Detection of SARS-CoV-2 nucleocapsid antigen from serum can aid in timing of COVID-19 infection

SARS-CoV-2 RNA can be detected in respiratory samples for weeks after onset of COVID-19 disease. Therefore, one of the diagnostic challenges of PCR positive cases is differentiating between acute COVID-19 disease and convalescent phase. The presence of SARS-CoV-2 nucleocapsid antigen in serum and plasma samples of COVID-19 patients has been demonstrated previously. Our study aimed to characterize the analytical specificity and sensitivity of an enzyme-linked immunosorbent assay (Salocor SARS-CoV-2 Antigen Quantitative Assay Kit (c) (Salofa Ltd, Salo, Finland)) for the detection of SARS-CoV-2 nucleocapsid antigen in serum, and to characterize the kinetics of antigenemia. The evaluation material included a negative serum panel of 155 samples, and 126 serum samples from patients with PCR-confirmed COVID-19. The specificity of the Salocor SARS-CoV-2 serum nucleocapsid antigen test was 98.0 %. In comparison with simultaneous positive PCR from upper respiratory tract (URT) specimens, the test sensitivity was 91.7 %. In a serum panel in which the earliest serum sample was collected two days before the collection of positive URT specimen, and the latest 48 days after (median 1 day post URT sample collection), the serum N antigen test sensitivity was 95.6 % within 14 days post onset of symptoms. The antigenemia resolved approximately two weeks after the onset of disease and diagnostic PCR. The combination of simultaneous SARS-CoV-2 antigen and antibody testing appeared to provide useful in-formation for timing of COVID-19. Our results suggest that SARS-CoV-2 N-antigenemia may be used as a diag-nostic marker in acute COVID-19.Peer reviewe

Fatal Tick-Borne Encephalitis Virus Infections Caused by Siberian and European Subtypes, Finland, 2015

In most locations except for Russia, tick-borne encephalitis is mainly caused by the European virus subtype. In 2015, fatal infections caused by European and Siberian tick-borne encephalitis virus subtypes in the same Ixodes ricinus tick focus in Finland raised concern over further spread of the Siberian subtype among widespread tick species.Peer reviewe

Exploring options for sustainable intensification in different farming system types of four Africa RISING countries

Sustainable intensification is proposed as a promising way to increase the productivity of agricultural systems while reducing pressure on ecosystems, safeguarding equitable relations among societal groups, and supporting the economic viability of households, enterprises, and communities. In sub-Saharan Africa, the identification and dissemination of options for sustainable intensification is hampered by the large diversity within and between farming systems, and their complexity arising from the interactions among different farm components and external factors. This study therefore uses an integrated farming systems approach to identify and assess context-specific improvements that can then be implemented and tested on-farm to foster experiential learning and facilitate adoption. We conducted a farming systems analysis for nine Africa RISING intervention sites across four countries, based on rapid and detailed farm characterizations, followed by model-supported diagnosis, and exploration of options for sustainable intensification. Farm diversity was described and analyzed by means of typologies and cross-site comparisons. Identified constraints varied depending on site and farming system type, but commonly included low input availability, climatic variability, poor soil fertility, sub-optimal livestock feeding, biotic stresses, and poor access to training and technical advice, all impairing farm productivity, returns to labor and capital inputs, income generation and food security. We investigated entry points that tackle the above constraints by exploring alternative farm configurations, technologies and practices for representative farms. By assessing potential impact of these changes on indicators beyond productivity, trade-offs were identified and assessed, for instance between profitability and household food self-sufficiency, and between nitrogen availability for crop uptake and increased nutrient losses. Taking a systems perspective during the entry point evaluation allowed differentiating potential effects on indicators at the field level versus the farm and household level. The exploration of options for specific farming system types now enables more targeted testing of promising innovations with farmers in the second project phase

Molecular detection and phylogenetic analysis of Borrelia miyamotoi strains from ticks collected in the capital region of Finland

Borrelia miyamotoi is an emerging pathogen that shares high similarity with relapsing fever Borrelia, but has an atypical clinical presentation. Within the framework of tick-borne disease surveillance in Finland, human serum samples suspected for tick-borne encephalitis (n=974) and questing ticks (n=739) were collected from the capital region in Finland to determine the prevalence of B. miyamotoi. All tested human samples were negative and 5 (0.68 %) Ixodes ricinus ticks were positive for B. miyamotoi. Partial sequencing of the flagellin (flaB) gene of 3 positive samples and 27 B. miyamotoi-positive tick samples obtained from previous studies across Finland were amplified, sequenced, and included in the phylogenetic analysis.The phylogenetic tree revealed that most B. miyamotoi strains isolated from ticks in Finland share high similarity with other European strains, including strains related to human infection. Possible disease transmission may occur during exposure to tick bites. A single strain collected from an I. persulcatus tick in Pajujärvi grouped with an outlier of B. miyamotoi strains isolated from Russia and Far East Asian countries. Further studies should investigate the pathogen’s role in human infection in Finland.Another important finding is the occurrence of I. persulcatus ticks (8%) collected by crowdsourcing from the coastal southern part of Finland. This suggests a regular introduction and a possible wide expansion of this tick species in the country. This could be associated with transmission of new pathogens.</p

Nanomolar inhibition of SARS-CoV-2 infection by an unmodified peptide targeting the prehairpin intermediate of the spike protein

