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1.
European Respiratory Review ; 31(166):31, 2022.
Article in English | MEDLINE | ID: covidwho-2162291

ABSTRACT

BACKGROUND: The coronavirus disease 2019 pandemic has accelerated the adoption of virtual care strategies for the management of patients with obstructive sleep apnoea/hypopnoea syndrome (OSAHS).

2.
Asia Pac J Clin Oncol ; 2022.
Article in English | PubMed | ID: covidwho-2152580

ABSTRACT

INTRODUCTION: Cancer clinical trials have traditionally occurred in-person. However, the COVID-19 pandemic has forced adaptions of all aspects of cancer care (including clinical trials) so they can be delivered remotely. We aimed to quantify and qualify current use of telehealth and how it can be further improved and routinely integrated into cancer clinical trials in Australia. METHODS: We used a mixed-method study design, involving surveys of 14 multi-site Collaborative Cancer Clinical Trial Groups members across Australia (n = 98) and qualitative interviews with trial administrators and clinicians (n = 21). RESULTS: The results of our study indicated a strong willingness to use telehealth for certain transactions of clinical trials because it was perceived as a way of increasing efficiency and reach of services. Hybrid models (including telehealth and in-person methods), which considered transaction, cancer type, and patient preferences were most favorable. Additionally, telehealth allowed for greater equity to access and reduced trial burden but interestingly had little effect on increased diversity and recruitment. Factors influencing telehealth service implementation and uptake included communication among trial stakeholders, training, and learning from the experience of others in the clinical trials community. CONCLUSION: Many but not all aspects of clinical trial care are appropriate to be delivered via telehealth. A hybrid approach provides flexibility to trial delivery and may support greater equity of access to trials in the future. Our findings and actionable recommendations support the need for greater planning, training, and guidelines to enable telehealth to be better integrated into clinical trials. Opportunities exist to expand the use of remote patient monitoring to enable more objective data collection from trial participants in the future.

3.
Journal of Clinical Investigation ; 01:01, 2022.
Article in English | MEDLINE | ID: covidwho-2138387

ABSTRACT

BACKGROUND: The presence and reactivation of chronic viral infections such as Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV) have been proposed as potential contributors to Long COVID (LC), but studies in well-characterized post-acute cohorts of individuals with COVID-19 over a longer time course consistent with current case definitions of LC are limited.

