Separating Daily 1 km PM2.5 Inorganic Chemical Composition in China since 2000 via Deep Learning Integrating Ground, Satellite, and Model Data.

Fine particulate matter (PM2.5) chemical composition has strong and diverse impacts on the planetary environment, climate, and health. These effects are still not well understood due to limited surface observations and uncertainties in chemical model simulations. We developed a four-dimensional spatiotemporal deep forest (4D-STDF) model to estimate daily PM2.5 chemical composition at a spatial resolution of 1 km in China since 2000 by integrating measurements of PM2.5 species from a high-density observation network, satellite PM2.5 retrievals, atmospheric reanalyses, and model simulations. Cross-validation results illustrate the reliability of sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), and chloride (Cl-) estimates, with high coefficients of determination (CV-R2) with ground-based observations of 0.74, 0.75, 0.71, and 0.66, and average root-mean-square errors (RMSE) of 6.0, 6.6, 4.3, and 2.3 µg/m3, respectively. The three components of secondary inorganic aerosols (SIAs) account for 21% (SO42-), 20% (NO3-), and 14% (NH4+) of the total PM2.5 mass in eastern China; we observed significant reductions in the mass of inorganic components by 40-43% between 2013 and 2020, slowing down since 2018. Comparatively, the ratio of SIA to PM2.5 increased by 7% across eastern China except in Beijing and nearby areas, accelerating in recent years. SO42- has been the dominant SIA component in eastern China, although it was surpassed by NO3- in some areas, e.g., Beijing-Tianjin-Hebei region since 2016. SIA, accounting for nearly half (∼46%) of the PM2.5 mass, drove the explosive formation of winter haze episodes in the North China Plain. A sharp decline in SIA concentrations and an increase in SIA-to-PM2.5 ratios during the COVID-19 lockdown were also revealed, reflecting the enhanced atmospheric oxidation capacity and formation of secondary particles.

Effects of SARS-CoV-2 Omicron BA.1 Spike Mutations on T-Cell Epitopes in Mice.

T-cell immunity plays an important role in the control of SARS-CoV-2 and has a great cross-protective effect on the variants. The Omicron BA.1 variant contains more than 30 mutations in the spike and severely evades humoral immunity. To understand how Omicron BA.1 spike mutations affect cellular immunity, the T-cell epitopes of SARS-CoV-2 wild-type and Omicron BA.1 spike in BALB/c (H-2d) and C57BL/6 mice (H-2b) were mapped through IFNγ ELISpot and intracellular cytokine staining assays. The epitopes were identified and verified in splenocytes from mice vaccinated with the adenovirus type 5 vector encoding the homologous spike, and the positive peptides involved in spike mutations were tested against wide-type and Omicron BA.1 vaccines. A total of eleven T-cell epitopes of wild-type and Omicron BA.1 spike were identified in BALB/c mice, and nine were identified in C57BL/6 mice, only two of which were CD4+ T-cell epitopes and most of which were CD8+ T-cell epitopes. The A67V and Del 69-70 mutations in Omicron BA.1 spike abolished one epitope in wild-type spike, and the T478K, E484A, Q493R, G496S and H655Y mutations resulted in three new epitopes in Omicron BA.1 spike, while the Y505H mutation did not affect the epitope. These data describe the difference of T-cell epitopes in SARS-CoV-2 wild-type and Omicron BA.1 spike in H-2b and H-2d mice, providing a better understanding of the effects of Omicron BA.1 spike mutations on cellular immunity.

Analysis of the current situation and related influencing factors of cervical precancer screening under the COVID-19.

