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1.
Cell Host Microbe ; 2022 Oct 21.
Article in English | MEDLINE | ID: covidwho-2082311

ABSTRACT

The rapid emergence of SARS-CoV-2 variants challenges vaccination strategies. Here, we collected 201 serum samples from persons with a single infection or multiple vaccine exposures, or both. We measured their neutralization titers against 15 natural variants and 7 variants with engineered spike mutations and analyzed antigenic diversity. Antigenic maps of primary infection sera showed that Omicron sublineages BA.2, BA.4/BA.5, and BA.2.12.1 are distinct from BA.1 and more similar to Beta/Gamma/Mu variants. Three mRNA COVID-19 vaccinations increased neutralization of BA.1 more than BA.4/BA.5 or BA.2.12.1. BA.1 post-vaccination infection elicited higher neutralization titers to all variants than three vaccinations alone, although with less neutralization to BA.2.12.1 and BA.4/BA.5. Those with BA.1 infection after two or three vaccinations had similar neutralization titer magnitude and antigenic recognition. Accounting for antigenic differences among variants when interpreting neutralization titers can aid the understanding of complex patterns in humoral immunity that informs the selection of future COVID-19 vaccine strains.

2.
PLoS One ; 17(10): e0276241, 2022.
Article in English | MEDLINE | ID: covidwho-2079762

ABSTRACT

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 augments this immunity To accomplish these goals, we studied healthy adult healthcare workers who were (a) uninfected and unvaccinated (n = 12), (b) uninfected and vaccinated with Pfizer-BioNTech BNT162b2 vaccine (2 doses n = 177, one dose n = 1) or Moderna mRNA-1273 vaccine (one dose, n = 1), and (c) previously infected with SARS-CoV-2 and vaccinated (BNT162b2, two doses, n = 6, one dose n = 1; mRNA-1273 two doses, n = 1). Infection status was determined by repeated PCR testing of participants. We used FluoroSpot Interferon-gamma (IFN-γ) and Interleukin-2 (IL-2) assays, using subpools of 15-mer peptides covering the S (10 subpools), N (4 subpools) and M (2 subpools) proteins. Responses were expressed as frequencies (percent positive responders) and magnitudes (spot forming cells/106 cytokine-producing peripheral blood mononuclear cells [PBMCs]). Almost all vaccinated participants with no prior infection exhibited IFN-γ, IL-2 and IFN-γ+IL2 responses to S glycoprotein subpools (89%, 93% and 27%, respectively) mainly directed to the S2 subunit and were more robust than responses to the N or M subpools. However, in previously infected and vaccinated participants IFN-γ, IL-2 and IFN-γ+IL2 responses to S subpools (100%, 100%, 88%) were substantially higher than vaccinated participants with no prior infection and were broader and directed against nine of the 10 S glycoprotein subpools spanning the S1 and S2 subunits, and all the N and M subpools. 50% of uninfected and unvaccinated individuals had IFN-γ but not IL2 or IFN-γ+IL2 responses against one S and one M subpools that were not increased after vaccination of uninfected or SARS-CoV-2-infected participants. Summed IFN-γ, IL-2, and IFN-γ+IL2 responses to S correlated with IgG responses to the S glycoprotein. These studies demonstrated that vaccinations with BNT162b2 or mRNA-1273 results in T cell-specific responses primarily against epitopes in the S2 subunit of the S glycoprotein, and that individuals that are vaccinated after SARS-CoV-2 infection develop broader and greater T cell responses to S1 and S2 subunits as well as the N and M proteins.


