The US Department of Veterans Affairs Science and Health Initiative to Combat Infectious and Emerging Life-Threatening Diseases (VA SHIELD): A Biorepository Addressing National Health Threats.

Background: The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has demonstrated the need to share data and biospecimens broadly to optimize clinical outcomes for US military Veterans. Methods: In response, the Veterans Health Administration established VA SHIELD (Science and Health Initiative to Combat Infectious and Emerging Life-threatening Diseases), a comprehensive biorepository of specimens and clinical data from affected Veterans to advance research and public health surveillance and to improve diagnostic and therapeutic capabilities. Results: VA SHIELD now comprises 12 sites collecting de-identified biospecimens from US Veterans affected by SARS-CoV-2. In addition, 2 biorepository sites, a data processing center, and a coordinating center have been established under the direction of the Veterans Affairs Office of Research and Development. Phase 1 of VA SHIELD comprises 34 157 samples. Of these, 83.8% had positive tests for SARS-CoV-2, with the remainder serving as contemporaneous controls. The samples include nasopharyngeal swabs (57.9%), plasma (27.9%), and sera (12.5%). The associated clinical and demographic information available permits the evaluation of biological data in the context of patient demographics, clinical experience and management, vaccinations, and comorbidities. Conclusions: VA SHIELD is representative of US national diversity with a significant potential to impact national healthcare. VA SHIELD will support future projects designed to better understand SARS-CoV-2 and other emergent healthcare crises. To the extent possible, VA SHIELD will facilitate the discovery of diagnostics and therapeutics intended to diminish COVID-19 morbidity and mortality and to reduce the impact of new emerging threats to the health of US Veterans and populations worldwide.

Identification of virus-specific B-cell epitopes by convalescent plasma from COVID-19 patients.

Identification of immunologic epitopes against SARS-CoV-2 is crucial for the discovery of diagnostic, therapeutic, and preventive targets. In this study, we used a pan-coronavirus peptide microarray to screen for potential B-cell epitopes and validated the results with peptide-based ELISA. Specifically, we identified three linear B-cell epitopes on the SARS-CoV-2 proteome, which were recognized by convalescent plasma from COVID-19 patients. Interestingly, two epitopes (S 809-823 and R1ab 909-923) strongly reacted to convalescent plasma collected at the early phase (< 90 days) of COVID-19 symptom onset, whereas one epitope (M 5-19) reacted to convalescent plasma collected > 90 days after COVID-19 symptom onset. Neutralization assays using antibody depletion with the identified spike (S) peptides revealed that three S epitopes (S 557-571, S 789-803, and S 809-823) elicited neutralizing antibodies in COVID-19 patients. However, the levels of virus-specific antibody targeting S 789-803 only positively correlated with the neutralizing rates at the early phase (<60 days) after disease onset, and the antibody titers diminished quickly with no correlation to the neutralizing activity beyond two months after recovery from COVID-19. Importantly, stimulation of peripheral blood mononuclear cells from COVID-19-recovered patients with these SARS-CoV-2 S peptides resulted in poor virus-specific B cell activation, proliferation, differentiation into memory B cells, and production of immunoglobulin G (IgG) antibodies, despite the B-cells being functionally competent as demonstrated by their response to non-specific stimulation. Taken together, these findings indicate that these newly identified SARS-CoV-2-specific B-cell epitopes can elicit neutralizing antibodies, with titers and/or neutralizing activities declining significantly within 2-3 months in the convalescent plasma of COVID-19 patients.

Plasma biomarkers for systemic inflammation in COVID-19 survivors.

