Antibody neutralization to SARS-CoV-2 and variants after one year in Wuhan

Most COVID-19 patients can build effective humoral immunity against SARS-CoV-2 after recovery(1, 2). However, it remains unknown how long the protection can maintain and how efficiently it can protect people from the reinfection of the emerging SARS-CoV-2 variants. Here we evaluated the sera from 248 COVID-19 convalescents around one year post-infection in Wuhan, the earliest epicenter of SARS-CoV-2. We demonstrated that the SARS-CoV-2 immunoglobulin G (IgG) maintains at a high level and potently neutralizes the infection of the original strain (WT) and the B.1.1.7 variant in most patients. However, they showed varying degrees of efficacy reduction against the other variants of concern (P.1, B.1.525, and especially B.1.351) in a patient-specific manner. Mutations in RBD including K417N, E484K, and E484Q/L452R (B.1.617) remarkably impair the neutralizing activity of the convalescents sera. Encouragingly, we found that a small fraction of patients sera showed broad neutralization potency to multiple variants and mutants, suggesting the existence of broadly neutralizing antibodies recognizing the epitopes beyond the mutation sites. Our results suggest that the SARS-CoV-2 vaccination effectiveness relies more on the timely re-administration of the epitope-updated vaccine than the durability of the neutralizing antibodies.

Antibody Cocktail Exhibits Broad Neutralization against SARS-CoV-2 and SARS-CoV-2 variants

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated multiple variants resistant to therapeutic antibodies. In this study, 12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries. Of them, two RBD-binding antibodies (F61 and H121) showed high affinity neutralization against SARS-CoV-2, whereas three S2-target antibodies failed to neutralize SARS-CoV-2. Following structure analysis, F61 identified a linear epitope located in residues G446 -S494, which overlapped with angiotensin-converting enzyme 2 (ACE2) binding sites, while H121 recognized a conformational epitope located on the side face of RBD, outside from ACE2 binding domain. Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-CoV-2. Importantly, F61 and H121 exhibited efficient neutralizing activity against variants B.1.1.7 and B.1.351, those showed immune escape. Efficient neutralization of F61 and H121 against multiple mutations within RBD revealed a broad neutralizing activity against SARS-CoV-2 variants, which mitigated the risk of viral escape. Our findings defined the basis of therapeutic cocktails of F61 and H121 with broad neutralization and delivered a guideline for the current and future vaccine design, therapeutic antibody development, and antigen diagnosis of SARS-CoV-2 and its novel variants.

Assessment of the global status of COVID-19 epidemics / 公共卫生与预防医学

Objective To analyze the global status of COVID-19 epidemics, so as to preliminarily forecast the epidemic trend. Methods The epidemiological data of 208 countries and the prevention and control policies implemented by typical countries from December 31, 2019 to December 14, 2020 were collected. We use the cumulative incidence rate, cumulative mortality, cumulative fatality and real-time dependent reproduction number (Rt) to analyze the epidemic status. We use the provenance package to group different countries and discuss the effect of prevention and control measures. Results As of December 14, 2020, a cumulative incidence of 93.49 per 10000, a cumulative mortality rate of 0.21‰, and a cumulative fatality rate of 3.1‰ had been reported globally.112 of the 208 countries still had Rt ≥ 1.0, and 96 countries had Rt t , and the government had adopted more relaxed epidemic prevention measures. The epidemic situation in this region may continue to deteriorate, and needs to be focused in the later period.

Abnormal Upregulation of Cardiovascular Disease Biomarker PLA2G7 Induced by Proinflammatory Macrophages in COVID-19 patients

BACKGROUNDCoronavirus disease 2019 (COVID-19) triggers distinct patterns of pneumonia progression with multiorgan disease, calling for cell- and/or tissue-type specific host injury markers. METHODSAn integrated hypothesis-free single biomarker analysis framework was performed on nasal swabs (n = 484) from patients with COVID-19 in GSE152075. The origin of candidate biomarker was assessed in single-cell RNA data (GSE145926). The candidate biomarker was validated in a cross-sectional cohort (n = 564) at both nucleotide and protein levels. RESULTSPhospholipase A2 group VII (PLA2G7) was identified as a candidate biomarker in COVID-19. PLA2G7 was predominantly expressed by proinflammatory macrophages in lungs emerging with progression of COVID-19. In the validation stage, PLA2G7 was found in patients with COVID-19 and pneumonia, especially in severe pneumonia, rather than patients suffered mild H1N1 influenza infection. Up to 100% positive rates of PLA2G7 were positively correlated with not only viral loads in patients with COVID-19 but also severity of pneumonia in non-COVID-19 patients. Although Ct values of PLA2G7 in severe pneumonia was significantly lower than that in moderate pneumonia (P = 7.2e-11), no differences were observed in moderate pneumonia with COVID-19 between severe pneumonia without COVID-19 (P = 0.81). Serum protein levels of PLA2G7, also known as lipoprotein-associated phospholipase A2 (Lp-PLA2), were further found to be elevated and beyond the upper limit of normal in patients with COVID-19, especially among the re-positive patients. CONCLUSIONSWe firstly identified and validated PLA2G7, a biomarker for cardiovascular diseases (CVDs), was abnormally enhanced in COVID-19 patients at both nucleotide and protein aspects. These findings provided indications into the prevalence of cardiovascular involvements seen in COVID-19 patients. PLA2G7 could be a hallmark of COVID-19 for monitoring disease progress and therapeutic response. FUNDINGThis study was supported by grants from China Mega-Projects for Infectious Disease (2018ZX10711001), National Natural Science Foundation of China (82041023).

