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1.
PLOS ONE ; 17(5):e0268237-e0268237, 2022.
Article in English | PMC | ID: covidwho-1822298

ABSTRACT

COVID-19 remains a challenge worldwide, and testing of asymptomatic individuals remains critical to pandemic control measures. Starting March 2020, a total of 7497 hospital employees were tested at least weekly for SARS CoV-2;the cumulative incidence of asymptomatic infections was 5.64%. Consistently over a 14-month period half of COVID-19 infections (414 of 820, total) were detected through the asymptomatic screening program, a third of whom never developed any symptoms during follow-up. Prompt detection and isolation of these cases substantially reduced the risk of potential workplace and outside of workplace transmission. COVID-19 vaccinations of the workforce were initiated in December 2020. Twenty-one individuals tested positive after being fully vaccinated (3.9 per 1000 vaccinated). Most (61.9%) remained asymptomatic and in majority (75%) the virus could not be sequenced due to low template RNA levels in swab samples. Further routine testing of vaccinated asymptomatic employees was stopped and will be redeployed if needed;routine testing for those not vaccinated continues. Asymptomatic SARS-CoV-2 testing, as a part of enhanced screening, monitors local dynamics of the COVID-19 pandemic and can provide valuable data to assess the ongoing impact of COVID-19 vaccination and SARS-CoV-2 variants, inform risk mitigation, and guide adaptive, operational planning including titration of screening strategies over time, based on infection risk modifiers such as vaccination.

2.
Vaccines ; 10(5):717, 2022.
Article in English | MDPI | ID: covidwho-1820450

ABSTRACT

The COVID-19 pandemic has had a staggering impact on social, economic, and public health systems worldwide. Vaccine development and mobilization against SARS-CoV-2 (the etiologic agent of COVID-19) has been rapid. However, novel strategies are still necessary to slow the pandemic, and this includes new approaches to vaccine development and/or delivery that will improve vaccination compliance and demonstrate efficacy against emerging variants. Here, we report on the immunogenicity and efficacy of a SARS-CoV-2 vaccine comprising stabilized, pre-fusion spike protein trimers displayed on a ferritin nanoparticle (SpFN) adjuvanted with either conventional aluminum hydroxide or the Army Liposomal Formulation QS-21 (ALFQ) in a cynomolgus macaque COVID-19 model. Vaccination resulted in robust cell-mediated and humoral responses and a significant reduction in lung lesions following SARS-CoV-2 infection. The strength of the immune response suggests that dose sparing through reduced or single dosing in primates may be possible with this vaccine. Overall, the data support further evaluation of SpFN as a SARS-CoV-2 protein-based vaccine candidate with attention to fractional dosing and schedule optimization.

3.
Front Pediatr ; 9: 752993, 2021.
Article in English | MEDLINE | ID: covidwho-1779952

ABSTRACT

Objectives: Studies of household transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) focused on households with children are limited. We investigated household secondary attack rate (SAR), transmission dynamics, and contributing factors in households with children. Materials and Methods: In this prospective case-ascertained study in Los Angeles County, California, all households members were enrolled if ≥1 member tested positive for SARS-CoV-2 by polymerase chain reaction (PCR). Nasopharyngeal PCRs, serology, and symptom data were obtained over multiple visits. Results: A total of 489 individuals in 105 households were enrolled from June to December 2020. The majority (77.3%) reported a household annual income of <$50,000, and most (92.9%) were of Hispanic/Latinx ethnicity. Children <18 years old accounted for 46.9% index cases, of whom 45.3% were asymptomatic. Household index cases were predominantly children during low community transmission and adults during the high community transmission period (χ2 = 7.647, p = 0.0036. The mean household SAR was 77.0% (95% CI: 69.4-84.6%). Child and adult index cases both efficiently transmitted SARS-CoV-2 within households [81.9%, (95% CI: 72.1-91.9%) vs. 72.4% (95% CI: 59.8-85.1%), p = 0.23]. Household income and pets were significantly associated with higher SAR in the multivariable analysis of household factors (p = 0.0013 and 0.004, respectively). Conclusions: The SAR in households with children in an urban setting with a large ethnic minority population is much higher than previously described. Children play important roles as index cases. SAR was disproportionately impacted by household income. Vaccination and public health efforts need special focus on children and vulnerable communities to help mitigate SARS-CoV-2 spread.

