Introduction
Most cases of SARS-CoV-2 infection are asymptomatic or experience self-limiting flu-like manifestations 1. The risk of developing severe COVID-19 is known to be associated to several characterized individual conditions 2, although additional still undisclosed factors are likely to play a role as severe infections are also seen when no comorbidities are present. In order to properly manage patients presenting with a newly discovered positive swab, several prognostic scores are under evaluation to predict in-hospital death and discriminate between patients requiring hospital admission or not 3,4. However, these scores rely upon variables that are extremely dependent on the timing of the evaluation along COVID-19 course, with the potential of sudden changes in few hours. While similar scores have proven validity in acute infectious diseases presenting with full-blown illness, the same parameters might be misleading in dealing with the initial phase of SARS-CoV-2 infection. A tri-phasic progressive pattern has been described in infected patients evolving toward severe clinical pictures 5, and an early assessment might not rule out the subsequent worsening of the disease. As a consequence, reliance upon indicators providing better prognostic predictions would be critical in order to properly select patients requiring hospital admission, especially when exponentially increasing numbers of infections occur in a short time interval and hospitals become crowded.
As opposite to other viral infections like HIV, HBV or CMV, no pathogen-specific prognostic biomarkers are yet readily available for SARS-CoV-2. Further to the recognized risk factors for severity, the initial prognostic workup of persons infected by SARS-CoV-2 would benefit also from viral biomarkers able to predict COVID-19 evolution. In this regard, it is a current matter of debate whether SARS-CoV-2 viral load is an impactful factor in determining disease outcomes6–16. Previous evidence from SARS-CoV and Influenza suggests that the higher is the initial viral load the worse is the clinical evolution 17,18. To date, few studies have investigated the relationship between SARS-CoV-2 viral load (usually measured by the proxy PCR cycle threshold value, Ct), and mortality, disease progression or overall severity 7–15. Current data point towards a plausible positive correlation between the amount of detected virus and the degree of SARS-CoV-2 pneumonia severity, hypoxemia intensity, risk of death, as well as of haematological, biochemical and inflammatory alterations6,9–12,19,20. However, heterogeneous recruitment criteria have so far hampered to reach a final firm conclusion on the relationship between initial nasopharyngeal viral load and individual prognosis.
Hence, the aim of this study was to assess whether SARS-CoV-2 Ct at diagnosis may predict COVID-19 severity, related clinical outcomes and 6-month sequelae. The study was performed in a representative sample of hospitalised and outpatient COVID-19 cases whose infection was diagnosed in March and data collected at a median follow-up time of 6 months by phone interviews and from the regional database for COVID-19 emergency, which collects data of the entire Piedmont (Italy).