SARS-CoV-2 Reduction in Shared Indoor Air

To the Editor A recent Viewpoint made a compelling case for improving indoor air quality and provided an excellent overview of different approaches and considerations. However, an important question that remains unclear from this Viewpoint and from official recommendations from the US Centers for Disease Control and Prevention (CDC) is the frequency of air changes needed to sufficiently reduce transmission of SARS-CoV-2 and other airborne pathogens in non–health care settings. Many schools, businesses, and other indoor venues do not have even a ballpark sense about the number of air changes per hour they need to achieve, much less how much money to budget for this process, because the cost increases with more air changes per hour.

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Dicembre 2022

Rapamycin and inulin for third-dose vaccine response stimulation (RIVASTIM): Inulin – study protocol for a pilot, multicentre, randomised, double-blinded, controlled trial of dietary inulin to improve SARS-CoV-2 vaccine response in kidney transplant recipients

Introduction
Kidney transplant recipients (KTRs) are at an increased risk of hospitalisation and death from COVID-19. Vaccination against SARS-CoV-2 is our primary risk mitigation strategy, yet vaccine effectiveness in KTRs is suboptimal. Strategies to enhance vaccine efficacy are therefore required. Current evidence supports the role of the gut microbiota in shaping the immune response to vaccination. Gut dysbiosis is common in KTRs and is a potential contributor to impaired COVID-19 vaccine responses. We hypothesise that dietary fibre supplementation will attenuate gut dysbiosis and promote vaccine responsiveness in KTRs.

Methods and analysis
Rapamycin and inulin for third-dose vaccine response stimulation-inulin is a multicentre, randomised, prospective, double-blinded, placebo-controlled pilot trial examining the effect of dietary inulin supplementation prior to a third dose of COVID-19 vaccine in KTRs who have failed to develop protective immunity following a 2-dose COVID-19 vaccine schedule. Participants will be randomised 1:1 to inulin (active) or maltodextrin (placebo control), administered as 20 g/day of powdered supplement dissolved in water, for 4 weeks prior to and following vaccination. The primary outcome is the proportion of participants in each trial arm that achieve in vitro neutralisation of live SARS-CoV-2 virus at 4 weeks following a third dose of COVID-19 vaccine. Secondary outcomes include the safety and tolerability of dietary inulin, the diversity and differential abundance of gut microbiota, and vaccine-specific immune cell populations and responses.

Ethics and dissemination
Ethics approval was obtained from the Central Adelaide Local Health Network (CALHN) Human Research Ethics Committee (HREC) (approval number: 2021/HRE00354) and the Sydney Local Health District (SHLD) HREC (approval numbers: X21-0411 and 2021/STE04280). Results of this trial will be published following peer-review and presented at scientific meetings and congresses.

Trial registration number
ACTRN12621001465842.

Leggi
Dicembre 2022

SARS-CoV-2 antibody responses post-vaccination in UK healthcare workers with pre-existing medical conditions: a cohort study

Objectives
To examine antibody responses after the second vaccination in healthcare workers (HCWs) with underlying health conditions.

Design
Cohort study.

Setting
Oxford University Hospitals in the United Kingdom.

Participants
Healthcare workers who had SARS-CoV-2 serological data available and received two SARS-CoV- 2 vaccinations.

Primary outcome
Peak SARS-CoV-2 anti-spike IgG responses after the second vaccination and associations with underlying health conditions and the estimated risk of severe COVID-19 using an occupational health risk assessment tool.

Methods
We used univariable and multivariable linear regression models to investigate associations between antibody levels and demographics (age, sex, ethnicity), healthcare role, body mass index, underlying health conditions, vaccination status, prior infection and the Association of Local Authority Medical Advisors COVID-age risk score.

