Slow waning of antibodies following a third dose of BNT162b2 in adults who had previously received two doses of inactivated vaccine.

We administered BNT162b2 as a third dose to 314 adults aged ≥30 years who had previously received two doses of inactivated vaccination. We collected blood samples before the third dose and again after one month and six months, and found robust antibody responses to the ancestral strain at six months after receipt of BNT162b2. Antibody responses to Omicron BA.2 by live virus neutralization were weaker after the third dose and had declined to a low level by six months.

Immunogenicity of a third dose of BNT162b2 to ancestral SARS-CoV-2 & Omicron variant in adults who received two doses of inactivated vaccine.

BACKGROUND: Limited data exist on antibody responses to mixed vaccination strategies involving inactivated COVID-19 vaccines, particularly in the context of emerging variants. METHODS: We conducted an open label trial of a third vaccine dose of an mRNA vaccine (BNT162b2, Fosun Pharma/BioNTech) in adults aged ≥30 years who had previously received two doses of inactivated COVID-19 vaccine. We collected blood samples before administering the third dose and 28 days later, and tested for antibodies to the ancestral virus using a binding assay (ELISA), a surrogate virus neutralization test (sVNT) and a live virus plaque reduction neutralization test (PRNT). We also tested for antibodies against the Omicron variant using live-virus PRNT. RESULTS: In 315 participants, a third dose of BNT162b2 substantially increased antibody titers on each assay. Mean ELISA levels increased from an optical density (OD) of 0.3 to 2.2 (p < 0. 001), and mean sVNT levels increased from an inhibition of 17% to 96% (p < 0.001). In a random subset of 20 participants, the geometric mean PRNT50 titers rose very substantially by 45 fold from Day 0 to Day 28 against the ancestral virus (p < 0.001) and rose by 11 fold against the Omicron variant (p < 0.001). In daily monitoring, post-vaccination reactions subsided within 7 days for over 99% of participants. CONCLUSIONS: A third dose of COVID-19 vaccination with an mRNA vaccine substantially improved antibody levels against the ancestral virus and the Omicron variant with well-tolerated safety profile, in adults who had received two doses of inactivated vaccine 6 months earlier.

Priming conditions shape breadth of neutralizing antibody responses to sarbecoviruses.

Vaccines that are broadly cross-protective against current and future SARS-CoV-2 variants of concern (VoC) or across the sarbecoviruses subgenus remain a priority for public health. Virus neutralization is the best available correlate of protection. To define the magnitude and breadth of cross-neutralization in individuals with different exposure to SARS-CoV-2 infection and vaccination, we here use a multiplex surrogate neutralization assay based on virus spike receptor binding domains of multiple SARS-CoV-2 VoC, as well as related bat and pangolin viruses. We include sera from cohorts of individuals vaccinated with two or three doses of mRNA (BNT162b2) or inactivated SARS-CoV-2 (Coronavac or Sinopharm) vaccines with or without a history of previous SARS-CoV-2 or SARS-CoV-1 infection. SARS-CoV-2 or SARS-CoV-1 infection followed by BNT162b2 vaccine, Omicron BA.2 breakthrough infection following BNT162b2 vaccine or a third dose of BNT162b2 following two doses of BNT162b2 or Coronavac elicit the highest and broadest neutralization across VoCs. For both breadth and magnitude of neutralization across all sarbecoviruses, those infected with SARS-CoV-1 immunized with BNT162b2 outperform all other combinations of infection and/or vaccination. These data may inform vaccine design strategies for generating broadly neutralizing antibodies to SARS-CoV-2 variants or across the sarbecovirus subgenus.

Strength and durability of antibody responses to BNT162b2 and CoronaVac.

We studied 2780 adults in Hong Kong who received CoronaVac inactivated virus vaccine (Sinovac) and BNT162b2 mRNA vaccine ("Comirnaty", BioNTech/Fosun Pharma). We compared rates of antibody waning over time using an enzyme-linked immunosorbent assay for spike receptor binding domain and a surrogate virus neutralization test. We found stronger and more durable antibody responses to two doses of the mRNA vaccine, and slightly stronger initial antibody responses to each vaccine in younger adults and women. The weaker and less durable responses following CoronaVac support earlier provision of third doses to persons who previously received two doses of this vaccine.

Incorporating temporal distribution of population-level viral load enables real-time estimation of COVID-19 transmission.