Subject(s)
COVID-19 , Interferon-gamma , Interleukin-2 , Adult , Humans , 2019-nCoV Vaccine mRNA-1273 , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , Epitopes , Immunoglobulin G , Interferon-gamma/immunology , Interleukin-2/immunology , Leukocytes, Mononuclear , Proteome , SARS-CoV-2 , Vaccination
3.
Clin Infect Dis ; 2022 May 24.
Article in English | MEDLINE | ID: covidwho-1860831

ABSTRACT

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 = 932), vaccine-after-infection (n = 869), and vaccine-breakthrough-infection (n = 154). Peak anti-spike-IgG responses through 183 days were compared, with adjustment for vaccine product, demography, and comorbidities. We excluded those with evidence of clinical or sub-clinical SARS-CoV-2 reinfection from all groups. RESULTS: Multivariable regression results indicated vaccine-after-infection anti-spike-IgG responses were higher than infection-alone (p < 0.01), regardless of prior infection severity. An increased time between infection and vaccination was associated with a greater post-vaccination IgG response (p < 0.01). Vaccination-alone elicited a greater IgG response, but more rapid waning of IgG (p < 0.01), compared to infection-alone (p < 0.01). BNT162b2 and mRNA-1273 vaccine-receipt was associated with greater IgG responses compared to JNJ-78436735 (p < 0.01), regardless of infection history. Those with vaccine-after-infection or vaccine-breakthrough-infection had a more durable anti-spike-IgG response compared to infection-alone (p < 0.01). CONCLUSIONS: Vaccine-receipt elicited higher anti-spike-IgG responses than infection-alone, although IgG levels waned faster in those vaccinated (compared to infection-alone). Vaccine-after-infection elicits a greater humoral response compared to vaccine or infection alone; and the timing, but not disease severity, of prior infection predicted these post-vaccination IgG responses. While differences between groups were small in magnitude, these results offer insights into vaccine immunogenicity variations that may help inform vaccination timing strategies.

4.
Transbound Emerg Dis ; 69(5): e2366-e2377, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1819931

ABSTRACT

Due to their geographical isolation and small populations, insular bats may not be able to maintain acute immunizing viruses that rely on a large population for viral maintenance. Instead, endemic transmission may rely on viruses establishing persistent infections within hosts or inducing only short-lived neutralizing immunity. Therefore, studies on insular populations are valuable for developing broader understanding of viral maintenance in bats. The Christmas Island flying-fox (CIFF; Pteropus natalis) is endemic on Christmas Island, a remote Australian territory, and is an ideal model species to understand viral maintenance in small, geographically isolated bat populations. Serum or plasma (n = 190), oral swabs (n = 199), faeces (n = 31), urine (n = 32) and urine swabs (n = 25) were collected from 228 CIFFs. Samples were tested using multiplex serological and molecular assays, and attempts at virus isolation to determine the presence of paramyxoviruses, betacoronaviruses and Australian bat lyssavirus. Analysis of serological data provides evidence that the species is maintaining a pararubulavirus and a betacoronavirus. There was little serological evidence supporting the presence of active circulation of the other viruses assessed in the present study. No viral nucleic acid was detected and no viruses were isolated. Age-seropositivity results support the hypothesis that geographically isolated bat populations can maintain some paramyxoviruses and coronaviruses. Further studies are required to elucidate infection dynamics and characterize viruses in the CIFF. Lastly, apparent absence of some pathogens could have implications for the conservation of the CIFF if a novel disease were introduced into the population through human carriage or an invasive species. Adopting increased biosecurity protocols for ships porting on Christmas Island and for researchers and bat carers working with flying-foxes are recommended to decrease the risk of pathogen introduction and contribute to the health and conservation of the species.


Subject(s)
Chiroptera , Lyssavirus , Nucleic Acids , Animals , Australia/epidemiology , Betacoronavirus , Humans
5.
Sci Transl Med ; 14(645): eabn8543, 2022 05 18.
Article in English | MEDLINE | ID: covidwho-1774930

