Early Warning Diagnostics for Emerging Infectious Diseases in Developing into Late-Stage Pandemics.

The spread of infectious diseases due to travel and trade can be seen throughout history, whether from early settlers or traveling businessmen. Increased globalization has allowed infectious diseases to quickly spread to different parts of the world and cause widespread infection. Posthoc analysis of more recent outbreaks-SARS, MERS, swine flu, and COVID-19-has demonstrated that the causative viruses were circulating through populations for days or weeks before they were first detected, allowing disease to spread before quarantines, contact tracing, and travel restrictions could be implemented. Earlier detection of future novel pathogens could decrease the time before countermeasures are enacted. In this Account, we examined a variety of novel technologies from the past 10 years that may allow for earlier detection of infectious diseases. We have arranged these technologies chronologically from pre-human predictive technologies to population-level screening tools. The earliest detection methods utilize artificial intelligence to analyze factors such as climate variation and zoonotic spillover as well as specific species and geographies to identify where the infection risk is high. Artificial intelligence can also be used to monitor health records, social media, and various publicly available data to identify disease outbreaks faster than traditional epidemiology. Secondary to predictive measures is monitoring infection in specific sentinel animal species, where domestic animals or wildlife are indicators of potential disease hotspots. These hotspots inform public health officials about geographic areas where infection risk in humans is high. Further along the timeline, once the disease has begun to infect humans, wastewater epidemiology can be used for unbiased sampling of large populations. This method has already been shown to precede spikes in COVID-19 diagnoses by 1 to 2 weeks. As total infections increase in humans, bioaerosol sampling in high-traffic areas can be used for disease monitoring, such as within an airport. Finally, as disease spreads more quickly between humans, rapid diagnostic technologies such as lateral flow assays and nucleic acid amplification become very important. Minimally invasive point-of-care methods can allow for quick adoption and use within a population. These individual diagnostic methods then transfer to higher-throughput methods for more intensive population screening as an infection spreads. There are many promising early warning technologies being developed. However, no single technology listed herein will prevent every future outbreak. A combination of technologies from across our infection timeline would offer the most benefit in preventing future widespread disease outbreaks and pandemics.

Brucellosis in a patient diagnosed with Coronavirus Disease 2019 (COVID-19).

Brucellosis is a common zoonotic infection. Brucellosis typically presents with fever, weakness, night sweats, and arthralgias. Symptoms associated with Coronavirus Disease 2019 (COVID-19) and infection with Brucella spp. are similar to one another, which may lead to delayed diagnosis of the latter condition. There are no previous reports of brucellosis in a patient previously diagnosed with COVID-19. We present here the case of a 20-year-old male who we diagnosed with brucellosis after joint pains and fever that persisted after resolution of COVID-19.

Recent advances in biomedical, biosensor and clinical measurement devices for use in humans and the potential application of these technologies for the study of physiology and disease in wild animals.

The goal of achieving enhanced diagnosis and continuous monitoring of human health has led to a vibrant, dynamic and well-funded field of research in medical sensing and biosensor technologies. The field has many sub-disciplines which focus on different aspects of sensor science; engaging engineers, chemists, biochemists and clinicians, often in interdisciplinary teams. The trends which dominate include the efforts to develop effective point of care tests and implantable/wearable technologies for early diagnosis and continuous monitoring. This review will outline the current state of the art in a number of relevant fields, including device engineering, chemistry, nanoscience and biomolecular detection, and suggest how these advances might be employed to develop effective systems for measuring physiology, detecting infection and monitoring biomarker status in wild animals. Special consideration is also given to the emerging threat of antimicrobial resistance and in the light of the current SARS-CoV-2 outbreak, zoonotic infections. Both of these areas involve significant crossover between animal and human health and are therefore well placed to seed technological developments with applicability to both human and animal health and, more generally, the reviewed technologies have significant potential to find use in the measurement of physiology in wild animals. This article is part of the theme issue 'Measuring physiology in free-living animals (Part II)'.

The Second Wave of SARS-CoV-2 Circulation-Antibody Detection in the Domestic Cat Population in Germany.

