Burden of Respiratory Syncytial Virus-Associated Acute Respiratory Infections During Pregnancy.

BACKGROUND: With the licensure of maternal respiratory syncytial virus (RSV) vaccines in Europe and the United States, data are needed to better characterize the burden of RSV-associated acute respiratory infections (ARI) in pregnancy. The current study aimed to determine among pregnant individuals the proportion of ARI testing positive for RSV and the RSV incidence rate, RSV-associated hospitalizations, deaths, and perinatal outcomes. METHODS: We conducted a systematic review, following PRISMA 2020 guidelines, using 5 databases (Medline, Embase, Global Health, Web of Science, and Global Index Medicus), and including additional unpublished data. Pregnant individuals with ARI who had respiratory samples tested for RSV were included. We used a random-effects meta-analysis to generate overall proportions and rate estimates across studies. RESULTS: Eleven studies with pregnant individuals recruited between 2010 and 2022 were identified, most of which recruited pregnant individuals in community, inpatient and outpatient settings. Among 8126 pregnant individuals, the proportion with ARI that tested positive for RSV ranged from 0.9% to 10.7%, with a meta-estimate of 3.4% (95% confidence interval [CI], 1.9%-54%). The pooled incidence rate of RSV among pregnant individuals was 26.0 (95% CI, 15.8-36.2) per 1000 person-years. RSV hospitalization rates reported in 2 studies were 2.4 and 3.0 per 1000 person-years. In 5 studies that ascertained RSV-associated deaths among 4708 pregnant individuals, no deaths were reported. Three studies comparing RSV-positive and RSV-negative pregnant individuals found no difference in the odds of miscarriage, stillbirth, low birth weight, and small size for gestational age. RSV-positive pregnant individuals had higher odds of preterm delivery (odds ratio, 3.6 [95% CI, 1.3-10.3]). CONCLUSIONS: Data on RSV-associated hospitalization rates are limited, but available estimates are lower than those reported in older adults and young children. As countries debate whether to include RSV vaccines in maternal vaccination programs, which are primarily intended to protect infants, this information could be useful in shaping vaccine policy decisions.

Epidemiology and clinical features of SARS-CoV-2 infection in children and adolescents in the pre-Omicron era: A global systematic review and meta-analysis.

Methods: We searched MEDLINE, Embase, Global Health, CINAHL, China National Knowledge Infrastructure, Wanfang, CQvip, and the World Health Organization (WHO) COVID-19 global literature databases for primary studies recruiting children aged ≤18 years with a diagnosis of SARS-CoV-2 infection confirmed either by molecular or antigen tests. We used the Joanna Briggs Institute critical appraisal tools to appraise the study quality and conducted meta-analyses using the random effects model for all outcomes except for race/ethnicity as risk factors of SARS-CoV-2 infection. Results: We included 237 studies, each reporting at least one of the study outcomes. Based on data from 117 studies, the pooled SARS-CoV-2 positivity rate was 9.30% (95% confidence interval (CI) = 7.15-11.73). Having a comorbidity was identified as a risk factor for SARS-CoV-2 infection (risk ratio (RR) = 1.33; 95% CI = 1.04-1.71) based on data from 49 studies. Most cases in this review presented with mild disease (n = 50; 52.47% (95% CI = 44.03-60.84)). However, 20.70% of paediatric SARS-CoV-2 infections were hospitalised (67 studies), 7.19% required oxygen support (57 studies), 4.26% required intensive care (93 studies), and 2.92% required assisted ventilation (63 studies). The case fatality ratio (n = 119) was 0.87% (95% CI = 0.54-1.28), which included in-hospital and out-of-hospital deaths. Conclusions: Our data showed that children were at risk for SARS-CoV-2 infections and severe outcomes in the pre-Omicron era. These findings underscore the need for effective vaccination strategies for the paediatric population to protect against the acute and long-term sequelae of COVID-19. Registration: PROSPERO: CRD42022327680.

Adjusting for Case Under-Ascertainment in Estimating RSV Hospitalisation Burden of Older Adults in High-Income Countries: a Systematic Review and Modelling Study.

