A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates.

While the rapid development of COVID-19 vaccines has been a scientific triumph, the need remains for a globally available vaccine that provides longer-lasting immunity against present and future SARS-CoV-2 variants of concern (VOCs). Here, we describe DCFHP, a ferritin-based, protein-nanoparticle vaccine candidate that, when formulated with aluminum hydroxide as the sole adjuvant (DCFHP-alum), elicits potent and durable neutralizing antisera in non-human primates against known VOCs, including Omicron BQ.1, as well as against SARS-CoV-1. Following a booster ~one year after the initial immunization, DCFHP-alum elicits a robust anamnestic response. To enable global accessibility, we generated a cell line that can enable production of thousands of vaccine doses per liter of cell culture and show that DCFHP-alum maintains potency for at least 14 days at temperatures exceeding standard room temperature. DCFHP-alum has potential as a once-yearly (or less frequent) booster vaccine, and as a primary vaccine for pediatric use including in infants.

COVID-19 and Psychosocial Well-Being: Did COVID-19 Worsen U.S. Frontline Healthcare Workers' Burnout, Anxiety, and Depression?

Healthcare workers are highly regarded for their compassion, dedication, and composure. However, COVID-19 created unprecedented demands that rendered healthcare workers vulnerable to increased burnout, anxiety, and depression. This cross-sectional study assessed the psychosocial impact of COVID-19 on U.S. healthcare frontliners using a 38-item online survey administered by Reaction Data between September and December 2020. The survey included five validated scales to assess self-reported burnout (Maslach Summative Burnout Scale), anxiety (GAD-7), depression (PHQ-2), resilience (Brief Resilience Coping Scale), and self-efficacy (New Self-Efficacy Scale-8). We used regression to assess the relationships between demographic variables and the psychosocial scales index scores and found that COVID-19 amplified preexisting burnout (54.8%), anxiety (138.5%), and depression (166.7%), and reduced resilience (5.70%) and self-efficacy (6.5%) among 557 respondents (52.6% male, 47.5% female). High patient volume, extended work hours, staff shortages, and lack of personal protective equipment (PPE) and resources fueled burnout, anxiety, and depression. Respondents were anxious about the indefinite duration of the pandemic/uncertain return to normal (54.8%), were anxious of infecting family (48.3%), and felt conflicted about protecting themselves versus fulfilling their duty to patients (44.3%). Respondents derived strength from their capacity to perform well in tough times (74.15%), emotional support from family/friends (67.2%), and time off work (62.8%). Strategies to promote emotional well-being and job satisfaction can focus on multilevel resilience, safety, and social connectedness.

COVID-19 and Psychosocial Well-Being: Did COVID-19 Worsen U.S. Frontline Healthcare Workers' Burnout, Anxiety, and Depression?

Healthcare workers are highly regarded for their compassion, dedication, and composure. However, COVID-19 created unprecedented demands that rendered healthcare workers vulnerable to increased burnout, anxiety, and depression. This cross-sectional study assessed the psychosocial impact of COVID-19 on U.S. healthcare frontliners using a 38-item online survey administered by Reaction Data between September and December 2020. The survey included five validated scales to assess self-reported burnout (Maslach Summative Burnout Scale), anxiety (GAD-7), depression (PHQ-2), resilience (Brief Resilience Coping Scale), and self-efficacy (New Self-Efficacy Scale-8). We used regression to assess the relationships between demographic variables and the psychosocial scales index scores and found that COVID-19 amplified preexisting burnout (54.8%), anxiety (138.5%), and depression (166.7%), and reduced resilience (5.70%) and self-efficacy (6.5%) among 557 respondents (52.6% male, 47.5% female). High patient volume, extended work hours, staff shortages, and lack of personal protective equipment (PPE) and resources fueled burnout, anxiety, and depression. Respondents were anxious about the indefinite duration of the pandemic/uncertain return to normal (54.8%), were anxious of infecting family (48.3%), and felt conflicted about protecting themselves versus fulfilling their duty to patients (44.3%). Respondents derived strength from their capacity to perform well in tough times (74.15%), emotional support from family/friends (67.2%), and time off work (62.8%). Strategies to promote emotional well-being and job satisfaction can focus on multilevel resilience, safety, and social connectedness.

The effects of COVID-19 stressors and family life on anxiety and depression one-year into the COVID-19 pandemic.

