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1.
J Nanobiotechnology ; 20(1): 6, 2022 Jan 04.
Article in English | MEDLINE | ID: covidwho-1608546

ABSTRACT

BACKGROUND: Gold nanoparticles (AuNPs) have been widely used in local surface plasmon resonance (LSPR) immunoassays for biomolecule sensing, which is primarily based on two conventional methods: absorption spectra analysis and colorimetry. The low figure of merit (FoM) of the LSPR and high-concentration AuNP requirement restrict their limit of detection (LOD), which is approximately ng to µg mL-1 in antibody detection if there is no other signal or analyte amplification. Improvements in sensitivity have been slow in recent for a long time, and pushing the boundary of the current LOD is a great challenge of current LSPR immunoassays in biosensing. RESULTS: In this work, we developed spectral image contrast-based flow digital nanoplasmon-metry (Flow DiNM) to push the LOD boundary. Comparing the scattering image brightness of AuNPs in two neighboring wavelength bands near the LSPR peak, the peak shift signal is strongly amplified and quickly detected. Introducing digital analysis, the Flow DiNM provides an ultrahigh signal-to-noise ratio and has a lower sample volume requirement. Compared to the conventional analog LSPR immunoassay, Flow DiNM for anti-BSA detection in pure samples has an LOD as low as 1 pg mL-1 within only a 15-min detection time and 500 µL sample volume. Antibody assays against spike proteins of SARS-CoV-2 in artificial saliva that contained various proteins were also conducted to validate the detection of Flow DiNM in complicated samples. Flow DiNM shows significant discrimination in detection with an LOD of 10 pg mL-1 and a broad dynamic detection range of five orders of magnitude. CONCLUSION: Together with the quick readout time and simple operation, this work clearly demonstrated the high sensitivity and selectivity of the developed Flow DiNM in rapid antibody detection. Spectral image contrast and digital analysis further provide a new generation of LSPR immunoassay with AuNPs.


Subject(s)
COVID-19 Serological Testing/methods , COVID-19/diagnosis , SARS-CoV-2/isolation & purification , Surface Plasmon Resonance/methods , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19 Serological Testing/instrumentation , Equipment Design , Gold/chemistry , Humans , Immunoassay/instrumentation , Immunoassay/methods , Metal Nanoparticles/chemistry , SARS-CoV-2/immunology , Saliva/virology , Spike Glycoprotein, Coronavirus/immunology , Surface Plasmon Resonance/instrumentation
2.
Sci Rep ; 11(1): 24392, 2021 12 22.
Article in English | MEDLINE | ID: covidwho-1585793

ABSTRACT

Most public health measures to contain the COVID-19 pandemic are based on preventing the pathogen spread, and the use of oral antiseptics has been proposed as a strategy to reduce transmission risk. The aim of this manuscript is to test the efficacy of mouthwashes to reduce salivary viral load in vivo. This is a multi-centre, blinded, parallel-group, placebo-controlled randomised clinical trial that tests the effect of four mouthwashes (cetylpyridinium chloride, chlorhexidine, povidone-iodine and hydrogen peroxide) in SARS-CoV-2 salivary load measured by qPCR at baseline and 30, 60 and 120 min after the mouthrinse. A fifth group of patients used distilled water mouthrinse as a control. Eighty-four participants were recruited and divided into 12-15 per group. There were no statistically significant changes in salivary viral load after the use of the different mouthwashes. Although oral antiseptics have shown virucidal effects in vitro, our data show that salivary viral load in COVID-19 patients was not affected by the tested treatments. This could reflect that those mouthwashes are not effective in vivo, or that viral particles are not infective but viral RNA is still detected by PCR. Viral infectivity studies after the use of mouthwashes are therefore required. ( https://clinicaltrials.gov/ct2/show/NCT04707742 ; Identifier: NCT04707742).


