Viral RNA Load and Infectivity of SARS-CoV-2 in Paired Respiratory and Oral Specimens from Symptomatic, Asymptomatic, or Postsymptomatic Individuals

Tallmadge, Rebecca L.; Laverack, Melissa; Cronk, Brittany D.; Venugopalan, Roopa; Martins, Mathias; Zhang, Xiulin; Elvinger, François; Plocharczyk, Elizabeth; Diel, Diego G.

doi:10.1128/spectrum.02264-21

Cited by 14 publications

(9 citation statements)

References 49 publications

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“…Viral propagation in culture was also achieved more frequently in samples from the immunosuppressed group. All these findings were consistent with earlier reports [1,[27][28][29]. In immunocompetent patients, considering only samples collected ten or more days after onset of disease, 3.6%, 1.9% and 0.25% of blood, anal and urine samples were positive for SARS-CoV-2.…”

Section: Discussionsupporting

confidence: 92%

SARS-CoV-2 Detection and Culture in Different Biological Specimens from Immunocompetent and Immunosuppressed COVID-19 Patients Infected with Two Different Viral Strains

Mendes-Corrêa¹,

Salomão²,

Ghilardi³

et al. 2023

Preprint

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Introduction- The dynamics of SARS-CoV-2 shedding and replication in humans remain incompletely understood. Methods- We analyzed SARS-CoV-2 shedding from multiple sites in individuals with an acute COVID-19 infection by weekly sampling for five weeks in 98 immunocompetent and 25 immunosuppressed individuals. Samples and culture supernatants were tested by RT-PCR for SARS-CoV-2 to determine viral clearance rates and in vitro replication. Results- A total of 2447 clinical specimens were evaluated, including 557 nasopharyngeal swabs, 527 saliva samples, 464 urine specimens, 437 anal swabs and 462 blood samples. The SARS-CoV-2 genome sequences at each site were classified as belonging to the B.1.128 (ancestral strain) or Gamma lineage. SARS CoV-2 detection was highest in nasopharyngeal swabs regardless of the virus strain involved or the immune status of infected individuals. The duration of viral shedding varied between clinical specimens and individual patients. Prolonged shedding of potentially infectious virus varied from 10 days up to 191 days, and primarily occurred in immunosuppressed individuals. Virus was isolated in culture from 18 nasal swab or saliva samples collected 10 or more days after onset of disease. Conclusions-Our findings indicate that persistent SARS-CoV-2 shedding may occur in both competent or immunosuppressed individuals, at multiple clinical sites and in a minority of subjects is capable of in vitro replication.

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Section: Discussionsupporting

confidence: 92%

SARS-CoV-2 Detection and Culture in Different Biological Specimens from Immunocompetent and Immunosuppressed COVID-19 Patients Infected with Two Different Viral Strains

Mendes-Corrêa¹,

Salomão²,

Ghilardi³

et al. 2023

Preprint

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“…The anatomical site chosen to collect the swab specimen for detection of SARS-CoV-2 might influence viral load detection. Higher RNA viral load was reported from nasopharyngeal than oropharyngeal swabs 28,124,181 . As a result, nasopharyngeal samples show the highest diagnostic accuracy compared with other upper respiratory tract samples 182 .…”

Section: Specimen Selection Sitementioning

confidence: 95%

“…As a result, nasopharyngeal samples show the highest diagnostic accuracy compared with other upper respiratory tract samples 182 . Similarly, higher virus isolation success was reported from nasopharyngeal swabs than from saliva, nasal or sublingual swabs 124 . However, another study found higher RNA viral loads in the throat and sputum than from nasal swabs 30 .…”

Section: Specimen Selection Sitementioning

confidence: 97%

“…There are limited data regarding the presence of infectious virus in asymptomatic patients. One study showed lower virus isolation success from asymptomatic patients 124 , but only a small number of patients were included. Therefore, more studies evaluating infectious virus in asymptomatic patients would help to elucidate the differences in their infectivity compared with symptomatic patients.…”

