Respiratory syncytial virus, human metapneumovirus, and influenza virus infection in Bangkok, 2016-2017

Children and adults residing in densely populated urban centers around the world are at risk of seasonal influenza-like illness caused by respiratory viruses such as influenza virus, human metapneumovirus (hMPV), and respiratory syncytial virus (RSV). In a large metropolitan of Thailand’s capital city Bangkok, most respiratory infections are rarely confirmed by molecular diagnostics. We therefore examined the frequency of RSV, hMPV, and influenza virus in 8,842 patients who presented influenza-like illness and sought medical care at a large hospital in Bangkok between 2016 and 2017. Using a multiplex real-time reverse-transcription polymerase chain reaction (RT-PCR), 30.5% (2,699/8,842) of nasopharyngeal (NP) swab samples tested positive for one or more of these viruses. Influenza virus comprised 17.3% (1,528/8,842), of which the majority were influenza A/H3N2. Such infection was most prevalent among adults and the elderly. RSV was identified in 11.4% (1,011/8,842) and were mostly ON1 and BA9 genotypes. Of the hMPV-positive samples (3.6%, 318/8,842), genotypes A2, B1, and B2 were detected. A small number of individuals experienced co-infections (1.8%, 155/8,842), most commonly between RSV and influenza A/H3N2. RSV and hMPV co-infections were also found, but mainly in young children. Viral respiratory tract infection peaked locally in the rainy season (June to September). These findings support the utility of rapid nucleic acid testing of RSV, hMPV, and influenza virus in patients with ILI

Global patterns in monthly activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus: a systematic analysis

Background: Influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus are the most common viruses associated with acute lower respiratory infections in young children (<5 years) and older people (≥65 years). A global report of the monthly activity of these viruses is needed to inform public health strategies and programmes for their control. Methods: In this systematic analysis, we compiled data from a systematic literature review of studies published between Jan 1, 2000, and Dec 31, 2017; online datasets; and unpublished research data. Studies were eligible for inclusion if they reported laboratory-confirmed incidence data of human infection of influenza virus, respiratory syncytial virus, parainfluenza virus, or metapneumovirus, or a combination of these, for at least 12 consecutive months (or 52 weeks equivalent); stable testing practice throughout all years reported; virus results among residents in well-defined geographical locations; and aggregated virus results at least on a monthly basis. Data were extracted through a three-stage process, from which we calculated monthly annual average percentage (AAP) as the relative strength of virus activity. We defined duration of epidemics as the minimum number of months to account for 75% of annual positive samples, with each component month defined as an epidemic month. Furthermore, we modelled monthly AAP of influenza virus and respiratory syncytial virus using site-specific temperature and relative humidity for the prediction of local average epidemic months. We also predicted global epidemic months of influenza virus and respiratory syncytial virus on a 5° by 5° grid. The systematic review in this study is registered with PROSPERO, number CRD42018091628. Findings: We initally identified 37 335 eligible studies. Of 21 065 studies remaining after exclusion of duplicates, 1081 full-text articles were assessed for eligibility, of which 185 were identified as eligible. We included 246 sites for influenza virus, 183 sites for respiratory syncytial virus, 83 sites for parainfluenza virus, and 65 sites for metapneumovirus. Influenza virus had clear seasonal epidemics in winter months in most temperate sites but timing of epidemics was more variable and less seasonal with decreasing distance from the equator. Unlike influenza virus, respiratory syncytial virus had clear seasonal epidemics in both temperate and tropical regions, starting in late summer months in the tropics of each hemisphere, reaching most temperate sites in winter months. In most temperate sites, influenza virus epidemics occurred later than respiratory syncytial virus (by 0·3 months [95% CI −0·3 to 0·9]) while no clear temporal order was observed in the tropics. Parainfluenza virus epidemics were found mostly in spring and early summer months in each hemisphere. Metapneumovirus epidemics occurred in late winter and spring in most temperate sites but the timing of epidemics was more diverse in the tropics. Influenza virus epidemics had shorter duration (3·8 months [3·6 to 4·0]) in temperate sites and longer duration (5·2 months [4·9 to 5·5]) in the tropics. Duration of epidemics was similar across all sites for respiratory syncytial virus (4·6 months [4·3 to 4·8]), as it was for metapneumovirus (4·8 months [4·4 to 5·1]). By comparison, parainfluenza virus had longer duration of epidemics (6·3 months [6·0 to 6·7]). Our model had good predictability in the average epidemic months of influenza virus in temperate regions and respiratory syncytial virus in both temperate and tropical regions. Through leave-one-out cross validation, the overall prediction error in the onset of epidemics was within 1 month (influenza virus −0·2 months [−0·6 to 0·1]; respiratory syncytial virus 0·1 months [−0·2 to 0·4]). Interpretation: This study is the first to provide global representations of month-by-month activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus. Our model is helpful in predicting the local onset month of influenza virus and respiratory syncytial virus epidemics. The seasonality information has important implications for health services planning, the timing of respiratory syncytial virus passive prophylaxis, and the strategy of influenza virus and future respiratory syncytial virus vaccination. Funding: European Union Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU)