Subject(s)
Anti-Infective Agents, Local/pharmacology , Mouthwashes/pharmacology , SARS-CoV-2/drug effects , Saliva/virology , Adolescent , Adult , Aged , Anti-Infective Agents, Local/chemistry , COVID-19/prevention & control , COVID-19/virology , Child , Child, Preschool , Double-Blind Method , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Mouthwashes/chemistry , Placebo Effect , SARS-CoV-2/isolation & purification , Viral Load/drug effects , Young Adult
3.
PLoS One ; 16(12): e0260894, 2021.
Article in English | MEDLINE | ID: covidwho-1581768

ABSTRACT

BACKGROUND: Performance of the SD Biosensor saliva antigen rapid test was evaluated at a large designated testing site in non-hospitalized patients, with or without symptoms. METHOD: All eligible people over 18 years of age presenting for a booked appointment at the designated SARS-CoV-2 testing site were approached for inclusion and enrolled following verbal informed consent. One nasopharyngeal swab was taken to carry out the default antigen rapid test from which the results were reported back to the patient and one saliva sample was self-taken according to verbal instruction on site. This was used for the saliva antigen rapid test, the RT-PCR and for virus culture. Sensitivity of the saliva antigen rapid test was analyzed in two ways: i, compared to saliva RT-PCR; and ii, compared to virus culture of the saliva samples. Study participants were also asked to fill in a short questionnaire stating age, sex, date of symptom onset. Recommended time of ≥30mins since last meal, drink or cigarette if applicable was also recorded. The study was carried out in February-March 2021 for 4 weeks. RESULTS: We could include 789 people with complete records and results. Compared to saliva RT-PCR, overall sensitivity and specificity of the saliva antigen rapid test was 66.1% and 99.6% which increased to 88.6% with Ct ≤30 cutoff. Analysis by days post onset did not result in higher sensitivities because the large majority of people were in the very early phase of disease ie <3 days post onset. When breaking down the data for symptomatic and asymptomatic individuals, sensitivity ranged from 69.2% to 50% respectively, however the total number of RT-PCR positive asymptomatic participants was very low (n = 5). Importantly, almost all culture positive samples were detected by the rapid test. CONCLUSION: Overall, the potential benefits of saliva antigen rapid test, could outweigh the lower sensitivity compared to nasopharyngeal antigen rapid test in a comprehensive testing strategy, especially for home/self-testing and in vulnerable populations like elderly, disabled or children where in intrusive testing is either not possible or causes unnecessary stress.


Subject(s)
Biosensing Techniques/methods , COVID-19 Serological Testing/methods , Saliva/virology , Adolescent , Adult , Aged , COVID-19/diagnosis , COVID-19/etiology , Carrier State/virology , Female , Hospitalization , Humans , Male , Middle Aged , Nasopharynx/virology , Sensitivity and Specificity , Young Adult
4.
Front Immunol ; 12: 777858, 2021.
Article in English | MEDLINE | ID: covidwho-1581332

ABSTRACT

Background: Developing an understanding of the antibody response, seroprevalence, and seroconversion from natural infection and vaccination against SARS-CoV-2 will give way to a critical epidemiological tool to predict reinfection rates, identify vulnerable communities, and manage future viral outbreaks. To monitor the antibody response on a larger scale, we need an inexpensive, less invasive, and high throughput method. Methods: Here we investigate the use of oral mucosal fluids from individuals recovered from SARS-CoV-2 infection to monitor antibody response and persistence over a 12-month period. For this cohort study, enzyme-linked immunosorbent assays (ELISAs) were used to quantify anti-Spike(S) protein IgG antibodies in participants who had prior SARS-CoV-2 infection and regularly (every 2-4 weeks) provided both serum and oral fluid mucosal fluid samples for longitudinal antibody titer analysis. Results: In our study cohort (n=42) with 17 males and 25 females with an average age of 45.6 +/- 19.3 years, we observed no significant change in oral mucosal fluid IgG levels across the time course of antibody monitoring. In oral mucosal fluids, all the participants who initially had detectable antibodies continued to have detectable antibodies throughout the study. Conclusions: Based on the results presented here, we have shown that oral mucosal fluid-based assays are an effective, less invasive tool for monitoring seroprevalence and seroconversion, which offers an alternative to serum-based assays for understanding the protective ability conferred by the adaptive immune response from viral infection and vaccination against future reinfections.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Immunoglobulin G/immunology , Saliva/immunology , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Longitudinal Studies , Male , Middle Aged , Mouth Mucosa/immunology , SARS-CoV-2 , Seroconversion , Spike Glycoprotein, Coronavirus/immunology
5.
Front Immunol ; 12: 798859, 2021.
Article in English | MEDLINE | ID: covidwho-1581315