Results
1635 HCWs had anti-spike IgG measurements 14–84 days after second vaccination and data on any underlying health conditions. Only five HCWs (0.3%), all on immunosuppressive treatment, (including four organ transplant recipients), did not seroconvert after second vaccination. Antibody levels were independently lower with older age, diabetes, immunosuppression, respiratory disorders other than asthma and markedly so in organ transplant recipients. Levels were independently lower in ChAdOx1 versus BNT162b2 recipients and higher following previous infection. HCWs with ‘very high’ COVID-age risk scores had lower median antibody levels than those with ‘low’, ‘medium’ or ‘high’ risk scores; 4379 AU/mL, compared with 12 337 AU/mL, 9430 AU/mL and 10 524 AU/mL, respectively.

Conclusions
Two vaccine doses are effective in generating antibody responses among HCWs, including those with a high occupational risk. However, HCWs with underlying health conditions, especially diabetes, immunosuppression and organ transplant, had lower antibody levels, and vaccine response monitoring may be needed.

Leggi
Dicembre 2022

Immunogenicity of COVID-19 vaccines and levels of SARS-CoV-2 neutralising antibody in the Bruneian population: Protocol for a national longitudinal study

Introduction
Neutralising antibodies (NAbs) have been shown to be correlative of immune protection against SARS-CoV-2. We report the protocol for a national longitudinal study to assess and compare the level of NAbs generated in response to COVID-19 vaccines in Brunei Darussalam in adults 2–6 weeks post primary series (BBIBP-CorV, AZD1222, or mRNA-1273 vaccines) and their subsequent follow-up after administration of a third (booster-1) dose (BBIBP-CorV, mRNA-1273, or BNT162b2).

Methods and analysis
Participant data will be extracted and processed from the national electronic health record system (Bru-HIMS) and the national mobile health application (BruHealth) into a research data platform. Eligible adults who have received their primary or booster vaccine will be invited using a stratified random sampling strategy based on age, gender and vaccine type (baseline target population, n=3000; 2–6 weeks post last dose). Blood serum will be isolated, and NAb levels assessed using the cPass surrogate virus neutralisation test. Baseline participants will then be screened for eligibility for subsequent longitudinal analysis. Those who have received a third dose will be followed up at 1, 3, 6, 9 and up to 12 months. NAb levels will be evaluated across the participant population according to vaccine platform/booster type, time since the last dose and correlated with demographic data. The study period is from December 2021 to January 2023 and aims to evaluate how NAb levels wane following a third vaccine dose across different vaccine platforms and determine the impact and rate of breakthrough infections.

Ethics and dissemination
This study has been approved by the Medical and Ethical Research Committee of Ministry of Health, Brunei Darussalam. Individual NAb test results will be shared with each participant by text message. The findings from this study will help policy-makers in Brunei develop future vaccination strategies and establish regulations across multiple agencies.

Leggi
Dicembre 2022

Study protocol for developing a novel approach for improving supply chain management for SARS-CoV-2 point of care diagnostic services in resource-limited settings: a case study of Mopani District in Limpopo province, South Africa

Introduction
Recent evidence shows that point-of-care (POC) testing is a more feasible alternative for diagnosis of COVID-19 in settings that have poor access to laboratory diagnostic services. Equitable access to POC testing can be optimised through well-established supply chain management (SCM) systems. The proposed study aims to develop a novel approach for improving SCM for COVID-19 POC diagnostic services in resource-limited settings with poor access to laboratory diagnostic services, using Mopani District in Limpopo Province, South Africa as a study setting.

Methods and analysis
This study was guided by results of the scoping review. Following the scoping review, we propose a mixed-methods study, which will be implemented in three phases. First, we will perform a geospatial analysis to investigate the spatial distribution of COVID-19 testing services. Second, we will perform an audit of POC diagnostic services including its supply chain to evaluate the effect of SCM on accessibility of COVID-19 POC diagnostic services and reveal SCM barriers and enablers of accessibility of COVID-19 POC diagnostic services. Third, we will perform a nominal group technique to collaborate with key stakeholders in co-creation of a novel approach for improving SCM systems for COVID-19 POC diagnostic services. For the geospatial analysis, we will employ the ArcGIS Software. For the analysis of quantitative and qualitative data that will be generated from the audit and nominal group discussion, we will employ Stata software and NVivo software, respectively.