5.
JAMA Netw Open ; 5(11): e2242240, 2022 Nov 01.
Article in English | MEDLINE | ID: covidwho-2119149

ABSTRACT

Importance: Herpes zoster infection after COVID-19 vaccination has been reported in numerous case studies. It is not known whether these cases represent increased reporting or a true increase in risk. Objective: To assess whether COVID-19 vaccination is associated with an increased risk of herpes zoster infection. Design, Setting, and Participants: This cohort study used a self-controlled risk interval (SCRI) design to compare the risk of herpes zoster in a risk interval of 30 days after COVID-19 vaccination or up to the date of the second vaccine dose with a control interval remote from COVID-19 vaccination (defined as 60-90 days after the last recorded vaccination date for each individual, allowing for a 30-day washout period between control and risk intervals). A supplemental cohort analysis was used to compare the risk of herpes zoster after COVID-19 vaccination with the risk of herpes zoster after influenza vaccination among 2 historical cohorts who received an influenza vaccine in the prepandemic period (January 1, 2018, to December 31, 2019) or the early pandemic period (March 1, 2020, to November 30, 2020). Data were obtained from Optum Labs Data Warehouse, a US national deidentified claims-based database. A total of 2 039 854 individuals who received any dose of a COVID-19 vaccine with emergency use authorization (BNT162b2 [Pfizer-BioNTech], mRNA-1273 [Moderna], or Ad26.COV2.S [Johnson & Johnson]) from December 11, 2020, through June 30, 2021, were eligible for inclusion. Individuals included in the SCRI analysis were a subset of the COVID-19-vaccinated cohort who had herpes zoster during either a risk or control interval. Exposures: Any dose of a COVID-19 vaccine. Main Outcomes and Measures: Incident herpes zoster, defined by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes and a prescription of a new antiviral medication or a dose increase in antiviral medication within 5 days of diagnosis. Results: Among 2 039 854 individuals who received any dose of a COVID-19 vaccine during the study period, the mean (SD) age was 43.2 (16.3) years; 1 031 149 individuals (50.6%) were female, and 1 344 318 (65.9%) were White. Of those, 1451 patients (mean [SD] age, 51.6 [12.6] years; 845 [58.2%] female) with a herpes zoster diagnosis were included in the primary SCRI analysis. In the SCRI analysis, COVID-19 vaccination was not associated with an increased risk of herpes zoster after adjustment (incidence rate ratio, 0.91; 95% CI, 0.82-1.01; P = .08). In the supplementary cohort analysis, COVID-19 vaccination was not associated with a higher risk of herpes zoster compared with influenza vaccination in the prepandemic period (first dose of COVID-19 vaccine: hazard ratio [HR], 0.78 [95% CI, 0.70-0.86; P < .001]; second dose of COVID-19 vaccine: HR, 0.79 [95% CI, 0.71-0.88; P < .001]) or the early pandemic period (first dose of COVID-19 vaccine: HR, 0.89 [95% CI, 0.80-1.00; P = .05]; second dose: HR, 0.91 [95% CI, 0.81-1.02; P = .09]). Conclusions and Relevance: In this study, there was no association found between COVID-19 vaccination and an increased risk of herpes zoster infection, which may help to address concerns about the safety profile of the COVID-19 vaccines among patients and clinicians.


Subject(s)
COVID-19 Vaccines , COVID-19 , Herpes Zoster , Adult , Female , Humans , Male , Middle Aged , Ad26COVS1 , Antiviral Agents/therapeutic use , BNT162 Vaccine , Cohort Studies , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Herpes Zoster/epidemiology , Herpes Zoster/prevention & control , Herpes Zoster/drug therapy , Herpes Zoster Vaccine/adverse effects , Influenza, Human/drug therapy
6.
Open Forum Infect Dis ; 9(11): ofac563, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2115743

ABSTRACT

Background: SARS-CoV-2 nucleocapsid antigen can be detected in plasma, but little is known about its performance as a diagnostic test for acute SARS-CoV-2 infection or infectious viral shedding among nonhospitalized individuals. Methods: We used data generated from anterior nasal and blood samples collected in a longitudinal household cohort of SARS-CoV-2 cases and contacts. Participants were classified as true positives if polymerase chain reaction (PCR) positive for SARS-CoV-2 and as true negatives if PCR negative and seronegative. Infectious viral shedding was determined by the cytopathic effect from viral culture. Stratified by 7 days after symptom onset, we constructed receiver operating characteristic (ROC) curves to describe optimized accuracy (Youden index), optimized sensitivity, and specificity. Results: Of 80 participants, 58 (73%) were true positives while 22 (27%) were true negatives. Using the manufacturer's cutoff of 1.25 pg/mL for evaluating infection, sensitivity was higher from 0 to 7 days (77.6% [95% confidence interval {CI}, 64%-88.2%]) than from 8 to 14 days (43.2% [95% CI, 31.1%-54.5%]) after symptom onset; specificity was unchanged at 100% (95% CI, 88.1%-100%). This test had higher sensitivity (100% [95% CI, 88.4%-100%]) and lower specificity (65% [95% CI, 40.8%-84.6%]) for infectious viral shedding as compared with infection, particularly within the first week of symptom onset. Although the presence of N-antigen correlated with infectious viral shedding (r = 0.63; P < .01), sensitivity still declined over time. Additional cutoffs from ROC curves were identified to optimize sensitivity and specificity. Conclusions: We found that this SARS-CoV-2 N-antigen test was highly sensitive for detecting early but not late infectious viral shedding, making it a viable screening test for community-dwelling individuals to inform isolation practices.

