Fatal Pneumonia Associated With a Novel Genotype of Human Coronavirus OC43

Since its first discovery in 1967, human coronavirus OC43 (HCoV-OC43) has been associated with mild self-limiting upper respiratory infections worldwide. Fatal primary pneumonia due to HCoV-OC43 is not frequently described. This study describes a case of fatal primary pneumonia associated with HCoV-OC43 in a 75-year-old patient with good past health. The viral loads of the respiratory tract specimens (bronchoalveolar lavage and endotracheal aspirate) from diagnosis to death were persistently high (3.49 × 106–1.10 × 1010 copies/ml). HCoV-OC43 at a 6.46 × 103 copies/ml level was also detected from his pleural fluid 2 days before his death. Complete genome sequencing and phylogenetic analysis showed that the present HCoV-OC43 forms a distinct cluster with three other HCoV-OC43 from United States, with a bootstrap value of 100% and sharing 99.9% nucleotide identities. Pairwise genetic distance between this cluster and other HCoV-OC43 genotypes ranged from 0.27 ± 0.02% to 1.25 ± 0.01%. In contrast, the lowest pairwise genetic distance between existing HCoV-OC43 genotypes was 0.26 ± 0.02%, suggesting that this cluster constitutes a novel HCoV-OC43 genotype, which we named genotype I. Unlike genotypes D, E, F, G, and H, no recombination event was observed for this novel genotype. Structural modeling revealed that the loop with the S1/S2 cleavage site was four amino acids longer than other HCoV-OC43, making it more exposed and accessible to protease, which may have resulted in its possible hypervirulence.

Ageing societies and the first and second waves of the COVID-19 pandemic – Statements of the European Geriatric Medicine Society and measures of the Hungarian Government concerning older people

Purpose Ageing of the societies is a demographic phenomenon in the developed world. SARS-CoV-2 is a novel human coronavirus responsible for a pandemic of coronavirus disease 2019 (COVID-19). World Health Organization (WHO) data demonstrated that the first two waves of the pandemic had the most severe impact on older people and that is why new guidelines and protocols were necessary in geriatric medicine to protect senior citizens. Materials and methods In our publication, we summarise the three statements of EuGMS concerning the first and second waves of COVID-19 pandemic in Europe. Besides following the European recommendations, a proper local response was necessary in each country. Results The Hungarian Government has successfully completed the necessary measures during the first two waves, which are summarised in our publication. Those measures took into consideration not only the international guidelines, but the capacities of the healthcare system, as well as the sociodemographic and economic characteristics of the country. Conclusions Successful local defence against COVID-19 required adequate and optimised interpretation of the international guidelines to save the life of thousands of older adults in Hungary.

COVID-19

Since December 2019, a pneumonia outbreak with unknown etiology occurred in Wuhan, China. Later, the pathogen was identified as novel human coronavirus and named as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The disease was named corona virus disease 2019 (COVID-19) and caused a pandemic. As of 23 June 2020, the global COVID-19 pandemic has battered the world. More than 1.5 million people have died with over 80 million people confirmed infected. This outbreak is spreading in approximately 216 countries and regions as of 22 July 2020. Comparing the three human coronavirus, SARS and MERS have significantly higher case fatality rates than COVID-19, but COVID-19 is more infectious and spreads more easily among people. Therefore, in this chapter, the authors summarize the most fatal pandemic in recorded history. Also, they collected all information about the current knowledge about COVID-19 pandemic including similarity and differences with other human coronaviruses.

Exploring the Lethality of Human-Adapted Coronavirus through Alignment-Free Machine Learning Approaches Using Genomic Sequences

Background: A newly emerging novel coronavirus appeared and rapidly spread worldwide and World Health Organization declared a pandemic on March 11, 2020. The roles and characteristics of coronavirus have captured much attention due to its power of causing a wide variety of infectious diseases, from mild to severe, on humans. The detection of the lethality of human coronavirus is key to estimate the viral toxicity and provide perspectives for treatment. Methods: We developed an alignment-free framework that utilizes machine learning approaches for an ultra-fast and highly accurate prediction of the lethality of human-adapted coronavirus using genomic sequences. We performed extensive experiments through six different feature transformation and machine learning algorithms combining digital signal processing to identify the lethality of possible future novel coronaviruses using existing strains. Results: The results tested on SARS-CoV, MERS-CoV and SARS-CoV-2 datasets show an average 96.7% prediction accuracy. We also provide preliminary analysis validating the effectiveness of our models through other human coronaviruses. Our framework achieves high levels of prediction performance that is alignment-free and based on RNA sequences alone without genome annotations and specialized biological knowledge. Conclusion: The results demonstrate that, for any novel human coronavirus strains, this study can offer a reliable real-time estimation for its viral lethality.

The NSP14/NSP10 RNA repair complex as a Pan-coronavirus therapeutic target

The risk of zoonotic coronavirus spillover into the human population, as highlighted by the SARS-CoV-2 pandemic, demands the development of pan-coronavirus antivirals. The efficacy of existing antiviral ribonucleoside/ribonucleotide analogs, such as remdesivir, is decreased by the viral proofreading exonuclease NSP14-NSP10 complex. Here, using a novel assay and in silico modeling and screening, we identified NSP14-NSP10 inhibitors that increase remdesivir’s potency. A model compound, sofalcone, both inhibits the exonuclease activity of SARS-CoV-2, SARS-CoV, and MERS-CoV in vitro, and synergistically enhances the antiviral effect of remdesivir, suppressing the replication of SARS-CoV-2 and the related human coronavirus OC43. The validation of top hits from our primary screenings using cellular systems provides proof-of-concept for the NSP14 complex as a therapeutic target.

Continuously Active Disinfectant Inactivates SARS-CoV-2 and Human Coronavirus 229E Two Days After the Disinfectant Was Applied and Following Wear Exposures

The surface environment in COVID-19 patient’s rooms may be persistently contaminated despite disinfection. A continuously active disinfectant demonstrated excellent sustained antiviral activity following a 48-hour period of wear and abrasion exposures with reinoculations. Reductions of >4-log10 were achieved within a 1-minute contact time for SARS-CoV-2 and the human coronavirus, 229E.