Eric D Laing's research while affiliated with Uniformed Services University of the Health Sciences and other places

Publications (58)

Article
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The associations between clinical phenotypes of coronavirus disease 2019 (COVID-19) and the host inflammatory response during the transition from peak illness to convalescence are not yet well understood. Blood plasma samples were collected from 129 adult SARS-CoV-2 positive inpatient and outpatient participants between April 2020 and January 2021,...
Article
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Background Congregate military populations remain at risk of SARS-CoV-2 outbreaks and the optimal surveillance approach in such settings remains unclear. We enrolled midshipmen at the United States Naval Academy (USNA) in a setting of frequent PCR screening use of prevention strategies. Methods Dried blood spots (DBS) and saliva were collected in...
Article
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Background We sought to determine the frequency of asymptomatic SARS-CoV-2 infections, the BNT162b2 mRNA COVID 19 vaccine-related symptoms, and the correlates of immunity in post-vaccination breakthrough infections in a prospective cohort of healthcare workers. Methods We have been conducting a single-center, observational cohort study of healthca...
Article
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Background Infection with SARS-CoV-2 and the resulting host immune response has been primarily characterized in middle and older aged populations due to a higher incidence of symptoms in these age groups. Due to reduced severity of disease, children were poorly studied and assumed to be less frequently infected compared to older age groups. We meas...
Article
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Class I- and Class II-restricted epitopes have been identified across the SARS-CoV-2 structural proteome. Vaccine-induced and post-infection SARS-CoV-2 T-cell responses are associated with COVID-19 recovery and protection, but the precise role of T-cell responses remains unclear, and how post-infection vaccination ('hybrid immunity') further augmen...
Article
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The rapid emergence of SARS-CoV-2 variants challenges vaccination strategies. Here, we collected 201 serum samples from persons with well-characterized single or multiple infection and/or vaccine exposures. We measured their neutralization titers against 15 natural variants and 7 variants with engineered spike mutations and analyzed antigenic diver...
Chapter
Bioluminescence imaging (BLI) is a technique that can be employed to quantify biological processes in living cells. When used in small animal models such as mice, BLI can provide both longitudinal and positional information regarding the biological process under investigation. Although perhaps best known for its utility in non-invasively quantifyin...
Article
Background Comparing humoral responses in SARS-CoV-2 vaccinees, those with SARS-CoV-2 infection, or combinations of vaccine/infection (‘hybrid immunity’), may clarify predictors of vaccine immunogenicity. Methods We studied 2660 U.S. Military Health System beneficiaries with a history of SARS-CoV-2 infection-alone (n = 705), vaccination-alone (n =...
Article
Rabies virus and related lyssaviruses cause uniformly fatal disease, once the infection progresses to the central nervous system. Current lyssavirus immunotherapies are directed toward peripheral neutralization of virus to prevent CNS infection during the pre-symptomatic stage of disease. In this study, using an anti-lyssavirus human monoclonal ant...
Article
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The rapid spread of the highly contagious Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) along with its high number of mutations in the spike gene has raised alarms about the effectiveness of current medical countermeasures. To address this concern, we measured neutralization of the Omicron BA.1 variant pseudovirus...
Article
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We identified and isolated a novel Hendra virus (HeV) variant not detected by routine testing from a horse in Queensland, Australia, that died from acute illness with signs consistent with HeV infection. Using whole-genome sequencing and phylogenetic analysis, we determined the variant had ≈83% nt identity with prototypic HeV. In silico and in vitr...
Article
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies decay but persist 6 months postvaccination; lower levels of neutralizing titers persist against Delta than wild-type virus. Of 227 vaccinated healthcare workers tested, only 2 experienced outpatient symptomatic breakthrough infections, despite 59/227 exhibiting serologic eviden...
Article
Background The frequency of asymptomatic SARS-CoV-2 infections is unclear and may be influenced by how symptoms are evaluated. In this study, we sought to determine the frequency of asymptomatic SARS-CoV-2 infections in a prospective cohort of healthcare workers (HCWs). Methods and findings A prospective cohort of HCWs, confirmed negative for SARS...