ABSTRACT

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 the neutralization of the Omicron BA.1 variant pseudovirus by postvaccination serum samples after two and three immunizations with the Pfizer/BioNTech162b2 SARS-CoV-2 mRNA (Pfizer/BNT162b2) vaccine, convalescent serum samples from unvaccinated individuals infected by different variants, and clinical-stage therapeutic antibodies. We found that titers against the Omicron variant were low or undetectable after two immunizations and in many convalescent serum samples, regardless of the infecting variant. A booster vaccination increased titers more than 30-fold against Omicron to values comparable to those seen against the D614G variant after two immunizations. Neither age nor sex was associated with the differences in postvaccination antibody responses. We also evaluated 18 clinical-stage therapeutic antibody products and an antibody mimetic protein product obtained directly from the manufacturers. Five monoclonal antibodies, the antibody mimetic protein, three antibody cocktails, and two polyclonal antibody preparations retained measurable neutralization activity against Omicron with a varying degree of potency. Of these, only three retained potencies comparable to the D614G variant. Two therapeutic antibody cocktails in the tested panel that are authorized for emergency use in the United States did not neutralize Omicron. These findings underscore the potential benefit of mRNA vaccine boosters for protection against Omicron and the need for rapid development of antibody therapeutics that maintain potency against emerging variants.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , COVID-19/therapy , COVID-19 Vaccines , Humans , Immunization, Passive , Vaccination , Vaccines, Synthetic , mRNA Vaccines
6.
Emerg Infect Dis ; 28(4): 828-832, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1771000

ABSTRACT

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 evidence of SARS-CoV-2 infection, defined as presence of nucleocapsid protein antibodies.


Subject(s)
COVID-19 , Antibodies, Viral , Antibody Formation , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Health Personnel , Humans , SARS-CoV-2 , Vaccination
7.
Open Forum Infect Dis ; 9(3): ofac030, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1706326

ABSTRACT

BACKGROUND: The frequency of asymptomatic severe acute respiratory syndrome coronavirus 2 (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 health care workers (HCWs). METHODS: A prospective cohort of HCWs, confirmed negative for SARS-CoV-2 exposure upon enrollment, were evaluated for SARS-CoV-2 infection by monthly analysis of SARS-CoV-2 antibodies as well as referral for polymerase chain reaction testing whenever they exhibited symptoms of coronavirus disease 2019 (COVID-19). Participants completed the standardized and validated FLU-PRO Plus symptom questionnaire scoring viral respiratory disease symptom intensity and frequency at least twice monthly during baseline periods of health and each day they had any symptoms that were different from their baseline. RESULTS: Two hundred sixty-three participants were enrolled between August 25 and December 31, 2020. Through February 28, 2021, 12 participants were diagnosed with SARS-CoV-2 infection. Symptom analysis demonstrated that all 12 had at least mild symptoms of COVID-19, compared with baseline health, near or at time of infection. CONCLUSIONS: These results suggest that asymptomatic SARS-CoV-2 infection in unvaccinated, immunocompetent adults is less common than previously reported. While infectious inoculum doses and patient factors may have played a role in the clinical manifestations of SARS-CoV-2 infections in this cohort, we suspect that the high rate of symptomatic disease was due primarily to participant attentiveness to symptoms and collection of symptoms in a standardized, prospective fashion. These results have implications for studies that estimate SARS-CoV-2 infection prevalence and for public health measures to control the spread of this virus.

8.
Clin Infect Dis ; 74(5): 897-900, 2022 03 09.
Article in English | MEDLINE | ID: covidwho-1702282

ABSTRACT

Little is known about severe acute respiratory syndrome coronavirus 2 "vaccine-breakthrough" infections (VBIs). Here we characterize 24 VBIs in predominantly young healthy persons. While none required hospitalization, a proportion endorsed severe symptoms and shed live virus as high as 4.13 × 103 plaque-forming units/mL. Infecting genotypes included both variant-of-concern (VOC) and non-VOC strains.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/prevention & control , COVID-19 Vaccines , Genetic Variation , Humans , Phenotype , RNA, Messenger , SARS-CoV-2/genetics , Vaccines, Synthetic , Virus Shedding
9.
Open Forum Infect Dis ; 9(3): ofab623, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1684764

