Genomic Surveillance for SARS-CoV-2 - China, September 26, 2022 to January 29, 2023.

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has generated 2,431 variants over the course of its global transmission over the past 3 years. To better evaluate the genomic variation of SARS-CoV-2 before and after the optimization of coronavirus disease 2019 (COVID-19) prevention and control strategies, we analyzed the genetic evolution branch composition and genomic variation of SARS-CoV-2 in both domestic and imported cases in China (the data from Hong Kong and Macau Special Administrative Regions and Taiwan, China were not included) from September 26, 2022 to January 29, 2023. Methods: Analysis of the number of genome sequences, sampling time, dynamic changes of evolutionary branches, origin, and clinical typing of SARS-CoV-2 variants submitted by 31 provincial-level administrative divisions (PLADs) and Xinjiang Production and Construction Corps (XPCC) was conducted to assess the accuracy and timeliness of SARS-CoV-2 variant surveillance. Results: From September 26, 2022 to January 29, 2023, 20,013 valid genome sequences of domestic cases were reported in China, with 72 evolutionary branches. Additionally, 1,978 valid genome sequences of imported cases were reported, with 169 evolutionary branches. The prevalence of the Omicron variants of SARS-CoV-2 in both domestic and imported cases was consistent with that of international epidemic variants. Conclusions: This study provides an overview of the prevalence of Omicron variants of SARS-CoV-2 in China. After optimizing COVID-19 prevention and control strategies, no novel Omicron variants of SARS-CoV-2 with altered biological characteristics or public health significance have been identified since December 1, 2022.

Positive Emotion and Media Dependence: Measuring Risk Information Seeking and Perception in the COVID-19 Pandemic Prevention.

Risk perception and information seeking behaviors are affected by individual psychological and situational factors. In the background of COVID-19 prevailing for a long period, this study examined Chinese people's information seeking and processing behavior by the RISP model, which focused on the impact of individual risk perception, affective response, perceived information-gathering capacity, and media trust and the impact of the above factors on information seeking. This study designed an online survey with gender and age quotas among the Chinese population, including a total of 675 valid samples. It was found that the Chinese public's risk perception to pandemic had a positive effect on perceived information-gathering capacity and media trust. Furthermore, both positive emotional responses and negative emotional responses had a positive effect on information seeking behavior. Nurturing positive emotion engendered a holistic perception in pandemic information seeking. In addition, media trust, perceived information-gathering capacity, and subjective norms also positively impact information seeking behavior.

Surveillance and Analysis of SARS-CoV-2 Variant Importation - China, January-June 2022.

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is the dominant circulating strain worldwide. To assess the importation of SARS-CoV-2 variants in the mainland of China during the Omicron epidemic, the genomic surveillance data of SARS-CoV-2 from imported coronavirus disease 2019 (COVID-19) cases in the mainland of China during the first half of 2022 were analyzed. Methods: Sequences submitted from January to July 2022, with a collection date before June 30, 2022, were incorporated. The proportions of SARS-CoV-2 variants as well as the relationships between the origin and destination of each Omicron imported case were analyzed. Results: 4,946 sequences of imported cases were submitted from 27 provincial-level administrative divisions (PLADs), and the median submission interval was within 1 month after collection. In 3,851 Omicron sequences with good quality, 1 recombinant (XU) and 4 subvariants under monitoring (BA.4, BA.5, BA.2.12.1, and BA.2.13) were recorded, and 3 of them (BA.4, BA.5, and BA.2.12.1) caused local transmissions in the mainland of China later than that recorded in the surveillance. Omicron subvariants dominated in the first half of 2022 and shifted from BA.1 to BA.2 then to BA.4 and BA.5. The percentage of BA.2 in the imported SARS-CoV-2 surveillance data was far higher than that in the Global Initiative on Sharing All Influenza Data (GISAID). The imported cases from Hong Kong Special Administrative Region, China, accounted for 32.30% of Omicron cases sampled, and 98.71% of them were BA.2. Conclusions: The Omicron variant showed the intra-Omicron evolution in the first half of 2022, and all of the Omicron subvariants were introduced into the mainland of China multiple times from multiple different locations.

