Public information needs and preferences on COVID-19: a cross-sectional study.

BACKGROUND: Right from the beginning of the SARS-CoV-2 pandemic the general public faced the challenge to find reliable and understandable information in the overwhelming flood of information. To enhance informed decision-making, evidence-based information should be provided. Aim was to explore the general public's information needs and preferences on COVID-19 as well as the barriers to accessing evidence-based information. METHODS: We performed a cross-sectional study. Nine hundred twenty-seven panel members were invited to an online survey (12/2020-02/2021). The HeReCa-online-panel is installed at the Martin Luther University Halle-Wittenberg to assess regularly the general public's view on health issues in five regions in Germany. The survey was set up in LimeSurvey, with nine items, multiple-choice and open-ended questions that allowed to gather qualitative data. Quantitative data were analysed descriptively and a content analysis was carried out to categorise the qualitative data. RESULTS: Six hundred thirty-six panel members provided data; mean age 52 years, 56.2% female, and 64.9% with higher education qualifications. Asked about relevant topics related to COVID-19, most participants selected vaccination (63.8%), infection control (52%), and long-term effects (47.8%). The following 11 categories were derived from the qualitative analysis representing the topics of interest: vaccination, infection control, long-term effects, therapies, test methods, mental health, symptoms, structures for pandemic control, infrastructure in health care, research. Participants preferred traditional media (TV 70.6%; radio 58.5%; newspaper 32.7%) to social media, but also used the internet as sources of information, becoming aware of new information on websites (28.5%) or via email/newsletter (20.1%). The knowledge question (Which European country is most affected by the SARS-CoV-2 pandemic?) was correctly answered by 7.5% of participants. The Robert Koch Institute (93.7%) and the World Health Organization (78%) were well known, while other organisations providing health information were rarely known (< 10%). Barriers to accessing trustworthy information were lack of time (30.7%), little experience (23.1%), uncertainty about how to get access (22.2%), complexity and difficulties in understanding (23.9%), and a lack of target group orientation (15,3%). CONCLUSIONS: There are extensive information needs regarding various aspects on COVID-19 among the general population. In addition, target-specific dissemination strategies are still needed to reach different groups.

Perspectives, benefits and challenges of a live OSCE during the COVID-19 pandemic in a cross-sectional study.

OBJECTIVES: Restrictions due to the COVID-19 pandemic mandated fundamental changes to student evaluations, including the administration of the observed structured clinical examination (OSCE). This study aims to conduct an in-person OSCE to verify students' practical skills under necessary infection control practices and the impact of face masks on student-patient interactions. DESIGN: Cross-sectional design. SETTING: The OSCE at Medical School of Tuebingen takes place in October 2020. PARTICIPANTS: A total of 149 students (third year of study) completed the survey (RR=80.1%). It was their first OSCE. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measure was how this type of OSCE was evaluated by participating students in regard to preparation, content and difficulty as well as in real life. Secondary outcome measures were how the implemented hygiene actions influenced the OSCE, including the interaction and communication between students and standardised patients (SPs). Items were rated on a 6-point Likert scale (1=completely to 6=not at all). Means, SDs, frequencies and percentages were calculated. RESULTS: 149 students, 32 SPs and 59 examiners participated. The students rated the OSCE with 2.37 (±0.52) for preparation and 2.07 (±0.32) for content. They perceived the interaction to be significantly disrupted by the use of face masks (3.03±1.54) (p<0.001) compared with the SPs (3.84±1.44) and the examiners (4.14±1.55). In general, the three groups considered the use of face masking the OSCE to be helpful (1.60±1.15). CONCLUSIONS: An in-person OSCE, even in the midst of a global pandemic, is feasible and acceptable to both students and faculty. When compared the students' results to previous students' results who completed the OSCE before the pandemic, the results indicated that students felt less prepared than under non-pandemic circumstances; however, their performances on this OSCE were not lower.

The role of face masks within in-patient psychotherapy: Results of a survey among inpatients and healthcare professionals.