Ethics and dissemination
This study has been ethically reviewed and approved by two institutional review boards: University of Pretoria Faculty of Health Sciences Research Ethics Committee (approval number 655/2021) and Limpopo Department of Health Research Ethics Committee (approval number LP-2021-12-007). The results of this study will be disseminated through national and international presentations and peer-reviewed publications.

Leggi
Novembre 2022

Time-varying risk of death after SARS-CoV-2 infection in Swedish long-term care facility residents: a matched cohort study

Objectives
To evaluate whether SARS-CoV-2 infection in residents of long-term care (LTC) facilities is associated with higher mortality after the acute phase of infection, and to estimate survival in uninfected residents.

Design
Extended follow-up of a previous, propensity score-matched, retrospective cohort study based on the Swedish Senior Alert register.

Setting
LTC facilities in Sweden.

Participants
n=3604 LTC residents with documented SARS-CoV-2 until 15 September 2020 matched to 3604 uninfected controls using time-dependent propensity scores on age, sex, health status, comorbidities, prescription medications, geographical region and Senior Alert registration time. In a secondary analysis (n=3731 in each group), geographical region and Senior Alert registration time were not matched for in order to increase the follow-up time in controls and allow for an estimation of median survival.

Primary outcome measures
All-cause mortality until 24 October 2020, tracked using the National Cause of Death Register.

Results
Median age was 87 years and 65% were women. Excess mortality peaked at 5 days after documented SARS-CoV-2-infection (HR 21.5, 95% CI 15.9 to 29.2), after which excess mortality decreased. From the second month onwards, mortality rate became lower in infected residents than controls. The HR for death during days 61–210 of follow-up was 0.76 (95% CI 0.62 to 0.93). The median survival of uninfected controls was 1.6 years, which was much lower than the national life expectancy in Sweden at age 87 (5.05 years in men, 6.07 years in women).

Conclusions
The risk of death after SARS-CoV-2 infection in LTC residents peaked after 5 days and decreased after 2 months, probably because the frailest residents died during the acute phase, leaving healthier residents remaining. The limited life expectancy in this population suggests that LTC resident status should be accounted for when estimating years of life lost due to COVID-19.

Leggi
Novembre 2022

Investigating transmission of SARS-CoV-2 using novel face mask sampling: a protocol for an observational prospective study of index cases and their contacts in a congregate setting

Introduction
This study aims to measure how transmission of SARS-CoV-2 occurs in communities and to identify conditions that lend to increased transmission focusing on congregate situations. We will measure SARS-CoV-2 in exhaled breath of asymptomatic and symptomatic persons using face mask sampling—a non-invasive method for SARS-CoV-2 detection in exhaled air. We aim to detect transmission clusters and identify risk factors for SARS-CoV-2 transmission in presymptomatic, asymptomatic and symptomatic individuals.

Methods and analysis
In this observational prospective study with daily follow-up, index cases and their respective contacts are identified at each participating institution. Contact definitions are based on Centers for Disease Control and Prevention and local health department guidelines. Participants will wear masks with polyvinyl alcohol test strips adhered to the inside for 2 hours daily. The strips are applied to all masks used over at least 7 days. In addition, self-administered nasal swabs and (optional) finger prick blood samples are performed by participants. Samples are tested by standard PCR protocols and by novel antigen tests.

Ethics and dissemination
This study was approved by the Colorado Multiple Institutional Review Board and the WHO Ethics Review Committee. From the data generated, we will analyse transmission clusters and risk factors for transmission of SARS-CoV-2 in congregate settings. The kinetics of asymptomatic transmission and the evaluation of non-invasive tools for detection of transmissibility are of crucial importance for the development of more targeted control interventions—and ultimately to assist with keeping congregate settings open that are essential for our social fabric.

