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., 2020Nikolai L.A. Meyer C.G. Kremsner P.G. Velavan T.P. Asymptomatic SARS Coronavirus 2 infection: Invisible yet invincible.Int J Infect Dis. 2020; 100: 112-116Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar). 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., 2020Long Q.X. Tang X.J. Shi Q.L. Li Q. Deng H.J. Yuan J. Hu J.L. Xu W. Zhang Y. Lv F.J. et al.Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections.Nat Med. 2020; 26: 1200-1204Crossref PubMed Scopus (1929) Google Scholar). 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., 2020Nikolai L.A. Meyer C.G. Kremsner P.G. Velavan T.P. Asymptomatic SARS Coronavirus 2 infection: Invisible yet invincible.Int J Infect Dis. 2020; 100: 112-116Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar). 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., 2020Young B.E. Ong S.W.X. Kalimuddin S. Low J.G. Tan S.Y. Loh J. Ng O.T. Marimuthu K. Ang L.W. Mak T.M. et al.Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore.JAMA. 2020; 323: 1488-1494Crossref PubMed Scopus (1420) Google Scholar). 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., 2020Rao S.N. Manissero D. Steele V.R. Pareja J. A Systematic Review of the Clinical Utility of Cycle Threshold Values in the Context of COVID-19.Infect Dis Ther. 2020; 9: 573-586Crossref PubMed Scopus (242) Google Scholar). 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., 2020Rao S.N. Manissero D. Steele V.R. Pareja J. A Systematic Review of the Clinical Utility of Cycle Threshold Values in the Context of COVID-19.Infect Dis Ther. 2020; 9: 573-586Crossref PubMed Scopus (242) Google Scholar, Aquino-Jarquin, 2020Aquino-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/ciaa830Crossref PubMed Scopus (10) Google Scholar). 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., 2020Li 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.2020.07.008Abstract Full Text Full Text PDF Scopus (48) Google Scholar). 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 (Zhou et al., 2020Zhou R. Li F. Chen F. Liu H. Zheng J. Lei C. Wu X. Viral dynamics in asymptomatic patients with COVID-19.Int J Infect Dis. 2020; 96: 288-290Abstract Full Text Full Text PDF PubMed Scopus (159) Google Scholar). 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., 2020Long Q.X. Tang X.J. Shi Q.L. Li Q. Deng H.J. Yuan J. Hu J.L. Xu W. Zhang Y. Lv F.J. et al.Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections.Nat Med. 2020; 26: 1200-1204Crossref PubMed Scopus (1929) Google Scholar). 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., 2020Busco G. Yang S.R. Seo J. Hassan Y.A. Sneezing and asymptomatic virus transmission.Phys Fluids. 2020; 32073309Crossref PubMed Scopus (137) Google Scholar). 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., 2020Nikolai L.A. Meyer C.G. Kremsner P.G. Velavan T.P. Asymptomatic SARS Coronavirus 2 infection: Invisible yet invincible.Int J Infect Dis. 2020; 100: 112-116Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar). 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. Not applicable.
Tópico:
SARS-CoV-2 and COVID-19 Research
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3
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FuenteInternational Journal of Infectious Diseases