BACKGROUND: While the majority of COVID-19 patients fully recover from the infection and become asymptomatic, a significant proportion of COVID-19 survivors experience a broad spectrum of symptoms lasting weeks to months post-infection, a phenomenon termed "post-acute sequelae of COVID-19 (PASC)." The aim of this study is to determine whether inflammatory proteins are dysregulated and can serve as potential biomarkers for systemic inflammation in COVID-19 survivors. METHODS: We determined the levels of inflammatory proteins in plasma from 22 coronavirus disease 2019 (COVID-19) long haulers (COV-LH), 22 COVID-19 asymptomatic survivors (COV-AS), and 22 healthy subjects (HS) using an Olink proteomics assay and assessed the results by a beads-based multiplex immunoassay. RESULTS: Compared to HS, we found that COVID-19 survivors still exhibited systemic inflammation, as evidenced by significant changes in the levels of multiple inflammatory proteins in plasma from both COV-LH and COV-AS. CXCL10 was the only protein that significantly upregulated in COV-LH compared with COV-AS and HS. CONCLUSIONS: Our results indicate that several inflammatory proteins remain aberrantly dysregulated in COVID-19 survivors and CXCL10 might serve as a potential biomarker to typify COV-LH. Further characterization of these signature inflammatory molecules might improve the understanding of the long-term impacts of COVID-19 and provide new targets for the diagnosis and treatment of COVID-19 survivors with PASC.

Trained Immunity: An Overview and the Impact on COVID-19.

Effectively treating infectious diseases often requires a multi-step approach to target different components involved in disease pathogenesis. Similarly, the COVID-19 pandemic has become a global health crisis that requires a comprehensive understanding of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection to develop effective therapeutics. One potential strategy to instill greater immune protection against COVID-19 is boosting the innate immune system. This boosting, termed trained immunity, employs immune system modulators to train innate immune cells to produce an enhanced, non-specific immune response upon reactivation following exposure to pathogens, a process that has been studied in the context of in vitro and in vivo clinical studies prior to the COVID-19 pandemic. Evaluation of the underlying pathways that are essential to inducing protective trained immunity will provide insight into identifying potential therapeutic targets that may alleviate the COVID-19 crisis. Here we review multiple immune training agents, including Bacillus Calmette-Guérin (BCG), ß-glucan, and lipopolysaccharide (LPS), and the two most popular cell types involved in trained immunity, monocytes and natural killer (NK) cells, and compare the signaling pathways involved in innate immunity. Additionally, we discuss COVID-19 trained immunity clinical trials, emphasizing the potential of trained immunity to fight SARS-CoV-2 infection. Understanding the mechanisms by which training agents activate innate immune cells to reprogram immune responses may prove beneficial in developing preventive and therapeutic targets against COVID-19.

A Report on the Impact of the COVID-19 Pandemic on the Health and Social Welfare of the Native Hawaiian Population in Hawai'i

Native Hawaiians (NHs) are among the most vulnerable groups at greater risk for coronavirus disease 2019 (COVID-19). To understand the impact of COVID-19 on the state's population, a 35-question cross-sectional survey was administered across the state of Hawai'i. NH data from the larger report are provided here. The findings indicate that the impact of COVID-19 is disproportionately affecting NH households in areas of income and housing stability, chronic disease prevalence, emotional wellness, and COVID-19 prevention. Short-, medium-, and long-term recommendations are presented as next steps to addressing the health inequities among NHs. ©Copyright 2021 by University Health Partners of Hawai‘i (UHP Hawai‘i).

A Report on the Impact of the COVID-19 Pandemic on the Health and Social Welfare in the State of Hawai'i

The coronavirus disease 2019 (COVID-19) pandemic has had a profound impact on the world. To address the impact of COVID-19 in the state of Hawai'i, the Hawai'i Emergency Management Agency (HI-EMA) Community Care Outreach Unit conducted an assessment survey to determine the impact of COVID-19 on the health and social welfare of individuals and their families across the state. This article presents key statewide findings from this assessment, including areas of need and community-based recommendations to help mitigate the impact of the pandemic, particularly for vulnerable groups. A total of 7927 participants responded to the assessment survey from across the state's counties. In all questions related to paying for essentials, the percentage of participants that expect to have problems in the future, as compared to now, almost doubled. Slightly higher than one-third reported that they would know how to care for a family member in the home with COVID-19, and half of the respondents reported a lack of space for isolation in their home. About half reported that if they got COVID-19, they would have someone available to care for them. Overall, Native Hawaiian, Pacific Islander, and Filipino groups reported greater burden in almost all areas surveyed. The results presented provide a baseline in understanding the impact, needs, and threats to the health and social welfare of individuals and their families across the state of Hawai'i. Local stakeholders can utilize this information when developing priorities, strategies, and programs to address current and future pandemics in the state. ©Copyright 2021 by University Health Partners of Hawai‘i (UHP Hawai‘i).

