The number of similar epitopes determines the longevity of immunological memory (preprint)

The half-life of specific antibodies against various antigens varies tremendously from a few months to over 10,000 years. The reasons are largely unknown. Through epitope analysis of representative viruses, we found that the longevity of immunological memory may be correlated with the number of epitopes with similar sequences (EWSS) within each virus. Accordingly, a vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with 4.5-times higher antibody titers and over 100 months of half-life was developed in a rabbit model. The decay pattern of antibodies against each epitope or the entire SARS-CoV-2 spike protein was roughly correlated with the number of EWSS in immunizationtreatments, –that is, for every additional EWSS, the half-life of the antibody would be doubled. After immunization, proportions of antigen-specific memory B cells (MBC) first increased and then decreased. In the descending phase, the antibody titers were positively correlated with the numbers of MBC. This study also discusses improvement measures for vaccines against other viruses.

TMPRSS2 Protease Inhibitors May Prolong But Heparins Accelerate SARS-CoV-2 Clearance (preprint)

The 2019 novel SARS-like coronavirus (SARS-CoV-2) entry depends on the host membrane serine protease TMPRSS2, which can be blocked by some clinically-proven drugs. Here we analyzed spatial relevance between glycosylation sequons and antibody epitopes and found that, different from SARS-CoV S, most high-surface-accessible epitopes of SARS-CoV-2 S are blocked by the glycosylation, and the optimal epitope with the highest surface accessibility is covered by the S1 cap. TMPRSS2 inhibitor treatments may prevent unmasking of this epitope and therefore prolong virus clearance and may induce antibody-dependent enhancement. Interestingly, a heparin-binding sequence immediately upstream of the S1/S2 cleavage site has been found in SARS-CoV-2 S but not in SARS-CoV S. Binding of SARS-CoV-2 with heparins may lead to exposure of S686, which then facilitates the S1/S2 cleavage, induces exposure of the optimal epitope, and therefore increases the antibody titres. A combination of heparin and vaccine (or convalescent serum) treatments thus is recommended.

COVID-19 versus non-COVID-19 pneumonia: A retrospective cohort study (preprint)

Background and Objective: Since the outbreak of coronavirus disease 2019 (COVID-19) in December 2019 in Wuhan, Hubei Province, China, it has spread around the world and become a global public health emergency. It is important to distinguish COVID-19 from other viral pneumonias in order to properly screen and diagnose patients, reduce nosocomial infections, and complement the inadequacy of nucleic acid testing. In this study, we retrospectively analysed the clinical data of COVID-19 versus non-COVID-19 patients treated at our hospital between January 17 and February 27, 2020 in order to summarize our clinical experience in the differential diagnosis of COVID-19. Methods: In this retrospective cohort study, 23 confirmed COVID-19 patients were consecutively enrolled from January 17 to February 27, 2020, while 29 confirmed non-COVID-19 patients were enrolled in West China Hospital of Sichuan University. We collected baseline data, epidemiological data, clinical characteristics, imaging findings, viral nucleic acid test results, and survival data. SPSS v22.0 was used for statistical analysis. Outcomes were followed up until March 25. Results: A total of 52 patients were included in this study, including 23 COVID-19 patients and 29 non-COVID-19 patients. No significant between-group difference was observed in age, sex, primary signs or symptoms, cellular immunity, or platelet count. Significant between-group differences were observed in clinical characteristics such as dry cough, contact with individuals from Wuhan, some underlying diseases, nucleated cell count, chest imaging findings, viral nucleic acid test result,28-day mortality, and 28-day survival. Conclusion: Epidemiological data, clinical symptoms, nucleic acid test results for COVID-19 and chest CT manifestation may help distinguish COVID-19 from non-COVID-19 cases, prevent imported cases and nosocomial infections.