4.
Journal of Veterinary Behavior ; 2022.
Article in English | ScienceDirect | ID: covidwho-1778355

ABSTRACT

Trained dogs can detect many biochemical traces, from the most hostile, such as COVID-19, to the most expensive, such as truffles. However, it is still unclear how the interplay of genetic disposition, education, experience, personality, and environmental conditions influences the performance of dogs. Here, we combine published evidence with the knowledge of truffle hunters to assess direct and indirect factors that affect the hunting performance of truffle dogs. Since the transport of truffle aroma into the canine nasal cavity is most puzzling, we propose five experiments to further investigate the role of weather conditions, soil parameters, and bacterial composition on the dispersal of truffle volatiles perceived by trained dogs. We also suggest exploring whether the application of multiple dogs increases the success of truffle hunting. Moreover, we argue that interdisciplinary research on dog behavior and performance, including insights from veterinary science and comparative psychology as well as the experience of truffle hunters and farmers, is needed to improve the quantity and quality of truffle harvests.

5.
Nat Immunol ; 2022 Apr 05.
Article in English | MEDLINE | ID: covidwho-1778617

ABSTRACT

Although mRNA vaccine efficacy against severe coronavirus disease 2019 remains high, variant emergence has prompted booster immunizations. However, the effects of repeated exposures to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens on memory T cells are poorly understood. Here, we utilize major histocompatibility complex multimers with single-cell RNA sequencing to profile SARS-CoV-2-responsive T cells ex vivo from humans with one, two or three antigen exposures, including vaccination, primary infection and breakthrough infection. Exposure order determined the distribution between spike-specific and non-spike-specific responses, with vaccination after infection leading to expansion of spike-specific T cells and differentiation to CCR7-CD45RA+ effectors. In contrast, individuals after breakthrough infection mount vigorous non-spike-specific responses. Analysis of over 4,000 epitope-specific T cell antigen receptor (TCR) sequences demonstrates that all exposures elicit diverse repertoires characterized by shared TCR motifs, confirmed by monoclonal TCR characterization, with no evidence for repertoire narrowing from repeated exposure. Our findings suggest that breakthrough infections diversify the T cell memory repertoire and current vaccination protocols continue to expand and differentiate spike-specific memory.

6.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331501

ABSTRACT

The COVID-19 pandemic has had a staggering impact on social, economic, and public health systems worldwide. Vaccine development and mobilization against SARS-CoV-2 (the etiologic agent of COVID-19) has been rapid. However, novel strategies are still necessary to slow the pandemic, and this includes new approaches to vaccine development and/or delivery, which improve vaccination compliance and demonstrate efficacy against emerging variants. Here we report on the immunogenicity and efficacy of a SARS-CoV-2 vaccine comprised of stabilized, pre-fusion Spike protein trimers displayed on a ferritin nanoparticle (SpFN) adjuvanted with either conventional aluminum hydroxide or the Army Liposomal Formulation QS-21 (ALFQ) in a cynomolgus macaque COVID-19 model. Vaccination resulted in robust cell-mediated and humoral responses and a significant reduction of lung lesions following SARS-CoV-2 infection. The strength of the immune response suggests that dose sparing through reduced or single dosing in primates may be possible with this vaccine. Overall, the data support further evaluation of SpFN as a SARS-CoV-2 protein-based vaccine candidate with attention to fractional dosing and schedule optimization.

7.
Cell Reports Medicine ; : 100562, 2022.
Article in English | ScienceDirect | ID: covidwho-1705044

ABSTRACT

Summary Robust T-cell responses have been associated with milder outcomes in many infections. T-cells also establish long-term memory pools and, as they are predominantly directed towards epitopes encompassing conserved peptides, can respond to SARS-CoV-2 variants, including Omicron. Here, we discuss epitope-specific CD8+ and CD4+ T-cell responses towards SARS-CoV-2 infection and vaccination, their subsequent persistence into long-term memory, and ongoing work to determine their role in limiting disease severity.