ABSTRACT

SARS-CoV-2 antibodies in saliva serve as first line of defense against the virus. They are present in the mucosa, more precisely in saliva, after a recovered infection and also following vaccination. We report here the antibody persistence in plasma and in saliva up to 15 months after mild COVID-19. The IgG antibody response was measured every two months in 72 participants using an established and validated in-house ELISA assay. In addition, the virus inhibitory activity of plasma antibodies was assessed in a surrogate virus neutralization test before and after vaccination. SARS-CoV-2-specific antibody concentrations remained stable in plasma and saliva and the response was strongly boosted after one dose COVID-19 vaccination.


Subject(s)
Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , Immunoglobulin G/immunology , Saliva/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/immunology , Female , Humans , Male , Middle Aged , SARS-CoV-2
6.
Front Public Health ; 9: 743300, 2021.
Article in English | MEDLINE | ID: covidwho-1581123

ABSTRACT

In January 2021, the Chilean city of Concepción experienced a second wave of coronavirus 2019 (COVID-19) while in early April 2021, the entire country faced the same situation. This outbreak generated the need to modify and validate a method for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in saliva, thereby expanding the capacity and versatility of testing for COVID-19. This study was conducted in February 2021 in the Chilean city of Concepción during which time, the town was under total quarantine. The study participants were mostly symptomatic (87.4%), not hospitalized, and attended care centers because of their health status rather than being asked by the researchers. People coming to the health center in Concepción to be tested for COVID-19 (via reverse transcriptase polymerase chain reaction [RT-PCR]) from a specimen of nasopharyngeal swab (NPS) were then invited to participate in this study. A total of 131 participants agreed to sign an informed consent and to provide saliva and NPS specimens to validate a method in terms of sensitivity, specificity, and statistical analysis of the cycle threshold (Ct) values from the RT-PCR. Calculations pertaining to the 127 participants who were ultimately included in the analysis showed sensitivity and specificity at 94.34% (95% CI: 84.34-98.82%) and 98.65% (95% CI: 92.70-99.97%), respectively. The saliva specimen showed a performance comparable to NPS as demonstrated by the diagnostic parameters. This RT-PCR method from the saliva specimen is a highly sensitive and specific alternative compared to the reference methodology, which uses the NPS specimen. This modified and validated method is intended for use in the in vitro diagnosis of SARS-CoV-2, which provides health authorities in Chile and local laboratories with a real testing alternative to RT-PCR from NPS.


Subject(s)
COVID-19 , SARS-CoV-2 , Saliva/virology , COVID-19/diagnosis , COVID-19 Testing , Chile , Humans , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/isolation & purification , Specimen Handling
7.
Infect Control Hosp Epidemiol ; 42(11): 1340-1344, 2021 11.
Article in English | MEDLINE | ID: covidwho-1574695

ABSTRACT

BACKGROUND: Widespread testing for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) is necessary to curb the spread of coronavirus disease 2019 (COVID-19), but testing is undermined when the only option is a nasopharyngeal swab. Self-collected swab techniques can overcome many of the disadvantages of a nasopharyngeal swab, but they require evaluation. METHODS: Three self-collected non-nasopharyngeal swab techniques (saline gargle, oral swab and combined oral-anterior nasal swab) were compared to a nasopharyngeal swab for SARS-CoV-2 detection at multiple COVID-19 assessment centers in Toronto, Canada. The performance characteristics of each test were assessed. RESULTS: The adjusted sensitivity of the saline gargle was 0.90 (95% CI 0.86-0.94), the oral swab was 0.82 (95% CI, 0.72-0.89) and the combined oral-anterior nasal swab was 0.87 (95% CI, 0.77-0.93) compared to a nasopharyngeal swab, which demonstrated a sensitivity of ˜90% when all positive tests were the reference standard. The median cycle threshold values for the SARS-CoV-2 E-gene for concordant and discordant saline gargle specimens were 17 and 31 (P < .001), for the oral swabs these values were 17 and 28 (P < .001), and for oral-anterior nasal swabs these values were 18 and 31 (P = .007). CONCLUSIONS: Self-collected saline gargle and an oral-anterior nasal swab have a similar sensitivity to a nasopharyngeal swab for the detection of SARS-CoV-2. These alternative collection techniques are cheap and can eliminate barriers to testing, particularly in underserved populations.


