Pretest Symptom Duration and Cycle Threshold Values for Severe Acute Respiratory Syndrome Coronavirus 2 Reverse-Transcription Polymerase Chain Reaction Predict Coronavirus Disease 2019 Mortality

Miller, Emily Happy; Zucker, Jason; Castor, Delivette; Annavajhala, Medini K.; Sepulveda, Jorge L.; Green, Daniel A.; Whittier, Susan; Scherer, Matthew; Medrano, Nicola; Sobieszczyk, Magdalena E.; Yin, Michael T.; Kuhn, Louise; Uhlemann, Anne Catrin

doi:10.1093/ofid/ofab003

Cited by 50 publications

(46 citation statements)

References 22 publications

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“…Our results with a SARS-CoV-2 population, from a cohort that is different from those in previous studies on the influence of viral load on disease, suggest a positive association between viral load and COVID-19 disease severity. This conclusion is in agreement with many studies to date [5–10, 12–15, 28, 29] (see also [16] for a review), but in contrast, others did not show such an association [17–22]. A possibility to explain such disparate conclusions is the multiple differential criteria considered among studies, such as the sample size, the genomic region analysed, the clinical severity of the patients to be compared, or the standards to classify patients in clinical categories, among other features.…”

Section: Discussionsupporting

confidence: 88%

High SARS-CoV-2 viral load is associated with a worse clinical outcome of COVID-19 disease

Soria

Cortón

Martínez-González

et al. 2021

Access Microbiology

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COVID-19 severity and progression are determined by several host and virological factors that may influence the final outcome of SARS-CoV-2-infected patients. The objective of this work was to determine a possible association between viral load, obtained from nasopharyngeal swabs, and the severity of the infection in a cohort of 448 SARS-CoV-2-infected patients from a hospital in Madrid during the first outbreak of the pandemic in Spain. To perform this, we clinically classified patients as mild, moderate and severe COVID-19 according to a number of clinical parameters such as hospitalization requirement, need of oxygen therapy, admission to intensive care units and/or death. Also, Ct values were determined using SARS-CoV-2-specific oligonucleotides directed to ORF1ab. Here we report a statistically significant association between viral load and disease severity, a high viral load being associated with worse clinical prognosis, independently of several previously identified risk factors such as age, sex, hypertension, cardiovascular disease, diabetes, obesity and lung disease (asthma and chronic obstructive pulmonary disease). The data presented here reinforce viral load as a potential biomarker for predicting disease severity in SARS-CoV-2-infected patients. It is also an important parameter in viral evolution since it relates to the numbers and types of variant genomes present in a viral population, a potential determinant of disease progression.

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Section: Discussionsupporting

confidence: 88%

High SARS-CoV-2 viral load is associated with a worse clinical outcome of COVID-19 disease

Soria

Cortón

Martínez-González

et al. 2021

Access Microbiology

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“…We demonstrated that the Ct value of nasopharyngeal swab samples obtained on initial presentation can act as a predictor of patient outcomes during hospitalization. Many studies correlated a higher SARS-CoV-2 viral load with increased severity of illness [ 3 , 5 , 6 , 10 , 18 , 19 ]. A recent systematic review of 18 studies also supported that lower Ct values are associated with worse outcomes [ 20 ], and this study adds to the growing body of medical knowledge that a high initial nasopharyngeal viral load is an independent predictor of in-hospital mortality and intubation.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 infection: Initial viral load (iVL) predicts severity of illness/outcome, and declining trend of iVL in hospitalized patients corresponds with slowing of the pandemic

