The impact of COVID-19 epidemic phase and changes in mean viral loads: implications for SARS-CoV-2 testing strategies.
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ABSTRACT:
SUBMITTER: Buckley C
PROVIDER: S-EPMC8603442 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The urgent need for large-scale diagnostic testing for SARS-CoV-2 has prompted pursuit of sample-collection methods of sufficient sensitivity to replace sampling of the nasopharynx (NP). Among these alternatives is collection of nasal-swab samples, which can be performed by the patient, avoiding the need for healthcare personnel and personal protective equipment. Previous studies have reached opposing conclusions regarding whether nasal sampling is concordant or discordant with NP. To resolve this disagreement, we compared nasal and NP specimens collected by healthcare workers in a cohort consisting of individuals clinically suspected of COVID-19 and outpatients known to be SARS-CoV-2 RT-PCR positive undergoing follow-up. We investigated three different transport conditions, including traditional viral transport media (VTM) and dry swabs, for each of two different nasal-swab collection protocols on a total of 308 study participants, and compared categorical results and Ct values to those from standard NP swabs collected at the same time from the same patients. All testing was performed by RT-PCR on the Abbott SARS-CoV-2 RealTime EUA (limit of detection [LoD], 100 copies viral genomic RNA/mL transport medium). We found high concordance (Cohen's kappa >0.8) only for patients with viral loads above 1,000 copies/mL. Those with viral loads below 1,000 copies/mL, the majority in our cohort, exhibited low concordance (Cohen's kappa = 0.49); most of these would have been missed by nasal testing alone. Previous reports of high concordance may have resulted from use of assays with higher LoD (?1,000 copies/mL). These findings counsel caution in use of nasal testing in healthcare settings and contact-tracing efforts, as opposed to screening of asymptomatic, low-prevalence, low-risk populations. Nasal testing is an adjunct, not a replacement, for NP.
| S-EPMC7310639 | biostudies-literature
Project description:BackgroundEarly in the COVID-19 pandemic, peak viral loads coincided with symptom onset. We hypothesized that in a highly immune population, symptom onset might occur earlier in infection, coinciding with lower viral loads.MethodsWe assessed SARS-CoV-2 and influenza A viral loads relative to symptom duration in recently-tested adults. Symptomatic participants ≥16y presenting to testing sites in Georgia (4/2022-4/2023; Omicron variant predominant) provided symptom duration. Nasal swab samples were tested by the Xpert Xpress SARS-CoV-2/Flu/RSV assay and Ct values recorded. Nucleoprotein concentrations in SARS-CoV-2 PCR-positive samples were measured by Single Molecule Array. To estimate hypothetical antigen rapid diagnostic test (Ag RDT) sensitivity on each day after symptom onset, percentages of individuals with Ct value ≤30 or ≤25 were calculated.ResultsOf 621 SARS-CoV-2 PCR-positive individuals (64.1% women, median 40.9y), 556/621 (89.5%) had a history of vaccination, natural infection, or both. By both Ct value and antigen concentration measurements, median viral loads rose from the day of symptom onset and peaked on the fourth day. Ag RDT sensitivity estimates were 35.7-71.4% on the first day, 63.9-78.7% on the third day, and 78.6-90.6% on the fourth day of symptoms.In 74 influenza A PCR-positive individuals (55.4% women; median 35.0y), median influenza viral loads peaked on the second day of symptoms.ConclusionsIn a highly immune adult population, median SARS-CoV-2 viral loads peaked on the fourth day of symptoms. Influenza A viral loads peaked soon after symptom onset. These findings have implications for ongoing use of Ag RDTs for COVID-19 and influenza.Key pointsIn a highly immune adult population, median SARS-CoV-2 viral loads by cycle threshold and antigen measurements peaked on the fourth day of symptoms, with implications for testing practice. In contrast, viral loads for influenza A peaked soon after symptom onset.
