Analysis of the Virus SARS-CoV-2 as a Potential Bioweapon in Light of International Literature.

INTRODUCTION: As of early 2022, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic still represents a worldwide medical emergency situation. The ongoing vaccination programs can slow down the spread of the virus; however, from time to time, the newly emerging variants of concern and antivaccination movements carry the possibility for the disease to remain in our daily lives. After the appearance of SARS-CoV-2, there was scholarly debate whether the virus was of natural origin, or it emerged from a laboratory, some even thinking the agent's potential biological weapon properties suggest the latter scenario. Later, the bioweapon theory was dismissed by the majority of experts, but the question remains that despite its natural origin, how potent a biological weapon the SARS-CoV-2 virus can become over time. MATERIALS AND METHODS: Based on 12 bioweapon threat assessment criteria already published in 2018, we performed a literature search and review, focusing on relevant potential bioweapon properties of the virus SARS-CoV-2. Instead of utilizing a survey among experts, we tried to qualify and quantify characteristics according to the available data found in peer-reviewed papers. We also identified other key elements not mentioned in the original 12 bioweapon criteria, which can play an important role in assessing future biological weapons. RESULTS: According to the international literature we analyzed, SARS-CoV-2 is a moderately infectious agent (ID50 estimated between 100 and 1,000), with high infection-to-disease ratio (35%-45% rate of asymptomatic infected) and medium incubation period (1-34 days, mean 6-7 days). Its morbidity and mortality rate can be categorized as medium (high morbidity rate with significant mortality rate). It can be easily produced in large quantities, has high aerosol stability, and has moderate environmental stability. Based on laboratory experiments and statistical model analysis, it can form and is contagious with droplet nuclei, and with spray technique utilization, it could be weaponized effectively. Several prophylactic countermeasures are available in the form of vaccines; however, specific therapeutic options are much more limited. In connection with the original assessment criteria, the SARS-CoV-2 only achieved a "0" score on the ease of detection because of readily available, relatively sensitive, and specific rapid antigen tests. Based on the pandemic experience, we also propose three new assessment categories: one that establishes a mean to measure the necessary quarantine restrictions related to a biological agent, another one that can represent the personal protective equipment required to work safely with a particular agent, and a third one that quantifies the overall disruptive capability, based on previous real-life experiences. These factors could further specify the threat level related to potential biological weapons. CONCLUSIONS: Our results show that the virus can become a potent bioweapon candidate in the future, achieving a total score of 24 out of 36 on the original 12 criteria. The SARS-CoV-2 has already proven its pandemic generating potential and, despite worldwide efforts, still remains an imminent threat. In order to be prepared for the future possibility of the virus arising as a bioweapon, we must remain cautious and take the necessary countermeasures.

Isolation of infectious Lloviu virus from Schreiber's bats in Hungary.

Some filoviruses can be transmitted to humans by zoonotic spillover events from their natural host and filovirus outbreaks have occured with increasing frequency in the last years. The filovirus Lloviu virus (LLOV), was identified in 2002 in Schreiber's bats (Miniopterus schreibersii) in Spain and was subsequently detected in bats in Hungary. Here we isolate infectious LLOV from the blood of a live sampled Schreiber's bat in Hungary. The isolate is subsequently sequenced and cultured in the Miniopterus sp. kidney cell line SuBK12-08. It is furthermore able to infect monkey and human cells, suggesting that LLOV might have spillover potential. A multi-year surveillance of LLOV in bats in Hungary detects LLOV RNA in both deceased and live animals as well as in coupled ectoparasites from the families Nycteribiidae and Ixodidae. This correlates with LLOV seropositivity in sampled Schreiber's bats. Our data support the role of bats, specifically Miniopterus schreibersii as hosts for LLOV in Europe. We suggest that bat-associated parasites might play a role in the natural ecology of filoviruses in temperate climate regions compared to filoviruses in the tropics.

