Malagón-Rojas et al. comments on the need for a widely accepted definition of asymptomatic carriers and pre-symptomatic patients and to report asymptomatic individuals in official COVID-19 statistics are well acknowledged (
Nikolai et al., 2020
).Malagón-Rojas et al. show in a longitudinal follow-up of 202 airport employees that no significant differences in Ct values were observed when comparing asymptomatic and symptomatic patients (median Ct 33.4 vs. 34.1 in asymptomatic and symptomatic patients, respectively). Their findings are consistent with another study that examined asymptomatic individuals and symptomatic patients (
Long et al., 2020
).The virus load is assessed semi-quantitatively by the cycle threshold (Ct) value, which corresponds to the number of amplification cycles in the diagnostic RT-PCR assays. Ct values decrease with increasing viral loads and high Ct values correspond to low viral loads (
Nikolai et al., 2020
). In addition, the duration of virus detectability serves as an indicator of infectivity. Several SARS-CoV-2 PCR assays use a Ct cut-off value of <40 for positivity, and in the early stages of infection patients usually have Ct values of 20-30 (Young et al., 2020
). A recent narrative systematic review suggests that lower Ct values are associated with poorer outcomes and thus beneficial in predicting the clinical prognosis of COVID-19 patients (Rao et al., 2020
). Higher Ct values normally correlate with lower viral loads. However the Ct values are not directly proportional to the viral load, due to the dynamic range of the assay and/or the potential presence of any inhibitory factors in samples used ( Rao et al., 2020
, Aquino-Jarquin, 2020
).- Aquino-Jarquin G.
The raw Ct values from RT-PCR detection are not viral load quantitation units.
Clin Infect Dis. 2020; https://doi.org/10.1093/cid/ciaa830
The current literature gives indications of the median duration of virus shedding of 11.5 days for pre-symptomatic, 28 days for asymptomatic and 31 days for mildly symptomatic patients (
Li et al., 2020
). Another study using the similar gene target ORF1ab as described by Malagón-Rojas et al. shows that median Ct values during hospitalization were significantly higher in asymptomatic patients (39.0, IQR 37.5-39.5) than in asymptomatic patients during the incubation period (34.5, IQR 32.2-37.0), indicating a significantly lower viral load (- Li W.
- Su Y.Y.
- Zhi S.S.
- Huang J.
- Zhuang C.L.
- Bai W.Z.
- Wan Y.
- Meng X.R.
- Zhang L.
- Zhou Y.B.
- et al.
Virus shedding dynamics in asymptomatic and mildly symptomatic patients infected with SARS-CoV-2.
Clin Microbiol Infect. 2020; https://doi.org/10.1016/j.cmi.2020.07.008
Zhou et al., 2020
). Long-term virus shedding was documented rather in asymptomatic than in symptomatic patients and virus shedding did not correspond to viral infectivity (Long et al., 2020
).We agree with the authors that the absence of respiratory symptoms such as sneezing or coughing limits the potential of spread by asymptomatic individuals, however, virus transmission may occur through occasional and also more frequent sneezing during the allergy season may also increase the risk (
Busco et al., 2020
). The risk still exists.Asymptomatic and presymptomatic stages can currently be assigned only retrospectively, namely after the occurrence or non-occurrence of clinical symptoms and it is virtually impossible to accurately determine the extent of asymptomatic infections. The true incidence of asymptomatic infections can only be determined if closest surveillance and extensive testing is installed and continued for a period of time exceeding the estimated average incubation period of at least five days in order not to miss a possible onset of symptoms (
Nikolai et al., 2020
).Asymptomatic infections are an important aspect of SARS-CoV-2 infection, in particular on the viral transmission, and globally remain a significant epidemiologic challenge, as health systems could become severely overburdened and the pandemic could continue to elude control, hitting those hardest with the least protection.
Funding source
Not applicable.
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Conflict of interest
All authors disclose no conflict of interest.
Contribution statement
All authors have an academic interest and contributed equally.
References
- The raw Ct values from RT-PCR detection are not viral load quantitation units.Clin Infect Dis. 2020; https://doi.org/10.1093/cid/ciaa830
- Sneezing and asymptomatic virus transmission.Phys Fluids. 2020; 32073309
- Virus shedding dynamics in asymptomatic and mildly symptomatic patients infected with SARS-CoV-2.Clin Microbiol Infect. 2020; https://doi.org/10.1016/j.cmi.2020.07.008
- Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections.Nat Med. 2020; 26: 1200-1204
- Asymptomatic SARS Coronavirus 2 infection: Invisible yet invincible.Int J Infect Dis. 2020; 100: 112-116
- A Systematic Review of the Clinical Utility of Cycle Threshold Values in the Context of COVID-19.Infect Dis Ther. 2020; 9: 573-586
- Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore.JAMA. 2020; 323: 1488-1494
- Viral dynamics in asymptomatic patients with COVID-19.Int J Infect Dis. 2020; 96: 288-290
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Published online: October 16, 2020
Received:
October 5,
2020
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- Letter to the editor on “Asymptomatic infection by SARS 2 coronavirus: Invisible but invincible” by Nikolai et al. 2020International Journal of Infectious DiseasesVol. 101
- PreviewWe send this letter regarding the article "Asymptomatic infection by SARS 2 coronavirus: invisible but invincible," published in the International Journal of Infectious Diseases (Nikolai et al., 2020). The review was interesting in many aspects, particularly those related to the lack of a widely accepted definition of asymptomatic carriers and presymptomatic patients and the need to include these types of cases in regular epidemiological surveillance.
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