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Background The emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants BA.1, BA.2, and BA.4/5 demonstrate higher transmission and infection rates than previous variants of concern. To evaluate effectiveness of heterologous and homologous booster vaccination, we directly compared cellular and humoral immune responses as well as neutralizing capacity against replication-competent SARS-CoV-2 wild type, Delta, and Omicron variants BA.1, BA.2, and BA.4/5. Methods Peripheral blood mononuclear cells and serum samples from 137 participants were investigated, in 3 major groups. Individuals in the first group were vaccinated twice with ChAdOx1 and boosted with a messenger RNA (mRNA) vaccine (BNT162b2 or mRNA-1273); the second group included triple mRNA-–vaccinated participants, and the third group, twice-vaccinated and convalescent individuals. Results Vaccination and convalescence resulted in the highest SARS-CoV-2–specific antibody levels, stronger T-cell responses, and best neutralization against wild type, Delta Omicron BA.2, and BA.4/5, while a combination of ChAdOx1 and BNT162b2 vaccination elevated neutralizing capacity against Omicron BA.1. In addition, heterologous booster regimens, compared with homologous regimens, showed higher efficacy against Omicron BA.2 as well as BA.4/5. Conclusions We showed that twice-vaccinated and convalescent individuals demonstrated the strongest immunity against Omicron BA.2 and BA.4/5 variant, followed by those receiving heterologous and homologous booster vaccine regimens. [ABSTRACT FROM AUTHOR]

After COVID-19, patients have reported various complaints such as fatigue, neurological symptoms, and insomnia. Immune-mediated changes in amino acid metabolism might contribute to the development of these symptoms. Patients who had had acute, PCR-confirmed COVID-19 infection about 60 days earlier were recruited within the scope of the prospective CovILD study. We determined the inflammatory parameters and alterations in tryptophan and phenylalanine metabolism in 142 patients cross-sectionally. Symptom persistence (pain, gastrointestinal symptoms, anosmia, sleep disturbance, and neurological symptoms) and patients' physical levels of functioning were recorded. Symptoms improved in many patients after acute COVID-19 (n = 73, 51.4%). Still, a high percentage of patients had complaints, and women were affected more often. In many patients, ongoing immune activation (as indicated by high neopterin and CRP concentrations) and enhanced tryptophan catabolism were found. A higher phenylalanine to tyrosine ratio (Phe/Tyr) was found in women with a lower level of functioning. Patients who reported improvements in pain had lower Phe/Tyr ratios, while patients with improved gastrointestinal symptoms presented with higher tryptophan and kynurenine values. Our results suggest that women have persistent symptoms after COVID-19 more often than men. In addition, the physical level of functioning and the improvements in certain symptoms appear to be associated with immune-mediated changes in amino acid metabolism. [ABSTRACT FROM AUTHOR]