The purpose of this study was to examine the effects of Coronavirus (COVID-19)-related stressors and family health on adult anxiety and depressive symptoms 1 year into the pandemic. The sample consisted of 442 adults living in the United States who were recruited via Amazon Mechanical Turk. Data were analyzed using multiple logistic regression. Results indicated that compared to a sample 1 month into the pandemic, participants in the current sample reported worse family health and increases in both positive and negative perceptions of the pandemic on family life and routines. COVID-19 stressors and perceived negative effects of the pandemic on family life increased the odds for moderate-to-severe depression and anxiety while having more family health resources decreased the odds for depression and anxiety symptoms. Participants reported lower odds for worse depression and anxiety since the beginning of the pandemic when they reported more positive family meaning due to the pandemic. The results suggest a need to consider the impact of family life on mental health in pandemics and other disasters.

COVID-19 Stress, Religious Affiliation, and Mental Health Outcomes Among Adolescents.

PURPOSE: To examine the relationship between religious affiliation, stressors due to the COVID-19 pandemic, and mental health challenges in a representative sample of adolescents. METHODS: The sample was composed of 71,001 Utah adolescents who participated in a survey by the Utah Department of Health in 2021. Data are representative of all Utah adolescents in grades 6, 8, 10, and 12. Bootstrapped mediation was used to test indirect effects of religious affiliation on mental health challenges through COVID-19 stressors. RESULTS: Religious affiliation was related to significantly lower rates of teen mental health challenges as measured by suicidal thoughts, suicide attempts, and depression. For religiously affiliated adolescents, the rate of considering and attempting suicide was nearly half of that of unaffiliated adolescents. In mediation analyses, affiliation was indirectly related to mental health challenges (suicide ideation, suicide attempt, and depression) through stressors from COVID-19, including affiliated adolescents experiencing the following: less anxiety, fewer family fights, fewer school difficulties, and fewer skipped meals. However, affiliation was positively related to becoming sick with COVID-19 (or having COVID-19 symptoms), which was related to more suicidal thoughts. DISCUSSION: Findings suggest that adolescent religious affiliation may be a promotive factor that decreases mental health challenges through a reduction in COVID-19-related stressors, except religious individuals may be more likely to become sick. To increase positive mental health outcomes among adolescents during pandemic times, consistent and clear policies that facilitate religious connections that also align with good physical health measures will be critical.

Protection Motivation During COVID-19: A Cross-Sectional Study of Family Health, Media, and Economic Influences.

BACKGROUND: Protection motivation to practice preventive behaviors is necessary for sustained mitigation during coronavirus disease 2019 (COVID-19); however, limited research exists on the ecological sources of influence for COVID-19 protection motivation. AIM: To explore sources of influence (family health, media consumption, and loss of work hours) on COVID-19 protection motivation. METHOD: An online quantitative survey of U.S. adults (N = 501) aged 18 years or older was administered using Qualtrics with participants recruited through Amazon Mechanical Turk. Data were collected on constructs related to the protection motivation theory and theory of planned behavior as well as sources of influence and intention to socially distance and socially isolate during COVID-19. Constructs were further defined through exploratory and confirmatory factor analyses. Structural equation modeling was used to determine relationships between constructs. RESULTS: A two-factor model was identified with threat appraisal as one factor and subjective norms appraisal, coping appraisal, and behavioral intention loading as another factor. Higher news media consumption and loss of work hours due to COVID-19 were both significant predictors of increased threat appraisal. Family healthy lifestyle and family health resources were significantly related to increases in the subjective norms, coping appraisal, and behavioral intention appraisal factor. CONCLUSIONS: Family health, news media consumption, and loss of work hours are associated with COVID-19 protection motivation. COVID-19 protection motivation might be enhanced through policies and messaging that can affect ecological sources of influence.

