Corrigendum: Evolution, ecology, and zoonotic transmission of betacoronaviruses: a review.

[This corrects the article DOI: 10.3389/fvets.2021.644414.].

Insight of Zoonotic Viruses at Human-Animal Interfaces in Cambodia

*Presenting author Emerging infectious diseases have been causing outbreaks in humans for centuries and most infectious diseases originate in animals. Re-emerging zoonotic pathogens are rapidly increasing in prevalence or geographic range and causing a significant and growing threat to global health. The present work provides an insight of zoonotic viruses risk at human-bat/rodent interfaces in Cambodia. We conducted studies to investigate the circulation of zoonotic viruses and the risk of exposure in human living at the interfaces with bats and rodents. Rodent's samples were collected in rural and urban areas of Cambodia. Organs were tested for Hantavirus, Orthohepevirus species C and Arenavirus. Bat's samples were collected in Steung Treng for Sarbecovirus and in Battambang and Kandal for Nipah virus detection. People working/living at the human-animal interfaces were screened for IgG antibodies. In rodents (750), hantavirus was detected in 3.3% rodents from urban areas only. Seoul orthohantavirus was the most predominant virus followed by Thottapalayam virus. HEV-C was detected only in rodents from urban settings (1.8%). Arenavirus was detected in both rural (6.8%) and urban (2.5%) areas. In humans (788), the seroprevalence of IgG antibodies against hantavirus, HEV-A and Arenavirus was 10.0%, 24% and 23.4% respectively. NiV was detected in flying fox's urines collected between 2013-2016 in Kandal (0.63%) and in Battambang (1.03%). Blood samples collected in both provinces were negative for NiV antibodies. SARS-CoV-2 related virus was detected in Rhinolphus shameli in Steung Treng in 2010, 2020 and 2021. Blood samples from people living at the vicinity of positive bats were positive for antibodies against CoV (7.7%), but no specific neutralizing SARS-CoV2 antibodies were detected. Our studies provided insight of the risk of zoonoses in Cambodia and highlighted the importance of zoonotic surveillance and further One Health effort to prevent, detect, and respond to future cross-species transmission.Copyright © 2023

ORIGINS OF HIV-1 AND SARS-CoV-2

Dr. Worobey will discuss the scientific evidence for when, where and how both the HIV/AIDS pandemic and the COVID-19 pandemic originated, and what we can learn from this knowledge to prevent or mitigate future pandemics?. In both cases, cross-species transmission into humans via wildlife consumption, versus via laboratory accident, were plausible hypotheses of origin. And in both cases, there is now overwhelming evidence in favor of the natural zoonosis route. Indeed, in the case of COVID-19, we have insights into the genesis of the pandemic that are in many ways unparalleled in the history of investigating pandemic origins.

Zooanthropogenic potential of SARS-CoV-2 virus: Implications for vaccine-mediated immunity

The human pandemic caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that started in December, 2019 is still continuing in various parts of the world. The SARS-CoV-2 has evolved through sporadic mutations and recombination events and the emergence of alternate variants following adaptations in humans and human-to-animal transmission (zooanthraponosis) has raised concerns over the efficacy of vaccines against new variants. The animal reservoir of SARS-CoV-2 is unknown despite reports of SARS-CoV- 2-related viruses in bats and pangolins. A recent report of back-andforth transmission of SARS-CoV-2 between humans and minks on mink farms in the Netherlands has sparked widespread interest in zooanthroponotic transmission of SARS-CoV-2 followed by reemergence to infect human populations. The risk of animal to human transmission depends on virus-host interaction in susceptible species that may be short-term or long term risks. The short term risk might be due to infection to humans during the viremic stage in susceptible animals. The long term risk might be either due to persistence of the virus at population level or latency of infection leading to risk of evolution and re-emergence of the virus. Experimental studies have identified a range of animals that are susceptible and permissive to SARS-CoV-2 infection viz. cats, ferrets, hamsters, mink, non-human primates, tree shrews, raccoon dogs, fruit bats, and rabbits. The health impacts of SARS-CoV-2 infection in animals are unknown and it is likely that other susceptible species have not been discovered yet. Apart from farmed animals, stray cats and rodents have been identified as a potential opportunity for ongoing transmission in intense farming situations. Recognizing animal species that are most susceptible to infection is the first step in preventing ongoing transmission from humans. Minimizing the risk of zooanthraponosis requires multi-sectoral coordination that includes implementation of strict biosecurity measures such as controlled access to farms that house susceptible animals, bio-secure entry and exit protocols, disinfection protocols in farm, down time for animal transport vehicles and daily assessments of human handlers for exposure to SARS-CoV- 2. Hence, active surveillance in animal species that are prioritized based on risk assessment need to be initiated in coordination with health and environment sectors for early identification of emerging and re-emerging variants of SARS-CoV-2 virus in animals.