Registered cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the German human population increased rapidly during the second wave of the SARS-CoV-2 pandemic in winter 2020/21. Since domestic cats are susceptible to SARS-CoV-2, the occurrence of trans-species transmission needs to be monitored. A previous serosurvey during the first wave of the pandemic detected antibodies against SARS-CoV-2 in 0.65% of feline serum samples that were randomly sampled across Germany. In the here-presented follow-up study that was conducted from September 2020 to February 2021, the seroprevalence rose to 1.36% (16/1173). This doubling of the seroprevalence in cats is in line with the rise of reported cases in the human population and indicates a continuous occurrence of trans-species transmission from infected owners to their cats.

COVID-19, a worldwide public health emergency.

A new coronavirus outbreak emerged on the 31st of December 2019 in Wuhan, China, causing commotion among the medical community and the rest of the world. This new species of coronavirus has been termed 2019-nCoV and has caused a considerable number of cases of infection and deaths in China and, to a growing degree, beyond China, becoming a worldwide public health emergency. 2019-nCoV has high homology to other pathogenic coronaviruses, such as those originating from bat-related zoonosis (SARS-CoV), which caused approximately 646 deaths in China at the start of the decade. The mortality rate for 2019-nCoV is not as high (approximately 2-3%), but its rapid propagation has resulted in the activation of protocols to stop its spread. This pathogen has the potential to become a pandemic. It is therefore vital to follow the personal care recommendations issued by the World Health Organization.

SARS-CoV-2 Exposure in Escaped Mink, Utah, USA.

In August 2020, outbreaks of coronavirus disease were confirmed on mink farms in Utah, USA. We surveyed mammals captured on and around farms for evidence of infection or exposure. Free-ranging mink, presumed domestic escapees, exhibited high antibody titers, suggesting a potential severe acute respiratory syndrome coronavirus 2 transmission pathway to native wildlife.

Next-generation diagnostics: virus capture facilitates a sensitive viral diagnosis for epizootic and zoonotic pathogens including SARS-CoV-2.

BACKGROUND: The detection of pathogens in clinical and environmental samples using high-throughput sequencing (HTS) is often hampered by large amounts of background information, which is especially true for viruses with small genomes. Enormous sequencing depth can be necessary to compile sufficient information for identification of a certain pathogen. Generic HTS combining with in-solution capture enrichment can markedly increase the sensitivity for virus detection in complex diagnostic samples. METHODS: A virus panel based on the principle of biotinylated RNA baits was developed for specific capture enrichment of epizootic and zoonotic viruses (VirBaits). The VirBaits set was supplemented by a SARS-CoV-2 predesigned bait set for testing recent SARS-CoV-2-positive samples. Libraries generated from complex samples were sequenced via generic HTS (without enrichment) and afterwards enriched with the VirBaits set. For validation, an internal proficiency test for emerging epizootic and zoonotic viruses (African swine fever virus, Ebolavirus, Marburgvirus, Nipah henipavirus, Rift Valley fever virus) was conducted. RESULTS: The VirBaits set consists of 177,471 RNA baits (80-mer) based on about 18,800 complete viral genomes targeting 35 epizootic and zoonotic viruses. In all tested samples, viruses with both DNA and RNA genomes were clearly enriched ranging from about 10-fold to 10,000-fold for viruses including distantly related viruses with at least 72% overall identity to viruses represented in the bait set. Viruses showing a lower overall identity (38% and 46%) to them were not enriched but could nonetheless be detected based on capturing conserved genome regions. The internal proficiency test supports the improved virus detection using the combination of HTS plus targeted enrichment but also points to the risk of cross-contamination between samples. CONCLUSIONS: The VirBaits approach showed a high diagnostic performance, also for distantly related viruses. The bait set is modular and expandable according to the favored diagnostics, health sector, or research question. The risk of cross-contamination needs to be taken into consideration. The application of the RNA-baits principle turned out to be user friendly, and even non-experts can easily use the VirBaits workflow. The rapid extension of the established VirBaits set adapted to actual outbreak events is possible as shown for SARS-CoV-2. Video abstract.

The novel zoonotic Coronavirus disease 2019 (COVID-19) pandemic: Health perspective on the outbreak.

