SARS-CoV-2 BA.2.86 enters lung cells and evades neutralizing antibodies with high efficiency.

BA.2.86, a recently identified descendant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 sublineage, contains ∼35 mutations in the spike (S) protein and spreads in multiple countries. Here, we investigated whether the virus exhibits altered biological traits, focusing on S protein-driven viral entry. Employing pseudotyped particles, we show that BA.2.86, unlike other Omicron sublineages, enters Calu-3 lung cells with high efficiency and in a serine- but not cysteine-protease-dependent manner. Robust lung cell infection was confirmed with authentic BA.2.86, but the virus exhibited low specific infectivity. Further, BA.2.86 was highly resistant against all therapeutic antibodies tested, efficiently evading neutralization by antibodies induced by non-adapted vaccines. In contrast, BA.2.86 and the currently circulating EG.5.1 sublineage were appreciably neutralized by antibodies induced by the XBB.1.5-adapted vaccine. Collectively, BA.2.86 has regained a trait characteristic of early SARS-CoV-2 lineages, robust lung cell entry, and evades neutralizing antibodies. However, BA.2.86 exhibits low specific infectivity, which might limit transmissibility.

The Omicron variant is highly resistant against antibody-mediated neutralization: Implications for control of the COVID-19 pandemic.

The rapid spread of the SARS-CoV-2 Omicron variant suggests that the virus might become globally dominant. Further, the high number of mutations in the viral spike protein raised concerns that the virus might evade antibodies induced by infection or vaccination. Here, we report that the Omicron spike was resistant against most therapeutic antibodies but remained susceptible to inhibition by sotrovimab. Similarly, the Omicron spike evaded neutralization by antibodies from convalescent patients or individuals vaccinated with the BioNTech-Pfizer vaccine (BNT162b2) with 12- to 44-fold higher efficiency than the spike of the Delta variant. Neutralization of the Omicron spike by antibodies induced upon heterologous ChAdOx1 (Astra Zeneca-Oxford)/BNT162b2 vaccination or vaccination with three doses of BNT162b2 was more efficient, but the Omicron spike still evaded neutralization more efficiently than the Delta spike. These findings indicate that most therapeutic antibodies will be ineffective against the Omicron variant and that double immunization with BNT162b2 might not adequately protect against severe disease induced by this variant.

Status of HIV and comorbidities in refugees with HIV from Ukraine.

PURPOSE: To describe the clinical characteristics of refugees with HIV from Ukraine that seek continuation of medical care in Germany. METHODS: Fourty-six refugees with HIV that had left Ukraine between 24 February and 30 December 2022 were examined. Information on patients' history was obtained using a standardized questionnaire for clinical care. Interviews were conducted in Russian during their first clinical presentation. RESULTS: Fourty-six persons (41 females and 5 males) were included and their mean age was 39.6 (±8.4) years. The mean time since HIV diagnosis was 8.0 (median, IQR 7.15) years and 70.3% of participants currently received tenfofovir-DF, lamividine and dolutegravir. Most refugees had an undetectable HIV viral load and their current mean CD4 T cell count was 702 (SD ± 289) per µL. Serology revealed previous hepatitis B infection in 50.4% without evidence for replication, with undetectable anti-hepatitis B surface antigen in the remaining refugees. Antibodies against hepatitis C were present in 23 refugees (50%), but only 10 patients had been diagnosed with hepatitis C previously. Five refugees had undergone successful antiviral treatment for hepatitis C. Detectable HCV-RNA was evident in nine patients (19.6%). Sixteen (38.6%) refugees had a positive tuberculosis (TB) interferon gamma release assay, and four were on TB treatment for previously diagnosed infection. One had been diagnosed with multidrug-resistant (MDR) TB, two with pre-extensively drug-resistant (pre-XDR) TB and two with XDR TB and were treated with combinations of second-line and novel agents according to WHO guidelines. CONCLUSIONS: Based on this preliminary analysis of a not fully representative cohort, refugees with HIV from Ukraine were young, mostly healthy females highly adherent to antiretroviral therapy. The rate of transmittable co-infections urges early diagnostic evaluation and treatment.