Development of broadly reactive antibody therapeutics for SARS-CoV-2.

Various antibody therapeutics has been developed for the treatment and suppression of the 2019 outbreak of novel coronavirusSARS-CoV-2infection. A major limitation in the development DDS of SARS-CoV-2 neutralizing antibodies is the occurrence and spread of escape variants that have mutations in the spike glycoprotein. The coronaviruses are carried by various wild animals, domestic animals, and pets, and there have been cases of Severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus transmission from animals to people, resulting in a large spread of infection in people. There is also a possibility that cross-species transmission of SARS-CoV-2 may occur in the future. Considering these factors, the development of antibody therapeutics with broad cross-reactivity against SARS-CoV-2 variants and other coronaviruses is required.Copyright © 2022, Japan Society of Drug Delivery System. All rights reserved.

Development of broadly reactive antibody therapeutics for SARS-CoV-2.

Various antibody therapeutics has been developed for the treatment and suppression of the 2019 outbreak of novel coronavirus(SARS-CoV-2)infection. A major limitation in the development DDS of SARS-CoV-2 neutralizing antibodies is the occurrence and spread of escape variants that have mutations in the spike glycoprotein. The coronaviruses are carried by various wild animals, domestic animals, and pets, and there have been cases of Severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus transmission from animals to people, resulting in a large spread of infection in people. There is also a possibility that cross-species transmission of SARS-CoV-2 may occur in the future. Considering these factors, the development of antibody therapeutics with broad cross-reactivity against SARS-CoV-2 variants and other coronaviruses is required.Copyright © 2022, Japan Society of Drug Delivery System. All rights reserved.

Development of broadly reactive antibody therapeutics for SARS-CoV-2.

Various antibody therapeutics has been developed for the treatment and suppression of the 2019 outbreak of novel coronavirus(SARS-CoV-2)infection. A major limitation in the development DDS of SARS-CoV-2 neutralizing antibodies is the occurrence and spread of escape variants that have mutations in the spike glycoprotein. The coronaviruses are carried by various wild animals, domestic animals, and pets, and there have been cases of Severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus transmission from animals to people, resulting in a large spread of infection in people. There is also a possibility that cross-species transmission of SARS-CoV-2 may occur in the future. Considering these factors, the development of antibody therapeutics with broad cross-reactivity against SARS-CoV-2 variants and other coronaviruses is required.Copyright © 2022, Japan Society of Drug Delivery System. All rights reserved.

