Vaccine-induced protection against SARS-CoV-2 requires IFN-γ-driven cellular immune response.

The overall success of worldwide mass vaccination in limiting the negative effect of the COVID-19 pandemics is inevitable, however, recent SARS-CoV-2 variants of concern, especially Omicron and its sub-lineages, efficiently evade humoral immunity mounted upon vaccination or previous infection. Thus, it is an important question whether these variants, or vaccines against them, induce anti-viral cellular immunity. Here we show that the mRNA vaccine BNT162b2 induces robust protective immunity in K18-hACE2 transgenic B-cell deficient (µMT) mice. We further demonstrate that the protection is attributed to cellular immunity depending on robust IFN-γ production. Viral challenge with SARS-CoV-2 Omicron BA.1 and BA.5.2 sub-variants induce boosted cellular responses in vaccinated µMT mice, which highlights the significance of cellular immunity against the ever-emerging SARS-CoV-2 variants evading antibody-mediated immunity. Our work, by providing evidence that BNT162b2 can induce significant protective immunity in mice that are unable to produce antibodies, thus highlights the importance of cellular immunity in the protection against SARS-CoV-2.

A Phase 1, Randomized, Double-Blinded, Placebo-Controlled and Dose-Escalation Study to Evaluate the Safety and Immunogenicity of the Intranasal DelNS1-nCoV-RBD LAIV for COVID-19 in Healthy Adults.

An intranasal COVID-19 vaccine, DelNS1-based RBD vaccines composed of H1N1 subtype (DelNS1-nCoV-RBD LAIV) was developed to evaluate the safety and immunogenicity in healthy adults. We conducted a phase 1 randomized, double-blinded, placebo-controlled study on healthy participants, age 18-55 and COVID-19 vaccines naïve, between March and September 2021. Participants were enrolled and randomly assigned (2:2:1) into the low and high dose DelNS1-nCoV-RBD LAIV manufactured in chicken embryonated eggs or placebo groups. The low and high-dose vaccine were composed of 1 × 107 EID50/ dose and 1 × 107.7 EID50/ dose in 0.2 mL respectively. The placebo vaccine was composed of inert excipients/dose in 0.2 mL. Recruited participants were administered the vaccine intranasally on day 0 and day 28. The primary end-point was the safety of the vaccine. The secondary endpoints included cellular, humoral, and mucosal immune responses post-vaccination at pre-specified time-points. The cellular response was measured by the T-cell ELISpot assay. The humoral response was measured by the serum anti-RBD IgG and live-virus neutralizing antibody against SARS-CoV-2. The saliva total Ig antibody responses in mucosal secretion against SARS-CoV-2 RBD was also assessed. Twenty-nine healthy Chinese participants were vaccinated (low-dose: 11; high-dose: 12 and placebo: 6). The median age was 26 years. Twenty participants (69%) were male. No participant was discontinued due to an adverse event or COVID-19 infection during the clinical trial. There was no significant difference in the incidence of adverse events (p = 0.620). For the T-cell response elicited after full vaccination, the positive PBMC in the high-dose group increased to 12.5 SFU/106 PMBC (day 42) from 0 (baseline), while it increased to 5 SFU/106 PBMC (day 42) from 2.5 SFU/106 PBMC (baseline) in the placebo group. The high-dose group showed a slightly higher level of mucosal Ig than the control group after receiving two doses of the vaccine (day 31, 0.24 vs. 0.21, p = 0.046; day 56 0.31 vs. 0.15, p = 0.45). There was no difference in the T-cell and saliva Ig response between the low-dose and placebo groups. The serum anti-RBD IgG and live virus neutralizing antibody against SARS-CoV-2 were undetectable in all samples. The high-dose intranasal DelNS1-nCoV-RBD LAIV is safe with moderate mucosal immunogenicity. A phase-2 booster trial with a two-dose regimen of the high-dose intranasal DelNS1-nCoV-RBD LAIV is warranted.

Phylogenomic analysis of COVID-19 summer and winter outbreaks in Hong Kong: An observational study.

