Association between SARS-CoV-2 viral kinetics and clinical score evolution in hospitalized patients

Autores da FMUP

• José Artur Osório De Carvalho Paiva

  Autor

Participantes de fora da FMUP

• N?ant, N
• Lingas, G
• Gaymard, A
• Belhadi, D
• Hites, M
• Staub, T
• Greil, R
• Poissy, J
• Peiffer Smadja, N
• Costagliola, D
• Yazdanpanah, Y
• Bouscambert Duchamp, M
• Gagneux Brunon, A
• Ader, F
• Mentr?, F
• Wallet, F
• Burdet, C
• Guedj, J

Unidades de investigação

• Medicina

Abstract

The role of antiviral treatment in coronavirus disease 2019 hospitalized patients is controversial. To address this question, we analyzed simultaneously nasopharyngeal viral load and the National Early Warning Score 2 (NEWS-2) using an effect compartment model to relate viral dynamics and the evolution of clinical severity. The model is applied to 664 hospitalized patients included in the DisCoVeRy trial (NCT04315948; EudraCT 2020-000936-23) randomly assigned to either standard of care (SoC) or SoC+remdesivir. Then we use the model to simulate the impact of antiviral treatments on the time to clinical improvement, defined by a NEWS-2 score lower than 3 (in patients with NEWS-2<7 at hospitalization) or 5 (in patients with NEWS-2 7 at hospitalization), distinguishing between patients with low or high viral load at hospitalization. The model can fit well the different observed patients trajectories, showing that clinical evolution is associated with viral dynamics, albeit with large interindividual variability. Remdesivir antiviral activity was 22% and 78% in patients with low or high viral loads, respectively, which is not sufficient to generate a meaningful effect on NEWS-2. However, simulations predicted that antiviral activity greater than 99% could reduce by 2days the time to clinical improvement in patients with high viral load, irrespective of the NEWS-2 score at hospitalization, whereas no meaningful effect was predicted in patients with low viral loads. Our results demonstrate that time to clinical improvement is associated with time to viral clearance and that highly effective antiviral drugs could hasten clinical improvement in hospitalized patients with high viral loads.

Keywords

• Antiviral Agents; COVID-19; Hospitalization; Humans; SARS-CoV-2; Viral Load; antivirus agent; hypoxanthine phosphoribosyltransferase; remdesivir; antivirus agent; adult; aged; antiviral activity; antiviral therapy; Article; basic reproduction number; chronic lung disease; clinical outcome; controlled study; deterioration; disease severity; drug dose reduction; health care quality; hospitalization; human; kinetics; limit of quantitation; male; middle aged; nasopharyngeal swab; National Early Warning Score 2; obesity; prevalence; randomized controlled trial; real time reverse transcription polymerase chain reaction; scoring system; Severe acute respiratory syndrome coronavirus 2; viral clearance; virus load; virus particle; virus replication; coronavirus disease 2019; hospitalization