PCR Cycle Threshold Values and COVID-19 Outcomes

Can Quantitative (Real-time) Polymerase Chain Reaction (PCR) Cycle Threshold (Ct) Values be Used to Predict Poor Outcomes for Patients Infected With SARS-CoV-2? A Local Exploratory Sub-study at The University Hospitals of North Midlands NHS Trust in Collaboration With the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 Trial

This is a retrospective observational study. The study will use high quality, reliable data that has already been collected for the ISARIC 4C COVID-19 study in order to analyse the relation between predictor variables (laboratory polymerase chain reaction [PCR] cycle threshold [Ct] values) and outcomes for COVID-19 disease within a hospitalised population.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Diagnostic test: PCR Value

Detailed Description

Currently, in the United Kingdom, the recommended method for diagnostic testing and screening for COVID-19 is quantitative (real-time) reverse transcription polymerase chain reaction (PCR) analysis of viral RNA extracted from upper respiratory tract samples. A positive result indicates that SARS-CoV-2 RNA has been detected with a cycle threshold (Ct) value of less than 38 cycles of amplification (n.b. this is a locally agreed value, which is based on analysis of proficiency testing performance and other local testing data. Cycle threshold (Ct) values inversely correlate to the amount of target nucleic acid in the sample. Thus, a lower cycle threshold (Ct) value indicates a greater amount of target nucleic acid in a sample i.e. a higher viral load.

A recent scoping literature review has revealed only a handful of published studies to date that explore an association between cycle threshold (Ct) values and disease severity or clinical outcome in patients infected with the SARS-CoV-2 virus. The majority of these studies have been conducted in China with small patient sample sizes. Thus, a larger-scale study which explores the relationship between viral load and disease severity is required; indeed, the World Health Organization (WHO) has recently highlighted this as an area which needs further research.

• Study Type: Observational
• Enrollment (Actual): 934

Contacts and Locations

Study Locations

• United Kingdom
  • Staffordshire
    • Stoke-on-Trent, Staffordshire, United Kingdom, ST4 6QG
      • University Hospitals of North Midlands NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Adults (aged 18 years and over) patients presenting to UHNM with confirmed SARS-CoV-2 infection and who are enrolled onto the ISARIC 4C COVID-19 study. These patients must also have undergone an initial diagnostic or screening test for SARS-CoV-2 (from an upper respiratory tract sample) and a cycle threshold (Ct) value is available on the UHNM laboratory database.

Description

Inclusion Criteria:

1. Adult (aged 18 years and over) patients presenting to UHNM with confirmed SARS-CoV-2 infection AND who are enrolled onto the ISARIC COVID-19 study.
2. Patients who have undergone an initial diagnostic or screening test for SARS-CoV-2 (from an upper respiratory tract sample) AND a cycle threshold (Ct) value is available on the UHNM laboratory database.

Exclusion Criteria:

1. Paediatric patients (under 18 years).
2. Patients without a PCR Ct result on the UHNM laboratory database
3. Patients without confirmed SARS-CoV-2 infection
4. Patients who were not enrolled in to the ISARIC COVID-19 study

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Covid-19 Ct Value; All patients enrolled onto the ISARIC COVID-19 trial at The University Hospitals of North Midlands NHS Trust between the period 1st February 2020 to 1st July 2020 will be included in this study, provided that a laboratory cycle threshold (Ct) value is available.	Diagnostic test: PCR Value; Data collection and interpretation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine if there is an inverse correlation with risk of poor outcome including admission to intensive care; mechanical ventilation and 28-day mortality.	Determine if cycle threshold (Ct) levels are an independent predictor for: I. Hypoxia resulting in oxygen dependency or oxygen saturations < 92%, at admission and at any other point during the episode of care; II. admission to intensive care; III. mechanical ventilation and	01/02/2020 to 01/07/2020

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in cycle threshold (Ct) levels amongst patients with community acquired SARS-CoV-2	Determine if sociodemographic factors are significantly associated with lower cycle threshold (Ct) levels.	01/02/2020 to 01/07/2020

Collaborators and Investigators

• Sponsor: University Hospitals of North Midlands NHS Trust
• Investigators: Principal Investigator: Timothy Kemp, UHNM

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2020
• Primary Completion (Actual): March 31, 2021
• Study Completion (Actual): October 14, 2021

Study Registration Dates

• First Submitted: December 2, 2020
• First Submitted That Met QC Criteria: December 2, 2020
• First Posted (Actual): December 3, 2020

Study Record Updates

• Last Update Posted (Actual): May 18, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 286389

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No