Effect of Moderate to Severe Hepatic Steatosis on Vaccine Immunogenicity against Wild-Type and Mutant Virus and COVID-19 Infection among BNT162b2 Recipients.

BACKGROUND: We aimed to investigate the effect of non-alcoholic fatty liver disease (NAFLD) on BNT162b2 immunogenicity against wild-type SARS-CoV-2 and variants and infection outcome, as data are lacking. METHODS: Recipients of two doses of BNT162b2 were prospectively recruited. Outcomes of interest were seroconversion of neutralizing antibody by live virus microneutralization (vMN) to SARS-CoV-2 strains (wild-type, delta and omicron variants) at day 21, 56 and 180 after first dose. Exposure of interest was moderate-to-severe NAFLD (controlled attenuation parameter ≥ 268 dB/M on transient elastography). We calculated adjusted odds ratio (aOR) of infection with NAFLD by adjusting for age, sex, overweight/obesity, diabetes and antibiotic use. RESULTS: Of 259 BNT162b2 recipients (90 (34.7%) male; median age: 50.8 years (IQR: 43.6-57.8)), 68 (26.3%) had NAFLD. For wild type, there was no difference in seroconversion rate between NAFLD and control groups at day 21 (72.1% vs. 77.0%; p = 0.42), day 56 (100% vs. 100%) and day 180 (100% and 97.2%; p = 0.22), respectively. For the delta variant, there was no difference also at day 21 (25.0% vs. 29.5%; p = 0.70), day 56 (100% vs. 98.4%; p = 0.57) and day 180 (89.5% vs. 93.3%; p = 0.58), respectively. For the omicron variant, none achieved seroconversion at day 21 and 180. At day 56, there was no difference in seroconversion rate (15.0% vs. 18.0%; p = 0.76). NAFLD was not an independent risk factor of infection (aOR: 1.50; 95% CI: 0.68-3.24). CONCLUSIONS: NAFLD patients receiving two doses of BNT162b2 had good immunogenicity to wild-type SARS-CoV-2 and the delta variant but not the omicron variant, and they were not at higher risk of infection compared with controls.

Association between Gut Microbiota and SARS-CoV-2 Infection and Vaccine Immunogenicity.

Gut microbiota is increasingly recognized to play a pivotal role in various human physiological functions and diseases. Amidst the COVID-19 pandemic, research has suggested that dysbiosis of the gut microbiota is also involved in the development and severity of COVID-19 symptoms by regulating SARS-CoV-2 entry and modulating inflammation. Previous studies have also suggested that gut microbiota and their metabolites could have immunomodulatory effects on vaccine immunogenicity, including influenza vaccines and oral rotavirus vaccines. In light of these observations, it is possible that gut microbiota plays a role in influencing the immune responses to COVID-19 vaccinations via similar mechanisms including effects of lipopolysaccharides, flagellin, peptidoglycan, and short-chain fatty acids. In this review, we give an overview of the current understanding on the role of the gut microbiota in COVID-19 manifestations and vaccine immunogenicity. We then discuss the limitations of currently published studies on the associations between gut microbiota and COVID-19 vaccine outcomes. Future research directions shall be focused on the development of microbiota-based interventions on improving immune response to SARS-CoV-2 infection and vaccinations.

COVID-19 vaccine immunogenicity among chronic liver disease patients and liver transplant recipients: A meta-analysis.