Coronavirus Pandemic: Role of Bats And Zoonotic Transmission in Humans

Background: In the past two decades, the human coronavirus (HCoV) outbreaks have gripped the international communities almost six times in different forms [HCoV-OC43 (2001);HCoV-NL63 (2004);SARS-CoV (2003);HCoV HKU1 (2005);MERS-CoV (2012);SARS-CoV--2 (2019)]. These emerging pathogens have been proven very challenging from medical perspec-tives, economic conditions, and psychological impact on human society. Introduction: SARS-CoV-2, a novel coronavirus, has evidenced a historic yet troublesome pandemic across the globe. In humans, its clinical manifestations may range from asymptomatic, severe pneumonia to mortality. Bats are the natural reservoirs of a variety of viruses belonging to the family Coronaviridae. Most of the bats harboring coronaviruses mainly reside in Asian and African regions. Objective(s): The objective was to describe the various characteristic features of all coronaviruses, clinical manifestations, and complications associated with SARS-CoV-2. The major goal was to highlight the involvement of the strong immune system of bats in the cross-species transmission of coronaviruses in intermediate hosts and, finally, zoonotic transmission in humans. Methodology: A systematic literature search was conducted for high quality research and review ar-ticles. We searched the databases for articles published between the year 1972 to 2020 with search terms zoonosis, coronaviruses, zoonotic transmissions, clinical manifestations, and the immune system of bats. Conclusion(s): The domestic and non-domestic animals come in closer contact with humans. Some requisite measures should be taken to decrease the contact with livestock to prevent further threatening viral transmissions. Furthermore, the remarkable immune system of bats is required to in-quire thoroughly to develop novel therapeutics to conquer the evolving coronaviruses in the future.Copyright © 2021 Bentham Science Publishers.

Corrigendum: Evolution, ecology, and zoonotic transmission of betacoronaviruses: A review.

[This corrects the article DOI: 10.3389/fvets.2021.644414.].

One Health Investigation of SARS-CoV-2 in People and Animals on Multiple Mink Farms in Utah.

From July−November 2020, mink (Neogale vison) on 12 Utah farms experienced an increase in mortality rates due to confirmed SARS-CoV-2 infection. We conducted epidemiologic investigations on six farms to identify the source of virus introduction, track cross-species transmission, and assess viral evolution. Interviews were conducted and specimens were collected from persons living or working on participating farms and from multiple animal species. Swabs and sera were tested by SARS-CoV-2 real-time reverse transcription polymerase chain reaction (rRT-PCR) and serological assays, respectively. Whole genome sequencing was attempted for specimens with cycle threshold values <30. Evidence of SARS-CoV-2 infection was detected by rRT-PCR or serology in ≥1 person, farmed mink, dog, and/or feral cat on each farm. Sequence analysis showed high similarity between mink and human sequences on corresponding farms. On farms sampled at multiple time points, mink tested rRT-PCR positive up to 16 weeks post-onset of increased mortality. Workers likely introduced SARS-CoV-2 to mink, and mink transmitted SARS-CoV-2 to other animal species; mink-to-human transmission was not identified. Our findings provide critical evidence to support interventions to prevent and manage SARS-CoV-2 in people and animals on mink farms and emphasizes the importance of a One Health approach to address emerging zoonoses.

Chapter 2 - Severe acute respiratory syndrome (SARS)

In 2002, a severe-to-fatal respiratory disease began in China and was named severe acute respiratory syndrome (SARS). The causative agent was soon found to be a coronavirus and was named SARS-coronavirus (SARS-CoV). Infection was traced to contact with live palm civet cats or raccoon dogs in live animal food markets (“wet markets”) and later, person-to-person. Visiting these markets or restaurants housing these animals before preparing them for customer consumption were among the risk factors for infection in addition to frequent use of taxis and comorbidities. After its initial appearance, SARS spread rapidly through parts of Asia and then to countries around the world before almost completely disappearing in 2003. It caused 8096 cases and 774 deaths. SARS-CoV is a betacoronavirus linage B. The single-stranded RNA genome of coronaviruses is the largest among RNA viruses. The size of the genome, the inaccuracy of replication in most coronaviruses, and homogenous and heterogenous genetic recombination contribute to the high frequency of mutation. The viral spike (S) protein binds to angiotensin-converting enzyme 2 on the host cell before entry. Mutations in the S protein make a substantial contribution to viral transmission to additional host species and cell types in addition to viral virulence as the virus adapted to its new hosts. Interestingly, SARS-CoV isolates from the initial stages of the 2002–2003 epidemic were more virulent than those isolated later and are associated with a 29-nucleotide deletion in the S protein gene. Several insectivorous Chinese bats appear to serve as reservoir hosts for the ancestorial coronavirus. New forms of protection against infection were implemented in China and some other countries and include wearing face masks, thermal screening, and avoiding travel in taxis and public transportation. Their effectiveness in decreasing transmission and the rapid end of the epidemic is unknown.

