Omicron BA.1-specific T-cell responses in adults vaccinated with CoronaVac or BNT162b2 in Hong Kong: an observational cohort study.

BACKGROUND: The primary aim of using vaccines in public health responses to SARS-CoV-2 variants of concern is to reduce incidence of severe disease, for which T-cell responses are essential. There is a paucity of data on vaccine-induced T-cell immunity to omicron (B.1.1.529). We aimed to compare SARS-CoV-2 omicron BA.1-specific T-cell responses in adults vaccinated with CoronaVac or BNT162b2. METHODS: For this observational cohort, we recruited adults (aged ≥18 years) from three vaccination centres in Hong Kong. We included participants from four cohorts (cohort 1: participants who received two doses of either BNT162b2 or CoronaVac, cohort 2: participants who received two doses and a booster, cohort 3: participants who received two doses and a booster and had a breakthrough omicron infection, and cohort 4: participants who had a previous non-omicron infection and subsequently received one dose of vaccine). People with confirmed history of COVID-19 at recruitment were excluded from cohort 1 and cohort 2. We collected blood samples before vaccination (for cohort 1 and 2), 1-month following vaccination (for all cohorts), and during convalescence for cohort 3 and 4) and determined the proportion of IFNγ+CD4+ and IFNγ+CD8+ T cells in peripheral blood against SARS-CoV-2 using flow cytometry with peptide pools of SARS-CoV-2 wild type or omicron BA.1. The primary outcome was proportion of CD4+ and CD8+ T cells against SARS-CoV-2 1 month after exposure (ie, vaccination or breakthrough infection). FINDINGS: Overall, between May 21, 2020, and Aug 31, 2021, we recruited 659 participants (231 [35%] men and 428 [65%] women). Of these participants, 428 were included in cohort 1 (214 [50%] received BNT162b2 and 214 [50%] received CoronaVac); 127 in cohort 2 (48 [38%] received all BNT162b2, 40 [31%] received all CoronaVac, and 39 [31%] received two CoronaVac and a booster with BNT162b2); 58 in cohort 3, and 46 in cohort 4 (16 [35%] received CoronaVac and 30 [65%] received BNT162b2). Vaccine-induced T-cell responses to the wild-type and omicron BA.1 variants were generally similar in adults receiving two doses of either CoronaVac (CD4+ cells p=0·33; CD8+ cells p=0·70) or BNT162b2 (CD4+ cells p=0·28; CD8+ cells p=1·0). Using a peptide pool of all structural proteins for stimulation, BNT162b2 induced a higher median frequency of omicron-specific CD4+ T cells in adults younger than 60 years (CD4+ cells 0·012% vs 0·010%, p=0·031; CD8+ cells 0·003% vs 0·000%, p=0·055) and omicron-specific CD8+ T cells in people aged 60 years or older (CD4+ cells 0·015% vs 0·006%, p=0·0070; CD8+ cells 0·007% vs 0·000%, p=0·035). A booster dose of either BNT162b2 or CoronaVac after two doses of CoronaVac boosted waning T-cell responses, but T-cell responses did not exceed those at 1 month after the second dose (CoronaVac CD4+ p=0·41, CD8+ p=0·79; BNT162b2 CD4+ p=0·70 CD8+ p=0·80). INTERPRETATION: The evidence that mRNA and inactivated vaccines based on the ancestral SARS-CoV-2 virus elicited T-cell responses to SARS-CoV-2 omicron variants might explain the high observed vaccine effectiveness against severe COVID-19 shown by both types of vaccine, despite great differences in neutralising antibody responses. The use of either vaccine can be considered if the primary aim is to reduce severity and death caused by the new omicron subvariants; however, BNT162b2 is preferable for adults older than 60 years. FUNDING: The Health and Medical Research Fund Commissioned Research on the Novel Coronavirus Disease and S H Ho Foundation.

Phenotyping empyema by pleural fluid culture results and macroscopic appearance: an 8-year retrospective study.

Background: The clinical impact of phenotyping empyema is poorly described. This study was designed to evaluate clinical characteristics and outcomes based on the two readily available parameters, pleural fluid culture status and macroscopic fluid appearance. Methods: A retrospective study was conducted on patients with empyema hospitalised between 2013 and 2020. Empyema was classified into culture-positive empyema (CPE) or culture-negative empyema (CNE) and pus-appearing empyema (PAE) or non-pus-appearing empyema (non-PAE) based on the pleural fluid culture status and macroscopic fluid appearance, respectively. Results: Altogether, 212 patients had confirmed empyema (CPE: n=188, CNE: n=24; PAE: n=118, non-PAE: n=94). The cohort was predominantly male (n=163, 76.9%) with a mean age of 65.0±13.6 years. Most patients (n=180, 84.9%) had at least one comorbidity. Patients with CPE had higher rates of in-hospital mortality (19.1% versus 0.0%, p=0.017) and 90-day mortality (18.6% versus 0.0%, p=0.017) and more extrapulmonary sources of infection (29.8% versus 8.3%, p=0.026) when compared with patients with CNE. No significant difference in mortality rate was found between PAE and non-PAE during the in-hospital stay and at 30 days and 90 days. Patients with PAE had less extrapulmonary sources of infection (20.3% versus 36.2%, p=0.010) and more anaerobic infection (40.9% versus 24.5%, p=0.017) than those with non-PAE. The median RAPID (renal, age, purulence, infection source, and dietary factors) scores were higher in the CPE and non-PAE groups. After adjusting for covariates, culture positivity was not independently associated with mortality on multivariable analysis. Conclusion: Empyema is a heterogeneous disease with different clinical characteristics. Phenotyping empyema into different subclasses based on pleural fluid microbiological results and macroscopic fluid appearance provides insight into the underlying bacteriology, source of infection and subsequent clinical outcomes.