Many locations around the world have used real-time estimates of the time-varying effective reproductive number ([Formula: see text]) of COVID-19 to provide evidence of transmission intensity to inform control strategies. Estimates of [Formula: see text] are typically based on statistical models applied to case counts and typically suffer lags of more than a week because of the latent period and reporting delays. Noting that viral loads tend to decline over time since illness onset, analysis of the distribution of viral loads among confirmed cases can provide insights into epidemic trajectory. Here, we analyzed viral load data on confirmed cases during two local epidemics in Hong Kong, identifying a strong correlation between temporal changes in the distribution of viral loads (measured by RT-qPCR cycle threshold values) and estimates of [Formula: see text] based on case counts. We demonstrate that cycle threshold values could be used to improve real-time [Formula: see text] estimation, enabling more timely tracking of epidemic dynamics.

Transmissibility and transmission of respiratory viruses.

Human respiratory virus infections lead to a spectrum of respiratory symptoms and disease severity, contributing to substantial morbidity, mortality and economic losses worldwide, as seen in the COVID-19 pandemic. Belonging to diverse families, respiratory viruses differ in how easy they spread (transmissibility) and the mechanism (modes) of transmission. Transmissibility as estimated by the basic reproduction number (R0) or secondary attack rate is heterogeneous for the same virus. Respiratory viruses can be transmitted via four major modes of transmission: direct (physical) contact, indirect contact (fomite), (large) droplets and (fine) aerosols. We know little about the relative contribution of each mode to the transmission of a particular virus in different settings, and how its variation affects transmissibility and transmission dynamics. Discussion on the particle size threshold between droplets and aerosols and the importance of aerosol transmission for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus is ongoing. Mechanistic evidence supports the efficacies of non-pharmaceutical interventions with regard to virus reduction; however, more data are needed on their effectiveness in reducing transmission. Understanding the relative contribution of different modes to transmission is crucial to inform the effectiveness of non-pharmaceutical interventions in the population. Intervening against multiple modes of transmission should be more effective than acting on a single mode.

Upper Respiratory Infections in Schools and Childcare Centers Reopening after COVID-19 Dismissals, Hong Kong.

A large number of common cold outbreaks in Hong Kong schools and childcare centers during October-November 2020 led to territorywide school dismissals. Increased susceptibility to rhinoviruses during prolonged school closures and dismissals for coronavirus disease and varying effectiveness of nonpharmaceutical interventions may have heightened transmission of cold-causing viruses after school attendance resumed.

Author Correction: Respiratory virus shedding in exhaled breath and efficacy of face masks.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

SARS-CoV-2 environmental contamination associated with persistently infected COVID-19 patients.

BACKGROUND: Severe COVID-19 patients typically test positive for SARS-CoV-2 RNA for extended periods of time, even after recovery from severe disease. Due to the timeframe involved, these patients may have developed humoral immunity to SARS-CoV-2 while still testing positive for viral RNA in swabs. Data are lacking on exposure risks in these situations. Here, we studied SARS-CoV-2 environmental contamination in an ICU and an isolation ward caring for such COVID-19 patients. METHODS: We collected air and surface samples in a hospital caring for critical and severe COVID-19 cases from common areas and areas proximal to patients. RESULTS: Of the 218 ICU samples, an air sample contained SARS-CoV-2 RNA. Of the 182 isolation ward samples, nine contained SARS-CoV-2 RNA. These were collected from a facemask, the floor, mobile phones, and the air in the patient room and bathroom. Serum antibodies against SARS-CoV-2 were detected in these patients at the beginning of the study. CONCLUSIONS: While there is a perception of increased risk in the ICU, our study demonstrates that isolation wards may pose greater risks to healthcare workers and exposure risks remain with clinically improved patients, weeks after their initial diagnoses. As these patients had serum antibodies, further studies may be warranted to study the utility of serum antibodies as a surrogate of viral clearance in allowing people to return to work. We recommend continued vigilance even with patients who appear to have recovered from COVID-19.

Respiratory virus shedding in exhaled breath and efficacy of face masks.

We identified seasonal human coronaviruses, influenza viruses and rhinoviruses in exhaled breath and coughs of children and adults with acute respiratory illness. Surgical face masks significantly reduced detection of influenza virus RNA in respiratory droplets and coronavirus RNA in aerosols, with a trend toward reduced detection of coronavirus RNA in respiratory droplets. Our results indicate that surgical face masks could prevent transmission of human coronaviruses and influenza viruses from symptomatic individuals.