Section: Human Respiratory Syncytial Virusmentioning

confidence: 99%

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SARS-CoV-2 viral load and shedding kinetics

2022

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SARS-CoV-2 viral load and detection of infectious virus in the respiratory tract are the two key parameters for estimating infectiousness. As shedding of infectious virus is required for onward transmission, understanding shedding characteristics is relevant for public health interventions. Viral shedding is influenced by biological characteristics of the virus, host factors and pre-existing immunity (previous infection or vaccination) of the infected individual. Although the process of human-to-human transmission is multifactorial, viral load substantially contributed to human-to-human transmission, with higher viral load posing a greater risk for onward transmission. Emerging SARS-CoV-2 variants of concern have further complicated the picture of virus shedding. As underlying immunity in the population through previous infection, vaccination or a combination of both has rapidly increased on a global scale after almost 3 years of the pandemic, viral shedding patterns have become more distinct from those of ancestral SARS-CoV-2. Understanding the factors and mechanisms that influence infectious virus shedding and the period during which individuals infected with SARS-CoV-2 are contagious is crucial to guide public health measures and limit transmission. Furthermore, diagnostic tools to demonstrate the presence of infectious virus from routine diagnostic specimens are needed.

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“…Finally, we mainly collected saliva samples rather than NP swabs because the latter are logistically challenging in longitudinal sampling. As there is a lower chance of successful virus isolation from saliva sample, 28 our study may have underestimated the probability of viable virus shedding.…”

Section: Discussionmentioning

confidence: 84%

Virological characteristics and the rapid antigen test as deisolation criteria in immunocompromised patients with COVID‐19: A prospective cohort study

Kang,

Kim,

Kim

et al. 2023

Journal of Medical Virology

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There are limited data supporting current Centers for Disease Control and Prevention guidelines for the isolation period in moderate to severely immunocompromised patients with coronavirus disease 2019 (COVID‐19). Adult COVID‐19 patients who underwent solid organ transplantation (SOT) or received active chemotherapy against hematologic malignancy were enrolled and weekly respiratory samples were collected. Samples with positive genomic real‐time polymerase chain reaction results underwent virus culture and rapid antigen testing (RAT). A total of 65 patients (40 with hematologic malignancy and 25 SOT) were enrolled. The median duration of viable virus shedding was 4 weeks (interquartile range: 3–7). Multivariable analysis revealed that B‐cell depletion (hazard ratio [HR]: 4.76) was associated with prolonged viral shedding, and COVID‐19 vaccination (≥3 doses) was negatively associated with prolonged viral shedding (HR: 0.22). The sensitivity, specificity, positive predictive value, and negative predictive value of RAT for viable virus shedding were 79%, 76%, 74%, and 81%, respectively. The negative predictive value of RAT was only 48% (95% confidence interval [CI]: 33–65) in the samples from those with symptom onset ≤20 days, but it was as high as 92% (95% CI: 85–96) in the samples from those with symptom onset >20 days. About half of immunocompromised COVID‐19 patients shed viable virus for ≥4 weeks from the diagnosis, and virus shedding was prolonged especially in unvaccinated patients with B‐cell‐depleting therapy treatment. RAT beyond 20 days in immunocompromised patients had a relatively high negative predictive value for viable virus shedding.

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Viral RNA Load and Infectivity of SARS-CoV-2 in Paired Respiratory and Oral Specimens from Symptomatic, Asymptomatic, or Postsymptomatic Individuals

Cited by 14 publications

References 49 publications

SARS-CoV-2 Detection and Culture in Different Biological Specimens from Immunocompetent and Immunosuppressed COVID-19 Patients Infected with Two Different Viral Strains

SARS-CoV-2 Detection and Culture in Different Biological Specimens from Immunocompetent and Immunosuppressed COVID-19 Patients Infected with Two Different Viral Strains

SARS-CoV-2 viral load and shedding kinetics

Virological characteristics and the rapid antigen test as deisolation criteria in immunocompromised patients with COVID‐19: A prospective cohort study

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