Building capacity for equitable healthcare workforce policy, learning from migrant healthcare workers: A qualitative study with Romanian physicians working in Germany during COVID-19.

BACKGROUND: Attention to the healthcare workforce has increased, yet comprehensive information on migrant healthcare workers is missing. This study focuses on migrant healthcare workers' experiences and mobility patterns in the middle of a global health crisis, aiming to explore the capacity for circular migration and support effective and equitable healthcare workforce policy. METHODS: Romanian physicians working in Germany during the COVID-19 pandemic served as an empirical case study. We applied a qualitative explorative approach; interviews (n = 21) were collected from mid of September to early November 2022 and content analysis was performed. RESULTS AND DISCUSSION: Migrant physicians showed strong resilience during the COVID-19 crisis and rarely complained. Commitment to high professional standards and career development were major pull factors towards Germany, while perceptions of limited career choices, nepotism and corruption in Romania caused strong push mechanisms. We identified two major mobility patterns that may support circular migration policies: well-integrated physicians with a wish to give something back to their home country, and mobile cosmopolitan physicians who flexibly balance career opportunities and personal/family interests. Health policy must establish systematic monitoring of the migrant healthcare workforce including actor-centred approaches, support integration in destination countries as well as health system development in sending countries, and invest in evidence-based circular migration policy.

Amino acids, post-translational modifications, nitric oxide, and oxidative stress in serum and urine of long COVID and ex COVID human subjects.

In this study, we investigated the status of amino acids, their post-translational modifications (PTM), major nitric oxide (NO) metabolites and of malondialdehyde (MDA) as a biomarker of oxidative stress in serum and urine samples of long COVID (LoCo, n = 124) and ex COVID (ExCo, n = 24) human subjects collected in 2022. Amino acids and metabolites were measured by gas chromatography-mass spectrometry (GC-MS) methods using stable-isotope labelled analogs as internal standards. There were no differences with respect to circulating and excretory arginine and asymmetric dimethylarginine (ADMA). LoCo participants excreted higher amounts of guanidino acetate than ExCo participants (17.8 ± 10.4 µM/mM vs. 12.6 ± 8.86 µM/mM, P = 0.005). By contrast, LoCo participants excreted lower amounts of the advanced glycation end-product (AGE) NG-carboxyethylarginine (CEA) than ExCo participants did (0.675 ± 0.781 µM/mM vs. 1.16 ± 2.04 µM/mM, P = 0.0326). The serum concentrations of MDA did not differ between the groups, indicating no elevated oxidative stress in LoCo or ExCo. The serum concentration of nitrite was lower in LoCo compared to ExCo (1.96 ± 0.92 µM vs. 2.56 ± 1.08 µM; AUC, 0.718), suggesting altered NO synthesis in the endothelium. The serum concentration of nitrite correlated inversely with the symptom anxiety (r = - 0.293, P = 0.0003). The creatinine-corrected urinary excretion of Lys and its metabolite L-5-hydroxy-Lys correlated positively with COVID toes (r = 0.306, P = 0.00027) and sore throat (r = 0.302, P = 0.0003). Our results suggest that amino acid metabolism, PTM and oxidative stress are not severely affected in long COVID. LoCo participants may have a lower circulating NO reservoir than ExCo.

"There is no one who helps you with it": experiences of people with long COVID regarding medical care, therapeutic measures, and barriers in the German healthcare system: results of a qualitative study with four focus groups.