COVID-19 Breakthrough Infection after Inactivated Vaccine Induced Robust Antibody Responses and Cross-Neutralization of SARS-CoV-2 Variants, but Less Immunity against Omicron

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the waning of immunity in vaccinated individuals is resulting in increased numbers of SARS-CoV-2 breakthrough infections. This study investigated binding antibody responses and neutralizing activities against SARS-CoV-2 variants, in patients with COVID-19 who had been fully vaccinated with CoronaVac (n = 77), individuals who had been fully vaccinated with CoronaVac but had not contracted COVID-19 (n = 170), and individuals who had received AZD1222 as a third vaccination (n = 210). Breakthrough infection was generally detected approximately 88 days after the second CoronaVac vaccination (interquartile range 68&ndash;100 days). Blood samples were collected at a median of 34 days after infection. Binding antibody levels in sera from patients with breakthrough infection were significantly higher than those in individuals who had received AZD1222 as a third vaccination. However, neutralizing activities against wild-type and variants, including alpha (B.1.1.7), beta (B.1.351), and delta (B.1.617.2), were comparable in patients with breakthrough infections and individuals who received a third vaccination with AZD1222, which exceeds 90%. Omicron (B.1.1.529) was neutralized less effectively by serum from breakthrough infection patients, with a 6.3-fold reduction compared to delta variants. The study suggests that breakthrough infection after two doses of an inactivated vaccine can induce neutralizing antibodies against omicron. Further investigation is needed to assess the long-term persistence of antibodies against the omicron variant

Pivoting to protein: the immunogenicity and safety of protein-based NVX-CoV2373 as a heterologous booster for inactivated and viral vector COVID-19 vaccines

Introduction Approximately half of the 13.4 billion COVID-19 vaccine doses administered globally were inactivated or viral vector platforms. The harmonization and optimization of vaccine regimens has become a key focus of policymakers and health-care providers and presents an opportunity to reassess the continued use of pandemic-era vaccines. Areas covered Immunological evidence from studies of various homologous and heterologous regimens has been rapidly published; however, interpretation of these data is complicated by the many vaccine types and highly variable participant viral exposure and vaccination histories. Recent studies demonstrate that after primary series doses of inactivated (i.e. BBV152, and BBIBP-CorV), and viral vector (ChAdOx1 nCov-2019) vaccines, a heterologous boost with protein-based NVX-CoV2373 elicits more potent ancestral strain and omicron-specific antibody responses compared to homologous and heterologous inactivated and viral vector boosts. Expert opinion While mRNA vaccines likely yield similar performance to protein-based heterologous booster doses, the latter offers notable advantages to countries with high uptake of inactivated and viral vector vaccines in terms of transportation and storage logistics and can potentially appeal to vaccine hesitant individuals. Moving forward, vaccine-mediated protection in inactivated and viral vector recipients may be optimized with the use of a heterologous protein-based booster such as NVX-CoV2373. Pivoting to Protein The Immunogenicity and Safety of Protein-based NVX-CoV2373 as a Heterologous Booster for Inactivated and Viral Vector COVID-19 Vaccines. Inactivated or viral vector primary series following a booster dose with homologous or heterologous inactivated vaccines (i.e., BBV152, BBIBP-CorV), and homologous or heterologous viral vector vaccines (i.e., ChAd-Ox1 nCov-19) induces suboptimal immunogenicity compared to the enhanced immunogenicity of heterologous protein-based vaccine NVX-CoV2373