INTRODUCTION: Previous studies suggest diagnostic testing characteristics (i.e. variations in clinical specimens and diagnostic tests) can contribute to underestimation of RSV disease burden. We aimed to improve the understanding of RSV hospitalisation burden in older adults (aged ≥ 65 years) in high-income countries through adjusting for case under-ascertainment. METHODS: We conducted a systematic review to include data on RSV-associated acute respiratory infection (ARI) hospitalisation burden in older adults in high-income countries. To adjust for case under-ascertainment, we developed a two-step framework that incorporated empirical data on the RSV detection proportion of different clinical specimens and testing approaches as well as their statistical uncertainty. We estimated the unadjusted and adjusted RSV-associated hospitalisation burden through multilevel random-effects meta-analysis. We further explored RSV-associated in-hospital mortality burden. RESULTS: We included 12 studies with eligible RSV hospitalisation burden data. We estimated that pooled unadjusted hospitalisation rate was 157 per 100,000 (95% CI 98-252) for adults aged ≥ 65 years; the rate was adjusted to 347 per 100,000 (203-595) after accounting for under-ascertainment. The adjusted rate could be translated into 787,000 (460,000-1,347,000) RSV-associated hospitalisations in high-income countries in 2019, which was about 2.2 times the unadjusted estimate. Stratified analysis by age group showed that the adjusted rate increased with age, from 231 per 100,000 in adults aged 65-74 years to 692 per 100,000 in adults aged > 85 years. The in-hospital case fatality ratio of RSV was 6.1% (3.3-11.0) and the total RSV-associated in-hospital deaths in high-income countries in 2019 could be between 22,000 and 47,000. CONCLUSION: This study improves the understanding of RSV-associated hospitalisation burden in older adults and shows that the true RSV-associated hospitalisation burden could be 2.2 times what was reported in existing studies. This study has implications for calculating the benefit of interventions to treat and prevent RSV-associated disease.

Incidence and outcome of SARS-CoV-2 reinfection in the pre-Omicron era: A global systematic review and meta-analysis.

Background: With the emergence of new variants and sub-lineages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reinfections can significantly impact herd immunity, vaccination policies, and decisions on other public health measures. We conducted a systematic review and meta-analysis to synthesise the global evidence on SARS-CoV-2 reinfections in the pre-Omicron era. Methods: We searched five global databases (MEDLINE, Embase, CINAHL Plus, Global Health, WHO COVID-19) on 12 May 2022 and 28 July 2023 and three Chinese databases (CNKI, Wanfang, CQvip) on 16 October 2022 for articles reporting incidence and outcomes of SARS-CoV-2 reinfection before the period of Omicron (B.1.1.529) predominance. We assessed risk of bias using Joanna Briggs Institute critical appraisal tools and conducted meta-analyses with random effects models to estimate the proportion of SARS-CoV-2 reinfection among initially infected cases and hospitalisation and mortality proportions among reinfected ones. Results: We identified 7593 studies and extracted data from 64 included ones representing 21 countries. The proportion of SARS-CoV-2 reinfection was 1.16% (95% confidence interval (CI) = 1.01-1.33) based on 11 639 247 initially infected cases, with ≥45 days between the two infections. Healthcare providers (2.28%; 95% CI = 1.37-3.40) had a significantly higher risk of reinfection than the general population (1.00%; 95% CI = 0.81-1.20), while young adults aged 18 to 35 years (1.01%; 95% CI = 0.8-1.25) had a higher reinfection burden than other age groups (children <18 years old: 0.57%; 95% CI = 0.39-0.79, older adults aged 36-65 years old: 0.53%; 95% CI = 0.41-0.65, elderly >65 years old: 0.37%; 95% CI = 0.15-0.66). Among the reinfected cases, 8.12% (95% CI = 5.30-11.39) were hospitalised, 1.31% (95% CI = 0.29-2.83) were admitted to the intensive care unit, and 0.71% (95% CI = 0.02-2.01) died. Conclusions: Our data suggest a relatively low risk of SARS-CoV-2 reinfection in the pre-Omicron era, but the risk of hospitalisation was relatively high among the reinfected cases. Considering the possibility of underdiagnosis, the reinfection burden may be underestimated. Registration: PROSPERO: CRD42023449712.

