Introduction: We describe epidemiology and outcomes of confirmed SARS-CoV-2 infection and admissions among children <18 years in South Africa, an upper-middle income setting with high inequality. Methods: Laboratory and hospital COVID-19 surveillance data, 28 January - 19 September 2020 was used. Testing rates were calculated as number of tested for SARS-CoV-2 divided by population at risk; test positivity rates were calculated as positive tests divided by total number of tests. In-hospital case fatality ratio (CFR) was calculated based on hospitalized positive admissions with outcome data who died in-hospital and death was judged SARS-CoV-2 related by attending physician. Findings: 315,570 children aged <18 years were tested for SARS-CoV-2; representing 8.9% of all 3,548,738 tests and 1.6% of all children in the country. Of children tested, 46,137 (14.6%) were positive. Children made up 2.9% (n=2,007) of all SARS-CoV-2 positive admissions to sentinel hospitals. Among children, 47 died (2.6% case-fatality). In-hospital deaths were associated with male sex [adjusted odds ratio (aOR) 2.18 (95% confidence intervals (CI) 1.08 - 4.40)] vs female; age <1 year [aOR 4.11 (95% CI 1.08-15.54)], age 10-14 years [aOR 4.20 (95% CI1.07-16.44)], age 15-17 years [aOR 4.86 (95% 1.28 -18.51)] vs age 1-4 years; admission to a public hospital [aOR 5.07(95% 2.01 -12.76)] vs private hospital and ≥1 underlying conditions [aOR 12.09 (95% CI 4.19-34.89)] vs none Conclusions: Children with underlying conditions were at greater risk of severe SARS-CoV-2 outcomes. Children > 10 years and those with underlying conditions should be considered for increased testing and vaccination.

Few seroprevalence studies were performed on coronavirus disease (COVID-19) in Nepal. Here, we aimed to estimate seroprevalence and assess risk factors for infection in the general population of Nepal by conducting two rounds of sampling. The first round in October 2020 at the peak of the first generalized wave of COVID-19 and the second round in July-August 2021 following the peak of the wave caused by the delta variant of SARS-COV-2. We used cross-sectional probability-to-size (PPS)-based multistage cluster sampling to estimate the seroprevalence in the general population of Nepal at the national and provincial levels. We tested for the presence of anti-SARS-CoV-2 total antibody using the WANTAI SARS-CoV-2 Ab ELISA kit. In Round 1, the overall national seroprevalence was 14.4%, with provincial estimates ranging from 5.3% in Sudurpaschim to 27.3% in Madesh province. In Round 2, the estimated national seroprevalence was 70.7%, with the highest estimated seroprevalence in Madesh Province (84.8%) and the lowest in the Gandaki Province (62.9%). Seroprevalence was comparable between males and females (Round 1, 15.8% vs 12.2% and Round 2, 72.3% vs. 68.7%). The seroprevalence in the ecozones—terai, hills, and mountains—was 76.3%, 65.3%, and 60.5% in Round 2 and 17.7%, 11.7%, and 4.6% in Round 1, respectively. In Nepal, COVID-19 vaccination was introduced in January, 2021. At the peak of the first generalized wave of COVID-19, most of the population of Nepal remained unexposed to SARS-COV-2 and towards the end of the second generalized wave in April 2021, two-thirds of the population was exposed.

Cameroon was among the most affected African countries during the first wave of the COVID-19 pandemic; however, the true prevalence of SARS-CoV-2 remains unknown. From October-December 2020 we conducted a cross-sectional, age-stratified SARS-CoV-2 seroepidemiological survey at 30 purposively selected community-based sites across Cameroon’s 10 regional capitals, sampling 10,000 individuals aged 5 years or older. We employed a parallel SARS-CoV-2 antibody testing algorithm (WANTAI ELISA and Abbot Architect) to improve both the positive predictive value and negative predictive value of seroprevalence. The overall weighted and adjusted seroprevalence of SARS-CoV-2 antibodies across the 10 urban capitals of Cameroon was 10.5% (95% CI: 9.1%-12.0%) among participants aged ≥5 years. Of the 9332 participants, 730 males (13.1%, 95% CI: 11.5%-14.9%) had SARS-CoV-2 antibodies compared to 293 females (8.0%, 95% CI: 6.8%—9.3%). Among those who reported a comorbidity at the time of testing, 15.8% (95% CI: 12.8%-19.4%) were seropositive. We estimated that over 2 million SARS-CoV-2 infections occurred in the 10 regional capitals of Cameroon between October and December 2020, compared to 21,160 cases officially reported at that time translating to one laboratory-confirmed case was reported for every 110 SARS-CoV-2 infections across the 10 urban capitals. This study’s findings point to extensive and under-reported circulation of SARS-CoV-2 in Cameroon– an almost 100-fold more cases compared to the number of cases reported to the World Health Organization. This finding highlights the importance of conducting serosurveys, especially in settings where access to testing may be limited and to repeat such surveys as part of pandemic tracking.