Introduction: Face-to-face medical and psychotherapeutic treatments during the Corona pandemic often involve patients and health care providers wearing face masks. We performed a pilot survey assessing the subjective experience of wearing face masks during psychotherapy sessions regarding (i) feasibility, (ii) psychotherapeutic treatment and (iii) communication, emotion and working alliance in patients and healthcare professionals. Methods: A total of n = 62 inpatients (RR = 95.4%) and n = 33 healthcare professionals (RR = 86.8%) at an academic department of Psychosomatic Medicine and Psychotherapy participated in this survey anonymously. The items of the questionnaire were created by the interprofessional expert team and were based on existing instruments: (i) the Therapeutic Relationship Questionnaire and (ii) the German translation of Yalom's Questionnaire on Experiencing in Group Psychotherapy. Results: The majority of patients rate their psychotherapy as highly profitable despite the mask. In individual therapy, face masks seem to have a rather low impact on subjective experience of psychotherapy and the relationship to the psychotherapist. Most patients reported using alternative facial expressions and expressions. In the interactional group therapy, masks were rather hindering. On the healthcare professional side, there were more frequent negative associations of face masks in relation to (i) experiencing connectedness with colleagues, (ii) forming relationships, and (iii) therapeutic treatment. Discussion: Information should be given to patients about the possible effects of face masks on the recognition of emotions, possible misinterpretations and compensation possibilities through alternative stimuli (e.g., eye area) and they should be encouraged to ask for further information. Especially in group therapy, with patients from other cultural backgrounds and in cases of need for help (e.g., hearing impairment) or complex disorders, appropriate non-verbal gestures and body language should be used to match the intended emotional expression.

Where there are challenges, there are opportunities: An undergraduate medical students' teaching concept for mental health in times of COVID-19.

COVID-19 had a tremendous effect on medical education. Most teaching sessions had to be shifted online, posing additional stress and potential isolation on medical students. However, it also offered the promotion of innovative digital teaching concepts. In this article, an approach to undergraduate mental health training is presented and evaluated. The curriculum was designed according to Kern's six-step approach and consisted of asynchronous online material as well synchronous digital teaching and was accompanied by a plethora of newly developed teaching material (videos, fact sheets, etc.). Content covered the whole spectrum of diseases seen in a service of psychosomatic medicine and psychotherapy (i.e. anxiety, depression, trauma, somatoform and eating disorders, as well as motivational interviewing). Feedback from participants was collected, and exam results (written and practical) were compared to pre-COVID-19 times using t-tests for dependent and independent samples. Students were highly satisfied with the teaching (rating of 1.3 ± 0.6, n = 139 students). There was no significant difference from course evaluations before COVID-19 (1.5 ± 0.5, p > .05). The teaching also received an award in the students' competition "best digital teaching concept in summer term 2020". In the written exams, there was no significant difference between before COVID-19 (2.4 ± 0.45) and during COVID-19 times (1.6 ± 0.39; p > .05). In the practical objective structured clinical examination (OSCE), there was also no significant difference between students' judgement of the difficulty of the station (1.9 ± 0.22 vs 1.9 ± 0.31; p > .05) or how well-prepared they felt for the exam (2.0 ± 0.24 vs 2.0 ± 0.31; p > .05). However, there was a significant difference in terms of grades, with the pre-COVID-19 grades being significantly better (2.7 ± 0.37 vs 2.0 ± 0.44; p < .05), which reflects the difficulty of transferring practical skills training to an online setting. Students particularly valued the possibility of self-directed learning combined with personal guidance by departmental experts, reflecting the importance of wellbeing-centred medical education. The pandemic triggered overnight challenges for teaching mental health that may also offer the opportunity to think about worldwide teaching standards with easily accessible material and courses online. This may offer the opportunity to enthral medical students to become mental health specialists themselves.

Online student tutorials for effective peer teaching in digital times: a longitudinal quantitative study.