Subject(s)
COVID-19 , Outpatients , Humans , Nasopharynx , SARS-CoV-2 , Saliva , Specimen Handling
8.
Rev Invest Clin ; 73(6): 339-346, 2021 11 05.
Article in English | MEDLINE | ID: covidwho-1574413

ABSTRACT

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is a current public health concern. Rapid diagnosis is crucial, and reverse transcription polymerase chain reaction (RT-PCR) is presently the reference standard for SARS-CoV-2 detection. OBJECTIVE: Automated RT-PCR analysis (ARPA) is a software designed to analyze RT-PCR data for SARSCoV-2 detection. ARPA loads the RT-PCR data, classifies each sample by assessing its amplification curve behavior, evaluates the experiment's quality, and generates reports. METHODS: ARPA was implemented in the R language and deployed as a Shiny application. We evaluated the performance of ARPA in 140 samples. The samples were manually classified and automatically analyzed using ARPA. RESULTS: ARPA had a true-positive rate = 1, true-negative rate = 0.98, positive-predictive value = 0.95, and negative-predictive value = 1, with 36 samples correctly classified as positive, 100 samples correctly classified as negative, and two samples classified as positive even when labeled as negative by manual inspection. Two samples were labeled as invalid by ARPA and were not considered in the performance metrics calculation. CONCLUSIONS: ARPA is a sensitive and specific software that facilitates the analysis of RT-PCR data, and its implementation can reduce the time required in the diagnostic pipeline.


Subject(s)
COVID-19/diagnosis , Diagnosis, Computer-Assisted , SARS-CoV-2/isolation & purification , Software , COVID-19 Testing , Humans , Reverse Transcriptase Polymerase Chain Reaction , Saliva/virology
9.
Clin Infect Dis ; 73(9): e3106-e3109, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1565979

ABSTRACT

We compared self-collected oral fluid swab specimens with and without clinician supervision, clinician-supervised self-collected anterior nasal swab specimens, and clinician-collected nasopharyngeal swab specimens for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Supervised oral fluid and nasal swab specimens performed similarly to clinician-collected nasopharyngeal swab specimens. No sample type could detect SARS-CoV-2 infections amongst all positive participants.


Subject(s)
COVID-19 , Humans , Nasopharynx , SARS-CoV-2 , Saliva , Specimen Handling
10.
Indian J Dent Res ; 32(2): 206-210, 2021.
Article in English | MEDLINE | ID: covidwho-1547550

ABSTRACT

Context: The Corona Virus Disease 2019 (COVID-19) is a contagious disease caused by the novel Coronavirus (2019-nCoV) and was declared a pandemic disease by the World Health Organization (WHO) in March 2020. The nasopharyngeal and the oropharyngeal swabs are being taken during the screening procedure. However, the virus is also present in the oral bio-fluid and hence it could be a potential tool for screening COVID-19 cases. Aim: The aim of the present study was to test the accuracy of whole saliva as a diagnostic specimen in COVID-19. Settings and Design: This cross-sectional, analytical study was conducted on out-patients visiting the COVID-19 hospital. Methods and Material: The whole saliva and the nasopharyngeal/oropharyngeal samples from 309 COVID-19 suspected patients were collected and subjected to RT-PCR analysis. Statistical Analysis Used: The paired t test was used to compare the measured variables (CT values) between the saliva and the swab samples. The positive predictive value (PPV), negative predictive value (NPV), the sensitivity, and the specificity of the tests were calculated for the saliva sample. Results: The saliva and swab results revealed a similar result (ties) in 86.73% of the samples. The sensitivity and the specificity between the swab and saliva samples were 40% and 96.85%, respectively. The positive predictive value of the saliva sample was 73.3%. Conclusions: The sensitivity of whole saliva when compared to the swab samples is low. Large sample studies are needed to validate the role of saliva as a diagnostic tool in COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Cross-Sectional Studies , Humans , Nasopharynx , Pandemics , Saliva
11.
J Med Virol ; 93(12): 6837-6840, 2021 12.
Article in English | MEDLINE | ID: covidwho-1544319

