(C) UVCvis absorption spectra of QBs and QDs, respectively. about one order of magnitude improvement in analytical sensitivity compared to standard platinum nanoparticle-based LFIA. In addition, the developed QB-LFIA performed well in clinical study in dynamic monitoring of serum antibody levels in the whole course of SARS-CoV-2 contamination. In conclusion, we successfully developed a encouraging fluorescent immunological sensing tool for characterizing the host immune response to SARS-CoV-2 contamination and confirming the acquired immunity to COVID-19 by evaluating the SRAS-CoV-2 total antibody level in the masses. 1.?Introduction Since early December of 2019 and up to November 18, 2020, over 54 million cases of coronavirus disease 2019 (COVID-19) caused by novel coronavirus (SARS-CoV-2) contamination, with over 1.9 million deaths have been reported in 223 countries [1]. The timely and accurate diagnosis of SARS-CoV-2 infections is crucial for e? ;ectively managing the infected patients and controlling the epidemic of SARS-CoV-2 in a population [[2], [3], [4]]. Currently, the detection of viral nucleic acid using reverse transcription-polymerase chain reaction (RT-PCR) has been widely regarded as the gold standard for confirming SARS-CoV-2 infection [[5], Hoechst 33258 analog 2 [6], [7]]. However, the accessibility and reliability of this method was largely compromised by the high test cost, the delayed feedback of test results, the need of specialized instrument, high-level biosafety laboratories and skilled technicians, Hoechst 33258 analog 2 as well as the high false negative rates (even up to 30 %30 %) [[8], [9], [10], [11]]. Increasing studies indicated that COVID-19 infection can also be determined indirectly by monitoring the host immune response to EDA SARS-CoV-2 infection [[12], [13], [14], [15]]. Serological diagnosis by measuring the level of specific antibodies against SARS-CoV-2 in the host is becoming another important approach supplemental to assist COVID-19 diagnosis because the antibodies have been reported with nearly 100 % positive rate within 2 weeks after symptom onset [16,17]. It has been reported that IgM could be found to be positive in the blood of patients even as early as the fourth day after symptom onset [8,18,19]. In addition, serological Hoechst 33258 analog 2 detection contributes not only to the better knowledge of the antibody response characteristics to SARS-CoV-2 infection, but also the extent of COVID-19 within the community and the identification of individuals who have immunity and are likely to protect against infection [16,20,21]. The total antibodies against SARS-CoV-2 are considered as the most sensitive and earliest serological marker compared to IgM or IgG, and has been recommended as the diagnosis standard for COVID-19 by the World Health Organization (WHO) [22]. Therefore, developing a rapid, sensitive and specific method for detecting total antibodies is capable of serving as a valuable and promising tool to improve the diagnosis of COVID-19 [[23], [24], [25]]. To Hoechst 33258 analog 2 date, a number of serologic testing strategies, including enzyme linked immunosorbent assay (ELISA) [26], lateral flow immunoassay (LFIA) [27], and chemiluminescent immunoassay (CLIA) [28] have been recently reported for the detection of total antibodies, IgM and IgG to SARS-CoV-2. Among the available immunoassays, LFIA has attracted increasing interest due to its simplicity, convenience, rapidity and low cost [29]. In particular, colloidal gold nanoparticle-based LFIA (AuNP-LFIA) for the detection of SARS-CoV-2 infection has experienced rapid development in a short period and some commercial products approved for serological assays have sprung up in various countries and regions [8,30,31]. However, the widespread use of AuNP-LFIA in aiding the COVID-19 diagnosis is still controversial because of its low sensitivity and high false negative rates [32,33]. Recent studies have suggested that the use of fluorescent materials Hoechst 33258 analog 2 with highly luminescent intensity as alternative LFIA label to AuNPs is beneficial to improving the analytical sensitivity [34,35]. As a novel fluorescent nanomatieral, quantum dot nanobeads (QBs) have been well demonstrated with great potential in enhancing target detection through LFIA based on their high luminescence and resistance to matrix interference [36,37]. Hence, in this work, we design and develop a QB-based LFIA (QB-LFIA) for the detection of total antibodies to SARS-CoV-2 in.