BACKGROUND: Peer-assisted learning represents a favoured method of teaching in universities. The COVID-19 pandemic has necessitated transferring medical education to digital formats, and subsequently, the question has arisen of whether online tutorials might be effective. This study, thus, investigated the efficacy of online tutorials in a communication course by assessing the interaction, verbal communication, and nonverbal communication of tutors and students. METHODS: Second-year medical students were invited to participate in this longitudinal quantitative study. Validated and self-developed questionnaires (e.g., Jefferson Empathy Scale) including 39 questions (rated on a 7- or 5-point Likert scale) were used to assess the different variables including interaction, verbal and nonverbal communication and students' learning success. RESULTS: Out of 165 medical students, 128 took part in the study. The students as well as tutors reported that they found each other likeable (Mstudents = 4.60±0.71; Mtutors = 4.38±0.53; p > .05). Learning success increased throughout the communication course (Cohen's d = 0.36-0.74). The nonverbal and verbal communication in the simulated patient (SP) encounter was also rated as high by all three groups (Mnonverbal = 3.90±0.83; Mverbal = 4.88±0.35). CONCLUSIONS: Interaction as well as nonverbal and verbal communication occurred in the online format, indicating that online tutorials can be effective. The implementation of SPs increases the efficiency of synchronous online learning as it enhances the simulation of a real patient-physician encounter. Thus, online tutorials are a valuable amendment to medical education.

Medical student attitudes on vaccination relevance: A mixed-method study.

BACKGROUND AND OBJECTIVES: The study aims to investigate the attitudes of medical students regarding the importance and relevance of vaccinations, whether vaccinations should be compulsory and how to employ a new teaching concept to deal with vaccination-critical parents. METHODS: This mixed-method study consists of a quantitative questionnaire and focus groups. Quantitative data were analysed by calculating the descriptive statistics, and interviews were analysed using Mayring's content analysis. RESULTS: A total of 170 medical students completed the questionnaire, and 59 students participated in 9 focus groups. Students reported that they felt more confident dealing with vaccination-critical parents after learning the new teaching concept. Similar results were found for medical students prior to and during the pandemic. During the pandemic, medical students viewed vaccinations for several diseases, such as measles or COVID-19, as important (range: M = 3.56, SD = 0.54 to M = 3.97, SD = 0.17). Similar results were found for medical students prior to the pandemic (range: M = 3.26, SD = 0.77 to M = 3.94, SD = 0.24). In the focus groups, however, medical students displayed controversial attitudes regarding compulsory vaccinations. CONCLUSIONS: While the medical students agreed on the use of vaccination for highly infectious diseases, their level of agreement decreased depending on the severity of the disease. Practical recommendations that come out of the study are creating a trustful relationship with and delivering information to patients.

COVID-19 Intensive Care-Evaluation of Public Information Sources and Current Standards of Care in German Intensive Care Units: A Cross Sectional Online Survey on Intensive Care Staff in Germany.

Backround: In February 2021, the first formal evidence and consensus-based (S3) guidelines for the inpatient treatment of patients with COVID-19 were published in Germany and have been updated twice during 2021. The aim of the present study is to re-evaluate the dissemination pathways and strategies for ICU staff (first evaluation in December 2020 when previous versions of consensus-based guidelines (S2k) were published) and question selected aspects of guideline adherence of standard care for patients with COVID-19 in the ICU. Methods: We conducted an anonymous online survey among German intensive care staff from 11 October 2021 to 11 November 2021. We distributed the survey via e-mail in intensive care facilities and requested redirection to additional intensive care staff (snowball sampling). Results: There was a difference between the professional groups in the number, selection and qualitative assessment of information sources about COVID-19. Standard operating procedures were most frequently used by all occupational groups and received a high quality rating. Physicians preferred sources for active information search (e.g., medical journals), while nurses predominantly used passive consumable sources (e.g., every-day media). Despite differences in usage behaviour, the sources were rated similarly in terms of the quality of the information on COVID-19. The trusted organizations have not changed over time. The use of guidelines was frequently stated and highly recommended. The majority of the participants reported guideline-compliant treatment. Nevertheless, there were certain variations in the use of medication as well as the criteria chosen for discontinuing non-invasive ventilation (NIV) compared to guideline recommendations. Conclusions: An adequate external source of information for nursing staff is lacking, the usual sources of physicians are only appropriate for the minority of nursing staff. The self-reported use of guidelines is high.

'Student tutors go online' - Investigation of cognitive and social congruence in online student tutorials - a longitudinal study.