9.
Ir J Psychol Med ; 38(2): 93-98, 2021 06.
Article in English | MEDLINE | ID: covidwho-2096534

ABSTRACT

The medium- to long-term consequences of COVID-19 are not yet known, though an increase in mental health problems are predicted. Multidisciplinary strategies across socio-economic and psychological levels may be needed to mitigate the mental health burden of COVID-19. Preliminary evidence from the rapidly progressing field of psychedelic science shows that psilocybin therapy offers a promising transdiagnostic treatment strategy for a range of disorders with restricted and maladaptive habitual patterns of cognition and behaviour, notably depression, addiction and obsessive compulsive disorder. The COMPASS Pathways (COMPASS) phase 2b double-blind trial of psilocybin therapy in antidepressant-free, treatment-resistant depression (TRD) is underway to determine the safety, efficacy and optimal dose of psilocybin. Results from the Imperial College London Psilodep-RCT comparing the efficacy and mechanisms of action of psilocybin therapy to the selective serotonin reuptake inhibitor (SSRI) escitalopram will soon be published. However, the efficacy and safety of psilocybin therapy in conjunction with SSRIs in TRD is not yet known. An additional COMPASS study, with a centre in Dublin, will begin to address this question, with potential implications for the future delivery of psilocybin therapy. While at a relatively early stage of clinical development, and notwithstanding the immense challenges of COVID-19, psilocybin therapy has the potential to play an important therapeutic role for various psychiatric disorders in post-COVID-19 clinical psychiatry.


Subject(s)
COVID-19 , Hallucinogens , Psychiatry , Hallucinogens/therapeutic use , Humans , Psilocybin/therapeutic use , SARS-CoV-2
10.
PLoS One ; 17(10): e0276165, 2022.
Article in English | MEDLINE | ID: covidwho-2089421

ABSTRACT

The COVID-19 pandemic has posed unique academic, social, financial, and health-related challenges for young adults. While numerous studies have documented average increases in reported mental health issues in the general population, few have measured the magnitude of changes in mental health symptoms and sleep difficulties within individuals. Here, we measure the impact of the COVID-19 pandemic on mental health and sleep of university students pre- and mid-pandemic. Prior to the pandemic (Fall 2019), individuals (n = 23) were recruited to participate in an eight-day, comprehensive sleep study using Fitbit® actigraphy. Participants also completed detailed mental health and sleep surveys, including depression (BDI-II), anxiety (STAI), and sleep disturbance (PROMIS) surveys. One year later, these individuals repeated the study during the pandemic (Fall 2020); participants completed the original surveys and sleep study, in addition to a targeted survey on mental and sleep health due to the pandemic. Self-reported levels of anxiety, depression, and sleep disturbance, and sleep parameters, measured by actigraphy, were compared within the same individuals pre- and mid-pandemic. Self-report survey data revealed that three-quarters of participants experienced an increase in stress and anxiety due to the pandemic. In addition, intra-individual depression and anxiety symptoms increased to clinically significant levels within individuals from pre- to mid-pandemic. Over two-thirds of participants reported sleeping less, and more than half reported that their sleep health had worsened during the pandemic. Changes in sleep disturbance were positively associated with changes in depression and anxiety, reinforcing the robust relationship between poor sleep quality and mental health. Furthermore, individuals who reported greater sleep disturbance during the pandemic experienced lower relative proportions of both REM and deep sleep. The impact of the COVID-19 pandemic on university students is multi-faceted-mental health, sleep quality, and the amount of restorative sleep are negatively affected by the pandemic environment. These compounded effects exacerbate the health consequences of the pandemic and highlight a need for increased attention to the prevention and treatment of mental health disorders, particularly in vulnerable populations of young adults.