Abstract: Objectives: Our work assessed the prevalence of co-infections in patients with SARS-CoV-2. Methods: All patients hospitalized in a Parisian hospital during the first wave of COVID-19 were tested by mPCR if they presented ILI symptoms. Results: A total of 806 patients (21%) were positive for SARS-CoV-2, 755 (20%) were positive for other respiratory viruses. Among the SARS-CoV-2 positive patients, 49 (6%) had viral co-infections. They presented similar age, symptoms, except for fever (p=0.013) and headaches (p=0.048), than single SARS-CoV-2 infections. Conclusions: SARS-CoV-2 infected patients presenting viral co-infections had similar clinical characteristics and prognosis than patients solely infected with SARS-CoV-2.

Background: In France, each year, influenza viruses are responsible for seasonal epidemics leading to 2-6 million cases. Influenza can cause severe disease that may lead to hospitalization or death. As severe disease may be due to the virus itself or to disease complications, estimating the burden of severe influenza is complex. The present study aimed at estimating the epidemiological and economic burden of severe influenza in France during eight consecutive influenza seasons (2010-2018). Methods: Influenza-related hospitalization and mortality data and patient characteristics were taken from the French hospital information database, PMSI. An ecological approach using cyclic regression models integrating the incidence of influenza syndrome from the Sentinelles Network supplemented the PMSI data analysis in estimating excess hospitalization and mortality (CépiDc – 2010-2015) and medical costs. Results: Each season, the average number of influenza-related hospitalizations was 18,979 (range: 8,627-44,024), with an average length of stay of 8 days. The average number of respiratory hospitalizations indirectly related with influenza (i.e., influenza-associated) was 31,490 (95% CI: 24,542-39,012), with an average cost of \euro141 million (range: 54-217); 70% of these hospitalizations and 77% of their costs concerned individuals ≥ 65 years of age (65+). More than 90% of excess mortality was in 65+ subjects. Conclusions: The combination of two complementary approaches allowed estimation of both influenza-related and associated hospitalizations and deaths and their burden in France, showing the substantial impact of complications. The present study highlighted the major public health burden of influenza and its severe complications, especially in 65+ subjects.

Background. Respiratory syncytial virus (RSV) infection is a cause of substantial morbidity and mortality in young children. There is currently no effective therapy available. Methods. This was a phase 2 study of the oral RSV fusion protein inhibitor AK0529 in infants aged 1-24 months, hospitalized with RSV infection. In part 1 patients (n=24) were randomized 2:1 to receive a single dose of AK0529 up to 4 mg/kg or placebo. In part 2 patients (n=48) were randomized 2:1 to receive AK0529 at 0.5, 1 or 2 mg/kg bid or placebo for five days. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modelling. Safety, tolerability, viral load, signs and symptoms were assessed daily during treatment. Results. No safety or tolerability signals were detected for AK0529: grade ≥3 treatment-emergent adverse events occurred in 4.1% of patients in AK0529 and 4.2% in placebo groups, respectively, and none led to death or withdrawal from the study. In part 2, targeted drug exposure was reached with 2 mg/kg bid. A numerically greater reduction in median viral load with 2 mg/kg bid AK0529 than with placebo at 96 hours was observed. A -4.0 (95% CI: -4.51, -2.03) median reduction in RSV signs and symptom score from baseline to 96 hours was observed in the 2 mg/kg group, compared with -2.0 (95% CI: -3.42, -1.82) in the placebo group. Conclusions. AK0529 was well tolerated in hospitalized RSV-infected infants. Treatment with AK0529 2 mg/kg bid was observed to reduce viral load and clinical signs and symptoms.