ABSTRACT

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 swab samples collected on the same day among participants with at least one positive PCR test. RESULTS: Overall, 755 participants had at least one set of paired swabs. Concordance between NP and other swab types was 75% (NS), 72% (OP), 54% (rectal swabs [RS]), and 78% (NS/OP combined). Kappa values were moderate for the NS, OP, and NS/OP comparisons (0.50, 0.45, and 0.54, respectively). Highest sensitivity relative to NP (0.87) was observed with a combination of NS/OP tests (positive if either NS or OP was positive). Sensitivity of the non-NP swab types was highest in the first week postsymptom onset and decreased thereafter. Similarly, virus RNA quantity was highest in the NP swabs as compared with NS, OP, and RS within two weeks postsymptom onset. OP and NS performance decreased as virus RNA quantity decreased. No differences were noted between NS specimens collected at home or in clinic. CONCLUSIONS: NP swabs detected more SARS-CoV-2 cases than non-NP swabs, and the sensitivity of the non-NP swabs decreased with time postsymptom onset. While other swabs may be simpler to collect, NP swabs present the best chance of detecting SARS-CoV-2 RNA, which is essential for clinical care as well as genomic surveillance.

10.
Open Forum Infect Dis ; 9(1): ofab575, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1631248

ABSTRACT

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, observational cohort study consisting of generally healthy adult participants that were not severely immunocompromised, had no history of coronavirus disease 2019, and were seronegative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein before vaccination. Severity of vaccine-associated symptoms was obtained through participant-completed questionnaires. Testing for immunoglobulin G antibodies against SARS-CoV-2 spike protein and receptor-binding domain was conducted using microsphere-based multiplex immunoassays performed on serum samples collected at monthly visits. Neutralizing antibody titers were determined by microneutralization assays. RESULTS: Two hundred six participants were evaluated (69.4% female, median age 41.5 years old). We found no correlation between vaccine-associated symptom severity scores and vaccine-induced antibody titers 1 month after vaccination. We also observed that (1) postvaccination symptoms were inversely correlated with age and weight and more common in women, (2) systemic symptoms were more frequent after the second vaccination, (3) high symptom scores after first vaccination were predictive of high symptom scores after second vaccination, and (4) older age was associated with lower titers. CONCLUSIONS: Lack of postvaccination symptoms after receipt of the BNT162b2 vaccine does not equate to lack of vaccine-induced antibodies 1 month after vaccination.

11.
J Infect Dis ; 224(12): 2010-2019, 2021 12 15.
Article in English | MEDLINE | ID: covidwho-1574912

ABSTRACT

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 infection. Analysis of the function, durability, and diversity of cellular response long after natural infection, over a range of ages and disease phenotypes, is needed to identify preventative and therapeutic interventions. METHODS: We identified participants in our multisite longitudinal, prospective cohort study 12 months after SARS-CoV-2 infection representing a range of disease severity. We investigated function, phenotypes, and frequency of T cells specific for SARS-CoV-2 using intracellular cytokine staining and spectral flow cytometry, and compared magnitude of SARS-CoV-2-specific antibodies. RESULTS: SARS-CoV-2-specific antibodies and T cells were detected 12 months postinfection. Severe acute illness was associated with higher frequencies of SARS-CoV-2-specific CD4 T cells and antibodies at 12 months. In contrast, polyfunctional and cytotoxic T cells responsive to SARS-CoV-2 were identified in participants over a wide spectrum of disease severity. CONCLUSIONS: SARS-CoV-2 infection induces polyfunctional memory T cells detectable at 12 months postinfection, with higher frequency noted in those who experienced severe disease.


Subject(s)
COVID-19/immunology , COVID-19/virology , Immunologic Memory , SARS-CoV-2/immunology , T-Lymphocyte Subsets/immunology , Adult , Antibodies, Viral , Antigens, Viral , Biomarkers , COVID-19/diagnosis , COVID-19/epidemiology , Female , Humans , Immunity, Cellular , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Severity of Illness Index , T-Lymphocyte Subsets/metabolism , Time Factors
12.
Open Forum Infect Dis ; 8(12): ofab556, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1575421