BACKGROUND: Viral genomic surveillance is vital for understanding the transmission of COVID-19. In Hong Kong, breakthrough outbreaks have occurred in July (third wave) and November (fourth wave) 2020. We used whole viral genome analysis to study the characteristics of these waves. METHODS: We analyzed 509 SARS-CoV-2 genomes collected from Hong Kong patients between 22nd January and 29th November, 2020. Phylogenetic and phylodynamic analyses were performed, and were interpreted with epidemiological information. FINDINGS: During the third and fourth waves, diverse SARS-CoV-2 genomes were identified among imported infections. Conversely, local infections were dominated by a single lineage during each wave, with 96.6% (259/268) in the third wave and 100% (73/73) in the fourth wave belonging to B.1.1.63 and B.1.36.27 lineages, respectively. While B.1.1.63 lineage was imported 2 weeks before the beginning of the third wave, B.1.36.27 lineage has circulated in Hong Kong for 2 months prior to the fourth wave. During the fourth wave, 50.7% (37/73) of local infections in November was identical to the viral genome from an imported case in September. Within B.1.1.63 or B.1.36.27 lineage in our cohort, the most common non-synonymous mutations occurred at the helicase (nsp13) gene. INTERPRETATION: Although stringent measures have prevented most imported cases from spreading in Hong Kong, a single lineage with low-level local transmission in October and early November was responsible for the fourth wave. A superspreading event or lower temperature in November may have facilitated the spread of the B.1.36.27 lineage.

A prospective follow-up of thyroid volume and thyroiditis features on ultrasonography among survivors of predominantly mild to moderate COVID-19.

Background: We previously showed that higher SARS-CoV-2 viral load correlated with smaller thyroid volumes among COVID-19 survivors at 2 months after acute COVID-19. Our current follow-up study evaluated the evolution of thyroid volumes and thyroiditis features within the same group of patients 6 months later. Methods: Adult COVID-19 survivors who underwent thyroid ultrasonography 2 months after infection (USG1) were recruited for follow-up USG 6 months later (USG2). The primary outcome was the change in thyroid volume. We also reassessed thyroiditis features on USG, thyroid function and anti-thyroid antibodies. Results: Fifty-four patients were recruited (mean age 48.1 years; 63% men). The mean thyroid volume increased from USG1 to USG2 (11.9 ± 4.8 to 14.5 ± 6.2 mL, p < 0.001). Thirty-two patients (59.3%) had significant increase in thyroid volume by ≥15%, and they had a median increase of +33.3% (IQR: +20.0% to +45.0%). Multivariable logistic regression analysis showed that only higher baseline SARS-CoV-2 viral load independently correlated with significant thyroid volume increase on USG2 (p = 0.022). Among the seven patients with thyroiditis features on USG1, six (85.7%) had the features resolved on USG2. None had new thyroiditis features on USG2. All abnormal thyroid function during acute COVID-19 resolved upon USG1 and USG2. Conclusion: Most COVID-19 survivors had an increase in thyroid volume from early convalescent phase to later convalescent phase. This increase correlated with high initial SARS-CoV-2 viral load. Together with the resolution of thyroiditis features, these may suggest a transient direct atrophic effect of SARS-CoV-2 on the thyroid gland with subsequent recovery of thyroid volume and thyroiditis features.

Evolution and Control of COVID-19 Epidemic in Hong Kong.

Hong Kong SAR has adopted universal masking, social distancing, testing of all symptomatic and high-risk groups for isolation of confirmed cases in healthcare facilities, and quarantine of contacts as epidemiological control measures without city lockdown or border closure. These measures successfully suppressed the community transmission of pre-Omicron SARS-CoV-2 variants or lineages during the first to the fourth wave. No nosocomial SARS-CoV-2 infection was documented among healthcare workers in the first 300 days. The strategy of COVID-19 containment was adopted to provide additional time to achieve population immunity by vaccination. The near-zero COVID-19 situation for about 8 months in 2021 did not enable adequate immunization of the eligible population. A combination of factors was identified, especially population complacency associated with the low local COVID-19 activity, together with vaccine hesitancy. The importation of the highly transmissible Omicron variant kickstarted the fifth wave of COVID-19, which could no longer be controlled by our initial measures. The explosive fifth wave, which was partially contributed by vertical airborne transmission in high-rise residential buildings, resulted in over one million cases of infection. In this review, we summarize the epidemiology of COVID-19 and the infection control and public health measures against the importation and dissemination of SARS-CoV-2 until day 1000.