Article
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Background The relationship between postvaccination symptoms and strength of antibody responses is unclear. The goal of this study was to determine whether adverse effects caused by vaccination with the Pfizer/BioNTech BNT162b2 vaccine are associated with the magnitude of vaccine-induced antibody levels. Methods We conducted a single-center, obser...
Preprint
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The rapid spread of the highly contagious Omicron variant of SARS-CoV-2 along with its high number of mutations in the spike gene has raised alarm about the effectiveness of current medical countermeasures. To address this concern, we measured neutralizing antibodies against Omicron in three important settings: (1) post-vaccination sera after two a...
Article
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Background Characterizing the longevity and quality of cellular immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enhances understanding of coronavirus disease 2019 (COVID-19) immunity that influences clinical outcomes. Prior studies suggest SARS-CoV-2–specific T cells are present in peripheral blood 10 months after i...
Article
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Background: Nasopharyngeal (NP) swabs are the standard for SARS-CoV-2 diagnosis. If less invasive alternatives to NP swabs (eg, oropharyngeal [OP] or nasal swabs [NS]) are comparably sensitive, the use of these techniques may be preferable in terms of comfort, convenience, and safety. Methods: This study compared the detection of SARS-CoV-2 in s...
Article
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Background The USNS COMFORT deployed to New York City to augment the inpatient health care capacity in March 2020. The aim of this study was to determine the prevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection among US Navy personnel upon return from deployment, and to identify incident cases of SARS-CoV-2 infection...
Article
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Background The Prospective Assessment of SARS-CoV-2 Seroconversion (PASS) study is following over 200 healthcare workers who have received the Pfizer-BioNTech BNT162b2 COVID-19 mRNA vaccine. A major aim of the study is to determine whether baseline antibody titers against the seasonal human coronaviruses are associated with altered levels of vaccin...
Article
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Background University students, including those at military service academies, are at increased risk of acute respiratory infection (ARI), including SAR-CoV-2, due to crowded living conditions, frequent social interaction and other factors that facilitate pathogen transmission. Unlike many universities, the United States Naval Academy (USNA) contin...
Article
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Background Approximately 10-20% of patients with critical COVID-19 harbor neutralizing autoantibodies (auto-Abs) that target type I interferons (IFN), a family of cytokines that induce critical innate immune defense mechanisms upon viral infection. Studies to date indicate that these auto-Abs are mostly detected in men over age 65. Methods We scre...
Article
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Background We evaluated the clinical outcomes, functional burden, and complications one month after COVID-19 infection in a prospective United States Military Health System (MHS) cohort of active duty, retiree, and dependent populations using serial patient-reported outcome surveys and electronic medical record (EMR) review. Methods MHS beneficiar...
Preprint
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Antibodies against SARS-CoV-2 decay but persist six months post-vaccination, with lower levels of neutralizing titers against Delta than wild-type. Only 2 of 227 vaccinated healthcare workers experienced outpatient symptomatic breakthrough infections despite 59 of 227 exhibiting serological evidence of exposure to SARS-CoV-2 as defined by developme...
Preprint
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Background Characterizing the longevity and quality of cellular immune responses to SARS-CoV-2 is critical to understanding immunologic approaches to protection against COVID-19. Prior studies suggest SARS-CoV-2-specific T cells are present in peripheral blood 10 months after infection. Further analysis of the function, durability, and diversity of...
Article
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Background: The mechanisms underlying the association between obesity and COVID-19 severity remain unclear. After verifying that obesity was a correlate of severe COVID-19 in U.S. Military Health System (MHS) beneficiaries, we compared immunological and virological phenotypes of SARS-CoV-2 infection in both obese and non-obese participants. Metho...
Preprint
Background: mRNA COVID-19 vaccines are playing a key role in controlling the COVID-19 pandemic. The relationship between post-vaccination symptoms and strength of antibody responses is unclear. Objective: To determine whether adverse effects caused by vaccination with the Pfizer/BioNTech BNT162b2 vaccine are associated with the magnitude of vaccine...
