Attitudes of French adults toward COVID-19 vaccination.

Reticence toward COVID-19 vaccination is more prevalent among women, people with low income, people who feel close to parties on the Far Right and Far Left and people who feel close to no party at all. It illustrates a mistrust of state institutions and policy-makers in general. The arguments in favor of Covid vaccine refusal are safety concern, and the contention that COVID is a mild disease. That said, vaccine hesitancy is vaccine-specific, with a major difference between Pfizer/Moderna and Oxford-AstraZeneca vaccines. Aside from vaccine hesitancy, vaccination intention rate has approached 80%.

What are the prospects for durable immune control?

During the SARS CoV-2 primary infection, the neutralizing antibodies focused against the spike (S) glycoproteins are responsible for blockage of virus-host cell interaction. The cellular response mediated by CD4+ and CD8+ T-cells is responsible for control of viremia. Immune memory against SARS-CoV-2 depends on virus type, replication kinetics and route of penetration. The formation and persistence of germinal centers are critical for the generation of affinity-matured plasma cells and memory B cells capable of mediating durable immunity. They can persist up to 30 weeks after vaccination and several months after infection. Heterogeneity in the longevity of the vaccination-induced GC response is significant.

Longitudinal humoral immune response against COVID-19 adenovirus-based vaccines in patients with multiple sclerosis from Argentina undergoing immunosuppressive treatment

Introduction: Most reports related to humoral immune response to COVID 19 vaccines in people with Multiple Sclerosis (pwMS) were performed on mRNA-based vaccines. Objective(s): to analyze the longitudinal humoral immune responses to adenovirus-based vaccines (Sputnik V and AZD1222) in pwMS under different diseases modifying therapies (DMTs) Methods: IgG anti- SARS-COV-2 spike titers in a cohort of 101 pwMS and 28 healthy controls (HC) were measured 6 weeks after vaccination using the COVID-AR kit according to the manufacture instructions. Both patients and controls received two or three doses of Sputnik, AZD1222 or a mixed schedule (MS) of both vaccines. The neutralizing capacity was evaluated by measuring antibody neutralizing titers using SARS COV-2 pseudotyped particles. Result(s): 60.5% of pwMS were female, mean EDSS: 2.49 +/-1.5, age: 36.6 +/-10.7, disease duration 7.6 +/- 5.1 years. DMTs: 45 pwMS were under fingolimod, 23 under dimethyl fumarate, 14 under cladribine and 19 under antiCD20 monoclonal antibodies. Vaccines: 35.7% Sputnik V, 51.9% AZD1222 and 12.4 % MS. No antibody response to a 2nd dose was found in 41.3% of pwMS under fingolimod and 73.6% under antiCD20. We found a correlation between lower lymphocyte count and lower antibody titers in pwMS under fingolimod (r: 0.67, 95% CI: 0.46-0.81, p=<=0.0001). A correlation was also found between the antibody titer and the last dose of antiCD20 (r: 0.49, 95% CI: 0.03-0.7, p=0.03). In March 2022, 57 pwMS received their 3nddose, 6 patients under fingolimod and 7 under antiCD20 remained without any antibody response. We did not find differences in the neutralization capacity with different DMT and or vaccines. Multivariate regression analysis showed antiCD20 (beta= -,349, 95% CI: -3655.6-369.01, p=0.017) and fingolimod (beta=-,399, 95% CI: -3363.8-250.9, p=0.023) treatments as independent factor associated with low antibody response (r2 adjusted=0.157). Conclusion(s): This is the first report of longitudinal humoral immune response of patients under adenovirus-based vaccines, specially Sputnik V, that demonstrate that these vaccines have similar results to those obtained with mRNA-based vaccines.

What progress has been made in treatment of immunocompromised COVID-19 patients?