Structural basis of a two-antibody cocktail exhibiting highly potent and broadly neutralizing activities against SARS-CoV-2 variants including diverse Omicron sublineages.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs), especially the latest Omicron, have exhibited severe antibody evasion. Broadly neutralizing antibodies with high potency against Omicron are urgently needed for understanding the working mechanisms and developing therapeutic agents. In this study, we characterized the previously reported F61, which was isolated from convalescent patients infected with prototype SARS-CoV-2, as a broadly neutralizing antibody against all VOCs including Omicron BA.1, BA.1.1, BA.2, BA.3 and BA.4 sublineages by utilizing antigen binding and cell infection assays. We also identified and characterized another broadly neutralizing antibody D2 with epitope distinct from that of F61. More importantly, we showed that a combination of F61 with D2 exhibited synergy in neutralization and protecting mice from SARS-CoV-2 Delta and Omicron BA.1 variants. Cryo-Electron Microscopy (Cryo-EM) structures of the spike-F61 and spike-D2 binary complexes revealed the distinct epitopes of F61 and D2 at atomic level and the structural basis for neutralization. Cryo-EM structure of the Omicron-spike-F61-D2 ternary complex provides further structural insights into the synergy between F61 and D2. These results collectively indicated F61 and F61-D2 cocktail as promising therapeutic antibodies for combating SARS-CoV-2 variants including diverse Omicron sublineages.

Genomic Surveillance for SARS-CoV-2 Variants of Concern from Imported COVID-19 Cases - the Mainland of China, 2021.

Introduction: After the epidemic in Wuhan City was brought under control in 2020, local outbreaks of coronavirus disease 2019 (COVID-19) in the mainland of China were mainly due to imported COVID-19 cases. The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to generate new variants. Some have been designated as variants of concern (VOCs) by the World Health Organization (WHO). To better assess the role of imported SARS-CoV-2 surveillance and the prevalence of VOCs in 2021, the genomic surveillance data of SARS-CoV-2 from imported COVID-19 cases of 2021 in the mainland of China were analyzed. Methods: The analyses included the number of sequence submissions, time of sequence deposition, and time of detection of the VOCs in order to determine the timeliness and sensitivity of the surveillance. The proportions of VOCs were analyzed and compared with data from the Global Initiative of Sharing All Influenza Data (GISAID). Results: A total of 3,355 sequences of imported cases were submitted from 29 provincial-level administrative divisions, with differences in the number of sequence submissions and median time of sequence deposition. A total of 2,388 sequences with more than 90% genomic coverage were used for lineage analysis. The epidemic trend from Alpha to Delta to Omicron in imported cases was consistent with that in the GISAID. In addition, VOCs from imported cases were usually identified after WHO designation and before causing local outbreaks. Conclusions: The global distribution of SARS-CoV-2 VOCs changed rapidly in 2021. Robust genomic surveillance of the imported SARS-CoV-2 in the mainland of China is of great significance.

Nasal delivery of broadly neutralizing antibodies protects mice from lethal challenge with SARS-CoV-2 delta and omicron variants.

Multiple new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have constantly emerged, as the delta and omicron variants, which have developed resistance to currently gained neutralizing antibodies. This highlights a critical need to discover new therapeutic agents to overcome the variants mutations. Despite the availability of vaccines against coronavirus disease 2019 (COVID-19), the use of broadly neutralizing antibodies has been considered as an alternative way for the prevention or treatment of SARS-CoV-2 variants infection. Here, we show that the nasal delivery of two previously characterized broadly neutralizing antibodies (F61 and H121) protected K18-hACE2 mice against lethal challenge with SARS-CoV-2 variants. The broadly protective efficacy of the F61 or F61/F121 cocktail antibodies was evaluated by lethal challenge with the wild strain (WIV04) and multiple variants, including beta (B.1.351), delta (B.1.617.2), and omicron (B.1.1.529) at 200 or 1000 TCID50, and the minimum antibody administration doses (5-1.25 â€‹mg/kg body weight) were also evaluated with delta and omicron challenge. Fully prophylactic protections were found in all challenged groups with both F61 and F61/H121 combination at the administration dose of 20 â€‹mg/kg body weight, and corresponding mice lung viral RNA showed negative, with almost all alveolar septa and cavities remaining normal. Furthermore, low-dose antibody treatment induced significant prophylactic protection against lethal challenge with delta and omicron variants, whereas the F61/H121 combination showed excellent results against omicron infection. Our findings indicated the potential use of broadly neutralizing monoclonal antibodies as prophylactic and therapeutic agent for protection of current emerged SARS-CoV-2 variants infection.

