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BACKGROUND: Serial screening is critical for restricting spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by facilitating timely identification of infected individuals to interrupt transmission. Variation in sensitivity of different diagnostic tests at different stages of infection has not been well documented. METHODS: In a longitudinal study of 43 adults newly infected with SARS-CoV-2, all provided daily saliva and nasal swabs for quantitative reverse transcription polymerase chain reaction (RT-qPCR), Quidel SARS Sofia antigen fluorescent immunoassay (FIA), and live virus culture. RESULTS: Both RT-qPCR and Quidel SARS Sofia antigen FIA peaked in sensitivity during the period in which live virus was detected in nasal swabs, but sensitivity of RT-qPCR tests rose more rapidly prior to this period. We also found that serial testing multiple times per week increases the sensitivity of antigen tests. CONCLUSIONS: RT-qPCR tests are more effective than antigen tests at identifying infected individuals prior to or early during the infectious period and thus for minimizing forward transmission (given timely results reporting). All tests showed >98% sensitivity for identifying infected individuals if used at least every 3 days. Daily screening using antigen tests can achieve approximately 90% sensitivity for identifying infected individuals while they are viral culture positive.
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Prueba de COVID-19 , COVID-19/diagnóstico , Pruebas Diagnósticas de Rutina , SARS-CoV-2/aislamiento & purificación , Adulto , Anciano , Animales , Antígenos Virales/análisis , Chlorocebus aethiops , Femenino , Humanos , Estudios Longitudinales , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Saliva , Sensibilidad y Especificidad , Células Vero , Adulto JovenRESUMEN
The dynamics of SARS-CoV-2 replication and shedding in humans remain poorly understood. We captured the dynamics of infectious virus and viral RNA shedding during acute infection through daily longitudinal sampling of 60 individuals for up to 14 days. By fitting mechanistic models, we directly estimated viral expansion and clearance rates and overall infectiousness for each individual. Significant person-to-person variation in infectious virus shedding suggests that individual-level heterogeneity in viral dynamics contributes to 'superspreading'. Viral genome loads often peaked days earlier in saliva than in nasal swabs, indicating strong tissue compartmentalization and suggesting that saliva may serve as a superior sampling site for early detection of infection. Viral loads and clearance kinetics of Alpha (B.1.1.7) and previously circulating non-variant-of-concern viruses were mostly indistinguishable, indicating that the enhanced transmissibility of this variant cannot be explained simply by higher viral loads or delayed clearance. These results provide a high-resolution portrait of SARS-CoV-2 infection dynamics and implicate individual-level heterogeneity in infectiousness in superspreading.
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COVID-19 , SARS-CoV-2 , Humanos , Carga Viral , Esparcimiento de VirusRESUMEN
Background: The global effort to vaccinate people against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during an ongoing pandemic has raised questions about how vaccine breakthrough infections compare with infections in immunologically naive individuals and the potential for vaccinated individuals to transmit the virus. Methods: We examined viral dynamics and infectious virus shedding through daily longitudinal sampling in 23 adults infected with SARS-CoV-2 at varying stages of vaccination, including 6 fully vaccinated individuals. Results: The durations of both infectious virus shedding and symptoms were significantly reduced in vaccinated individuals compared with unvaccinated individuals. We also observed that breakthrough infections are associated with strong tissue compartmentalization and are only detectable in saliva in some cases. Conclusions: Vaccination shortens the duration of time of high transmission potential, minimizes symptom duration, and may restrict tissue dissemination.