Article
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Little is known about SARS-CoV-2 ‘vaccine-breakthrough’ infections (VBI). Here we characterize 24 VBI in predominantly young healthy persons. While none required hospitalization, a proportion endorsed severe symptoms and shed live virus as high as 4.13 x 10 3 PFU/mL. Infecting genotypes included both variant-of-concern (VOC) and non-VOC strains.
Article
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Background SARS-CoV-2 is a recently emerged pandemic coronavirus (CoV) capable of causing severe respiratory illness. However, a significant number of infected people present as asymptomatic or pauci-symptomatic. In this prospective assessment of at-risk healthcare workers (HCWs) we seek to determine whether pre-existing antibody or T cell response...
Article
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We investigated serological responses following a SARS-CoV-2 outbreak in spring 2020 on a US Marine recruit training base. 147 participants that were isolated during an outbreak of respiratory illness were enrolled in this study, with visits approximately 6 and 10 weeks post-outbreak (PO). This cohort is comprised of young healthy adults, ages 18-2...
Preprint
A novel Hendra virus (HeV) variant, not detected by routine testing, was identified and isolated from a Queensland horse that suffered acute, fatal disease consistent with HeV infection. Whole genome sequencing and phylogenetic analysis demonstrated the variant to have ~83% nucleotide identity to the prototype HeV strain. An updated RT-qPCR assay w...
Preprint
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Importance The persistence of SARS-CoV-2 antibodies may be a predictive correlate of protection for both natural infections and vaccinations. Identifying predictors of robust antibody responses is important to evaluate the risk of re-infection / vaccine failure and may be translatable to vaccine effectiveness. Objective To 1) determine the durabil...
Article
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Australian bat lyssavirus (ABLV) is a rhabdovirus that circulates in four species of pteropid bats (ABLVp) and the yellow-bellied sheath-tailed bat (ABLVs) in mainland Australia. In the three confirmed human cases of ABLV, rabies illness preceded fatality. As with rabies virus (RABV), post-exposure prophylaxis (PEP) for potential ABLV infections co...
Preprint
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Sensitive and specific SARS-CoV-2 antibody assays remain critical for community and hospital-based SARS-CoV-2 sero-surveillance. With the rollout of SARS-CoV-2 vaccines, such assays must be able to distinguish vaccine from natural immunity to SARS-CoV-2 and related human coronaviruses. Here, we developed and implemented multiplex microsphere-based...
Preprint
Full-text available
Australian bat lyssavirus (ABLV) is a rhabdovirus that circulates in four species of pteropid bats (ABLVp) and the yellow-bellied sheath-tailed bat (ABLVs) in mainland Australia. In the three confirmed human cases of ABLV, rabies illness preceded fatality. As with rabies virus (RABV), post-exposure prophylaxis (PEP) for potential ABLV infections co...
Article
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Background Coronavirus disease 2019 (COVID-19) presents a unique challenge to United States Navy hospital ships. The aim of this study was to determine the prevalence of SARS-CoV-2 infection among US Navy personnel deployed on the USNS COMFORT to augment the inpatient healthcare capacity in New York City. Methods Cross-sectional study conducted on...
Preprint
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Sensitive and specific SARS-CoV-2 antibody assays remain critical for community and hospital-based SARS-CoV-2 surveillance. Here, we developed and applied a multiplex microsphere-based immunoassay (MMIA) for COVD-19 antibody studies that incorporates spike protein trimers of SARS-CoV-2, SARS-CoV-1, MERS-CoV, and the seasonal human betacoronaviruses...
Preprint
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With growing concern of persistent or multiple waves of SARS-CoV-2 in the United States, sensitive and specific SARS-CoV-2 antibody assays remain critical for community and hospital-based SARS-CoV-2 surveillance. Here, we describe the development and application of a multiplex microsphere-based immunoassay (MMIA) for COVD-19 antibody studies, utili...
Article
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Rousettus bat coronavirus GCCDC1 (RoBat-CoV GCCDC1) is a cross-family recombinant coronavirus that has previously only been reported in wild-caught bats in Yúnnan, China. We report the persistence of a related strain in a captive colony of lesser dawn bats captured in Singapore. Genomic evidence of the virus was detected using targeted enrichment s...