Chapter 3 - Middle Eastern respiratory syndrome

Middle East respiratory virus syndrome (MERS) is a viral disease that primarily affects the respiratory system, but also has a major impact on the kidneys and nervous system and, to a lesser extent, on the intestines, liver, and heart. Over 2500 cases and 850 deaths have been confirmed as of 2019. The fatality rate is approximately 35%, more than that caused by severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 (that causes COVID-19). The first known case of MERS in humans was reported in 2012 in Saudi Arabia but the virus was present in stored serum samples from dromedary (one-humped) camels from Africa and the Middle East for decades before that time. Since then, it spread to at least 27 countries around the world, most of which are related to travel to the Arabian Peninsula. The coronavirus that causes MERS, MERS-CoV, is related to several other human coronaviruses that typically cause cold-like illness as well as to SARS-CoV and SARS-CoV-2. MERS-CoV is from the subgenus Merbecovirus, while SARS-CoV and SARS-CoV-2 are in Sarbecovirus. MERS-CoV also uses dipeptidyl peptidase 4 as its host cell receptor, while SARS-CoV and SARS-CoV-2 use angiotensin-converting enzyme 2. While MERS-CoV is transmittable between people in close contact with an infected person, many infections are zoonotic and are due to inhaling infectious respiratory droplets from dromedaries or consuming their raw milk or urine. Many cases are nosocomial (acquired in healthcare facilities). Fortunately, MERS-CoV only can pass through several rounds of human-to-human transmission, unlike SARS-CoV-2. Much of the pathology is due to an excessive inflammatory type of immune response caused by cytokines and chemokines, abnormal blood coagulation, and virus-induced apoptosis (programmed cell death). Bats appear to be the reservoir hosts and should be monitored for possible zoonotic transmission outside of the Middle East, in line with the One Health approach.

Chapter 1 - Introduction

Coronaviruses infect humans and multiple animal species. The seven coronaviruses of humans are the following: HCoV-NL63, HCoV-229E, HCoV-OC43, HCoV-KHU1, SARS-CoV, MERS-CoV, and SARS-CoV-2. The former four coronaviruses usually cause mild upper respiratory disease, such as the common cold, but can also cause croup and other more serious diseases, especially in the elderly and people with comorbidities. The latter three coronaviruses cause lower respiratory tract diseases which can be severe to life-threatening. The genome of coronaviruses is positive-sense single-stranded RNA composed of 4–5 structural proteins and up to 16 nonstructural proteins. The spike protein binds to several different host target cell receptors, depending on the virus. This protein directs the host species and cell types that may be infected by each coronavirus. Coronaviruses are divided into four genera: Alpha-, Beta-, Gamma-, and Delta-voronavirus. All known human coronaviruses are alpha- and beta-coronaviruses, while gamma- and delta-coronaviruses are primarily found in birds. Human and other mammalian coronaviruses are believed to have originated in bats and rodents and entered the human population via zoonotic transmission from intermediate hosts. SARS-CoV and SARS-CoV-2 are believed to have used civet cats, raccoon dogs, and, perhaps, pangolins from live animal markets “wet markets” in China as their intermediate hosts while dromedary camels in Saudi Arabia are the intermediate host for MERS-CoV., This chapter briefly reviews basic information about the history of infectious agents in humans, an introduction to viruses and other microbes, and basic characteristics of the immune system, including vaccines, in addition to an introduction of the shared features of coronaviruses and treatment regimens.