While immunocompromised patients are at very high risk of developing severe COVID 19, few of them have been enrolled in studies aimed at evaluating treatments. In the early stages of research on this disease, glucocorticoid therapy became the standard of care for patients requiring oxygen supplementation. It has been demonstrated that the neutralizing monoclonal antibody combination of Casirivimab and Imdevimab reduced (by 28 days) mortality in COVID-19 patients admitted to hospital who were seronegative at baseline, but not in those who were seropositive. There is still a need to determine the place of available various antivirals (Molnupiravir or Nirmatrelvir plus Ritonavir) and passive immunotherapies (Sotrovimab…) as well as convalescent plasma therapy in immunocompromised settings.

SARS-CoV-2 genetic diversity: Its impact on vaccine efficacy.

SARS CoV 2 S-glycoproteins play a crucial role in the entry steps of viral particles. Due to their surface location, they are the main target for host immune responses and the focus of most vaccine strategies. The D614G mutation identified in late January became dominant during March 2020, rendering SARS-CoV-2 more infectious. In April 2020, the Alpha, Beta and Gamma variants emerged simultaneously in Asia, South Africa, and South America, respectively. They were 1.6 to 2 times more transmissible than the ancestral strain. The currently dominant Omicron variant (BA.2) is not a direct descendant from the D614G lineage, but rather emerged from the BA.1 variant (as did BA.4 and BA.5). It is substantially different from all the other variants. It presents significantly reduced susceptibility to antibody neutralization: after 2 doses of mRNA-vaccine, neutralizing titers to Omicron are 41 to 84 times lower than neutralization titers to D614G. That said, a booster dose of mRNA-vaccine increases Omicron neutralization titers and reduces the risk of severe infection.

SCARED INTO SCURVY: NUTRITIONAL DEFICIENCIES DUE TO FEAR OF COVID-19

CASE: A 26-year-old male presented to the hospital with 2 weeks of difficulty ambulating, bilateral lower extremity rash, and diffuse myalgia with arthralgia. Symptoms began suddenly with lower extremity pain and difficulty getting up from his chair. He denied sensory changes, and pain was most prominent at the hips and knees. He also noticed a new rash on his thighs and mild bleeding from his gums. All other review of systems were negative. He denied family history of autoimmune disease and was without any personal chronic medical conditions. He was the primary caretaker of his grandmother and had stayed isolated at home throughout the COVID-19 pandemic. Vital signs were normal, and physical exam revealed 3/5 right hip flexion, 4/5 left hip flexion, and 4/5 right knee flexion and extension. Inspection of his rash demonstrated follicular hyperkeratosis, perifollicular erythema, and corkscrew hairs. Initial lab work revealed anemia, hypothyroidism, hypotonic hyponatremia, hypocalcemia, an elevated CK, ESR, and CRP. Extensive infectious and autoimmune workup was unrevealing. Further interview revealed that his diet consisted of soy milk, potato chips, crackers, peanut butter, and water in the preceding 6 months. This was intentionally done to reduce exposure to SARS- CoV-2. Further evaluation revealed Vitamin C, Vitamin D, Zinc, and Iron deficiencies. His presenting symptoms and rash were ultimately attributed to hypothyroid myopathy and Scurvy. Following thyroid replacement therapy, dietary education, and nutritional supplementation, he experienced improvement in his symptoms and rash. IMPACT/DISCUSSION: It has become evident that the COVID-19 pandemic has had significant psychosocial impact on the public, with substantial portions of our population experiencing increased fear and anxiety. Interestingly, a longitudinal study by Pan et al. found that Dutch patients without prior mental health disorders, such as our patient, had a more significant increase in depression, anxiety, and worry during the pandemic. To add to this, a study by Izzo et al. found that a substantial part of their study population had turned to unhealthy nutritional behaviors during the pandemic. Furthermore, Nguyen et al. demonstrated that increased health literacy was protective against the negative psychological impacts of the COVID-19 pandemic. Our case presents an outcome of merging pandemic fears with poor health literacy. It also highlights the critical role of the clinician as historian. Conceptualizing the patient's clinical presentation with their daily life ultimately led to appropriate diagnostic workup and treatment. CONCLUSION: As the COVID-19 pandemic continues, its broader and less apparent effects will continue to be seen. Clinicians must remain vigilant in assessing the changes in their patients' daily lives with open and invested communication. Early identification of potentially harmful changes and improved health education could prevent potential complications.

