Viral kinetics of SARS-CoV-2 over the preclinical, clinical, and postclinical period

Jang, Shin Yi; Rhee, Ji-Young; Wi, Yu Mi; Jung, Boo Hee

doi:10.1016/j.ijid.2020.10.099

Cited by 51 publications

(44 citation statements)

References 3 publications

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“…Thus, RATs for NP swabs can be promising tools for the rapid detection of SARS-CoV-2 for patients in the initial phase of symptomatic infection and/or with high viral loads. However, sensitivity for specimens with lower viral loads and for specimens collected after 7-days PSO gradually decreased, and antigen kinetics showed a more acute decrease in COI for both RATs with an increase in Ct values, which was consistent with the results of previous studies [ 11 , 14 , 15 ]. Moreover, several studies reported that NP specimens with Ct > 25 do permit recovery of virus from viral culture, and this is possible even for Ct > 35 [ 16 ].…”

Section: Discussionsupporting

confidence: 91%

Evaluation of rapid SARS-CoV-2 antigen tests, AFIAS COVID-19 Ag and ichroma COVID-19 Ag, with serial nasopharyngeal specimens from COVID-19 patients

et al. 2021

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We evaluated the diagnostic accuracy of two newly developed, point-of-care, rapid antigen tests (RATs) for detecting SARS-CoV-2, the AFIAS COVID-19 Ag and the ichromaTM COVID-19 Ag, and investigated antigen kinetics. A total of 200 serially collected nasopharyngeal (NP) specimens from 38 COVID-19 patients and 122 specimens from negative controls were analyzed. Diagnostic sensitivity and specificity were assessed in comparison to molecular test results and subdivided according to targeted genes (E, RdRP, and N) and days post-symptom onset (PSO). For the kinetics evaluation, cut-off-indices from serial NP specimens were used according to the number of days PSO. Both RATs showed sensitivity of 91.3‒100% for specimens with cycle threshold (Ct) < 25. The specificity of AFIAS was 98.7‒98.9% and that of ichromaTM was 100.0%. The kappa values of AFIAS and ichromaTM for the molecular testing of specimens with Ct < 25 (RdRP) were 0.97 and 1.00, respectively. The sensitivity of AFIAS and ichromaTM for all genes was lower for specimens collected at 8‒14 PSO than for those collected before 7-days PSO. The kinetics profiles showed that antigen levels gradually decreased from ≤ 7-days PSO to > 22-days PSO. Both RATs showed excellent specificity and acceptable sensitivity for NP specimens with higher viral loads and for specimens collected within 7-days PSO. Hence, they have the potential to become useful tools for the early detection of SARS-CoV-2. However, because of concerns about false negativity, RATs should be used in conjunction with molecular tests.

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Section: Discussionsupporting

confidence: 91%

Evaluation of rapid SARS-CoV-2 antigen tests, AFIAS COVID-19 Ag and ichroma COVID-19 Ag, with serial nasopharyngeal specimens from COVID-19 patients

et al. 2021

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“…As highlighted by other authors [ 34 , 36 ], timing since disease onset must be acknowledged as well. Data of temporal profiles of SARS-CoV-2 show that the number of RNA copies peaks close to symptom onset and tapers steeply by the end of the first week [ 9 , 21 , 22 ]. Thus, finding different Ct values in infected patients may tell more about the disease’s timing than the severity itself [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…A key aspect in response to the COVID-19 pandemic has been the early detection and prompt isolation of infected patients [ 4 ]. For this purpose, real-time reverse transcriptase-polymerase chain reaction (RT-PCR) has been regarded as the gold standard diagnostic test [ 5 ], with an estimated 70 and 95 % sensitivity and specificity, respectively [ 6 ] RT-PCR reveals the broadest range of detection: becoming positive days before symptom onset and detecting viral nucleic acids up to several weeks in infected patients [ 7 – 9 ]. However, it is essential to clarify that test performance may differ due to the inherent variability between assays, extraction method/instrument combination, targeted regions of the viral genome, and clinical matrix tested.…”

Section: Introductionmentioning

confidence: 99%

“…Ct values have also been used to assess viral load dynamics of SARS-CoV-2 in both symptomatic and asymptomatic cases [ 9 , 21 , 22 ]. Most of these studies report that RNA copies and infectivity start rapidly rising 0-to-6 days before the onset of symptoms, reaching a peak near symptom onset, to quickly decline within seven days [ 9 , 22 ]. These findings had shed light on the role of asymptomatic and presymptomatic patients in the spread of SARS-CoV-2 and the importance of contact tracing and isolation precautions for close contacts [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Contrasting SARS-CoV-2 RNA copies and clinical symptoms in a large cohort of Colombian patients during the first wave of the COVID-19 pandemic