Effectiveness of eccentric-biased exercise interventions in reducing the incidence of falls and improving functional performance in older adults: a systematic review.

BACKGROUND: Exercise has been known to preserve and enhance functional performance in older adults. Eccentric exercise involves muscle contractions characterised by unique features such as lengthening of the muscle-tendon complex by a greater opposing force. AIMS: To systematically review randomised-controlled trials (RCTs) investigating the effectiveness of eccentric exercises in reducing the incidence of falls and improving the functional performance in older adults. KEY METHODS: We conducted a systematic review of RCTs following the PRISMA-P guidelines. Searches were completed in the Cochrane Central Register of Controlled Trials, Embase, CINAHL, Medline, and Global Health CABI. We included RCTs reporting at least one of the following outcomes-falls, Berg balance scale, timed-up and go test, chair stand test, stair climb test, maximal walking speed, and minute walking distance. Two reviewers screened papers for eligibility and assessed the quality of included papers using the Cochrane Collaborative risk-of-bias tool for randomised trials. Data were extracted by a single reviewer and cross-checked by the second reviewer. A narrative synthesis was undertaken, given the high level of heterogeneity across studies. RESULTS: Ten studies were assessed as eligible for inclusion in the review. Overall, eccentric exercises were as effective as conventional resistance exercises in improving the selected outcomes by most studies. Additionally, when pre-exercise and post-eccentric exercise functional performance measures were compared, there was a statistically significant improvement in nearly all measures. The quality of trials was mixed (one high, four moderate, two low-moderate, and three low risk of bias). CONCLUSIONS: Our systematic review suggests that eccentric exercises can be as effective as conventional exercises in older adults. Evidence suggests that such exercise interventions can lead to an improvement in geriatric function.

The global burden of hospitalisation due to pneumonia caused by Staphylococcus aureus in the under-5 years children: A systematic review and meta-analysis.

BACKGROUND: Pneumonia is a leading cause of childhood morbidity and mortality. This study aimed to estimate the global hospitalisation due to Staphylococcus aureus pneumonia in under-5 children. METHODS: We conducted a systematic review and meta-analysis of primary studies following the PRISMA-P guidelines. We searched Medline, Embase, Global Health, CINAHL, Global Index Medicus, Scopus, China National Knowledge Infrastructure, Wanfang, and CQvip. We included studies reporting data on Staphylococcus aureus pneumonia, confirmed by detection of the pathogen in sterile-site samples in under-5 hospitalised children, published in English or Chinese language and conducted between 1st January 1990 and 4th November 2021 and between 1st January 1990 and 30th September 2020, respectively. We excluded those testing upper respiratory tract samples and not reporting data on samples with other bacteria or absence of bacteria. We screened papers against pre-specified criteria, extracted data and assessed the bacteriological quality, and combined epidemiological and microbiological quality of studies using two self-designed checklists. Pooled proportions of hospitalisation episodes for Staphylococcus aureus pneumonia amongst all-cause pneumonia and the 95% confidence intervals were calculated using the random-effects model. The review protocol was registered on PROSPERO (CRD42021236606). FINDINGS: Of 26,218 studies identified, thirty-five studies enroling 20,708 hospitalised pneumonia episodes were included. Out of the total hospitalised pneumonia cases in this population, the pooled proportion of Staphylococcal pneumonia cases was 3% (95% CI 2% to 4%; I2=96%). amongst 12 studies with higher microbiological quality, the pooled estimate was 6% (95% CI 2% to 10%; I2= 98%). Based on the recent global estimates of hospitalised pneumonia in this age group, the 3% and 6% estimates represent 738 thousand and 1.48 million hospitalisations in 2019, respectively. Based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), the overall quality of evidence was considered to be moderate. INTERPRETATION: Our findings are probably an underestimate because of the unknown and the likely limited sensitivity of current testing methods for Staphylococcal pneumonia diagnosis and widespread reported use of antibiotics before recruitment (in 46% of cases). Staphylococcus aureus is an important cause of hospitalisation for pneumonia in young children globally. FUNDING: Bill and Melinda Gates Foundation (OPP 1,172,551) through a prime award to John Hopkins University.