BACKGROUND: Many people experience long-term symptoms such as fatigue, cognitive problems, or shortness of breath after an acute infection with COVID-19. This emerging syndrome, known as long COVID, is new and complex in many aspects. This study aims to collect the experiences of people with long COVID with ambulatory healthcare structures. METHODS: Four focus groups were conducted with a total of 23 adults with long COVID in June and July 2022. These discussions were audio-recorded, subsequently transcribed, and analyzed using the qualitative content analysis of Mayring and Kuckartz. RESULTS: Fourteen out of 19 participants who had a primary care encounter regarding their long COVID symptoms did not perceive it as helpful. Many respondents reported that their general practitioners did not take their long COVID symptoms seriously and did not refer them to specialists or made therapeutic recommendations. However, some participants reported that they were prescribed non-pharmaceutical therapies (e.g., group meetings supported by psychotherapists, occupational therapy, etc.) that improved their condition. 14 of 23 respondents perceived care barriers such as providers' lack of awareness of long COVID, poor access to specialists, a lack of specialized care (e.g., long COVID clinics), or high bureaucratic hurdles for specific healthcare services. To improve medical care, participants suggested campaigns to raise awareness of long COVID among healthcare providers and the general population, increase research and government investments regarding the development of treatment structures for long COVID, expanding existing therapeutic services, and establishing one-stop shops for integrated specialist healthcare for people with long COVID. CONCLUSIONS: Several implications for healthcare professionals and policymakers can be derived from this study: (1) general practitioners should take the symptoms of long COVID seriously, assume a care coordinating role, make referrals, and establish contact with long COVID clinics; (2) care planners should focus on developing interprofessional evidence-based care and treatment approaches for long COVID; (3) existing care structures such as long COVID outpatient clinics should be expanded. The overarching goal must be to develop consistent guidelines for long COVID diagnosis, care, and treatment. TRIAL REGISTRATION: The study is registered in the German register for clinical trials (DRKS00026007, first registration on 09/09/2021).

[Immunosuppressed people's beliefs, expectations, and experiences with COVID-19 vaccinations : Results of a longitudinal study]. / Impfeinstellung, Erwartungen und Impferfahrung von Immunsupprimierten bei COVID-19-Impfungen : Ergebnisse einer Längsschnittstudie.

BACKGROUND: Immunocompromised people are less likely to be vaccinated, despite an increased benefit of many vaccinations in terms of benefit-risk assessment, including the vaccines against SARS CoV-2 (COVID-19). Attitudes, expectations, and experiences with previous vaccinations influence the decision to get vaccinated. OBJECTIVE: To explore the attitudes of immunocompromised people towards vaccinations in general and COVID-19 vaccination in particular and their experiences with COVID-19 vaccinations. MATERIAL AND METHODS: As part of the CoCo Immune study, immunocompromised participants were surveyed in the spring and summer of 2021 (1 November 2021-7 September 2021) using questionnaires. Initially, they were asked about their expectations concerning a COVID-19 vaccination and followed up about their experience after COVID-19 vaccination. In addition, sociodemographic data, general attitudes toward vaccinations and experiences with previous vaccinations were collected. Analysis was performed using descriptive and bivariate statistics. RESULTS: The 243 participants mostly approved vaccinations and expected the COVID-19 vaccination to be effective and well-tolerated. Women were more concerned about the safety of vaccinations and were more often worried about side effects. Older persons felt better informed than younger persons. Participants who reported subjective side effects of previous vaccinations were more skeptical about vaccinations as well as the government institutions that recommend vaccinations. They less often agreed with the statement "in retrospect, the COVID-19 vaccination has been harmless for me so far". DISCUSSION: The participants mostly expressed a positive attitude and anticipation towards COVID-19 vaccinations; however, the age and sex differences found suggest that there are different information needs which should be addressed when educating individuals about vaccinations or designing vaccination campaigns.

Diminishing Immune Responses against Variants of Concern in Dialysis Patients 4 Months after SARS-CoV-2 mRNA Vaccination.