COVID-19 Health Beliefs Regarding Mask Wearing and Vaccinations on Twitter: Deep Learning Approach

Background Amid the global COVID-19 pandemic, a worldwide infodemic also emerged with large amounts of COVID-19–related information and misinformation spreading through social media channels. Various organizations, including the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC), and other prominent individuals issued high-profile advice on preventing the further spread of COVID-19. Objective The purpose of this study is to leverage machine learning and Twitter data from the pandemic period to explore health beliefs regarding mask wearing and vaccines and the influence of high-profile cues to action. Methods A total of 646,885,238 COVID-19–related English tweets were filtered, creating a mask-wearing data set and a vaccine data set. Researchers manually categorized a training sample of 3500 tweets for each data set according to their relevance to Health Belief Model (HBM) constructs and used coded tweets to train machine learning models for classifying each tweet in the data sets. Results In total, 5 models were trained for both the mask-related and vaccine-related data sets using the XLNet transformer model, with each model achieving at least 81% classification accuracy. Health beliefs regarding perceived benefits and barriers were most pronounced for both mask wearing and immunization;however, the strength of those beliefs appeared to vary in response to high-profile cues to action. Conclusions During both the COVID-19 pandemic and the infodemic, health beliefs related to perceived benefits and barriers observed through Twitter using a big data machine learning approach varied over time and in response to high-profile cues to action from prominent organizations and individuals.

Neutralizing Immunity Induced Against the Omicron BA.1 and BA.2 Variants in Vaccine Breakthrough Infections.

BACKGROUND: As of early 2022, the Omicron variants are the predominant circulating lineages globally. Understanding neutralizing antibody responses against Omicron BA.1 and BA.2 after vaccine breakthrough infections will provide insights into BA.2 infectivity and susceptibility to subsequent reinfection. METHODS: Live virus neutralization assays were used to study immunity against Delta and Omicron BA.1 and BA.2 variants in samples from 86 individuals, 24 unvaccinated (27.9%) and 62 vaccinated (72.1%), who were infected with Delta (n = 42, 48.8%) or BA.1 (n = 44, 51.2%). Among the 62 vaccinated individuals, 39 were unboosted (62.9%), whereas 23 were boosted (37.1%). RESULTS: In unvaccinated infections, neutralizing antibodies (nAbs) against the three variants were weak or undetectable, except against Delta for Delta-infected individuals. Both Delta and BA.1 breakthrough infections resulted in strong nAb responses against ancestral wild-type and Delta lineages, but moderate nAb responses against BA.1 and BA.2, with similar titers between unboosted and boosted individuals. Antibody titers against BA.2 were generally higher than those against BA.1 in breakthrough infections. CONCLUSIONS: These results underscore the decreased immunogenicity of BA.1 compared to BA.2, insufficient neutralizing immunity against BA.2 in unvaccinated individuals, and moderate to strong neutralizing immunity induced against BA.2 in Delta and BA.1 breakthrough infections.

Converting non-neutralizing SARS-CoV-2 antibodies into broad-spectrum inhibitors.

Omicron and its subvariants have rendered most authorized monoclonal antibody-based treatments for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ineffective, highlighting the need for biologics capable of overcoming SARS-CoV-2 evolution. These mostly ineffective antibodies target variable epitopes. Here we describe broad-spectrum SARS-CoV-2 inhibitors developed by tethering the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), to known non-neutralizing antibodies that target highly conserved epitopes in the viral spike protein. These inhibitors, called receptor-blocking conserved non-neutralizing antibodies (ReconnAbs), potently neutralize all SARS-CoV-2 variants of concern (VOCs), including Omicron. Neutralization potency is lost when the linker joining the binding and inhibitory ReconnAb components is severed. In addition, a bi-functional ReconnAb, made by linking ACE2 to a bi-specific antibody targeting two non-overlapping conserved epitopes, defined here, shows sub-nanomolar neutralizing activity against all VOCs, including Omicron and BA.2. Given their conserved targets and modular nature, ReconnAbs have the potential to act as broad-spectrum therapeutics against SARS-CoV-2 and other emerging pandemic diseases.

Detection of neutralizing antibodies against multiple SARS-CoV-2 strains in dried blood spots using cell-free PCR.

An easily implementable serological assay to accurately detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies is urgently needed to better track herd immunity, vaccine efficacy and vaccination rates. Herein, we report the Split-Oligonucleotide Neighboring Inhibition Assay (SONIA) which uses real-time qPCR to measure the ability of neutralizing antibodies to block binding between DNA-barcoded viral spike protein subunit 1 and the human angiotensin-converting enzyme 2 receptor protein. The SONIA neutralizing antibody assay using finger-prick dried blood spots displays 91-97% sensitivity and 100% specificity in comparison to the live-virus neutralization assays using matched serum specimens for multiple SARS-CoV-2 variants-of-concern. The multiplex version of this neutralizing antibody assay, using easily collectable finger-prick dried blood spots, can be a valuable tool to help reveal the impact of age, pre-existing health conditions, waning immunity, different vaccination schemes and the emergence of new variants-of-concern.

