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. 2022 Jun 15:9:855639.
doi: 10.3389/fmed.2022.855639. eCollection 2022.

SARS-CoV-2 Viremia Precedes an IL6 Response in Severe COVID-19 Patients: Results of a Longitudinal Prospective Cohort

Emilia Roy-Vallejo  1 , Laura Cardeñoso  2 , Ana Triguero-Martínez  3 , Marta Chicot Llano  4 , Nelly Zurita  2 , Elena Ávalos  5 , Ana Barrios  1 , Julia Hernando  6 , Javier Ortiz  7 , Sebastián C Rodríguez-García  3 , Marianela Ciudad Sañudo  1 , Celeste Marcos  5 , Elena García Castillo  5 , Leticia Fontán García-Rodrigo  2 , Begoña González  4 , Rosa Méndez  6 , Isabel Iturrate  7 , Ancor Sanz-García  8 , Almudena Villa  1 , Ana Sánchez-Azofra  5 , Begoña Quicios  4 , David Arribas  6 , Jesús Álvarez Rodríguez  1 , Pablo Patiño  4 , Marina Trigueros  4 , Miren Uriarte  3 , Alexandra Martín-Ramírez  2 , Cristina Arévalo Román  1 , José María Galván-Román  1 , Rosario García-Vicuña  3 , Julio Ancochea  5 , Cecilia Muñoz-Calleja  9 , Elena Fernández-Ruiz  10 , Rafael de la Cámara  7 , Carmen Suárez Fernández  1 , Isidoro González-Álvaro  3 , Diego A Rodríguez-Serrano  4 ; PREDINMUN-COVID Group
Collaborators, Affiliations

SARS-CoV-2 Viremia Precedes an IL6 Response in Severe COVID-19 Patients: Results of a Longitudinal Prospective Cohort

Emilia Roy-Vallejo et al. Front Med (Lausanne). .

Abstract

Background: 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.

Keywords: COVID-19; SARS-CoV-2; interleukin 6 (IL-6); prognosis; viremia.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The peak of viral load precedes the IL6 increase. Graphic representation of time-course of IL6 levels and SARS-CoV-2 viral load from symptom onset. (A) representation of raw data. (B) Representation of data after applying the LOCF strategy. The fractional polynomial prediction was performed using the twoway command of Stata.
FIGURE 2
FIGURE 2
Patients with worse outcomes have an early peak of SARS-CoV-2 viral load before a prominent increase in IL6 levels. Graphic representation of IL6 levels and SARS-CoV-2 viral load from symptom onset in: (A) patients with low IL6; (B) patients with at least one IL6 > 30 pg/ml (high IL6); (C) non-persistent viremia; and (D) persistent viremia. (E) Represents the percentage of patients with persistent viremia according to IL6 levels (low vs. high). (A–D) The fractional polynomial predictions were performed using the twoway command of Stata.
FIGURE 3
FIGURE 3
Males had more relevant increases of IL6 and viral load. (A) Represents the levels of IL6 and viral load from symptom onset by sex (both panels using the same scale), while (B) shows levels of IL6 and viral load by age and sex (both panels using the same scale). The fractional polynomial predictions were performed using the twoway command of Stata.
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