Evaluating the Relationship between Cycle Threshold Values and Reported COVID-19 Symptoms among Healthcare Workers

Background: SARS-CoV-2 detected by reverse transcription polymerase chain reaction (RT-PCR) can persist for weeks to months in some individuals. Cycle threshold (Ct) values represent the number of cycles needed to amplify viral ribonucleic acid (RNA) to reach a detectable level. As such, Ct values are inversely related to the amount of virus in a sample. As knowledge of SARS-CoV-2 viral dynamics continues to evolve, understanding the relationship between Ct values, type of symptoms, and timing of symptom onset can help determine when infected individuals are most likely to be infectious. Methods: We conducted a retrospective cohort study of 1,027 healthcare workers (HCWs) who tested positive for SARS-CoV-2 by RT-PCR from nasopharyngeal specimens between June 27, 2020, and September 21, 2020. All HCWs were interviewed within 72 hours of their diagnosis for symptom history. Due to multiple PCR platforms being in use in our facility, only 360 HCWs (35%) had Ct values available for analysis. Multivariate linear regression models examined the effect of COVID-19–related symptoms and timing of symptom onset to test on Ct values. Results: The most frequently reported symptoms were congestion (55.6%), cough (50.3%), and headache (46.7%). Other symptoms less commonly reported were fatigue (36.7%), loss of taste or smell (36.4%), fever (35.4%), muscle aches (33.3%), sore throat (27.4%), and diarrhea (26.7%). Symptomatic HCWs (88.3% of sample) had lower Ct values (ORF-1 M = 22.66, SD = 5.17; E-Gene M = 24.34, SD = 6.60) than asymptomatic individuals (ORF-1 M = 25.46, SD = 6.06; E-Gene M = 29.34, SD = 7.96). Of all symptoms measured, only presence of fever, congestion, and muscle aches predicted significantly lower Ct values. Mean Ct values decreased 2 days prior to symptom onset, were lowest the day of symptom onset, then increased in a curvilinear fashion. There were no significant 2-way interactions between symptoms and time of symptom onset to testing. Conclusions: The curvilinear pattern of Ct values over time from symptom onset are consistent with disease progression patterns and support current understanding of infectivity being highest 2 days prior to symptom onset through day 8. Presence of fever, congestion, and muscle aches are significantly correlated with lower Ct values, suggesting that these symptoms are associated with higher viral load. Although Ct values are not without limitations, our findings support the current understanding that presymptomatic and symptomatic individuals, particularly those with fever, congestion, and muscle aches, may pose higher risk of transmission to others.Funding: NoDisclosures: None

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Asymptomatic Transmission During the Coronavirus Disease 2019 Pandemic and Implications for Public Health Strategies

Clinical Infectious Diseases ◽

10.1093/cid/ciaa654 ◽

2020 ◽

Vol 71 (10) ◽

pp. 2752-2756 ◽

Cited By ~ 30

Author(s):

Hanalise V Huff ◽

Avantika Singh

Keyword(s):

Public Health ◽

Viral Load ◽

Symptom Onset ◽

High Frequency ◽

Healthcare Workers ◽

Global Public Health ◽

Viral Shedding ◽

Universal Testing ◽

Asymptomatic Individuals ◽

Public Health Strategies

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly in a few months despite global public health strategies to curb transmission by testing symptomatic patients and social distancing. This review summarizes evidence that highlights transmission by asymptomatic and presymptomatic individuals. Viral load of asymptomatic and symptomatic cases is comparable. Viral shedding is highest before symptom onset, suggesting high transmissibility before symptoms. Within universally tested subgroups, high percentages of SARS-CoV-2 infected asymptomatic individuals were found. Asymptomatic transmission was reported in several clusters, including a Wuhan study showing an alarming rate of intrahospital transmission. Several countries reported higher prevalence among healthcare workers than general population raising concern that healthcare workers could act as silent vectors. Therefore, current strategies that rely solely on “symptom onset” for infection identification need urgent reassessment. Extensive universal testing irrespective of symptoms may be considered, with priority placed on groups with high frequency exposure to positive patients.

