Dynamics of SARS-CoV-2 seroassay sensitivity: a systematic review and modelling study.

BackgroundSerological surveys have been the gold standard to estimate numbers of SARS-CoV-2 infections, the dynamics of the epidemic, and disease severity. Serological assays have decaying sensitivity with time that can bias their results, but there is a lack of guidelines to account for this phenomenon for SARS-CoV-2.AimOur goal was to assess the sensitivity decay of seroassays for detecting SARS-CoV-2 infections, the dependence of this decay on assay characteristics, and to provide a simple method to correct for this phenomenon.MethodsWe performed a systematic review and meta-analysis of SARS-CoV-2 serology studies. We included studies testing previously diagnosed, unvaccinated individuals, and excluded studies of cohorts highly unrepresentative of the general population (e.g. hospitalised patients).ResultsOf the 488 screened studies, 76 studies reporting on 50 different seroassays were included in the analysis. Sensitivity decay depended strongly on the antigen and the analytic technique used by the assay, with average sensitivities ranging between 26% and 98% at 6 months after infection, depending on assay characteristics. We found that a third of the included assays departed considerably from manufacturer specifications after 6 months.ConclusionsSeroassay sensitivity decay depends on assay characteristics, and for some types of assays, it can make manufacturer specifications highly unreliable. We provide a tool to correct for this phenomenon and to assess the risk of decay for a given assay. Our analysis can guide the design and interpretation of serosurveys for SARS-CoV-2 and other pathogens and quantify systematic biases in the existing serology literature.

Diabetes during the COVID-19 pandemic: are people getting access to the right level of care?

INTRODUCTION: Avoidance of health services, in particular hospital and community services, is problematic for people with diabetes. Evidence has demonstrated that such missed attendances are associated with worse health, faster declines in functioning, and higher rates of mortality long-term. This paper investigated the impact of the pandemic on healthcare access across community and hospital care, including Virtual Care (VC) using several large datasets of General Practice (GP) and hospital services in western Sydney. METHODS: A retrospective cohort study using a time-series database of 173,805 HbA1c tests done at Blacktown and Mt Druitt hospitals and 1.8 million recorded consultations at GP clinics in the region was undertaken. RESULTS: The average rate of diabetes in Emergency Department fell from 17.8% pre-pandemic to 11% after January 2020 (p < 0.001). This rate varied substantially over time, and correlated well with large outbreaks of COVID-19 in the state. Conversely, attendances of people with diabetes to GP clinics, especially using VC services, increased substantially over the pandemic period. DISCUSSION/CONCLUSION: During the pandemic there was a substantial avoidance of hospital care by patients with diabetes. However, this may have been replaced by VC offered in the community for those with less severe diseases.

COVID-19 Vaccine Misperceptions in a Community Sample of Adults Aged 18-49 Years in Australia.

Central to a successful population vaccination program is high uptake of vaccines. However, COVID-19 vaccine uptake may be impeded by beliefs based on misinformation. We sought to understand the prevalence and nature of misbeliefs about COVID-19 vaccines, and identify associated factors, shortly after commencement of Australia's national vaccine rollout. A cross-sectional survey was administered to unvaccinated young adults (n = 2050) in Australia aged 18-49 years (mean age 33 years), 13 July-21 August 2021. This sample was previously under-represented in COVID-19 research but shown to have less willingness to vaccinate. Two thirds of participants agreed with at least one misbelief item. Misperceptions about COVID-19 vaccines were found to be significantly associated with lower health literacy, less knowledge about vaccines, lower perceived personal risk of COVID-19, greater endorsement of conspiracy beliefs, and lower confidence and trust in government and scientific institutions. Misbeliefs were more common in participants with less educational attainment, in younger age groups, and in males, as per previous research. Understanding determinants and barriers to vaccination uptake, such as knowledge and beliefs based on misinformation, can help to shape effective public health communication and inform debunking efforts at this critical time and in the future.

Plausibility of Claimed Covid-19 Vaccine Efficacies by Age: A Simulation Study.

BACKGROUND: Multiple vaccines against Covid-19 have passed through phase-3 trials; however, concerns have been raised about alleged excessive similarity of efficacy across age groups for the Sputnik V vaccine. STUDY QUESTION: How likely are the observed efficacies for all age subgroups to fall within the range of by-age efficacies claimed for the AstraZeneca, Janssen, Moderna, Pfizer, and Sputnik V vaccines, assuming that there is no effect of age on efficacy? STUDY DESIGN: We performed a simulation study using R of 1000 and then 50,000 simulated trials for each vaccine, with random allocation to each arm but fixed enrollment numbers by age group. We used study-wide efficacy and infection rate for all age groups. We recorded the observed vaccine efficacies in each age group and summated how many simulations had all observed efficacies fall within the range of efficacies described in the relevant article. RESULTS: In the 1000-trial simulation for the AstraZeneca vaccine, in 23.8% of simulated trials, the observed efficacies of all age subgroups fell within the efficacy bounds for age subgroups in the published article. The J + J simulation showed 44.7%, Moderna 51.1%, Pfizer 30.5%, and 0.0% of the Sputnik simulated trials had all age subgroups fall within the limits of the efficacy estimates described by the published article. In 50,000 simulated trials of the Sputnik vaccine, 0.026% had all age subgroups fall within the limits of the efficacy estimates described by the published article, whereas 99.974% did not. CONCLUSIONS: The distribution of alleged vaccine efficacies of the Sputnik vaccine by age in the phase-III trial is very unlikely to occur in genuine experimental data, even if the number of patients recruited, vaccine efficacy, and overall infection rate are true and there is no underlying difference in vaccine efficacy by age.

