timely and the investigators showed great courage and leadership in a very difcult time when the Chinese authority failed to recognize widespread person-to-person transmission of SARS-CoV-2 before January 20, 2020. Several interesting papers on SARS-CoV-2 and COVID-19 have been published in the past few weeks to report on the evolutionary reservoir [3], possible intermediate host [4] and genomic sequence [5] of Open Access Cell & Bioscience *Correspondence: dyjin@hku.hk 1 School of Biomedical Sciences, The University of Hong Kong, 3/F Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong Full list of author information is available at the end of the article Yuen et al. Cell Biosci (2020) 10:40 Page 2 of 5 SARS-CoV-2 as well as clinical characteristics of COVID19 [6, 7]. In view of these fndings and the urgent needs in the prevention and control of SARS-CoV-2 and COVID19, in this commentary we highlight the most important research questions in the feld from our personal perspectives. Te frst question concerns how SARS-CoV-2 is transmitted currently in the epicenter of Wuhan. In order to minimize the spreading of SARS-CoV-2, China has locked down Wuhan and nearby cities since January 23, 2020. Te unprecedented control measures including suspension of all urban transportation have apparently been successful in preventing further spreading of SARSCoV-2 to other cities. However, the number of confrmed cases in Wuhan continued to rise. It is therefore crucial to determine whether the rise is due to a large number of infected individuals before the lock down and/ or failure in the prevention of widespread intra-familial, nosocomial or community transmission. Based on the number of exported cases from Wuhan to cities outside of mainland China, it was predicted that there might be more than 70,000 individuals infected with SARS-CoV-2 on January 25, 2020 in Wuhan [8]. Tis should be determined experimentally in Wuhan as discussed below and it will reveal whether the real numbers of infected people and asymptomatic carriers are indeed underestimated severely. In addition to viral RNA detection, measurement of IgM and IgG antibodies as well as antigens would be very helpful. Several representative residential areas should be selected for detailed analysis so that a big picture can be deduced. Te analysis should include all healthy and diseased individuals within the area with the aim of identifying people who have recovered from an infection or are having an active infection. Te ratio of asymptomatic carriers should also be determined. Te analysis should also be extended to detect RNA and antigen of infuenza viruses. Te activity of seasonal fu in Wuhan also reached a peak at the beginning of 2020. It will be of interest to see whether the fu season had ended and how many people having a fever now are actually infected with infuenza virus. Precision control measures for SARS-CoV-2 should be tailor-designed for high-risk groups based on the results of this analysis. Diferentiating people having a fu and preventing them from infecting with SARS-CoV-2 in a hospital setting might also be critical. Te second question is how transmissible and pathogenic is SARS-CoV-2 in tertiary and quaternary spreading within humans. Continued transmission of SARS-CoV-2 in Wuhan suggests that tertiary and quaternary spreading has occurred. Compared to the primary and secondary spreading during which SARS-CoV-2 was transmitted from animal to human and from human to human, has the transmission rate increased and has the pathogenicity decreased? Alternatively, is the virus less transmissible after several passages in humans? Retrospective analysis of all confrmed cases in Wuhan should be very informative. Te answers to the above questions hold the key to the outcome of the outbreak. If the transmission is weakened, the outbreak may ultimately come to an end at which SARS-CoV-2 is eradicated from humans. On the contrary, if efective transmission can be sustained, the chance is increased that SARS-CoV-2 will become another community-acquired human coronavirus just like the other four human coronaviruses (229E, OC43, HKU1 and NL63) causing common cold only. Te basic reproductive number (R0) of SARS-CoV-2 has been estimated to be 2.68, resulting in an epidemic doubling time of about 6.4 days [8]. Other estimates of R0 could go up to 4, higher than that of SARS-CoV, which is lower than 2. Determining the real R0 will shed light on whether and to what extent infection control measures are efective. Te third question relates to the importance of asymptomatic and presymptomatic virus shedding in SARSCoV-2 transmission. Asymptomatic and presymptomatic virus shedding posts a big challenge to infection control [1, 2]. In addition, patients with mild and unspecifc symptoms are also difcult to identify and quarantine. Notably, the absence of fever in SARS-CoV-2 infection (12.1%) is more frequent than in SARS-CoV (1%) and Middle East respiratory syndrome coronavirus (MERSCoV; 2%) infection [6]. In light of this, the efectiveness of using fever detection as the surveillance method should be reviewed. However, based on previous studies of infuenza viruses and community-acquired human coronaviruses, the viral loads in asymptomatic carriers are relatively low [9]. If this is also the case for