COVID-19 Pandemia: Neuropsychiatric Comorbidity and Consequences.

Infection with the new corona virus (SARS-CoV-2) was first registered in December 2019 in China, and then later spread rapidly to the rest of the world. On December 31, 2019, the World Health Organization (WHO) informed the public for the first time about causes of pneumonnia of unknown origin, in the city of Wuhan (Hubei Province, China), in people who were epidemiologically linked to a seafood and wet animal whole sale local market in Wuhan. Coronavrus disease, called COVID-19 (Corona virus disease 2019), after China quickly spread to most countries in the wold, and the WHO on March 11, 2020 declared a pandmic with this virus. SARS-CoV-2, has a high level of sequential similarities to the SARS-CoV-1 and uses the same receptors when it enters the human body (angiotensin-converting enzyme 2/ACE2). COVID-19 is respiratry infection that is primarily transmitted via respiratry droplets. Typical symptoms of COVID-19 infection can be very moderate (infected can be even asymptomatic) to very severe, with severe respiratory symptoms (bilateral severe pneumonia), septic schock, and fatal outcome. Numeous unknows regarding the biological, epidemilogical adn clinical characteristics of COVID-19, still exist, and make it impossible to predict with certainty the further course of the current pandemic. COVID-19 is primarily a disease of the respiratory system, but SARS-CoV-2, in a number of patients also penetrates the CNS, and apparently could be responsible for fatal outcome in some cases. The entrry of the virus into the brain can lead to neurological and psychiatric manifestationss, which are not uncommon, including headache, paresthesia, myalgia, impaired consciousnessm, confusion or delirum and cerebrovascular diseases. SARS-CoV-2 positive individuals should be evaluated in a timely manner for neurological and psychiatic symptoms because tretament of infection-related neurological and psychiatric complications is an important factor in better prognosis of severe COVID-19 patients.From the current point of view, it seems that in COVID-19 survivors, in the coming years and decades, the inflammatory systemic process and/or the inflammatory process of the brain could trigger long-term mechanisms that generally lead to an increase of neurological and neurodegenerative disorders. Psychosocial consequences as well as consequences for mental health are also significant, both for the general population and especially for health workers of all profiles. COVID-19 pandemia is associtaed with negative psychosocial consequences, including depressive symptoms, anxiety, anger and stress, sleep disorders, simpotms of posttrauamtic stres disorder, social isolation, loneliness and stigmatization.

Frequency of SARS-CoV-2 infection in dogs and cats: Results of a retrospective serological survey in Sumadija District, Serbia.

It has long been known that coronaviruses cause various infectious diseases in animals. Although SARS-CoV-2 is genetically related to viruses isolated from Rhinolophus bats, the exact origin, mode of transmission, and how the human species has become the epidemiological reservoir of the virus have not yet been established with certainty. Although the main route of transmission is human-to-human, there are considerable numbers of reported cases of infection in animal species, predominantly among pet animals. The aim of this retrospective study was to assess SARS-CoV-2 seropositivity in dogs and cats during the COVID-19 pandemic in Sumadija District, Serbia. We used serology to identify household contacts of pet animals with infected pet owners and the degree of association. The study presented in this paper is also the first study of this type in Serbia. The results of a retrospective serosurvey, which was conducted in dogs and cats with different exposure risk factors, were analyzed to find the possible modes of transmission between humans and animals. The relative frequency of SARS-CoV-2 infection in dogs was 1.45% bounded with a 95% confidence interval (CI) of 0.0007-7.73%, while in cats, it was 5.56% (95% CI: 0.77-4.13%). The relative frequency of SARS-CoV-2 infection in pet owners was 11% (95% CI: 6.25-18.63%). In pets that were in close contact with COVID-19 positive owners, the seropositivity was found to be 9%. Out of a total of five stray dogs and cats tested, seropositivity was observed in two animals. Detected SARS-CoV-2 infection in pets shows that these animals are susceptible to infection and that the most common means of virus transmission to pets is through contact with diseased owners. However, the presence of infection in stray dogs and cats is not clear and needs further research.

Second round of an interlaboratory comparison of SARS-CoV2 molecular detection assays used by 45 veterinary diagnostic laboratories in the United States.