ABSTRACT

BACKGROUND: Gargle samples have been proposed as a noninvasive method for detection of SARS-CoV-2 RNA. The clinical performance of gargle specimens diluted in Cobas® PCR Media and in Cobas® Omni Lysis Reagent was compared to oropharyngeal/nasopharyngeal swab (ONPS) for the detection of SARS-CoV-2 RNA. STUDY DESIGN: Participants were recruited prospectively in two COVID-19 screening clinics. In addition to the ONPS, participants gargled with 5 ml of natural spring water split in the laboratory as follows: 1 ml was added to 4.3 ml of polymerase chain reaction (PCR) media and 400 µl was added to 200 µl of lysis buffer. Testing was performed with the Cobas® SARS-CoV-2 test on the Cobas® 6800 or 8800 platforms. RESULTS: Overall, 134/647 (20.7%) participants were considered infected because the ONPS or at least one gargle test was positive. ONPS had, respectively, a sensitivity of 96.3% (95% confidence interval [CI]: 91.3-98.5); both gargle processing methods were slightly less but equally sensitive (90.3% [95% CI: 83.9-94.3]). When ONPS and gargle specimens were both positive, the mean cycle threshold (Ct ) was significantly higher for gargles, suggesting lower viral loads. CONCLUSION: Gargle specimens directly added in PCR Media provide a similar clinical sensitivity to chemical lysis, both having a slightly, not significantly, lower sensitivity to ONPS.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , COVID-19/virology , Nasopharynx/virology , Oropharynx/virology , SARS-CoV-2/genetics , Diagnostic Tests, Routine/methods , Humans , Mass Screening/methods , Prospective Studies , RNA, Viral/genetics , Saliva/virology , Specimen Handling/methods , Viral Load/genetics
13.
14.
Sci Rep ; 11(1): 22493, 2021 11 18.
Article in English | MEDLINE | ID: covidwho-1526101

ABSTRACT

The COVID-19 pandemic caused by SARS-CoV-2 has infected millions worldwide, therefore there is an urgent need to increase our diagnostic capacity to identify infected cases. Although RT-qPCR remains the gold standard for SARS-CoV-2 detection, this method requires specialised equipment in a diagnostic laboratory and has a long turn-around time to process the samples. To address this, several groups have recently reported the development of loop-mediated isothermal amplification (LAMP) as a simple, low cost and rapid method for SARS-CoV-2 detection. Herein we present a comparative analysis of three LAMP-based assays that target different regions of the SARS-CoV-2: ORF1ab RdRP, ORF1ab nsp3 and Gene N. We perform a detailed assessment of their sensitivity, kinetics and false positive rates for SARS-CoV-2 diagnostics in LAMP or RT-LAMP reactions, using colorimetric or fluorescent detection. Our results independently validate that all three assays can detect SARS-CoV-2 in 30 min, with robust accuracy at detecting as little as 1000 RNA copies and the results can be visualised simply by color changes. Incorporation of RT-LAMP with fluorescent detection further increases the detection sensitivity to as little as 100 RNA copies. We also note the shortcomings of some LAMP-based assays, including variable results with shorter reaction time or lower load of SARS-CoV-2, and false positive results in some experimental conditions and clinical saliva samples. Overall for RT-LAMP detection, the ORF1ab RdRP and ORF1ab nsp3 assays have faster kinetics for detection but varying degrees of false positives detection, whereas the Gene N assay exhibits no false positives in 30 min reaction time, which highlights the importance of optimal primer design to minimise false-positives in RT-LAMP. This study provides validation of the performance of LAMP-based assays as a rapid, highly sensitive detection method for SARS-CoV-2, which have important implications in development of point-of-care diagnostics for SARS-CoV-2.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19 , Molecular Diagnostic Techniques , Nucleic Acid Amplification Techniques , SARS-CoV-2/genetics , Saliva/metabolism , Adult , COVID-19/diagnosis , COVID-19/genetics , COVID-19/metabolism , Female , Humans , Male , Saliva/virology
15.
NPJ Biofilms Microbiomes ; 7(1): 81, 2021 11 18.
Article in English | MEDLINE | ID: covidwho-1526078