Limited cross-variant immunity from SARS-CoV-2 Omicron without vaccination.

SARS-CoV-2 Delta and Omicron are globally relevant variants of concern. Although individuals infected with Delta are at risk of developing severe lung disease, infection with Omicron often causes milder symptoms, especially in vaccinated individuals1,2. The question arises of whether widespread Omicron infections could lead to future cross-variant protection, accelerating the end of the pandemic. Here we show that without vaccination, infection with Omicron induces a limited humoral immune response in mice and humans. Sera from mice overexpressing the human ACE2 receptor and infected with Omicron neutralize only Omicron, but not other variants of concern, whereas broader cross-variant neutralization was observed after WA1 and Delta infections. Unlike WA1 and Delta, Omicron replicates to low levels in the lungs and brains of infected animals, leading to mild disease with reduced expression of pro-inflammatory cytokines and diminished activation of lung-resident T cells. Sera from individuals who were unvaccinated and infected with Omicron show the same limited neutralization of only Omicron itself. By contrast, Omicron breakthrough infections induce overall higher neutralization titres against all variants of concern. Our results demonstrate that Omicron infection enhances pre-existing immunity elicited by vaccines but, on its own, may not confer broad protection against non-Omicron variants in unvaccinated individuals.

A multitope SARS-CoV-2 vaccine provides long-lasting B cell and T cell immunity against Delta and Omicron variants.

BackgroundThe Delta and Omicron variants of SARS-CoV-2 are currently responsible for breakthrough infections due to waning immunity. We report phase I/II trial results of UB-612, a multitope subunit vaccine containing S1-RBD-sFc protein and rationally designed promiscuous peptides representing sarbecovirus conserved helper T cell and cytotoxic T lymphocyte epitopes on the nucleocapsid (N), membrane (M), and spike (S2) proteins.MethodWe conducted a phase I primary 2-dose (28 days apart) trial of 10, 30, or 100 µg UB-612 in 60 healthy young adults 20 to 55 years old, and 50 of them were boosted with 100 µg of UB-612 approximately 7 to 9 months after the second dose. A separate placebo-controlled and randomized phase II study was conducted with 2 doses of 100 µg of UB-612 (n = 3,875, 18-85 years old). We evaluated interim safety and immunogenicity of phase I until 14 days after the third (booster) dose and of phase II until 28 days after the second dose.ResultsNo vaccine-related serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, mostly mild and transient. In both trials, UB-612 elicited respective neutralizing antibody titers similar to a panel of human convalescent sera. The most striking findings were long-lasting virus-neutralizing antibodies and broad T cell immunity against SARS-CoV-2 variants of concern (VoCs), including Delta and Omicron, and a strong booster-recalled memory immunity with high cross-reactive neutralizing titers against the Delta and Omicron VoCs.ConclusionUB-612 has presented a favorable safety profile, potent booster effect against VoCs, and long-lasting B and broad T cell immunity that warrants further development for both primary immunization and heterologous boosting of other COVID-19 vaccines.Trial RegistrationClinicalTrials.gov: NCT04545749, NCT04773067, and NCT04967742.FundingUBI Asia, Vaxxinity Inc., and Taiwan Centers for Disease Control, Ministry of Health and Welfare.

Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants.

Virus-like particle (VLP) and live virus assays were used to investigate neutralizing immunity against Delta and Omicron SARS-CoV-2 variants in 259 samples from 128 vaccinated individuals. Following Delta breakthrough infection, titers against WT rose 57-fold and 3.1-fold compared with uninfected boosted and unboosted individuals, respectively, versus only a 5.8-fold increase and 3.1-fold decrease for Omicron breakthrough infection. Among immunocompetent, unboosted patients, Delta breakthrough infections induced 10.8-fold higher titers against WT compared with Omicron (p = 0.037). Decreased antibody responses in Omicron breakthrough infections relative to Delta were potentially related to a higher proportion of asymptomatic or mild breakthrough infections (55.0% versus 28.6%, respectively), which exhibited 12.3-fold lower titers against WT compared with moderate to severe infections (p = 0.020). Following either Delta or Omicron breakthrough infection, limited variant-specific cross-neutralizing immunity was observed. These results suggest that Omicron breakthrough infections are less immunogenic than Delta, thus providing reduced protection against reinfection or infection from future variants.