Subject(s)
COVID-19 , Sleep Initiation and Maintenance Disorders , Sleep Wake Disorders , Humans , Young Adult , COVID-19/epidemiology , Pandemics , Mental Health , SARS-CoV-2 , Depression/epidemiology , Depression/psychology , Anxiety/epidemiology , Anxiety/psychology , Sleep , Sleep Initiation and Maintenance Disorders/epidemiology , Sleep Wake Disorders/epidemiology
11.
J Infect Dis ; 2022 Sep 12.
Article in English | MEDLINE | ID: covidwho-2087789

ABSTRACT

Interferon (IFN)-specific autoantibodies have been implicated in severe COVID-19 and have been proposed as a potential driver of the persistent symptoms characterizing Long COVID, a type of post-acute sequelae of SARS-CoV-2 infection (PASC). We report than only two of 215 SARS-CoV-2 convalescent participants tested over 394 timepoints, including 121 people experiencing Long COVID symptoms, had detectable IFN-α2 antibodies. Both had been hospitalized during the acute phase of the infection. These data suggest that persistent anti-IFN antibodies, although a potential driver of severe COVID-19, are unlikely to contribute to Long COVID symptoms in the post-acute phase of the infection.

12.
JAMA ; 328(14): 1427-1437, 2022 10 11.
Article in English | MEDLINE | ID: covidwho-2084928

ABSTRACT

Importance: Evidence describing the incidence of severe COVID-19 illness following vaccination and booster with BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines is needed, particularly for high-risk populations. Objective: To describe the incidence of severe COVID-19 illness among a cohort that received vaccination plus a booster vaccine dose. Design, Setting, and Participants: Retrospective cohort study of adults receiving care at Veterans Health Administration facilities across the US who received a vaccination series plus 1 booster against SARS-CoV-2, conducted from July 1, 2021, to May 30, 2022. Patients were eligible if they had received a primary care visit in the prior 2 years and had documented receipt of all US Food and Drug Administration-authorized doses of the initial mRNA vaccine or viral vector vaccination series after December 11, 2020, and a subsequent documented booster dose between July 1, 2021, and April 29, 2022. The analytic cohort consisted of 1 610 719 participants. Exposures: Receipt of any combination of mRNA-1273 (Moderna), BNT162b2 (Pfizer-BioNTech), and Ad26.COV2.S (Janssen/Johnson & Johnson) primary vaccination series and a booster dose. Main Outcomes and Measures: Outcomes were breakthrough COVID-19 (symptomatic infection), hospitalization with COVID-19 pneumonia and/or death, and hospitalization with severe COVID-19 pneumonia and/or death. A subgroup analysis of nonoverlapping populations included those aged 65 years or older, those with high-risk comorbid conditions, and those with immunocompromising conditions. Results: Of 1 610 719 participants, 1 100 280 (68.4%) were aged 65 years or older and 132 243 (8.2%) were female; 1 133 785 (70.4%) had high-risk comorbid conditions, 155 995 (9.6%) had immunocompromising conditions, and 1 467 879 (91.1%) received the same type of mRNA vaccine (initial series and booster). Over 24 weeks, 125.0 (95% CI, 123.3-126.8) per 10 000 persons had breakthrough COVID-19, 8.9 (95% CI, 8.5-9.4) per 10 000 persons were hospitalized with COVID-19 pneumonia or died, and 3.4 (95% CI, 3.1-3.7) per 10 000 persons were hospitalized with severe pneumonia or died. For high-risk populations, incidence of hospitalization with COVID-19 pneumonia or death was as follows: aged 65 years or older, 1.9 (95% CI, 1.4-2.6) per 10 000 persons; high-risk comorbid conditions, 6.7 (95% CI, 6.2-7.2) per 10 000 persons; and immunocompromising conditions, 39.6 (95% CI, 36.6-42.9) per 10 000 persons. Subgroup analyses of patients hospitalized with COVID-19 pneumonia or death by time after booster demonstrated similar incidence estimates among those aged 65 years or older and with high-risk comorbid conditions but not among those with immunocompromising conditions. Conclusions and Relevance: In a US cohort of patients receiving care at Veterans Health Administration facilities during a period of Delta and Omicron variant predominance, there was a low incidence of hospitalization with COVID-19 pneumonia or death following vaccination and booster with any of BNT162b2, mRNA-1273, or Ad26.COV2.S vaccines.


