The emerging new VOC B.1.1.529 (Omicron) variant has raised serious concerns due to multiple mutations, reported significant immune escape, and unprecedented rapid spreading speed. Currently, studies describing the neutralization ability of different homologous and heterologous booster vaccination against Omicron are still lacking. In this study, we explored the immunogenicity of COVID-19 breakthrough patients, BBIBP-CorV homologous booster group and BBIBP-CorV/ZF2001 heterologous booster group against SARS-CoV-2 pseudotypes corresponding to the prototype, Beta, Delta, and the emergent Omicron variant. Notably, at 14 days post two-dose inactivated vaccines, pVNT titre increased to 67.4 GMTs against prototype, 8.85 against Beta and 35.07 against Delta, while neutralization activity against Omicron was below the lower limit of quantitation in 80% of the samples. At day 14 post BBIBP-CorV homologous booster vaccination, GMTs of pVNT significantly increased to 285.6, 215.7, 250.8, 48.73 against prototype, Beta, Delta, and Omicron, while at day 14 post ZF2001 heterologous booster vaccination, GMTs of pVNT significantly increased to 1436.00, 789.6, 1501.00, 95.86, respectively. Post booster vaccination, 100% samples showed positive neutralization activity against Omicron, albeit illustrated a significant reduction (5.86- to 14.98-fold) of pVNT against Omicron compared to prototype at 14 days after the homologous or heterologous vaccine boosters. Overall, our study demonstrates that vaccine-induced immune protection might more likely be escaped by Omicron compared to prototypes and other VOCs. After two doses of inactivated whole-virion vaccines as the “priming” shot, a third heterologous protein subunit vaccine and a homologous inactivated vaccine booster could improve neutralization against Omicron.

Background and aims We aim to assess the safety and immunogenicity of inactivated whole-virion SARS-CoV-2 vaccines in patients with chronic liver diseases (CLD) in this study. Methods This was a prospective, multi-center, open-label study. Participants aged over 18 years with confirmed CLD and healthy volunteers were enrolled. All participants received 2 doses of inactivated whole-virion SARS-CoV-2 vaccines. Adverse reactions were recorded within 14 days after any dose of SARS-CoV-2 vaccine, laboratory testing results were collected after the second dose, and serum samples of enrolled subjects were collected and tested for SARS-CoV-2 neutralizing antibodies at least 14 days after the second dose. Results A total of 581 participants (437 patients with CLD and 144 healthy volunteers) were enrolled from 15 sites in China. Most adverse reactions were mild and transient, and injection site pain (36 [8.2%]) was the most frequently reported adverse event. Three participants had Grade 3 aminopherase elevation (defined as alanine aminopherase>5 upper limits of normal) after the second dose of inactivated whole-virion SARS-CoV-2 vaccination, and only one of them was judged as severe adverse event potentially related to SARS-CoV-2 vaccination. The positive rates of SARS-CoV-2 neutralizing antibodies were 76.8% in non-cirrhotic CLD group, 78.9% in compensated cirrhotic group, 76.7% in decompensated cirrhotic group (P=0.894 among CLD subgroups) and 90.3% in healthy controls (P=0.008 versus CLD group). Conclusion Inactivated whole-virion SARS-CoV-2 vaccines are safe in patients with CLD. Patients with CLD had lower immunological response to SARS-CoV-2 vaccines than healthy population. The immunogenicity is similarly low in non-cirrhotic CLD, compensated cirrhosis and decompensated cirrhosis.

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Background: Coronavirus disease 2019 (COVID-19) has infected more than 4 million people within 4 months. There is an urgent need to properly identify high-risk cases that are more likely to deteriorate even if they present mild diseases on admission. Methods: A multicenter nested case-control study was conducted in four designated hospitals in China enrolling confirmed COVID-19 patients who were mild on admission. Baseline clinical characteristics were compared between patients with stable mild illness (stable mild group) and those who deteriorated from mild to severe illness (progression group). Results: From Jan 17, 2020, to Feb 1, 2020, 85 confirmed COVID-19 patients were enrolled, including 16 in the progression group and 69 in the stable mild group. Compared to stable mild group (n = 69), patients in the progression group (n = 16) were more likely to be older, male, presented with dyspnea, with hypertension, and with higher levels of lactase dehydrogenase and c-reactive protein. In multivariate logistic regression analysis, advanced age (odds ratio [OR], 1.012; 95% confidence interval [CI], 1.020-1.166; P = 0.011) and the higher level of lactase dehydrogenase (OR, 1.012; 95% CI, 1.001-1.024; P = 0.038) were independently associated with exacerbation in mild COVID-19 patients. Conclusion: Advanced age and high LDH level are independent risk factors for exacerbation in mild COVID-19 patients. Among the mild patients, clinicians should pay more attention to the elderly patients or those with high LDH levels.