Chapter 7 - Pulling it all together: where do we go from here?

Coronaviruses are Baltimore Class I viruses of the family Coronaviridae. Similarities and differences to other members of these groups are discussed. Proposed reservoir/intermediate hosts of severe acute respiratory system coronavirus (SARS-CoV), Middle Eastern respiratory system coronavirus, and SARS-CoV-2 are presented. Bats appear to be reservoir hosts for these and some animal coronaviruses. Other potential reservoir/intermediate hosts of pathogenic coronaviruses are presented, with particular emphasis on rodents and birds. Potential methods to predict or prevent future pandemics include the One Health Approach and SpillOver. Factors driving epidemics and pandemics are discussed, particularly microbial, host-related, and environmental factors as well as ‘The Human Factor,’ medical and behavioral interventions that decrease disease spread and severity. The author’s vision for Infectious Disease Centers (IDCs), similar to Ebola Centers, is presented. IDCs would respond to a broad range of infectious diseases, utilizing separated, negative-pressure areas of existing hospitals with specialized, trained healthcare personnel, microbiologists, public health officials, and lab technicians on call. The proposed IDCs would have stockpiles of personal protective equipment (PPE), equipment, and laboratory facilities on hand to respond to a range of infections. Equipment could include ventilators, autoclaves, dialysis equipment, and three-dimensional printers. The latter was used to produce PPE and ventilators during the COVID-19 pandemic. Other innovative plans would be encouraged, such as the conversions of a deck of a long-distance Italian ferry for patients needing an intermediate level of care during the COVID-19 pandemic. Problems associated with infectious disease epidemics in developing countries are examined, with suggestions for the inclusion of appropriate personnel, such as local cultural experts and interpreters, as well as innovative planners and, perhaps, 3-D printers.

Chapter 6 - Coronaviruses of agricultural and companion animals with the potential for zoonotic transmission

Several human coronaviruses cause high mortality rates and are highly contagious, while others cause cold-like illnesses. These viruses are believed to enter human populations by zoonotic transmission from animal intermediate hosts from live animal markets in China [severe acute respiratory syndrome coronaviruses (SARS-CoV) from palm civets/raccoon dogs and SARS-CoV-2 possibly from pangolins] or dromedary camels in the Arabian Peninsula (Middle East respiratory syndrome coronavirus). Some bats may act as reservoir hosts. While much focus on the possible reservoir and intermediate hosts for future zoonotic transmission focuses on bats or rodents, humans spend much more time with agricultural animals, including cattle, pigs, camelids, and horses, particularly pigs, which host six coronaviruses. One pig coronavirus is a deltacoronavirus, a genus that almost exclusively contains bird viruses. The species Betacoronavirus-1, represented by a bovine coronavirus, contains members that infect other animal hosts, as do the Alphacoronavirus-1 species. Humans spend large amounts of time in the company of their companion animals, such as cats and dogs. Some contact is intimate, including allowing these animals to sleep with their owners and lick their faces. In addition to possible zoonotic transmission, humans transmit coronaviruses, including SARS-CoV-2, to domestic and captive exotic cats, some of which are endangered. Human-to-cat transmission of SARS-CoV-2 has caused severe disease in juvenile domestic cats. People are also regularly in contact with animal fecal material. Some diseases caused by animal coronaviruses are typically mild, while others cause severe, life-threatening diseases. Both morbidity and mortality in agricultural animals have a great economic impact on developing and developed regions of the world. Due to close, prolonged contact between humans and agricultural and companion animals, it may be a matter of great importance to spend more time and resources studying the potential for coronaviruses of domestic animals to cause zoonotic transmission.