Publisher Copyright: © 2022 National Academy of Sciences. All rights reserved.Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge currently available coronavirus disease 2019 vaccines and monoclonal antibody therapies through epitope change on the receptor binding domain of the viral spike glycoprotein. Hence, there is a specific urgent need for alternative antivirals that target processes less likely to be affected by mutation, such as the membrane fusion step of viral entry into the host cell. One such antiviral class includes peptide inhibitors, which block formation of the so-called heptad repeat 1 and 2 (HR1HR2) six-helix bundle of the SARS-CoV-2 spike (S) protein and thus interfere with viral membrane fusion. We performed structural studies of the HR1HR2 bundle, revealing an extended, well-folded N-terminal region of HR2 that interacts with the HR1 triple helix. Based on this structure, we designed an extended HR2 peptide that achieves single-digit nanomolar inhibition of SARS-CoV-2 in cell-based and virus-based assays without the need for modifications such as lipidation or chemical stapling. The peptide also strongly inhibits all major SARS-CoV-2 variants to date. This extended peptide is ∼100-fold more potent than all previously published short, unmodified HR2 peptides, and it has a very long inhibition lifetime after washout in virus infection assays, suggesting that it targets a prehairpin intermediate of the SARS-CoV-2 S protein. Together, these results suggest that regions outside the HR2 helical region may offer new opportunities for potent peptide-derived therapeutics for SARS-CoV-2 and its variants, and even more distantly related viruses, and provide further support for the prehairpin intermediate of the S protein.Peer reviewe

Detection of novel tick-borne pathogen, Alongshan virus, in Ixodes ricinus ticks, south-eastern Finland, 2019

The newly identified tick-borne Alongshan virus (ALSV), a segmented Jingmen virus group flavivirus, was recently associated with human disease in China. We report the detection of ALSV RNA in Ixodes ricinus ticks in south-eastern Finland. Screening of sera from patients suspected for tick-borne encephalitis for Jingmen tick virus-like virus RNA and antibodies revealed no human cases. The presence of ALSV in common European ticks warrants further investigations on its role as a human pathogen.Peer reviewe

Imaging of αvβ3 integrin expression in experimental myocardial ischemia with [68Ga]NODAGA-RGD positron emission tomography

BACKGROUND: Radiolabeled RGD peptides detect αvβ3 integrin expression associated with angiogenesis and extracellular matrix remodeling after myocardial infarction. We studied whether cardiac positron emission tomography (PET) with [68Ga]NODAGA-RGD detects increased αvβ3 integrin expression after induction of flow-limiting coronary stenosis in pigs, and whether αvβ3 integrin is expressed in viable ischemic or injured myocardium.METHODS: We studied 8 Finnish landrace pigs 13 ± 4 days after percutaneous implantation of a bottleneck stent in the proximal left anterior descending coronary artery. Antithrombotic therapy was used to prevent stent occlusion. Myocardial uptake of [68Ga]NODAGA-RGD (290 ± 31 MBq) was evaluated by a 62 min dynamic PET scan. The ischemic area was defined as the regional perfusion abnormality during adenosine-induced stress by [15O]water PET. Guided by triphenyltetrazolium chloride staining, tissue samples from viable and injured myocardial areas were obtained for autoradiography and histology.RESULTS: Stent implantation resulted in a partly reversible myocardial perfusion abnormality. Compared with remote myocardium, [68Ga]NODAGA-RGD PET showed increased tracer uptake in the ischemic area (ischemic-to-remote ratio 1.3 ± 0.20, p = 0.0034). Tissue samples from the injured areas, but not from the viable ischemic areas, showed higher [68Ga]NODAGA-RGD uptake than the remote non-ischemic myocardium. Uptake of [68Ga]NODAGA-RGD correlated with immunohistochemical detection of αvβ3 integrin that was expressed in the injured myocardial areas.CONCLUSIONS: Cardiac [68Ga]NODAGA-RGD PET demonstrates increased myocardial αvβ3 integrin expression after induction of flow-limiting coronary stenosis in pigs. Localization of [68Ga]NODAGA-RGD uptake indicates that it reflects αvβ3 integrin expression associated with repair of recent myocardial injury.</p

Quantification of porcine myocardial perfusion with modified dual bolus MRI : a prospective study with a PET reference

Abstract Background The reliable quantification of myocardial blood flow (MBF) with MRI, necessitates the correction of errors in arterial input function (AIF) caused by the T1 saturation effect. The aim of this study was to compare MBF determined by a traditional dual bolus method against a modified dual bolus approach and to evaluate both methods against PET in a porcine model of myocardial ischemia. Methods Local myocardial ischemia was induced in five pigs, which were subsequently examined with contrast enhanced MRI (gadoteric acid) and PET (O-15 water). In the determination of MBF, the initial high concentration AIF was corrected using the ratio of low and high contrast AIF areas, normalized according to the corresponding heart rates. MBF was determined from the MRI, during stress and at rest, using the dual bolus and the modified dual bolus methods in 24 segments of the myocardium (total of 240 segments, five pigs in stress and rest). Due to image artifacts and technical problems 53% of the segments had to be rejected from further analyses. These two estimates were later compared against respective rest and stress PET-based MBF measurements. Results Values of MBF were determined for 112/240 regions. Correlations for MBF between the modified dual bolus method and PET was rs = 0.84, and between the traditional dual bolus method and PET rs = 0.79. The intraclass correlation was very good (ICC = 0.85) between the modified dual bolus method and PET, but poor between the traditional dual bolus method and PET (ICC = 0.07). Conclusions The modified dual bolus method showed a better agreement with PET than the traditional dual bolus method. The modified dual bolus method was found to be more reliable than the traditional dual bolus method, especially when there was variation in the heart rate. However, the difference between the MBF values estimated with either of the two MRI-based dual-bolus methods and those estimated with the gold-standard PET method were statistically significant