The concept of peer-assisted learning (PAL) has been implemented at many medical faculties. Due to the Covid-19 pandemic, parts of the medical education experience transitioned to digital formats. However, little is known about PAL and online student tutorials. PAL is effective due to cognitive and social congruence. This study aims to investigate these concepts in an online student tutorial on taking a patient's medical history. This longitudinal study took place in a preclinical communication course on how to take a patient's medical history. In an online student tutorial, the students learned how to take a patient's psychosocial medical history. Using standardised questionnaires, cognitive and social congruence were assessed. T-tests of independent samples were performed for data comparison. The participants included 128 second-year medical students and 5 student tutors. Cognitive congruence (Mstudent = 4.19 ± 0.56; Mstudenttutor = 4.04 ± 0.57) and social congruence (MStudent = 4.25 ± 0.56; MStudenttutor = 4.06 ± 0.57) were high for both students and student tutors in the online setting. In comparison to the face-to-face group, students in the online setting considered the student tutors to be significantly (p < .05) more socially congruent. Learning success increased during the course; however, it was not influenced by cognitive congruence. Cognitive and social congruence are high in an online setting. The students' learning success increased during the online tutorial. Based on the higher level of social congruence, student tutors might be very motivated to be open and approachable in an online setting. Simultaneously, students might pay more attention and participate actively in the online setting. Social and cognitive congruence contribute to the effectiveness of online student tutorials and, thus, online student tutorials should be integrated into medical training.

Perspectives, benefits and challenges of a live OSCE during the COVID-19 pandemic in a cross-sectional study

Objectives Restrictions due to the COVID-19 pandemic mandated fundamental changes to student evaluations, including the administration of the observed structured clinical examination (OSCE). This study aims to conduct an in-person OSCE to verify students’ practical skills under necessary infection control practices and the impact of face masks on student–patient interactions. Design Cross-sectional design. Setting The OSCE at Medical School of Tuebingen takes place in October 2020. Participants A total of 149 students (third year of study) completed the survey (RR=80.1%). It was their first OSCE. Primary and secondary outcome measures Primary outcome measure was how this type of OSCE was evaluated by participating students in regard to preparation, content and difficulty as well as in real life. Secondary outcome measures were how the implemented hygiene actions influenced the OSCE, including the interaction and communication between students and standardised patients (SPs). Items were rated on a 6-point Likert scale (1=completely to 6=not at all). Means, SDs, frequencies and percentages were calculated. Results 149 students, 32 SPs and 59 examiners participated. The students rated the OSCE with 2.37 (±0.52) for preparation and 2.07 (±0.32) for content. They perceived the interaction to be significantly disrupted by the use of face masks (3.03±1.54) (p<0.001) compared with the SPs (3.84±1.44) and the examiners (4.14±1.55). In general, the three groups considered the use of face masking the OSCE to be helpful (1.60±1.15). Conclusions An in-person OSCE, even in the midst of a global pandemic, is feasible and acceptable to both students and faculty. When compared the students’ results to previous students’ results who completed the OSCE before the pandemic, the results indicated that students felt less prepared than under non-pandemic circumstances;however, their performances on this OSCE were not lower.

mRNA vaccination in octogenarians 15 and 20 months after recovery from COVID-19 elicits robust immune and antibody responses that include Omicron.

Knowledge about the impact of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of the elderly on mRNA vaccination response is needed to appropriately address the demand for additional vaccinations in this vulnerable population. Here, we show that octogenarians, a high-risk population, mount a sustained SARS-CoV-2 spike-specific immunoglobulin G (IgG) antibody response for 15 months following infection. This response boosts antibody levels 35-fold upon receiving a single dose of BNT162b2 mRNA vaccine 15 months after recovery from coronavirus disease 2019 (COVID-19). In contrast, antibody responses in naive individuals boost only 6-fold after a second vaccine. Spike-specific angiotensin-converting enzyme 2 (ACE2) antibody binding responses in the previously infected octogenarians following two vaccine doses exceed those found in a naive cohort after two doses. RNA sequencing (RNA-seq) demonstrates activation of interferon-induced genetic programs, which persist only in the previously infected. A preferential increase of specific immunoglobulin G heavy chain variable (IGHV) clonal transcripts that are the basis of neutralizing antibodies is observed only in the previously infected nuns.

AMEE Guide to ethical teaching in online medical education: AMEE Guide No. 146.