OBJECTIVE: This study aims to compare the results of cervical cancer screening in Shanghai General Hospital before and after the COVID-19 epidemic, and analyze the current status and related influencing factors of precervical cancer screening in our hospital under the COVID-19 pandemic. METHODS: The data of 13,748 women of cervical precancer screening with HPV in Shanghai General Hospital were selected.The data included human papillomavirus (HPV), thin-layer liquid-based cytology test (TCT), colposcopy and cervical biopsy, and pathological diagnosis results after trachelectomy in 2019 and 2020, and were analyzed and compared. RESULTS: The detection rates of precancerous lesions and cervical cancer were 2.9061/10,000 and 29.26/10,000 respectively. There was a significant difference in the rate of comparison (χ2 = 30.361, P = 0.000; χ2 = 7.682, P = 0.006);(2) Missing detection rate: In 2020, other positive subtypes other than HPV 16 and 18 who need TCT, the colposcopy, and the histopathological examination missing detection rate were higher than those in 2019 (P < 0.05);(3) Abnormal rate of examination: the abnormal rate of HPV, TCT, and histopathology in 2020 was higher than those in 2019 (P < 0.05);(4) Histopathological analysis: The detection rate of high-grade lesions and invasive cancer in 2020 was higher than those in 2019, and the detection rate of low-grade lesions was lower than that in 2019 (P < 0.05); Conclusion: Health authorities should formulate intervention measures to cope with the safe and timely implementation of cervical cancer screening and subsequent follow-up management during public health emergency.

Comparative characterization of antibody responses induced by Ad5-vectored spike proteins of emerging SARS-CoV-2 VOCs.

Highly divergent SARS-CoV-2 variants have continuously emerged and spread around the world, and updated vaccines and innovative vaccination strategies are urgently needed to address the global SARS-COV2 pandemic. Here, we established a series of Ad5-vectored SARS-CoV-2 variant vaccines encoding multiple spike proteins derived from the Alpha, Beta, Gamma, Epsilon, Kappa, Delta and Omicron lineages and analyzed the antibody immune responses induced by single-dose and prime-boost vaccination strategies against emerging SARS-CoV-2 variants of concern (VOCs). Single-dose vaccination with SARS-CoV-2 variant vaccines tended to elicit the optimal self-matched neutralizing effects, and Ad5-B.1.351 produced more broad-spectrum cross-neutralizing antibodies against diverse variants. In contrast, prime-boost vaccination further strengthened and broadened the neutralizing antibody responses against highly divergent SARS-CoV-2 variants. The heterologous administration of Ad5-B.1.617.2 and Ad5-B.1.429 to Ad5-WT-primed mice resulted in superior antibody responses against most VOCs. In particular, the Omicron spike could only stimulate self-matched neutralizing antibodies with infrequent cross-reactivities to other variants used in single-dose vaccination strategies; moreover, with prime-boost regimens, this vaccine elicited an optimal specific neutralizing antibody response to Omicron, and prompted cross-antibody responses against other VOCs that were very similar to those obtained with Ad5-WT booster. Overall, this study delineated the unique characteristics of antibody responses to the SARS-CoV-2 VOC spikes with the single-dose or prime-boost vaccination strategies and provided insight into the vaccine development of next SARS-CoV-2 VOCs.

Safety, tolerability, and immunogenicity of an aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in adults: preliminary report of an open-label and randomised phase 1 clinical trial.