Objective: To describe and evaluate the impact of diseases control and prevention on epidemics dynamics and clinical features of SARS-CoV-2 outbreak in Shanghai. Design: A retrospective descriptive study Setting: China Participants: Epidemiology information was collected from publicly accessible database. 265 patients admitted to Shanghai Public Health Center with confirmed COVID-19 were enrolled for clinical features analysis. Main outcome measure: Prevention and control measures taken by Shanghai government, epidemiological, demographic, clinical, laboratory and radiology data were collected. Weibull distribution, Chi-square test, Fisher's exact test, t test or Mann-Whitney U test were used in statistical analysis. Results: COVID-19 transmission rate within Shanghai had reduced over 99% than previous speculated, and the exponential growth has been stopped so far. Epidemic was characterized by the first stage mainly composed of imported cases and the second stage where >50% of cases were local. The incubation period was 6.4 (95% CI 5.3 to 7.6) days and the mean onset-admission interval was 5.5 days (95% CI, 5.1 to 5.9). Median time for COVID-19 progressed to severe diseases were 8.5 days (IQR: 4.8-11.0 days). By February 11th, proportion of patients being mild, moderate, severe and critically ill were 1.9%(5/265), 89.8%(238/265), 3.8%(10/265), 4.5%(12/265), respectively; 47 people in our cohort were discharged, and 1 patient died. Conclusion: Strict controlling of the transmission rate at the early stage of an epidemic in metropolis can quickly prohibit the spread of the diseases. Controlling local clusters is the key to prevent outbreaks from imported cases. Most COVID-19 severe cases progressed within 14 days of disease onset. Multiple systemic laboratory abnormalities had been observed before significant respiratory dysfunction. Keyword: COVID-19, SARS-CoV-2, epidemics dynamics, diseases control, clinical features

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Background Data on safety and immunogenicity of coronavirus disease 2019 (COVID-19) vaccination in patients with compensated (C-cirrhosis) and decompensated cirrhosis (D-cirrhosis) are limited. Methods In this prospective multicenter study, adult participants with C-cirrhosis and D-cirrhosis were enrolled and received two doses of inactivated whole-virion COVID-19 vaccines. Adverse events were recorded within 14 days after any dose of vaccination, and serum samples of enrolled patients were collected and tested for SARS-CoV-2 neutralizing antibodies at least 14 days after the second dose. Risk factors for negative neutralizing antibody were analyzed. Results In total, 553 patients were enrolled from 15 centers in China, including 388 and 165 patients with C-cirrhosis and D-cirrhosis. The vaccines were well tolerated, most adverse reactions were mild and transient, and injection site pain (23/388 [5.9%] vs 9/165 [5.5%]) and fatigue (5/388 [1.3%] vs 3/165 [1.8%]) were the most frequently local and systemic adverse events in both the C-cirrhosis and D-cirrhosis groups. Overall, 4.4% (16/363) and 0.3% (1/363) of patients were reported Grades 2 and 3 alanine aminotransferase (ALT) elevations (defined as ALT > 2 upper limit of normal [ULN] but ≤ 5 ULN, and ALT > 5 ULN, respectively). The positive rates of COVID-19 neutralizing antibodies were 71.6% (278/388) and 66.1% (109/165) in C-cirrhosis and D-cirrhosis groups. Notably, Child–Pugh score of B and C levels was an independent risk factor of negative neutralizing antibody. Conclusions Inactivated COVID-19 vaccinations are safe with acceptable immunogenicity in cirrhotic patients, and Child–Pugh score of B and C levels is associated with hyporesponsive to COVID-19 vaccination.

Critically ill patients with coronavirus diseases 2019 (COVID-19) are of grave concern. Those patients usually underwent a stage of excessive inflammation before developing acute respiratory distress syndrome. In this study, we test the hypothesis that short-term, low-to-moderate-dose corticosteroids would benefit patients when used in the early phase of excessive inflammation, namely, the therapeutic window. Among a Shanghai cohort and a validation cohort, we enrolled COVID-19 patients showing marked radiographic progression. Short-term, low-to-moderate-dose corticosteroids were considered for them. After identifying the possible markers for the therapeutic window, we then divided the patients, based on whether they were treated with corticosteroids within the therapeutic window, into the early-start group and control group. We identified that the therapeutic window for corticosteroids was characterized by a marked radiographic progression and lactase dehydrogenase (LDH) less than two times the upper limit of normal (ULN). The Shanghai cohort comprised of 68 patients, including 47 in the early-start group and 21 in the control group. The proportion of patients requiring invasive mechanical ventilation was significantly lower in the early-start group than in the control group (10.6% vs. 33.3%, difference, 22.7%, 95% confidence interval 2.6-44.8%). Among the validation cohort of 51 patients, similar difference of the primary outcome was observed (45.0% vs. 74.2%, P = 0.035). Among COVID-19 patients with marked radiologic progression, short-term, low-to-moderate-dose corticosteroids benefits patients with LDH levels of less than two times the ULN, who may be in the early phase of excessive inflammation.