Article
Traditional mouse models of lyssavirus pathogenesis rely on euthanizing large groups of animals at various time points post-infection, processing infected tissues, and performing histological and molecular analyses to determine anatomical sites of infection. While powerful by some measures, this approach is limited by the inability to monitor disea...
Preprint
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SARS-CoV-2 is a zoonotic virus that has caused a pandemic of severe respiratory disease—COVID-19— within several months of its initial identification. Comparable to the first SARS-CoV, this novel coronavirus’s surface Spike (S) glycoprotein mediates cell entry via the human ACE-2 receptor, and, thus, is the principal target for the development of v...
Article
Bat-borne zoonotic pathogens belonging to the family Paramxyoviridae, including Nipah and Hendra viruses, and the family Filoviridae, including Ebola and Marburg viruses, can cause severe disease and high mortality rates on spillover into human populations. Surveillance efforts for henipaviruses and filoviruses have been largely restricted to the O...
Article
Nipah virus (NiV) is a bat-borne zoonotic pathogen that can cause severe respiratory distress and encephalitis upon spillover into humans. Nipah virus is capable of infecting a broad range of hosts including humans, pigs, ferrets, dogs, cats, hamsters, and at least 2 genera of bats. Little is known about the biology of NiV in the bat reservoir. In...
Article
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Bats are reservoirs for several zoonotic pathogens, including filoviruses. Recent work highlights the diversity of bat borne filoviruses in Asia. High risk activities at the bat-human interface pose the threat of zoonotic virus transmission. We present evidence for prior exposure of bat harvesters and two resident fruit bat species to filovirus sur...
Article
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Cedar virus (CedV) is a bat-borne henipavirus related to Nipah virus (NiV) and Hendra virus (HeV), zoonotic agents of fatal human disease. CedV receptor-binding protein (G) shares only ∼30% sequence identity with those of NiV and HeV, although they can all use ephrin-B2 as an entry receptor. We demonstrate that CedV also enters cells through additi...
Article
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Bats are increasingly implicated as hosts of highly pathogenic viruses. The underlying virus–host interactions and cellular mechanisms that promote co-existence remain ill-defined, but physiological traits such as flight and longevity are proposed to drive these adaptations. Autophagy is a cellular homeostatic process that regulates ageing, metabol...
Article
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Background: Hendra virus and Nipah virus are zoonotic viruses that have caused severe to fatal disease in livestock and human populations. The isolation of Cedar virus, a non-pathogenic virus species in the genus Henipavirus, closely-related to the highly pathogenic Hendra virus and Nipah virus offers an opportunity to investigate differences in p...
Data
Median fluorescence intensity cutoff value determination and results for filoviruses in serum from fruit bats, Singapore, 2011–2016.
Article
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To determine whether fruit bats in Singapore have been exposed to filoviruses, we screened 409 serum samples from bats of 3 species by using a multiplex assay that detects antibodies against filoviruses. Positive samples reacted with glycoproteins from Bundibugyo, Ebola, and Sudan viruses, indicating filovirus circulation among bats in Southeast As...
Article
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CD8⁺ central memory (CM) and effector memory (EM) T-cell subsets exhibit well-established differences in proliferative and protective capacity after infectious challenge. However, their relative sensitivity to apoptosis has been largely overlooked, despite the importance of programmed cell death in regulating effector T-cell homeostasis. Here we de...
Article
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Australian bat lyssavirus (ABLV), a rhabdovirus of the genus Lyssavirus which circulates in both pteropid fruit bats and insectivorous bats in mainland Australia, has caused three fatal human infections, the most recent in February 2013, manifested as acute neurological disease indistinguishable from clinical rabies. Rhabdoviruses infect host cells...

Citations

... This methodology allows analyzing complex serological data beyond primary exposures, as more cross-reactive sera will have flatter landscapes than strain-specific firstexposure sera. While this change in cross-neutralization could be visualized in an antigenic map with variants occupying a smaller space 23 , antibody landscapes are necessary to examine titer magnitude and distribution over mapped space. Grouping by exposure history, we found that at least two distant variant encounters increased crossreactivity of neutralizing antibodies to other variants. ...