Subject(s)
2019-nCoV Vaccine mRNA-1273 , Ad26COVS1 , BNT162 Vaccine , COVID-19 , Immunization, Secondary , 2019-nCoV Vaccine mRNA-1273/therapeutic use , Ad26COVS1/therapeutic use , Adult , Aged , BNT162 Vaccine/therapeutic use , COVID-19/epidemiology , COVID-19/mortality , COVID-19/prevention & control , Female , Hospitalization/statistics & numerical data , Humans , Immunization, Secondary/statistics & numerical data , Incidence , Male , Pneumonia/epidemiology , Pneumonia/etiology , Retrospective Studies , SARS-CoV-2 , United States/epidemiology , Vaccination , Veterans Health Services/statistics & numerical data
13.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.11.14.516398

ABSTRACT

COVID-19 placentitis, a rare complication of maternal SARS-CoV-2 infection, only shows detectable virus in the placenta of a subset of cases. We provide a deep multi-omic spatial characterisation of placentitis from obstetrically complicated maternal COVID-19 infection. We found that SARS-CoV-2 infected placentas have a distinct transcriptional and immunopathological signature. This signature overlaps with virus-negative cases supporting a common viral aetiology. An inverse correlation between viral load and disease duration suggests viral clearance over time. Quantitative spatial analyses revealed a unique microenvironment surrounding virus-infected trophoblasts characterised by PDL1-expressing macrophages, T-cell exclusion, and interferon blunting. In contrast to uninfected mothers, ACE2 was localised to the maternal side of the placental trophoblast layer of almost all mothers with placental SARS-CoV-2 infection, which may explain variable susceptibility to placental infection. Our results demonstrate a pivotal role for direct placental SARS-CoV-2 infection in driving the unique immunopathology of COVID-19 placentitis.

14.
Mmwr-Morbidity and Mortality Weekly Report ; 71(36):1151-1154, 2022.
Article in English | Web of Science | ID: covidwho-2068408

ABSTRACT

What is already known about this topic? Before emergence of the SARS-CoV-2 B.1.1.529 (Omicron) variant, infectious SARS-CoV-2 was unlikely to be cultured at high cycle threshold (Ct) values. Based on this, low Ct values, which are suggestive of high RNA levels, are sometimes used as surrogate markers for infectiousness. What is added by this report? In a longitudinal study including daily nasal swabbing, although Omicron BA.1 sublineage infections exhibited higher Ct values than did pre-Omicron infections, culturable Omicron virus was still detected. Among virus-positive specimens, Ct values were higher for Omicron than for pre-Omicron specimens, especially during the first week of illness. What are the implications for public health practice? Supporting CDC guidance, these data show that Ct values likely do not provide a consistent proxy for infectiousness across SARS-CoV-2 variants.

15.
European Eating Disorders Review ; 30(6):833-834, 2022.
Article in English | Web of Science | ID: covidwho-2068021
16.
Clin Infect Dis ; 75(Supplement_2): S193-S204, 2022 Oct 03.
Article in English | MEDLINE | ID: covidwho-2051359