HEALTH CARE NEEDS OF RURAL OLDER ADULT CANCER SURVIVORS

Introduction Older (65+) cancer survivors have unique complications after chemotherapy, including physical and cognitive impairments and geriatric syndromes. Survivorship research has generally focused on younger and urban populations. We explored the survivorship needs of rural older adult survivors. Methods Thirteen rural older adults who finished curative-intent chemotherapy completed open-ended interviews and health surveys. Transcripts were coded independently by two coders using thematic analysis. Results Mean age was 74 (SD=5.1). Most participants were non-Hispanic White (92.3%), female (69.2%), and married (46.2%). All had health insurance and 76.9% had an annual income <$50k. Most were diagnosed with colon (46.2%) or lung (23.1%) cancer. Themes (Table 1) included: 1) No survivorship care plan developed (100%), 2) No coordination between primary and oncology team (100%), 3) Symptomatic toxicities present (100%), 4) No discussion on long-term chemotherapy effects (61.4%);5) Financial challenges (53.8%), 6) Isolation due to COVID19 pandemic (38.5%), 7) Organizational barriers to care (30.8%), 8) Patient does what doctor says (23.1%), and Recommendations included: 1) referral to support groups (23.1%), 2) discussion on survivorship care (23.1%), and 2) information on exercise (15.4%) Conclusions Rural older survivors have unmet survivorship needs. Aging-sensitive interventions may lead to improved survivorship health post-treatment among rural older adult survivors.

Pre-existing and post-covid-19 immune responses to sars-cov-2 in cancer patients

Cancer patients are at increased risk for critical illness upon COVID-19. We assessed antibody and T cell responses in unexposed and SARS-CoV-2 convalescent cancer patients to characterize SARS-CoV-2 immunity and to identify immunological parameters contributing to increased morbidity and mortality in COVID-19 cancer patients. Immune responses were assessed in unexposed (n = 199) and SARS-CoV-2-infected cancer patients (n = 17), comprising different hematological malignancies (HM) and solid tumor entities. T cell responses were assessed by IFN-g ELISPOT using previously defined cross-reactive and SARS-CoV-2-specific T cell epitopes (Nelde et al., Nat Immunol 2021). SARS-CoV-2 convalescents without cancer (n = 193) and unexposed healthy volunteers (HV, n = 94) served as reference groups. Whereas pre-existing SARS-CoV-2 cross-reactive CD4+ T cell responses were detectable in a high proportion of HV (78%) and solid tumor patients (77%), frequency was substantially lower in unexposed HM patients (34%). Concordantly, HM patients showed significantly higher proportions of CD4+ T cells expressing PD-1, LAG-3 and TIM-3, indicating T cell exhaustion as a potential underlying cause for the reduced T cell reactivity. In SARS-CoV-2 convalescents, no difference in antibody positivity was noted between cancer patients and HV. T cell response analyses showed comparable recognition frequencies of SARS-CoV-2-specific HLA class I and HLA-DR epitopes in both groups, whereas the frequency of HLA-DR cross-reactive T cell responses was significantly reduced in cancer patients. Again, this was attributable to a markedly reduced frequency of cross-reactive CD4+ T cell responses in HM patients. Analysis of T cell responses to single HLA-DR peptides (n = 20) after 12-day in vitro expansion further revealed reduced T cell expandability for 73% of SARS-CoV-2-derived peptides in COVID-19 cancer patients. Moreover, diversity of SARS-CoV-2 T cell responses (i.e. recognition of multiple different T cell epitopes) was significantly reduced in COVID-19 HM patients (20% recognized peptides) compared to solid tumor patients (35%) and HV (50%), and reduced T cell diversity was associated with a more severe course of COVID-19. In summary, our results identify impaired SARS-CoV-2 T cell immunity as a determinant for poor outcome of COVID-19 in cancer patients, particularly in HM. These findings guide the development of therapeutic measures and vaccines for this vulnerable patient population. Disclosure: Malte Roerden: No conflict of interest disclosed. Juliane S. Walz: Honoraria: Juliane S. Walz is listed as inventor for patents on peptides described in the research.;Expert Testimony: Bundesministerium für Bildung und Forschung (BMBF), German Cancer Consortium (DKTK), Deutsche Forschungsgemeinschaft (DFG), Wilhelm Sander Stiftung, José Carreras Leukämie-Stiftung, Fortüne-Programm der Universität Tübingen.

