Preparedness of Military Public Health for Epidemic and Pandemic Recognition and Response.

Disease epidemics have threatened American military preparedness and operational capabilities since 1775. The ongoing Severe Acute Respiratory Syndrome Coronavirus 2 (COVID-19) pandemic, which began in 2019, again demonstrates the significant potential for infectious diseases to impact military units and threaten military readiness. We reviewed the historical and continuing threats to the U.S. Military from infectious disease outbreaks, as well as changes in U.S. Military capabilities for conducting meaningful surveillance and response. We concluded that a structured review of military public health and preventive medicine capabilities should be conducted to assess the response to the COVID-19 pandemic and determine the capabilities necessary for infectious disease surveillance and response to future threats.

Follow-Up: Effects of a Pandemic and Isolation on Alcohol and Psychoactive Medication Use in a Population of Rehabilitation and Pain Patients.

OBJECTIVE: The conjunction of the coronavirus disease lockdown and the use of illicit drugs suggests the potential increase in drug usage and opioid deaths. Because of other studies, we felt the need to examine if the lockdown has caused a change in the drug intake of our population of substance abuse and pain management patients. Our initial study indicated no increase in the use of illicit and antianxiety drugs. This study is a continuation of that work. MATERIALS: Urine drug testing is a strategy to reduce harm to patients in pain management and substance abuse treatment programs. We analyzed trends in the clinical drug testing patterns of urine specimens sent by substance abuse and pain clinics to monitor their patients. These specimens were tested by a national clinical laboratory using LC-MS/MS definitive methods. The time frame of these comparative observations was the past six years, including the two years of the pandemic. RESULTS: We observed a 30% reduction in test requests during the second quarter of 2020, the number of test requests and specimens submitted was similar during other times of the six-year period. The observed drug use pattern was similar to the earlier study. Among the patients tested, positivity decreased greatly for the illicit drugs heroin and cocaine but increased for methamphetamine and fentanyl. Use of the antidepressant and anxiolytic drugs remained consistent or declined for some drugs, relative to pre-pandemic patterns. The percent of patients prescribed the opiates morphine and oxycodone decreased, while the use of hydrocodone increased. Positivity for the drug gabapentin increased greatly. The use of alcohol did not increase significantly during the lockdown period. CONCLUSION: In summary, these findings demonstrate relatively consistent drug use, with decreased positivity for high-risk drugs and dangerous drug combinations. We speculate that monitoring of these patients mitigates the possibility of drug misuse and potential overdose and is in concordance with the goals of these monitoring programs.

Military Epidemics, Then and Now: Smallpox and COVID-19.

We compared the COVID-19 experience in the first year of the current pandemic in the US with the smallpox experience of the 18th century, focusing on the US military but recognizing civilian and military populations are not separate and distinct. Despite the epidemics being separated by 21/2 centuries and with great advancements in technology having occurred over that time, we observed similarities which led us to several conclusions: • Infectious disease outbreaks will continue to occur and novel agents, naturally occurring or manipulated by humans, will threaten military and civilian populations nationally and globally. • Infectious disease outbreaks can affect both military and civilian populations, persist for long periods, and be catastrophic to military peacetime and wartime operations. • Effective surveillance is a prerequisite for early identification and subsequent meaningful responses to novel and reemerging threat agents and diseases. • Socio-cultural, religious, or political factors may limit the implementation of effective interventions in military or civilian populations. Public health officials must assess impediments to implementation of interventions and develop plans to overcome them.

Acute Bilateral Descemet Membrane Endothelial Keratoplasty Graft Rejection After the BNT162b2 mRNA COVID-19 Vaccine.