A Report on the Impact of the COVID-19 Pandemic on the Health and Social Welfare in the City and County of Honolulu, Hawai'i

To address the impact of COVID-19 in the state of Hawai'i, the Hawai'i Emergency Management Agency Medical Public Health Branch activated its' Community Care Outreach Unit (CCO Unit). A team from this unit developed a survey to assess the impact, needs, and threats to the health and social welfare of individuals and their families as they pertain to COVID-19. This article presents key findings for the City and County of Honolulu (CCH). A total of 5598 CCH residents responded. Approximately half of these respondents reported they or their household members experienced reduced work hours or lost their job as a result of COVID-19. In all questions related to paying for essential living costs, at the time of the survey, the percentage of participants who expected to have future problems nearly doubled. Those preparing for school in the fall school semester expected challenges centered on insufficient funds to purchase school supplies, lack of available face-coverings, and language barriers. Financial assistance, rental assistance, and food assistance seemed to be more difficult to apply for compared to health care services. The most common reasons for difficulty with applications noted by residents included that they could not figure out how to complete the form, did not have all the documents, or could not get through on the telephone. About one-half of CCH participants reported feeling nervous more than half of the days or nearly every day in the past 2 weeks. Most perceived the severity of COVID-19 to be moderate to very high. Less than half reported knowing how to provide care for someone in their family with COVID-19. Half of the CCH participants reported that they practice social distancing usually or all of the time, and the majority reported wearing a face-covering usually or always when outside of the home. A significant portion of respondents reported barriers for providing care for a household member exposed or infected with COVID-19. Such barriers included a lack of space in their home for isolation;not having enough cleaning supplies;no working thermometer in the home, or no family member available to care for them. The results presented may provide a baseline for understanding the impact, needs, and threats to the health and social welfare of individuals and their families in CCH and across the state of Hawai'i. Local stakeholders can utilize this information in developing priorities, strategies, and programs to address the pandemic as it continues to unfold and learn lessons for future pandemics.

A Report on the Impact of the COVID-19 Pandemic on the Health and Social Welfare in the County of Hawai'i, Hawai'i

The Community Care Outreach Unit (CCO) of the Hawai'i Emergency Management Medical/Public Health Services Branch conducted a survey to gauge the impact of coronavirus disease 2019 (COVID-19) on the health and social welfare of individuals and families in the state of Hawai'i. A mixed-methods framework was utilized for survey distribution;7927 respondents participated in the survey. This article presents key findings for the state's Hawai'i County (HC). It presents a descriptive analysis of the data to provide a basic overview of the impact of COVID-19 in HC, as assessed in August-September 2020. A total of 936 participants from HC responded to the survey. Approximately one-third reported that they or their family members experienced reduced work hours, and one-fifth lost their jobs because of COVID-19. Many reported difficulties paying for many types of living essentials and expected these difficulties to increase in the near future. Challenges for the fall school semester included lack of access to funds for school supplies and face-coverings. The majority perceived the severity of COVID-19 to be moderate/very high and most had at least a moderate level of knowledge about risks for developing severe COVID-19. Approximately half reported maintaining social distancing usually/all of the time, and about two-thirds reported wearing a face-covering usually/always when needed. Other barriers for COVID disease prevention and response included a lack of space for quarantine/isolation of family members, not having enough cleaning supplies, low knowledge of how to care for a household member with COVID disease and not having someone available to care for them if they contracted the virus. The results provide a baseline for understanding the impact, needs, and threats to the health and social welfare of individuals and their families as a result of COVID-19 in HC. Local stakeholders can utilize this information when developing priorities, strategies, and programs to address the pandemic where needed.