Psychosocial interventions for depression delivered by non-mental health specialists to people living with HIV/AIDS in low- and middle-income countries: A systematic review.

Background: Depression commonly co-exists with human immunodeficiency virus (HIV), but in low- and middle-income countries (LMICs), where the HIV burden is greatest, mental health resources are limited. These settings may benefit from psychosocial interventions delivered to people living with HIV/AIDS (PLWH) by non-mental health specialists. We aimed to systematically review randomised controlled trials (RCTs) that investigated the effectiveness of psychosocial interventions delivered by non-mental health specialists to prevent depression in PLWH in LMICs. Methods: We used a comprehensive electronic search strategy to identify RCTs of any stage, including pilot studies, which reported on the effectiveness of a psychosocial intervention on depression among adults living with HIV/AIDS in a LMIC setting. Screening, study selection and data extraction was completed independently by two authors. We assessed risk of bias using the Cochrane risk of bias (RoB) tool and performed a narrative synthesis. Results: We identified 3431 studies, from which we included 15 studies corresponding to 14 RCTs and a total of 3997 PLWH. Eleven studies were parallel RCTs, one was a stepped-wedged RCT, one was a full factorial RCT, one was a three-arm RCT and four were pilot studies. Studies were generally small, with eight including depression as a primary outcome. All but four trials included men and women and most studies followed participants for less than one year. Twelve trials had at least one domain in which there was a high risk of bias, with the remaining two trials having at least one domain of concern, due to lack of reporting of items. In 12 studies people in the intervention arm had statistically significantly (P < 0.05) lower or more reduced depressive symptom scores, or were less likely to have major depression, at final follow-up than people in the control group. Conclusions: Psychosocial interventions delivered by non-specialist mental health workers may be effective in preventing or reducing depression in PLWH in LMICs. However, existing studies are small with a relatively short follow-up period and have methodological limitations. Future trials should address these shortcomings, establish whether intervention effects are clinically meaningful and investigate cost-effectiveness.

To what extent is alcohol consumption in social gatherings associated with observance of COVID-19 restrictions? A rapid review.

Background: Pre-pandemic research found a connection between alcohol consumption and reduced physical distancing among strangers. Understanding the association between alcohol consumption at social gatherings and observance of COVID-19 restrictions can help inform policy related to the safe operation of public spaces where alcohol is typically consumed, as well as guidance related to the safe conduct of social events in private spaces. Methods: We conducted a rapid review using adapted systematic review methods to explore the association between alcohol consumption in social gatherings and compliance with COVID-19 public health measures and produced a narrative synthesis of our findings. We ran searches in eleven health-related databases (MEDLINE, PubMed, CINAHL, Scopus, Embase (Ovid), ProQuest Public Health, ProQuest Coronavirus, Global Health (Ovid), WHO COVID-19 literature database, PsycInfo (Ovid) and ASSIA) between July 9, 2021, and July 31, 2021. We assessed methodological quality using the relevant Joanna Briggs Institute (JBI) checklists. This review was conducted and reported in accordance with PRISMA-P guidelines. Results: We identified 7936 studies from the searches. After title, abstract and full-text review, three cross-sectional studies were eligible for inclusion. One study found that people who adhered strongly to physical distancing rules were engaged in about 40% fewer weekly drinks and 60% fewer heavy episodic drinking occasions in a week than people who adhered poorly to physical distancing rules (P < 0.01). One study found that people who reported low-risk alcohol consumption patterns had a higher chance of adhering to hand hygiene measures than those who reported high-risk alcohol consumption (odds ratio (OR) = 4.24, 95% confidence interval (CI) = 1.08-16.64). No other statistically significant results on patterns of alcohol consumption and compliance with individual public health measures or with non-pharmaceutical interventions (NPIs) were found. The direction of effect between alcohol consumption and non-adherence to NPIs and the effect of confounding factors has not been established. The quality of studies found was low to moderate, with risk of recall bias and selection bias due to study design; and the extent to which those studies can be generalised beyond their original settings may be limited. Conclusions: Despite existing evidence suggesting an association between alcohol consumption, reduced physical distancing, and increased social interaction, we found few studies of variable quality exploring the relationship between alcohol consumption and compliance with public health measures. A possible association between higher-risk alcohol behaviours and lower compliance with certain NPIs was suggested, but the direction of effect is unknown, and further studies are required to confirm this finding.