Effectiveness of Molnupiravir and Nirmatrelvir-Ritonavir in Hospitalized Patients With COVID-19 : A Target Trial Emulation Study.

BACKGROUND: Whether hospitalized patients benefit from COVID-19 oral antivirals is uncertain. OBJECTIVE: To examine the real-world effectiveness of molnupiravir and nirmatrelvir-ritonavir in hospitalized patients with COVID-19 during the Omicron outbreak. DESIGN: Target trial emulation study. SETTING: Electronic health databases in Hong Kong. PARTICIPANTS: The molnupiravir emulated trial included hospitalized patients with COVID-19 aged 18 years or older between 26 February and 18 July 2022 (n = 16 495). The nirmatrelvir-ritonavir emulated trial included hospitalized patients with COVID-19 aged 18 years or older between 16 March and 18 July 2022 (n = 7119). INTERVENTION: Initiation of molnupiravir or nirmatrelvir-ritonavir within 5 days of hospitalization with COVID-19 versus no initiation of molnupiravir or nirmatrelvir-ritonavir. MEASUREMENTS: Effectiveness against all-cause mortality, intensive care unit (ICU) admission, or use of ventilatory support within 28 days. RESULTS: The use of oral antivirals in hospitalized patients with COVID-19 was associated with a lower risk for all-cause mortality (molnupiravir: hazard ratio [HR], 0.87 [95% CI, 0.81 to 0.93]; nirmatrelvir-ritonavir: HR, 0.77 [CI, 0.66 to 0.90]) but no significant risk reduction in terms of ICU admission (molnupiravir: HR, 1.02 [CI, 0.76 to 1.36]; nirmatrelvir-ritonavir: HR, 1.08 [CI, 0.58 to 2.02]) or the need for ventilatory support (molnupiravir: HR, 1.07 [CI, 0.89 to 1.30]; nirmatrelvir-ritonavir: HR, 1.03 [CI, 0.70 to 1.52]). There was no significant interaction between drug treatment and the number of COVID-19 vaccine doses received, thereby supporting the effectiveness of oral antivirals regardless of vaccination status. No significant interaction between nirmatrelvir-ritonavir treatment and age, sex, or Charlson Comorbidity Index was observed, whereas molnupiravir tended to be more effective in older people. LIMITATION: The outcome of ICU admission or need for ventilatory support may not capture all severe COVID-19 cases; unmeasured confounders, such as obesity and health behaviors, may exist. CONCLUSION: Molnupiravir and nirmatrelvir-ritonavir reduced all-cause mortality in both vaccinated and unvaccinated hospitalized patients. No significant reduction in ICU admission or the need for ventilatory support was observed. PRIMARY FUNDING SOURCE: Health and Medical Research Fund Research on COVID-19, Government of the Hong Kong Special Administrative Region; Research Grants Council, Collaborative Research Fund; and Health Bureau, Government of the Hong Kong Special Administrative Region.

Epidemiology and Outcomes of Hypernatraemia in Patients with COVID-19-A Territory-Wide Study in Hong Kong.

BACKGROUND: Dysnatraemias are commonly reported in COVID-19. However, the clinical epidemiology of hypernatraemia and its impact on clinical outcomes in relation to different variants of SARS-CoV-2, especially the prevailing Omicron variant, remain unclear. METHODS: This was a territory-wide retrospective study to investigate the clinical epidemiology and outcomes of COVID-19 patients with hypernatraemia at presentation during the period from 1 January 2020 to 31 March 2022. The primary outcome was 30-day mortality. Key secondary outcomes included rates of hospitalization and ICU admission, and costs of hospitalization. RESULTS: In this study, 53,415 adult COVID-19 patients were included for analysis. Hypernatraemia was observed in 2688 (5.0%) patients at presentation, of which most cases (99.2%) occurred during the local "5th wave" dominated by the Omicron BA.2 variant. Risk factors for hypernatraemia at presentation included age, institutionalization, congestive heart failure, dementia, higher SARS-CoV-2 Ct value, white cell count, C-reactive protein and lower eGFR and albumin levels (p < 0.001 for all). Patients with hypernatraemia showed significantly higher 30-day mortality (32.0% vs. 5.7%, p < 0.001) and longer lengths of stay (12.9 ± 10.9 vs. 11.5 ± 12.1 days, p < 0.001) compared with those with normonatraemia. Multivariate analysis revealed hypernatraemia at presentation as an independent predictor for 30-day mortality (aHR 1.32, 95% CI 1.14-1.53, p < 0.001) and prolonged hospital stays (OR 1.55, 95% CI 1.17-2.05, p = 0.002). CONCLUSIONS: Hypernatraemia is common among COVID-19 patients, especially among institutionalized older adults with cognitive impairment and other comorbidities during large-scale outbreaks during the Omicron era. Hypernatraemia is associated with unfavourable outcomes and increased healthcare utilization.

