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Background: The SARS-CoV-2 non-Spike (S) structural protein targets on nucleocapsid (N), membrane (M) and envelope (E), critical in the host cell interferon response and memory T-cell immunity, are grossly overlooked in COVID vaccine development. The current Spike-only vaccines bear an intrinsic shortfall for promotion of a fuller T cell immunity. Vaccines designed to target conserved epitopes could elicit strong cellular immune responses that would synergize with B cell responses and lead to long-term vaccine success. We pursue a universal (pan-SARS-CoV-2) vaccine against Delta, Omicrons and ever-emergent new mutants. Methods and findings: We explored booster immunogenicity of UB-612, a multitope-vaccine that contains S1-RBD-sFc protein and sequence-conserved promiscuous Th and CTL epitope peptides on the Sarbecovirus N, M and S2 proteins. To a subpopulation (N = 1,478) of infection-free participants (aged 18–85 years) involved in a two-dose Phase-2 trial, a UB-612 booster (third dose) was administered 6–8 months after the second dose. The immunogenicity was evaluated at 14 days post-booster with overall safety monitored until the end of study. The booster induced high viral-neutralizing antibodies against live Wuhan WT (VNT50, 1,711) and Delta (VNT50, 1,282); and against pseudovirus WT (pVNT50, 11,167) vs. Omicron BA.1/BA.2/BA.5 variants (pVNT50, 2,314/1,890/854), respectively. The lower primary neutralizing antibodies in the elderly were uplifted upon boosting to approximately the same high level in young adults. UB-612 also induced potent, durable Th1-oriented (IFN-γ+-) responses (peak/pre-boost/post-boost SFU/106 PBMCs, 374/261/444) along with robust presence of cytotoxic CD8+ T cells (peak/pre-boost/post-boost CD107a+-Granzyme B+, 3.6%/1.8%/1.8%). This UB-612 booster vaccination is safe and well tolerated without SAEs. Conclusions: By targeting conserved epitopes on viral S2, M and N proteins, UB-612 could provide potent, broad and long-lasting B-cell and T-cell memory immunity and offers the potential as a universal vaccine to fend off Omicrons and new VoCs without resorting to Omicron-specific immunogens. Trial registration: ClinicalTrials.gov: NCT04773067; ClinicalTrials.gov ID: NCT05293665; ClinicalTrials.gov ID: NCT05541861. Author summary: The Omicron variant of SARS-CoV-2 has swept the globe with a rapid succession of dominating sublineages from BA.1, BA.2, to the current BA.5 with increasing infectivity and antibody evasion. Concerningly, the non-Spike structure proteins that promote T-cell immunity have been grossly overlooked in vaccine development. Looking beyond short-interval boosters and omicron-updated vaccines, a pragmatic approach to curbing ever-emergent new mutants would be "universal (pan-SARS-CoV-2) vaccines" as exemplified by UB-612, a multitope-vaccine armed with Spike (S1-RBD and S2) and non-Spike (Nucleocapsid N and Membrane M) targets, allowing booster vaccination to elicit broadly-recognizing and durable B-/T-cell memory immunity. Sequence-conserved Th/CTL epitope peptides were designed from S2, N and M proteins to synergistically enhance memory helper and cytotoxic T-cell immunity and RBD targeted B-cell immunity. [ABSTRACT FROM AUTHOR]

Purpose: To compare outcomes of deep anterior lamellar keratoplasty (DALK) and corneal cross-linking (CXL) in patients with advanced keratoconus, with the primary aim of assessing CXL as a potential therapeutic alternative. Study design: Retrospective, multi-center, comparative study. Methods: Patients with advanced keratoconus (maximum keratometry reading (K-max) > 58D, best spectacle-corrected visual acuity worse than 0.52logMAR), undergoing either DALK or CXL treatment at four tertiary ophthalmic centers in Wenzhou, Hangzhou, Nanjing and Wuhan were included. Visual acuity, refractive error, corneal topography and complications were evaluated at baseline and at least 2 year postoperatively. Results: 75 eyes of 72 patients were included, of which 37 eyes underwent DALK and 38 eyes, CXL. A larger reduction in Kmax was observed in the DALK group (-18.18 ± 9.44 D versus -1.10 ± 2.70D, p < 0.001). Seven eyes (18%) in the CXL group showed progression of keratoconus. No disease progression was observed in the DALK group. Greater improvements in best spectacle-corrected visual acuity (logMAR) were observed in the DALK group (-0.59 ± 0.25 versus -0.24 ± 0.44, p < 0.001). Conclusions: Compared to CXL, DALK leads to larger reductions in Kmax and better improvement in visual acuity in advanced keratoconus. [ABSTRACT FROM AUTHOR]

Background: The current coronavirus disease 2019 (COVID-19) is a public health emergency. In this study, we aimed to evaluate the risk factors for mortality in severe and critical COVID-19 patients.Methods: We performed a retrospective study of patients diagnosed with severe and critical COVID-19 from four hospitals in Wuhan, China, by evaluating the clinical characteristics and laboratory results, and using Cox proportional hazards model to assess the risk factors involved in disease progression.Results: In total, 446 patients with COVID-19 were enrolled. The study indicated a high mortality rate (20.2%) in severe and critical COVID-19 patients. At the time of admission, all patients required oxygen therapy, and 52 (12%) required invasive mechanical ventilation, of which 50 (96%) died. The univariate Cox proportional hazards model showed a white blood cell count of more than 10 × 109/L (HR 3.993,95%CI 2.469 to 6.459) that correlated with an increased mortality rate. The multivariable Cox proportional hazards model demonstrated that older age (HR 1.066, 95% CI 1.043 to 1.089) and higher white blood cell count (HR 1.135, 95% CI 1.080 to 1.192) were independent risk factors for determining COVID-19 associated mortality.Conclusions: COVID-19 is associated with a significant risk of morbidity and mortality in the population. Older age and higher white blood cell count were found to be independent risk factors for mortality. [ABSTRACT FROM AUTHOR]