Clinical features of COVID-19 for integration of COVID-19 into influenza surveillance: A systematic review.

Background: In November 2020, the World Health Organization (WHO) created interim guidance on how to integrate testing for SARS-CoV-2 into existing influenza surveillance systems. Influenza-like illness (ILI) and severe acute respiratory illness (SARI) case definitions have been used to specify the case definition of COVID-19 for surveillance purposes. This review aims to assess whether the common clinical features of COVID-19 have changed to the point that the criteria used to identify both COVID-19 and influenza in surveillance programs needs to be altered. Methods: A systematic review of reviews following PRISMA-P guidelines was conducted using the "COVID-19 evidence review" database from August 19, 2020, to August 19, 2021. Reviews providing pooled estimates of the prevalence of clinical features of COVID-19 within the general population, diagnosed by polymerase chain reaction or rapid diagnostic test, were included. These were critically appraised and sensitivity analysis was undertaken to examine potential causes of bias. Results: Fourteen reviews were identified, including three on adults only and three on children only. For all reviews, combined fever (median prevalence = 73.0%, IQR = 58.3-78.7) and cough (45.1%, IQR = 28.9-54.0) were the most common features. These were followed by loss of taste or smell (45.1%, IQR = 28.9-54.0), hypoxemia (33%, one review), fatigue (26.4%, IQR = 9.0-39.4) and expectoration (23.9%, IQR = 23.3-25.5). Fever and cough continued to be the most prevalent features for adults and children, with subsequent symptoms being similar for adults only. However, the pattern differed for children, with headache (34.3%, IQR = 18-50.7) and nasal congestion (20%, one review) being the third and fourth commonest symptoms. Conclusions: The prevalent features found in this recent review were the same as the ones identified at the beginning of the pandemic. Therefore, the current approach of using the ILI and SARI criteria which incorporate fever and cough will identify COVID-19 cases in addition to influenza. Interestingly, children may present with different features, as headaches and nasal congestion were more common in this group. Future research could examine this further and investigate whether symptomology changes with new variants of COVID-19.

The temporal association of introducing and lifting non-pharmaceutical interventions with the time-varying reproduction number (R) of SARS-CoV-2: a modelling study across 131 countries.