Patients undergoing chronic hemodialysis were among the first to receive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations because of their increased risk for severe coronavirus disease and high case-fatality rates. By using a previously reported cohort from Germany of at-risk hemodialysis patients and healthy donors, where antibody responses were examined 3 weeks after the second vaccination, we assessed systemic cellular and humoral immune responses in serum and saliva 4 months after vaccination with the Pfizer-BioNTech BNT162b2 vaccine using an interferon-γ release assay and multiplex-based IgG measurements. We further compared neutralization capacity of vaccination-induced IgG against 4 SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, and Delta) by angiotensin-converting enzyme 2 receptor-binding domain competition assay. Sixteen weeks after second vaccination, compared with 3 weeks after, cellular and humoral responses against the original SARS-CoV-2 isolate and variants of concern were substantially reduced. Some dialysis patients even had no detectable B- or T-cell responses.

Humoral immune response following prime and boost BNT162b2 vaccination in people living with HIV on antiretroviral therapy.

OBJECTIVES: People living with HIV (PLWH) with low CD4 T-cell counts may be at a higher risk for severe coronavirus disease 2019 (COVID-19) outcomes and in need of efficient vaccination. The World Health Organization (WHO) now recommends prioritizing PLHIV for COVID-19 vaccination. Data on immune responses after messenger RNA (mRNA) vaccination in PLHIV in relation to CD4 counts are scarce. We aimed at assessing the humoral immune response in PLHIV after mRNA vaccination against COVID-19. METHODS: We examined a cohort of PLHIV after prime (n = 88) and boost (n = 52) vaccination with BNT162b2. We assessed levels of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein-specific immunoglobulin G (IgG)/IgA and circulating neutralizing antibodies in plasma and correlated results to the cellular immune status. BNT162b2-vaccinated health care workers served as controls. RESULTS: All PLWH had a viral load of ≤ 200 HIV-1 RNA copies/mL and 96.5% had a viral load of < 50 copies/mL. Anti-S IgG and neutralizing antibody responses after BNT162b2 priming were significantly lower in PLHIV having a CD4:CD8 T-cell ratio of < 0.5. However, we observed robust humoral immunity in the majority of PLWH receiving antiretroviral therapy (ART) irrespective of CD4 T-cell nadir, current CD4 count or CD4:CD8 ratio after full BNT162b2 vaccination. Nevertheless, HIV-negative controls produced significantly higher mean anti-S IgG concentrations with less variability. CONCLUSIONS: The majority of PLWH mounted robust responses after complete BNT162b2 vaccination but overall amounts of antibodies directed against the SARS-CoV-2 receptor-binding domain were variable. The impact on clinical efficacy remains unclear.

Immunogenicity of COVID-19 Vaccination in Melanoma Patients under Immune Checkpoint Blockade.

BACKGROUND: Immunogenicity of SARS-CoV-2 vaccines is modestly impaired in cancer patients due to a generally weakened immune system. Immune checkpoint inhibitors (ICI) are expected to enhance immune response. This has already been described to be the case in influenza vaccines, and first data about COVID-19 vaccines show a trend in this direction. AIM: We aimed to investigate the immune response of patients with melanoma under ICI therapy after COVID-19 vaccination. PATIENTS AND METHODS: In the Skin Cancer Center Hanover (Germany), we recruited 60 patients with advanced melanoma who either received ICI therapy during or before the vaccination period. Serological blood analysis was performed using quantitative ELISA for Anti-SARS-CoV-2 spike protein 1 IgG antibodies. RESULTS: We did not observe an enhanced humoral immune response in patients under active or past ICI therapy after COVID-19 vaccination. Nevertheless, there is a tendency of higher antibody levels when ICI therapy was received within the last 6 months before vaccination. Subgroup analysis revealed that patients in our study population under ongoing targeted therapy during vaccination period had significantly higher median antibody levels than patients without any active antitumor treatment. CONCLUSION: Melanoma patients under ICI therapy show comparable antibody response after SARS-CoV-2 vaccination to healthy health care professionals. This finding is independent of the timing of ICI therapy.

SARS-CoV-2-specific immune responses in elderly and immunosuppressed participants and patients with hematologic disease or checkpoint inhibition in solid tumors: study protocol of the prospective, observational CoCo immune study.

