CMV seropositivity is a potential novel risk factor for severe COVID-19 in non-geriatric patients
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
COVID-19 has so far affected more than 250 million individuals worldwide, causing more than 5 million deaths. Several risk factors for severe disease have been identified, most of which coincide with advanced age. In younger individuals, severe COVID-19 often occurs in the absence of obvious comorbidities. Guided by the finding of cytomegalovirus (CMV)-specific T cells with some cross-reactivity to SARS-CoV-2 in a COVID-19 intensive care unit (ICU) patient, we decided to investigate whether CMV seropositivity is associated with severe or critical COVID-19.
Herpes simplex virus (HSV) serostatus was investigated as control.
Methods
National German COVID-19 bio-sample and data banks were used to retrospectively analyze the CMV and HSV serostatus of patients who experienced mild (n = 101), moderate (n = 130) or severe to critical (n = 80) disease by IgG serology. We then investigated the relationship between disease severity and herpesvirus serostatus via statistical models.
Results
Non-geriatric patients (< 60 years) with severe COVID-19 were found to have a very high prevalence of CMV-seropositivity, while CMV status distribution in individuals with mild disease was similar to the prevalence in the German population; interestingly, this was not detectable in older patients. Prediction models support the hypothesis that the CMV serostatus, unlike HSV, might be a strong biomarker in identifying younger individuals with a higher risk of developing severe COVID-19, in particular in absence of other co-morbidities.
Conclusions
We identified ‘CMV-seropositivity’ as a potential novel risk factor for severe COVID-19 in non-geriatric individuals in the studied cohorts. More mechanistic analyses as well as confirmation of similar findings in cohorts representing the currently most relevant SARS-CoV-2 variants should be performed shortly.
Article activity feed
-
-
SciScore for 10.1101/2021.12.22.21268268: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: All participants provided informed written consent.
IRB: Approval for the study design and sample collection was obtained from the local ethics committee of the Technical University of Munich (reference number 182/20 and 633/21 S-SR) and the COVIM steering committee.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources After incubation for 4 h at 37 °C in presence of 1 µg/ml GolgiPlug (Brefeldin A), cells were stained with EMA solution (1:1000) for live/dead discrimination and subsequently with surface antibodies: CD8-PE (1:200), CD3-BV421 (1:100) and murine TCR … SciScore for 10.1101/2021.12.22.21268268: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: All participants provided informed written consent.
IRB: Approval for the study design and sample collection was obtained from the local ethics committee of the Technical University of Munich (reference number 182/20 and 633/21 S-SR) and the COVIM steering committee.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources After incubation for 4 h at 37 °C in presence of 1 µg/ml GolgiPlug (Brefeldin A), cells were stained with EMA solution (1:1000) for live/dead discrimination and subsequently with surface antibodies: CD8-PE (1:200), CD3-BV421 (1:100) and murine TCR β-chain-APC/Fire750 (1:50). CD8-PEsuggested: NoneCD3-BV421suggested: NoneCells were fixed using Cytofix/Cytoperm solution followed by staining for intracellular cytokines by IFN-γ-FITC antibody (1:10) and IL-2-APC (1:25). IL-2-APCsuggested: NoneSoftware and Algorithms Sentences Resources CMV IgG was measured in serum samples with a chemiluminescent microparticle immunoassay on Architect i1000 (Abbott GmbH, Wiesbaden). Abbottsuggested: (Abbott, RRID:SCR_010477)Analysis was performed using IBM SPSS version 26 (IBM Corp., SPSSsuggested: (SPSS, RRID:SCR_002865).Y., USA) and SAS 9.4 (SAS Institute Inc. SAS Institutesuggested: (Statistical Analysis System, RRID:SCR_008567)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:Although our study shows surprising results that are possibly impactful for COVID-19 patients’ outcomes, there are also some limitations that should be mentioned. Our cohort comprises patients and biological samples that were collected in Germany earlier in the pandemic. Therefore, it is important to initiate similar studies with additional subjects to confirm whether our findings can be generalized to patients from other countries. Also, socioeconomical factors should be taken into consideration. Additionally, the biomaterial was collected before the emergence of variants of concern that are currently dominating the pandemic (e.g. delta variant in Europe) and before the global vaccination campaign. Thus, it will be important to perform follow-up analyses in settings that also render the current infection and vaccination dynamics. Another limitation of our study is that the different patient subgroups are not fully balanced by age and gender – which is partly due to biological reasons (for example absence of mildly symptomatic elderly individuals > 80 years). As the biomaterial and patient data used for our analyses were collected in the context of different study protocols, availability of data varied. All of these factors added some challenges to the statistical analyses; however, despite these limitations, the main findings summarized in this report remain robust and highly significant. In summary, we identified ‘CMV-seropositivity’ as a novel risk factor for severe COVID-...
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.
-