Chapter 5 - Coronaviruses of wild and semidomesticated animals with the potential for zoonotic transmission

Coronaviruses are present in most animal species. Some animals may then serve as a reservoir or intermediate hosts of viruses causing mild or severe to fatal diseases in humans and other animals. Infected humans may also transmit coronaviruses, such as severe acute respiratory syndrome virus (SARS-CoV)-2, to animals, including captive endangered animal species. This chapter focuses on coronaviruses of wild and semidomesticated animals, including viruses from bats, rodents, nonhuman primates, ferrets, minks, and rabbits. The ability of coronaviruses to rapidly mutate and to exchange their genetic material with other coronaviruses leads to the production of variants able to infect and adapt to new host species. Special attention is given to coronaviruses of bats and rodents since they appear to have hosted ancestral coronaviruses that indirectly lead to zoonotic transmission of highly pathogenic human viruses, including SARS-CoV, the closely related SARS-CoV-2, and Middle East respiratory syndrome virus. The RNA genomes of several bat coronaviruses, such as WIV1 and WIV16, are very similar to SARS-CoV. Coronaviruses in animals primarily cause severe disease in the respiratory, central nervous, and digestive systems but may damage other organ systems as well. Further studies on wildlife coronaviruses are advisable to avoid human epidemics or pandemics as well as to protect endangered animal species.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and humoral responses against different variants of concern in domestic pet animals and stray cats from North-Eastern Spain.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic in humans, is able to infect several domestic, captive and wildlife animal species. Since reverse zoonotic transmission to pets has been demonstrated, it is crucial to determine their role in the epidemiology of the disease to prevent further spillover events and major spread of SARS-CoV-2. In the present study, we determined the presence of virus and the seroprevalence to SARS-CoV-2, as well as the levels of neutralizing antibodies (nAbs) against several variants of concern (VOCs) in pets (cats, dogs and ferrets) and stray cats from North-Eastern of Spain. We confirmed that cats and dogs can be infected by different VOCs of SARS-CoV-2 and, together with ferrets, are able to develop nAbs against the ancestral (B.1), Alpha (B.1.1.7), Beta (B.1.315), Delta (B.1.617.2) and Omicron (BA.1) variants, with lower titres against the latest in dogs and cats, but not in ferrets. Although the prevalence of active SARS-CoV-2 infection measured as direct viral RNA detection was low (0.3%), presence of nAbs in pets living in COVID-19-positive households was relatively high (close to 25% in cats, 10% in dogs and 40% in ferrets). It is essential to continue monitoring SARS-CoV-2 infections in these animals due to their frequent contact with human populations, and we cannot discard the probability of a higher animal susceptibility to new potential SARS-CoV-2 VOCs.