ABSTRACT

The oral microbiome has been connected with lung health and may be of significance in the progression of SARS-CoV-2 infection. Saliva-based SARS-CoV-2 tests provide the opportunity to leverage stored samples for assessing the oral microbiome. However, these collection kits have not been tested for their accuracy in measuring the oral microbiome. Saliva is highly enriched with human DNA and reducing it prior to shotgun sequencing may increase the depth of bacterial reads. We examined both the effect of saliva collection method and sequence processing on measurement of microbiome depth and diversity by 16S rRNA gene amplicon and shotgun metagenomics. We collected 56 samples from 22 subjects. Each subject provided saliva samples with and without preservative, and a subset provided a second set of samples the following day. 16S rRNA gene (V4) sequencing was performed on all samples, and shotgun metagenomics was performed on a subset of samples collected with preservative with and without human DNA depletion before sequencing. We observed that the beta diversity distances within subjects over time was smaller than between unrelated subjects, and distances within subjects were smaller in samples collected with preservative. Samples collected with preservative had higher alpha diversity measuring both richness and evenness. Human DNA depletion before extraction and shotgun sequencing yielded higher total and relative reads mapping to bacterial sequences. We conclude that collecting saliva with preservative may provide more consistent measures of the oral microbiome and depleting human DNA increases yield of bacterial sequences.


Subject(s)
Microbiota/genetics , Saliva/microbiology , Adult , Bacteria/genetics , COVID-19/genetics , DNA/genetics , DNA, Bacterial/genetics , Female , Humans , Male , Metagenome/genetics , Metagenomics/methods , Middle Aged , RNA, Ribosomal, 16S/genetics , SARS-CoV-2/pathogenicity , Sequence Analysis, DNA/methods
16.
Sci Rep ; 11(1): 21768, 2021 11 05.
Article in English | MEDLINE | ID: covidwho-1505016

ABSTRACT

Rapid design, screening, and characterization of biorecognition elements (BREs) is essential for the development of diagnostic tests and antiviral therapeutics needed to combat the spread of viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To address this need, we developed a high-throughput pipeline combining in silico design of a peptide library specific for SARS-CoV-2 spike (S) protein and microarray screening to identify binding sequences. Our optimized microarray platform allowed the simultaneous screening of ~ 2.5 k peptides and rapid identification of binding sequences resulting in selection of four peptides with nanomolar affinity to the SARS-CoV-2 S protein. Finally, we demonstrated the successful integration of one of the top peptides into an electrochemical sensor with a clinically relevant limit of detection for S protein in spiked saliva. Our results demonstrate the utility of this novel pipeline for the selection of peptide BREs in response to the SARS-CoV-2 pandemic, and the broader application of such a platform in response to future viral threats.


Subject(s)
COVID-19/immunology , Combinatorial Chemistry Techniques , Peptides/chemistry , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry , COVID-19/virology , Computational Biology , Electrochemistry/methods , Enzyme-Linked Immunosorbent Assay , Humans , Interferometry , Kinetics , Peptide Library , Protein Array Analysis , Protein Engineering , Saliva/immunology
19.
JAMA Netw Open ; 4(11): e2132563, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1499193