Quiroga

Hernández

Castañeda

et al. 2021

Ann Clin Microbiol Antimicrob

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Background There is limited and controverting evidence looking at possible associations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA copies and patient variables in large cohorts of symptomatic and asymptomatic patients. Methods We studied 2275 symptomatic and asymptomatic patients from Colombia with coronavirus disease 2019 (COVID-19) and analyzed the associations between RT-PCR cycle threshold (Ct) value with gender, age, comorbidities, symptomatology, and disease severity. Results 15.4 % of the samples (n = 428) reported at least one comorbidity. There were 2011 symptomatic cases (72.4 %), being the most common reported symptom cough (57.2 %, n = 1586). Respiratory distress was present in 21.4 % of patients (n = 595), and 435 patients (15.6 %) required hospital admission. We observed that patients with no prior medical history harbored higher RNA copies than patients with comorbidities (p = 0.02). No significant differences in RNA copies were observed between symptomatic and asymptomatic patients (p = 0.82). Strong correlations were detected between Ct values and the presence of odynophagia (p = 0.03), diarrhea (p = 0.04), and headache (p = 0.0008). An inverse association was found between RNA copy number and markers of disease severity, namely, respiratory distress (P < 0.0001) and hospitalization requirement (P < 0.0001). Conclusions SARS-CoV-2 RT-PCR cycle thresholds reveal strong associations with a prior medical history, specific symptomatology, and disease severity markers. Further research controlling potential confounding variables needs to be conducted to evaluate the nature and usefulness of these associations in managing COVID-19 patients.

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“…In other words, the lower the Ct value obtained, the more the gene exists in the sample, which can represent a higher viral load [ 216 ]. Despite the recommendation to perform the RT-qPCR test on samples collected from the appearance of symptoms, since the viral load is higher [ 217 ], some studies indicate that the Ct value between symptomatic and asymptomatic patients is similar [ 218 , 219 , 220 ]. This indicates that even if the appearance of symptoms is important for the performance of molecular tests, since it is related to the increase in viral load, these tests can also be used in samples from asymptomatic patients, once the found Ct value can be similar.…”

Section: Nucleic Acid-based Tests and Serological Tests: Practicalmentioning

confidence: 99%

The Main Molecular and Serological Methods for Diagnosing COVID-19: An Overview Based on the Literature

Machado

Hodel

Barbosa-Júnior

et al. 2020

Viruses

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Diagnostic tests have been considered as the main alternative for the control of coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as a correct diagnosis allows for decision making when facing the disease, particularly as there is a lack of effective therapeutic protocols and vaccines. Thus, in this review, we summarized the main diagnostic approaches currently available for the diagnosis of SARS-CoV-2 infection in humans based on studies available in article databases. The tests can be organized into two main categories: nucleic acid-based tests, recommended for the initial detection of the virus, and serological tests, recommended for assessing the disease progression. The studies have shown that the performance of diagnostic methods depends on different factors, such as the type of samples and the characteristics of each assay. It was identified that the positivity of the tests is mainly related to the onset of symptoms. We also observed that point-of-care diagnoses are considered as one of the main trends in this area, due to the low-cost and simplicity of the assay; however, the analytical performance must be critically analyzed. Thus, the COVID-19 pandemic has highlighted the critical role of diagnostic technologies in the control of infectious diseases.

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Viral kinetics of SARS-CoV-2 over the preclinical, clinical, and postclinical period

Abstract: Graphical Abstract

Cited by 51 publications

References 3 publications

Evaluation of rapid SARS-CoV-2 antigen tests, AFIAS COVID-19 Ag and ichroma COVID-19 Ag, with serial nasopharyngeal specimens from COVID-19 patients

Evaluation of rapid SARS-CoV-2 antigen tests, AFIAS COVID-19 Ag and ichroma COVID-19 Ag, with serial nasopharyngeal specimens from COVID-19 patients

Contrasting SARS-CoV-2 RNA copies and clinical symptoms in a large cohort of Colombian patients during the first wave of the COVID-19 pandemic

The Main Molecular and Serological Methods for Diagnosing COVID-19: An Overview Based on the Literature

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