Point-of-care tests (POCTs) offer considerable potential for improving clinical and public health management of COVID-19 by providing timely information to guide decision-making, but data on real-world performance are in short supply. Besides SARS-CoV2-specific tests, there is growing interest in the role of surrogate (non-specific) tests such as FebriDx, a biochemical POCT which can be used to distinguish viral from bacterial infection in patients with influenza-like illnesses. This short communication assesses what is currently known about FebriDx performance across settings and populations by comparison with some of the more intensively evaluated SARS-CoV2-specific POCTs. While FebriDx shows some potential in supporting triage for early-stage infection in acute care settings, this is dependent on SARS-CoV2 being the most likely cause for influenza-like illnesses, with reduction in discriminatory power when COVID-19 case numbers are low, and when co-circulating viral respiratory infections become more prevalent during the autumn and winter. Too little is currently known about its performance in primary care and the community to support use in these contexts and further evaluation is needed. Reliable SARS CoV2-specific POCTs – when they become available – are likely to rapidly overtake surrogates as the preferred option given the greater specificity they provide.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has been the most significant public health challenge in over a century. SARS-COV-2 has infected over 765 million people worldwide, resulting in over 6.9 million deaths. This study aimed to detect community transmission of SARS-CoV-2 and monitor the co-circulation of SARS-CoV-2 with other acute respiratory pathogens in Rift Valley, Kenya. We conducted a cross-sectional active sentinel surveillance for the SARS-CoV-2 virus among patients with acute respiratory infections at four sites in Rift Valley from January 2022 to December 2022. 1271 patients of all ages presenting with influenza-like illness were recruited into the study. Nasopharyngeal swab specimens were screened using a multiplex RT–qPCR for SARS-CoV-2, Influenza A, Influenza B and RSV. Influenza A and RSV samples were subtyped, and all the SARS-CoV-2 positive samples were further screened for 12 viral and 7 bacterial respiratory pathogens. We had a prevalence of 13.93% SARS-CoV-2, Influenza A 5.7%, Influenza B 1.96% and 0.94%. Influenza A-H1pdm09 and RSV B were the most dominant circulating subtypes of Influenza A and RSV, respectively. The most common co-infecting pathogens were Streptococcus pneumoniae and Haemophilus influenzae, accounting for 16.4% and 10.7% of all the SARS-CoV-2 positive samples. Augmenting syndromic testing in ARI surveillance is crucial to inform evidence-based clinical and public health interventions.

Background We used data from a prospective cohort to explore two-year trajectories of “long COVID” (persistent symptoms after SARS-CoV-2 infection) and their association with illness perception. Methods RECoVERED participants (adults; prospectively enrolled following laboratory-confirmed SARS-CoV-2 infection, May 2020-June 2021) completed symptom questionnaires at months 2-12, 18 and 24, and the Brief Illness Perception Questionnaire (B-IPQ) at months 1, 6, and 12. Using group-based trajectory models (GBTM), we modelled symptoms (mean total numbers and proportion with 4 specific complaints), including age, sex, BMI and timing of infection as covariates. In a multivariable linear mixed-effects model, we assessed the association between symptom trajectories and repeated B-IPQ scores. Results Among 292 participants (42% female; median age 51 [IQR=36-62]), four trajectories were identified, ranging from Trajectory 4 (8.9%; 6+ symptoms) to Trajectory 1 (24.8%; no symptoms). The occurrence of fatigue and myalgia increased among 23% and 12% of participants, respectively. Individuals in Trajectory 4 experienced more negative adjusted B-IPQ scores over time than those in Trajectories 1-3. Conclusions We observed little fluctuation in the total number of symptoms but individual symptoms may develop as others resolve. Reporting a greater number of symptoms was congruent with more negative illness perception over time.

A document by J. Kevin Yin. Click on the document to view its contents.

Abstract. The Controlled Human Infection Model and specifically the Human Viral Challenge Model are not dissimilar to standard clinical trials while adding another layer of complexity and safety considerations. The models deliberately infect volunteers, with an infectious challenge agent (CA) to determine the effect of the infection and the potential benefits of the experimental interventions. The Human Viral Challenge Model studies can shorten the time to assess the efficacy of a new vaccine or treatment by combining this with the assessment of safety. The newly emerging SARS-COV-2 virus is highly contagious and the cause pandemic disease COVID-19. An urgent race in is on to develop a new vaccine against this virus in a timeframe never attempted before. The use of the Human Viral Challenge Model has been proposed to accelerate the development of the vaccine. In the early 2000’s the authors successfully developed a pathogenic Human Viral Challenge Model for another virus for which there was no effective treatment and established it to evaluate potential therapies and vaccines against Respiratory Syncytial Virus. The authors feel that the experience gained in the development of that model can help with the development of a COVID-19 HVCM and describe it here. Word count: 197

