Are viral loads in the febrile phase a predictive factor of dengue disease severity?

Background As many studies have shown conflicting results regarding the extent of viraemia and clinical disease severity, we sought to investigate if viraemia during early dengue illness is associated with subsequent clinical disease severity. Methodology/Principal Findings 424 adult patients, in whom the dengue virus (DENV) serotype could be identified, who presented within the first 4 days of illness, were recruited from a tertiary care hospital from Sri Lanka from September 2016 to September 2022 following informed written consent. To characterize subsequent clinical disease severity, all patients were followed throughout their illness daily and disease severity classified according to WHO 1997 and 2009 disease classification. 315 patients had DF, 109 progressed to develop DHF and of those 17 developed shock (DSS). Although the viral loads were higher in the febrile phase in patients who progressed to develop DHF than in patients with DF this was not significant (p=0.15). Significant differences were observed in viral loads in patients infected with different DENV serotypes (p=0.0001), with patients infected with DENV2 having the lowest viral loads and the highest viral loads in DENV1. Although those infected with DENV2 had lower viral loads, infection with DENV2 was significantly associated with a higher risk of developing DHF (p=0.016, Odds ratio 1.8; 95% CI 1.116 to 2.905). Based on the WHO 2009 disease classification, 268 had dengue with warning signs (DWW), 139 dengue without warning signs (DWoWS), and 17 had severe dengue (SD). No significant difference was observed in the viral loads between those with SD, DWW and DWoWS (p=0.34). Conclusions/Significance Viral loads in the febrile phase do not appear to significantly associate with subsequent clinical disease severity in a large Sri Lankan cohort. Author summary As many studies have shown conflicting results regarding the extent of viraemia and clinical disease severity, we sought to investigate if viraemia during early dengue illness was associated with subsequent clinical disease severity. We assessed the viral loads and subsequent clinical disease severity in 424 patients, during early illness, to determine if viral loads associate with disease subsequent disease severity. Although the viral loads were higher in early illness in patients who progressed to develop dengue haemorrhagic fever (DHF) than in patients with dengue fever, this was not significant. Significant differences were observed in viral loads in patients infected with different DENV serotypes, with patients infected with DENV2 having the lowest viral loads and the highest viral loads in DENV1. Although those infected with DENV2 had lower viral loads, infection with DENV2 was significantly associated with a higher risk of developing DHF. Therefore, viral loads in early illness, do not appear to strongly associate with subsequent clinical disease severity in this Sri Lankan cohort. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Yes ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Not Applicable The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was obtained from the Ethics Review Committee of the Faculty of Medical Sciences, University of Sri Jayewardenepura. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Not Applicable I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Not Applicable I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Not Applicable Data is available within the manuscript and figures.