Title: Age-related risk of household transmission of COVID-19 in SingaporeRachael Pung1, Minah Park2,3, Alex R Cook2,3, Vernon J Lee1,21 Ministry of Health, Singapore2 Saw Swee Hock School of Public Health, National University of Singapore3 National University Health System

Objectives: To understand the epidemiological and clinical characteristics of pediatric SARS-CoV-2 infection during the early stage of Omicron variant outbreak in Shanghai. Study designs: This study included local COVID-19 cases<18 years in Shanghai referred to the exclusively designated hospital by the end of March 2022 since emergence of Omicron epidemic. Clinical data, epidemiological exposure and COVID-19 vaccination status were collected. Relative risks (RR) were calculated to assess the effect of vaccination on symptomatic infection and febrile disease. Results: A total of 376 pediatric cases of COVID-19 (median age:6.0±4.2 years) were referred to the designated hospital during the period of March 7-31, including 257 (68.4%) symptomatic cases and 119 (31.6%) asymptomatic cases. Of the 307 (81.6%) children ≥3 years eligible for COVID-19 vaccination, 110 (40.4%) received 2-dose vaccines and 16 (4.0%) received 1-dose vaccine. The median interval between 2-dose vaccination and infection was 3.5 (IQR: 3, 4.5) months (16 days-7 months). Two-dose COVID-19 vaccination reduced the risks of symptomatic infection and febrile disease by 35%(RR 0.65, 95% CI: 0.53-0.79) and 33% (RR 0.64, 95% CI: 0.51-0.81). Two hundred and sixteen (83.4%) symptomatic cases had fever (mean duration:1.7±1.0.8 days), 104 (40.2%) had cough, 16.4% had transient leukopenia; 307 (81.6%) had an epidemiological exposure in household (69.1%) , school (21.8%) and residential area (8.8%). Conclusion: The surge of pediatric COVID-19 cases and multiple transmission model reflect wide dissemination of Omicron variant in the community. Asymptomatic infection is common among Omicron-infected children. COVID-19 vaccination can offer some protection against symptomatic infection and febrile dise

Background: Measures introduced during the COVID-19 pandemic intended to address the spread of SARS-CoV-2 may also influence the incidence of other common seasonal respiratory viruses (SRV). This evaluation reports laboratory confirmed cases of common SRV in a well-defined region of central Canada to address this issue. Methods: Surveillance data for common non-SARS-CoV-2 SRV in the Ottawa, Canada region was provided by the Eastern Ontario Regional Laboratory Association (EORLA) reference virology lab. Weekly reports of the number of positive tests and proportion that yielded positive results was analyzed from August 26, 2018 to January 2, 2022. Results: A drastic reduction in influenza and other common SRV was observed during the 2020-2021 influenza season in the Ottawa region. Influenza was virtually undetected post SARS-CoV-2 emergence. Rhinoviruses and enteroviruses were the only viruses that remained relatively unaffected during this period. Conclusions: We speculated that the introduction of non-pharmaceutical measures including masking to prevent SARS-CoV-2 transmission contributed to the near absence of SRV in the Ottawa region. These measures should remain a key component in addressing spikes in SRV activity and future pandemics.

Background: Human respiratory syncytial virus (HRSV) is a major cause of severe viral acute respiratory illness and contributes significantly to severe pneumonia cases in Africa. Little is known about its spatial-temporal distribution as defined by its genetic diversity. Methods: A retrospective study conducted utilizing archived nasopharyngeal specimens from patients attending outpatient clinics in hospitals located in five demographically and climatically distinct regions of Kenya; Coast, Western, Highlands, Eastern and Nairobi. The viral total RNA was extracted and tested using multiplex real time RT-PCR (reverse transcriptase polymerase chain reaction). A segment of the G-gene was amplified using one-step RT-PCR and sequenced by Sanger di-deoxy method. Bayesian analysis of phylogeny was utilized and subsequently median joining methods for haplotype network reconstruction. Results: Three genotypes of HRSVA were detected; GA5 (14.0%), GA2 (33.1%) and NA1 (52.9%). HRSVA prevalence varied by location from 33% to 13.2% in the Highlands and the Eastern regions respectively. The mean nucleotide diversity (Pi(π)) varied by genotype: highest of 0.018 for GA5 and lowest of 0.005 for NA1. A total of 58 haplotypes were identified (GA5 10; GA2 20; NA1 28). These haplotypes were introduced into the population locally by single haplotypes and additional subsidiary seeds amongst the GA2 and the NA1 haplotypes. Conclusions: HRSVA was found across all the regions throughout the study period and comprised three genotypes; GA5, GA2 and NA1 genotypes. The genotypes were disproportionately distributed across the regions with GA5 gradually increasing towards the Western zones and decreasing towards the Eastern zones of the country.