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Why get tested? Linking Intentions for Seeking SARS-CoV-2 Testing with RT-PCR Results and Cycle Threshold Values at Community Testing Sites

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqab189.024 ◽

2021 ◽

Vol 156 (Supplement_1) ◽

pp. S14-S14

Author(s):

Andrew Laitman ◽

Alex Greninger ◽

Patrick Mathias ◽

Noah Hoffman

Keyword(s):

Laboratory Data ◽

Free Text ◽

Strongly Correlated ◽

Demographic Information ◽

Rt Pcr ◽

Duration Of Symptoms ◽

Recent Onset ◽

Cycle Threshold ◽

Keywords And Phrases ◽

Asymptomatic Individuals

Abstract During the SARS-CoV-2 pandemic, community-based testing sites have provided free COVID testing to millions of people who would have otherwise faced substantial barriers. In one metropolitan area, over 700,000 tests were performed from September 2020 through February 2021. To make appointments online, people not only provided basic demographic information such as age, gender, and address but also free-text reasons for seeking testing. We sought to examine how reason for testing, coded as free text, in combination with other collected demographic information, correlated with rates of SARS-CoV-2 positivity and measures of infectiousness such as the Real-Time Polymerase Chain Reaction (RT-PCR) Cycle Threshold (Ct) value. Data from the scheduling software used to coordinate the on site testing workflow was extracted and linked to SARS-CoV-2 PCR assay metadata stored in a laboratory data warehouse, including Ct values. We categorized individual text responses into 3 separate categories: symptomatic, exposed but asymptomatic, and asymptomatic without exposure. Symptomatic individuals were identified based on the presence of common keywords and phrases like “symptom”, “fever”, “cough”, and “sore throat.” Similarly, exposed individuals were identified by keywords such as “exposed”, “exposure”, and “roommate.” All others were categorized as asymptomatic. We found that symptomatic individuals had the highest frequency of testing positive at 11.6% (21,150/181,868). Exposed individuals and asymptomatic individuals had lower rates of detection with frequencies of 7.4% (10,266/138,721) and 4.9% (8,987/185,026) respectively. Repeat testing represented 29.9% of the results and positivity rates were calculated using the first result for each individual. In addition, among those who tested positive, symptomatic individuals exhibited the lowest average Ct values, while those who are asymptomatic exhibit the highest average Ct values. Among those who self-reported duration of symptoms, recent onset of symptoms was strongly correlated with lower Ct values. Across more than 700,000 results, self-reported symptomatic people, based on free text responses, have a higher likelihood of testing positive for SARS-CoV-2. People who claim a more recent onset of symptoms are more likely to exhibit higher concentrations of viral RNA.

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Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19, England, January to May 2020

Eurosurveillance ◽

10.2807/1560-7917.es.2020.25.32.2001483 ◽

2020 ◽

Vol 25 (32) ◽

Cited By ~ 43

Author(s):

Anika Singanayagam ◽

Monika Patel ◽

Andre Charlett ◽

Jamie Lopez Bernal ◽

Vanessa Saliba ◽

...

Keyword(s):

Viral Load ◽

Severe Acute Respiratory Syndrome ◽

Respiratory Tract ◽

Symptom Onset ◽

Infectious Virus ◽

Upper Respiratory Tract ◽

Threshold Values ◽

Rt Pcr ◽

Cycle Threshold ◽

Upper Respiratory

Severe acute respiratory syndrome coronavirus 2 viral load in the upper respiratory tract peaks around symptom onset and infectious virus persists for 10 days in mild-to-moderate coronavirus disease (n = 324 samples analysed). RT-PCR cycle threshold (Ct) values correlate strongly with cultivable virus. Probability of culturing virus declines to 8% in samples with Ct > 35 and to 6% 10 days after onset; it is similar in asymptomatic and symptomatic persons. Asymptomatic persons represent a source of transmissible virus.

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496. Higher SARS-CoV-2 RT-PCR Cycle Threshold (Ct) Values Associated with Longer Symptom Duration Among Patients Hospitalized with COVID-19

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.689 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S314-S314

Author(s):

Lillian B Brown ◽

Lisa Gail Winston ◽

Barbara Haller ◽

Phong Pham ◽

Beatrice Marcelo ◽

...

