Effectiveness of BNT162b2 and CoronaVac COVID-19 vaccination against asymptomatic and symptomatic infection of SARS-CoV-2 omicron BA.2 in Hong Kong: a prospective cohort study.

BACKGROUND: COVID-19 vaccines provide protection against symptomatic infection that might require medical attention and against severe outcomes; however, there is a paucity of evidence regarding the effectiveness of the BNT162b2 and CoronaVac vaccines and their booster regimens against asymptomatic or mild omicron infections in the community. We aimed to measure the effectiveness of BNT162b2 and CoronaVac vaccines against asymptomatic and symptomatic SARS-CoV-2 omicron infections, during a period of omicron BA.2 predominance in Hong Kong. METHODS: In this prospective cohort study in a population that was generally infection-naive before the large omicron BA.2 wave between January and late May, 2022, we established a public health surveillance platform to monitor the evolving activity of SARS-CoV-2 infections in the community. We recruited a cohort of individuals aged 5 years and older between March 1 and March 7, 2022, from the general population. Individuals were enrolled from all 18 districts of Hong Kong, according to a predefined age-stratified quota, primarily by random digit dialing (generating suitable eight-digit local telephone numbers by randomly picking sets of the first four digits from a sampling frame, and randomly generating the last four digits), and supplemented by our existing cohorts (which included cohorts for studying influenza vaccination from school-based vaccination programmes and cohorts for SARS-CoV-2 seroprevalence from the community), to ensure representativeness of the population in Hong Kong. Participants did weekly rapid antigen testing with a self-collected pooled nasal and throat swab, regardless of symptom and exposure status, from March 1 to April 15, 2022. Individuals reporting a history of SARS-CoV-2 infection confirmed by laboratory PCR testing before enrolment were excluded from the vaccine effectiveness analysis to avoid potential bias due to infection-induced immunity. The primary outcomes of the study were the incidence of SARS-CoV-2 infection, including asymptomatic and symptomatic infections, and the vaccine effectiveness of BNT162b2 and CoronaVac vaccines. The effectiveness of one, two, and three doses of vaccination was estimated with a Cox proportional hazards regression model with time-dependent covariates, allowing for changes in vaccination status over time, after adjustment for demographic factors and pre-existing medical conditions. FINDINGS: Of the 8636 individuals included in the analysis, 7233 (84%) received at least two doses of vaccine, 3993 (46%) received booster doses, and 903 (10%) reported SARS-CoV-2 infection. Among these infections 589 (65·2%) were symptomatic and 314 (34·8%) were asymptomatic at the time of testing. Statistically significant protection against asymptomatic and symptomatic SARS-CoV-2 omicron infection was found only for those who received a BNT162b2 or CoronaVac booster dose, with a vaccine effectiveness of 41·4% (23·2 to 55·2; p=0·0001) and 32·4% (9·0 to 49·8; p=0·0098), respectively. The vaccine effectiveness of BNT162b2 and CoronaVac boosters was further increased to 50·9% (95% CI 31·0-65·0; p<0·0001) and 41·6% (15·0-59·8; p=0·0049), respectively, for symptomatic omicron infections. A similar pattern of vaccine effectiveness (55·8%, 22·9-74·6; p=0·0040) was also conferred after receipt of a BNT162b2 booster by individuals who received a CoronaVac primary vaccination series. INTERPRETATION: Two doses of either vaccine did not provide significant protection against COVID-19 infection. However, receipt of a BNT162b2 booster or CoronaVac booster was associated with a significantly lower risk of omicron BA.2 infection and symptomatic infection. Our findings confirm the effectiveness of booster doses to protect against mild and asymptomatic infection. FUNDING: Henry Fok Foundation and Hong Kong Health Bureau.

Performance of saline and water gargling for SARS-CoV-2 reverse transcriptase PCR testing: a systematic review and meta-analysis.