Epidemiology and outcomes of hyponatremia in patients with COVID-19-A territory-wide study in Hong Kong.

Background: Hyponatremia is common in COVID-19, but its epidemiology and impact on clinical outcomes in relation to different variants, especially the Omicron variant, requires further clarification. Methods: This was a territory-wide retrospective study to investigate the epidemiology and outcomes of COVID-19 patients with hyponatremia from January 1, 2020 to March 31, 2022 in Hong Kong. The primary outcome was 30-day mortality of patients with COVID-19 and hyponatremia at presentation. Secondary outcomes included rate of hospitalization, intensive care unit (ICU) hospitalization, overall duration of hospitalization, and duration of ICU hospitalization. Results: A total of 53,415 COVID-19 patients were included for analysis, of which 14,545 (27.2%) had hyponatremia at presentation. 9813 (67.5%), 2821 (19.4%), and 1911 (13.1%) had mild (130 to <135 mmol/L), moderate (125 to <130 mmol/L), and severe hyponatremia (<125 mmol/L) at presentation respectively. Age, male sex, diabetes, active malignancy, white cell count, serum creatinine, hypoalbuminemia, C-reactive protein, and viral loads were independent predictors for hyponatremia in COVID-19 patients (P < 0.001, for all). Hyponatremic patients had increased 30-day mortality (9.7 vs. 5.7%, P < 0.001), prolonged hospitalization (11.9 ± 15.1 days vs. 11.5 ± 12.1 days, P < 0.001), and more ICU admissions (7.0% vs. 3.3%, P < 0.001). Patients diagnosed during the "fifth wave" Omicron BA.2 outbreak had 2.29-fold risk (95% CI 2.02-2.59, P < 0.001) of presenting with hyponatremia compared to other waves. Conclusion: Hyponatremia is common among COVID-19 patients, and may serve as a prognostic indicator for unfavorable outcomes and increased healthcare utilization in the evolving COVID-19 outbreak.

mRNA (BNT162b2) COVID-19 vaccination increased risk of Bell's palsy: a nested case control and self-controlled case series study.

BACKGROUND: Observable symptoms of Bell's palsy following vaccinations may arouse concern over the safety profiles of novel COVID-19 vaccines in the general public. However, there are only a few studies on Bell's palsy following mRNA COVID-19 vaccination with inconclusive findings. This study aimed to update the previous analysis on the risk of Bell's palsy following mRNA (BNT162b2) COVID-19 vaccination. METHODS: This study included cases aged ≥16-years-old with a new diagnosis of Bell's palsy within 28 days after BNT162b2 vaccinations from the population-based electronic health records in Hong Kong, using a nested case-control and self-controlled case series (SCCS) analyses were employed. The association between Bell's palsy and BNT162b2 was evaluated using conditional logistic and Poisson regression in nested case-control and SCCS analysis, respectively. RESULTS: A total of 54 individuals were newly diagnosed with Bell's palsy after BNT162b2 vaccinations. The incidence of Bell's palsy was 1.58 (95% CI:1.19-2.07) per 100,000 doses administered. The nested case-control analysis showed significant association between BNT162b2 vaccinations and Bell's palsy (Adjusted OR: 1.543, 95%CI:1.123 - 2.121), with up to 1.112 excess events per 100,000 people receiving two doses of BNT162b2. An increased risk of Bell's palsy was observed during the first 14 days after the second dose of BNT162b2 in both nested case-control (Adjusted OR: 2.325, 95%CI:1.414 - 3.821) and SCCS analysis (Adjusted IRR=2.44, 95%CI:1.32-4.50). CONCLUSION: There is an overall increased risk of Bell's palsy following BNT162b2 vaccination, particularly within the first 14 days after the second dose, but the absolute risk was very low.