BACKGROUND: Immunocompromised people (ICP) and elderly individuals (older than 80 years) are at increased risk for severe coronavirus infections. To protect against serious infection with SARS-CoV-2, ICP are taking precautions that may include a reduction of social contacts and participation in activities which they normally enjoy. Furthermore, for these people, there is an uncertainty regarding the effectiveness of the vaccination. The COVID-19 Contact (CoCo) Immune study strives to characterize the immune response to COVID-19 vaccination in immunocompromised, elderly people, and patients with hematological or oncological diseases. The study uses blood-based screenings to monitor the humoral and cellular immune response in these groups after vaccination. Questionnaires and qualitative interviews are used to describe the level of social participation. METHODS: The CoCo Immune Study is a mixed methods prospective, longitudinal, observational study at two large university hospitals in Northern Germany. Starting in March 2021, it monitors anti-SARS-CoV-2 immune responses and collects information on social participation in more than 600 participants, at least 18 years old. Inclusion criteria and subcohorts: Participants with (1) regularly intake of immunosuppressive medication (ICP-cohort) or (2) age ≥ 80 years (80 + -cohort). Additionally, patients with current or former (3) myeloid, (4) lymphatic disease or (5) solid tumor under checkpoint inhibition (3-5: HO-cohort). EXCLUSION CRITERIA: (1) refusal to give informed consent, (2) contraindication to blood testing, (3) inability to declare consent. Participants complete a questionnaire at four different time points: prior to full vaccination, and 1, 6 and 12 months after completed vaccination. In addition, participants draw blood samples themselves or through a local health care provider and send them with their questionnaires per post at the respective time points after vaccination. Patients of the HO cohort dispense additional blood samples at week 3 to 12 and at month 6 to 9 after 2nd vaccination to gain additional knowledge in B and T cell responses. Selected participants are invited to qualitative interviews about social participation. DISCUSSION: This observational study is designed to gain insight into the immune response of people with weakened immune systems and to find out how social participation is affected after COVID-19 vaccination. TRIAL REGISTRATION: This study was registered with German Clinical Trial Registry (registration number: DRKS00023972) on 30th December 2020.

Humoral and Cellular Immune Responses Against Severe Acute Respiratory Syndrome Coronavirus 2 Variants and Human Coronaviruses After Single BNT162b2 Vaccination.

BACKGROUND: Vaccine-induced neutralizing antibodies are key in combating the coronavirus disease 2019 (COVID-19) pandemic. However, delays of boost immunization due to limited availability of vaccines may leave individuals vulnerable to infection and prolonged or severe disease courses. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC)-B.1.1.7 (United Kingdom), B.1.351 (South Africa), and P.1 (Brazil)-may exacerbate this issue, as the latter two are able to evade control by antibodies. METHODS: We assessed humoral and T-cell responses against SARS-CoV-2 wild-type (WT), VOC, and endemic human coronaviruses (hCoVs) that were induced after single and double vaccination with BNT162b2. RESULTS: Despite readily detectable immunoglobulin G (IgG) against the receptor-binding domain of the SARS-CoV-2 S protein at day 14 after a single vaccination, inhibition of SARS-CoV-2 S-driven host cell entry was weak and particularly low for the B.1.351 variant. Frequencies of SARS-CoV-2 WT and VOC-specific T cells were low in many vaccinees after application of a single dose and influenced by immunity against endemic hCoV. The second vaccination significantly boosted T-cell frequencies reactive for WT and B.1.1.7 and B.1.351 variants. CONCLUSIONS: These results call into question whether neutralizing antibodies significantly contribute to protection against COVID-19 upon single vaccination and suggest that cellular immunity is central for the early defenses against COVID-19.

Navigating uncertainty: occupational therapists' experiences of Long COVID management in Germany, Austria and Switzerland.

