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Observational Study
. 2022 Nov;94(11):5260-5270.
doi: 10.1002/jmv.27989. Epub 2022 Aug 9.

Relevant SARS-CoV-2 viremia is associated with COVID-19 severity: Prospective cohort study and validation cohort

Laura Cardeñoso Domingo  1 , Emilia Roy Vallejo  2 , Nelly D Zurita Cruz  1 , Marta Chicot Llano  3 , Elena Ávalos Pérez-Urria  4 , Ana Barrios  2 , Julia Hernando Santos  5 , Javier Ortiz  6 , Sebastián C Rodríguez García  7 , Alexandra Martín Ramírez  1 , Marianela Ciudad Sañudo  2 , Celeste Marcos  4 , Elena García Castillo  4 , Leticia Fontán García-Rodrigo  1 , Begoña González  3 , Rosa Méndez  5 , Isabel Iturrate  6 , Ancor Sanz García  8 , Almudena Villa  2 , Ana Sánchez Azofra  4 , Begoña Quicios  3 , David Arribas  5 , Jesús Álvarez Rodríguez  2 , Pablo Patiño  3 , Marina Trigueros  3 , Miren Uriarte  7 , Ana Triguero Martínez  7 , Cristina Arévalo  2 , José M Galván Román  2 , Rosario García-Vicuña  7 , Julio Ancochea  4 , Joan B Soriano  4 , Alfonso Canabal  3 , Cecilia Muñoz Calleja  9 , Rafael De la Cámara  6 , Carmen Suarez Fernández  2 , Isidoro González Álvaro  7 , Diego A Rodríguez-Serrano  3 ; PREDINMUN-COVID Group
Affiliations
Observational Study

Relevant SARS-CoV-2 viremia is associated with COVID-19 severity: Prospective cohort study and validation cohort

Laura Cardeñoso Domingo et al. J Med Virol. 2022 Nov.

Abstract

Early kinetics of SARS-CoV-2 viral load (VL) in plasma determined by quantitative reverse-transcription polymerase chain reaction (RT-PCR) was evaluated as a predictor of poor clinical outcome in a prospective study and assessed in a retrospective validation cohort. Prospective observational single-center study including consecutive adult patients hospitalized with COVID-19 between November 2020 and January 2021. Serial plasma samples were obtained until discharge. Quantitative RT-PCR was performed to assess SARS-CoV-2 VL. The main outcomes were in-hospital mortality, admission to the Intensive Care Unit (ICU), and their combination (Poor Outcome). Relevant viremia (RV), established in the prospective study, was assessed in a retrospective cohort including hospitalized COVID-19 patients from April 2021 to May 2022, in which plasma samples were collected according to clinical criteria. Prospective cohort: 57 patients were included. RV was defined as at least a twofold increase in VL within ≤2 days or a VL > 300 copies/ml, in the first week. Patients with RV (N = 14; 24.6%) were more likely to die than those without RV (35.7% vs. 0%), needed ICU admission (57% vs. 0%) or had Poor Outcome (71.4% vs. 0%), (p < 0.001 for the three variables). Retrospective cohort: 326 patients were included, 18.7% presented RV. Patients with RV compared with patients without RV had higher rates of ICU-admission (odds ratio [OR]: 5.6 [95% confidence interval [CI]: 2.1-15.1); p = 0.001), mortality (OR: 13.5 [95% CI: 6.3-28.7]; p < 0.0001) and Poor Outcome (OR: 11.2 [95% CI: 5.8-22]; p < 0.0001). Relevant SARS-CoV-2 viremia in the first week of hospitalization was associated with higher in-hospital mortality, ICU admission, and Poor Outcome. Findings observed in the prospective cohort were confirmed in a larger validation cohort.

Keywords: COVID-19; SARS-CoV-2; disease severity; poor outcome; viremia.

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Conflict of interest statement

The authors of this manuscript have the following competing interests: Julio Ancochea reports grants and personal fees from GlaxoSmithKline and Boehringer Ingelheim; grants from Linde Healthcare; and grants, personal fees, and nonfinancial support from Roche and from Chiesi, outside the submitted work. Diego A. R. Serrano reports personal fees from MSD and Pfizer, outside the submitted work. Rafael de la Cámara reports personal fees from MSD, ASTELLAS, Clinigen, Janssen, Roche, and IQONE Health Care outside the submitted work. Rosario G. Vicuña reports grants, personal fees, and nonfinancial support from Abbvie, BMS, Lilly, Novartis, Sanofi, Sandoz, and MSD; personal fees from Biogen and Celltrion and from Mylan, outside the submitted work; personal fees and nonfinancial support from Pfizer; grants from Roche; and grants and personal fees from Janssen. Carmen S. Fernández reports personal fees from Bayer, BMS, Daichi Sankyo, MSD, and Pfizer, outside the submitted work. Cecilia M. Calleja reports competitive grants from ISCIII during the conduct of the study. Isidoro G. Álvaro reports grants from Instituto de Salud Carlos III, during the course of the study; Personal fees from Lilly and Sanofi; personal fees and nonfinancial support from BMS and Abbvie; research support, personal fees, and nonfinancial support from Roche Laboratories; and nonfinancial support from MSD, Pfizer, and Novartis, not related to the submitted work. The rest of the authors declare that they have no relevant conflicts of interests.

Figures

Figure 1
Figure 1
ROC analysis curve for the combined endpoint of ICU admission and in‐hospital mortality. ICU, intensive care unit; ROC, receiver operating characteristic.
Figure 2
Figure 2
Percentage of patients in the prospective cohort with the main clinical outcomes according to the presence or absence of relevant viremia. (A) Intensive Care Unit (ICU) admission, (B) in‐hospital mortality and (C) at least one of these variables (Poor Outcome). Differences were analysed by the χ 2 test or Fisher exact test, as appropriate.
Figure 3
Figure 3
Viral load in plasma of patients with relevant viremia was significantly higher than in those patients without relevant viremia. Differences were analysed with Mann–Whitney test.
Figure 4
Figure 4
Relevant viremia in the first week was associated with survival and time to discharge. (A) Survival analysis with Kaplan–Meier estimator of patients without relevant viremia (dashed line) and patients with relevant viremia (solid line). (B) Time to discharge analysis with Kaplan–Meier estimator of patients with relevant viremia (solid line) and without relevant viremia (dashed line).
Figure 5
Figure 5
Percentage of patients in the retrospective cohort with the main clinical outcomes according to the presence or absence of relevant viremia. (A) Intensive Care Unit (ICU) admission, (B) in‐hospital mortality and (C) at least one of these variables (Poor prognosis) Comparison was performed by χ 2 test or Fisher exact test, as appropriate.
Figure 6
Figure 6
Kaplan–Meier curves for duration of hospital admission and survival. (A) Hospital admission was longer in patients with relevant viremia compared to those without relevant viremia. (B) The two groups of patients in this cohort did not show significant differences in survival. Analysis was performed with the long‐rank method.
See this image and copyright information in PMC

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