Genome-wide data inferring the evolution and population demography of the novel pneumonia coronavirus (SARS-CoV-2)

As the highly risk and infectious diseases, the outbreak of coronavirus disease 2019 (COVID-19) poses unprecedent challenges to global health. Up to March 3, 2020, SARS-CoV-2 has infected more than 89,000 people in China and other 66 countries across six continents. In this study, we used 10 new sequenced genomes of SARS-CoV-2 and combined 136 genomes from GISAID database to investigate the genetic variation and population demography through different analysis approaches (e.g. Network, EBSP, Mismatch, and neutrality tests). The results showed that 80 haplotypes had 183 substitution sites, including 27 parsimony-informative and 156 singletons. Sliding window analyses of genetic diversity suggested a certain mutations abundance in the genomes of SARS-CoV-2, which may be explaining the existing widespread. Phylogenetic analysis showed that, compared with the coronavirus carried by pangolins (Pangolin-CoV), the virus carried by bats (bat-RaTG13-CoV) has a closer relationship with SARS-CoV-2. The network results showed that SARS-CoV-2 had diverse haplotypes around the world by February 11. Additionally, 16 genomes, collected from Huanan seafood market assigned to 10 haplotypes, indicated a circulating infection within the market in a short term. The EBSP results showed that the first estimated expansion date of SARS-CoV-2 began from 7 December 2019.

Estimation of hospitalization rate of laboratory confirmed influenza cases in Jingzhou city, Hubei province, 2010-2012 / 中华流行病学杂志

<p><b>OBJECTIVE</b>To estimate the hospitalization rate of severe acute respiratory infection (SARI) cases attributable to influenza in Jingzhou city, Hubei province from 2010 to 2012.</p><p><b>METHODS</b>SARI surveillance was conducted at four hospitals in Jingzhou city, Hubei province from 2010 to 2012. Inpatients meeting the SARI case definition and with informed consent were enrolled to collect their demographic information, clinical features, treatment, and disease outcomes, with their respiratory tract specimens collected for PCR test of influenza virus.</p><p><b>RESULTS</b>From April, 2010 to September, 2012, 19 679 SARI cases enrolled were residents of Jingzhou, and nasopharyngeal swab was collected from 18 412 (93.6%) cases of them to test influenza virus and 13.3% were positive for influenza. During the three consecutive 2010-2012 flu seasons, laboratory-confirmed influenza was associated with 102 per 100 000, 132 per 100 000 and 244 per 100 000, respectively. As for the hospitalization rate attributable to specific type/subtype of influenza virus, 48 per 100 000, 30 per 100 000 and 24 per 100 000 were attributable to A (H3N2), A (H1N1) pdm2009, and influenza B, respectively in 2010-2011 season; 42 per 100 000 [A (H3N2)] and 90 per 100 000 (influenza B) in 2011-2012 season; 90 per 100 000 [A (H3N2)] and one per 100 000 [influenza B] from April, 2010 to September, 2012. SARI hospitalization caused by influenza A or B occurred both mainly among children younger than five years old, with the peak in children aged 0.5 year old.</p><p><b>CONCLUSION</b>Influenza could cause a substantial number of hospitalizations and different viral type/subtype result in different hospitalizations over influenza seasons in Jingzhou city, Hubei province. Children less than five years old should be prioritized for influenza vaccination in China.</p>

Sequence variation in the env V3-V4 region of human immunodeficiency virus-1 predominant subtype B strains in Hubei Province / 中华传染病杂志

Objective To study the sequence variation in the env V3-V4 human immunodeficiency virus (HIV)-1 predominant subtype B strains in Hubei Province and to understand the epidemic characteristics and mutations of HIV-1. Methods Epidemiologic survey was done in the HIV-1 carriers in Hubei area. HIV-1 env V3-V4 regions were amplified by nested-polymerase chain reaction (nPCR). The sequences were determined and then phylogenetic analysis was performed. The difference of gene distance were checked by chi square test and the variation of gene distance were descriptively analyzed. Results Four HIV-1 strains or circulating recombinant forms (CRF) were identified in Hubei Province subtype B', B'/C, CRF01_AE and C were 82.69%, 7.69%, 7.69% and 1.92% ,respectively. B' strains were closely related with B. CN. RL 42 from Yunnan Province and B. CN. 02. 02HN from Province Henan, the gene distances were 7.08 ± 2.19 and 7.88 ± 2.28, respectively. Genetic divergence of env of B' strains showed that subtype B' has existed in Hubei area for about 10 years. Amino acid sequence analysis of section env showed V4 was more variable than C3, V3. The top four peptides of V3 loop were GPGR (46.5%), GPGK (30.2%), GPGQ (13.6%) and GQGR (9.3%). Predictions for the potential use of co-receptors on the basis of the critical amino acids within V3 loop disclosed that 16.28% were CCR5-using (R5/NSI), 13.95% were CXCR4-using (X4/SI) while the co-receptor usage of the vast majority (69.77%) could not be predicted. The analysis of glycosylation sites showed that there were 9 sites in env V3-V4 regions of HIV-1 strains in Hubei area and there were deletions in 8 of them, Conclusions Subtype B' is still the main epidemic subtype in Hubei Province and high homologous to the strains from Yunan and Henan Province.