The B.1.427/1.429 (epsilon) SARS-CoV-2 variants are more virulent than ancestral B.1 (614G) in Syrian hamsters.

As novel SARS-CoV-2 variants continue to emerge, it is critical that their potential to cause severe disease and evade vaccine-induced immunity is rapidly assessed in humans and studied in animal models. In early January 2021, a novel SARS-CoV-2 variant designated B.1.429 comprising 2 lineages, B.1.427 and B.1.429, was originally detected in California (CA) and it was shown to have enhanced infectivity in vitro and decreased antibody neutralization by plasma from convalescent patients and vaccine recipients. Here we examine the virulence, transmissibility, and susceptibility to pre-existing immunity for B 1.427 and B 1.429 in the Syrian hamster model. We find that both variants exhibit enhanced virulence as measured by increased body weight loss compared to hamsters infected with ancestral B.1 (614G), with B.1.429 causing the most marked body weight loss among the 3 variants. Faster dissemination from airways to parenchyma and more severe lung pathology at both early and late stages were also observed with B.1.429 infections relative to B.1. (614G) and B.1.427 infections. In addition, subgenomic viral RNA (sgRNA) levels were highest in oral swabs of hamsters infected with B.1.429, however sgRNA levels in lungs were similar in all three variants. This demonstrates that B.1.429 replicates to higher levels than ancestral B.1 (614G) or B.1.427 in the oropharynx but not in the lungs. In multi-virus in-vivo competition experiments, we found that B.1. (614G), epsilon (B.1.427/B.1.429) and gamma (P.1) dramatically outcompete alpha (B.1.1.7), beta (B.1.351) and zeta (P.2) in the lungs. In the nasal cavity, B.1. (614G), gamma, and epsilon dominate, but the highly infectious alpha variant also maintains a moderate size niche. We did not observe significant differences in airborne transmission efficiency among the B.1.427, B.1.429 and ancestral B.1 (614G) and WA-1 variants in hamsters. These results demonstrate enhanced virulence and high relative oropharyngeal replication of the epsilon (B.1.427/B.1.429) variant in Syrian hamsters compared to an ancestral B.1 (614G) variant.

Predominance of antibody-resistant SARS-CoV-2 variants in vaccine breakthrough cases from the San Francisco Bay Area, California.

Associations between vaccine breakthrough cases and infection by different SARS coronavirus 2 (SARS-CoV-2) variants have remained largely unexplored. Here we analysed SARS-CoV-2 whole-genome sequences and viral loads from 1,373 persons with COVID-19 from the San Francisco Bay Area from 1 February to 30 June 2021, of which 125 (9.1%) were vaccine breakthrough infections. Vaccine breakthrough infections were more commonly associated with circulating antibody-resistant variants carrying ≥1 mutation associated with decreased antibody neutralization (L452R/Q, E484K/Q and/or F490S) than infections in unvaccinated individuals (78% versus 48%, P = 1.96 × 10-8). Differences in viral loads were non-significant between unvaccinated and fully vaccinated cases overall (P = 0.99) and according to lineage (P = 0.09-0.78). Symptomatic vaccine breakthrough infections had comparable viral loads (P = 0.64), whereas asymptomatic breakthrough infections had decreased viral loads (P = 0.023) compared with infections in unvaccinated individuals. In 5 cases with serial samples available for serologic analyses, vaccine breakthrough infections were found to be associated with low or undetectable neutralizing antibody levels attributable to an immunocompromised state or infection by an antibody-resistant lineage. Taken together, our results show that vaccine breakthrough infections are overrepresented by antibody-resistant SARS-CoV-2 variants, and that symptomatic breakthrough infections may be as efficient in spreading COVID-19 as unvaccinated infections, regardless of the infecting lineage.

Family well-being and individual mental health in the early stages of COVID-19.

