Here, we describe a serological enzyme-linked immunosorbent assay for the screening and identification of human SARS-CoV-2 seroconverters. This assay does not require the handling of infectious ...virus, can be adjusted to detect different antibody types in serum and plasma and is amenable to scaling. Serological assays are of critical importance to help define previous exposure to SARS-CoV-2 in populations, identify highly reactive human donors for convalescent plasma therapy and investigate correlates of protection.
As SARS-CoV-2 has been circulating for over a year, dozens of vaccine candidates are under development or in clinical use. The BNT162b2 mRNA COVID-19 vaccine induces spike protein-specific ...neutralizing antibodies associated with protective immunity. The emergence of the B.1.1.7 and B.1.351 variants has raised concerns of reduced vaccine efficacy and increased re-infection rates. Here we show, that after the second dose, the sera of BNT162b2-vaccinated health care workers (n = 180) effectively neutralize the SARS-CoV-2 variant with the D614G substitution and the B.1.1.7 variant, whereas the neutralization of the B.1.351 variant is five-fold reduced. Despite the reduction, 92% of the seronegative vaccinees have a neutralization titre of >20 for the B.1.351 variant indicating some protection. The vaccinees' neutralization titres exceeded those of recovered non-hospitalized COVID-19 patients. Our work provides evidence that the second dose of the BNT162b2 vaccine induces cross-neutralization of at least some of the circulating SARS-CoV-2 variants.
Summary We review the epidemiological and clinical characteristics of tick-borne encephalitis, and summarise biological and virological aspects that are important for understanding the life-cycle and ...transmission of the virus. Tick-borne encephalitis virus is a flavivirus that is transmitted by Ixodes spp ticks in a vast area from western Europe to the eastern coast of Japan. Tick-borne encephalitis causes acute meningoencephalitis with or without myelitis. Morbidity is age dependent, and is highest in adults of whom half develop encephalitis. A third of patients have longlasting sequelae, frequently with cognitive dysfunction and substantial impairment in quality of life. The disease arises in patchy endemic foci in Europe, with climatic and ecological conditions suitable for circulation of the virus. Climate change and leisure habits expose more people to tick-bites and have contributed to the increase in number of cases despite availability of effective vaccines. The serological diagnosis is usually straightforward. No specific treatment for the disease exists, and immunisation is the main preventive measure.
The causative agent of coronavirus disease 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For many viruses, tissue tropism is determined by the availability of ...virus receptors and entry cofactors on the surface of host cells. In this study, we found that neuropilin-1 (NRP1), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity, an effect blocked by a monoclonal blocking antibody against NRP1. A SARS-CoV-2 mutant with an altered furin cleavage site did not depend on NRP1 for infectivity. Pathological analysis of olfactory epithelium obtained from human COVID-19 autopsies revealed that SARS-CoV-2 infected NRP1-positive cells facing the nasal cavity. Our data provide insight into SARS-CoV-2 cell infectivity and define a potential target for antiviral intervention.
Two COVID-19 mRNA (of BNT162b2, mRNA-1273) and two adenovirus vector vaccines (ChAdOx1 and Janssen) are licensed in Europe, but optimization of regime and dosing is still ongoing. Here we show in ...health care workers (n = 328) that two doses of BNT162b2, mRNA-1273, or a combination of ChAdOx1 adenovirus vector and mRNA vaccines administrated with a long 12-week dose interval induce equally high levels of anti-SARS-CoV-2 spike antibodies and neutralizing antibodies against D614 and Delta variant. By contrast, two doses of BNT162b2 with a short 3-week interval induce 2-3-fold lower titers of neutralizing antibodies than those from the 12-week interval, yet a third BNT162b2 or mRNA-1273 booster dose increases the antibody levels 4-fold compared to the levels after the second dose, as well as induces neutralizing antibody against Omicron BA.1 variant. Our data thus indicates that a third COVID-19 mRNA vaccine may induce cross-protective neutralizing antibodies against multiple variants.
The current outbreak of Zika virus (ZIKV) infection has been associated with an apparent increased risk of congenital microcephaly. We describe a case of a pregnant woman and her fetus infected with ...ZIKV during the 11th gestational week. The fetal head circumference decreased from the 47th percentile to the 24th percentile between 16 and 20 weeks of gestation. ZIKV RNA was identified in maternal serum at 16 and 21 weeks of gestation. At 19 and 20 weeks of gestation, substantial brain abnormalities were detected on ultrasonography and magnetic resonance imaging (MRI) without the presence of microcephaly or intracranial calcifications. On postmortem analysis of the fetal brain, diffuse cerebral cortical thinning, high ZIKV RNA loads, and viral particles were detected, and ZIKV was subsequently isolated.