Purpose: We report a case of acute bilateral Descemet membrane endothelial keratoplasty (DMEK) rejection two weeks following BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech), reflecting on possible changes to the management of patients with DMEK scheduled for COVID-19 vaccination. Patients and Methods: A 94-year-old woman with Fuchs' endothelial dystrophy who underwent DMEK 24 months earlier (right eye) and 20 months earlier (left eye) demonstrated bilateral graft rejection two weeks after the first dose of COVID-19 vaccine. Standard treatment regimen was followed, and clinical status documented with slit-lamp examination and swept-source optical coherence tomography throughout. Results: Preoperative best corrected visual acuity (BCVA) and corneal thickness (CT) were 0.3 and 679µm right eye and 0.2 and 668µm left eye. Postoperative BCVA and CT were 0.7 and 559µm right eye and 0.4 and 590µm left eye. Standard treatment regimen consisted of dexamethasone/tobramycin and ketorolac, four times daily. At one month, both preparations were discontinued, replaced by dexamethasone 0.1% four times daily. At three months, this was tapered to once daily. Post-rejection, BCVA and CT were 0.2 and 710µm right eye and 0.3 and 710µm left eye. Treatment was with dexamethasone/tobramycin six times daily. Poor response resulted in re-DMEK transplantation, starting in the left eye. At one-month follow-up, BCVA and CT were 0.5 and 538µm right eye and 0.63 and 504µm left eye. Conclusion: We report the first acute bilateral DMEK graft rejection after a single dose of COVID-19 vaccine. We recommend clinicians exercise vigilance and consider dexamethasone 0.1% during the vaccination period.

A large outbreak of COVID-19 in a UK prison, October 2020 to April 2021.

Prisons are susceptible to outbreaks. Control measures focusing on isolation and cohorting negatively affect wellbeing. We present an outbreak of coronavirus disease 2019 (COVID-19) in a large male prison in Wales, UK, October 2020 to April 2021, and discuss control measures.We gathered case-information, including demographics, staff-residence postcode, resident cell number, work areas/dates, test results, staff interview dates/notes and resident prison-transfer dates. Epidemiological curves were mapped by prison location. Control measures included isolation (exclusion from work or cell-isolation), cohorting (new admissions and work-area groups), asymptomatic testing (case-finding), removal of communal dining and movement restrictions. Facemask use and enhanced hygiene were already in place. Whole-genome sequencing (WGS) and interviews determined the genetic relationship between cases plausibility of transmission.Of 453 cases, 53% (n = 242) were staff, most aged 25-34 years (11.5% females, 27.15% males) and symptomatic (64%). Crude attack-rate was higher in staff (29%, 95% CI 26-64%) than in residents (12%, 95% CI 9-15%).Whole-genome sequencing can help differentiate multiple introductions from person-to-person transmission in prisons. It should be introduced alongside asymptomatic testing as soon as possible to control prison outbreaks. Timely epidemiological investigation, including data visualisation, allowed dynamic risk assessment and proportionate control measures, minimising the reduction in resident welfare.

Effect of Relative Humidity on Transfer of Aerosol-Deposited Artificial and Human Saliva from Surfaces to Artificial Finger-Pads.

Surface to hand transfer of viruses represents a potential mechanism for human exposure. An experimental process for evaluating the touch transfer of aerosol-deposited material is described based on controlling surface, tribological, and soft matter components of the transfer process. A range of high-touch surfaces were evaluated. Under standardized touch parameters (15 N, 1 s), relative humidity (RH) of the atmosphere around the contact transfer event significantly influenced transfer of material to the finger-pad. At RH < 40%, transfer from all surfaces was <10%. Transfer efficiency increased markedly as RH increased, reaching a maximum of approximately 50%. The quantity of material transferred at specific RHs above 40% was also dependent on roughness of the surface material and the properties of the aerosol-deposited material. Smooth surfaces, such as melamine and stainless steel, generated higher transfer efficiencies compared to those with textured roughness, such as ABS pinseal and KYDEX® plastics. Pooled human saliva was transferred at a lower rate compared to artificial saliva, indicating the role of rheological properties. The artificial saliva data were modeled by non-linear regression and the impact of environmental humidity and temperature were evaluated within a Quantitative Microbial Risk Assessment model using SARS-CoV-2 as an example. This illustrated that the trade-off between transfer efficiency and virus survival may lead to the highest risks of fomite transmissions in indoor environments with higher humidity.

A review of the role of non-invasive ventilation in critical care responses to COVID-19 in low- and middle-income countries: lessons learnt from Baghdad.