PURPOSE: Long COVID presents global challenges for healthcare professionals. Occupational therapists responded by seeking effective treatment strategies. The approaches of occupational therapists supporting long-haulers in German-speaking countries remain under-explored. The purpose of this study is to explore how occupational therapists in Germany, Austria and Switzerland navigate and apply profession-specific strategies in the new clinical landscape of Long COVID care. MATERIALS AND METHODS: This study used qualitative-descriptive design and content analysis to extract insights from seven semi-structured interviews with occupational therapists in inpatient and outpatient settings from three countries. RESULTS: Four overarching themes emerged: how Long COVID was encountered within the scope of occupational therapy, the multifaceted repertoire experts used to support long haulers, triumphs and challenges that emerged in Long COVID treatment, and recommendations and opportunities for occupational therapy practice. The results underscore the complex support needed for long-haulers, achieved through a multifaceted occupational therapy repertoire, incorporating client-centred, occupation-focused, and context-referencing strategies with shared decision-making and collaborative therapy planning. CONCLUSIONS: Occupational therapy concepts, with their focus on human occupation, may offer new treatment options and strategies for managing emerging conditions such as Long COVID.

Long COVID-RehabilitationSymptom management in relation to the clients' occupational repertoire improves participation and social function in everyday life.Actively involving clients in the therapy process through shared decision-making enhances tailored rehabilitation.Contextualized interventions take into account clients' needs and concerns, as well as the requirements of their social and professional environment.Teletherapy can be a pragmatic solution to improve the accessibility of rehabilitation services for those affected by long COVID.

Rapid spread of the SARS-CoV-2 JN.1 lineage is associated with increased neutralization evasion.

In July/August 2023, the highly mutated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.2.86 lineage emerged and its descendant JN.1 is on track to become the dominant SARS-CoV-2 lineage globally. Compared to the spike (S) protein of the parental BA.2.86 lineage, the JN.1 S protein contains one mutation, L455S, which may affect receptor binding and antibody evasion. Here, we performed a virological assessment of the JN.1 lineage employing pseudovirus particles bearing diverse SARS-CoV-2 S proteins. Using this strategy, it was found that S protein mutation L455S confers increased neutralization resistance but reduces ACE2 binding capacity and S protein-driven cell entry efficiency. Altogether, these data suggest that the benefit of increased antibody evasion outweighs the reduced ACE2 binding capacity and further enabled the JN.1 lineage to effectively spread in the human population.

Evaluating the Feasibility, Acceptance, and Beneficial Effects of Online Occupational Therapy for Post-COVID-19 Condition: Protocol for a Randomized Controlled Trial (ErgoLoCo Study).

BACKGROUND: Post-COVID-19 syndrome (PCS; also known as "long COVID") is a relatively novel disease comprising physical, psychological, and cognitive complaints persisting several weeks to months after acute infection with SARS-CoV-2. Approximately 10% of patients with COVID-19 are affected by long-term symptoms. However, effective treatment strategies are lacking. The ErgoLoCo (Occupational Therapy [Ergotherapie] for Long COVID) study was designed to develop and evaluate a novel occupational therapy (OT) concept of online delivery of therapy for long COVID. OBJECTIVE: The primary study objective is to assess the feasibility of the online OT intervention in PCS. Secondary aims include the evaluation of online OT concerning cognitive problems, occupational performance, and social participation. METHODS: This randomized controlled interventional pilot study involves parallel mixed methods process analyses and a realist evaluation approach. A total of 80 clients with PCS aged at least 16 years will be recruited into two interventional groups. The control cohort (watch and wait) comprises 80 clients with long COVID. Treatment is provided through teletherapy (n=40) or delivery of prerecorded videos (n=40) using the same standardized OT concept twice weekly over 12 weeks. Analyses of quantitative questionnaires and qualitative interviews based on the theoretical framework of acceptability will be performed to assess feasibility. Focus group meetings will be used to assess how acceptable and helpful the intervention was to the participating occupational therapists. Standardized tests will be used to assess the initial efficacy of the intervention on neurocognitive performance; limitations in mobility, self-care, and everyday activities; pain; disabilities; quality of life (QoL); social participation; and anxiety and depression in PCS, and the possible effects of online OT on these complaints. RESULTS: The German Ministry of Education and Research provided funding for this research in March 2022. Data collection took place from October 2022 to August 31, 2023. Data analysis will be completed by the end of April 2024. We anticipate publishing the results in the fall of 2024. CONCLUSIONS: Despite the enormous clinical need, effective and scalable treatment options for OT clients who have PCS remain scarce. The ErgoLoCo study will assess whether online-delivered OT is a feasible treatment approach in PCS. Furthermore, this study will assess the effect of the intervention on cognitive symptoms, QoL, and occupational performance and participation in everyday life. Particular emphasis will be placed on the experiences of clients and occupational therapists with digitally delivered OT. This study will pave the way for novel and effective treatment strategies in PCS. TRIAL REGISTRATION: German Clinical Trial Registry DRKS00029990; https://drks.de/search/de/trial/DRKS00029990. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/50230.