8.
Sci Transl Med ; 14(632): eabi5735, 2022 Feb 16.
Article in English | MEDLINE | ID: covidwho-1691438

ABSTRACT

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against coronavirus disease 2019 (COVID-19). We developed and evaluated an adjuvanted SARS-CoV-2 spike ferritin nanoparticle (SpFN) vaccine in nonhuman primates. High-dose (50 µg) SpFN vaccine, given twice 28 days apart, induced a Th1-biased CD4 T cell helper response and elicited neutralizing antibodies against SARS-CoV-2 wild-type and variants of concern, as well as against SARS-CoV-1. These potent humoral and cell-mediated immune responses translated into rapid elimination of replicating virus in the upper and lower airways and lung parenchyma of nonhuman primates following high-dose SARS-CoV-2 respiratory challenge. The immune response elicited by SpFN vaccination and resulting efficacy in nonhuman primates supports the utility of SpFN as a vaccine candidate for SARS-causing betacoronaviruses.


Subject(s)
COVID-19 , Nanoparticles , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , Ferritins , Humans , Immunity , Macaca mulatta , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-322485

ABSTRACT

Background: Household transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) significantly contributes to increased community cases. Methods: We conducted a prospective case-ascertained study to investigate the household secondary attack rate (SAR) and contributing factors in urban Los Angeles, California, USA. Household members were enrolled prospectively if ≥1 member tested positive for SARS-CoV-2 by polymerase chain reaction (PCR). Nasopharyngeal swabs for PCR and symptom data were obtained over multiple longitudinal visits. Serology was obtained at enrollment. Findings: A total of 489 individuals in 105 households were enrolled from June to December 2020. The mean household SAR was 77.7% (95%CI: 71.4-84.0). A third (32.1%) of index cases were asymptomatic. High SAR was associated with both symptomatic and asymptomatic index cases (76.4% [95%CI: 68.8-83.9%] vs. 79.7% [95% CI: 66.2-93.3%], p=0.66). The most common age for index cases was children <18 years old during low community transmission periods and adults ≥18 years old during peak community transmission (p=0.003). Children and adults index cases both efficiently transmitted SARS-CoV-2 within households (SAR 74.0% [95%CI: 63.4-84.6%] vs. 81.3% [95%CI: 72.3-90.3%], p=0.49). Hispanic/Latinx ethnicity was significantly associated with higher SAR in the multivariable analysis of household factors (p= 0.030). Interpretation: The SAR in our urban setting with large ethnic minority populations is much higher than previously described. SAR was disproportionately and significantly impacted by Hispanic/Latinx ethnicity. Asymptomatic individuals and children play important roles as index cases. Future vaccination and public health efforts need special focus on these groups to help mitigate SARS-CoV-2 spread.Funding: NIH/NIAID U01AI144616-02S1, Open PhilanthropyDeclaration of Interests: PSP has received consultant fees from Sanofi-Pasteur and Seqirus. She also receives research funding from AstraZeneca for an unrelated study. AG has received consultant fees from Janssen. All other authors have no conflicts of interest to report.Ethics Approval Statement: The study was approved by the Institutional Review Board at Children’sHospital Los Angeles.