Safety of COVID-19 vaccines in patients with multiple sclerosis from Latin America

Introduction: Patients with MS (pwMS) are currently receiving different COVID-19 vaccines in several Latin American countries. However, questions arise around the safety of these vaccines and whether vaccination might increase the risk of relapse activity. Therefore, we aimed to assess the safety and occurrence of relapses following COVID-19 vaccination in Latin American pwMS. Methods: A web-based survey was completed by 207 pwMS from Latin America to assess for adverse events associated with COVID-19 vaccination between February 1 and April 30, 2021. Results: All participants received the first dose and 84 the second. The different vaccines administered were: inactivated virus vaccines [(IVV);CoronaVac, BBIBP-CorV) ] in 117 (56.5%) patients, adenovirus vector vaccines [(AdV);Gam-COVID-Vac, AZD1222] in 53 (25.6%) and mRNA vaccines (BNT162b2) in 37 (17.9%). The mean follow-up after vaccination was 24 ± 16 days. Three (1.4%) patients reported having COVID-19 infection after vaccination (all occurring after the first dose). Any adverse events were reported in 61 (29.5%) and 23 (27.4%) individuals after the first and second doses respectively. These included pain at the injection site, headache, fever, flu-like symptoms, fatigue, and muscle or joint pain. A lower frequency of adverse events was found with IVV (x?=7.2, p=0.03). Four (1.9%) patients reported an MS relapse, all occurring after an IVV first dose. Mean time to relapse: 18 ± 13 days. None of these patients had stopped or postponed their MS treatment before vaccination. Conclusion: COVID-19 vaccines seem to be safe for pwMS from Latin America. No major safety signals appeared in this patientreported study.

Intersectoral online training and exchange during the covid-19 pandemic in a district: Component for intersectoral communication of care

In anticipation of the pressure of the rising numbers in COVID-19 cases on the regional health system, an exchange between the actors engaged in handling the pandemic from a medical perspective in the district of Rhein-Neckar/ Heidelberg was initiated in October 2020. The outpatient and inpatient sector as well as the public health office of the district and the Department of Family Medicine and Health Services Research of the University Hospital participated. A mutual online meeting was planned to enable bidirectional exchange at the intersection of primary care. The mutually identified topics, like criteria for admission, therapy and nursing homes were ver-ified via an online survey (n = 63 participants, 76 % family physicians). Additional topics that had been suggested were passed on to the intersectional actors and, wherever possible, included in the meeting. On 11 December 2020, 71 physicians attended the meeting. In addition to the presentations, 53 questions were asked and discussed by the presenters via chat. Demand for a follow-up meeting was high. In January, a follow-up event with n = 115 participants focusing on COVID-19 vaccinations war organized, again with an active participation and a high request for a follow-up meeting. So, the experiences encourage to continue this format, involving all the actors relevant for a medical management of the pan-demic. This could be a component for fostering a bilateral communication, on the one hand engaging the actors of the primary care sector and on the other hand providing continuing medical education in the dynamic pandemic.

Pan-European Study on Functional and Medical Recovery and Geriatric Rehabilitation Services of Post-COVID-19 Patients: Protocol of the EU-COGER Study.

