Impairment of health after overcoming the acute phase of COVID-19 is being observed more and more frequently. Here different symptoms of neurological and/or cardiological origin have been reported. ...With symptoms, which are very similar to the ones reported but are not caused by SARS-CoV-2, the occurrence of functionally active autoantibodies (fAABs) targeting G-protein coupled receptors (GPCR-fAABs) has been discussed to be involved.
We, therefore investigated, whether GPCR-fAABs are detectable in 31 patients suffering from different Long-COVID-19 symptoms after recovery from the acute phase of the disease.
The spectrum of symptoms was mostly of neurological origin (29/31 patients), including post-COVID-19 fatigue, alopecia, attention deficit, tremor and others. Combined neurological and cardiovascular disorders were reported in 17 of the 31 patients. Two recovered COVID-19 patients were free of follow-up symptoms. All 31 former COVID-19 patients had between 2 and 7 different GPCR-fAABs that acted as receptor agonists. Some of those GPCR-fAABs activate their target receptors which cause a positive chronotropic effect in neonatal rat cardiomyocytes, the read-out in the test system for their detection (bioassay for GPCR-fAAB detection). Other GPCR-fAABs, in opposite, cause a negative chronotropic effect on those cells. The positive chronotropic GPCR-fAABs identified in the blood of Long-COVID patients targeted the β2-adrenoceptor (β2-fAAB), the α1-adrenoceptor (α1-fAAB), the angiotensin II AT1-receptor (AT1-fAAB), and the nociceptin—like opioid receptor (NOC-fAAB). The negative chronotropic GPCR-fAABs identified targeted the muscarinic M2-receptor (M2-fAAB), the MAS-receptor (MAS-fAAB), and the ETA-receptor (ETA-fAAB). It was analysed which of the extracellular receptor loops was targeted by the autoantibodies.
•Sera from Long-COVID syndrome patients contained functionally active autoantibodies targeting G-protein coupled receptors.•Autoantibodies target β2- and α1-adrenoceptors, angiotensin II AT1-, muscarinic M2-, MAS-, nociceptin- and ETA-receptors.•Included syndromes were of neurological and cardiological origin, or a combination of both.•Such autoantibody patterns have previously been seen in COVID independent neurological deficits and cardiovascular disease.
•Does prior infection with seasonal human coronavirus OC43 protect against critical COVID-19?•Findings: In an international multi-center study inpatients without anti-HCoV OC43 NP antibodies had an ...increased risk of critical disease.•Meaning: Prior infections with seasonal HCoV OC43 have a protective effect against critical COVID-19.
The vast majority of COVID-19 patients experience a mild disease. However, a minority suffers from critical disease with substantial morbidity and mortality.
To identify individuals at risk of critical COVID-19, the relevance of a seroreactivity against seasonal human coronaviruses was analyzed.
We conducted a multi-center non-interventional study comprising 296 patients with confirmed SARS-CoV-2 infections from four tertiary care referral centers in Germany and France. The ICU group comprised more males, whereas the outpatient group contained a higher percentage of females. For each patient, the serum or plasma sample obtained closest after symptom onset was examined by immunoblot regarding IgG antibodies against the nucleocapsid protein (NP) of HCoV 229E, NL63, OC43 and HKU1.
Median age was 60 years (range 18-96). Patients with critical disease (n=106) had significantly lower levels of anti-HCoV OC43 nucleocapsid protein (NP)-specific antibodies compared to other COVID-19 inpatients (p=0.007). In multivariate analysis (adjusted for age, sex and BMI), OC43 negative inpatients had an increased risk of critical disease (adjusted odds ratio (AOR) 2.68 95% CI 1.09 - 7.05), higher than the risk by increased age or BMI, and lower than the risk by male sex. A risk stratification based on sex and OC43 serostatus was derived from this analysis.
Our results suggest that prior infections with seasonal human coronaviruses can protect against a severe course of COVID-19. Therefore, anti-OC43 antibodies should be measured for COVID-19 inpatients and considered as part of the risk assessment for each patient. Hence, we expect individuals tested negative for anti-OC43 antibodies to particularly benefit from vaccination against SARS-CoV-2, especially with other risk factors prevailing.
Intestinal microbiota such as Fusobacterium nucleatum play an important role in the pathogenesis of colorectal cancer. Here, we describe the case of a 47-year-old patient presenting with ...endophthalmitis and a liver abscess due to Fusobacterium nucleatum that prompted the diagnosis of colorectal cancer as the most likely source of infection. This case highlights that colorectal cancer needs to be considered in patients with systemic infection with Fusobacterium nucleatum and colonoscopy should be performed.