BACKGROUND: SARS-CoV-2 has caused millions of deaths, and, since Aug 11, 2020, 20 intramuscular COVID-19 vaccines have been approved for use. We aimed to evaluate the safety and immunogenicity of an aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in adults without COVID-19 from China. METHOD: This was a randomised, single-centre, open-label, phase 1 trial done in Zhongnan Hospital (Wuhan, China), to evaluate the safety and immunogenicity of the Ad5-nCoV vaccine by aerosol inhalation in adults (≥18 years) seronegative for SARS-CoV-2. Breastfeeding or pregnant women and people with major chronic illnesses or history of allergies were excluded. Participants were enrolled and randomly assigned (1:1:1:1:1) into five groups to be vaccinated via intramuscular injection, aerosol inhalation, or both. Randomisation was stratified by sex and age (18-55 years or ≥56 years) using computer-generated randomisation sequences (block sizes of five). Only laboratory staff were masked to group assignment. The participants in the two aerosol groups received an initial high dose (2 × 1010 viral particles; HDmu group) or low dose (1 × 1010 viral particles; LDmu group) of Ad5-nCoV vaccine on day 0, followed by a booster on day 28. The mixed vaccination group received an initial intramuscular (5 × 1010 viral particles) vaccine on day 0, followed by an aerosolised booster (2 × 1010 viral particles) vaccine on day 28 (MIX group). The intramuscular groups received one dose (5 × 1010 viral particles; 1Dim group) or two doses (10 × 1010 viral particles; 2Dim group) of Ad5-nCoV on day 0. The primary safety outcome was adverse events 7 days after each vaccination, and the primary immunogenicity outcome was anti-SARS-CoV-2 spike receptor IgG antibody and SARS-CoV-2 neutralising antibody geometric mean titres at day 28 after last vaccination. This trial is registered with ClinicalTrials.gov, number NCT04552366. FINDINGS: Between Sept 28, 2020, and Sept 30, 2020, 230 individuals were screened for inclusion, of whom 130 (56%) participants were enrolled into the trial and randomly assigned into one of the five groups (26 participants per group). Within 7 days after vaccination, adverse events occurred in 18 (69%) in the HDmu group, 19 (73%) in the LDmu group, 19 (73%) in the MIX group, 19 (73%) in the 1Dim group, and 15 (58%) in the 2Dim group. The most common adverse events reported 7 days after the first or booster vaccine were fever (62 [48%] of 130 participants), fatigue (40 [31%] participants), and headache (46 [35%] participants). More adverse events were reported in participants who received intramuscular vaccination, including participants in the MIX group (49 [63%] of 78 participants), than those who received aerosol vaccine (13 [25%] of 52 participants) after the first vaccine vaccination. No serious adverse events were noted within 56 days after the first vaccine. At days 28 after last vaccination, geometric mean titres of SARS-CoV-2 neutralising antibody was 107 (95% CI 47-245) in the HDmu group, 105 (47-232) in the LDmu group, 396 (207-758) in the MIX group, 95 (61-147) in the 1Dim group, and 180 (113-288) in the 2Dim group. The geometric mean concentrations of receptor binding domain-binding IgG was 261 EU/mL (95% CI 121-563) in the HDmu group, 289 EU/mL (138-606) in the LDmu group, 2013 EU/mL (1180-3435) in the MIX group, 915 EU/mL (588-1423) in the 1Dim group, and 1190 EU/mL (776-1824) in the 2Dim group. INTERPRETATION: Aerosolised Ad5-nCoV is well tolerated, and two doses of aerosolised Ad5-nCoV elicited neutralising antibody responses, similar to one dose of intramuscular injection. An aerosolised booster vaccination at 28 days after first intramuscular injection induced strong IgG and neutralising antibody responses. The efficacy and cost-effectiveness of aerosol vaccination should be evaluated in future studies. FUNDING: National Key Research and Development Programme of China and National Science and Technology Major Project. TRANSLATION: For the Chinese translation of the Summary see Supplementary Material.

Assessment value of neutrophil-to-lymphocyte ratio for prognosis in coronavirus disease 2019

Objective: To explore the assessment value of neutrophil-to-lymphocyte ratio(NLR) for prognosis in coronavirus disease 2019(COVID-19).

Acute Kidney Injury in Hospitalized Patients Infected with COVID-19 from Wuhan, China: A Retrospective Study.