Early treatment of high-risk hospitalized COVID-19 patients with a combination of interferon beta-1b and remdesivir: a phase 2 open-label randomized controlled trial.

BACKGROUND: Early antiviral therapy was effective in the treatment of COVID-19. We assessed the efficacy and safety of combined interferon beta-1b and remdesivir treatment in hospitalized COVID-19 patients. METHODS: We conducted a multicentre, prospective open-label, randomized-controlled trial involving high-risk adults hospitalized for COVID-19. Patients were randomly assigned to a 5-day interferon beta-1b 16 million units daily and remdesivir 200mg loading on day 1 followed by 100mg daily on day 2 to 5 (combination-group), or to remdesivir only of similar regimen (control-group) (1:1). The primary end-point was the time to complete alleviation of symptoms (NEWS2 = 0). RESULTS: Two-hundred and twelve patients were enrolled. The median days of starting treatment from symptom-onset was 3 days. The median age was 65 years and 159 patients (75%) had chronic disease. The baseline demographics were similar. There was no mortality. For the primary-endpoint, the combination-group was significantly quicker to NEWS2 = 0 (4 versus 6.5 days; hazard-ratio [HR],6.59; 95% confidence-interval [CI],6.1-7.09; p < 0.0001) when compared to the control-group. For the secondary endpoints, the combination-group was quicker to negative NPS VL (6 versus 8 days; HR,8.16; 95% CI,7.79-8.52; p < 0.0001) and develop seropositive IgG (8 versus 10 days; HR,10.78; 95% CI,9.98-11.58; p < 0.0001). All adverse events resolved upon follow-up. Combination group (HR,4.1 95%CI,1.9-8.6, p < 0.0001), was the most significant independent factor associated with NEWS2 = 0 on day 4. CONCLUSIONS: Early treatment with interferon beta-1b and remdesivir was safe and better than remdesivir only in alleviating symptoms, shorten viral shedding and hospitalization with earlier seropositivity in high-risk COVID-19 patients.

Correlations of Myeloperoxidase (MPO), Adenosine deaminase (ADA), C-C motif chemokine 22 (CCL22), Tumour necrosis factor alpha (TNFα) and Interleukin-6 (IL-6) mRNA expression in the nasopharyngeal specimens with the diagnosis and severity of SARS-CoV-2 infections.

Cytokine dynamics in patients with coronavirus disease 2019 (COVID-19) have been studied in blood but seldomly in respiratory specimens. We studied different cell markers and cytokines in fresh nasopharyngeal swab specimens for the diagnosis and for stratifying the severity of COVID-19. This was a retrospective case-control study comparing Myeloperoxidase (MPO), Adenosine deaminase (ADA), C-C motif chemokine ligand 22 (CCL22), Tumour necrosis factor alpha (TNFα) and Interleukin-6 (IL-6) mRNA expression in 490 (327 patients and 163 control) nasopharyngeal specimens from 317 (154 COVID-19 and 163 control) hospitalized patients. Of the 154 COVID-19 cases, 46 died. Both total and normalized MPO, ADA, CCL22, TNFα, and IL-6 mRNA expression levels were significantly higher in the nasopharyngeal specimens of infected patients when compared with controls, with ADA showing better performance (OR 5.703, 95% CI 3.424-9.500, p < 0.001). Receiver operating characteristics (ROC) curve showed that the cut-off value of normalized ADA mRNA level at 2.37 × 10-3 had a sensitivity of 81.8% and specificity of 83.4%. While patients with severe COVID-19 had more respiratory symptoms, and elevated lactate dehydrogenase, multivariate analysis showed that severe COVID-19 patients had lower CCL22 mRNA (OR 0.211, 95% CI 0.060-0.746, p = 0.016) in nasopharyngeal specimens, while lymphocyte count, C-reactive protein, and viral load in nasopharyngeal specimens did not correlate with disease severity. In summary, ADA appears to be a better biomarker to differentiate between infected and uninfected patients, while CCL22 has the potential in stratifying the severity of COVID-19.