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to an adaptive immune response in the host and the formation of anti-SARS-CoV-2 specific antibodies. While IgG ...responses against SARS-CoV-2 have been characterized quite well, less is known about IgA. IgA2 activates immune cells and induces inflammation and neutrophil extracellular trap (NET) formation which may contribute to organ injury and fatal outcome in SARS-CoV-2-infected patients. SARS-CoV-2 spike protein specific antibody levels were measured in plasma samples of 15 noninfected controls and 82 SARS-CoV-2-infected patients with no or mild symptoms, moderate symptoms (hospitalization) or severe disease (intensive care unit, ICU). Antibody levels were compared to levels of C-reactive protein (CRP) and circulating extracellular DNA (ecDNA) as markers for general inflammation and NET formation, respectively. While levels of SARS-CoV-2-specific IgG were similar in all patient groups, IgA2 antibodies were restricted to severe disease and showed the strongest discrimination between nonfatal and fatal outcome in patients with severe SARS-CoV-2 infection. While anti-SARS-CoV-2 IgG and IgA2 levels correlated with CRP levels in severely diseased patients, only anti-SARS-CoV-2 IgA2 correlated with ecDNA. These data suggest that the formation of anti-SARS-CoV-2 IgA2 during SARS-CoV-2 infection is a marker for more severe disease related to NET formation and poor outcome.
Clinical syndrome coronavirus disease 2019 (COVID-19) induced by severe acute respiratory syndrome coronavirus 2 is characterized by rapid spreading and high mortality worldwide. Although the ...pathology is not yet fully understood, hyperinflammatory response and coagulation disorders leading to congestions of microvessels are considered to be key drivers of the still-increasing death toll. Until now, physical changes of blood cells have not been considered to play a role in COVID-19 related vascular occlusion and organ damage. Here, we report an evaluation of multiple physical parameters including the mechanical features of five frequent blood cell types, namely erythrocytes, lymphocytes, monocytes, neutrophils, and eosinophils. More than four million blood cells of 17 COVID-19 patients at different levels of severity, 24 volunteers free from infectious or inflammatory diseases, and 14 recovered COVID-19 patients were analyzed. We found significant changes in lymphocyte stiffness, monocyte size, neutrophil size and deformability, and heterogeneity of erythrocyte deformation and size. Although some of these changes recovered to normal values after hospitalization, others persisted for months after hospital discharge, evidencing the long-term imprint of COVID-19 on the body.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), affects the pulmonary systems via angiotensin-converting enzyme-2 (ACE-2) receptor, ...being an entry to systemic infection. As COVID-19 disease features ACE-2 deficiency, a link to microcirculation is proposed. Optical coherence tomography angiography (OCT-A) enables non-invasive analysis of retinal microvasculature. Thus, an impaired systemic microcirculation might be mapped on retinal capillary system. As recent OCT-A studies, analyzing microcirculation in two subdivided layers, yielded contrary results, an increased subdivision of retinal microvasculature might offer an even more fine analysis. The aim of the study was to investigate retinal microcirculation by OCT-A after COVID-19 infection in three subdivided layers (I). In addition, short-term retinal affections were monitored during COVID-19 disease (II). Considering (I), a prospective study (33 patients
post−COVID
and 28 controls) was done. Macula and peripapillary vessel density (VD) were scanned with the Spectralis II. Macula VD was measured in three layers: superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Analysis was done by the EA-Tool, including an Anatomical Positioning System and an analysis of peripapillary VD by implementing Bruch's membrane opening (BMO) landmarks. Overall, circular (c
1
, c
2
, and c
3
) and sectorial VD (s
1
-s
12
) was analyzed. Considering (II), in a retrospective study, 29 patients with severe complications of COVID-19 infection, hospitalized at the intensive care unit, were monitored for retinal findings at bedside during hospitalization. (I) Overall (
p
= 0.0133) and circular (c
1
,
p
= 0.00257; c
2
,
p
= 0.0067; and c
3
,
p
= 0.0345). VD of the ICP was significantly reduced between patients
post−COVID
and controls, respectively. Overall (
p
= 0.0179) and circular (c
1
,
p
= 0.0189) peripapillary VD was significantly reduced between both groups. Subgroup analysis of hospitalized vs. non-hospitalized patients
post−COVID
yielded a significantly reduced VD of adjacent layers (DCP and SVP) with increased severity of COVID-19 disease. Clinical severity parameters showed a negative correlation with VD (ICP) and peripapillary VD. (II) Funduscopy yielded retinal hemorrhages and cotton wool spots in 17% of patients during SARS-CoV-2 infection. As VD of the ICP and peripapillary regions was significantly reduced after COVID-19 disease and showed a link to clinical severity markers, we assume that the severity of capillary impairment after COVID-19 infection is mapped on retinal microcirculation, visualized by non-invasive OCT-A.