BACKGROUND/AIMS: Data of coronavirus disease 2019 (COVID-19) vaccine immunogenicity among chronic liver disease (CLD) and liver transplant (LT) patients are conflicting. We performed meta-analysis to examine vaccine immunogenicity regarding etiology, cirrhosis status, vaccine platform and type of antibody. METHODS: We collected data via three databases from inception to February 16, 2022, and reported pooled seroconversion rate, T cell response and safety data after two vaccine doses. RESULTS: Twenty-eight (CLD only: 5; LT only: 18; both: 2; LT with third dose: 3) observational studies of 3,945 patients were included. For CLD patients, seroconversion rate ranged between 84% (95% confidence interval [CI], 76-90%) and 91% (95% CI, 83-95%), based predominantly on neutralizing antibody and anti-spike antibody, respectively. Seroconversion rate was 81% (95% CI, 76-86%) in chronic hepatitis B, 96% (95% CI, 93-97%) in non-alcoholic fatty liver disease, 85% (95% CI, 75-91%) in cirrhosis and 85% (95% CI, 78-90%) in non-cirrhosis, 86% (95% CI, 78-92%) for inactivated vaccine and 89% (95% CI, 71-96%) for mRNA vaccine. The pooled seroconversion rate of anti-spike antibody was 66% (95% CI, 55-75%) after two doses of mRNA vaccines and 88% (95% CI, 58-98%) after third dose among LT recipients. T cell response rate was 65% (95% CI, 30-89%). Prevalence of adverse events was 27% (95% CI, 18-38%) and 63% (95% CI, 39-82%) among CLD and LT groups, respectively. CONCLUSION: CLD patients had good humoral response to COVID-19 vaccine, while LT recipients had lower response.

Association between Recent Usage of Antibiotics and Immunogenicity within Six Months after COVID-19 Vaccination.

Background: Gut microbiota can be associated with COVID-19 vaccine immunogenicity. We investigated whether recent antibiotic use influences BNT162b2 vaccine immunogenicity. Methods: BNT162b2 recipients from three centers were prospectively recruited. Outcomes of interest were seroconversion of neutralising antibody (NAb) at day 21, 56 and 180 after first dose. We calculated the adjusted odds ratio (aOR) of seroconversion with antibiotic usage (defined as ever use of any antibiotics within six months before first dose of vaccine) by adjusting for covariates including age, sex, smoking, alcohol, and comorbidities. Results: Of 316 BNT162b2 recipients (100 [31.6%] male; median age: 50.1 [IQR: 40.0-57.0] years) recruited, 29 (9.2%) were antibiotic users. There was a trend of lower seroconversion rates in antibiotic users than non-users at day 21 (82.8% vs. 91.3%; p = 0.14) and day 56 (96.6% vs. 99.3%; p = 0.15), but not at day 180 (93.3% vs. 94.1%). A multivariate analysis showed that recent antibiotic usage was associated with a lower seroconversion rate at day 21 (aOR 0.26;95% CI: 0.08-0.96). Other factors associated with a lower seroconversion rate after first dose of the BNT162b2 vaccine included age ≥ 60 years (aOR: 0.34;95% CI: 0.13-0.95) and male sex (aOR: 0.14, 95% CI: 0.05-0.34). There were no significant factors associated with seroconversion after two doses of BNT16b2, including antibiotic use (aOR: 0.03;95% CI: 0.001-1.15). Conclusions: Recent antibiotic use may be associated with a lower seroconversion rate at day 21 (but not day 56 or 180) among BNT162b2 recipients. Further long-term follow-up data with a larger sample size is needed to reach a definite conclusion on how antibiotics influence immunogenicity and the durability of the vaccine response.

Effect of moderate-to-severe hepatic steatosis on neutralising antibody response among BNT162b2 and CoronaVac recipients.

BACKGROUND/AIMS: Studies of hepatic steatosis (HS) effect on COVID-19 vaccine immunogenicity are lacking. We aimed to compare immunogenicity of BNT162b2 and CoronaVac among moderate/severe HS and control subjects. METHODS: Two hundred ninety-five subjects who received BNT162b2 or CoronaVac vaccines from five vaccination centers were categorized into moderate/severe HS (controlled attenuation parameter ≥268 dB/m on transient elastography) (n=74) or control (n=221) groups. Primary outcomes were seroconversion rates of neutralising antibody by live virus Microneutralization (vMN) assay (titer ≥10) at day21 (BNT162b2) or day28 (CoronaVac) and day56 (both). Secondary outcome was highest-tier titer response (top 25% of vMN titer; cutoff: 160 [BNT162b2] and 20 [CoronaVac]) at day 56. RESULTS: For BNT162b2 (n=228, 77.3%), there was no statistical differences in seroconversion rates (day21: 71.7% vs. 76.6%; day56: 100% vs. 100%) or vMN geometric mean titer (GMT) (day21: 13.2 vs. 13.3; day56: 91.9 vs. 101.4) among moderate/severe HS and control groups respectively. However, lower proportion of moderate/severe HS patients had highest-tier response (day56: 5.0% vs. 15.5%; P=0.037). For CoronaVac (n=67, 22.7%), there was no statistical differences in seroconversion rates (day21: 7.1% vs. 15.1%; day56: 64.3% vs. 83.0%) or vMN GMT (5.3 vs. 5.8,) at day28. However, moderate/severe HS patients had lower vMN GMT (9.1 vs. 14.8, P=0.021) at day 56 with lower proportion having highest-tier response (21.4% vs. 52.8%, P=0.036). CONCLUSION: While there was no difference in seroconversion rate between moderate/severe HS and control groups after two doses of vaccine, a lower proportion of moderate/severe HS patients achieved highest-tier response for either BNT162b2 or CoronaVac.