Role of duties related to COVID-19 suspected, probable and confirmed fatality cases / [Elhunytakkal kapcsolatos teendok COVID­19-gyanús, valószínusített és megerosített esetekben]

The outbreak caused by SARS-CoV-2 beta-coronavirus, first identified in Wuhan, China, was declared a pandemic by the World Health Organization on 11th March, 2020. In Hungary, the first confirmed COVID-19 case was reported on 4th March, 2020, and on 15th March, the first fatality related to the infection was announced. At the moment of the latter event, there was no central, standardized guideline, which could explain the necessary precautions, and provide an unequivocal description on how to handle the dead body. The procedure of transportation, storage, occurent autopsy or final disposition of the deceased raise a lot of questions, especially on how to carry out these tasks. Legislation related to infectious diseases and decedent management in general do not provide enough information on how to perform duties in a COVID-19 fatality case. The chief medical officer suspended the execution of autopsies, except in cases of unnatural death, since 19th March, however, the transportation and storage of fatalities can still be a problem. The Department of Pathology of the Healthcare Professional College of the Ministry of Human capacities published a procedure on recommended post-mortem duties on 21st March, but the suggested protocols only represent a narrow spectrum of international recommendations. Therefore supplementation may be necessary. Sadly, post-mortem protocols, in spite of their importance, are also underrepresented in the international literature. A further problem, wich makes adoptability difficult, is that available foreign guidelines and algorithms are optimized for different legislation, and organisations, resources not available in our country. In this article, besides providing a summary of literature, we would also like to make practical recommendations which may increase the safety of healthcare providers participating in the treatment or pathological duties with COVID-19 suspected, probable and confirmed cases. Orv Hetil. 2020; 161(17): 713­722.

Multiple SARS-CoV-2 Introductions Shaped the Early Outbreak in Central Eastern Europe: Comparing Hungarian Data to a Worldwide Sequence Data-Matrix.

Severe Acute Respiratory Syndrome Coronavirus 2 is the third highly pathogenic human coronavirus in history. Since the emergence in Hubei province, China, during late 2019, the situation evolved to pandemic level. Following China, Europe was the second epicenter of the pandemic. To better comprehend the detailed founder mechanisms of the epidemic evolution in Central-Eastern Europe, particularly in Hungary, we determined the full-length SARS-CoV-2 genomes from 32 clinical samples collected from laboratory confirmed COVID-19 patients over the first month of disease in Hungary. We applied a haplotype network analysis on all available complete genomic sequences of SARS-CoV-2 from GISAID database as of 21 April 2020. We performed additional phylogenetic and phylogeographic analyses to achieve the recognition of multiple and parallel introductory events into our region. Here, we present a publicly available network imaging of the worldwide haplotype relations of SARS-CoV-2 sequences and conclude the founder mechanisms of the outbreak in Central-Eastern Europe.

Chlamydia pneumoniae in coronary bypass grafts of redo patients. The concept of the 'adventitial baseline infection'.

The pathogenic role of Chlamydia pneumoniae in late coronary bypass graft failure has not yet been extensively investigated. We examined failed and new arterial/venous bypass grafts using immunohistochemistry, polymerase chain reaction (PCR), and serology. Thirty-four long-term failed grafts and 28 new grafts were examined in 21 patients undergoing redo coronary artery bypass grafting (CABG). Immunohistochemically, 28 (82%) failed grafts were positive in the intimal-medial compartment, and 33 grafts (97%) were positive for C. pneumoniae in the adventitia. Thirteen (46%) and 27 (96%) new grafts showed infection in the intima-media and in the adventitia, respectively (p < 0.05). Immunohistochemically, the overall presence of C. pneumoniae in all vessels examined was 66% in the intima-media and 97% in the adventitia (p < 0.05). C. pneumoniae was detected by PCR in 19 (31%) of all the vessels examined. C. pneumoniae seems to be frequently present in grafts of patients considered for redo CABG in Hungary. The adventitia of both failed, and new grafts particularly often contained C. pneumoniae. The results suggest that there exists an adventitial baseline infection from which infection of the inner wall layers develops, depending on local microenvironmental conditions. This is the first study to evaluate chlamydial infection in arterial/venous coronary grafts by immunohistochemistry, PCR, and serology.