Background: Following a locally transmitted case in Sukhbaatar city, Selenge province, we conducted a study with two objectives. First, we aimed to estimate the basic reproduction number of COVID-19, leveraging the epidemiological and clinical characteristics observed in the first 67 confirmed cases. Second, we aimed to model the outbreak considering different patient profiles - asymptomatic, symptomatic, and pre-symptomatic - with the goal of predicting the ultimate scale of the epidemic in the scenario of uninterrupted transmission. Methods: We conducted a prospective case study following the WHO FFX cases generic protocol. The rapid response teams collected the surveillance data from November 14–29, 2020. We created a stochastic process to draw many transmission chains from this greater distribution to better understand and make inferences regarding the outbreak under investigation. Results: The majority of the cases involved household transmissions (35, 52.2%), work transmissions (20, 29.9%), index (5, 7.5%), same apartment transmissions (2, 3.0%), school transmissions (2, 3.0%), and meetup transmissions (1, 1.5%). The posterior means of the basic reproduction number of both the asymptomatic cases, R_0^Asy and pre-symptomatic cases R_0^Pre (1·35 [95% CrI 0·88−1·86] and 1·29 [95% CrI 0·67−2·10], respectively), were lower than that of the symptomatic cases. Conclusion: Our study highlights the heterogeneity of COVID-19 transmission across different symptom statuses and underscores the importance of early identification and isolation of symptomatic cases in disease control. Detailed contact tracing data with advanced statistical methods, can be applied to other infectious diseases, facilitating a more nuanced understanding of disease transmission dynamics.

Background We estimated the secondary attack rate of SARS-CoV-2 among household contacts of PCR-confirmed cases of COVID-19 in rural Kenya and analysed risk factors for transmission. Methods We enrolled incident PCR-confirmed cases and their household members. At baseline, a questionnaire, a blood sample, and naso-oropharyngeal swabs were collected. Household members were followed 4, 7, 10, 14, 21 and 28 days after the date of the first PCR-positive in the household; naso-oropharyngeal swabs were collected at each visit and used to define secondary cases. Blood samples were collected every 1-2 weeks. Symptoms were collected in a daily symptom diary. We used binomial regression to estimate secondary attack rates and survival analysis to analyze risk factors for transmission. Results A total of 119 households with at least one positive household member were enrolled between October 2020 and September 2022, comprising 503 household members; 226 remained in follow up at day-14 (45%). A total of 43 secondary cases arose within 14 days of identification of the primary case, 81 household members remained negative. The 7-day secondary attack rate was 4% (95%CI 1-10%), the 14-day secondary attack rate was 28% (95%CI 17-40%). Of 38 secondary cases with data, 8 reported symptoms (21%, 95%CI 8-34%). Antibody to SARS-CoV-2 spike protein at enrolment was not associated with risk of becoming a secondary case. Conclusion Households in our setting experienced a lower 7-day attack rate than a recent meta-analysis indicated as the global average (23-43% depending on variant), and infection is mostly asymptomatic in our setting.

Background: Several countries, including Bahrain, used Wastewater surveillance for disease activity monitoring. This study aimed to determine the presence of SARS-COV-2 in untreated wastewater and to correlate it with the disease spread. Methods: A retrospective review was conducted for all wastewater samples tested for SARS-CoV-2 in public health laboratories from October 2020 to October 2022. Samples were collected weekly between February and October 2022 from different areas across Bahrain. Real-time polymerase chain reaction (PCR) was used to test for the presence of SARS-CoV-2 in wastewater, and the results were correlated with the number of COVID-19 cases in the same area. Results: Of a total of 387 wastewater samples, 103 (26.6%) samples tested positive for SARS-CoV-2. In late 2020, of 42 samples collected initially, 4 (9.5%) samples tested positive for SARS-CoV-2 in the 4 locations that hosted COVID-19 isolation facilities. Between February and October 2022, 345 specimens of wastewater were tested, and 99 (28.7%) were positive. The highest detection rate was in February, June, and July (60%, 45%, and 43%, respectively), which corresponded to COVID-19 peaks during 2022, and the lowest detection rate was in August and September (11% and 0%, respectively), corresponding to the low number of COVID-19 cases. Conclusion: The detection rate of SARS-COV-2 in wastewater samples from Bahrain was high and was significantly correlated with the number of reported COVID-19 cases. Wastewater surveillance can aid the existing surveillance system in monitoring SARS-CoV-2 spread.

Evaluation of population-based COVID-19 control measures informs strategies to quell the current pandemic and reduce the impact of those yet to come. Effective COVID-19 control measures may simultaneously reduce the incidence of other acute respiratory infections (ARIs) due to shared transmission modalities. To assess the impact of stay-at-home orders and other physical distancing measures on the prevalence of ARI-related symptoms, we compared symptoms reported by prospective college cohorts enrolled during two consecutive academic years. ARI-related symptoms declined following campus closure and implementation of stay-at-home orders, demonstrating the impact of population-based physical distancing measures on control of a broad range of respiratory infections.