Keyword(s):

Viral Load ◽

San Francisco ◽

Symptom Onset ◽

Diagnostic Testing ◽

Symptom Duration ◽

Rt Pcr ◽

Duration Of Symptoms ◽

Cycle Threshold ◽

Asymptomatic Patients

Abstract Background Most diagnostic tests for SARS-CoV-2, the causative agent of COVID-19, are RT-PCR based. This method is sensitive but cannot distinguish replicating from non-replicating virus. RT-PCR cycle threshold (Ct) values are inversely correlated with viral load, and higher Ct values have been correlated with lower in vitro viral infectivity. However, relatively few data exist on the association between Ct values and patients’ duration of symptoms remains unclear. We thus evaluated Ct values and symptom duration in a cohort of patients hospitalized with COVID-19. Methods We assessed all patients admitted to San Francisco General Hospital between April 1 and May 18, 2020 with confirmed COVID-19 infection based on RT-PCR testing (Abbott m2000 platform). We included patients having diagnostic testing for suspected COVID-19 and patients having asymptomatic testing per hospital policy. For symptomatic patients, date of symptom onset was abstracted from hospital records, and time from symptom onset to test date was calculated. RT-PCR Ct values were manually extracted. Median Ct and IQR were calculated for patients with < 10 days of symptoms, ≥10 days of symptoms, and asymptomatic disease. Between-group comparisons were performed using the Kruskal-Wallis test. Results Among 61 patients with positive RT-PCR tests, 40 patients reported < 10 days of symptoms at the time of testing, 15 reported ≥10 days of symptoms, and 6 were asymptomatic. The median Ct value was 14.2 cycles (IQR, 10.2, 18.3) among patients reporting < 10 days of symptoms, 19.7 cycles (IQR, 15.3, 23.9) among patients reporting ≥10 days of symptoms, and 26.3 (IQR, 25.0, 29.1) among asymptomatic patients. Ct values were significantly lower among patients with < 10 days of symptoms compared to patients with >=10 days of symptoms (p=0.01) and when compared to asymptomatic patients (p=0.0002) [Figure]. Cycle threshold (Ct) by days of symptoms at time of testing Conclusion SARS-CoV-2 RT-PCR cycle threshold values were higher (indicating lower viral load) in patients with longer symptom duration and were highest in asymptomatic patients. These results add to emerging data suggesting that strategies for optimal isolation of patients in both community and hospital settings could be informed by a combination of symptom duration and RT-PCR Ct values. Disclosures All Authors: No reported disclosures

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370. Examining the Relationship Between SARS-CoV-2 PCR Cycle Threshold, Disease Severity and Epidemiologic Trends

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.571 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S287-S287

Author(s):

Jessica Penney ◽

Amanda Jung ◽

Benjamin Koethe ◽

Shira Doron

Keyword(s):

Logistic Regression ◽

Disease Severity ◽

Symptom Onset ◽

Temporal Trends ◽

Clinical Severity ◽

Cycle Threshold ◽

Inflammatory Phase ◽

Significant Difference ◽

Mean Cycle ◽

The Relationship

Abstract Background Real-time reverse transcriptase PCR (rRT-PCR) has become the primary method for detection of SARS-CoV-2. Specific measurements of cycle threshold (Ct) values can give an estimate of viral load. Previous studies have shown temporal trends in Ct values, which could be used to predict the phase of the pandemic. This study’s goal was to examine the relationship between Ct and disease severity, as well as Ct trends. Methods Testing was performed using the Abbott M2000 SARS-CoV-2 assay. Data was collected for 262 SARS-CoV-2 positive patients from March-May 2020. Kruskal-Wallis testing was performed to determine differences in median Ct based on age, gender, race and ethnicity. To determine relationship between symptom onset and clinical severity with Ct, linear and logistic regression were performed. Results The majority of the patients had mild to moderate disease. Average time since symptom onset was 5.9 days, and 92% were symptomatic. Figure 1 demonstrates the distribution of Ct by disease severity at time of testing. There was no significant difference in cycle threshold by sex, age, race or ethnicity. Figure 2 shows weekly mean cycle threshold by total new cases in Massachusetts to reflect temporal trend of Ct and cases. In the multivariable linear regression model, Ct increased with days since symptom onset (P< 0.001). Cycle threshold was inversely associated with disease severity in multivariable logistic regression though (OR 1.06, 95%CI 1.01-1.11, p=0.03), even when controlling for time since symptom onset. Figure 1. Distribution of Ct by disease severity at time of SARS-CoV-2 testing Boxplot demonstrating distribution of Ct by disease severity at time of testing. There was no significant difference between groups. Figure 2. Weekly Mean Cycle Threshold by Total New MA Cases Line represents mean Ct over time period included in this study overlaid on total new cases in Massachusetts. Lower Ct were seen in the course as cases were increasing which peaked as cases stabilized. Conclusion Cycle threshold increased with time since symptom onset, consistent with prior data showing increasing Ct from time since infection due to decreasing viral replication. This study showed an inverse relationship between cycle threshold and disease severity, which differs from previous studies which demonstrated higher odds of progression to severe disease and mortality with lower Ct. This finding may reflect the disease severity associated with the secondary inflammatory phase of SARS-CoV-2 seen later in the disease course, although there was only moderate correlation between Ct and time since symptom onset. Further research is needed to better understand the role of Ct in predicting clinical severity of SARS-CoV-2 infections. Disclosures All Authors: No reported disclosures