Effect of vaccine booster, vaccine type, and hybrid immunity on humoral and cellular immunity against SARS-CoV-2 ancestral strain and Omicron variant sublineages BA.2 and BA.5 among older adults with comorbidities: a cross sectional study.

BACKGROUND: Vaccination reduces COVID-19-related hospitalization among older adults. However, how SARS-CoV-2 infection and vaccine regimens affect vaccine-elicited immunity remain unclear. METHODS: This is a cross-sectional study recruiting adults aged ≥70 years with comorbidities in Hong Kong. Demographic and clinical information were collected using a questionnaire. Neutralizing antibody (nAb) titers (against ancestral and Omicron strains) and SARS-CoV-2-specific T cell response were analyzed according to infection and vaccination status. Multivariable regression analysis was performed to assess the associations of BNT162b2 and booster doses with higher nAb titers, with adjustment for comorbidities. FINDINGS: In July 2022, 101 patients were recruited, of whom 25 (24%) had previous infection. Overall, the geometric mean titer (GMT) of BA.5 nAb was 2.8-fold lower than that against BA.2 (P < 0.0001). The ancestral strain and BA.2 titers were higher for the 3-4-dose-BNT162 group than the 2-dose-BNT162b2 group. Non-infected individuals in the 3-4-dose-CoronaVac group had a more robust T cell response than the 2-dose-CoronaVac group (P = 0.0181), but there was no significant difference between the 2-dose-BNT162b2 and 3-4-dose-BNT162b groups. Patients who had heterologous CoronaVac-BNT162b2 prime-boost regimen had 3.22-fold higher BA.5 nAb titers than those who were primed/boosted with CoronaVac (P = 0.0207). Patients with hybrid immunity had higher Omicron nAb titers than those with vaccine-only immunity. Multivariable analysis showed that BNT162b2 and booster doses were independently associated with higher ancestral strain nAb titers. INTERPRETATION: Our data support the use of booster doses for older adults with or without prior infection. Non-infected individuals primed with CoronaVac will benefit from heterologous mRNA vaccine booster. FUNDING: Richard and Carol Yu, May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Michael Tong, Marina Lee, Government Consultancy Service (See acknowledgements for full list).

A prospective follow-up on thyroid function, thyroid autoimmunity and long COVID among 250 COVID-19 survivors.

PURPOSE: We evaluated the evolution of thyroid function and autoimmunity among COVID-19 survivors over 6 months in relation to interferon beta-1b treatment and long COVID. METHODS: We included COVID-19 survivors managed in a major COVID-19 centre between July 2020 and May 2021 who were reassessed three and/or six months after acute COVID-19. Thyroid function tests (TFTs) and anti-thyroid antibody titres were measured at acute COVID-19, 3-month and 6-month. RESULTS: 250 COVID-19 survivors were included (mean age 52.7 years, 50.4% men). Persistent thyroid function abnormalities were more likely in those with abnormal TFTs in acute COVID-19 (P < 0.001). Among 51 patients with abnormal TFTs in acute COVID-19, 82.4% resolved upon follow-up. Of 199 patients with normal TFTs in acute COVID-19, only 4.5% had incident abnormal TFTs, more likely in interferon-treated patients (P = 0.044) and none clinically overt. Among 129 patients with complete 6-month follow-up for anti-thyroid antibody titres, there was no significant change overall, except for modest increase in anti-thyroid antibody titres among the 84 interferon-treated patients (P < 0.05 at both 3 months and 6 months). Long COVID occurred in 19.5% and 10.4% at 3 and 6 months respectively, where TFTs and anti-thyroid antibody titres were not predictive of its occurrence. CONCLUSION: Over 6 months, most abnormal TFTs in acute COVID-19 resolved, with no significant incident thyroid dysfunction. SARS-CoV-2 infection did not lead to change in thyroid autoimmunity, while interferon treatment was associated with modest increase in anti-thyroid antibody titres. Thyroid function and anti-thyroid antibodies did not play a significant role in long COVID.