OBJECTIVES: There is insufficient knowledge about the functional and medical recovery of older people infected with SARS-CoV-2. This study aims to gain insight into the course of functional and medical recovery of persons who receive geriatric rehabilitation (GR) following SARS-CoV-2 infection across Europe. Special attention will be paid to the recovery of activities of daily living (ADL) and to the GR services offered to these patients. DESIGN: A multi-center observational cohort study. SETTING AND PARTICIPANTS: This study will include several European countries (EuGMS member states) each providing at least 52 comparable routine datasets (core dataset) of persons recovering from a SARS-CoV-2 infection and receiving geriatric rehabilitation. The routine data will be anonymously collected in an online CASTOR database. The ethical regulations of each participating country will be followed. PRIMARY OUTCOME: ADL functioning. SECONDARY OUTCOMES: length of stay, discharge destination, hospital readmission and mortality. Other variables that will be collected are quality of life, treatment modalities, complications, cognition, frailty, mood/anxiety, BMI, nutrition and pain. All variables will be reported at admission and compared with follow-up scores (discharge, 6 weeks and 6 months follow-up). CONCLUSION: This study will explore the effect of geriatric rehabilitation on post-COVID-19 patients, especially on ADL recovery, and the variety of geriatric rehabilitation services across Europe. Information from this study may help improve recovery of older persons infected with SARS-CoV-2 and improve geriatric rehabilitation services in the ongoing COVID-19 pandemic.

[Psychosocial effects of the pandemic on staff and residents of nursing homes as well as their relatives-A systematic review]. / Psychosoziale Auswirkungen der Pandemie auf Pflegekräfte und Bewohner von Pflegeheimen sowie deren Angehörige ­ Ein systematisches Review.

BACKGROUND: Following the COVID-19 pandemic residents of nursing homes, their visitors and families as well as employees are faced with new challenges. Protective measures have a strong impact on the well-being of all these groups of persons. MATERIAL AND METHODS: A systematic search was carried out for studies investigating the psychosocial consequences of the COVID-19 pandemic for residents, their visitors and families as well as nursing home staff. Results were analyzed by narrative synthesis. RESULTS: A total of 756 studies were screened and 15 studies were included. These studies were conducted between February and June 2020 with participants from 14 countries. Participants reported loneliness, grief and depressive symptoms among residents. Some gave an account of fear as a reaction of residents to social distancing. Residents with cognitive impairment suffered more although there are conflicting reports. The well-being of visitors and friends was compromised and their feeling of loneliness increased. Nursing home personnel reported fear of getting infected and of infecting residents or their own families. Infected workers in the USA expressed anger about a lack of protection. Furthermore, an increase in workload was reported. CONCLUSION: Studies conducted during the first months of the pandemic reported negative consequences for the psychosocial well-being of residents, their visitors and nursing home staff. Individual needs for future support of these groups are distinct and need further evaluation during the on-going pandemic.

[COVID-19 in old age-The geriatric perspective]. / COVID-19 im Alter ­ Die geriatrische Perspektive.

Predominantly the older population is affected by a severe course of COVID-19. The mortality of hospitalized patients with COVID-19 above the age of 80 years is up to 54% in international studies. These observations indicate the necessity to highlight the geriatric perspective on this disease. The diagnostics and treatment of COVID-19 do not differ between younger and older patients but atypical symptoms should be expected more frequently in old age. Older subjects show an increased need for rehabilitation after COVID-19. Paradoxically, increasing rehabilitation demands go along with a reduced availability of geriatric rehabilitation options, the latter being a consequence of closure or downsizing of rehabilitation departments during the pandemic. In general, measures of isolation and quarantine should be diligently balanced as the health and emotional consequences of such measures may be severe in older persons. In light of the poor prognosis of older COVID-19 patients, advanced care planning becomes even more relevant. Caregivers and physicians should be encouraged to compose advanced care directives that also reflect the specific circumstances of COVID-19. Fortunately, current data suggest that the effectiveness of the vaccination with the mRNA-vaccines approved in Germany may be equally high in older compared to younger persons.