Although there has been an effective seasonal influenza vaccine available for more than 60 years, influenza continues to circulate and cause illness. The Eastern Mediterranean Region (EMR) is very diverse in health systems capacities, capabilities, and efficiencies, which affect the performance of services, especially vaccinations, including seasonal influenza vaccination. In this article, we have analyzed data from a regional seasonal influenza survey conducted in 2022, Joint Reporting Form (JRF), and verified their validity by the focal points. We also compared our results with those of the regional seasonal influenza survey conducted in 2016. This analysis provides a comprehensive overview on country-specific influenza vaccination policies, vaccine delivery, and coverage in EMR. Fourteen countries (64%) had reported having a national seasonal influenza vaccine policy. About (44%) countries recommended influenza vaccine for all SAGE recommended target groups. Up to (69%) of countries reported that COVID-19 had an impact on influenza vaccine supply in the country, with most of them (82%) reporting increases in procurement and supply of influenza vaccine, with the other countries reporting decreases in procurement due to COVID-19. We suggest supporting countries to develop a roadmap for influenza vaccine uptake and utilization, assessment of barriers and burden of influenza, including measuring the economic burden to enhance vaccine acceptance.

Background: Influenza is a persistent public health problem associated with severe morbidity and mortality. Drug use is related to myriad health complications, but the relationship between drug use and severe influenza outcomes is not well understood. The study objective was to evaluate the relationship between drug use and severe influenza-associated outcomes. Methods: Data were collected by the Influenza Hospitalization Surveillance Network (FluSurv-NET) from the 2016-2017 through 2018-2019 influenza seasons. Among persons hospitalized with influenza, descriptive statistics and logistic regression models were used to analyze differences in demographic characteristics, risk and behavioral factors, and severe outcomes (intensive care unit [ICU] admission, mechanical ventilation, or death) between people who used drugs (PWUD), defined as having documented drug use within the past year, and non-PWUD. Results: Among 48,430 eligible hospitalized influenza cases, 2,019 were PWUD and 46,411 were non-PWUD. PWUD were younger than non-PWUD and more likely to be male, non-Hispanic Black or Hispanic/Latino, smoke tobacco, abuse alcohol, and have chronic conditions including asthma, chronic liver disease, chronic lung disease, or immunosuppressive conditions. PWUD had greater odds of ICU admission and mechanical ventilation, but not death compared with non-PWUD. Opioid use specifically was associated with increased risk of ICU admission and mechanical ventilation. Conclusion: PWUD had greater odds of ICU admission and mechanical ventilation than non-PWUD hospitalized with influenza. These results support targeted initiatives to prevent influenza and associated severe outcomes among this population.

Pandemic influenza viruses may emerge from animal reservoirs and spread among humans in the absence of cross-reactive antibodies in the human population. Immune response to highly conserved T cell epitopes in vaccines may still reduce morbidity and limit the spread of the new virus even when cross-protective antibody responses are lacking. We used an established epitope content prediction and comparison tool, EpiCC, to assess the potential for emergent H1N1 G4 swine influenza A virus (G4) to impact swine and human populations. We identified and computed the total cross-conserved T cell epitope content in HA sequences of human seasonal and experimental influenza vaccines, swine influenza vaccines from Europe and the United States (US) against G4. The overall T cell epitope content of US commercial swine vaccines was poorly conserved with G4, with an average T cell epitope coverage of 35.7%. EpiCC scores for the comparison between current human influenza vaccines and circulating human influenza strains were also very low. In contrast, the T cell epitope coverage of a recent European swine influenza vaccine (HL03) was 65.8% against G4. Poor T cell epitope cross-conservation between emergent G4 and swine and human influenza vaccines in the US may enable G4 to spread in swine and spillover to human populations in the absence of protective antibody response. One European influenza vaccine, HL03, may protect against emergent G4. This study illustrates the use of the EpiCC tool for prospective assessment of existing vaccine strains against emergent viruses in swine and human populations.