In 2021, the burden of the coronavirus disease 2019 (COVID-19) pandemic became especially severe in low- and middle-income countries (LMICs). With high numbers of patients requiring advanced respiratory support and invasive mechanical ventilation (IMV), many ICUs were overwhelmed. This problem is particularly pronounced in LMICs, where the availability of intensive care beds may be limited. Non-invasive ventilation (NIV) has been increasingly used in COVID-19, as both a bridge to intubation as well as a definitive treatment. Use of NIV may be a feasible management strategy in settings where performing IMV is not possible on a large scale due to resource constraints. During 2020-2021, Médecins Sans Frontière helped manage a COVID-19 ICU in Baghdad, Iraq. The predominant mode of treatment was NIV. Due to a shortage of intensive care ventilators, NIV was delivered in the majority of cases by home continuous positive airway pressure machines. In total, 709 patients were admitted to the ICU during the study period with an overall mortality of 61.1%. In addition to the ventilation strategy, patients must be treated holistically, with a comprehensive package of critical care. We aim to highlight the role of NIV in this setting and summarise our experiences to assist future critical care projects during the pandemic.

A large outbreak of COVID-19 in a UK prison, October 2020 to April 2021 (preprint)

Introduction Prisons are susceptible to outbreaks. Control measures focusing on isolation and cohorting negatively affect wellbeing. We present an outbreak of COVID-19 in a large male prison in Wales, UK, 14 October 2020 to 21 April 2021, and discuss control measures. Methods We gathered case-information, including: demographics, staff-residence postcode, resident cell number, work areas/dates, test results, staff interview dates/notes and resident prison-transfer dates. Epidemiological curves were mapped by prison location. Control measures included isolation (exclusion from work or cell-isolation), cohorting (new admissions and work-area groups), asymptomatic testing (case-finding), removal of communal dining and movement restrictions. Facemask use and enhanced hygiene were already in place. Whole genome sequencing (WGS) and interviews determined genetic relationship between cases plausibility of transmission. Results Of 453 cases, 53% (n=242) were staff, most aged 25-34 years (11.5% females, 27.15% males) and symptomatic (64%). Crude attack-rate was higher in staff (29%, 95%CI: 26-64%) than in residents (12%, 95%CI: 9-15%). Conclusions Whole genome sequencing can help differentiate multiple introductions from person-to-person transmission in prisons. It should be introduced alongside asymptomatic testing as soon as possible to control prison outbreaks. Timely epidemiological investigation, including data visualization, allowed dynamic risk assessment and proportionate control measures, minimizing reduction in resident welfare.

Emergence of immune escape at dominant SARS-CoV-2 killer T-cell epitope (preprint)

The adaptive immune system protects against infection via selection of specific antigen receptors on B-cells and T-cells. We studied the prevalent CD8 killer T-cell response mounted against SARS-CoV-2 Spike269-277 epitope YLQPRTFLL via the most frequent Human Leukocyte Antigen (HLA) class I worldwide, HLA A*02. The widespread Spike P272L mutation has arisen in five different SARS-CoV-2 lineages to date and was common in the B.1.177 lineage associated with establishing the second wave in Europe. The large CD8 T-cell response seen across a cohort of HLA A*02+ convalescent patients, comprising of over 120 different TCRs, failed to respond to the P272L variant suggesting that proline 272 dominates TCR contacts with this epitope. Additionally, sizable populations (0.01%-0.2%) of total CD8 T-cells from individuals vaccinated against SARS-CoV-2 stained with HLA A*02-YLQPRTFLL multimers but failed to bind to the P272L reagent. Viral escape at prevalent T-cell epitopes restricted by high frequency HLA may be particularly problematic when vaccine immunity is focussed on a single protein such as SARS-CoV-2 Spike and provides a strong argument for inclusion of multiple viral proteins in next generation vaccines and highlights the urgent need for monitoring T-cell escape in new SARS-CoV-2 variants.

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.

Transformative Approach To Investigate the Microphysical Factors Influencing Airborne Transmission of Pathogens.