The Covid-19 pandemic necessitated Emergency Remote Teaching (ERT): the sudden move of educational materials online. While ERT served its purpose, medical teachers are now faced with the long-term and complex demands of formal online teaching. One of these demands is ethical online teaching. Although ethical teaching is practiced in face-to-face situations, online teaching has new ethical issues that must be accommodated, and medical teachers who wish to teach online must be aware of these and need to teach ethically. This Guide leads the medical teacher through this maze of complex ethical issues to transform ERT into ethical online teaching. It begins by setting the context and needs and identifies the relevant fundamental ethical principles and issues. It then guides the medical teacher through the practical application of these ethical principles, covering course design and layout (including the curriculum document, implementation, on-screen layouts, material accessibility), methods of interaction (synchronous and asynchronous), feedback, supervision and counselling, deeper accessibility issues, issues specific to clinical teaching, and assessment. It then discusses course reviews (peer-review and student evaluations), student monitoring and analytics, and archiving. The Guide aims to be a useful tool for medical teachers to solidly ground their online teaching practices in ethical principles.

mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits similar B cell expansion, neutralizing responses, and protection from Omicron.

SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-matched vaccines would enhance protection. Here, nonhuman primates that received mRNA-1273 at weeks 0 and 4 were boosted at week 41 with mRNA-1273 or mRNA-Omicron. Neutralizing titers against D614G were 4,760 and 270 reciprocal ID50 at week 6 (peak) and week 41 (preboost), respectively, and 320 and 110 for Omicron. 2 weeks after the boost, titers against D614G and Omicron increased to 5,360 and 2,980 for mRNA-1273 boost and 2,670 and 1,930 for mRNA-Omicron, respectively. Similar increases against BA.2 were observed. Following either boost, 70%-80% of spike-specific B cells were cross-reactive against WA1 and Omicron. Equivalent control of virus replication in lower airways was observed following Omicron challenge 1 month after either boost. These data show that mRNA-1273 and mRNA-Omicron elicit comparable immunity and protection shortly after the boost.

[COVID-19 pandemic: preferences and barriers for dissemination of evidence syntheses : Survey of intensive care personnel in Germany]. / COVID-19-Pandemie: Präferenzen und Barrieren für die Disseminierung von Evidenzsynthesen : Befragung des intensivmedizinischen Personals in Deutschland.

BACKGROUND: In the context of COVID-19, the German CEOsys project (COVID-19 Evidenz Ökosystem, www.covid-evidenz.de ) identifies, evaluates and summarizes the results of scientific studies to obtain evidence on this disease. The evidence syntheses are used to derive specific recommendations for clinical practice and to contribute to national guidelines. Besides the necessity of conducting good quality evidence syntheses during a pandemic, just as important is that the dissemination of evidence needs to be quick and efficient, especially in a health crisis. The CEOsys project has set itself this challenge. OBJECTIVE: Preparing the most suitable distribution of evidence syntheses as part of the CEOsys project tasks. METHODS: Intensive care unit (ICU) personnel in Germany were surveyed via categorical and free text questions. The survey focused on the following topics: evidence syntheses, channels and strategies of distribution, possibility of feedback, structure and barriers of dissemination and trustworthiness of various organizations. Profession, qualification, setting and size of the facility were recorded. Questionnaires were pretested throughout the queried professions (physician, nurse, others). The survey was anonymously carried out online through SosciSurvey® and an e­mail was sent directly to 940 addresses. The survey was launched on 3 December, a reminder was sent after 14 days and it ended on 31 December. The survey was also announced via e­mail through DIVI. RESULTS: Of 317 respondents 200 completed the questionnaire. All information was analyzed including the responses from incomplete questionnaires. The most stated barriers were lack of time and access. Especially residents and nurses without specialization in intensive care mentioned uncertainty or insufficient experience in dealing with evidence syntheses as a barrier. Active distribution of evidence syntheses was clearly preferred. More than half of the participants chose websites of public institutions, medical journals, professional societies and e­mail newsletters for drawing attention to new evidence syntheses. Short versions, algorithms and webinars were the most preferred strategies for dissemination. Trust in organizations supplying information on the COVID-19 pandemic was given to professional societies and the Robert Koch Institute (RKI) as the German governmental institute for infections and public health. The respondents' prioritized topics are long-term consequences of the disease, protection of medical personnel against infection and possibilities of ventilation treatment. CONCLUSION: Even though universally valid, evidence syntheses should be actively brought to the target audience, especially during a health crisis such as the COVID-19 pandemic with its exceptional challenges including lack of time and uncertainties in patient care. The contents should be clear, short (short versions, algorithms) and with free access. E­mail newsletters, websites or medical journals should continuously report on new evidence syntheses. Professional societies and the governmental institute for infections and public health should be involved in dissemination due to their obvious trustworthiness.