SARS-CoV-2 infection has a risk to develop into life-threatening COVID-19 disease. Whereas age, hypertension, and chronic inflammatory conditions are risk factors, underlying host factors and markers ...for disease severity, e.g. requiring intensive care unit (ICU) treatment, remain poorly defined. To this end, we longitudinally profiled blood inflammation markers, antibodies, and 101 plasma proteins of hospitalized COVID-19 patients who did or did not require ICU admission. While essentially all patients displayed SARS-CoV-2-specific antibodies and virus-neutralization capacity within 12-15 days, a rapid, mostly transient upregulation of selective inflammatory markers including IL-6, CXCL10, CXCL11, IFNγ, IL-10, and monocyte-attracting CCL2, CCL7 and CCL8, was particularly evident in ICU patients. In addition, there was consistent and sustained upregulation of apoptosis-associated proteins CASP8, TNFSF14, HGF, and TGFB1, with HGF discriminating between ICU and non-ICU cohorts. Thus, COVID-19 is associated with a selective inflammatory milieu within which the apoptotic pathway is a cardinal feature with potential to aid risk-based patient stratification.
Viral infections may trigger type 1 diabetes (T1D), and recent reports suggest an increased incidence of paediatric T1D and/or diabetic ketoacidosis (DKA) during the COVID-19 pandemic.
To study ...whether the number of children admitted to the paediatric intensive care unit (PICU) for DKA due to new-onset T1D increased during the COVID-19 pandemic, and whether SARS-CoV-2 infection plays a role.
This retrospective cohort study comprises two datasets: (1) children admitted to PICU due to new-onset T1D and (2) children diagnosed with new-onset T1D and registered to the Finnish Pediatric Diabetes Registry in the Helsinki University Hospital from 1 April to 31 October in 2016-2020. We compared the incidence, number and characteristics of children with newly diagnosed T1D between the prepandemic and pandemic periods.
The number of children admitted to PICU due to new-onset T1D increased from an average of 6.25 admissions in 2016-2019 to 20 admissions in 2020 (incidence rate ratio IRR 3.24 95% CI 1.80 to 5.83; p=0.0001). On average, 57.75 children were registered to the FPDR in 2016-2019, as compared with 84 in 2020 (IRR 1.45; 95% CI 1.13 to 1.86; p=0.004). 33 of the children diagnosed in 2020 were analysed for SARS-CoV-2 antibodies, and all were negative.
More children with T1D had severe DKA at diagnosis during the pandemic. This was not a consequence of SARS-CoV-2 infection. Instead, it probably stems from delays in diagnosis following changes in parental behaviour and healthcare accessibility.
Abstract
Background
SARS-CoV-2 related research has increased in importance worldwide since December 2019. Several new variants of SARS-CoV-2 have emerged globally, of which the most notable and ...concerning currently are the UK variant B.1.1.7, the South African variant B1.351 and the Brazilian variant P.1. Detecting and monitoring novel variants is essential in SARS-CoV-2 surveillance. While there are several tools for assembling virus genomes and performing lineage analyses to investigate SARS-CoV-2, each is limited to performing singular or a few functions separately.
Results
Due to the lack of publicly available pipelines, which could perform fast reference-based assemblies on raw SARS-CoV-2 sequences in addition to identifying lineages to detect variants of concern, we have developed an open source bioinformatic pipeline called
HAVoC
(Helsinki university Analyzer for Variants of Concern).
HAVoC
can reference assemble raw sequence reads and assign the corresponding lineages to SARS-CoV-2 sequences.
Conclusions
HAVoC
is a pipeline utilizing several bioinformatic tools to perform multiple necessary analyses for investigating genetic variance among SARS-CoV-2 samples. The pipeline is particularly useful for those who need a more accessible and fast tool to detect and monitor the spread of SARS-CoV-2 variants of concern during local outbreaks.
HAVoC
is currently being used in Finland for monitoring the spread of SARS-CoV-2 variants.
HAVoC
user manual and source code are available at
https://www.helsinki.fi/en/projects/havoc
and
https://bitbucket.org/auto_cov_pipeline/havoc
, respectively.
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