COVID-19 Vaccine Allergy Safety Track (VAS-Track) pathway: real-world outcomes on vaccination rates and antibody protection.

BACKGROUND: Misdiagnosed vaccine-related "allergies" lead to unnecessary vaccine deferrals and incomplete vaccinations, leaving patients unprotected against COVID-19. To overcome limitations and queues for Allergist assessment, the "VAS-Track" pathway was developed to evaluate patients via a multi-disciplinary triage model including nurses, non-specialists, and Allergists. OBJECTIVE: We assessed the effectiveness and safety of VAS-Track and evaluate its real-world impact in terms of vaccination rates and COVID-19 protection. METHODS: Patients referred to VAS-Track between September 2021 and March 2022 were recruited. Subgroup analysis was performed with prospective pre- and post-clinic antibody levels. RESULTS: Nurse-assisted screening identified 10,412 (76%) referrals as inappropriate. 369 patients were assessed by VAS-Track. Overall, 100% of patients were recommended to complete vaccination and 332 (90%) completed their primary series. No patients reported any significant allergic reactions following subsequent vaccination. Vaccination completion rates between patients seen by non-specialists and additional Allergist review were similar (90% vs. 89%, p = 0.617). Vaccination rates were higher among patients with prior history of immediate-type reactions (odds ratio: 2.43, p = 0.025). Subgroup analysis revealed that only 20% (56/284) of patients had seropositive COVID-19 neutralizing antibody levels (≥ 15 AU/mL) prior to VAS-Track, which increased to 92% after vaccine completion (pre-clinic antibody level 6.0 ± 13.5 AU/mL vs. post-clinic antibody level 778.8 ± 337.4 AU/mL, p > 0.001). CONCLUSIONS: A multi-disciplinary allergy team was able to streamline our COVID-19 VAS services, enabling almost all patients to complete their primary series, significantly boosting antibody levels and real-world COVID-19 protection. We propose similar multidisciplinary models to be further utilized, especially in the settings with limited allergy services.

Comparing hybrid and regular COVID-19 vaccine-induced immunity against the Omicron epidemic.

Evidence on the effectiveness of COVID-19 vaccines among people who recovered from a previous SARS-CoV-2 infection is warranted to inform vaccination recommendations. Using the territory-wide public healthcare and vaccination records of over 2.5 million individuals in Hong Kong, we examined the potentially differential risk of SARS-CoV-2 infection, hospitalization, and mortality between those receiving two homologous doses of BNT162b2 or CoronaVac versus those with a previous infection receiving only one dose amid the Omicron epidemic. Results show a single dose after a SARS-CoV-2 infection is associated with a lower risk of infection (BNT162b2: adjusted incidence rate ratio [IRR] = 0.475, 95% CI: 0.410-0.550; CoronaVac: adjusted IRR = 0.397, 95% CI: 0.309-0.511) and no significant difference was detected in the risk of COVID-19-related hospitalization or mortality compared with a two-dose vaccination regimen. Findings support clinical recommendations that those with a previous infection could receive a single dose to gain at least similar protection as those who received two doses without a previous infection.

mRNA (BNT162b2) and Inactivated (CoronaVac) COVID-19 Vaccination and Risk of Adverse Events and Acute Diabetic Complications in Patients with Type 2 Diabetes Mellitus: A Population-Based Study.