A Report on the Impact of the COVID-19 Pandemic on the Health and Social Welfare in the County of Maui, Hawai'i

The Community Care Outreach Unit of the Hawai'i Emergency Management Agency (HI-EMA) Medical/Public Heath Branch conducted a survey to gauge the impact, needs, and threats to the health and social welfare of individuals and their families pertaining to coronavirus disease 2019 (COVID-19). This article presents key findings for the County of Maui (MC) in the state. A mixed-methods framework was utilized for survey distribution and recruitment of participants from across the state. Recruitment strategies included snowball sampling via website and social media, and paper surveys. Descriptive analysis of the data is presented to give a basic overview of the impact of COVID-19 in MC. A total of 883 participants in MC responded to the survey. Approximately one-third reported that they or family members experienced reduced work hours or lost their job because of COVID-19. In all questions related to paying for essential living needs, the percentage of participants who expected to have future problems was higher than the percentage who reported having current problems. Of those preparing for the fall 2020 school semester, expected challenges included lack of funds to purchase school supplies, lack of face coverings, and language barriers. Most participants in MC perceived the severity of COVID-19 to be moderate to very high, and there was a moderate level of knowledge about which groups are more at risk for contracting severe COVID-19. Less than half would know how to provide care for someone in their family with COVID-19. Several resource barriers for caring for a family member with COVID-19 were identified. The COVID-19 pandemic has had a more severe impact on Native Hawaiian and Pacific Islander groups compared to others in the county. The results may provide a baseline for understanding the impact, needs, and threats to the health and social welfare of individuals and their families in MC. Local stakeholders can utilize this information to develop priorities, strategies, and programs to address the COVID-19 pandemic response in MC.

A Report on the Impact of the COVID-19 Pandemic on the Health and Social Welfare in the County of Kaua'i, Hawai'i

The Hawai'i Emergency Management Agency Community Care Outreach Unit (CCO) conducted a survey to gauge the impact of coronavirus disease 2019 (COVID-19) on the health and social welfare of individuals and their families across the state of Hawai'i. A mixed-methods framework was utilized for survey distribution. This article presents a descriptive analysis of the data to provide a basic overview of the impact of COVID-19 in Kaua'i County (KC), as assessed in August/September 2020. A total of 420 participants in KC responded to the statewide survey. Approximately one-third reported that they or their family members experienced reduced work hours or lost their job because of COVID-19. Many reported difficulties paying for many types of living essentials and expected these difficulties to increase in the near future. Prevalent challenges for the fall school semester included access to funds for school supplies and face-coverings. About one-third reported feeling nervous more than half the time or nearly every day in the past 2 weeks, and one-fourth reported feeling worried more than half the time or nearly every day in the past 2 weeks. The majority perceived the severity of COVID-19 to be moderate/very high and most had at least a moderate level of knowledge about risks for contracting severe COVID-19. Less than half said they would know how to provide care for someone in their family with COVID-19. Half of the respondents in KC reported maintaining social distancing usually/all of the time, the majority reported wearing a face-covering usually/always when needed. The results provide a baseline for understanding the impact, needs, and threats to the health and social welfare of households and their families in KC as a result of COVID-19. Local stakeholders can utilize this information for developing priorities, strategies, and programs to address the pandemic where needed and also to assess progress in areas of need.

A Report on the Impact of the COVID-19 Pandemic on the Health and Social Welfare of the Filipino Population in Hawai'i

Hawai'i's Filipino community has been deeply impacted by coronavirus disease 2019 (COVID-19). This article reports the findings for the Filipino population from the Hawai'i Emergency Management Agency (HI-EMA) Community Care Outreach Unit (CCO) Unit evaluation assessment of the impact of COVID-19 on the health and social welfare of individuals across the state. The survey was conducted from August-September 2020. We propose recommendations to mitigate the impact of the pandemic on this community, including the following actions: (1) developing linguistically and culturally appropriate support for all COVID-19 related services, especially for the high number of older Filipinos with limited English proficiency, (2) providing support and resource information in locations that are accessible to Filipino communities, and (3) supporting those already doing work to address the deep and diverse needs in the Filipino community with funding. Building partnerships between existing Filipino organizations, health and social service providers, and state agencies will contribute to sustainability over time.

Severe methanol poisoning treated with a novel hemodialysis system: a case report, analysis, and review.