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The Scleractinian corals Orbicella annularis and O. faveolata have survived by acclimatizing to environmental changes in water depth and sea surface temperature (SST). However, the complex physiological mechanisms by which this is achieved remain only partially understood, limiting the accurate prediction of coral response to future climate change. This study quantitatively tracks spatial and temporal changes in Symbiodiniaceae and biomolecule (chromatophores, calmodulin, carbonic anhydrase and mucus) abundance that are essential to the processes of acclimatization and biomineralization. Decalcified tissues from intact healthy Orbicella biopsies, collected across water depths and seasonal SST changes on Curaçao, were analyzed with novel autofluorescence and immunofluorescence histology techniques that included the use of custom antibodies. O. annularis at 5 m water depth exhibited decreased Symbiodiniaceae and increased chromatophore abundances, while O. faveolata at 12 m water depth exhibited inverse relationships. Analysis of seasonal acclimatization of the O. faveolata holobiont in this study, combined with previous reports, suggests that biomolecules are differentially modulated during transition from cooler to warmer SST. Warmer SST was also accompanied by decreased mucus production and decreased Symbiodiniaceae abundance, which is compensated by increased photosynthetic activity enhanced calcification. These interacting processes have facilitated the remarkable resiliency of the corals through geological time.
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Trastornos del Sueño-Vigilia/fisiopatología , Animales , Antozoos/fisiología , Cambio Climático , Dinoflagelados/fisiología , Femenino , Angiografía por Resonancia Magnética , Masculino , Fotosíntesis/fisiologíaRESUMEN
WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?: Diagnostic tests and sample types for SARS-CoV-2 vary in sensitivity across the infection period. WHAT IS ADDED BY THIS REPORT?: We show that both RTqPCR (from nasal swab and saliva) and the Quidel SARS Sofia FIA rapid antigen tests peak in sensitivity during the period in which live virus can be detected in nasal swabs, but that the sensitivity of RTqPCR tests rises more rapidly in the pre-infectious period. We also use empirical data to estimate the sensitivities of RTqPCR and antigen tests as a function of testing frequency. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: RTqPCR tests will be more effective than rapid antigen tests at identifying infected individuals prior to or early during the infectious period and thus for minimizing forward transmission (provided results reporting is timely). All modalities, including rapid antigen tests, showed >94% sensitivity to detect infection if used at least twice per week. Regular surveillance/screening using rapid antigen tests 2-3 times per week can be an effective strategy to achieve high sensitivity (>95%) for identifying infected individuals.
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The dynamics of SARS-CoV-2 replication and shedding in humans remain poorly understood. We captured the dynamics of infectious virus and viral RNA shedding during acute infection through daily longitudinal sampling of 60 individuals for up to 14 days. By fitting mechanistic models, we directly estimate viral reproduction and clearance rates, and overall infectiousness for each individual. Significant person-to-person variation in infectious virus shedding suggests that individual-level heterogeneity in viral dynamics contributes to superspreading. Viral genome load often peaked days earlier in saliva than in nasal swabs, indicating strong compartmentalization and suggesting that saliva may serve as a superior sampling site for early detection of infection. Viral loads and clearance kinetics of B.1.1.7 and non-B.1.1.7 viruses in nasal swabs were indistinguishable, however B.1.1.7 exhibited a significantly slower pre-peak growth rate in saliva. These results provide a high-resolution portrait of SARS-CoV-2 infection dynamics and implicate individual-level heterogeneity in infectiousness in superspreading.
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The global effort to vaccinate people against SARS-CoV-2 in the midst of an ongoing pandemic has raised questions about the nature of vaccine breakthrough infections and the potential for vaccinated individuals to transmit the virus. These questions have become even more urgent as new variants of concern with enhanced transmissibility, such as Delta, continue to emerge. To shed light on how vaccine breakthrough infections compare with infections in immunologically naive individuals, we examined viral dynamics and infectious virus shedding through daily longitudinal sampling in a small cohort of adults infected with SARS-CoV-2 at varying stages of vaccination. The durations of both infectious virus shedding and symptoms were significantly reduced in vaccinated individuals compared with unvaccinated individuals. We also observed that breakthrough infections are associated with strong tissue compartmentalization and are only detectable in saliva in some cases. These data indicate that vaccination shortens the duration of time of high transmission potential, minimizes symptom duration, and may restrict tissue dissemination.