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Clinical and laboratory characteristics of symptomatic healthcare workers with suspected COVID-19: a prospective cohort study

Scientific Reports ◽

10.1038/s41598-021-93828-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Antonin Bal ◽

Karen Brengel-Pesce ◽

Alexandre Gaymard ◽

Grégory Quéromès ◽

Nicolas Guibert ◽

...

Keyword(s):

Viral Load ◽

Symptom Onset ◽

Healthcare Workers ◽

Respiratory Pathogens ◽

Rt Pcr ◽

Front Line ◽

Mild Form ◽

Pcr Screening ◽

Viral Culture

AbstractA comprehensive clinical and microbiological assessments of COVID-19 in front-line healthcare workers (HCWs) is needed. Between April 10th and May 28th, 2020, 319 HCWs with acute illness were reviewed. In addition to SARS-CoV-2 RT-PCR screening, a multiplex molecular panel was used for testing other respiratory pathogens. For SARS-CoV-2 positive HCWs, the normalized viral load, viral culture, and virus neutralization assays were performed weekly. For SARS-CoV-2 negative HCWs, SARS-CoV-2 serological testing was performed one month after inclusion. Among the 319 HCWs included, 67 (21.0%) were tested positive for SARS-CoV-2; 65/67 (97.0%) developed mild form of COVID-19. Other respiratory pathogens were found in 6/66 (9.1%) SARS-CoV-2 positive and 47/241 (19.5%) SARS-Cov-2 negative HCWs (p = 0.07). The proportion of HCWs with a viral load > 5.0 log10 cp/mL (Ct value < 25) was less than 15% at 8 days after symptom onset; 12% of HCWs were positive after 40 days (Ct > 37). More than 90% of cultivable virus had a viral load > 4.5 log10 cp/mL (Ct < 26) and were collected within 10 days after symptom onset. Among negative HCWs, 6/190 (3.2%) seroconverted. Our data suggest that the determination of viral load can be used for appreciating the infectiousness of infected HCWs. These data could be helpful for facilitating their return to work.

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Equivalent SARS-CoV-2 viral loads by PCR between nasopharyngeal swab and saliva in symptomatic patients

Scientific Reports ◽

10.1038/s41598-021-84059-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Isao Yokota ◽

Takeshi Hattori ◽

Peter Y. Shane ◽

Satoshi Konno ◽

Atsushi Nagasaka ◽

...

Keyword(s):

Symptom Onset ◽

Diagnostic Tool ◽

Healthcare Workers ◽

Detection Sensitivity ◽

Nasopharyngeal Swab ◽

Cycle Threshold ◽

Viral Loads ◽

Ct Value ◽

High Degree ◽

Over Time

AbstractEmerging evidences have shown the utility of saliva for the detection of SARS-CoV-2 by PCR as alternative to nasopharyngeal swab (NPS). However, conflicting results have been reported regarding viral loads between NPS and saliva. We conducted a study to compare the viral loads between NPS and saliva in 42 COVID-19 patients. Viral loads were estimated by the cycle threshold (Ct) values. SARS-CoV-2 was detected in 34 (81%) using NPS with median Ct value of 27.4, and 38 (90%) using saliva with median Ct value of 28.9 (P = 0.79). Kendall’s W was 0.82, showing a high degree of agreement, indicating equivalent viral loads in NPS and saliva. After symptom onset, the Ct values of both NPS and saliva continued to increase over time, with no substantial difference. Self-collected saliva has a detection sensitivity comparable to that of NPS and is a useful diagnostic tool with mitigating uncomfortable process and the risk of aerosol transmission to healthcare workers.

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Testing of Healthcare Workers Exposed to COVID19 with Rapid Antigen Detection

10.1101/2020.08.12.20172726 ◽

2020 ◽

Author(s):

Victor Herrera ◽

Vincent Hsu ◽

Ademola Adewale ◽

Timothy Hendrix ◽

Lee Johnson ◽

...