Correlation of COVID-19 Biomarkers with Disease Severity: A Retrospective Study

Introduction: Many viruses through aerosols, droplets, and droplet nuclei utilize the respiratory passages to establish not only localized respiratory tract infections but also systemic disease. The coronaviruses (CoV) are no exception. The two most common illnesses that occurred in the recent past were severe acute respiratory syndrome (SARS, 2003) and the Middle East respiratory syndrome (MERS, 2012).1 The current pandemic, which broke out in late December 2019, has been a major threat to global public health due to significant morbidity and mortality, akin to snapping of Thanos' fingers. The novel coronavirus was initially named the 2019-novel CoV (2019-nCoV), but because of nearly 80% genetic homology to SARS-CoV, the Coronavirus Study Group of International Committee rechristened this virus as SARS-CoV-2.1 The disease was named coronavirus disease 2019 (COVID-19) on January 12, 2020, by the World Health Organization (WHO).2 According to the Advisory Committee on dangerous pathogens UK, COVID-19 is assigned as a hazardous group-3 organism, meaning that it can cause severe human disease.3 The novel coronavirus was named the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, 2019-nCoV) due to its high homology (∼80%) to SARS-CoV, which caused acute respiratory distress syndrome (ARDS) and high mortality during 2002-2003.4 The outbreak of SARS-CoV-2 was considered to have originally started via a zoonotic transmission associated with the seafood market in Wuhan, China. Later it was recognized that human-to-human transmission played a major role in the subsequent outbreak.5 The most common clinical manifestations of COVID-19 include fever, cough, dyspnea, fatigue, and myalgia. A few patients have developed severe pneumonia and they may present with acute respiratory distress syndrome (ARDS), extrapulmonary organ dysfunction, or even death. SARS-CoV-2 virus primarily affects the respiratory system, although other organ systems are also involved. Lower respiratory tract infection-related symptoms including fever, dry cough, and dyspnea were reported in the initial case series.6 In addition, headache, dizziness, generalized weakness, vomiting, and diarrhea were observed.7 It is now widely recognized that respiratory symptoms of COVID-19 are extremely heterogeneous, ranging from minimal symptoms to significant hypoxia with ARDS. The heterogeneous disease course of COVID-19 is unpredictable with most patients experiencing mild self-limiting symptoms. However, up to 30% require hospitalisation, and up to 17% of these require intensive care support for acute respiratory distress syndrome (ARDS), hyperinflammation, and multiorgan failure. 8-10 A cytokine storm in patients with severe disease was identified in the early reports of Wuhan patients and is intrinsic to disease pathology. In this cohort, elevated plasma interleukin (IL)-2, IL-7, IL-10, granulocyte colony-stimulating factor (GCSF), interferon γ-induced protein 10 (IP10, monocyte chemoattractant protein-1 (MCP1), macrophage inflammatory protein 1-alpha (MIP1A), and tumor necrosis factor-alpha (TNF-α) levels in ICU patients were identified. 6 Studies have shown that severe or fatal cases of COVID-19 disease are associated with an elevated white cell count, blood urea nitrogen, creatinine, markers of liver and kidney function, C-reactive protein (CRP), interleukin-6 (IL-6), lower lymphocyte (<1000/μL) and platelet counts (<100 × 109/L) as well as albumin levels compared with milder cases in which survival is the outcome. Subsequent studies have implicated IL-6 as a valuable predictor of adverse clinical outcome and a potential therapeutic target.11,12 One or more clinical and wet biomarkers may enable early identification of high-risk cases, assisting disease stratification and effective use of limited specialist resources. Age is a strong risk factor for severe illness, complications, and death.13,14 Patients with no underlying medical comorbid conditions have an overall case fatality rate of <1%. Case fatality is higher for patients with comorbidit es. The severe cases are associated with elevated levels of inflammatory biomarkers such as serum lactate dehydrogenase, creatine kinase, C-reactive protein (CRP), d-dimer, procalcitonin, and ferritin.15 Since laboratory medicine has always supported clinical decision-making in various infectious diseases, it is important to assess the ability of laboratory-derived biomarkers to facilitate risk stratification of COVID-19 disease. This study will comprehensively explore clinical disease features and routine laboratory tests associated with COVID-19 disease and its complications, to address their association with disease severity and outcome. Hence, the present retrospective study will be done at our tertiary care centre to assess the association between different laboratory biomarkers and disease severity and outcomes in COVID-19 patients. Aims and objectives: Clinical correlation of biomarkers and disease severity in COVID-19 patients-a retrospective study. Review of Literature: Xia et al.16 in 2020 defined disease stages and identified stages' determining factors are instructive for the definition of standards for home quarantine. The authors demonstrated pulmonary involvement on a chest CT scan in 97.9% of cases. It took 16.81 ± 8.54 (3-49) days from the appearance of the first symptom until 274 patients tested virus-negative in naso- and oropharyngeal (NP) swabs, blood, urine, and stool, and 234 (83%) patients were asymptomatic for 9.09 ± 7.82 (1-44) days. Subsequently, 131 patients were discharged. One hundred and sixty-nine remained in the hospital;these patients tested virus-free and were clinically asymptomatic because of widespread persisting or increasing pulmonary infiltrates. Hospitalization took 16.24 ± 7.57 (2-47) days;the time interval from the first symptom to discharge was 21.37 ± 7.85 (3-52) days. The authors concluded that with an asymptomatic phase, disease courses are unexpectedly long until the stage of virus negativity. NP swabs are not reliable in the later stages of COVID-19. Pneumonia outlasts virus-positive tests if sputum is not acquired. Imminent pulmonary fibrosis in high-risk groups demands follow-up examinations. Investigation of promising antiviral agents should heed the specific needs of mild and moderate COVID-19 patients. Keddie et al.17 in 2020 investigated the routine laboratory tests and cytokines implicated in COVID-19 for their potential application as biomarkers of disease severity, respiratory failure, and need for higher-level care. The authors found CRP, IL-6, IL-10, and LDH were most strongly correlated with the WHO ordinal scale of illness severity, the fraction of inspired oxygen delivery, radiological evidence of ARDS, and level of respiratory support. IL-6 levels of ≥3.27 pg/mL provide a sensitivity of 0.87 and specificity of 0.64 for a requirement of ventilation, and a CRP of ≥37 mg/L of 0.91 and 0.66. The authors concluded that reliable stratification of highrisk cases has significant implications on patient triage, resource management, and potentially the initiation of novel therapies in severe patients. Malik et al.18 in 2020 in a systematic review and meta-analysis assessed the role of biomarkers in evaluating the severity of disease and appropriate allocation of resources. Studies having biomarkers, including lymphocyte, platelets, d-dimer, lactate dehydrogenase (LDH), C-reactive protein (CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, procalcitonin (PCT), and creatine kinase (CK), and describing outcomes were selected with the consensus of three independent reviewers. The authors found lymphopenia, thrombocytopenia, elevated d-dimer, elevated CRP, elevated PCT, elevated CK, elevated AST, elevated ALT, elevated creatinine, and LDH were independently associated with a higher risk of poor outcomes. The authors concluded a significant association between lymphopenia, thrombocytopenia, and elevated levels of CRP, PCT, LDH, d-dimer, and COVID-19 severity. The results have the potential to be used as an early biomarker to impro e the management of COVID-19 patients, by identification of high-risk patients and appropriate allocation of healthcare resources in the pandemic. Tjendra et al.19 in 2020 assessed specific laboratory parameters and summarized the currently available literature on the predictive role of various biomarkers in COVID-19 patients.