10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-320401

ABSTRACT

Background: There is an urgent need to rapidly distinguish Covid-19 from other respiratory conditions, including influenza, at first-presentation. Point-of-care tests not requiring laboratory-support will speed diagnosis and protect health-care staff. We studied the feasibility of using breath-analysis to distinguish these conditions with near-patient gas chromatography-ion mobility spectrometry (GC-IMS).Methods: Independent studies at Edinburgh, UK, and Dortmund, Germany, recruited adult patients with possible Covid-19 at hospital presentation. Participants gave a single breath-sample for volatile organic compounds analysis by GC-IMS. Covid-19 infection was identified by RT-qPCR of oral/nasal swabs together with clinical-review. Following correction for environmental contaminants, potential Covid-19 breath-biomarkers were identified by multi-variate analysis and comparison to GC-IMS databases. A Covid-19 breath-score based on the relative abundance of a panel of volatile organic compounds was proposed and tested against the cohort data.Findings: Ninety-eight patients were recruited, of whom 21/33 (63.6%) and 10/65 (15.4%) had Covid-19 in Edinburgh and Dortmund, respectively. Other diagnoses included asthma, COPD, bacterial pneumonia, and cardiac conditions. Multivariate analysis identified aldehydes (ethanal, octanal), ketones (acetone, butanone), and methanol that discriminated Covid-19 from other conditions. An unidentified-feature with significant predictive power for severity/death was isolated in Edinburgh, while heptanal was identified in Dortmund. Differentiation of patients with definite diagnosis (25 and 65) of Covid-19 from non-Covid-19 was possible with 80% and 81.5% accuracy in Edinburgh and Dortmund respectively (sensitivity/specificity 82.4%/75%;area-under-the-receiver-operator-characteristic [AUROC] 0.87 95% CI 0.67 to 1) and Dortmund (sensitivity/ specificity 90%/80%;AUROC 0.91 95% CI 0.87 to 1).Interpretation: These two studies independently indicate that patients with Covid-19 can be rapidly distinguished from patients with other conditions at first healthcare contact. The identity of the marker compounds is consistent with Covid-19 derangement of breath-biochemistry by ketosis, gastrointestinal effects, and inflammatory processes. Development and validation of this approach may allow rapid diagnosis of Covid-19 in the coming endemic flu seasons.Funding Statement: MR was supported by an NHS Research Scotland Career Researcher Clinician award. DMR was supported by the University of Edinburgh ref COV_29Declaration of Interests: The authors have nothing to declare.Ethics Approval Statement: Two independent studies were set up in the emergency departments of the Royal Infirmary of Edinburgh (RIE, Institutional Review Board ref RIE, 20/SS/0042), UK, and Klinikum Dortmund (KD, Institutional Review Board ref IfADo 176/2020), Germany.

11.
Nat Immunol ; 23(2): 177-185, 2022 02.
Article in English | MEDLINE | ID: covidwho-1671601

ABSTRACT

Children and adolescents exhibit a broad range of clinical outcomes from SARS-CoV-2 infection, with the majority having minimal to mild symptoms. Additionally, some succumb to a severe hyperinflammatory post-infectious complication called multisystem inflammatory syndrome in children (MIS-C), predominantly affecting previously healthy individuals. Studies characterizing the immunological differences associated with these clinical outcomes have identified pathways important for host immunity to SARS-CoV-2 and innate modulators of disease severity. In this Review, we delineate the immunological mechanisms underlying the spectrum of pediatric immune response to SARS-CoV-2 infection in comparison with that of adults.


Subject(s)
COVID-19/complications , COVID-19/immunology , Immunity, Innate , SARS-CoV-2/immunology , Systemic Inflammatory Response Syndrome/immunology , Adolescent , Adolescent Development , Age Factors , Asymptomatic Diseases , COVID-19/diagnosis , COVID-19/virology , Child , Child Development , Comorbidity , Host-Pathogen Interactions , Humans , Risk Factors , SARS-CoV-2/pathogenicity , Severity of Illness Index , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/virology
12.
J Breath Res ; 16(2)2022 03 04.
Article in English | MEDLINE | ID: covidwho-1648455

ABSTRACT

Background. The SARS-CoV-2 pandemic changed the way the society functioned. The race to develop a rapid, non-invasive, widely available test resulted in multiple studies examining the potential of breath to be that 'game changing test'. Breath sampling is a non-invasive point of care test, but SAR-CoV-2 has introduced a level of danger into collection and analysis that requires a change in workflow to keep staff and participants safe. We developed a SARS-CoV 2 breath test work flow for collection and processing of breath samples in an ambulatory care setting and prospectively evaluated the protocol. Protocol development included testing the effect of respiratory filters on the integrity and reproducibility of breath samples.Methods. Prospective, observational study conducted at community COVID-19 testing sites, collecting breath samples from patients presenting for RT-PCR testing. Breath was collected via Tedlar®, and/or BioVOC-2™ as well as an environmental sample for all participants. Samples were transferred to Tenex tubes, dry purged and analyzed using a Centri automated sample introduction machine, GC, and a Bench-ToF-HD.Results. We successfully collected and processed 528 breath samples from 393 participants at community-based ambulatory COVID-19 test sites. The majority of samples were collected before vaccines were available and throughout the emergence of the Delta Variant. No staff member was infected.Conclusion. We demonstrated a safe workflow for the collection, handling, transport, storage, and analysis of breath samples during the pandemic collecting highly infectious SARS-CoV-2 positive breath samples. This was done without filters as they added complexity to the breath matrix, jeopardizing the sample integrity.