During late 2019, the first cases of the Coronavirus disease-2019 (COVID-19) were observed in a Seafood Market in Wuhan. As the first cases took place in a seafood market that consumed live animals, it has been identified as a zoonotic disease. Some reports suggested snakes were the animal host, while others reported bat and pangolin were the sources of infection because coronavirus-origin of these two animals had similar genomic sequences to COVID-19. The common diagnosis method for detection COVID-19 was according to clinical manifestation, epidemiological histories, and ancillary tests, like CT scan, nucleic acid detection, immune identification technology, blood culture, Radiology, and enzyme-linked immunosorbent assay (ELISA). This review presented a perspective about current knowledge about COVID-19 in different aspects including probable zoonotic origins, and Coronaviruses classification was discussed in this context. In addition, epidemiology, clinical signs, treatment, and management strategies for controlling COVID-19 were also highlighted.

The Virome of Acute Respiratory Diseases in Individuals at Risk of Zoonotic Infections.

The ongoing coronavirus disease 2019 (COVID-19) pandemic emphasizes the need to actively study the virome of unexplained respiratory diseases. We performed viral metagenomic next-generation sequencing (mNGS) analysis of 91 nasal-throat swabs from individuals working with animals and with acute respiratory diseases. Fifteen virus RT-PCR-positive samples were included as controls, while the other 76 samples were RT-PCR negative for a wide panel of respiratory pathogens. Eukaryotic viruses detected by mNGS were then screened by PCR (using primers based on mNGS-derived contigs) in all samples to compare viral detection by mNGS versus PCR and assess the utility of mNGS in routine diagnostics. mNGS identified expected human rhinoviruses, enteroviruses, influenza A virus, coronavirus OC43, and respiratory syncytial virus (RSV) A in 13 of 15 (86.7%) positive control samples. Additionally, rotavirus, torque teno virus, human papillomavirus, human betaherpesvirus 7, cyclovirus, vientovirus, gemycircularvirus, and statovirus were identified through mNGS. Notably, complete genomes of novel cyclovirus, gemycircularvirus, and statovirus were genetically characterized. Using PCR screening, the novel cyclovirus was additionally detected in 5 and the novel gemycircularvirus in 12 of the remaining samples included for mNGS analysis. Our studies therefore provide pioneering data of the virome of acute-respiratory diseases from individuals at risk of zoonotic infections. The mNGS protocol/pipeline applied here is sensitive for the detection of a variety of viruses, including novel ones. More frequent detections of the novel viruses by PCR than by mNGS on the same samples suggests that PCR remains the most sensitive diagnostic test for viruses whose genomes are known. The detection of novel viruses expands our understanding of the respiratory virome of animal-exposed humans and warrant further studies.

Seroprevalence of Middle East Respiratory Syndrome Corona Virus in dromedaries and their traders in upper Egypt.

INTRODUCTION: Camel trade in Egypt depends mainly on importation. Seemingly healthy imported camels are responsible for the ingress of serious diseases into Egypt. A striking example of this concerning public health globally is the Middle East respiratory coronavirus (MERS-CoV) which causes case fatalities of over 34%. Here, we determined the seroepidemiological situation of the MERS-CoV in imported camels and their traders in Upper Egypt. METHODOLOGY: Sera of sixty-three dromedaries and twenty-eight camel traders were recruited (January 2015-December 2016). The age, gender, and sampling locality of each sampled camel and human were obtained. Semi-quantitative anti-MERS-CoV IgG ELISAs which utilize the purified spike protein domain S1 antigen of MERS coronavirus (MERS-CoV S1) were used to detect specific IgG antibodies against the virus. RESULTS: The data showed that 58.73% of imported camels and 25% of traders had antibodies specific to MERS-CoV. Interestingly, like seroreactive camels, all seropositive humans were apparently healthy without any history of developing severe respiratory disease in the 14 days prior to sampling. Having specific antibodies among the examined camel sera was significantly different (P < 0.0001) in relation to various sampling localities, gender and age groups. In contrast, the seropositivity rate of MERS-CoV IgG in humans did not differ significantly by any of the studied factors. CONCLUSIONS: The current study provides the first serological evidence of occupational exposure of humans to MERS-CoV in Africa. Additionally, it reports that imported camels could be implicated in introducing MERS-CoV into Egypt. Accordingly, application of strict control measures to camel importation is a priority.