Stringent public health measures imposed across Canada to control the COVID-19 pandemic have nearly suppressed most seasonal respiratory viruses, with the notable exception of human rhinovirus/enterovirus (hRV/EV). Thanks to this unexpected persistence, we highlight that hRV/EV could serve as a sentinel for levels of contact rate in populations to inform on the efficiency¬, or the need of, public health measures to control the subsequent COVID-19 epidemic, but also for future epidemics from other seasonal or emerging respiratory pathogens.

As we approach the three-year anniversary of the pandemic, we are now facing a seasonal influenza epidemic after two years without one. In light of growing concerns over the potential risk of a “twindemic,” the Republic of Korea is currently experiencing the first peak of seasonal flu and the overall pattern is quite similar to that observed before the COVID-19 pandemic. Notably, no sudden or early increase in cases has been detected, which is unique compared to other countries.

Background First Few “X” (FFX) studies provide evidence to guide public health decision making and resource allocation. The adapted WHO Unity FFX protocol for COVID-19 was implemented to gain an understanding of the clinical, epidemiological, virological, and household transmission dynamics of the first cases of COVID-19 infection detected in Juba, South Sudan. Methods Laboratory-confirmed COVID-19 cases were identified through the national surveillance system, and an initial visit was conducted with eligible cases to identify all close contacts. Consenting cases and close contacts were enrolled between June 2020 and December 2020. Demographic, clinical information and biological samples were taken at enrolment and 14–21 days post-enrolment for all participants. Results Twenty-nine primary cases and 82 contacts were included in analyses. Most primary cases (n=23/29, 79.3%) and contacts (n=61/82, 74.4%) were male. Many primary cases (n=18/29, 62.1%) and contacts (n=51/82, 62.2%) were seropositive for SARS-CoV-2 at baseline. The secondary attack rate among susceptible contacts was 12.9% (4/31; 95% CI: 4.9%–29.7%). All secondary cases and most (72%) primary cases were asymptomatic. Reported symptoms included coughing (n=6/29, 20.7%), fever or history of fever (n=4/29, 13.8%), headache (n=3/29, 10.3%) and shortness of breath (n=3/29, 10.3%). Of 38 cases, two were hospitalised (5.3%) and one died (2.6%). Conclusions These findings were used to develop the South Sudanese Ministry of Health surveillance and contract tracing protocols, informing local COVID-19 case definitions, follow-up protocols and data management systems. This investigation demonstrates that rapid FFX implementation is critical in understanding the emerging disease and informing response priorities.

Background: The transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is complex and multifactorial. We aimed to identify the risk factors for infection among the household contacts of index patients and to determine the incubation period, serial interval, and estimates of secondary infection rate. Methods: We conducted a study in three districts of Kerala among the inhabitants of households of reverse transcriptase polymerase chain reaction (RT-PCR)-positive coronavirus disease (COVID-19) patients between January and July 2021. COVID-19-positive patients and corresponding contacts were enrolled and followed up for 28 days to determine RT-PCR positivity and the presence of total antibodies against SARS-CoV-2 on days 1, 7, 14, and 28 from the date of enrolment. Results: The mean incubation period, serial interval, and generation time were 1.6, 3, and 3.9 days, respectively. The secondary infection rate was 43.0%. Individuals who worked outside the home were protected, whereas those who had kissed the COVID-19-positive patients during illness were more than twice at risk of infection than those who had not kissed the COVID-19-positive patients. Similarly, the contacts who had shared a toilet with the COVID-19-positive patients were more at risk than those who had not shared a toilet. However, the contacts who reported using masks were at a higher risk of infection in household settings. Conclusions Assessment of SARS-CoV-2 transmission in household settings is important, considering its high secondary infection rate. Close physical contact and toilet sharing increase the risk of infection. This study demonstrates shorter incubation period and serial interval.

Background and objectives: To re-activate infuneza sentinel surveillance system in Yemen after disruption related to repurposing for COVID-19 pandemic. WHO Country Office (CO) in collaboration with Yemen’s Ministry of Public Health and Population (MOPH&P) jointly conducted an assessment mission to assess the current situation of the influenza sentinel surveillance system and assess its capacity to detect influenza epidemics and monitor trends in circulating influenza and other respiratory viruses of epidemic and pandemic potential. This study presents the results of the assessment for three sentinel sites located in Aden, Taiz and Hadramout/Mukalla. Methodology: A mixed methods approach was used to guide the assessment process and to help achieve the objectives. Data was collected as follows: desk review of the sentinel sites records and data; interviews with stakeholders, including key informants and partners; and direct observation through field visits to the sentinel sites, MOPH&P and the Central Public Health Laboratory (CPHL). Two assessment checklists were used: assessment of sentinel sites for SARI surveillance, and checklist for assessment of availability of SARI sentinel surveillance. Results and conclusion: COVID19 has affected health systems and services, and this was demonstrated in this assessment. The influenza sentinel surveillance system in Yemen is not effectively functional, however there’s plenty of room for improvement if investment in the system’s restructuring, training, building technical and laboratory capacities, and conducting continuous and regular supervision visits.