BACKGROUND: Since the first diagnosed case of infection with the novel coronavirus (SARS-CoV-2), there has been a rapid spread of the disease with an increasing number of cases confirmed every day, as well as a rising death toll. An association has been reported between acute kidney injury (AKI) and mortality in patients infected with SARS-CoV-2. Therefore, our study was conducted to explore possible risk factors of AKI as well as whether AKI was a risk factor for worse outcome, especially mortality among patients with coronavirus disease (COVID-19). METHODS: We included all hospital admissions with confirmed or clinically diagnosed COVID-19 from January 29 to February 25, 2020. We collected demographic and epidemiological information, past medical history, symptoms, laboratory tests, treatments, and outcome data from electronic medical records. A total of 492 patients with diagnosed or clinically diagnosed COVID-19 were included in this study. RESULTS: The prevalence rate of AKI was 7.32%. Among the factors associated with AKI, males versus females (aOR 2.73), chronic kidney disease (aOR 42.2), hypertension (aOR 2.82), increased leucocytes (aOR 6.08), and diuretic use (aOR 7.89) were identified as independent risk factors for AKI among patients infected by SARS-CoV-2. There was a significant difference in hospital fees and death in patients with and without AKI (p < 0.05). The mortality rate in patients with AKI was 63.9%. CONCLUSIONS: AKI was widespread among patients with COVID-19. The risk factors of AKI in COVID-19 patients included sex, chronic kidney disease, hypertension, infection, and diuretic use. AKI may be associated with a worse outcome, especially mortality in COVID-19 patients.

Clinical features of patients undergoing hemodialysis with COVID-19.

Hemodialysis patients are susceptible to coronavirus disease 2019 (COVID-19). The aim of this study was to describe the epidemiological, clinical characteristics, and mortality-related risk factors for those who undergoing hemodialysis with COVID-19. We conducted a retrospective study. A total of 49 hemodialysis patients with COVID-19 (Group 1) and 74 uninfected patients (Group 2) were included. For patients in Group 1, we found the median age was 62 years (36-89 years), 59.3% were male, and the median dialysis vintage was 26 months. Twenty-eight patients (57%) had three or more comorbidities and two patients (4%) died. The most common symptoms were fever (32.7%) and dry cough (46.9%), while nine patients (18.4%) were asymptomatic. Blood routine tests indicated lymphocytopenia, the proportion of lymphocyte subsets was generally reduced, and chest CT scans showed ground-glass opacity (45.8%) and patchy shadowing (35.4%). However, these findings were not specific to hemodialysis patients with COVID-19, and similar manifestations could be found in patients without SARS-CoV-2 infection. In conclusion, for hemodialysis patients with COVID-19, lymphocytopenia and ground-glass opacities or patchy opacities were common but not specific to them, early active treatment and interventions against nosocomial infection can significantly reduce the mortality and the risk of SARS-CoV-2 infection.

A single dose of an adenovirus-vectored vaccine provides protection against SARS-CoV-2 challenge.

The unprecedented coronavirus disease 2019 (COVID-19) epidemic has created a worldwide public health emergency, and there is an urgent need to develop an effective vaccine to control this severe infectious disease. Here, we find that a single vaccination with a replication-defective human type 5 adenovirus encoding the SARS-CoV-2 spike protein (Ad5-nCoV) protect mice completely against mouse-adapted SARS-CoV-2 infection in the upper and lower respiratory tracts. Additionally, a single vaccination with Ad5-nCoV protects ferrets from wild-type SARS-CoV-2 infection in the upper respiratory tract. This study suggests that the mucosal vaccination may provide a desirable protective efficacy and this delivery mode is worth further investigation in human clinical trials.

A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2.

Developing therapeutics against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be guided by the distribution of epitopes, not only on the receptor binding domain (RBD) of the Spike (S) protein but also across the full Spike (S) protein. We isolated and characterized monoclonal antibodies (mAbs) from 10 convalescent COVID-19 patients. Three mAbs showed neutralizing activities against authentic SARS-CoV-2. One mAb, named 4A8, exhibits high neutralization potency against both authentic and pseudotyped SARS-CoV-2 but does not bind the RBD. We defined the epitope of 4A8 as the N-terminal domain (NTD) of the S protein by determining with cryo-eletron microscopy its structure in complex with the S protein to an overall resolution of 3.1 angstroms and local resolution of 3.3 angstroms for the 4A8-NTD interface. This points to the NTD as a promising target for therapeutic mAbs against COVID-19.