The severity of coronavirus disease 2019 (COVID-19) is related to the presence of comorbidities including metabolic diseases. We herein present data from the longitudinal prospective CovILD trial, and investigate the recovery from COVID-19 in individuals with dysglycemia and dyslipidemia. A total of 145 COVID-19 patients were prospectively followed and a comprehensive clinical, laboratory and imaging assessment was performed at 60, 100, 180, and 360 days after the onset of COVID-19. The severity of acute COVID-19 and outcome at early post-acute follow-up were significantly related to the presence of dysglycemia and dyslipidemia. Still, at long-term follow-up, metabolic disorders were not associated with an adverse pulmonary outcome, as reflected by a good recovery of structural lung abnormalities in both, patients with and without metabolic diseases. To conclude, dyslipidemia and dysglycemia are associated with a more severe course of acute COVID-19 as well as delayed early recovery but do not impair long-term pulmonary recovery. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is responsible for the ongoing global COVID‐19 pandemic. One possibility to control the pandemic is to induce sterilizing immunity through the induction and maintenance of neutralizing antibodies preventing SARS‐CoV‐2 from entering human cells to replicate in. Methods: We report the construction and in vitro and in vivo characterization of a SARS‐CoV‐2 subunit vaccine (PreS‐RBD) based on a structurally folded recombinant fusion protein consisting of two SARS‐CoV‐2 Spike protein receptor‐binding domains (RBD) fused to the N‐ and C‐terminus of hepatitis B virus (HBV) surface antigen PreS to enable the two unrelated proteins serving as immunologic carriers for each other. Results: PreS‐RBD, but not RBD alone, induced a robust and uniform RBD‐specific IgG response in rabbits. Currently available genetic SARS‐CoV‐2 vaccines induce mainly transient IgG1 responses in vaccinated subjects whereas the PreS‐RBD vaccine induced RBD‐specific IgG antibodies consisting of an early IgG1 and sustained IgG4 antibody response in a SARS‐CoV‐2 naive subject. PreS‐RBD‐specific IgG antibodies were detected in serum and mucosal secretions, reacted with SARS‐CoV‐2 variants, including the omicron variant of concern and the HBV receptor‐binding sites on PreS of currently known HBV genotypes. PreS‐RBD‐specific antibodies of the immunized subject more potently inhibited the interaction of RBD with its human receptor ACE2 and their virus‐neutralizing titers (VNTs) were higher than median VNTs in a random sample of healthy subjects fully immunized with registered SARS‐CoV‐2 vaccines or in COVID‐19 convalescent subjects. Conclusion: The PreS‐RBD vaccine has the potential to serve as a combination vaccine for inducing sterilizing immunity against SARS‐CoV‐2 and HBV by stopping viral replication through the inhibition of cellular virus entry. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is frequently associated with iron dyshomeostasis. The latter is related to acute disease severity and COVID-19 convalescence. We herein describe iron dyshomeostasis at COVID-19 follow-up and its association with long-term pulmonary and symptomatic recovery. The prospective, multicentre, observational cohort study "Development of Interstitial Lung Disease (ILD) in Patients With Severe SARS-CoV-2 Infection (CovILD)" encompasses serial extensive clinical, laboratory, functional and imaging evaluations at 60, 100, 180 and 360 days after COVID-19 onset. We included 108 individuals with mild-to-critical acute COVID-19, whereas 75% presented with severe acute disease. At 60 days post-COVID-19 follow-up, hyperferritinaemia (35% of patients), iron deficiency (24% of the cohort) and anaemia (9% of the patients) were frequently found. Anaemia of inflammation (AI) was the predominant feature at early post-acute follow-up, whereas the anaemia phenotype shifted towards iron deficiency anaemia (IDA) and combinations of IDA and AI until the 360 days follow-up. The prevalence of anaemia significantly decreased over time, but iron dyshomeostasis remained a frequent finding throughout the study. Neither iron dyshomeostasis nor anaemia were related to persisting structural lung impairment, but both were associated with impaired stress resilience at long-term COVID-19 follow-up. To conclude, iron dyshomeostasis and anaemia are frequent findings after COVID-19 and may contribute to its long-term symptomatic outcome. [ABSTRACT FROM AUTHOR]

Background and purpose: To assess neurological manifestations and health‐related quality of life (QoL) 3 months after COVID‐19. Methods: In this prospective, multicenter, observational cohort study we systematically evaluated neurological signs and diseases by detailed neurological examination and a predefined test battery assessing smelling disorders (16‐item Sniffin Sticks test), cognitive deficits (Montreal Cognitive Assessment), QoL (36‐item Short Form), and mental health (Hospital Anxiety and Depression Scale, Posttraumatic Stress Disorder Checklist–5) 3 months after disease onset. Results: Of 135 consecutive COVID‐19 patients, 31 (23%) required intensive care unit (ICU) care (severe), 72 (53%) were admitted to the regular ward (moderate), and 32 (24%) underwent outpatient care (mild) during acute disease. At the 3‐month follow‐up, 20 patients (15%) presented with one or more neurological syndromes that were not evident before COVID‐19. These included polyneuro/myopathy (n = 17, 13%) with one patient presenting with Guillain‐Barré syndrome, mild encephalopathy (n = 2, 2%), parkinsonism (n = 1, 1%), orthostatic hypotension (n = 1, 1%), and ischemic stroke (n = 1, 1%). Objective testing revealed hyposmia/anosmia in 57/127 (45%) patients at the 3‐month follow‐up. Self‐reported hyposmia/anosmia was lower (17%) at 3 months, however, improved when compared to the acute disease phase (44%; p < 0.001). At follow‐up, cognitive deficits were apparent in 23%, and QoL was impaired in 31%. Assessment of mental health revealed symptoms of depression, anxiety, and posttraumatic stress disorders in 11%, 25%, and 11%, respectively. Conclusions: Despite recovery from the acute infection, neurological symptoms were prevalent at the 3‐month follow‐up. Above all, smelling disorders were persistent in a large proportion of patients. [ABSTRACT FROM AUTHOR]