Assessing the burden of COVID-19 in developing countries: systematic review, meta-analysis and public policy implications.

INTRODUCTION: The infection fatality rate (IFR) of COVID-19 has been carefully measured and analysed in high-income countries, whereas there has been no systematic analysis of age-specific seroprevalence or IFR for developing countries. METHODS: We systematically reviewed the literature to identify all COVID-19 serology studies in developing countries that were conducted using representative samples collected by February 2021. For each of the antibody assays used in these serology studies, we identified data on assay characteristics, including the extent of seroreversion over time. We analysed the serology data using a Bayesian model that incorporates conventional sampling uncertainty as well as uncertainties about assay sensitivity and specificity. We then calculated IFRs using individual case reports or aggregated public health updates, including age-specific estimates whenever feasible. RESULTS: In most locations in developing countries, seroprevalence among older adults was similar to that of younger age cohorts, underscoring the limited capacity that these nations have to protect older age groups.Age-specific IFRs were roughly 2 times higher than in high-income countries. The median value of the population IFR was about 0.5%, similar to that of high-income countries, because disparities in healthcare access were roughly offset by differences in population age structure. CONCLUSION: The burden of COVID-19 is far higher in developing countries than in high-income countries, reflecting a combination of elevated transmission to middle-aged and older adults as well as limited access to adequate healthcare. These results underscore the critical need to ensure medical equity to populations in developing countries through provision of vaccine doses and effective medications.

Making Statistical Sense of the Molnupiravir MOVe-OUT Clinical Trial.

Oral therapies for the early treatment of COVID-19 may prevent disease progression and health system overcrowding. A new oral therapeutic named molnupiravir has been promoted as providing an approximately 50% reduction in death or the need for hospitalization. The clinical trial evaluating this drug was stopped early at the recommendation of the Data Safety and Monitoring Board after approximately 50% of the sample had been recruited. At the point of discontinuing the trial, approximately 90% of the planned sample had been recruited and had available follow-up data accessible. We discuss issues about the study conduct, analysis, and interpretation, including 1) the authors and sponsors presented the interim analysis as the primary analysis; 2) communication between sponsors and the Data Safety and Monitoring Board was insufficient; 3) the treatment effects reverse when examining only the post-interim analysis population, and are substantially attenuated when examining the full data; 4) the choice of primary analysis is incorrect; 5) analysis of lost-to-follow-up patients favors the study drug; and 6) other known molnupiravir trials were not presented in the primary study findings. As a result of methodological and statistical concerns, it seems that external trials, separate from those supported by the sponsoring company, are required to determine the utility of this drug.

Correction of scientific literature: Too little, too late!

The Coronavirus Disease 2019 (COVID-19) pandemic has highlighted the limitations of the current scientific publication system, in which serious post-publication concerns are often addressed too slowly to be effective. In this Perspective, we offer suggestions to improve academia's willingness and ability to correct errors in an appropriate time frame.

Assessing the Age Specificity of Infection Fatality Rates for COVID-19: Systematic Review, Meta-analysis, & Public Policy Implications

To assess age-specific infection fatality rates (IFRs) for COVID-19, we have conducted a systematic review of seroprevalence studies as well as countries with comprehensive tracing programs. Age-specific IFRs were computed using the prevalence data in conjunction with reported fatalities four weeks after the midpoint date of each study, reflecting typical lags in fatalities and reporting. Using metaregression procedures, we find a highly significant log-linear relationship between age and IFR for COVID-19. The estimated age-specific IFRs are very low for children and younger adults but increase progressively to 0.4% at age 55, 1.3% at age 65, 4.2% at age 75, and 14% at age 85. About 90% of the geographical variation in population IFR is explained by differences in age composition of the population and age-specific prevalence. These results indicate that COVID-19 is hazardous not only for the elderly but also for middle-aged adults. Moreover, the population IFR for COVID-19 should not be viewed as a fixed parameter but as intrinsically linked to the age-specific pattern of infections. Consequently, public health measures to protect vulnerable age groups could substantially decrease total deaths.

People's Experiences and Satisfaction With Telehealth During the COVID-19 Pandemic in Australia: Cross-Sectional Survey Study.