Housing Market in the Time of Pandemic: A Price Gradient Analysis from the COVID-19 Epicentre in China

While the outbreak of the COVID-19 disease has caused asset markets to experience an unprecedented spike of risk and uncertainty worldwide, the real estate market in many global cities appears to be immune to the adverse effects. How does COVID-19 affect urban housing markets? This study is a first attempt to identify the pandemic’s impact on house prices by applying a price gradient analysis to the COVID-19 epicentre in China. Considering microlevel housing transaction data in 62 areas from nine districts in Wuhan City from January 2019 to July 2020, the hedonic pricing and the price gradient models suggest that there was, respectively, a 4.8% and a 5.0–7.0% year-on-year fall in house prices immediately after the pandemic outbreak. Although house prices rebounded after the lockdown period, the gradient models show that the price gradients were flattened from the epicentre to the urban peripherals. The price premiums in high-density areas were also substantially discounted after the city’s lockdown. Our findings are robust to different model specifications. The implication is that the risk associated with the pandemic is localised and transitory in nature. People may be able to internalise the risk by residing in low-density residential areas.

Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples From a Hong Kong Cohort: Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which has been characterized by fever, respiratory, and gastrointestinal symptoms as well as shedding of virus RNA into feces. We performed a systematic review and meta-analysis of published gastrointestinal symptoms and detection of virus in stool and also summarized data from a cohort of patients with COVID-19 in Hong Kong. METHODS: We collected data from the cohort of patients with COVID-19 in Hong Kong (N = 59; diagnosis from February 2 through February 29, 2020),and searched PubMed, Embase, Cochrane, and 3 Chinese databases through March 11, 2020, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We analyzed pooled data on the prevalence of overall and individual gastrointestinal symptoms (loss of appetite, nausea, vomiting, diarrhea, and abdominal pain or discomfort) using a random effects model. RESULTS: Among the 59 patients with COVID-19 in Hong Kong, 15 patients (25.4%) had gastrointestinal symptoms, and 9 patients (15.3%) had stool that tested positive for virus RNA. Stool viral RNA was detected in 38.5% and 8.7% among those with and without diarrhea, respectively (P = .02). The median fecal viral load was 5.1 log10 copies per milliliter in patients with diarrhea vs 3.9 log10 copies per milliliter in patients without diarrhea (P = .06). In a meta-analysis of 60 studies comprising 4243 patients, the pooled prevalence of all gastrointestinal symptoms was 17.6% (95% confidence interval [CI], 12.3-24.5); 11.8% of patients with nonsevere COVID-19 had gastrointestinal symptoms (95% CI, 4.1-29.1), and 17.1% of patients with severe COVID-19 had gastrointestinal symptoms (95% CI, 6.9-36.7). In the meta-analysis, the pooled prevalence of stool samples that were positive for virus RNA was 48.1% (95% CI, 38.3-57.9); of these samples, 70.3% of those collected after loss of virus from respiratory specimens tested positive for the virus (95% CI, 49.6-85.1). CONCLUSIONS: In an analysis of data from the Hong Kong cohort of patients with COVID-19 and a meta-analysis of findings from publications, we found that 17.6% of patients with COVID-19 had gastrointestinal symptoms. Virus RNA was detected in stool samples from 48.1% patients, even in stool collected after respiratory samples had negative test results. Health care workers should therefore exercise caution in collecting fecal samples or performing endoscopic procedures in patients with COVID-19, even during patient recovery.