Trial registration number
ClinicalTrials.gov (#NCT05145803).

Leggi
Novembre 2022

Aetiological and prognostic roles of frailty, multimorbidity and socioeconomic characteristics in the development of SARS-CoV-2 health outcomes: protocol for systematic reviews of population-based studies

Introduction
There is growing evidence that the impact of COVID-19 crisis may be stronger for individuals with multimorbidity, frailty and lower socioeconomic status. Existing reviews focus on few, mainly short-term effects of COVID-19 illness and patients with single chronic disease. Information is also largely missing for population representative samples.
Applying population-based approach, the systematic reviews will have two objectives: (1) to evaluate the aetiological roles of frailty, multimorbidity and socioeconomic status on SARS-CoV-2 infection probability, hospitalisation, intensive care unit (ICU) admission, mechanical ventilation and COVID-19 related mortality among general population and (2) to investigate the prognostic roles of frailty, multimorbidity and socioeconomic characteristics on the risk of hospitalisation, ICU admission, mechanical ventilation, COVID-19 mortality, functioning, quality of life, disability, mental health and work absence.

Methods and analysis
For this ongoing work, four databases were searched: PubMed, Embase, WHO COVID-19 Global literature on coronavirus disease and PsycINFO, for the period between January 2020 and April 7 2021. Peer-reviewed published literature in English and all types of population-based studies will be considered. Studies using standard tools to assess multimorbidity such as disease count, comorbidity indices or disease combinations will be retained, as well as studies with standard scales and scores for frailty or measurement of a socioeconomic gradient. Initial search included 10 139 articles, 411 for full-text reading. Results will be summarised by risk factor, objective and outcome. The feasibility of meta-analysis will be determined by the findings and will aim to better understand uncertainties of the results. Quality of studies will be assessed using standardised scales.

Ethics and dissemination
The study will be based on published evidence, and it is exempt from the ethical approval. This work is part of the Population Health Information Research Infrastructure (PHIRI) project. Dissemination of the results will imply conference presentation, submission for scientific publication and PHIRI project report.

PROSPERO registration number
CRD42021249444.

Leggi
Novembre 2022

Cross-sectional study of the knowledge, perception and attitude of first-year university students in Iraq towards SARS-CoV-2 Omicron variant and COVID-19 vaccines

Objectives
The aim of this study was to first assess the knowledge and perception of first-year university students in Iraq about COVID-19 in general and SARS-CoV-2 latest variant of concern, and to evaluate the attitudes towards protection measures including vaccination.

Study design
A cross-sectional study was conducted among newly enrolled students at the American University of Iraq-Baghdad. Mann-Whitney U and Kruskal-Wallis tests were used to test an association between the outcomes measured on a 5-point Likert scale and the binary and the categorical independent variables, respectively. 2 test was used to test the association between nominal categorical variables, while Kendall’s -b was used for ordinal variables.

Participants
Students (n=432) were invited to fill out a survey specifically tailored to assess their knowledge, perception and attitude towards Omicron variant and COVID-19 vaccines acceptance. 363 students enrolled in various majors participated in this study.

Results
Assessment of COVID-19 knowledge and perception revealed that students still lack reliable info and data about FDA-approved treatment options (70.5%), SARS-CoV-2 variants (96.5%) and approved vaccines. Students’ attitude and practices towards recommended safety measures should be reassessed to better manage the pandemic. Adherence level was shown to be associated with the belief in its capacity to effectively manage the new variant. Interestingly, 85% of the students have received at least one dose of approved vaccine. A significant positive correlation was detected between the level of adherence to recommended precautions and the intention to take a third booster shot if proven effective.

Conclusions
Students’ reliable knowledge about COVID-19 pandemic including the various strains and approved vaccines should be improved to better manage the pandemic and set foundations for a more appropriate approach when another pandemic occurs. Special workshops should be organised to ensure that students and the public have a more trusted source of information about COVID-19.