BACKGROUND: In response to the COVID-19 pandemic, telehealth has rapidly been adopted to deliver health care services around the world. To date, studies have not compared people's experiences with telehealth services during the pandemic in Australia to their experiences with traditional in-person visits. OBJECTIVE: This study aimed to compare participants' perceptions of telehealth consults to their perceptions of traditional in-person visits and investigate whether people believe that telehealth services would be useful after the pandemic. METHODS: A national, cross-sectional, community survey was conducted between June 5 and June 12, 2020 in Australia. In total, 1369 participants who were aged ≥18 years and lived in Australia were recruited via targeted advertisements on social media (ie, Facebook and Instagram). Participants responded to survey questions about their telehealth experience, which included a free-text response option. A generalized linear model was used to estimate the adjusted relative risks of having a poorer telehealth experience than a traditional in-person visit experience. Content analysis was performed to determine the reasons why telehealth experiences were worse than traditional in-person visit experiences. RESULTS: Of the 596 telehealth users, the majority of respondents (n=369, 61.9%) stated that their telehealth experience was "just as good as" or "better than" their traditional in-person medical appointment experience. On average, respondents perceived that telehealth would be moderately useful to very useful for medical appointments after the COVID-19 pandemic ends (mean 3.67, SD 1.1). Being male (P=.007), having a history of both depression and anxiety (P=.016), and lower patient activation scores (ie, individuals' willingness to take on the role of managing their health/health care) (P=.036) were significantly associated with a poor telehealth experience. In total, 6 overarching themes were identified from free-text responses for why participants' telehealth experiences were poorer than their traditional in-person medical appointment experiences, as follows: communication is not as effective, limitations with technology, issues with obtaining prescriptions and pathology results, reduced confidence in their doctor, additional burden for complex care, and inability to be physically examined. CONCLUSIONS: Based on our sample's responses, telehealth appointment experiences were comparable to traditional in-person medical appointment experiences. Telehealth may be worthwhile as a mode of health care delivery while the pandemic continues, and it may continue to be worthwhile after the pandemic.

Assessing the age specificity of infection fatality rates for COVID-19: systematic review, meta-analysis, and public policy implications.

Determine age-specific infection fatality rates for COVID-19 to inform public health policies and communications that help protect vulnerable age groups. Studies of COVID-19 prevalence were collected by conducting an online search of published articles, preprints, and government reports that were publicly disseminated prior to 18 September 2020. The systematic review encompassed 113 studies, of which 27 studies (covering 34 geographical locations) satisfied the inclusion criteria and were included in the meta-analysis. Age-specific IFRs were computed using the prevalence data in conjunction with reported fatalities 4 weeks after the midpoint date of the study, reflecting typical lags in fatalities and reporting. Meta-regression procedures in Stata were used to analyze the infection fatality rate (IFR) by age. Our analysis finds a exponential relationship between age and IFR for COVID-19. The estimated age-specific IFR is very low for children and younger adults (e.g., 0.002% at age 10 and 0.01% at age 25) but increases progressively to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75, and 15% at age 85. Moreover, our results indicate that about 90% of the variation in population IFR across geographical locations reflects differences in the age composition of the population and the extent to which relatively vulnerable age groups were exposed to the virus. These results indicate that COVID-19 is hazardous not only for the elderly but also for middle-aged adults, for whom the infection fatality rate is two orders of magnitude greater than the annualized risk of a fatal automobile accident and far more dangerous than seasonal influenza. Moreover, the overall IFR for COVID-19 should not be viewed as a fixed parameter but as intrinsically linked to the age-specific pattern of infections. Consequently, public health measures to mitigate infections in older adults could substantially decrease total deaths.

A systematic review and meta-analysis of published research data on COVID-19 infection fatality rates.

An important unknown during the coronavirus disease-2019 (COVID-19) pandemic has been the infection fatality rate (IFR). This differs from the case fatality rate (CFR) as an estimate of the number of deaths and as a proportion of the total number of cases, including those who are mild and asymptomatic. While the CFR is extremely valuable for experts, IFR is increasingly being called for by policy makers and the lay public as an estimate of the overall mortality from COVID-19. METHODS: Pubmed, Medline, SSRN, and Medrxiv were searched using a set of terms and Boolean operators on 25/04/2020 and re-searched on 14/05/2020, 21/05/2020 and 16/06/2020. Articles were screened for inclusion by both authors. Meta-analysis was performed in Stata 15.1 by using the metan command, based on IFR and confidence intervals extracted from each study. Google/Google Scholar was used to assess the grey literature relating to government reports. RESULTS: After exclusions, there were 24 estimates of IFR included in the final meta-analysis, from a wide range of countries, published between February and June 2020. The meta-analysis demonstrated a point estimate of IFR of 0.68% (0.53%-0.82%) with high heterogeneity (p < 0.001). CONCLUSION: Based on a systematic review and meta-analysis of published evidence on COVID-19 until July 2020, the IFR of the disease across populations is 0.68% (0.53%-0.82%). However, due to very high heterogeneity in the meta-analysis, it is difficult to know if this represents a completely unbiased point estimate. It is likely that, due to age and perhaps underlying comorbidities in the population, different places will experience different IFRs due to the disease. Given issues with mortality recording, it is also likely that this represents an underestimate of the true IFR figure. More research looking at age-stratified IFR is urgently needed to inform policymaking on this front.