BACKGROUND: The objective of the study was to examine the association of COVID-19 with family well-being and adult mental health 1 month into the COVID-19 pandemic in the United States. Prior pandemics have had long-term effects on mental health. COVID-19 and its related stressors, such as loss of work and social distancing requirements, may have a profound impact on short-term and long-term mental health. Family stress theory indicates that subjective family meaning making and family resources affect how stressors lead to outcomes. METHOD: Participants, adults ages 18 years and older (N = 416), completed a cross-sectional online survey measuring depressive and anxiety symptoms, family health, subjective family meaning making, and loss of work resulting from COVID-19. Data were analyzed using a structural equation modeling framework. RESULTS: Results indicated that subjective negative family meaning and effects were associated with more depression and anxiety. Higher family health resources were associated with less depression and anxiety. Family health resources mediated the relationships between COVID-19 loss of work with depression and anxiety. CONCLUSION: COVID-19 associated stressors 1 month into the pandemic had modest effects on family meaning making and family health resources. Individuals from families whose health resources were negatively impacted by COVID-19 reported more anxiety and depressive symptoms. Health care and public health systems should consider family health resources to help reduce the negative effects of COVID-19 on mental health. Longitudinal research is needed to examine the accumulation of stressors over time and the directionality of relationships. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Effectiveness of Abbott BinaxNOW Rapid Antigen Test for Detection of SARS-CoV-2 Infections in Outbreak among Horse Racetrack Workers, California, USA.

The Abbott BinaxNOW rapid antigen test is cheaper and faster than real-time reverse transcription PCR (rRT-PCR) for detecting severe acute respiratory syndrome coronavirus 2. We compared BinaxNOW with rRT-PCR in 769 paired specimens from 342 persons during a coronavirus disease outbreak among horse racetrack workers in California, USA. We found positive percent agreement was 43.3% (95% CI 34.6%-52.4%), negative percent agreement 100% (95% CI 99.4%-100%), positive predictive value 100% (95% CI 93.5%-100%), and negative predictive value 89.9% (95% CI 87.5%-92.0%). Among 127 rRT-PCR-positive specimens, the 55 with paired BinaxNOW-positive results had a lower mean cycle threshold than the 72 with paired BinaxNOW-negative results (17.8 vs. 28.5; p<0.001). Of 100 specimens with cycle threshold <30, a total of 51 resulted in positive virus isolation; 45 (88.2%) of those were BinaxNOW-positive. Our comparison supports immediate isolation for BinaxNOW-positive persons and confirmatory testing for negative persons.

Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant.

We identified an emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant by viral whole-genome sequencing of 2,172 nasal/nasopharyngeal swab samples from 44 counties in California, a state in the western United States. Named B.1.427/B.1.429 to denote its two lineages, the variant emerged in May 2020 and increased from 0% to >50% of sequenced cases from September 2020 to January 2021, showing 18.6%-24% increased transmissibility relative to wild-type circulating strains. The variant carries three mutations in the spike protein, including an L452R substitution. We found 2-fold increased B.1.427/B.1.429 viral shedding in vivo and increased L452R pseudovirus infection of cell cultures and lung organoids, albeit decreased relative to pseudoviruses carrying the N501Y mutation common to variants B.1.1.7, B.1.351, and P.1. Antibody neutralization assays revealed 4.0- to 6.7-fold and 2.0-fold decreases in neutralizing titers from convalescent patients and vaccine recipients, respectively. The increased prevalence of a more transmissible variant in California exhibiting decreased antibody neutralization warrants further investigation.

Quantification of antibody avidities and accurate detection of SARS-CoV-2 antibodies in serum and saliva on plasmonic substrates.

Accurate assays for the detection of antibodies to SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) are essential for the control of the COVID-19 (coronavirus disease 2019) pandemic. Here, we report antibody and antibody-avidity assays, relying on near-infrared-fluorescence amplification by nanostructured plasmonic gold substrates, for the simultaneous detection of antibodies to the S1 subunit of the spike protein and to the receptor binding domain of SARS-CoV-2 in human serum and saliva, and for quantifying immunoglobulin avidities against coronavirus antigens from SARS-CoV-2, SARS-CoV-1 and the common-cold viruses OC43, HKU1, NL63 and 229E. The antibody assay detected immunoglobulin M in 87% (52 of 60) COVID-19-positive serum samples collected 6 or more days after symptom onset (and the immunoglobulins M and G in all 33 samples collected at least 15 days after symptom onset), and correctly classified 456 out of the 457 COVID-19-negative serum samples tested (424 of them collected before the pandemic, including 73 that were positive for other viruses). We used the antibody-avidity assay to study antibody-maturation patterns, anamnestic responses, and cross-immunity to the common-cold coronaviruses.