Background: The nucleoprotein (N protein) of respiratory syncytial virus (RSV) is a candidate antigen for new RSV vaccine development. The aim of the present study was to investigate the association between maternal antibody titers against the RSV N protein at birth and the newborns’ risk of developing very-severe lower respiratory tract infection (VS-LRTI). Methods: In this single-center prospective cohort study, 578 infants born during the RSV epidemic season in France were included. Among these, 36 were hospitalized for RSV VS-LRTI. A generalized linear model was used to test the occurrence of a VS-LRTI in function of sex, mode of delivery, parity of the mother, type of pregnancy, date of birth in relation to the peak of the epidemic, and antibody titer against N protein. Results: All cord blood samples had detectable antibodies against N protein. The mean titers were significantly lower in newborns with risk factors for RSV severe LRTI (preterm infants, birth before the peak epidemic, multiparous mother). There was no association between antibody titer against the N protein and a protection against VS-LRTI. Conclusions The present study found that transfer of maternal antibodies against the RSV N protein may not provide a significant immune protection early in infancy. Clinical Trials Registration. NCT04144816.

Background There is a need for vaccines that can induce effective systemic, respiratory mucosal and cellular immunity to control the COVID-19 pandemic. We reported previously that a synthetic mucosal adjuvant SF-10 derived from human pulmonary surfactant works as an efficient antigen delivery vehicle to antigen presenting cells in the respiratory and gastrointestinal tracts and promotes induction of influenza virus antigen-specific serum IgG, mucosal IgA and cellular immunity. Methods The aim of the present study was to determine the effectiveness of a new administration method of intratracheal (IT) vaccine comprising recombinant SARS-CoV-2 spike protein 1 (S1) combined with SF-10 (S1-SF-10 vaccine) on systemic, local and cellular immunity in mice, compared with intramuscular injection (IM) of S1 with a potent adjuvant AS03 (S1-AS03 vaccine). Results S1-SF-10-IT vaccine induced S1-specific IgG and IgA in serum and lung mucosae. These IgG and IgA induced by S1-SF-10-IT showed significant protective immunity in a receptor binding inhibition test of S1 and angiotensin converting enzyme 2, a receptor of SARS-CoV-2, which were more potent and faster achievement than S1-AS03-IM. Enzyme-linked immunospot assay showed high numbers of S1-specific IgA and IgG secreting cells (ASCs) and S1-responsive IFN-γ, IL-4, IL-17A cytokine secreting cells (CSCs) in the spleen and lungs. S1-AS03-IM induced IgG ASCs and IL-4 CSCs in spleen higher than S1-SF10-IT, but the numbers of ASCs and CSCs in lungs were low and hardly detected. Conclusion Based on the need for effective systemic, respiratory and cellular immunity, the S1-SF-10-IT vaccine seems promising mucosal vaccine against respiratory infection of SARS-CoV-2.

Background: Influenza-associated pulmonary aspergillosis (IAPA) is an important complication of severe influenza with high morbidity and mortality. Methods: We conducted a retrospective multicenter study in tertiary hospitals in Switzerland during 2017/18 and 2019/20 influenza seasons. All adults with PCR-confirmed influenza infection and treatment on intensive-care unit (ICU) for >24h were included. IAPA was diagnosed according to previously published clinical, radiological and microbiological criteria. We assessed risk factors for IAPA and predictors for poor outcome which was a composite of in-hospital mortality, ICU length of stay ≥7d, mechanical ventilation ≥7d or extracorporeal membrane oxygenation. Results: 158 patients (median age 64 years, 45% females) with influenza were included, of which 17 (10.8%) had IAPA. Asthma was more common in IAPA patients (17% vs. 4% in non-IAPA, p=0.05). Asthma (OR 12.0 (95% CI 2.1-67.2)) and days of mechanical ventilation (OR 1.1 (1.1 – 1.2)) were associated with IAPA. IAPA patients frequently required organ supportive therapies including mechanical ventilation (88% in IAPA vs. 53% in non-IAPA, p=0.001) and vasoactive support (75% vs. 45%, p=0.03) and had more complications including ARDS (53% vs. 26%, p=0.04), respiratory bacterial infections (65% vs. 37%, p=0.04) and higher ICU-mortality (35% vs. 16.4%, p=0.05). IAPA (OR 28.8 (3.3–253.4)), influenza A (OR 3.3 (1.4-7.8)) and higher SAPS II score (OR 1.07 (1.05—1.10)) were independent predictors of poor outcome. Interpretation: High clinical suspicion, early diagnostics and therapy are indicated in IAPA because of high morbidity and mortality. Asthma is likely an underappreciated risk factor for IAPA.