Since the first case of COVID‐19 reported in late December of 2019 in Wuhan, China, the SARS‐CoV‐2 virus has caused approximately 20 million infections and 732 thousand deaths around the world by 11 August 2020. Although the pathogen generally infects the respiratory system, whether it is present in the bloodstream and whether it poses a threat to the blood supply during the period of the outbreak is of serious public concern. In this study, we used enzyme‐linked immunosorbent assay (ELISA) to screen total antibodies against SARS‐CoV‐2 in 2199 blood donors, who had donated blood at the Guangzhou Blood Center during the epidemic. The Ig‐reactive samples were further characterized for IgA, IgG, and IgM subtypes by ELISA and viral nucleic acid by real‐time polymerase chain reaction. Among the 2199 plasma samples, seven were reactive under total antibodies' screening. Further testing revealed that none of them had detectable viral nucleic acid or IgM antibody, but two samples contained IgA and IgG. The IgG antibody titers of both positive samples were 1:16 and 1:4, respectively. Our results indicated a low prevalence of past SARS‐CoV‐2 infection in our blood donors, as none of the tests were positive for viral nucleic acid and only 2 out of 2199 (0.09%) of samples were positive for IgG and IgA. There would be a limited necessity for the implementation of such testing in blood screening in a COVID‐19 low‐risk area. Highlights: The prevalence of past SARS‐CoV‐2 infection was relatively low among voluntary blood donors in Guangzhou, ChinaScreening of SARS‐CoV‐2 among voluntary blood donors may not be in priority in Guangzhou, China, because of the low risk of transmission via transfusion. [ABSTRACT FROM AUTHOR]

Harmonized development of urban agricultural functions is necessary to ensure sustainable urban development, in which rational utilization of land plays a key role. With rapid urbanization, urban agricultural land has been encroached, the development of urban agriculture functions has become unbalanced, and differences between land, agriculture, and urban systems have become more evident. In this study, we analyzed the characteristics of land use structure and the functional spatial differentiation of urban agriculture in Wuhan and studied the quantitative relationship and influence mechanisms between them. We found that the spatial differentiation of urban agricultural function in Wuhan was closely related to the urban developmental structure, comprehensive index of land use degree, and information entropy of land use structure; moreover, urban agricultural land rate showed different effects on urban agricultural functions of different clusters. Based on these results, we proposed optimization strategies for streets and towns with different development levels of urban agricultural functions to promote sustainable development of both urban agriculture and cities through the rational use of land. • Functional spatial differentiation and land use of urban agriculture were studied. • Urban agricultural functions represented typical spatial differentiation. • Land use structure showed varying effects on urban agricultural functions. • Strategies were proposed for sustainable urban development and urban agriculture. [ABSTRACT FROM AUTHOR]

• We first described the epidemiological characteristics of patients with SARS-CoV-2 in Hunan and these patients were early mild cases. • The clinical symptoms, laboratory results, and imaging reports of patients with COVID-19 in the Hunan area were different from Wuhan area. • For non-Wuhan epidemic areas, more attention should be paid to the nucleic acid test results of throat swabs and stools. • Reduced whole blood lymph count can be used as an adjuvant diagnosis of early SARS-CoV-2 infection. • Attention should be paid to asymptomatic carriers, and this is of great significance for the control of the global epidemic. In December 2019, coronavirus Disease 2019 (COVID-19) occurred in Wuhan, Hubei Province, China. The disease has rapidly spread from Wuhan to other regions. To describe the clinical manifestations and epidemiological characteristics of patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in Hunan Province in 2020. From January 19 to February 7, 2020, 33 patients with positive in nucleic acid test of pharyngeal swab were retrospectively collected and analyzed. There are 33 COVID-19 patients (16 male, 17 female), and the median age was 46 years. Nineteen patients (48 %) were associated with a family cluster outbreak. Seventeen patients (52 %) had traveled or lived in Hubei Province. These patients are early mild cases, most common symptoms are fever [23 (70 %)] and cough [13 (39 %)]. Most patients' white blood cell counts are normal, while they manifest as significant reduction in lymphocytes [17/28 (61 %)]. The levels of c-reactive protein and erythrocyte sedimentation rate suggest a typical viral infection. Procalcitonin did not increase and D-dimer increased slightly. Lactate dehydrogenase (LDH) levels have elevated in most patients. CT images of these patients showed bilateral multiple plaques or nodular ground-glass opacities (68.4 %). Fecal nucleic acid results were positive in eight COVID-19 patients accompanied with diarrhea. Tear nucleic acid results were negative in six COVID-19 patients. And four asymptomatic patients were infected with SARS-CoV-2. The clinical symptoms, laboratory results and imaging reports of patients with COVID-19 in Hunan area are significantly different from those in Wuhan area. For non-Wuhan epidemic areas, more attention should be paid to nucleic acid test results of throat swabs and stools, and it is not easily to diagnose based on clinical symptoms and CT results. Reduced whole blood lymph count can be used as an adjuvant diagnosis of early SARS-CoV-2 infection. Attention should be paid to asymptomatic carriers, which is of great significance for the control of the global epidemic. [ABSTRACT FROM AUTHOR]