ABSTRACT

BACKGROUND: We evaluated clinical outcomes, functional burden, and complications 1 month after coronavirus disease 2019 (COVID-19) infection in a prospective US 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 beneficiaries presenting at 9 sites across the United States with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test, a COVID-19-like illness, or a high-risk SARS-CoV-2 exposure were eligible for enrollment. Medical history and clinical outcomes were collected through structured interviews and International Classification of Diseases-based EMR review. Risk factors associated with hospitalization were determined by multivariate logistic regression. RESULTS: A total of 1202 participants were enrolled. There were 1070 laboratory-confirmed SARS-CoV-2 cases and 132 SARS-CoV-2-negative participants. In the first month post-symptom onset among the SARS-CoV-2-positive cases, there were 212 hospitalizations, 80% requiring oxygen, 20 ICU admissions, and 10 deaths. Risk factors for COVID-19-associated hospitalization included race (increased for Asian, Black, and Hispanic compared with non-Hispanic White), age (age 45-64 and 65+ compared with <45), and obesity (BMI≥30 compared with BMI<30). Over 2% of survey respondents reported the need for supplemental oxygen, and 31% had not returned to normal daily activities at 1 month post-symptom onset. CONCLUSIONS: Older age, reporting Asian, Black, or Hispanic race/ethnicity, and obesity are associated with SARS-CoV-2 hospitalization. A proportion of acute SARS-CoV-2 infections require long-term oxygen therapy; the impact of SARS-CoV-2 infection on short-term functional status was substantial. A significant number of MHS beneficiaries had not yet returned to normal activities by 1 month.

15.
Open forum infectious diseases ; 8(Suppl 1):S323-S323, 2021.
Article in English | EuropePMC | ID: covidwho-1564384

ABSTRACT

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 vaccine-induced antibody responses to SARS-CoV-2. Methods Serial serum samples obtained pre-vaccination and 1 month after the second dose were tested for IgG antibodies against the full pre-fusion spike protein and the receptor binding domain (RBD) of SARS-CoV-2, as well as the full pre-fusion spike proteins of OC43, HKU1, 229E, and NL63. Antibodies were measured using highly sensitive and specific multiplex assays based on Luminex-xMAP technology. Results Preliminary analyses of the first 103 subjects in whom we have 1 month post-vaccination serum demonstrate development of high IgG geometric mean titers (GMT) to both the full spike protein (GMT: 13,685, 12,014-15,589, 95% CI) and the RBD (GMT: 19,448, 17,264-21,908, 95% CI) of SARS-CoV-2 after the 2nd vaccine dose. Preliminary analysis demonstrates no association between baseline antibody titers against spike protein of OC43 and antibody titers against SARS-CoV-2 spike protein (Pearson’s r-value= 0.13, P-value= 0.21) or RBD (Pearson’s r-value= 0.09, P-value= 0.36) one month after vaccination. Future analyses will evaluate whether there is an association with baseline seasonal coronavirus antibody titers and either SARS-CoV-2 neutralization titers or anti-SARS-CoV-2 spike protein titers at 6 months after vaccination. Conclusion These preliminary results suggest that baseline antibody responses to seasonal coronaviruses neither boost nor impede SARS-CoV-2 vaccine-induced antibody responses. Longitudinal sampling will enable assessment of vaccine durability and determination of whether baseline seasonal coronavirus antibody levels are associated with altered duration of detectable COVID-19 vaccine-induced antibody responses. Disclosures Simon Pollett, MBBS, Astra Zeneca (Other Financial or Material Support, HJF, in support of USU IDCRP, funded under a CRADA to augment the conduct of an unrelated Phase III COVID-19 vaccine trial sponsored by AstraZeneca as part of USG response (unrelated work)) David Tribble, M.D., DrPH, Astra Zeneca (Other Financial or Material Support, HJF, in support of USU IDCRP, funded under a CRADA to augment the conduct of an unrelated Phase III COVID-19 vaccine trial sponsored by AstraZeneca as part of USG response (unrelated work))

