SARS-CoV-2 Viremia Precedes an IL6 Response in Severe COVID-19 Patients: Results of a Longitudinal Prospective Cohort
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Abstract
Interleukin 6 (IL6) levels and SARS-CoV-2 viremia have been correlated with COVID-19 severity. The association over time between them has not been assessed in a prospective cohort. Our aim was to evaluate the relationship between SARS-CoV-2 viremia and time evolution of IL6 levels in a COVID-19 prospective cohort.
Methods
Secondary analysis from a prospective cohort including COVID-19 hospitalized patients from Hospital Universitario La Princesa between November 2020 and January 2021. Serial plasma samples were collected from admission until discharge. Viral load was quantified by Real-Time Polymerase Chain Reaction and IL6 levels with an enzyme immunoassay. To represent the evolution over time of both variables we used the graphic command twoway of Stata.
Results
A total of 57 patients were recruited, with median age of 63 years (IQR [53–81]), 61.4% male and 68.4% Caucasian. The peak of viremia appeared shortly after symptom onset in patients with persistent viremia (more than 1 sample with > 1.3 log10 copies/ml) and also in those with at least one IL6 > 30 pg/ml, followed by a progressive increase in IL6 around 10 days later. Persistent viremia in the first week of hospitalization was associated with higher levels of IL6. Both IL6 and SARS-CoV-2 viral load were higher in males, with a quicker increase with age.
Conclusion
In those patients with worse outcomes, an early peak of SARS-CoV-2 viral load precedes an increase in IL6 levels. Monitoring SARS-CoV-2 viral load during the first week after symptom onset may be helpful to predict disease severity in COVID-19 patients.
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SciScore for 10.1101/2022.01.24.22269734: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The final model was reached through backward stepwise removal of variables with p value higher than 0.15. 2.9 Ethics: This study was approved by the Research Ethics Committee of Hospital Universitario La Princesa, Madrid, (register number 4267; 22-10-2020) and it was carried out following the ethical principles established in the Declaration of Helsinki.
Consent: As proposed by AEMPS (Agencia Española de Medicamentos y Productos Sanitarios, The Spanish Agency for Medicines and Medical Devices), only oral consent was required due to the COVID-19 emergency [17].Sex as a biological variable not detected. Randomization not detected. Blinding Attending physicians were blind to the viremia results. SciScore for 10.1101/2022.01.24.22269734: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The final model was reached through backward stepwise removal of variables with p value higher than 0.15. 2.9 Ethics: This study was approved by the Research Ethics Committee of Hospital Universitario La Princesa, Madrid, (register number 4267; 22-10-2020) and it was carried out following the ethical principles established in the Declaration of Helsinki.
Consent: As proposed by AEMPS (Agencia Española de Medicamentos y Productos Sanitarios, The Spanish Agency for Medicines and Medical Devices), only oral consent was required due to the COVID-19 emergency [17].Sex as a biological variable not detected. Randomization not detected. Blinding Attending physicians were blind to the viremia results. Power Analysis 2.2 Sample size: The sample size was estimated in 49 patients to validate the primary objective of the study “SARS-CoV-2 viremia as a biomarker of disease severity” (ongoing manuscript) based on the results of our previous retrospective studies [10,15]. Table 2: Resources
No key resources detected.
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:This study has several limitations. First of all, the sample size of our cohort was small, although it was sufficient to find different patterns in the kinetics of IL6 and viral load. Secondly, all patients included were hospitalized and their first sample was obtained at a median of 7 days after symptom onset, therefore, data from the first days of the disease were limited. In addition, information about different variants of SARS-CoV-2 in our cohort could not be obtained because viral sequencing was not available in our facilities. However, at the time our study was performed, the most prevalent variant in Madrid was the original strain [31]. In conclusion, in those patients with worse outcomes, an early peak of SARS-CoV-2 viral load precedes around 5-10 days a prominent increase in IL6 levels. This finding was very clear in males older than 40 years. Therefore, monitoring SARS-CoV-2 viral load during the first week after symptom onset may be helpful to stratify the severity of patients and predict those who are at high risk of developing hyperinflammatory syndrome and ARDS.
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.
Results from scite Reference Check: We found no unreliable references.
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