Comparison of the immunogenicity of BNT162b2 and CoronaVac COVID-19 vaccines in Hong Kong.

BACKGROUND AND OBJECTIVE: Few head-to-head evaluations of immune responses to different vaccines have been reported. METHODS: Surrogate virus neutralization test (sVNT) antibody levels of adults receiving either two doses of BNT162b2 (n = 366) or CoronaVac (n = 360) vaccines in Hong Kong were determined. An age-matched subgroup (BNT162b2 [n = 49] vs. CoronaVac [n = 49]) was tested for plaque reduction neutralization (PRNT) and spike-binding antibody and T-cell reactivity in peripheral blood mononuclear cells. RESULTS: One month after the second dose of vaccine, BNT162b2 elicited significantly higher PRNT50 , PRNT90 , sVNT, spike receptor binding, spike N-terminal domain binding, spike S2 domain binding, spike FcR binding and antibody avidity levels than CoronaVac. The geometric mean PRNT50 titres in those vaccinated with BNT162b2 and CoronaVac vaccines were 251.6 and 69.45, while PRNT90 titres were 98.91 and 16.57, respectively. All of those vaccinated with BNT162b2 and 45 (91.8%) of 49 vaccinated with CoronaVac achieved the 50% protection threshold for PRNT90. Allowing for an expected seven-fold waning of antibody titres over 6 months for those receiving CoronaVac, only 16.3% would meet the 50% protection threshold versus 79.6% of BNT162b2 vaccinees. Age was negatively correlated with PRNT90 antibody titres. Both vaccines induced SARS-CoV-2-specific CD4+ and CD8+ T-cell responses at 1 month post-vaccination but CoronaVac elicited significantly higher structural protein-specific CD4+ and CD8+ T-cell responses. CONCLUSION: Vaccination with BNT162b2 induces stronger humoral responses than CoronaVac. CoronaVac induces higher CD4+ and CD8+ T-cell responses to the structural protein than BNT162b2.

A territory-wide study on the factors associated with recurrent asthma exacerbations requiring hospitalization in Hong Kong.

BACKGROUND: The real-world relationships between the demographic and clinical characteristics of asthma patients, their prehospitalization management and the frequency of hospitalization due to asthma exacerbation is poorly established. OBJECTIVE: To determine the risk factors of recurrent asthma exacerbations requiring hospitalizations and evaluate the standard of baseline asthma care. METHODS: A territory-wide, multicentre retrospective study in Hong Kong was performed. Medical records of patients aged ≥18 years admitted to 11 acute general hospitals from January 1 to December 31, 2016 for asthma exacerbations were reviewed. RESULTS: There were 2280 patients with 3154 admissions (36.7% male, median age 66.0 [interquartile range: 48.0-81.0] years, 519 had ≥2 admissions). Among them, 1830 (80.3%) had at least one asthma-associated comorbidity, 1060 (46.5%) and 885 (38.9%) of patients had Accident and Emergency Department (AED) attendance and hospitalization in the preceding year, respectively. Patients with advancing age (incidence rate ratio [IRR]: 1.003 for every year increment), a history of AED visits or hospitalization (IRR: 1.018 and 1.070 for every additional episode, respectively) for asthma exacerbation in the preceding year, the presence of neuropsychiatric (IRR: 1.142) and gastrointestinal (IRR: 1.154) comorbidities were risk factors for an increasing number of admissions for asthma exacerbation. For patients with ≥2 admissions, 17.1% were not prescribed inhaled corticosteroid and only 44.6% had spirometry checked before the index admission. Asthma phenotyping was often incomplete, as assessment of atopy (total serum immunoglobulin E level and senitization to aeroallergens) was only performed in 30 (5.8%) patients with ≥2 admissions. CONCLUSIONS AND CLINICAL RELEVANCE: Improving asthma care, especially in elderly patients with a prior history of urgent healthcare utilization and comorbidities, may help reduce healthcare burden. Suboptimal management before the index admission was common in patients hospitalized for asthma exacerbations. Early identification of patients at risk and enhancement of baseline asthma management may help to prevent recurrent asthma exacerbation and subsequent hospitalization.