Emerging outbreaks of airborne pathogenic infections worldwide, such as the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, have raised the need to understand parameters affecting the airborne survival of microbes in order to develop measures for effective infection control. We report a novel experimental strategy, TAMBAS (tandem approach for microphysical and biological assessment of airborne microorganism survival), to explore the synergistic interactions between the physicochemical and biological processes that impact airborne microbe survival in aerosol droplets. This innovative approach provides a unique and detailed understanding of the processes taking place from aerosol droplet generation through to equilibration and viability decay in the local environment, elucidating decay mechanisms not previously described. The impact of evaporation kinetics, solute hygroscopicity and concentration, particle morphology, and equilibrium particle size on airborne survival are reported, using Escherichia coli MRE162 as a benchmark system. For this system, we report that (i) particle crystallization does not directly impact microbe longevity, (ii) bacteria act as crystallization nuclei during droplet drying and equilibration, and (iii) the kinetics of size and compositional change appear to have a larger effect on microbe longevity than the equilibrium solute concentration.IMPORTANCE A transformative approach to identify the physicochemical processes that impact the biological decay rates of bacteria in aerosol droplets is described. It is shown that the evaporation process and changes in the phase and morphology of the aerosol particle during evaporation impact microorganism viability. The equilibrium droplet size was found to affect airborne bacterial viability. Furthermore, the presence of Escherichia coli MRE162 in a droplet does not affect aerosol growth/evaporation but influences the dynamic behavior of the aerosol by processing the culture medium prior to aerosolization, affecting the hygroscopicity of the culture medium; this highlights the importance of the inorganic and organic chemical composition within the aerosolized droplets that impact hygroscopicity. Bacteria also act as crystallization nuclei. The novel approach and data have implications for increased mechanistic understanding of aerosol survival and infectivity in bioaerosol studies spanning the medical, veterinary, farming, and agricultural fields, including the role of microorganisms in atmospheric processing and cloud formation.

Exacerbation of Physical Intimate Partner Violence during COVID-19 Pandemic.

Background Intimate partner violence (IPV) is a global social and public health problem, but published literature regarding the exacerbation of physical IPV during the coronavirus disease 2019 (COVID-19) pandemic is lacking. Purpose To assess the incidence, patterns, and severity of injuries in IPV victims during the COVID-19 pandemic in 2020 compared with the prior 3 years. Materials and Methods The demographics, clinical presentation, injuries, and radiologic findings of patients reporting physical abuse arising from IPV during the statewide COVID-19 pandemic between March 11 and May 3, 2020, were compared with data from the same period for the past 3 years. Pearson χ2 and Fisher exact tests were used for analysis. Results A total of 26 victims of physical IPV from 2020 (mean age, 37 years ± 13 [standard deviation]; 25 women) were evaluated and compared with 42 victims of physical IPV (mean age, 41 years ± 15; 40 women) from 2017 to 2019. Although the overall number of patients who reported IPV decreased during the pandemic, the incidence of physical IPV was 1.8 times greater (95% CI: 1.1, 3.0; P = .01). The total number of deep injuries was 28 during 2020 versus 16 from 2017 to 2019; the number of deep injuries per victim was 1.1 during 2020 compared with 0.4 from 2017 to 2019 (P < .001). The incidence of high-risk abuse defined by mechanism was two times greater in 2020 (95% CI: 1.2, 4.7; P = .01). Patients who experienced IPV during the COVID-19 pandemic were more likely to be White; 17 (65%) victims in 2020 were White compared with 11 (26%) in the prior years (P = .007). Conclusion There was a higher incidence and severity of physical intimate partner violence (IPV) during the coronavirus disease 2019 (COVID-19) pandemic compared with the prior 3 years. These results suggest that victims of IPV delayed reaching out to health care services until the late stages of the abuse cycle during the COVID-19 pandemic. © RSNA, 2020.

Establishment & lineage dynamics of the SARS-CoV-2 epidemic in the UK (preprint)

The UK's COVID-19 epidemic during early 2020 was one of world's largest and unusually well represented by virus genomic sampling. Here we reveal the fine-scale genetic lineage structure of this epidemic through analysis of 50,887 SARS-CoV-2 genomes, including 26,181 from the UK sampled throughout the country's first wave of infection. Using large-scale phylogenetic analyses, combined with epidemiological and travel data, we quantify the size, spatio-temporal origins and persistence of genetically-distinct UK transmission lineages. Rapid fluctuations in virus importation rates resulted in >1000 lineages; those introduced prior to national lockdown were larger and more dispersed. Lineage importation and regional lineage diversity declined after lockdown, whilst lineage elimination was size-dependent. We discuss the implications of our genetic perspective on transmission dynamics for COVID-19 epidemiology and control.