Absolute and relative excess mortality across demographic and clinical subgroups during the COVID-19 pandemic: an individual-level cohort study from a nationwide healthcare system of US Veterans (preprint)

Background. Most analyses of excess mortality during the COVID-19 pandemic have employed aggregate data. Individual-level data from the largest integrated healthcare system in the US may enhance understanding of excess mortality. Methods. We performed an observational cohort study following patients receiving care from the Department of Veterans Affairs (VA) between 1 March 2018 and 28 February 2022. We estimated excess mortality on an absolute scale (i.e., excess mortality rates, number of excess deaths), and a relative scale by measuring the hazard ratio (HR) for mortality comparing pandemic and pre-pandemic periods, overall, and within demographic and clinical subgroups. Comorbidity burden and frailty were measured using the Charlson Comorbidity Index and Veterans Aging Cohort Study Index, respectively. Results. Of 5,905,747 patients, median age was 65.8 years and 91% were men. Overall, the excess mortality rate was 10.0 deaths/1000 person-years (PY), with a total of 103,164 excess deaths and pandemic HR of 1.25 (95% CI 1.25-1.26). Excess mortality rates were highest among the most frail patients (52.0/1000 PY) and those with the highest comorbidity burden (16.3/1000 PY). However, the largest relative mortality increases were observed among the least frail (HR 1.31, 95% CI 1.30-1.32) and those with the lowest comorbidity burden (HR 1.44, 95% CI 1.43-1.46). Conclusions. Individual-level data offered crucial clinical and operational insights into US excess mortality patterns during the COVID-19 pandemic. Notable differences emerged among clinical risk groups, emphasising the need for reporting excess mortality in both absolute and relative terms to inform resource allocation in future outbreaks.

Excess mortality in the general population versus Veterans Healthcare System during the first year of the COVID-19 pandemic in the United States (preprint)

Importance The COVID-19 pandemic had a substantial impact on the overall rate of death in the United States during the first year. It is unclear whether access to comprehensive medical care, such as through the VA healthcare system, altered death rates compared to the US population. Objective: Quantify the increase in death rates during the first year of the COVID-19 pandemic in the general US population and among individuals who receive comprehensive medical care through the Department of Veterans Affairs (VA). Design: Analysis of changes in all-cause death rates by quarter, stratified by age, sex race/ethnicity, and region, based on individual-level data. Hierarchical regression models were fit in a Bayesian setting. Standardized rates were used for comparison between populations. Setting and participants: General population of the United States, enrollees in the VA, and active users of VA healthcare. Exposure and main outcome: Changes in rates of death from any cause during the COVID-19 pandemic in 2020 compared to previous years. Results Sharp increases were apparent across all of the adult age groups (25 years and older) in both the general US population and the VA populations. Across all of 2020, the relative increase in death rates was similar in the general US population (RR: 1.20 (95% CI: 1.17, 1.22)), VA enrollees (RR: 1.20 (95% CI: 1.14, 1.29)), and VA active users (RR: 1.19 (95% CI: 1.14, 1.26)). Because the pre-pandemic standardized mortality rates were higher in the VA populations prior to the pandemic, the absolute rates of excess mortality were higher in the VA populations. Conclusions and Relevance: Despite access to comprehensive medical care, active users of the VA had similar relative mortality increases from all causes compared with the general US population. Factors that influenced baseline rates of death and that mitigated viral transmission in the community are more likely to have influenced the impact of the pandemic.

Localised community circulation of SARS-CoV-2 viruses with an increased accumulation of single nucleotide polymorphisms that adversely affect the sensitivity of real-time reverse transcription assays targeting Nucleocapsid protein. (preprint)

Currently the primary method for confirming acute SARS-CoV-2 infection is through the use of molecular assays that target highly conserved regions within the viral genome. Many, if not most of the diagnostic targets currently in use were produced early in the pandemic, using genomes sequenced and shared in early 2020. As viral diversity increases, mutations may arise in diagnostic target sites that have an impact on the performance of diagnostic tests. Here, we report on a local outbreak of SARS-CoV-2 which had gained an additional mutation at position 28890 of the nucleocapsid protein, on a background of pre-existing mutations at positions 28881, 28882, 28883 in one of the main circulating viral lineages in Wales at that time. The impact of this additional mutation had a statistically significant impact on the Ct value reported for the N gene target designed by the Chinese CDC and used in a number of commercial diagnostic products. Further investigation identified that, in viral genomes sequenced from Wales over the summer of 2020, the N gene had a higher rate of mutations in diagnostic target sites than other targets, with 115 issues identified affecting over 10% of all cases sequenced between February and the end of August 2020. In comparison an issue was identified for ORFab, the next most affected target, in less than 1.4% of cases over the same time period. This work emphasises the potential impact that mutations in diagnostic target sites can have on tracking local outbreaks, as well as demonstrating the value of genomics as a routine tool for identifying and explaining potential diagnostic primer issues as part of a laboratory quality management system. This work also indicates that with increasing genomic sequencing data availability, there is a need to re-evaluate the diagnostic targets that are in use for SARS-CoV-2 testing, to better target regions that are now demonstrated to be of lower variability.

Safety Recommendations for Evaluation and Surgery of the Head and Neck during the COVID-19 Pandemic (preprint)

Importance: The rapidly expanding 2019 novel coronavirus pandemic (COVID-19, caused by the SARS-CoV-2 virus) has challenged the medical community to an unprecedented degree. Physicians and healthcare workers are at added risk of exposure and infection during the course of the patient care. Due to the rapid spread of this disease through respiratory droplets, healthcare providers such as otolaryngologists-head & neck surgeons who come in close contact with the upper aerodigestive tract during diagnostic and therapeutic procedures are particularly at risk. Here we present a set of safety recommendations based on our review of literature and communications with physicians with first-hand knowledge of safety procedures during the 2019 COVID-19 pandemic.Observations: A high number of healthcare providers were infected during the first phase of the pandemic in Wuhan province. Subsequently, by adopting strict safety precautions, other regions were able to achieve high levels of safety for healthcare providers without jeopardizing the care of patients. We reviewed the most common procedures related to the examination and treatment of upper aerodigestive tract diseases. Each category was reviewed based on the potential risk imposed to healthcare workers. Specific recommendations were made, based on the literature, when available, or consensus best practices. Specific safety recommendations were made for performing tracheostomy in COVID-19 patients. Conclusions and Relevance: Preserving highly skilled healthcare work force is a top priority for any community and healthcare system. Based on the experience of healthcare systems in Asia and Europe, by following strict safety guidelines, the risk of exposure and infection of healthcare providers could be significantly reduced, while providing high levels of care. The provided recommendations could be used as broad guidance for all healthcare workers who are involved with the care of COVID-19 patients.