Subject(s)
COVID-19 Testing , COVID-19 , Animals , Breath Tests , Humans , Prospective Studies , Reproducibility of Results , SARS-CoV-2
13.
Journal of Engineering Education ; : 1, 2022.
Article in English | Academic Search Complete | ID: covidwho-1640738

ABSTRACT

Background Purpose/Hypothesis Design/Method Results Conclusions We evaluated the effect of three teaching strategies to facilitate teamwork in a systems analysis and design course during the COVID‐19 pandemic: (1) offering a HyFlex version of the course, (2) facilitating scheduled online teamwork sessions for all students, and (3) providing conflict resolution training to help teams overcome collaboration challenges.To identify the impact of these instructional strategies and answer four research questions, we measured (1) performance, dynamics, and cooperation strategies of teams and (2) students' perceptions of their own and team members' performance along with changes in their perceptions of their conflict management skills.We used a simultaneous triangulation mixed‐methods design to obtain distinct but complementary qualitative and quantitative data. We compared data from two offerings of the course: Fall 2019 and Fall 2020 semesters. In the Fall 2019 semester, an in‐person active learning strategy was used, while in the Fall 2020 semester, the course followed a HyFlex delivery mode due to the COVID‐19 pandemic.Findings suggest that the use of cooperative learning pedagogy along with HyFlex accommodations for safety and social distancing requirements for the Fall 2020 semester provided students with a comparable learning experience to a traditional in‐person mode.Learning strategies, pedagogical supports, and teamwork training can enhance social interactions, and consequently, students' social presence in online learning. Conflict resolution training could be a valuable tool for improving teamwork skills and communication among team members. [ FROM AUTHOR] Copyright of Journal of Engineering Education is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

14.
Cell Host Microbe ; 30(1): 83-96.e4, 2022 01 12.
Article in English | MEDLINE | ID: covidwho-1634725

ABSTRACT

SARS-CoV-2 infection causes diverse outcomes ranging from asymptomatic infection to respiratory distress and death. A major unresolved question is whether prior immunity to endemic, human common cold coronaviruses (hCCCoVs) impacts susceptibility to SARS-CoV-2 infection or immunity following infection and vaccination. Therefore, we analyzed samples from the same individuals before and after SARS-CoV-2 infection or vaccination. We found hCCCoV antibody levels increase after SARS-CoV-2 exposure, demonstrating cross-reactivity. However, a case-control study indicates that baseline hCCCoV antibody levels are not associated with protection against SARS-CoV-2 infection. Rather, higher magnitudes of pre-existing betacoronavirus antibodies correlate with more SARS-CoV-2 antibodies following infection, an indicator of greater disease severity. Additionally, immunization with hCCCoV spike proteins before SARS-CoV-2 immunization impedes the generation of SARS-CoV-2-neutralizing antibodies in mice. Together, these data suggest that pre-existing hCCCoV antibodies hinder SARS-CoV-2 antibody-based immunity following infection and provide insight on how pre-existing coronavirus immunity impacts SARS-CoV-2 infection, which is critical considering emerging variants.