The performance of gargling for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase (RT)-PCR testing has not been previously reviewed. This review systematically assessed the performance of saline and water gargling for SARS-CoV-2 RT-PCR testing in the settings of diagnosing and monitoring viral shedding.We included original studies comparing the performance of gargling and (oropharyngeal-)nasopharyngeal swabs for SARS-CoV-2 RT-PCR testing. Studies conducted in either suspected individuals or confirmed cases were included and analysed separately. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were examined using random-effects models.Gargles achieved a high overall sensitivity (91%), specificity (97%), PPV (95%) and NPV (91%) for SARS-CoV-2 RT-PCR testing. Studies using saline gargle and water gargle have an overall sensitivity of 97% and 86%, respectively. The sensitivity values were largely maintained for saline and water gargling on stratified analysis, for both diagnosis (96% and 92%) and viral shedding monitoring (98% and 78%). A higher sensitivity was also reported by studies using sterile saline (100%), a smaller amount of gargling solution (92% versus 87%) and a longer gargling duration (95% versus 86%).Our results supported the use of gargling as a sampling approach for SARS-CoV-2 RT-PCR testing, which achieved a high sensitivity for both diagnosis and viral shedding monitoring purposes. Further investigation on the comparative performance of different gargling mediums is needed to draw a definitive conclusion.

Diagnostic performance of different sampling approaches for SARS-CoV-2 RT-PCR testing: a systematic review and meta-analysis.

BACKGROUND: The comparative performance of different clinical sampling methods for diagnosis of SARS-CoV-2 infection by RT-PCR among populations with suspected infection remains unclear. This meta-analysis aims to systematically compare the diagnostic performance of different clinical specimen collection methods. METHODS: In this systematic review and meta-analysis, we systematically searched PubMed, Embase, MEDLINE, Web of Science, medRxiv, bioRxiv, SSRN, and Research Square from Jan 1, 2000, to Nov 16, 2020. We included original clinical studies that examined the performance of nasopharyngeal swabs and any additional respiratory specimens for the diagnosis of SARS-CoV-2 infection among individuals presenting in ambulatory care. Studies without data on paired samples, or those that only examined different samples from confirmed SARS-CoV-2 cases were not useful for examining diagnostic performance of a test and were excluded. Diagnostic performance, including sensitivity, specificity, positive predictive value, and negative predictive value, was examined using random effects models and double arcsine transformation. FINDINGS: Of the 5577 studies identified in our search, 23 studies including 7973 participants with 16 762 respiratory samples were included. Respiratory specimens examined in these studies included 7973 nasopharyngeal swabs, 1622 nasal swabs, 6110 saliva samples, 338 throat swabs, and 719 pooled nasal and throat swabs. Using nasopharyngeal swabs as the gold standard, pooled nasal and throat swabs gave the highest sensitivity of 97% (95% CI 93-100), whereas lower sensitivities were achieved by saliva (85%, 75-93) and nasal swabs (86%, 77-93) and a much lower sensitivity by throat swabs (68%, 35-94). A comparably high positive predictive value was obtained by pooled nasal and throat (97%, 90-100) and nasal swabs (96%, 87-100) and a slightly lower positive predictive value by saliva (93%, 88-97). Throat swabs have the lowest positive predictive value of 75% (95% CI 45-96). Comparably high specificities (range 97-99%) and negative predictive value (range 95-99%) were observed among different clinical specimens. Comparison between health-care-worker collection and self-collection for pooled nasal and throat swabs and nasal swabs showed comparable diagnostic performance. No significant heterogeneity was observed in the analysis of pooled nasal and throat swabs and throat swabs, whereas moderate to substantial heterogeneity (I2 ≥30%) was observed in studies on saliva and nasal swabs. INTERPRETATION: Our review suggests that, compared with the gold standard of nasopharyngeal swabs, pooled nasal and throat swabs offered the best diagnostic performance of the alternative sampling approaches for diagnosis of SARS-CoV-2 infection in ambulatory care. Saliva and nasal swabs gave comparable and very good diagnostic performance and are clinically acceptable alternative specimen collection methods. Throat swabs gave a much lower sensitivity and positive predictive value and should not be recommended. Self-collection for pooled nasal and throat swabs and nasal swabs was not associated with any significant impairment of diagnostic accuracy. Our results also provide a useful reference framework for the proper interpretation of SARS-CoV-2 testing results using different clinical specimens. FUNDING: Hong Kong Research Grants Council.