16.
Open forum infectious diseases ; 8(Suppl 1):294-294, 2021.
Article in English | EuropePMC | ID: covidwho-1564016

ABSTRACT

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 during 1 year of follow-up. Methods Crewmembers, the majority of whom were health care workers (HCW), were enrolled following deployment, in May 2020. PCR results from symptomatic crewmembers during deployment, and Day 0 and Day 14 post-deployment screening swabs conducted on all crewmembers, per military order, were ed. A questionnaire and serum were collected on Day 14 post-deployment. SARS-CoV-2 infection was defined as a positive SARS-CoV-2 spike glycoprotein immunoglobulin G antibody (IgG) or PCR. COVID-19 related medical encounters, PCR and antibody testing results within 1 year following deployment were ed from the Military Health System Data Repository (MDR). There was adequate provision of personal protective equipment (PPE) in the hospital and the COVID-19 vaccine roll-out for HCW began in December 2020. Results Of the 1200 crewmembers, 449 were enrolled and completed the questionnaire and screening swabs, and 432 (96.2%) completed the Day 14 blood draw (Table 1). The cumulative prevalence of SARS-CoV-2 infection was 3.01% (13/432;95% CI, 1.61%–5.09%). One of 17 subjects did not complete the blood draw and was PCR positive on Day 14. 433/449 (96.4%) had a PCR performed during the follow-up period (i.e. after the Day 14 post-deployment visit until Feb 2021), for HCW screening or symptomatic illness (median number of tests: 2 [IQR: 1, 2;range: 1,6]). 25 of 433 (5.8%) were PCR positive (Fig 1). 19 (76.0%) occurred in corpsmen, 23 (92.0%) were symptomatic and none were hospitalized. One asymptomatic re-infection occurred in a crewmember who was PCR negative and IgG positive at Day 14 post-deployment. Table 1. Characteristics of the overall cohort and by SARS-CoV-2 infection Figure 1. Number of PCR tests (bar graph) and positivity rate (red line) by month in 449 USNS COMFORT crewmembers during 1-year follow-up after return from deployment Conclusion The post-deployment prevalence of SARS-CoV-2 infection was low. A high proportion of HCW underwent PCR testing during 1-year follow-up but a low incidence of infection was observed. This was likely from community transmission as nosocomial transmission was mitigated by adequate PPE and vaccine roll-out. Disclosures All Authors: No reported disclosures

17.
J Infect Dis ; 224(9): 1462-1472, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1522217

ABSTRACT

BACKGROUND: The mechanisms underlying the association between obesity and coronavirus disease 2019 (COVID-19) severity remain unclear. After verifying that obesity was a correlate of severe COVID-19 in US Military Health System (MHS) beneficiaries, we compared immunological and virological phenotypes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in both obese and nonobese participants. METHODS: COVID-19-infected MHS beneficiaries were enrolled, and anthropometric, clinical, and demographic data were collected. We compared the SARS-CoV-2 peak IgG humoral response and reverse-transcription polymerase chain reaction viral load in obese and nonobese patients, stratified by hospitalization, utilizing logistic regression models. RESULTS: Data from 511 COVID-19 patients were analyzed, among whom 24% were obese and 14% severely obese. Obesity was independently associated with hospitalization (adjusted odds ratio [aOR], 1.91; 95% confidence interval [CI], 1.15-3.18) and need for oxygen therapy (aOR, 3.39; 95% CI, 1.61-7.11). In outpatients, severely obese had a log10 (1.89) higher nucleocapsid (N1) genome equivalents (GE)/reaction and log10 (2.62) higher N2 GE/reaction than nonobese (P = 0.03 and P < .001, respectively). We noted a correlation between body mass index and peak anti-spike protein IgG in inpatients and outpatients (coefficient = 5.48, P < .001). CONCLUSIONS: Obesity is a strong correlate of COVID-19 severity in MHS beneficiaries. These findings offer new pathophysiological insights into the relationship between obesity and COVID-19 severity.


Subject(s)
COVID-19/complications , Obesity/complications , SARS-CoV-2/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Viral , Body Weight , COVID-19/diagnosis , Female , Hospitalization , Humans , Immunoglobulin G/blood , Male , Middle Aged , Military Health Services , Obesity/epidemiology , Prevalence , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/isolation & purification , Severity of Illness Index , Viral Load , Young Adult
18.
Front Immunol ; 12: 681586, 2021.
Article in English | MEDLINE | ID: covidwho-1285292