Recent studies reporting widespread declines in arthropod biomass, abundance and species diversity raised wide concerns in research and conservation. However, repeated arthropod surveys over long ...periods are rare, even though they are key for assessing the causes of the decline and for developing measures to halt the losses. We repeatedly sampled arthropod fauna in a representative Swiss agricultural landscape over 32 years (1987, 1997, 2019). Sampling included eight study sites in four different semi-natural and agricultural habitat types and different trap types (pitfall, window, yellow bucket) over an annual period of 10 weeks to capture flying and ground dwelling arthropod taxa. In total, we analyzed 58,448 individuals from 1343 different species. Mean arthropod biomass, abundance and species richness per trap was significantly higher in 2019 than in the prior years. Also, species diversity of the study area was highest in 2019. Three main factors likely have contributed to the observed positive or at least stable development. First, the implementation of agri-environmental schemes has improved habitat quality since 1993, 6 years after the first sampling. Second, landscape composition remained stable, and pesticide and fertilizer was constant over the study period. Third, climate warming might have favored the immigration and increase of warm adapted species. Our results support the idea that changes in arthropod communities over time is highly context-dependent and complex.
Implications for insect conservation
We conclude that the integration and long-term management of ecological compensation patches into a heterogenous agricultural landscape supports insect conservation and can contribute to stable or even increased arthropod abundance, biomass and diversity. Future studies are needed to clarify interdepending effects between agricultural management and climate change on insect communities.
•Deletion of content on Twitter, Youtube and Facebook in connection with the NetzDG.•Legal strength on Turkey, Russia, Germany, UK and USA with regard to Internet laws.•Influence of NetzDG on ...denunciation and a possible emergence of neo informers.
Facing the increasing prevalence of hate speech and other personality rights violations on social media, the legislature tries to improve the law enforcement by involving the social media companies. In 2017, the German Bundestag passed a new law, the Network Enforcement Act (NetzDG), which requires website owners to review the content published on their pages upon it being reported by users and to remove it as soon as possible in the event of a breach of the law. This forces social media operators to establish efficient reporting systems which can create breeding grounds for user denunciation. To get an overview of whether this is really the case, we briefly discuss state surveillance and denunciation and analyse the statistics of content blockings and deletions in five countries (USA, Germany, United Kingdom, Russia and Turkey). In Germany the number of blockings and deletions of content has risen for Facebook, Twitter and YouTube due to the NetzDG, but it has also been found that the majority of reports were unjustified as they did not lead to any restriction or deletion of the content. When comparing the German numbers with those of the other countries investigated, it becomes apparent that after the introduction of the NetzDG in Germany, more content is being blocked and deleted. Also, a comparison of the various laws regulating online content in these countries was conducted. It was found that not only Germany has tightened the regulation of online content and that other countries are also trying to transform the Internet into a more hate free environment.
spp. are frequently encountered in specimens from ICUs. However, most of these detections represent colonization. Nevertheless, clinical practice shows that a considerable proportion of these ...patients will receive antifungal therapy (AT). β-(1→3)-D-glucan (BDG) and mannan are fungal biomarkers with high negative predictive values. We aimed to examine whether biomarker-guided discontinuation of AT can reduce the antifungal consumption. Therefore, we conducted a prospective, randomized intervention study between 1 April 2019 and 31 March 2020. All adult ICU patients with a newly started systemic AT but without fungal infection were eligible for inclusion. Enrolled patients were randomized into an intervention and a control group. In both groups, serum BDG and mannan were determined on days 1 and 2 of AT. If all measurements were negative, AT was discontinued in the intervention group. The primary endpoint was antifungal use. The study was terminated after 12 months. Until this time-point, 41 patients had been included. In the intervention group (
= 19), AT was stopped in only two patients because all others showed either positive BDG and/or mannan levels. One of these two patients developed candidemia and AT had to be restarted. There was no significant difference in the primary and secondary endpoints. In summary, the strategy of using two negative BDG and mannan levels to stop AT failed to reduce antifungal consumption in our cohort. Indeed, there will inevitably be patients with invasive candidiasis in whom necessary AT is discontinued. The optimal patient population, biomarker set, and termination criteria are critical to the success of biomarker-based termination strategies.
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