In May and June 2020, an outbreak of methanol poisoning arose in the southwest United States linked to ingestion of contaminated hand sanitizer imported during the coronavirus disease 2019 pandemic, ultimately resulting in over a dozen hospitalizations and at least four deaths in New Mexico and Arizona. In this report, we describe one of these cases in which profound methanol intoxication was successfully treated with the Tablo® Hemodialysis System, the first reported case of toxic alcohol poisoning treated with this novel device. We carry out a formal regression analysis of the serial methanol levels obtained in this case to conservatively estimate that intermittent hemodialysis with Tablo achieved a clearance of methanol of 239 mL/min (95% confidence interval, 173-305 mL/min), a clearance that is well within the previously published standard of care. We conclude by reviewing both the treatment of toxic alcohol poisoning and the determinants of small molecule clearance with hemodialysis, emphasizing the importance of optimizing the dialytic treatment of intoxications with extended treatment times and the use of high-efficiency dialyzers.

SARS-CoV-2 specific memory T cell epitopes identified in COVID-19-recovered subjects.

The COVID-19 pandemic caused by SARS-CoV-2 infection poses a serious threat to public health. An explicit investigation of COVID-19 immune responses, particularly the host immunity in recovered subjects, will lay a foundation for the rational design of therapeutics and/or vaccines against future coronaviral outbreaks. Here, we examined virus-specific T cell responses and identified T cell epitopes using peptides spanning SARS-CoV-2 structural proteins. These peptides were used to stimulate peripheral blood mononuclear cells (PBMCs) derived from COVID-19-recovered subjects, followed by an analysis of IFN-γ-secreting T cells by enzyme-linked immunosorbent spot (ELISpot). We also evaluated virus-specific CD4 or CD8 T cell activation by flow cytometry assay. By screening 52 matrix pools (comprised of 315 peptides) of the spike (S) glycoprotein and 21 matrix pools (comprised of 102 peptides) spanning the nucleocapsid (N) protein, we identified 28 peptides from S protein and 5 peptides from N protein as immunodominant epitopes. The immunogenicity of these epitopes was confirmed by a second ELISpot using single peptide stimulation in memory T cells, and they were mapped by HLA restrictions. Notably, SARS-CoV-2 specific T cell responses positively correlated with B cell IgG and neutralizing antibody responses to the receptor-binding domain (RBD) of the S protein. Our results demonstrate that defined levels of SARS-CoV-2 specific T cell responses are generated in some, but not all, COVID-19-recovered subjects, fostering hope for the protection of a proportion of COVID-19-exposed individuals against reinfection. These results also suggest that these virus-specific T cell responses may induce protective immunity in unexposed individuals upon vaccination, using vaccines generated based on the immune epitopes identified in this study. However, SARS-CoV-2 S and N peptides are not potently immunogenic, and none of the single peptides could universally induce robust T cell responses, suggesting the necessity of using a multi-epitope strategy for COVID-19 vaccine design.

Blockade of SARS-CoV-2 spike protein-mediated cell-cell fusion using COVID-19 convalescent plasma.

The recent COVID-19 pandemic poses a serious threat to global public health, thus there is an urgent need to define the molecular mechanisms involved in SARS-CoV-2 spike (S) protein-mediated virus entry that is essential for preventing and/or treating this emerging infectious disease. In this study, we examined the blocking activity of human COVID-19 convalescent plasma by cell-cell fusion assays using SARS-CoV-2-S-transfected 293 T as effector cells and ACE2-expressing 293 T as target cells. We demonstrate that the SARS-CoV-2 S protein exhibits a very high capacity for membrane fusion and is efficient in mediating virus fusion and entry into target cells. Importantly, we find that COVID-19 convalescent plasma with high titers of IgG neutralizing antibodies can block cell-cell fusion and virus entry by interfering with the SARS-CoV-2-S/ACE2 or SARS-CoV-S/ACE2 interactions. These findings suggest that COVID-19 convalescent plasma may not only inhibit SARS-CoV-2-S but also cross-neutralize SARS-CoV-S-mediated membrane fusion and virus entry, supporting its potential as a preventive and/or therapeutic agent against SARS-CoV-2 as well as other SARS-CoV infections.