et al. 2021

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Background Hospitalization of patients infected with the severe acute respiratory syndrome virus 2 (SARS-CoV-2) have remained considerable worldwide. Patients often develop severe complications and have high mortality rates. The cycle threshold (Ct) value derived from nasopharyngeal swab samples using real time polymerase chain reaction (RT-PCR) may be a useful prognostic marker in hospitalized patients with SARS-CoV-2 infection, however, its role in predicting the course of the pandemic has not been evaluated thus far. Methods We conducted a retrospective cohort study which included all patients who had a nasopharyngeal sample positive for SARS-CoV-2 between April 4 –June 5, 2020. The Ct value was used to estimate the number of viral particles in a patient sample. The trend in initial viral load on admission on a population level was evaluated. Moreover, patient characteristics and outcomes stratified by viral load categories were compared and initial viral load was assessed as an independent predictor of intubation and in-hospital mortality. Results A total of 461 hospitalized patients met the inclusion criteria. This study consisted predominantly of acutely infected patients with a median of 4 days since symptom onset to PCR. As the severity of the pandemic eased, there was an increase in the percentage of samples in the low initial viral load category, coinciding with a decrease in deaths. Compared to an initial low viral load, a high initial viral load was an independent predictor of in-hospital mortality (OR 5.5, CI 3.1–9.7, p < 0.001) and intubation (OR 1.82 CI 1.07–3.11, p = 0.03), while an initial intermediate viral load was associated with increased risk of inpatient mortality (OR 1.9, CI 1.14–3.21, p = 0.015) but not with increased risk for intubation. Conclusion The Ct value obtained from nasopharyngeal samples of hospitalized patients on admission may serve as a prognostic marker at an individual level and may help predict the course of the pandemic when evaluated at a population level.

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“…1) in clinical samples known to be positive for SARS-CoV-2 and stored in the Columbia University Biobank, a biorepository of SARS-CoV-2 patient specimens from hospitals and outpatient clinics within our medical system. Patient and clinical testing information was extracted from the COVID-Care database 21 . Between November 1, 2020 and May 1, 2021, 3,433 SARS-CoV-2-positive nasopharyngeal swabs were available through the Columbia University Biobank for our study (Extended Data Fig.…”

Section: Rapid Screening For Signature Sars-cov-2 Mutationsmentioning

confidence: 99%

Emergence and Expansion of the SARS-CoV-2 Variant B.1.526 Identified in New York

Annavajhala

Mohri

Wang

et al. 2021

Preprint

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Recent months have seen surges of SARS-CoV-2 infection across the globe along with considerable viral evolution. Extensive mutations in the spike protein of variants B.1.1.7, B1.351, and P.1 have raised concerns that the efficacy of current vaccines and therapeutic monoclonal antibodies could be threatened. In vitro studies have shown that one mutation, E484K, plays a crucial role in the loss of neutralizing activity of some monoclonal antibodies as well as most convalescent and vaccinee sera against variant B.1.351. In fact, two vaccine trials have recently reported lower protective efficacy in South Africa, where B.1.351 is dominant. To survey for these novel variants in our patient population in New York City, PCR assays were designed to identify viruses with two signature mutations, E484K and N501Y. We observed a steady increase in the detection rate from late December to mid-February, with an alarming rise to 12.3% in the past two weeks. Whole genome sequencing further demonstrated that most of our E484K isolates (n=49/65) fell within a single lineage: NextStrain clade 20C or Pangolin lineage B.1.526. Patients with this novel variant came from diverse neighborhoods in the metropolitan area, and they were on average older and more frequently hospitalized. Phylogenetic analyses of sequences in the database further reveal that this B.1.526 variant is scattered in the Northeast of US, and its unique set of spike mutations may also pose an antigenic challenge for current interventions.

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Pretest Symptom Duration and Cycle Threshold Values for Severe Acute Respiratory Syndrome Coronavirus 2 Reverse-Transcription Polymerase Chain Reaction Predict Coronavirus Disease 2019 Mortality

Cited by 50 publications

References 22 publications

High SARS-CoV-2 viral load is associated with a worse clinical outcome of COVID-19 disease

High SARS-CoV-2 viral load is associated with a worse clinical outcome of COVID-19 disease

SARS-CoV-2 infection: Initial viral load (iVL) predicts severity of illness/outcome, and declining trend of iVL in hospitalized patients corresponds with slowing of the pandemic

Emergence and Expansion of the SARS-CoV-2 Variant B.1.526 Identified in New York

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