[Analysis of the stable metabolite of endothelium-derived nitric oxide of internal mammary artery bypass grafts at the venous drainage system of the recipient coronary artery. Morphologic implications and consequences]. / Az arteria mammaria interna bypass graft endotheliuma által termelt nitrogén-monoxid stabil metabolitjának mérése a recipiens coronariaág gyújtóeres rendszerében. Morfológiai vonatkozások és következmények.

INTRODUCTION: The internal mammary artery's endothelium continuously produces nitric oxide in a large quantity resulting in local and downstream vasodilatation, inhibition of platelet aggregation and in the tunica media prevents smooth muscle cell proliferation. OBJECTIVE: The aim of this study was to measure the concentration of the internal mammary artery bypass graft's endothelium derived nitric oxide's stable metabolite, (nitrite) at the venous drainage site (great cardiac vein) of the recipient coronary artery (left anterior descending), and to prove that the change of the biochemical milieu provides morphological stability (vasodilation and lack of atherosclerosis) in the recipient coronary artery based on recoronarographies. METHOD: Authors investigated the levels of endothelium derived nitric oxide in intraoperative settings of 50 off pump, partly heparinized coronary bypass surgery cases sampling from the internal mammary free cut end flow (81.2 +/- 12.1 mumol/l), the great cardiac vein (anterior interventricular vein) prior and after arterial bypass graft completion and in the systemic circulation (42.9 +/- 7.1 mumol/l), The stable metabolite concentration measurement was carried out with the modified Takafumi Ohta method utilizing fluoroscopy. Out of the 200 samples 164 were feasible to analyze. RESULTS: A significant increase was found in the great cardiac vein, comparing concentrations measured prior and after IMA anastomosis completion: 46.7 +/- 11.4 mumol/l, and 71.12 +/- 13.1 mumol/l, respectively (p < 0.05). CONCLUSION: Based on these findings, due to the continuous protective (vasodilatative and antiatherogen) effect of the IMA provided EDNO, the recipient artery shows no pathological changes in time. This was proved by studying recoronarographies of 103 patients--with prior coronary bypass surgery in 5-12 years using the IMA, and with new symptomatology. Out of 87 functioning IMA to LAD grafts, 85 LAD showed no atherosclerotic changes, while in the same patients' other coronary systems significant, de novo stenotic lesions had developed.

Glucose-mediated repression of autolysis and conidiogenesis in Emericella nidulans.

Glucose-mediated repression of autolysis and sporulation was studied in submerged Emericellanidulans (anam. Aspergillus nidulans) cultures. Null mutation of the creA gene, which encodes the major carbon catabolite repressor CreA in E. nidulans, resulted in a hyperautolytic phenotype characterized by increased extracellular hydrolase production and dry cell mass declination. Interestingly, glucose, as well as the glucose antimetabolite 2-deoxy-d-glucose, repressed autolysis and sporulation in both the control and the creA null mutant strains suggesting that these processes were also subjected to CreA-independent carbon regulation. For example, the glucose-mediated, but CreA-independent, repression of the sporulation transcription factor BrlA was likely to contribute to the negative regulation of conidiogenesis by glucose. Although CreA played a prominent role in the regulation of autolysis via the repression of genes encoding important autolytic hydrolases like ChiB chitinase and PrtA protease the age-related production of the chitinase activity was also negatively affected by the down-regulation of brlA expression. However, neither CreA-dependent nor CreA-independent elements of carbon regulation affected the initiation and regulation of cell death in E. nidulans under carbon starvation.