Durability of immune response against omicron BA.2 and BA.4/5 and T cell responses after boosting with mRNA and adenoviral vector-based vaccines following heterologous CoronaVac/ChAdOx-1nCov-19 vaccination

ABSTRACTHeterologous vaccination with inactivated vaccine followed by adenoviral vector-based vaccine has shown superiority in enhancing immune response compared to homologous primary series. However, data comparing immunity decline after a third booster following heterologous CoronaVac/ChAdOx-1nCov-19 has been limited. Here, we assessed neutralizing activity against omicron variant and T cell response at 3 months monitoring in 96 individuals who received ChAdOx-1nCov-19, BNT162b2, or mRNA-1273 as a third dose following heterologous CoronaVac/ChAdOx-1nCov-19. Comparing the antibody levels at 3 and 1 month(s) after the third booster, the results showed a persistence of anti-RBD IgG in all vaccine regimens, with the IgG level waning slower in the ChAdOx-1nCov-19 boosted group (geometric mean ratio (GMR): 0.64 (95%CI: 0.59–0.70)) compared to the BNT162b2 (0.34 (95%CI:0.31–0.38)) and mRNA-1273 boosted groups (0.32 (95%CI: 0.29–0.36)). Neutralizing activity against omicron BA.2 and BA.4/5 dropped by 1.2 to 1.5-fold but remained detectable, with the highest level observed in the mRNA-1273 group, followed by BNT162b2 and ChAdOx-1nCov-19 groups, respectively. Furthermore, the number of individuals with T cell reactivity decreased in BNT162b2 and mRNA-1273 groups, while it increased in ChAdOx-1nCov-19 group at 3-month post-boost compared to 1 month. Data on the durability of immune response could help comprehensively optimize the booster vaccine strategy

Evaluation of Anti-S1 IgA Response to Different COVID-19 Vaccination Regimens

IgA plays a crucial role in early virus neutralization. To identify the IgA stimulation by COVID-19 vaccine, this study aimed to evaluate the level of anti-S1 IgA in the serum of participants immunized with different COVID-19 vaccination regimens. Sera from 567 eligible participants vaccinated with two, three, or four doses of different types of COVID-19 vaccine were recruited. Post-vaccine anti-S1 IgA responses significantly varied according to vaccine type and regimen. The finding showed that heterologous boosters, especially after priming with an inactivated vaccine, elicited higher IgA levels than homologous boosters. Vaccination with SV/SV/PF produced the highest IgA level among all the immunization regimens after either two, three, or four doses. The different routes and amounts of vaccine used for vaccination showed non-significant differences in IgA levels. After the third dose of immunization for 4 months, the level of IgA decreased significantly from the level found on day 28 in both SV/SV/AZ and SV/SV/PF groups. In conclusion, our study showed that heterologous booster regimens for COVID-19 elicited higher anti-S1 IgA levels in serum, especially after priming with inactivated vaccine. The presented anti-S1 IgA may have advantages in preventing SARS-CoV-2 infection and severe disease

Climate factors influence seasonal influenza activity in Bangkok, Thailand.