Seroprevalence of Anti-Hepatitis E Virus Antibodies among Patients from a Tertiary Hospital from Northeast Romania.

Background and Objectives. Being an enterically transmitted pathogen with a growing prevalence in developed countries, hepatitis E virus (HEV) infection remains an underdiagnosed disease in Eastern Europe. As far as Romania is concerned, only a few studies address this issue. Our goal was to estimate the prevalence of serum anti-HEV IgA/IgM/IgG antibodies in a group of patients admitted to the Clinical Hospital for Infectious Diseases "St. Parascheva" Iasi. Materials and Methods. The cross-sectional study consisted of enrollment of 98 patients admitted to the clinic for COVID-19 over a period of three months in 2020. Results. The median age in our study was 73 years, with an equal gender ratio and with a predominance of people from the urban environment (75%). The overall HEV antibody seroprevalence was 12.2%. The main risk factors associated with HEV infection were consumption of water from unsafe sources (58.3% HEV-positive patients vs. 26.7% HEV-negative patients, p = 0.026) and improperly cooked meat (58.3% HEV-positive patients vs. 23.2% HEV-negative patients, p = 0.01). Zoonotic transmission was an important criterion in our study, with patients reporting contact with pigs, poultry, rats, or other farms animals, but no significant differences were found between HEV antibody positive and negative groups. Conclusions. The seroprevalence rate of HEV antibodies was similar to other previous reports from our area but higher than in most European countries. The fact that HEV antibodies were detected in patients without identifiable risk factors for hepatitis E is evidence of subclinical infection as a silent threat.