Attitudes toward a COVID-19 vaccine and vaccination status in cancer patients: a cross-sectional survey.

PURPOSE: We aim to assess attitudes toward a COVID-19 vaccine and vaccination status in cancer patients and to explore additional factors such as the level of information and comprehensibility and accessibility of this information, anxiety symptoms in general and toward COVID-19, and general health literacy. METHODS: We included 425 outpatients (mean age 61.4, age range 30-88 years, 60.5% women) of the Psychosocial Counseling Center for Cancer patients of the Department of Medical Psychology and Medical Sociology, Leipzig. We recorded attitudes toward a COVID-19 vaccine and vaccination status via self-report. The impact of psychosocial factors, including anxiety (GAD-7), COVID-19-specific anxiety (OCS; FCV-19S) and health literacy (HLS-EU-Q16) were analyzed with point-biserial correlations using Pearson's r. RESULTS: We found that the vast majority (95.5%) reported being vaccinated against COVID-19 and that overall trust in safety and protective effects of a COVID-19 vaccine was high (90.9%). The vaccination readiness among nonvaccinated cancer survivors was low to very low with "fear of side effects" the most mentioned (72.2%) reason against a COVID-19 vaccine. There was no significant correlation between vaccination status and fear or anxiety symptomatology, and health literacy. Obsessive thoughts about COVID-19 was significantly higher in nonvaccinated cancer patients. CONCLUSIONS: Majority of respondents are positive about COVID-19 vaccine, accompanied by a very high rate of COVID-19 immunization in our sample. Further studies with a larger sample of nonvaccinated cancer patients should further investigate the relationship on fear and vaccination hesitancy and align communication strategies accordingly.

Protection from SARS-CoV-2 Delta one year after mRNA-1273 vaccination in rhesus macaques coincides with anamnestic antibody response in the lung.

mRNA-1273 vaccine efficacy against SARS-CoV-2 Delta wanes over time; however, there are limited data on the impact of durability of immune responses on protection. Here, we immunized rhesus macaques and assessed immune responses over 1 year in blood and upper and lower airways. Serum neutralizing titers to Delta were 280 and 34 reciprocal ID50 at weeks 6 (peak) and 48 (challenge), respectively. Antibody-binding titers also decreased in bronchoalveolar lavage (BAL). Four days after Delta challenge, the virus was unculturable in BAL, and subgenomic RNA declined by ∼3-log10 compared with control animals. In nasal swabs, sgRNA was reduced by 1-log10, and the virus remained culturable. Anamnestic antibodies (590-fold increased titer) but not T cell responses were detected in BAL by day 4 post-challenge. mRNA-1273-mediated protection in the lungs is durable but delayed and potentially dependent on anamnestic antibody responses. Rapid and sustained protection in upper and lower airways may eventually require a boost.

Protection against SARS-CoV-2 Beta variant in mRNA-1273 vaccine-boosted nonhuman primates.

Neutralizing antibody responses gradually wane against several variants of concern (VOCs) after vaccination with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine messenger RNA-1273 (mRNA-1273). We evaluated the immune responses in nonhuman primates that received a primary vaccination series of mRNA-1273 and were boosted about 6 months later with either homologous mRNA-1273 or heterologous mRNA-1273.ß, which encompasses the spike sequence of the B.1.351 Beta variant. After boost, animals had increased neutralizing antibody responses across all VOCs, which was sustained for at least 8 weeks after boost. Nine weeks after boost, animals were challenged with the SARS-CoV-2 Beta variant. Viral replication was low to undetectable in bronchoalveolar lavage and significantly reduced in nasal swabs in all boosted animals, suggesting that booster vaccinations may be required to sustain immunity and protection.

Stabilized coronavirus spike stem elicits a broadly protective antibody.