Yearly increase in influenza activity is associated with cold and dry winter in the temperate regions, while influenza patterns in tropical countries vary significantly by regional climates and geographic locations. To examine the association between influenza activity in Thailand and local climate factors including temperature, relative humidity, and rainfall, we analyzed the influenza surveillance data from January 2010 to December 2018 obtained from a large private hospital in Bangkok. We found that approximately one in five influenza-like illness samples (21.6% or 6,678/30,852) tested positive for influenza virus. Influenza virus typing showed that 34.2% were influenza A(H1N1)pdm09, 46.0% were influenza A(H3N2), and 19.8% were influenza B virus. There were two seasonal waves of increased influenza activity. Peak influenza A(H1N1)pdm09 activity occurred in February and again in August, while influenza A(H3N2) and influenza B viruses were primarily detected in August and September. Time series analysis suggests that increased relative humidity was significantly associated with increased influenza activity in Bangkok. Months with peak influenza activity generally followed the most humid months of the year. We performed the seasonal autoregressive integrated moving average (SARIMA) multivariate analysis of all influenza activity on the 2011 to 2017 data to predict the influenza activity for 2018. The resulting model closely resembled the actual observed overall influenza detected that year. Consequently, the ability to predict seasonal pattern of influenza in a large tropical city such as Bangkok may enable better public health planning and underscores the importance of annual influenza vaccination prior to the rainy season

High seroprevalence of antibodies against human respiratory syncytial virus and evidence of respiratory syncytial virus reinfection in young children in Thailand

Objectives: To investigate the seroprevalence of respiratory syncytial virus (RSV) infections in young children, the correlation between RSV antibody levels in maternal and cord serum, and to provide evidence of RSV reinfection in Thai children after primary infections. Methods: Serum samples were collected from 302 mothers and 291 children between 2015 and 2021. Maternal and cord blood were collected at birth. Serial serum samples of children were collected at the ages of 2, 7, 18, 19, 24, 36, 48, and 60 months and the presence of anti-RSV immunoglobulin G (IgG) was tested using an enzyme-linked immunosorbent assay. Results: The cord: maternal serum antibody ratio was 1.09 (95% confidence interval 1.08-1.11). Although >90% of babies at birth were seropositive through transplacental transfer, antibody levels gradually declined, with the highest seronegative rate (91.9%) at 7 months of age. Subsequently, anti-RSV IgG levels increased with age, most likely due to natural infection. One-third of the children showed evidence of reinfection as determined by seroconversion of anti-RSV IgG or increased titers of at least 50 relative units/ml. Conclusion: Waning of RSV antibodies in infants is rapid, and RSV infection subsequently increases anti-RSV IgG titers. RSV vaccination in children before the age of 7 months should be recommended

Distribution of influenza A(H3N2) virus between January 2016 and June 2017 (n = 7,228).

<p>Total number of clinical samples evaluated (Y-axis on the right) and different influenza virus-positive samples are shown (Y-axis on the left). Numbers above the bar graphs denote influenza virus-positive samples identified each month.</p

Phylogenetic analysis of the nucleotide sequences of the HA coding region of A(H3N2).

<p>Sequences of randomly selected samples from this study (n = 62) (designated A/Thailand/CU and denoted in colored dots) and those identified in Thailand from the databases during 2016–2017 (n = 29) were compared to the A(H3N2) vaccine and reference strains of known clades reported by the WHO and others (squares). The phylogenetic tree was constructed using the maximum likelihood method and HKY+G model with 1,000 bootstrap replicates implemented in MEGA (version 6). Branch values of >70% are indicated at the nodes. Dominant epitope (A-E) determined for each sequence are marked with different colored dots (A = yellow, B = pink, C = purple, D = green, and E = blue). The signature amino acid substitutions (colored) occurring on the antigenic epitopes are also shown. Scale bar represents approximately 0.5% nucleotide difference between close relatives. Residue numbers are specific for HA1 (color-coded by epitope) and HA2 (dark blue). The vaccine strain A/Hong Kong/4801/2014 belonged to 3C.2a clade. Shaded area (Group V) highlights strains of interest.</p