ABSTRACT

Importance: Although several studies have provided information on short-term clinical outcomes in children with perinatal exposure to SARS-CoV-2, data on the immune response in the first months of life among newborns exposed to the virus in utero are lacking. Objective: To characterize systemic and mucosal antibody production during the first 2 months of life among infants who were born to mothers infected with SARS-CoV-2. Design, Setting, and Participants: This prospective cohort study enrolled 28 pregnant women who tested positive for SARS-CoV-2 infection and who gave birth at Policlinico Umberto I in Rome, Italy, from November 2020 to May 2021, and their newborns. Maternal and neonatal systemic immune responses were investigated by detecting spike-specific antibodies in serum, and the mucosal immune response was assessed by measuring specific antibodies in maternal breastmilk and infant saliva 48 hours after delivery and 2 months later. Exposures: Maternal infection with SARS-CoV-2 in late pregnancy. Main Outcomes and Measures: The systemic immune response was evaluated by the detection of SARS-CoV-2 IgG and IgA antibodies and receptor binding domain-specific IgM antibodies in maternal and neonatal serum. The mucosal immune response was assessed by measuring spike-specific antibodies in breastmilk and in infant saliva, and the presence of antigen-antibody spike IgA immune complexes was investigated in breastmilk samples. All antibodies were detected using an enzyme-linked immunosorbent assay. Results: In total, 28 mother-infant dyads (mean [SD] maternal age, 31.8 [6.4] years; mean [SD] gestational age, 38.1 [2.3] weeks; 18 [60%] male infants) were enrolled at delivery, and 21 dyads completed the study at 2 months' follow-up. Because maternal infection was recent in all cases, transplacental transfer of virus spike-specific IgG antibodies occurred in only 1 infant. One case of potential vertical transmission and 1 case of horizontal infection were observed. Virus spike protein-specific salivary IgA antibodies were significantly increased (P = .01) in infants fed breastmilk (0.99 arbitrary units [AU]; IQR, 0.39-1.68 AU) vs infants fed an exclusive formula diet (0.16 AU; IQR, 0.02-0.83 AU). Maternal milk contained IgA spike immune complexes at 48 hours (0.53 AU; IQR, 0.25-0.39 AU) and at 2 months (0.09 AU; IQR, 0.03-0.17 AU) and may have functioned as specific stimuli for the infant mucosal immune response. Conclusions and Relevance: In this cohort study, SARS-CoV-2 spike-specific IgA antibodies were detected in infant saliva, which may partly explain why newborns are resistant to SARS-CoV-2 infection. Mothers infected in the peripartum period appear to not only passively protect the newborn via breastmilk secretory IgA but also actively stimulate and train the neonatal immune system via breastmilk immune complexes.


Subject(s)
COVID-19/immunology , Immunoglobulin A/immunology , Milk, Human/immunology , Pregnancy Complications, Infectious/immunology , Adult , COVID-19/blood , COVID-19/transmission , COVID-19 Serological Testing , Female , Humans , Immunoglobulin A/isolation & purification , Immunoglobulin G/immunology , Immunoglobulin G/isolation & purification , Infant , Infant, Newborn , Infectious Disease Transmission, Vertical/prevention & control , Male , Pregnancy , Pregnancy Complications, Infectious/blood , Prospective Studies , SARS-CoV-2 , Saliva/immunology , Spike Glycoprotein, Coronavirus/immunology
20.
PLoS One ; 16(10): e0259094, 2021.
Article in English | MEDLINE | ID: covidwho-1496528

ABSTRACT

INTRODUCTION: We read, see and hear news from various media sources every day. A large majority of the news is negative. A previous study from our laboratory showed that reading negative news is associated with both increased stress reactivity (measured via the stress hormone cortisol) and recall of the negative news segments in women. OBJECTIVES: The present study investigated the effects of positive news on cortisol stress reactivity, memory and affect using a methodology highly similar to the study on negative news that was previously used by our team. METHODS: Sixty-two healthy participants aged between 18 and 35 years (81% women) were randomly exposed to either positive or neutral news segments, followed by a laboratory stressor. We assessed participants' affect three times during the procedure and measured cortisol in saliva eight times (at 10-minute intervals). Twenty-four hours later, participants were contacted by phone to assess their recall of the news segments. RESULTS: Results showed that exposure to positive news, relative to neutral news, did not modulate participants' cortisol levels in response to the laboratory stressor. Positive news had no impact on memory recall of the news and did not change participants' positive or negative affect. Bayes factors suggested that these nonsignificant results are not attributable to low statistical power. CONCLUSION: Contrary to negative news, positive and neutral news do not modulate stress reactivity, memory and affect. These results suggest that people can stay informed without physiological and psychological costs when the news to which they are exposed adopt a positive or neutral approach.


Subject(s)
Cognition/physiology , Emotions/physiology , Hydrocortisone/analysis , Mass Media , Memory/physiology , Stress, Psychological/physiopathology , Adolescent , Adult , Female , Humans , Male , Saliva/chemistry , Young Adult
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