key: cord-0904441-fdkg1b21
authors: Atripaldi, Luigi; Sale, Silvia; Capone, Mariaelena; Montesarchio, Vincenzo; Parrella, Roberto; Botti, Gerardo; Ascierto, Paolo Antonio; Madonna, Gabriele
title: Could asymptomatic carriers spread the SARS-CoV-2 infection? Experience from the Italian second wave
date: 2021-03-02
journal: J Transl Med
DOI: 10.1186/s12967-021-02762-0
sha: 68bc6f77c88a6968077a21f63765c7ae276789dd
doc_id: 904441
cord_uid: fdkg1b21

nan

We read with great interest the recent paper by Shiyi Cao et al. [1] entitled "Post-lockdown SARS-CoV-2 nucleic acid screening in nearly ten million residents of Wuhan, China" regarding the mass screening program of SARS-CoV-2 infection conducted in the metropolitan city of Wuhan, China. The authors reported the organization process, detailed technical methods used, and results of this citywide nucleic acid screening in which nearly 10 million people were recruited. This impressive screening program, conducted to evaluate the current status of infection at a given post-lockdown time point, provides a unique/extraordinary insight on the current status of the coronavirus pandemic. The authors reported 300 new asymptomatic positive cases and, in addition, 107 out 34424 previously recovered COVID-19 cases tested positive again. Interestingly, the authors highlighted that for all positive cases no "viable virus" was detected on cultures and all their close contacts tested negative for the COVID-19, which suggested the lack of evidence of transmission from asymptomatic cases. Although mass screening programs are a valid and extremely useful tools to collect important information with a high number of samples, we believe that the claims should be evaluated in the light of and compared to currently available data as well as the data cited in the article itself. There is a contradiction between the authors' conclusions and current health recommendations for preventing the spread of COVID-19 coupled with existing literature regarding SARS-CoV-2 transmission [2] . Data suggests and has taught us [3] that even among presymptomatic patients, the high levels of viral shedding in the upper respiratory tract are a key factor in the transmissibility of the infection. In addition, the viral loads of SARS-CoV-2 were found similarly high in the four canonical symptomatic groups (presymptomatic, asymptomatic, typical symptoms and atypical symptoms); SARS-CoV-2 spreads in high concentrations from the nasal cavities prior to symptom development and viable virus was found in culture also in presymptomatic cases [4] . Additional evidence cautions on the existence of transmissibility of the asymptomatic cases as an alarm signal: He et al. argue that the transmissibility of asymptomatic cases could be lower than that of the symptomatic case [5] and Chen et al. reported no statistical difference in the transmissibility of asymptomatic cases versus symptomatic cases among close contacts [6] .

In addition, data from our clinical experience underlines the potential involvement of asymptomatic cases in spreading Covid-19. At our Institution, ' Azienda Ospedaliera dei Colli Monaldi-Cotugno Hospital' , Italy, 130 subjects (69males, 61females, medianage41, range6-96) were diagnosed with SARS-COV-2 infection in postlockdown, between August 2020 and September 2020. As indicated by WHO guidelines, confirmation of SARS-CoV-2 infection was obtained by a positive RT-PCR oropharyngeal swab. We compared real-time PCR threshold

Journal of Translational Medicine N1-encoding RNA, respectively). The viral load in the sample is calculated by interpolation of the corresponding Ct value with the standard curve. We observed a statistically significant lower real-time PCR Ct median value for the RdRP, S, N and E genes in symptomatic cases versus asymptomatic cases. Interestingly, a number of samples from asymptomatic cases showed a low real-time PCR Ct and symptomatic cases a high real-time PCR Ct (Fig. 1a, Table 1 ). Nevertheless, a complete overlap of the confidence intervals between the two groups was observed (Table 1) . No statistically significant differences were observed between symptomatic and asymptomatic cases for real-time PCR Ct median values of the N1, N2 and N3 regions (Fig. 1b, Table 2 ). In addition, no notable differences in SARS-CoV-2 viral load between asymptomatic and symptomatic cases were observed. Important to note that also asymptomatic cases had marked SARS-CoV-2 viral load (Fig. 1c , Table 2 ). In our opinion, these data underline that also the viral loads of asymptomatic cases may be sufficient to hypothesize the transmission of the SARS-CoV-2 infection from asymptomatic subjects; measuring not only the presence but also the amount of virus in infected subjects could be precious information to help control the pandemic. We strongly believe that the rapid spread of the second wave of Covid-19 is linked to the circulation of the asymptomatic or pre-symptomatic subjects in postlockdown settings. It becomes therefore necessary to intensify mass screening programs and continue to test and quarantine all positive cases in order to prevent a potential SARS-CoV-2 third wave. To pursue this objective and continue the remarkable progress in the knowledge in the fields of prevention, treatment and management of Covid-19 disease, it is necessary to encourage scientific disclosure and continue to contribute to primary data on this "hot topic" in which still many questions remain unanswered. 

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Not applicable.Authors' contributions PAA, LA, and GM contributed to the conception and design of the study. PAA, LA, GM, RP, SS, MC, VM and GB contributed to patients' enrollment, data acquisition and data interpretation. GM and SS performed the experiments,