Effects of a randomized-controlled and online-supported physical activity intervention on exercise capacity, fatigue and health related quality of life in patients with post-COVID-19 syndrome.

BACKGROUND: The Post-COVID-19 syndrome (PCS), which can occur after acute respiratory syndrome coronavirus 2 infection, leads to restrictions in everyday activity. Our study assessed the impact of an online-guided intervention which intended to facilitate physical activity on the mental and physical capability of PCS patients. METHODS: We randomized 62 patients with PCS (20 male/ 42 female; age: 46 ± 12 years; body mass index: 28.7 ± 6.7 kg/m2) with a score ≥ 22 in the fatigue assessment scale (FAS) to a 3-month exercise-focused intervention (IG n = 30) or control period (CG n = 32). We assessed changes in exercise capacity (bicycle exercise test with measurements of gas exchange), fatigue, markers of health-related quality of life (HrQoL) and mental health. RESULTS: The FAS score decreased significantly in both study groups (IG: 35.1 ± 7.4 to 31.8 ± 8.5 points; CG: 35.6 ± 7.4 to 32.6 ± 7.5 points, both p < 0.01). Exercise capacity did not increase in the CG or IG (within-group changes for IG: peak oxygen uptake: 0.9 ± 2.6 ml/min/kg, p = 0.098; peak power output: 6.1 ± 17.8 W, p = 0.076) with no significant changes in HrQoL and work ability. Patients with a FAS score at baseline ≥ 35 (severe fatigue) showed no change in exercise capacity with the 3-month intervention whereas the sub-group of patients with FAS < 35 points (moderate fatigue) showed improvements, independent of the study group. CONCLUSIONS: Our 3-month intervention seems appropriate for patients with moderate fatigue, whereas those with more severe fatigue appear to be too restricted with respect to their mental or physical health status to perform exercise at a level which is sufficient to improve markers of physical performance. TRIAL REGISTRATION: German Clinical Trials Register (registration trial number: DRKS00026245) on September 2 2021.

Virological Traits of the SARS-CoV-2 BA.2.87.1 Lineage.

Transmissibility and immune evasion of the recently emerged, highly mutated SARS-CoV-2 BA.2.87.1 are unknown. Here, we report that BA.2.87.1 efficiently enters human cells but is more sensitive to antibody-mediated neutralization than the currently dominating JN.1 variant. Acquisition of adaptive mutations might thus be needed for efficient spread in the population.

Parenting and Gender as Impact Factors for Social Participation, Quality of Life, and Mental Health in Long COVID.