ABSTRACT

BACKGROUND: Households have emerged as important venues for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Little is known, however, regarding the magnitude and determinants of household transmission in increasingly vaccinated populations. METHODS: From September 2020 to January 2022, symptomatic nonhospitalized individuals with SARS-CoV-2 infection by RNA detection were identified within 5 days of symptom onset; all individuals resided with at least 1 other SARS-CoV-2-uninfected household member. These infected persons (cases) and their household members (contacts) were subsequently followed with questionnaire-based measurement and serial nasal specimen collection. The primary outcome was SARS-CoV-2 infection among contacts. RESULTS: We evaluated 42 cases and their 74 household contacts. Among the contacts, 32 (43%) became infected, of whom 5 (16%) were asymptomatic; 81% of transmissions occurred by 5 days after the case's symptom onset. From 21 unvaccinated cases, 14-day cumulative incidence of SARS-CoV-2 infection among contacts was 18/40 (45% [95% confidence interval {CI}, 29%-62%]), most of whom were unvaccinated. From 21 vaccinated cases, 14-day cumulative incidence of SARS-CoV-2 infection was 14/34 (41% [95% CI, 25%-59%]) among all contacts and 12/29 (41% [95% CI, 24%-61%]) among vaccinated contacts. At least 1 comorbid condition among cases and 10 or more days of RNA detection in cases were associated with increased risk of infection among contacts. CONCLUSIONS: Among households including individuals with symptomatic SARS-CoV-2 infection, both vaccinated-to-vaccinated and unvaccinated-to-unvaccinated transmission of SARS-CoV-2 to household contacts was common. Because vaccination alone did not notably reduce risk of infection, household contacts will need to employ additional interventions to avoid infection.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Cohort Studies , Humans , Longitudinal Studies , RNA
17.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.10.17.22281193

ABSTRACT

During the early months of the SARS-CoV-2 pandemic, notable uncertainty emerged regarding the role of children in transmission dynamics. With time, it became more clear that children were susceptible to infection with SARS-CoV-2, but that the vast majority of children experienced mild symptoms with lower incidence of severe disease. This pattern remained consistent despite the later emergence of SARS-CoV-2 variants, including Delta and Omicron, even among children <5 ineligible for vaccination. The relative lack of severe disease in the pediatric population raised questions regarding viral kinetics and infectivity in children versus adults. We hypothesized that unique virologic features in children could explain this apparent decrease in symptoms and transmissibility early in the pandemic.

18.
British Journal of Surgery ; 109:vi3, 2022.
Article in English | EMBASE | ID: covidwho-2042532

ABSTRACT

Introduction: Virtual classroom training (VCT) is a novel educational method that permits accessible, distanced interactive expert instruction. We aimed to evaluate the efficacy of VCT in comparison to face-to-face training (FFT) and non-interactive computer-based learning (CBL) for basic surgical skills training. Method: 72 participants recruited from five London medical schools underwent stratified block randomisation into three equal intervention groups based on subjective and objective suturing experience. VCT was delivered via the BARCO weConnect platform and FFT was provided by expert instructors. Optimal student-to-teacher ratio was used, 12:1 for VCT and 4:1 for FFT. The assessed task was interrupted suturing with hand-tied knots. The primary outcome was post-intervention Objective Structured Assessment of Technical Skills (OSATS) score, adjudicated by two blinded experts and adjusted for baseline proficiency. Results: VCT was non-inferior to FFT (adjusted difference 0.44, 95% CI: -0.54 to 1.75, delta 0.675), VCT was superior to CBL (adjusted difference 1.69, 95% CI 0.41 to 2.96) and FFT was superior to CBL (adjusted difference 1.25, 95% CI 0.20 to 2.29). FFT alone was associated with student travel expenses (mean £4.88, SD 3.70). Instructor hours used per student for VCT and FFT were 0.25 and 0.75, respectively. Conclusions: VCT has a similar educational benefit to FFT and is a suitable modality of high-quality surgical skills education. VCT provides greater accessibility and resource efficiency compared to FFT. VCT satisfies the requirement for social distancing during the COVID-19 pandemic and is better than non-interactive CBL. VCT has the potential to improve global availability and accessibility of surgical skills training.

20.
J Infect Dis ; 226(10): 1688-1698, 2022 Nov 11.
Article in English | MEDLINE | ID: covidwho-2034602

ABSTRACT

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.


Subject(s)
Antibodies, Neutralizing , Vaccines , Humans , Antibodies, Viral
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