Chemiluminescence Immunoassay Based Serological Immunoassays for Detection of SARS-CoV-2 Neutralizing Antibodies in COVID-19 Convalescent Patients and Vaccinated Population.

The development of rapid serological detection methods re urgently needed for determination of neutralizing antibodies in sera. In this study, four rapid methods (ACE2-RBD inhibition assay, S1-IgG detection, RBD-IgG detection, and N-IgG detection) were established and evaluated based on chemiluminescence technology. For the first time, a broadly neutralizing antibody with high affinity was used as a standard for the quantitative detection of SARS-CoV-2 specific neutralizing antibodies in human sera. Sera from COVID-19 convalescent patients (N = 119), vaccinated donors (N = 86), and healthy donors (N = 299) confirmed by microneutralization test (MNT) were used to evaluate the above methods. The result showed that the ACE2-RBD inhibition assay calculated with either ACE2-RBD binding inhibition percentage rate or ACE2-RBD inhibiting antibody concentration were strongly correlated with MNT (r ≥ 0.78, p < 0.0001) and also highly consistent with MNT (Kappa Value ≥ 0.94, p < 0.01). There was also a strong correlation between the two evaluation indices (r ≥ 0.99, p < 0.0001). Meanwhile, S1-IgG and RBD-IgG quantitative detection were also significantly correlated with MNT (r ≥ 0.73, p < 0.0001), and both methods were highly correlated with each other (r ≥ 0.95, p < 0.0001). However, the concentration of N-IgG antibodies showed a lower correlation with the MNT results (r < 0.49, p < 0.0001). The diagnostic assays presented here could be used for the evaluation of SARS-CoV-2 vaccine immunization effect and serological diagnosis of COVID-19 patients, and could also have guiding significance for establishing other rapid serological methods to surrogate neutralization tests for SARS-CoV-2.

Antibody Cocktail Exhibits Broad Neutralization Activity 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, these two antibodies also showed efficient neutralizing activities to the variants including B.1.1.7 and B.1.351, and reacted with mutations of N501Y, E484K, and L452R, indicated that it may also neutralize the recent India endemic strain B.1.617. The unchanged binding activity of F61 and H121 to RBD with multiple mutations revealed a broad neutralizing activity against variants, which mitigated the risk of viral escape. Our findings revealed the therapeutic basis of cocktail antibodies against constantly emerging SARS-CoV-2 variants and provided promising candidate antibodies to clinical treatment of COVID-19 patients infected with broad SARS-CoV-2 variants.

Abnormal upregulation of cardiovascular disease biomarker PLA2G7 induced by proinflammatory macrophages in COVID-19 patients.

High rate of cardiovascular disease (CVD) has been reported among patients with coronavirus disease 2019 (COVID-19). Importantly, CVD, as one of the comorbidities, could also increase the risks of the severity of COVID-19. Here we identified phospholipase A2 group VII (PLA2G7), a well-studied CVD biomarker, as a hub gene in COVID-19 though an integrated hypothesis-free genomic analysis on nasal swabs (n = 486) from patients with COVID-19. PLA2G7 was further found to be predominantly expressed by proinflammatory macrophages in lungs emerging with progression of COVID-19. In the validation stage, RNA level of PLA2G7 was identified in nasal swabs from both COVID-19 and pneumonia patients, other than health individuals. The positive rate of PLA2G7 were correlated with not only viral loads but also severity of pneumonia in non-COVID-19 patients. Serum protein levels of PLA2G7 were found to be elevated and beyond the normal limit in COVID-19 patients, especially among those re-positive patients. We identified and validated PLA2G7, a biomarker for CVD, was abnormally enhanced in COVID-19 at both nucleotide and protein aspects. These findings provided indications into the prevalence of cardiovascular involvements seen in patients with COVID-19. PLA2G7 could be a potential prognostic and therapeutic target in COVID-19.