OBJECTIVES: This study aims to investigate the impact of gender and parental tasks on social participation, health-related quality of life (hrQoL), and mental health in persons with long COVID. METHODS: A mixed-methods approach was followed including a cross-sectional web-based survey and semi-structured interviews. Multivariable linear regressions were used to quantify the effect of gender and parenting tasks on social participation, hrQoL, and mental health. Qualitative data from interviews with participants experiencing long COVID symptoms was analyzed using content analysis. RESULTS: Data from 920 participants in the quantitative study and 25 participants in the qualitative study was analyzed. Parenting tasks were associated with increased impairments in family and domestic responsibilities in persons with long COVID compared to lower impairments in persons without long COVID (P = .02). The qualitative data indicate that coping with long COVID and pursuing parenting tasks limit participants' ability to perform leisure activities and attend social gatherings. In long COVID, men had higher anxiety symptoms than women, and in those without long COVID, the opposite was observed (P < .001). In the qualitative study, participants expressed feelings of dejection and pessimism about their future private, occupational, and health situations. No differences between the genders could be observed. CONCLUSIONS: Long COVID is associated with impairments in family and domestic responsibilities in individuals who have parenting tasks. Among participants with long COVID, anxiety symptoms are higher in men than women.

Association of long COVID with health-related Quality of Life and Social Participation in Germany: Finding from an online-based cross-sectional survey.

Purpose: This study aims to examine the health-related Quality of Life (hrQoL) and social participation in participants with Long COVID compared to participants without symptoms after COVID-19 and participants with no prior SARS-CoV-2 infection. Methods: A cross-sectional online survey was conducted in Germany. The non-random sample consists of participants 18 years or older. Participants were divided in three groups: Lg COVID with a prior SARS-CoV-2 infection and new or persistent symptoms 28 days after infection, ExCOVID with a prior SARS-CoV-2 infection and without new or persistent symptoms after 28 days, and NoCOVID when participants had no prior SARS-CoV-2 infection. EQ-5D-3L was used as hrQoL measure and the Index for the Assessment of Health Impairments (IMET) to reflect social participation. Descriptive and inferential statistics were performed. Results: A total of 3188 participants were included in the analysis (1421 Lg COVID, 260 ExCOVID, 1507 NoCOVID). Lg COVID was associated with the lowest EQ-5D-3L index values (p < 0.001), Visual Analogue Scale (VAS) scores (p < 0.001), and IMET (p < 0.001) scores followed by NoCOVID and ExCOVID. After adjusting for sociodemographic and medical conditions in a multivariable model Long COVID was still associated with lower hrQoL compared to NoCOVID (p < 0.001). About 10% of Lg COVID participants showed no health impairments in all EQ-5D dimensions while 51.1% of NoCOVID and 60% of ExCOVID participants showed no health impairments. Conclusion: This study highlights the impairments of persons with Long COVID on hrQoL and social participation compared to individuals without Long COVID in Germany. Trial registration: German Clinical Trial Registry, DRKS00026007.

Systems biology analysis reveals distinct molecular signatures associated with immune responsiveness to the BNT162b COVID-19 vaccine.

BACKGROUND: Human immune responses to COVID-19 vaccines display a large heterogeneity of induced immunity and the underlying immune mechanisms for this remain largely unknown. METHODS: Using a systems biology approach, we longitudinally profiled a unique cohort of female high and low responders to the BNT162b vaccine, who were known from previous COVID-19 vaccinations to develop maximum and minimum immune responses to the vaccine. We utilized high dimensional flow cytometry, bulk and single cell mRNA sequencing and 48-plex serum cytokine analyses. FINDINGS: We revealed early, transient immunological and molecular signatures that distinguished high from low responders and correlated with B and T cell responses measured 14 days later. High responders featured a distinct transcriptional activity of interferon-driven genes and genes connected to enhanced antigen presentation. This was accompanied by a robust cytokine response related to Th1 differentiation. Both transcriptome and serum cytokine signatures were confirmed in two independent confirmatory cohorts. INTERPRETATION: Collectively, our data contribute to a better understanding of the immunogenicity of mRNA-based COVID-19 vaccines, which might lead to the optimization of vaccine designs for individuals with poor vaccine responses. FUNDING: German Center for Infection Research, German Center for Lung Research, German Research Foundation, Excellence Strategy EXC 2155 "RESIST" and European Regional Development Fund.