| S-EPMC10197800 | biostudies-literature
Project description: Not available
| S-EPMC9398939 | biostudies-literature
Project description:SARS-CoV-2 polymerase chain reaction (PCR) tests generally report only binary (positive or negative) outcomes. Quantitative PCR tests can provide epidemiological information on viral transmission patterns in populations. SARS-CoV-2 transmission patterns during India's SARS-CoV-2 viral waves remain largely undocumented. We analyzed 2.7 million real-time PCR testing records collected in Mumbai, a bellwether for other Indian cities. We used the inverse of cycle threshold (Ct) values to determine the community-level viral load. We quantified wave-specific differences by age, sex, and slum population density. Overall, PCR positivity was 3.4% during non-outbreak periods, rising to 23.2% and 42.8% during the original (June-November 2020) and Omicron waves (January 2022), respectively, but was a surprisingly low 9.9% during the Delta wave (March-June 2021; which had the largest increase in COVID deaths). The community-level median Ct values fell and rose ~7-14 days prior to PCR positivity rates. Viral loads were four-fold higher during the Delta and Omicron waves than during non-outbreak months. The Delta wave had high viral loads at older ages, in women, and in areas of higher slum density. During the Omicron wave, differences in viral load by sex and slum density had disappeared, but older adults continued to show a higher viral load. Mumbai's viral waves had markedly high viral loads representing an early signal of the pandemic trajectory. Ct values are practicable monitoring tools.
| S-EPMC10377402 | biostudies-literature
Project description:RT-qPCR detection of SARS-CoV-2 RNA still represents the method of reference to diagnose and monitor COVID-19. From the onset of the pandemic, however, doubts have been expressed concerning the sensitivity of this molecular diagnosis method. Droplet digital PCR (ddPCR) is a third-generation PCR technique that is particularly adapted to detecting low-abundance targets. We developed two-color ddPCR assays for the detection of four different regions of SARS-CoV-2 RNA, including non-structural (IP4-RdRP, helicase) and structural (E, N) protein-encoding sequences. We observed that N or E subgenomic RNAs are generally more abundant than IP4 and helicase RNA sequences in cells infected in vitro, suggesting that detection of the N gene, coding for the most abundant subgenomic RNA of SARS-CoV-2, increases the sensitivity of detection during the highly replicative phase of infection. We investigated 208 nasopharyngeal swabs sampled in March-April 2020 in different hospitals of Greater Paris. We found that 8.6% of informative samples (n = 16/185, P < 0.0001) initially scored as "non-positive" (undetermined or negative) by RT-qPCR were positive for SARS-CoV-2 RNA by ddPCR. Our work confirms that the use of ddPCR modestly, but significantly, increases the proportion of upper airway samples testing positive in the framework of first-line diagnosis of a French population.
| S-EPMC8273560 | biostudies-literature
Project description:SARS-CoV-2 remains a worldwide emergency. While vaccines have been approved and are widely administered, there is an ongoing debate whether children should be vaccinated or prioritized for vaccination. Therefore, in order to mitigate the spread of more transmissible SARS-CoV-2 variants among children, the use of non-pharmaceutical interventions is still warranted. We investigate the impact of different testing strategies on the SARS-CoV-2 infection dynamics in a primary school environment, using an individual-based modelling approach. Specifically, we consider three testing strategies: (1) symptomatic isolation, where we test symptomatic individuals and isolate them when they test positive, (2) reactive screening, where a class is screened once one symptomatic individual was identified, and (3) repetitive screening, where the school in its entirety is screened on regular time intervals. Through this analysis, we demonstrate that repetitive testing strategies can significantly reduce the attack rate in schools, contrary to a reactive screening or a symptomatic isolation approach. However, when a repetitive testing strategy is in place, more cases will be detected and class and school closures are more easily triggered, leading to a higher number of school days lost per child. While maintaining the epidemic under control with a repetitive testing strategy, we show that absenteeism can be reduced by relaxing class and school closure thresholds.