Subject(s)
Antibodies, Viral/immunology , Antibody Formation/immunology , COVID-19/immunology , Common Cold/immunology , Immunity, Humoral/immunology , SARS-CoV-2/immunology , Animals , Asymptomatic Infections , COVID-19/virology , Case-Control Studies , Cell Line , Common Cold/virology , Cross Reactions/immunology , Female , HEK293 Cells , Humans , Mice , Mice, Inbred C57BL , Spike Glycoprotein, Coronavirus/immunology
15.
Cell ; 185(4): 603-613.e15, 2022 02 17.
Article in English | MEDLINE | ID: covidwho-1588149

ABSTRACT

SARS-CoV-2 mRNA vaccines induce robust anti-spike (S) antibody and CD4+ T cell responses. It is not yet clear whether vaccine-induced follicular helper CD4+ T (TFH) cell responses contribute to this outstanding immunogenicity. Using fine-needle aspiration of draining axillary lymph nodes from individuals who received the BNT162b2 mRNA vaccine, we evaluated the T cell receptor sequences and phenotype of lymph node TFH. Mining of the responding TFH T cell receptor repertoire revealed a strikingly immunodominant HLA-DPB1∗04-restricted response to S167-180 in individuals with this allele, which is among the most common HLA alleles in humans. Paired blood and lymph node specimens show that while circulating S-specific TFH cells peak one week after the second immunization, S-specific TFH persist at nearly constant frequencies for at least six months. Collectively, our results underscore the key role that robust TFH cell responses play in establishing long-term immunity by this efficacious human vaccine.


Subject(s)
COVID-19/immunology , COVID-19/virology , Immunity/immunology , SARS-CoV-2/immunology , T Follicular Helper Cells/immunology , Vaccination , Vaccines, Synthetic/immunology , /immunology , Adult , B-Lymphocytes/immunology , COVID-19/blood , Clone Cells , Cohort Studies , Cytokines/metabolism , Female , Germinal Center/immunology , HLA-DP beta-Chains/immunology , Humans , Immunodominant Epitopes/immunology , Jurkat Cells , Lymph Nodes/metabolism , Male , Middle Aged , Peptides/chemistry , Peptides/metabolism , Protein Multimerization , Receptors, Antigen, T-Cell/metabolism
16.
J Interferon Cytokine Res ; 41(12): 477-481, 2021 12.
Article in English | MEDLINE | ID: covidwho-1585196
19.
Clin Infect Dis ; 2021 Dec 10.
Article in English | MEDLINE | ID: covidwho-1566002

ABSTRACT

BACKGROUND: Following SARS-CoV-2 infection or vaccination there is significant variability between individuals in protective antibody levels against SARS-CoV-2, and within individuals against different virus variants. However, host demographic or clinical characteristics that predict variability in cross-reactive antibody levels are not well-described. These data could inform clinicians, researchers, and policy makers on the populations most likely to require vaccine booster shots. METHODS: In an institutional review board-approved prospective observational cohort study of staff at St. Jude Children's Research Hospital, we identified participants with plasma samples collected after SARS-CoV-2 infection, after mRNA vaccination, and after vaccination following infection, and quantitated IgG levels by ELISA to the spike receptor binding domain (RBD) from five important SARS-CoV-2 variants (Wuhan Hu-1, B.1.1.7, B.1.351, P.1 and B.1.617.2). We used regression models to identify factors that contributed to cross-reactive IgG against one or multiple viral variants. RESULTS: Following infection, a minority of the cohort generated cross-reactive antibodies, IgG antibodies that bound all tested variants. Those that did had increased disease severity, poor metabolic health, and were of a particular ancestry. Vaccination increased the levels of cross-reactive IgG levels in all populations including immunocompromised, elderly and persons with poor metabolic health. Younger people with a healthy weight mounted the highest responses. CONCLUSIONS: Our findings provide important new information on individual antibody responses to infection/vaccination that could inform clinicians on the populations that may require follow-on immunization.

20.
Cell host & microbe ; 2021.
Article in English | EuropePMC | ID: covidwho-1564429

ABSTRACT

A major unresolved question is whether prior immunity to endemic, human common cold coronaviruses (hCCCoV) impacts susceptibility to SARS-CoV-2 infection. Lin et al. analyze hCCCoV antibodies in the same individuals before and after SARS-CoV-2 infection, finding pre-existing betacoronavirus antibodies may hinder SARS-CoV-2 effective immunity following infection.

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