ABSTRACT

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 18-26, with a high rate of asymptomatic infection or mild symptoms, and therefore differs from previously reported longitudinal studies on humoral responses to SARS-CoV-2, which often focus on more diverse age populations and worse clinical presentation. 80.9% (119/147) of the participants presented with circulating IgG antibodies against SARS-CoV-2 spike (S) receptor-binding domain (RBD) at 6 weeks PO, of whom 97.3% (111/114) remained positive, with significantly decreased levels, at 10 weeks PO. Neutralizing activity was detected in all sera from SARS-CoV-2 IgG positive participants tested (n=38) at 6 and 10 weeks PO, without significant loss between time points. IgG and IgA antibodies against SARS-CoV-2 RBD, S1, S2, and the nucleocapsid (N) protein, as well neutralization activity, were generally comparable between those participants that had asymptomatic infection or mild disease. A multiplex assay including S proteins from SARS-CoV-2 and related zoonotic and human endemic betacoronaviruses revealed a positive correlation for polyclonal cross-reactivity to S after SARS-CoV-2 infection. Overall, young adults that experienced asymptomatic or mild SARS-CoV-2 infection developed comparable humoral responses, with no decrease in neutralizing activity at least up to 10 weeks after infection.


Subject(s)
Antibodies, Neutralizing/metabolism , Antibodies, Viral/metabolism , COVID-19/immunology , Military Personnel , SARS-CoV-2/physiology , Adolescent , Adult , Antibody Formation , Asymptomatic Diseases , Cohort Studies , Disease Outbreaks , Disease Progression , Female , Humans , Male , Spike Glycoprotein, Coronavirus/immunology , United States/epidemiology , Young Adult
19.
BMC Infect Dis ; 21(1): 544, 2021 Jun 09.
Article in English | MEDLINE | ID: covidwho-1262498

ABSTRACT

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 responses to previous seasonal human coronavirus (HCoV) infections affect immunological or clinical responses to SARS-CoV-2 infection or vaccination. METHODS: A cohort of 300 healthcare workers, confirmed negative for SARS-CoV-2 exposure upon study entry, will be followed for up to 1 year with monthly serology analysis of IgM and IgG antibodies against the spike proteins of SARS-CoV-2 and the four major seasonal human coronavirus - HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63. Participants will complete monthly questionnaires that ask about Coronavirus Disease 2019 (COVID-19) exposure risks, and a standardized, validated symptom questionnaire (scoring viral respiratory disease symptoms, intensity and severity) at least twice monthly and any day when any symptoms manifest. SARS-CoV-2 PCR testing will be performed any time participants develop symptoms consistent with COVID-19. For those individuals that seroconvert and/or test positive by SARS-CoV-2 PCR, or receive the SARS-CoV-2 vaccine, additional studies of T cell activation and cytokine production in response to SARS-CoV-2 peptide pools and analysis of Natural Killer cell numbers and function will be conducted on that participant's cryopreserved baseline peripheral blood mononuclear cells (PBMCs). Following the first year of this study we will further analyze those participants having tested positive for COVID-19, and/or having received an authorized/licensed SARS-CoV-2 vaccine, quarterly (year 2) and semi-annually (years 3 and 4) to investigate immune response longevity. DISCUSSION: This study will determine the frequency of asymptomatic and pauci-symptomatic SARS-CoV-2 infection in a cohort of at-risk healthcare workers. Baseline and longitudinal assays will determine the frequency and magnitude of anti-spike glycoprotein antibodies to the seasonal HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63, and may inform whether pre-existing antibodies to these human coronaviruses are associated with altered COVID-19 disease course. Finally, this study will evaluate whether pre-existing immune responses to seasonal HCoVs affect the magnitude and duration of antibody and T cell responses to SARS-CoV-2 vaccination, adjusting for demographic covariates.


Subject(s)
COVID-19/immunology , Health Personnel/statistics & numerical data , SARS-CoV-2/immunology , Seroconversion , Vaccination/statistics & numerical data , Antibodies, Viral/blood , Antibodies, Viral/immunology , Asymptomatic Infections , COVID-19 Vaccines/immunology , Coronavirus/immunology , Cross Reactions , Humans , Prospective Studies , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology
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