... While vaccination induces systemic immunity, and the most widely used vaccines elicit only spike-specific humoral and cellular immunity, natural infection generates immunity against all viral proteins, and induces tissue-specific (e.g., mucosal) responses as well [648]. However, some vaccines evoke higher IgG levels compared to natural infection (regardless of severity) [659,660]. Short-term immunity after infection and vaccination might be similarly effective [661], but the duration of protection seem to be significantly shorter in the latter case (~6 months for reinfections [647] compared to the previously mentioned 8-12 months following SARS-CoV-2 infection), possibly due to the more rapid decay of antibody titers [659]. This might also explain why in real-world settings reinfection results in less severe disease compared to COVID-19 following vaccination [662]. ...
... Although the vaccines have been shown to be effective in protecting against infection and, in particular, in reducing the severity of the course of the disease in infected patients [2], immunity seems to decline over time within a few months [3], requiring repetitive administrations. Moreover, there is a continuous emergence of new virus variants capable of evading immunity acquired [4,5] either by infection or by vaccination [6]. In contrast to the vaccines, the therapeutic options for infected people are more limited, and the development of effective antiviral drugs has been slower and less effective. ...
... As these traditional diagnostic methods are targeted, they are necessarily limited in in their capacity to identify novel pathogens and co-infections. For example, although the reverse transcription polymerase chain reaction (RT-PCR) is both fast and relatively inexpensive, it often fails to detect novel organisms or where genetic variation occurs in the binding region of known pathogens targeted by primers or probe [1]. Furthermore, many disease-causing agents are difficult to grow using culture-based methods or unculturable in vitro; such that these approaches are inherently slow and limited for uncovering novel pathogen diversity. ...
... The most common method to identify BTIs is RT-PCR or antigen test for individuals experiencing symptoms, thereby identifying symptomatic BTIs. Detection of anti-nucleocapsid (N) protein antibody has potential to identify both symptomatic and asymptomatic BTIs among COVID-19naive vaccinees who received a spike (S)-based vaccine such as mRNA vaccines (21). Although recent studies reported potent and broad neutralizing antibodies induced by BTIs (22)(23)(24)(25)(26), how a BTI boosts neutralizing antibodies against VOC in individuals remains incompletely understood. ...
... Studies based on contact and outbreak investigations might obtain more detailed data about symptoms, resulting in lower estimates of the proportion that is classified as asymptomatic. Symptom report also differs between different groups of study participants, even within the same study, and could also contribute to heterogeneity [183]. Age might play a role as children appear more likely than adults to have an asymptomatic course of infection, but age was poorly reported and could not be examined in detail (Tables 1 and 2). ...
... Notably, AEs are more frequent and more severe after the second dose 15 , which strongly suggests that AEs are a consequence of immunological memory. However, previous reports did not reach a consensus concerning the association between AEs and vaccine-induced immune reactions, likely due to the small cohorts and variations of the definition of AEs [23][24][25][26][27] . Moreover, most studies have examined the associations of AEs with the humoral immune response but not with T cell responses, which can result in the production of cytokines and thus cause systemic effects. ...
... By December 2021, the highly transmissible Omicron variant had caused more than half of all daily SARS-CoV-2 infections [14]. Omicron carries numerous mutations, including 30 in the Spike (S) protein, which enhance binding to the cellular receptor ACE2 and increase immune evasion [15][16][17][18][19][20]. The BA.1.1 sublineage shows all the mutations found in BA.1 and the R346K substitution [21]. ...
... 1,12,24,25 Moreover, unlike antibodies, T cell responses are retained up to 6 to 12 months post-infection. [26][27][28] In this study, we show that while a third exposure significantly increased the proportion of individuals exhibiting a T cell response to SARS-CoV-2 spike, the magnitude of those responses was not affected by repeated exposures. Since antigen-specific T cells were measured in the memory phase, it is possible that vaccinationor infection-induced T cell responses had reached an immunologic plateau with limited evolution even upon repeated stimulation. ...
... Participants were enrolled in a prospective, multi-center COVID- 19 9 . All patients provided written informed consent and all procedures were performed in accordance with the ethical standards of the Helsinki Declaration of the World Medical Association. ...