BACKGROUND: Non-pharmaceutical interventions (NPIs) were implemented by many countries to reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID-19. A resurgence in COVID-19 cases has been reported in some countries that lifted some of these NPIs. We aimed to understand the association of introducing and lifting NPIs with the level of transmission of SARS-CoV-2, as measured by the time-varying reproduction number (R), from a broad perspective across 131 countries. METHODS: In this modelling study, we linked data on daily country-level estimates of R from the London School of Hygiene & Tropical Medicine (London, UK) with data on country-specific policies on NPIs from the Oxford COVID-19 Government Response Tracker, available between Jan 1 and July 20, 2020. We defined a phase as a time period when all NPIs remained the same, and we divided the timeline of each country into individual phases based on the status of NPIs. We calculated the R ratio as the ratio between the daily R of each phase and the R from the last day of the previous phase (ie, before the NPI status changed) as a measure of the association between NPI status and transmission of SARS-CoV-2. We then modelled the R ratio using a log-linear regression with introduction and relaxation of each NPI as independent variables for each day of the first 28 days after the change in the corresponding NPI. In an ad-hoc analysis, we estimated the effect of reintroducing multiple NPIs with the greatest effects, and in the observed sequence, to tackle the possible resurgence of SARS-CoV-2. FINDINGS: 790 phases from 131 countries were included in the analysis. A decreasing trend over time in the R ratio was found following the introduction of school closure, workplace closure, public events ban, requirements to stay at home, and internal movement limits; the reduction in R ranged from 3% to 24% on day 28 following the introduction compared with the last day before introduction, although the reduction was significant only for public events ban (R ratio 0·76, 95% CI 0·58-1·00); for all other NPIs, the upper bound of the 95% CI was above 1. An increasing trend over time in the R ratio was found following the relaxation of school closure, bans on public events, bans on public gatherings of more than ten people, requirements to stay at home, and internal movement limits; the increase in R ranged from 11% to 25% on day 28 following the relaxation compared with the last day before relaxation, although the increase was significant only for school reopening (R ratio 1·24, 95% CI 1·00-1·52) and lifting bans on public gatherings of more than ten people (1·25, 1·03-1·51); for all other NPIs, the lower bound of the 95% CI was below 1. It took a median of 8 days (IQR 6-9) following the introduction of an NPI to observe 60% of the maximum reduction in R and even longer (17 days [14-20]) following relaxation to observe 60% of the maximum increase in R. In response to a possible resurgence of COVID-19, a control strategy of banning public events and public gatherings of more than ten people was estimated to reduce R, with an R ratio of 0·71 (95% CI 0·55-0·93) on day 28, decreasing to 0·62 (0·47-0·82) on day 28 if measures to close workplaces were added, 0·58 (0·41-0·81) if measures to close workplaces and internal movement restrictions were added, and 0·48 (0·32-0·71) if measures to close workplaces, internal movement restrictions, and requirements to stay at home were added. INTERPRETATION: Individual NPIs, including school closure, workplace closure, public events ban, ban on gatherings of more than ten people, requirements to stay at home, and internal movement limits, are associated with reduced transmission of SARS-CoV-2, but the effect of introducing and lifting these NPIs is delayed by 1-3 weeks, with this delay being longer when lifting NPIs. These findings provide additional evidence that can inform policy-maker decisions on the timing of introducing and lifting different NPIs, although R should be interpreted in the context of its known limitations. FUNDING: Wellcome Trust Institutional Strategic Support Fund and Data-Driven Innovation initiative.

Influenza vaccination strategies for 2020-21 in the context of COVID-19.

BACKGROUND: Influenza vaccination prevents people from influenza-related diseases and thereby mitigates the burden on national health systems when COVID-19 circulates and public health measures controlling respiratory viral infections are relaxed. However, it is challenging to maintain influenza vaccine services as the COVID-19 pandemic has the potential to disrupt vaccination programmes in many countries during the 2020/21 winter. We summarise available recommendations and strategies on influenza vaccination, specifically the changes in the context of the COVID-19 pandemic. METHODS: We searched websites and databases of national and international public health agencies (focusing on Europe, North and South America, Australia, New Zealand, and South Africa). We also contacted key influenza immunization focal points and experts in respective countries and organizations including WHO and ECDC. RESULTS: Available global and regional guidance emphasises the control of COVID-19 infection in immunisation settings by implementing multiple measures, such as physical distancing, hand hygiene practice, appropriate use of personal protective equipment by health care workers and establishing separate vaccination sessions for medically vulnerable people. The guidance also emphasises using alternative models or settings (eg, outdoor areas and pharmacies) for vaccine delivery, communication strategies and developing registry and catch-up programmes to achieve high coverage. Several novel national strategies have been adopted, such as combining influenza vaccination with other medical visits and setting up outdoor and drive through vaccination clinics. Several Southern Hemisphere countries have increased influenza vaccine coverage substantially for the 2020 influenza season. Most of the countries included in our review have planned a universal or near universal influenza vaccination for health care workers, or have made influenza vaccination for health care workers mandatory. Australia has requested that all workers and visitors in long term care facilities receive influenza vaccine. The UK has planned to expand the influenza programme to provide free influenza vaccine for the first time to all adults 50-64 years of age, people on the shielded patient list and their household members and children in the first year of secondary school. South Africa has additionally prioritised people with hypertension for influenza vaccination. CONCLUSIONS: This review of influenza vaccination guidance and strategies should support strategy development on influenza vaccination in the context of COVID-19.