Background: After the detection of the first case of coronavirus disease 2019 (COVID-19) in South Korea on January 20, 2019, it has triggered three major outbreaks. To decrease the disease burden of COVID-19, social distancing and active mask wearing were encouraged, reducing the number of patients with influenza-like illness and altering the detection rate of influenza and respiratory viruses in the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS). We examined the changes in respiratory viruses due to COVID-19 in South Korea and virological causes of the high detection rate of human rhinovirus (hRV) in 2020. Methods: We collected 52,684 oropharyngeal or nasopharyngeal swab samples from patients with influenza-like illness in cooperation with KINRESS from 2016 to 2020. Influenza virus and other respiratory viruses were confirmed using real-time RT-PCR. The weekly detection rate was used to compare virus detection patterns. Results: Non-enveloped virus (hRV, human bocavirus, and human adenovirus) detection rates during the COVID-19 pandemic were maintained. The detection rate of hRV significantly increased in 2020 compared with that in 2019 and was negatively correlated with number of COVID-19-confirmed cases in 2020. The distribution of strains and genetic characteristics in hRV did not differ between 2019 and 2020. Conclusions: The extremely low detection rate of enveloped viruses resulted from efforts to prevent the spread of COVID-19 in South Korea. The high detection rate of hRV may be related to resistance against environmental conditions as a non-enveloped virus and the long period of viral shedding from patients.

Background: Anaphylaxis following influenza vaccination is a rare but serious problem. The underlying immune responses are not well understood. This study elucidated the IgE and IgG antibody responses in healthy children and adolescents following inactivated influenza vaccines (IIVs). Methods: The efficacy and safety of quadrivalent IIV (QIV) and trivalent IIV (TIV) were compared in healthy subjects aged 0-18 years. Serum IIV-specific IgE, IgG and IgG4 levels (sIgE, sIgG, sIgG4) were measured with ImmunoCAP. Hemagglutinin inhibition (HI) assay was performed for each influenza virus subtype. Sera from earlier patients who developed anaphylaxis to different IIVs were similarly tested. Results: A total of 393 subjects were enrolled: 96 were 6 months -2 years old, 100 were 3-5 years old, 100 were 6-12 years old, and 97 were 13-18 years old. No anaphylaxis was observed. Generally, QIV and TIV induced similar antibody responses. IIV-sIgE levels rose significantly after vaccination in the 6m-2y and 3-5y groups, did not change in the 6-12y group, and decreased in the 13-18y group. In contrast, the IIV-sIgG4/sIgE ratio increased significantly after vaccination in all age groups. Sensitized subjects had significantly higher HI titers and IIV-sIgG levels in the youngest age group and higher IIV-sIgG4 levels in all age groups compared with the non-sensitized. The IIV-sIgG4/sIgE ratio in 5 patients with anaphylaxis was significantly lower than in age-matched healthy subjects. Conclusion: IIVs induce IgE sensitization in healthy children, but also robust IgG4 responses that may protect them from anaphylaxis.

Background: The COVID-19 pandemic has highlighted the need for targeted local interventions given substantial heterogeneity within cities and counties. Publicly available case data are typically aggregated to the city or county level to protect patient privacy, but more granular data are necessary to identify and act upon community-level risk factors that can change over time. Methods: Individual COVID-19 case and mortality data from Massachusetts were geocoded to residential addresses and aggregated into two time periods: “Phase 1” (March–June 2020) and “Phase 2” (September 2020–February 2021). Institutional cases associated with long-term care facilities, prisons, or homeless shelters were identified using address data and modeled separately. Census tract sociodemographic and occupational predictors were drawn from the 2015-2019 American Community Survey. We used mixed-effects negative binomial regression to estimate incidence rate ratios (IRRs), accounting for town-level spatial autocorrelation. Results: Case incidence was elevated in census tracts with higher proportions of Black and Latinx residents, with larger associations in Phase 1 than Phase 2. Case incidence associated with proportion of essential workers was similarly elevated in both Phases. Mortality IRRs had differing patterns from case IRRs, decreasing less substantially between Phases for Black and Latinx populations and increasing between Phases for proportion of essential workers. Mortality models excluding institutional cases yielded stronger associations for age, race/ethnicity, and essential worker status. Conclusions: Geocoded home address data can allow for nuanced analyses of community disease patterns, identification of high-risk subgroups, and exclusion of institutional cases to comprehensively reflect community risk.