| S-EPMC9255973 | biostudies-literature
Project description:BackgroundDescribing the SARS-CoV-2 viral-load distribution in different patient groups and age categories.MethodsAll results from first nasopharyngeal (NP) and oropharyngeal (OP) swabs from unique patients tested via SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) collected between 1 January and 1 December 2020 predominantly in the Public Health Services regions Kennemerland and Hollands Noorden, province of North Holland, the Netherlands, were included in this study. SARS-CoV-2 PCR crossing-point (Cp)-values were used to estimate viral loads.ResultsIn total, 278 455 unique patients were tested, of whom 9.1% (n = 25.374) were SARS-CoV-2-positive. PCRs performed by Public Health Services (n = 211 914), in which sampling and inclusion were uniform, revealed a clear relation between age and SARS-CoV-2 viral load, with especially children aged <12 years showing lower viral loads than adults (β: -0.03, 95% confidence interval: -0.03 to -0.02, p < 0.001), independently of sex and/or symptom duration. Interestingly, the median Cp-values between the >79- and <12-year-old populations differed by more than four PCR cycles, suggesting an ∼16-fold difference in viral load. In addition, the proportion of children aged <12 years with a low load (Cp-value >30) was higher compared with other patients (31.1% vs 17.2%, p-value < 0.001).ConclusionsIn patients tested by Public Health Services, SARS-CoV-2 viral load increases with age. Further studies should elucidate whether the lower viral load in children is indeed related to their suggested limited role in SARS-CoV-2 transmission. Moreover, as rapid antigen tests are less sensitive than PCR, these results suggest that SARS-CoV-2 antigen tests have lower sensitivity in children than in adults.
| S-EPMC8499942 | biostudies-literature
Project description:BackgroundThe rapid spread of SARS-CoV-2, the causative agent of Coronavirus disease 2019 (COVID-19), has been accompanied by the emergence of distinct viral clades, though their clinical significance remains unclear. Here, we aimed to investigate the phylogenetic characteristics of SARS-CoV-2 infections in Chicago, Illinois, and assess their relationship to clinical parameters.MethodsWe performed whole-genome sequencing of SARS-CoV-2 isolates collected from COVID-19 patients in Chicago in mid-March, 2020. Using these and other publicly available sequences, we performed phylogenetic, phylogeographic, and phylodynamic analyses. Patient data was assessed for correlations between demographic or clinical characteristics and virologic features.FindingsThe 88 SARS-CoV-2 genome sequences in our study separated into three distinct phylogenetic clades. Clades 1 and 3 were most closely related to viral sequences from New York and Washington state, respectively, with relatively broad distributions across the US. Clade 2 was primarily found in the Chicago area with limited distribution elsewhere. At the time of diagnosis, patients infected with Clade 1 viruses had significantly higher average viral loads in their upper airways relative to patients infected with Clade 2 viruses, independent of disease severity.InterpretationThese results show that multiple variants of SARS-CoV-2 were circulating in the Chicago area in mid-March 2020 that differed in their relative viral loads in patient upper airways. These data suggest that differences in virus genotype can impact viral load and may influence viral spread.FundingDixon Family Translational Research Award, Northwestern University Clinical and Translational Sciences Institute (NUCATS), National Institute of Allergy and Infectious Diseases (NIAID), Lurie Comprehensive Cancer Center, Northwestern University Emerging and Re-emerging Pathogens Program.
| S-EPMC7655495 | biostudies-literature
Project description:Emerging 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.
| S-EPMC7904914 | biostudies-literature
Project description:The introduction of effective vaccines against SARS-CoV-2 is expected to prevent COVID-19. However, sporadic cases of infection in vaccinated persons have been reported. We describe a case of a double-dose vaccinated woman with COVID-19. All stages of infection were observed, from no identification of virus, then the start of the infection, a high viral load, coming out of viraemia, and finally no detection of the virus. Despite the high viral load, the woman demonstrated mild COVID-19 symptoms, manifested only by a sore throat. The antibody results showed that she produced both post-infectious and post-vaccination immune responses. Phylogenetic analysis of the obtained viral genome sequence indicated that the virus belonged to the UK SARS-CoV-2 lineage B.1.1.7 (GR 501Y.V1; 20I/S:501Y.V1; Alpha variant).
| S-EPMC8534434 | biostudies-literature