The pandemic of coronavirus disease (COVID)-19 is a global threat, causing high mortality, especially in the elderly. The main symptoms and the primary cause of death are related to interstitial pneumonia. Viral entry also into myocardial cells mainly via the angiotensin converting enzyme type 2 (ACE2) receptor and excessive production of pro-inflammatory cytokines, however, also make the heart susceptible to injury. In addition to the immediate damage caused by the acute inflammatory response, the heart may also suffer from long-term consequences of COVID-19, potentially causing a post-pandemic increase in cardiac complications. Although the main cause of cardiac damage in COVID-19 remains coagulopathy with micro- (and to a lesser extent macro-) vascular occlusion, open questions remain about other possible modalities of cardiac dysfunction, such as direct infection of myocardial cells, effects of cytokines storm, and mechanisms related to enhanced coagulopathy. In this opinion paper, we focus on these lesser appreciated possibilities and propose experimental approaches that could provide a more comprehensive understanding of the cellular and molecular bases of cardiac injury in COVID-19 patients. We first discuss approaches to characterize cardiac damage caused by possible direct viral infection of cardiac cells, followed by formulating hypotheses on how to reproduce and investigate the hyperinflammatory and pro-thrombotic conditions observed in the heart of COVID-19 patients using experimental in vitro systems. Finally, we elaborate on strategies to discover novel pathology biomarkers using omics platforms. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections cause coronavirus disease 2019 (COVID-19) and induce a specific antibody response. Serological assays detecting IgG against the receptor binding domain (RBD) of the spike (S) protein are useful to monitor the immune response after infection or vaccination. The objective of our study was to evaluate the clinical performance of the Siemens SARS-CoV-2 IgG (sCOVG) assay. Sensitivity and specificity of the Siemens sCOVG test were evaluated on 178 patients with SARS-CoV-2-infection and 160 pre-pandemic samples in comparison with its predecessor test COV2G. Furthermore, correlation with virus neutralization titers was investigated on 134 samples of convalescent COVID-19 patients. Specificity of the sCOVG test was 99.4% and sensitivity was 90.5% (COV2G assay 78.7%; p<0.0001). S1-RBD antibody levels showed a good correlation with virus neutralization titers (r=0.843; p<0.0001) and an overall qualitative agreement of 98.5%. Finally, median S1-RBD IgG levels increase with age and were significantly higher in hospitalized COVID-19 patients (median levels general ward: 25.7 U/mL; intensive care: 59.5 U/mL) than in outpatients (3.8 U/mL; p<0.0001). Performance characteristics of the sCOVG assay have been improved compared to the predecessor test COV2G. Quantitative SARS-CoV-2 S1-RBD IgG levels could be used as a surrogate for virus neutralization capacity. Further harmonization of antibody quantification might assist to monitor the humoral immune response after COVID-19 disease or vaccination. [ABSTRACT FROM AUTHOR]

In this review, we discuss spatiotemporal kinetics and inflammatory signatures of innate immune cells specifically found in response to SARS-CoV-2 compared to influenza virus infection. Importantly, we cover the current understanding on the mechanisms by which SARS-CoV-2 may fail to engage a coordinated type I response and instead may lead to exaggerated inflammation and death. This knowledge is central for the understanding of available data on specialized pro-resolving lipid mediators in severe SARS-CoV-2 infection pointing toward inhibited E-series resolvin synthesis in severe cases. By investigating a publicly available RNA-seq database of bronchoalveolar lavage cells from patients affected by COVID-19, we moreover offer insights into the regulation of key enzymes involved in lipid mediator synthesis, critically complementing the current knowledge about the mediator lipidome in severely affected patients. This review finally discusses different potential approaches to sustain the synthesis of 3-PUFA-derived pro-resolving lipid mediators, including resolvins and lipoxins, which may critically aid in the prevention of acute lung injury and death from COVID-19. [ABSTRACT FROM AUTHOR]