Leggi
Novembre 2022

Seroprevalence of SARS-CoV-2 antibodies among Forcibly Displaced Myanmar Nationals in Coxs Bazar, Bangladesh 2020: a population-based cross-sectional study

Objectives
The study aimed to determine the seroprevalence, the fraction of asymptomatic infections, and risk factors of SARS-CoV-2 infections among the Forcibly Displaced Myanmar Nationals (FDMNs).

Design
It was a population-based two-stage cross-sectional study at the level of households.

Setting
The study was conducted in December 2020 among household members of the FDMN population living in the 34 camps of Ukhia and Teknaf Upazila of Cox’s Bazar district in Bangladesh.

Participants
Among 860 697 FDMNs residing in 187 517 households, 3446 were recruited for the study. One individual aged 1 year or older was randomly selected from each targeted household.

Primary and secondary outcome measures
Blood samples from respondents were tested for total antibodies for SARS-CoV-2 using Wantai ELISA kits, and later positive samples were validated by Kantaro kits.

Results
More than half (55.3%) of the respondents were females, aged 23 median (IQR 14–35) years and more than half (58.4%) had no formal education. Overall, 2090 of 3446 study participants tested positive for SARS-CoV-2 antibody. The weighted and test adjusted seroprevalence (95% CI) was 48.3% (45.3% to 51.4%), which did not differ by the sexes. Children (aged 1–17 years) had a significantly lower seroprevalence 38.6% (95% CI 33.8% to 43.4%) compared with adults (58.1%, 95% CI 55.2% to 61.1%). Almost half (45.7%, 95% CI 41.9% to 49.5%) of seropositive individuals reported no relevant symptoms since March 2020. Antibody seroprevalence was higher in those with any comorbidity (57.8%, 95% CI 50.4% to 64.5%) than those without (47.2%, 95% CI 43.9% to 50.4%). Multivariate logistic regression analysis of all subjects identified increasing age and education as risk factors for seropositivity. In children (≤17 years), only age was significantly associated with the infection.

Conclusions
In December 2020, about half of the FDMNs had antibodies against SARS-CoV-2, including those who reported no history of symptoms. Periodic serosurveys are necessary to recommend appropriate public health measures to limit transmission.

Leggi
Novembre 2022

Persistent symptoms after SARS-CoV-2 infection in children: a cross-sectional population-based serological study

Objectives
To estimate the prevalence of children and adolescents reporting persistent symptoms after SARS-CoV-2 infection.

Design
A random sample of children and adolescents participated with their family members to a serological survey including a blood drawing for detecting antibodies targeting the SARS-CoV-2 nucleocapsid (N) protein and a questionnaire on COVID-19-related symptoms experienced since the beginning of the pandemic.

Setting
The study took place in the canton of Geneva, Switzerland, between June and July 2021.

Participant
660 children aged between 2 and 17 years old.

Primary and secondary outcome
The primary outcome was the persistence of symptoms beyond 4 weeks comparing seropositive and seronegative participants. The type of declared symptoms were also studied as well as associated risk factors.

Results
Among seropositive children, the sex-adjusted and age-adjusted prevalence of symptoms lasting longer than 2 weeks was 18.3%, compared with 11.1% among seronegatives (adjusted prevalence difference (aPrev)=7.2%, 95% CI: 1.5% to 13.0%). Among adolescents aged 12–17 years, we estimated the prevalence of experiencing symptoms lasting over 4 weeks to be 4.4% (aPrev,95% CI: –3.8% to 13.6%), whereas no seropositive child aged 2–11 reported symptoms of this duration. The most frequently declared symptoms were fatigue, headache and loss of smell.

Conclusions
We estimated the prevalence of experiencing persistent symptoms lasting over 4 weeks to be around 4% among adolescents, which represents a large absolute number, and should raise awareness and concern. We did not observe meaningful differences of persistent symptoms between seropositive and seronegative younger children, suggesting that they may be less affected than their older counterparts.

Leggi
Novembre 2022