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OBJECTIVES: To investigate in silico the presence of nucleotide sequence complementarity between the RNA genome of Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) and human non-coding (nc)RNA genes.METHODS: The FASTA sequence (NC_045512.2) of each of the 11 SARS-CoV-2 isolate Wuhan-Hu-1 genes was retrieved from NCBI.nlm.nih.gov/gene and the Ensembl.org library interrogated for any base-pair match with human ncRNA genes. SARS-CoV-2 gene-matched human ncRNAs were screened for functional activity using bioinformatic analysis. Finally, associations between identified ncRNAs and human diseases were searched in GWAS databases.RESULTS: A total of 252 matches were found between the nucleotide sequence of SARS-CoV-2 genes and human ncRNAs. With the exception of two small nuclear RNAs, all of them were long non-coding (lnc)RNAs expressed mainly in testis and central nervous system under physiological conditions. The percentage of alignment ranged from 91.30% to 100% with a mean nucleotide alignment length of 17.5 ± 2.4. Thirty-three (13.9%) of them contained predicted R-loop forming sequences, but none of these intersected the complementary sequences of SARS-CoV-2. However, in 31 cases matches fell on ncRNA regulatory sites, whose adjacent coding genes are mostly involved in cancer, immunological and neurological pathways. Similarly, several polymorphic variants of detected non-coding genes have been associated with neuropsychiatric and proliferative disorders.CONCLUSION: This pivotal in silico study shows that SARS-CoV-2 genes have Watson-Crick nucleotide complementarity to human ncRNA sequences, potentially disrupting ncRNA epigenetic control of target genes. It remains to be elucidated whether this could result in the development of human disease in the long term.

The IFNL4 gene is a recently discovered type III interferon, which in a significant fraction of the human population harbours a frameshift mutation abolishing the IFNk4 ORF. The expression of IFNk4 is correlated with both poor spontaneous clearance of hepatitis C virus (HCV) and poor response to treatment with type I interferon. Here, we show that the IFNL4 gene encodes an active type III interferon, named IFNk4, which signals through the IFNkR1 and IL-10R2 receptor chains. Recombinant IFNk4 is antiviral against both HCV and coronaviruses at levels comparable to IFNk3. However, the secretion of IFNk4 is impaired compared to that of IFNk3, and this impairment is not due to a weak signal peptide, which was previously believed. We found that IFNk4 gets N-linked glycosylated and that this glycosylation is required for secretion. Nevertheless, this glycosylation is not required for activity. Together, these findings result in the paradox that IFNk4 is strongly antiviral but a disadvantage during HCV infection. The IFNL4 gene is a recently discovered type III interferon, which in a significant fraction of the human population harbours a frameshift mutation abolishing the IFNλ4 ORF. The expression of IFNλ4 is correlated with both poor spontaneous clearance of hepatitis C virus (HCV) and poor response to treatment with type I interferon. Here, we show that the IFNL4 gene encodes an active type III interferon, named IFNλ4, which signals through the IFNλR1 and IL-10R2 receptor chains. Recombinant IFNλ4 is antiviral against both HCV and coronaviruses at levels comparable to IFNλ3. However, the secretion of IFNλ4 is impaired compared to that of IFNλ3, and this impairment is not due to a weak signal peptide, which was previously believed. We found that IFNλ4 gets N-linked glycosylated and that this glycosylation is required for secretion. Nevertheless, this glycosylation is not required for activity. Together, these findings result in the paradox that IFNλ4 is strongly antiviral but a disadvantage during HCV infection

Purpose. The pathogenesis of rhegmatogenous retinal detachment (RRD) remains incompletely understood, with no clinically effective treatment for potentially severe complications such as photoreceptor cell death and proliferative vitreoretinopathy. Here we investigate the protein profile of the vitreous following experimental retinal detachment using a comparative proteomic based approach.Materials and Methods. Retinal detachment was created in the right eyes of six New Zealand red pigmented rabbits. Sham surgery was undertaken in five other rabbits that were used as controls. After seven days the eyes were enucleated and the vitreous was removed. The vitreous samples were evaluated with two-dimensional polyacrylamide gel electrophoresis and the differentially expressed proteins were identified with tandem mass spectrometry.Results. Ten protein spots were found to be at least twofold differentially expressed when comparing the vitreous samples of the sham and retinal detachment surgery groups. Protein spots that were upregulated in the vitreous following retinal detachment were identified as albumin fragments, and those downregulated were found to be peroxiredoxin 2, collagen-Iα1 fragment, andα-1-antiproteinase F.Conclusions. Proteomic investigation of the rabbit vitreous has identified a set of proteins that help further our understanding of the pathogenesis of rhegmatogenous retinal detachment and its complications.

"Testing Denmark" is a national, large-scale, epidemiological surveillance study of SARS-CoV-2 in the Danish population. Between September and October 2020, approximately 1.3 million people (age >15 years) were randomly invited to fill in an electronic questionnaire covering COVID-19 exposures and symptoms. The prevalence of SARS-CoV-2 antibodies was determined by point-of care rapid test (POCT) distributed to participants' home addresses. In total, 318,552 participants (24.5% invitees) completed the study and 2,519 (0.79%) were seropositive. Of the participants with a prior positive PCR test (n = 1,828), 29.1% were seropositive in the POCT. Although seropositivity increased with age, participants 61 years and over reported fewer symptoms and were tested less frequently. Seropositivity was associated with physical contact with SARS-CoV-2 infected individuals (risk ratio [RR] 7.43, 95% CI: 6.57-8.41), particular in household members (RR 17.70, 95% CI: 15.60-20.10). A greater risk of seropositivity was seen in home care workers (RR 2.09, 95% CI: 1.58-2.78) compared to office workers. A high degree of adherence with national preventive recommendations was reported (e.g., >80% use of face masks), but no difference were found between seropositive and seronegative participants. The seroprevalence result was somewhat hampered by a lower-than-expected performance of the POCT. This is likely due to a low sensitivity of the POCT or problems reading the test results, and the main findings therefore relate to risk associations. More emphasis should be placed on age, occupation, and exposure in local communities. IMPORTANCE To date, including 318,522 participants, this is the largest population-based study with broad national participation where tests and questionnaires have been sent to participants' homes. We found that more emphasis from national and local authorities toward the risk of infection should be placed on age of tested individuals, type of occupation, as well as exposure in local communities and households. To meet the challenge that broad nationwide information can be difficult to gather. This study design sets the stage for a novel way of conducting studies. Additionally, this study design can be used as a supplementary model in future general test strategy for ongoing monitoring of COVID-19 immunity in the population, both from past infection and from vaccination against SARS-CoV-2, however, with attention to the complexity of performing and reading the POCT at home.

Association of Surgeons in Training Surgical Summit, online, 17 Oct 2020 - 17 Oct 2020 2021 Virtual Annual Meeting / Surgical Research Society, online, 24 Mar 2021 - 25 Mar 2021, National Research Collaborative Meeting, online, 10 Dec 2020 - 10 Dec 2020, Royal Australasian College of Surgeons Annual Academic Surgery Conference, online, 5 Nov 2020 - 5 Nov 2020; The British journal of surgery : BJS 108(12), 1448-1464 (2021). doi:10.1093/bjs/znab336 Published by Wiley, New York, NY [u.a.]