Keyword(s):

Healthcare Workers ◽

Cost Effective ◽

Antigen Detection ◽

Testing Strategy ◽

Rt Pcr ◽

Asymptomatic Individuals ◽

Antigen Testing

There is a need to develop safe and cost-effective ways to test healthcare workers for COVID19. Here we describe a rapid antigen testing strategy in a cohort of 497 Healthcare workers exposed to SARS-CoV-2 that can be applied by systems facing a surge of COVID19 cases, increased exposures in their workforce and limited RT-PCR availability. Our findings support an expanded use for antigen testing beyond its current indication and highlights the importance of further studying this modality for the diagnosis of COVID19 on asymptomatic individuals.

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Camouflaging in non-autistic adults is associated with poorer mental health

10.31234/osf.io/myp4g ◽

2019 ◽

Author(s):

Mark Somerville ◽

Sarah E. MacPherson ◽

Sue Fletcher-Watson

Keyword(s):

Mental Health ◽

Executive Function ◽

Autistic Traits ◽

Self Report ◽

Linear Regression Models ◽

Mental Health Symptoms ◽

Health Symptoms ◽

Autistic People ◽

Autistic Adults ◽

The Relationship

Camouflaging is a frequently reported behaviour in autistic people, which entails the use of strategies to compensate for and mask autistic traits in social situations. Camouflaging is associated with poor mental health in autistic people. This study examined the manifestation of camouflaging in a non-autistic sample, examining the relationship between autistic traits, camouflaging, and mental health. In addition, the role of executive functions as a mechanism underpinning camouflaging was explored. Sixty-three non-autistic adults completed standardised self-report questionnaires which measured: autistic traits, mental health symptoms, and camouflaging behaviours. In addition, a subset (n=51) completed three tests of executive function measuring inhibition, working memory, and set-shifting. Multiple linear regression models were used to analyse data. Results indicated that autistic traits are not associated with mental health symptoms when controlling for camouflaging, and camouflaging predicted increased mental health symptoms. Camouflaging did not correlate with any measure of executive function. These findings have implications for understanding the relationship between autistic traits and mental health in non-autistic people and add to the growing development of theory and knowledge about the mechanism and effects of camouflaging.

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Investigations, actions and learning from an outbreak of SARS-CoV-2 infection among healthcare workers in the United Kingdom

Journal of Infection Prevention ◽

10.1177/1757177420976798 ◽

2020 ◽

pp. 175717742097679

Author(s):

Kordo Saeed ◽

Emanuela Pelosi ◽

Nitin Mahobia ◽

Nicola White ◽

Christopher Labdon ◽

...

Keyword(s):

Real Time ◽

Healthcare Workers ◽

Healthcare Facility ◽

Rt Pcr ◽

Serum Samples ◽

The United Kingdom ◽

Key Issues ◽

Current Infection ◽

Polymerase Chain ◽

A Current

Background: We report an outbreak of SARS coronavirus-2 (SARS-CoV-2) infection among healthcare workers (HCW) in an NHS elective healthcare facility. Methodology: A narrative chronological account of events after declaring an outbreak of SARS-CoV-2 among HCWs. As part of the investigations, HCWs were offered testing during the outbreak. These were: (1) screening by real-time reverse transcriptase polymerase chain reaction (RT- PCR) to detect a current infection; and (2) serum samples to determine seroprevalence. Results: Over 180 HCWs were tested by real-time RT-PCR for SARS-CoV-2 infection. The rate of infection was 15.2% (23.7% for clinical or directly patient-facing HCWs vs. 4.8% in non-clinical non-patient-facing HCWs). Of the infected HCWs, 57% were asymptomatic. Seroprevalence (SARS-CoV-2 IgG) among HCWs was 13%. It was challenging to establish an exact source for the outbreak. The importance of education, training, social distancing and infection prevention practices were emphasised. Additionally, avoidance of unnecessary transfer of patients and minimising cross-site working for staff and early escalation were highlighted. Establishing mass and regular screening for HCWs are also crucial to enabling the best care for patients while maintaining the wellbeing of staff. Conclusion: To our knowledge, this is the first UK outbreak report among HCWs and we hope to have highlighted some key issues and learnings that can be considered by other NHS staff and HCWs globally when dealing with such a task in future.

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