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).