we are also reporting at a medium time point. As such, we would recommend that longitudinal studies are designed to assess patients at multiple time points and to examine the changes in immune markers and immune cell populations over time. It will also be illustrative to describe the persistence of fatigue at six months and beyond. It is important to note that there is no consensus on the nature of fatigue and its evaluation. However, the use of the widely applied Chalder Fatigue Scale is appropriate in this context. Further studies in large cohorts will be required to tease out fatigue subgroups and the potential complex factors at play. We also suggest that it is now time to consider the management of this post-COVID syndrome and advocate early analysis of multidisciplinary fatigue management strategies. Conclusions We present the first report, to our knowledge, of post-viral fatigue in those recovered from the acute phase of COVID-19 illness. In a similar fashion to previous coronavirus pandemics, COVID-19 appears to result in symptoms of severe fatigue that outlast the initial acute illness. Over half of individuals in the current study demonstrated symptoms consistent with severe fatigue a median of 10 weeks after their initial illness, while almost one-third of those previously employed had not returned to work. Most interestingly, fatigue was not associated with initial disease severity, and there were no detectable differences in pro-inflammatory cytokines or immune cell populations. Pre-existing diagnosis of depression is associated with severe post-COVID fatigue. This study highlights the burden of fatigue, the impact on return to work and the importance of following all patients diagnosed with COVID, not merely those who required hospitalisation. There are enormous numbers of patients recovering from SARS-CoV-2 infection worldwide. A lengthy post-infection fatigue burden will impair quality of life and will have significant impact on individuals, employers and healthcare systems. These important early observations highlight an emerging issue. These findings should be used to inform management strategies for convalescent patients, and allow intervention to occur in a timely manner.
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.
About SciScore
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.
-
SciScore for 10.1101/2020.07.29.20164293: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Ethical Approval Informed consent was obtained from all participants in the current study in accordance with the Declaration of Helsinki (37). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable These were consecutively enrolled (mean age: 49.5 15 years; 52.3% female) (See Table 1). Table 2: Resources
Software and Algorithms Sentences Resources Statistics All statistical analysis was carried out using STATA v15.0 (Texas, USA) and statistical significance considered p<0.05. …STATAsuggested: (Stata, RRID:SCR_012763)SciScore for 10.1101/2020.07.29.20164293: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Ethical Approval Informed consent was obtained from all participants in the current study in accordance with the Declaration of Helsinki (37). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable These were consecutively enrolled (mean age: 49.5 15 years; 52.3% female) (See Table 1). Table 2: Resources
Software and Algorithms Sentences Resources Statistics All statistical analysis was carried out using STATA v15.0 (Texas, USA) and statistical significance considered p<0.05. STATAsuggested: (Stata, RRID:SCR_012763)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:
Our single centre study in a predominantly Caucasian Irish population has several limitations worthy of discussion. Our study is cross-sectional in nature and only assessed participants at a single timepoint. As previously mentioned, we are also reporting at a medium time point. As such, we would recommend that longitudinal studies are designed to assess patients at multiple time points and to examine the changes in immune markers and immune cell populations over time. It will also be illustrative to describe the persistence of fatigue at six months and beyond. It is important to note that there is no consensus on the nature of fatigue and its evaluation. However, the use of the widely applied Chalder Fatigue Scale is appropriate in this context. Further studies in large cohorts will be required to tease out fatigue subgroups and the potential complex factors at play. We also suggest that it is now time to consider the management of this post-COVID syndrome and advocate early analysis of multidisciplinary fatigue management strategies. Conclusions We present the first report, to our knowledge, of post-viral fatigue in those recovered from the acute phase of COVID-19 illness. In a similar fashion to previous coronavirus pandemics, COVID-19 appears to result in symptoms of severe fatigue that outlast the initial acute illness. Over half of individuals in the current study demonstrated symptoms consistent with severe fatigue a median of 10 weeks after their initial illness, while almost one-third of those previously employed had not returned to work. Most interestingly, fatigue was not associated with initial disease severity, and there were no detectable differences in pro-inflammatory cytokines or immune cell populations. Pre-existing diagnosis of depression is associated with severe post-COVID fatigue. This study highlights the burden of fatigue, the impact on return to work and the importance of following all patients diagnosed with COVID, not merely those who required hospitalisation. There are enormous numbers of patients recovering from SARS-CoV-2 infection worldwide. A lengthy post-infection fatigue burden will impair quality of life and will have significant impact on individuals, employers and healthcare systems. These important early observations highlight an emerging issue. These findings should be used to inform management strategies for convalescent patients, and allow intervention to occur in a timely manner.