Background: Although the burden of influenza is well characterized, the burden of community-onset non-influenza respiratory viruses has not been systematically assessed. Understanding the severity and seasonality of non-influenza viruses, including human coronaviruses, will provide a better understanding of the overall disease burden from respiratory viruses that could better inform resource utilization for hospitals and highlight the value of preventative strategies, including vaccines. Methods: From October 2017 to September 2019, a retrospective study was performed in a pre-defined catchment area to estimate the population-based incidence of community-onset respiratory viruses associated with hospitalization. Included patients were >18 years old, resided in New York City, were hospitalized for >24 hours, and had a respiratory virus detected within 3 calendar-days of admission. Disease burden was measured by hospital length of stay (LOS), intensive care unit (ICU) admissions, and in-hospital mortality and compared among those with laboratory-confirmed influenza versus those with laboratory-confirmed non-influenza viruses (human coronaviruses, parainfluenza viruses, respiratory syncytial virus, human metapneumovirus, and adenovirus). Results: During the study period, 4,232 eligible patients were identified of whom 50.9% were >65 years of age. For each virus, the population-based incidence was highest for those >80 years of age. When compared to those with influenza viruses detected, those with non-influenza respiratory viruses detected (combined) had higher population-based incidence, significantly more ICU admissions, and higher in-house mortality. Conclusions: The burden of non-influenza respiratory viruses for hospitalized adults is substantial. Prevention and treatment strategies are needed for non-influenza respiratory viruses, particularly for older adults.

The emergence of SARS-CoV-2 Omicron variant has led to a complete reconfiguration of the therapeutic landscape, with most monoclonal antibodies having lost any neutralization activity. We report here a case series of 75 immunocompromised patients infected by the Omicron variant who benefited of convalescent plasma. At baseline, 49 (68%) of the participants had a WHO score of 5 and 23 (32%) a WHO score of 6. At day 28 the case fatality was 24%. We observed no significant difference in the clinical outcome between patients with hematological malignancies, solid organ transplantation or auto-immune diseases. These promising results require controlled studies.

Background Sarajevo Canton in the Federation of Bosnia and Herzegovina has recorded several waves of high SARS-CoV-2 transmission and has struggled to reach adequate vaccination coverage. We describe the evolution of infection- and vaccine-induced SARS-CoV-2 antibody response and persistence. Methods We conducted repeated cross-sectional analyses of blood donors aged 18-65 years in Sarajevo Canton in November-December 2020 and 2021. We analyzed serum samples for anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibodies. To assess immune durability, we conducted longitudinal analyses of seropositive participants at 6 and 12 months. Results 1015 participants were included in Phase 1 (November-December 2020), and 1152 in Phase 2 (November-December 2021). Seroprevalence increased significantly from 19.2% (95% CI: 17.2-21.4%) in Phase 1 to 91.6% (95% CI: 89.8-93.1%) in Phase 2. Anti-S IgG titers were significantly higher among vaccinated (58.5%) than unvaccinated infected participants across vaccine products (p<0.001), though highest among those who received an mRNA vaccine. At 6 months, 78/82 (95.1%) participants maintained anti-spike seropositivity; at 12 months, 58/58 (100.0%) participants were seropositive and 33 (56.9%) had completed the primary vaccine series within 6 months. Among 11 unvaccinated participants who were not reinfected at 12 months, anti-S IgG declined from median 770.1 (IQR 615.0-1321.7) to 290.8 (IQR 175.7-400.3). Anti-N IgG antibodies waned earlier; from 35.4% seropositive at 6 months to 24.1% at 12 months. Conclusions SARS-CoV-2 seroprevalence increased significantly over 12 months from end of 2020 to end of 2021. Although individuals with previous infection may have residual protection, COVID-19 vaccination is vital to strengthening population immunity.