Current coronavirus (CoV) vaccines primarily target immunodominant epitopes in the S1 subunit, which are poorly conserved and susceptible to escape mutations, thus threatening vaccine efficacy. Here, we use structure-guided protein engineering to remove the S1 subunit from the Middle East respiratory syndrome (MERS)-CoV spike (S) glycoprotein and develop stabilized stem (SS) antigens. Vaccination with MERS SS elicits cross-reactive ß-CoV antibody responses and protects mice against lethal MERS-CoV challenge. High-throughput screening of antibody-secreting cells from MERS SS-immunized mice led to the discovery of a panel of cross-reactive monoclonal antibodies. Among them, antibody IgG22 binds with high affinity to both MERS-CoV and severe acute respiratory syndrome (SARS)-CoV-2 S proteins, and a combination of electron microscopy and crystal structures localizes the epitope to a conserved coiled-coil region in the S2 subunit. Passive transfer of IgG22 protects mice against both MERS-CoV and SARS-CoV-2 challenge. Collectively, these results provide a proof of principle for cross-reactive CoV antibodies and inform the development of pan-CoV vaccines and therapeutic antibodies.

A platform incorporating trimeric antigens into self-assembling nanoparticles reveals SARS-CoV-2-spike nanoparticles to elicit substantially higher neutralizing responses than spike alone.

Antigens displayed on self-assembling nanoparticles can stimulate strong immune responses and have been playing an increasingly prominent role in structure-based vaccines. However, the development of such immunogens is often complicated by inefficiencies in their production. To alleviate this issue, we developed a plug-and-play platform using the spontaneous isopeptide-bond formation of the SpyTag:SpyCatcher system to display trimeric antigens on self-assembling nanoparticles, including the 60-subunit Aquifex aeolicus lumazine synthase (LuS) and the 24-subunit Helicobacter pylori ferritin. LuS and ferritin coupled to SpyTag expressed well in a mammalian expression system when an N-linked glycan was added to the nanoparticle surface. The respiratory syncytial virus fusion (F) glycoprotein trimer-stabilized in the prefusion conformation and fused with SpyCatcher-could be efficiently conjugated to LuS-SpyTag or ferritin-SpyTag, enabling multivalent display of F trimers with prefusion antigenicity. Similarly, F-glycoprotein trimers from human parainfluenza virus-type 3 and spike-glycoprotein trimers from SARS-CoV-2 could be displayed on LuS nanoparticles with decent yield and antigenicity. Notably, murine vaccination with 0.08 µg of SARS-CoV-2 spike-LuS nanoparticle elicited similar neutralizing responses as 2.0 µg of spike, which was ~ 25-fold higher on a weight-per-weight basis. The versatile platform described here thus allows for multivalent plug-and-play presentation on self-assembling nanoparticles of trimeric viral antigens, with SARS-CoV-2 spike-LuS nanoparticles inducing particularly potent neutralizing responses.

mRNA-1273 protects against SARS-CoV-2 beta infection in nonhuman primates.

B.1.351 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant most resistant to antibody neutralization. We demonstrate how the dose and number of immunizations influence protection. Nonhuman primates received two doses of 30 or 100 µg of Moderna's mRNA-1273 vaccine, a single immunization of 30 µg, or no vaccine. Two doses of 100 µg of mRNA-1273 induced 50% inhibitory reciprocal serum dilution neutralizing antibody titers against live SARS-CoV-2 p.Asp614Gly and B.1.351 of 3,300 and 240, respectively. Higher neutralizing responses against B.1.617.2 were also observed after two doses compared to a single dose. After challenge with B.1.351, there was ~4- to 5-log10 reduction of viral subgenomic RNA and low to undetectable replication in bronchoalveolar lavages in the two-dose vaccine groups, with a 1-log10 reduction in nasal swabs in the 100-µg group. These data establish that a two-dose regimen of mRNA-1273 will be critical for providing upper and lower airway protection against major variants of concern.

Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates.

Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. Here, nonhuman primates (NHPs) received either no vaccine or doses ranging from 0.3 to 100 µg of the mRNA-1273 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. mRNA-1273 vaccination elicited circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs after SARS-CoV-2 challenge in vaccinated animals and most strongly correlated with levels of anti­S antibody and neutralizing activity. Lower antibody levels were needed for reduction of viral replication in the lower airway than in the upper airway. Passive transfer of mRNA-1273­induced immunoglobulin G to naïve hamsters was sufficient to mediate protection. Thus, mRNA-1273 vaccine­induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 in NHPs.