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.
About SciScore
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.
-
SciScore for 10.1101/2020.07.29.20164293: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Ethical Approval Informed consent was obtained from all participants in the current study in accordance with the Declaration of Helsinki (37). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable These were consecutively enrolled (mean age: 49.5 15 years; 52.3% female) (See Table 1). Table 2: Resources
Software and Algorithms Sentences Resources Statistics All statistical analysis was carried out using STATA v15.0 (Texas, USA) and statistical significance considered p<0.05. …STATAsuggested: (Stata, RRID:SCR_012763)SciScore for 10.1101/2020.07.29.20164293: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Ethical Approval Informed consent was obtained from all participants in the current study in accordance with the Declaration of Helsinki (37). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable These were consecutively enrolled (mean age: 49.5 15 years; 52.3% female) (See Table 1). Table 2: Resources
Software and Algorithms Sentences Resources Statistics All statistical analysis was carried out using STATA v15.0 (Texas, USA) and statistical significance considered p<0.05. STATAsuggested: (Stata, RRID:SCR_012763)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:
Our single centre study in a predominantly Caucasian Irish population has several limitations worthy of discussion. Our study is cross-sectional in nature and only assessed participants at a single timepoint. As previously mentioned, we are also reporting at a medium time point. As such, we would recommend that longitudinal studies are designed to assess patients at multiple time points and to examine the changes in immune markers and immune cell populations over time. It will also be illustrative to describe the persistence of fatigue at six months and beyond. It is important to note that there is no consensus on the nature of fatigue and its evaluation. However, the use of the widely applied Chalder Fatigue Scale is appropriate in this context. Further studies in large cohorts will be required to tease out fatigue subgroups and the potential complex factors at play. We also suggest that it is now time to consider the management of this post-COVID syndrome and advocate early analysis of multidisciplinary fatigue management strategies. Conclusions We present the first report, to our knowledge, of post-viral fatigue in those recovered from the acute phase of COVID-19 illness. In a similar fashion to previous coronavirus pandemics, COVID-19 appears to result in symptoms of severe fatigue that outlast the initial acute illness. Over half of individuals in the current study demonstrated symptoms consistent with severe fatigue a median of 10 weeks after their initial illness, while almost one-third of those previously employed had not returned to work. Most interestingly, fatigue was not associated with initial disease severity, and there were no detectable differences in pro-inflammatory cytokines or immune cell populations. Pre-existing diagnosis of depression is associated with severe post-COVID fatigue. This study highlights the burden of fatigue, the impact on return to work and the importance of following all patients diagnosed with COVID, not merely those who required hospitalisation. There are enormous numbers of patients recovering from SARS-CoV-2 infection worldwide. A lengthy post-infection fatigue burden will impair quality of life and will have significant impact on individuals, employers and healthcare systems. These important early observations highlight an emerging issue. These findings should be used to inform management strategies for convalescent patients, and allow intervention to occur in a timely manner.
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.
About SciScore
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.
-
SciScore for 10.1101/2020.07.29.20164293: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Ethical Approval Informed consent was obtained from all participants in the current study in accordance with the Declaration of Helsinki (37). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Female gender and those with a pre-existing diagnosis of depression/anxiety were over-represented in those with fatigue. Table 2: Resources
Software and Algorithms Sentences Resources Statistics All statistical analysis was carried out using STATA v15.0 (Texas, USA) and statistical significance considered p<0.05. STATAsuggested: (Stata, SCR_012763)Our … SciScore for 10.1101/2020.07.29.20164293: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Ethical Approval Informed consent was obtained from all participants in the current study in accordance with the Declaration of Helsinki (37). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Female gender and those with a pre-existing diagnosis of depression/anxiety were over-represented in those with fatigue. Table 2: Resources
Software and Algorithms Sentences Resources Statistics All statistical analysis was carried out using STATA v15.0 (Texas, USA) and statistical significance considered p<0.05. STATAsuggested: (Stata, SCR_012763)Our findings would suggest that all patients diagnosed with SARS-CoV-2 will require screening for fatigue. SARS-CoV-2suggested: (Active Motif Cat# 91345, AB_2847847)Data from additional tools added to each annotation on a weekly basis.
About SciScore
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.
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