INTRODUCTION: In Hong Kong, CoronaVac and BNT162b2 have been approved for emergency use owing to the coronavirus disease 2019 (COVID-19) pandemic. Reactions towards the vaccine and the risk of post-vaccination adverse events may be different between recipients with and without type 2 diabetes mellitus (T2DM). OBJECTIVE: The aim of this study was to evaluate the risk of adverse events of special interest (AESI) and acute diabetic complications in the T2DM population after COVID-19 vaccination in Hong Kong. RESEARCH DESIGN AND METHODS: Self-controlled case-series analysis was conducted. Patients with T2DM who received at least one dose of BNT162b2 or CoronaVac between 23 February 2021 and 31 January 2022 from electronic health records in Hong Kong were included. The incidence rates of 29 AESIs and acute diabetic complications (any of severe hypoglycemia, diabetic ketoacidosis or hyperosmolar hyperglycemic syndrome) requiring hospitalization within 21 days after the first or second dose of vaccination were reported. The risks of these outcomes were evaluated using conditional Poisson regression. RESULTS: Among 141,224 BNT162b2 recipients and 209,739 CoronaVac recipients with T2DM, the incidence per 100,000 doses and incidence per 100,000 person-years of individual AESIs and acute diabetic complications ranged from 0 to 24.4 and 0 to 438.6 in BNT162b2 group, and 0 to 19.5 and 0 to 351.6 in CoronaVac group. We did not observe any significantly increased risk of individual AESIs or acute diabetic complications after first or second doses of BNT162b2 or CoronaVac vaccine. Subgroup analysis based on HbA1c < 7% and ≥ 7% also did not show significantly excess risk after vaccination. CONCLUSIONS: Patients with T2DM do not appear to have higher risks of AESI and acute diabetic complications after BNT162b2 or CoronaVac vaccination. Moreover, given the low incidence of AESIs and acute diabetic complications after vaccination, the absolute risk increment was likely minimal.

The Four Ws of the Fourth Dose COVID-19 Vaccines: Why, Who, When and What.

With the emergence of SARS-CoV-2 variants, vaccine breakthrough is a major public health concern. With evidence of reduced neutralizing antibody activity against Omicron variants and fading antibody level after the third-dose booster vaccine, there are suggestions of a fourth-dose booster vaccine. In this review, the benefits of a fourth-dose booster is evaluated from four perspectives, including the effectiveness of the booster dose against virus variants (Why), susceptible groups of individuals who may benefit from additional booster dose (Who), selection of vaccine platforms to better enhance immunity (What) and appropriate intervals between the third and fourth booster dose (When). In summary, a fourth dose can temporarily boost the immune response against SARS-CoV-2 variants and can be considered for specific groups of individuals. A heterologous vaccine strategy using mRNA vaccine in individuals primed with inactivated vaccine may boost immunity against variants. The timing of the fourth dose should be individualized but an interval of 4 months after the third-dose booster is appropriate. A universal fourth booster dose is not necessary.

Air and environmental sampling for SARS-CoV-2 around hospitalized patients with coronavirus disease 2019 (COVID-19).

BACKGROUND: The role of severe respiratory coronavirus virus 2 (SARS-CoV-2)-laden aerosols in the transmission of coronavirus disease 2019 (COVID-19) remains uncertain. Discordant findings of SARS-CoV-2 RNA in air samples were noted in early reports. METHODS: Sampling of air close to 6 asymptomatic and symptomatic COVID-19 patients with and without surgical masks was performed with sampling devices using sterile gelatin filters. Frequently touched environmental surfaces near 21 patients were swabbed before daily environmental disinfection. The correlation between the viral loads of patients' clinical samples and environmental samples was analyzed. RESULTS: All air samples were negative for SARS-CoV-2 RNA in the 6 patients singly isolated inside airborne infection isolation rooms (AIIRs) with 12 air changes per hour. Of 377 environmental samples near 21 patients, 19 (5.0%) were positive by reverse-transcription polymerase chain reaction (RT-PCR) assay, with a median viral load of 9.2 × 102 copies/mL (range, 1.1 × 102 to 9.4 × 104 copies/mL). The contamination rate was highest on patients' mobile phones (6 of 77, 7.8%), followed by bed rails (4 of 74, 5.4%) and toilet door handles (4 of 76, 5.3%). We detected a significant correlation between viral load ranges in clinical samples and positivity rate of environmental samples (P < .001). CONCLUSION: SARS-CoV-2 RNA was not detectable by air samplers, which suggests that the airborne route is not the predominant mode of transmission of SARS-CoV-2. Wearing a surgical mask, appropriate hand hygiene, and thorough environmental disinfection are sufficient infection control measures for COVID-19 patients isolated singly in AIIRs. However, this conclusion may not apply during aerosol-generating procedures or in cohort wards with large numbers of COVID-19 patients.