Baseline Severe Acute Respiratory Syndrome Viral Load Is Associated With Coronavirus Disease 2019 Severity and Clinical Outcomes: Post Hoc Analyses of a Phase 2/3 Trial

Abstract

Background: Elucidating the relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and clinical outcomes is critical for understanding coronavirus disease 2019 (COVID-19).

Methods: The SARS-CoV-2 levels were analyzed by quantitative real-time polymerase chain reaction (RT-qPCR) of nasopharyngeal or oropharyngeal swab specimens collected at baseline, and clinical outcomes were recorded over 60 days from 1362 COVID-19 hospitalized patients enrolled in a multicenter, randomized, placebo-controlled phase 2/3 trial of sarilumab for COVID-19 (ClinicalTrials.gov NCT04315298).

Results: In post hoc analyses, higher baseline viral load, measured by both RT-qPCR cycle threshold and log10 copies/mL, was associated with greater supplemental oxygenation requirements and disease severity at study entry. Higher baseline viral load was associated with higher mortality, lower likelihood of improvement in clinical status and supplemental oxygenation requirements, and lower rates of hospital discharge. Viral load was not impacted by sarilumab treatment over time versus placebo.

Conclusions: These data support viral load as an important determinant of clinical outcomes in hospitalized patients with COVID-19 requiring supplemental oxygen or assisted ventilation.

Keywords: COVID-19; hospital; outcomes; severity; viral load.

Figure 1.

Boxplot of baseline viral load grouped by disease severity* (A) and correlation matrix of baseline virology, clinical, and laboratory values** (B). *Each point represents an individual patient’s log₁₀ viral copies/mL at baseline, and the corresponding color depicts the type of oxygen delivery device. The horizontal blue lines represent each group’s median viral load. Significant Dunn pairwise comparisons are shown above the boxplots; ***, P < .001. **, Spearman correlation matrix of all continuous baseline clinical, virological (quantitative polymerase chain reaction log₁₀ copies/mL), and laboratory values with data collected on ≥50% of subjects in this study. Spearman correlations range from –1 to 1, with 1 indicating a perfect positive correlation and –1 indicating a perfect negative correlation. Variables are clustered together based on Spearman rho value using unsupervised hierarchical clustering with Euclidian distances. IMV, invasive mechanical ventilation; MSOD, multisystem organ dysfunction.

Figure 2.

Survival curves grouped by viral load tertiles for probability of survival (A), clinical improvement (1 point) (B), improvement in oxygen requirements (C), and hospitalization (D). Viral load tertiles were defined as follows: low (<3.32 log₁₀ copies/mL), middle (3.32–5.09 log₁₀ copies/mL), and high (>5.09 log₁₀ copies/mL). Tables of number of patients at risk at particular timepoints after baseline are shown below each plot.