The COVID-19 pandemic presents a continued public health challenge. Veterinary diagnostic laboratories in the United States use RT-rtPCR for animal testing, and many laboratories are certified for testing human samples; hence, ensuring that laboratories have sensitive and specific SARS-CoV2 testing methods is a critical component of the pandemic response. In 2020, the FDA Veterinary Laboratory Investigation and Response Network (Vet-LIRN) led an interlaboratory comparison (ILC1) to help laboratories evaluate their existing RT-rtPCR methods for detecting SARS-CoV2. All participating laboratories were able to detect the viral RNA spiked in buffer and PrimeStore molecular transport medium (MTM). With ILC2, Vet-LIRN extended ILC1 by evaluating analytical sensitivity and specificity of the methods used by participating laboratories to detect 3 SARS-CoV2 variants (B.1; B.1.1.7 [Alpha]; B.1.351 [Beta]) at various copy levels. We analyzed 57 sets of results from 45 laboratories qualitatively and quantitatively according to the principles of ISO 16140-2:2016. More than 95% of analysts detected the SARS-CoV2 RNA in MTM at ≥500 copies for all 3 variants. In addition, for nucleocapsid markers N1 and N2, 81% and 92% of the analysts detected ≤20 copies in the assays, respectively. The analytical specificity of the evaluated methods was >99%. Participating laboratories were able to assess their current method performance, identify possible limitations, and recognize method strengths as part of a continuous learning environment to support the critical need for the reliable diagnosis of COVID-19 in potentially infected animals and humans.

The impact of coronavirus disease 2019 (COVID-19) in Japanese companion animal clinics.

The coronavirus disease 2019 (COVID-19) pandemic has had a tremendous impact on people's lives throughout the world. A cross-sectional study was conducted to clarify the influence of COVID-19 on Japanese companion animal clinics. A self-administered electronic questionnaire regarding the incidence of COVID-19, hygiene management, the influence on clinical service and employment, and mental stress of staff was conducted for workers in animal clinics between 1 May and 10 June 2021. Questions concerning the hygiene management before the occurrence of COVID-19, under the first state of emergency, and at the time of the survey were asked using the Likert scale. Kessler 6 (K6) was used as an indicator of mental distress. In total, 430 individuals responded. Of these, 4.9% experienced COVID-19 infection in staff. Hygiene management was strengthened, but no particular practice was statistically associated with the occurrence of COVID-19 cases in staff. In Nakaya's variation of Scheffe's paired comparison, the highest prioritized goal in the clinics was the prevention of nosocomial infection with COVID-19. The prevalence of serious mental illness (K6 >=13) was 11.1% (95% confidence interval: 6.3-18.6%). Multivariable negative binomial regression found four risk factors for psychological distress: veterinary nurse (P=0.016 with veterinarians and P<0.01 with other staff), female (P=0.004), fear of infection at work (P<0.001), and stress by refraining from going out (P<0.001). Directors of clinics are recommended to take care of female veterinary nurses for distress.

Evaluation of the clinical evolution and transmission of SARS-CoV-2 infection in cats by simulating natural routes of infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current pandemic disease denominated as Coronavirus Disease 2019 (COVID-19). Several studies suggest that the original source of this virus was a spillover from an animal reservoir and its subsequent adaptation to humans. Of all the different animals affected, cats are one of the most susceptible species. Moreover, several cases of natural infection in domestic and stray cats have been reported in the last few months. Although experimental infection assays have demonstrated that cats are successfully infected and can transmit the virus to other cats by aerosol, the conditions used for these experiments have not been specified in terms of ventilation. We have, therefore, evaluated the susceptibility of cats using routes of infection similar to those expected under natural conditions (exposure to a sneeze, cough, or contaminated environment) by aerosol and oral infection. We have also evaluated the transmission capacity among infected and naïve cats using different air exchange levels. Despite being infected using natural routes and shed virus for a long period, the cats did not transmit the virus to contact cats when air renovation features were employed. The infected animals also developed gross and histological lesions in several organs. These outcomes confirm that cats are at risk of infection when exposed to infected people, but do not transmit the virus to other cats with high rates of air renovation.

Histologic pulmonary lesions of SARS-CoV-2 in 4 nonhuman primate species: An institutional comparative review.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an emergent, amphixenotic infection that resulted in a pandemic declaration in March 2020. A rapid search for appropriate animal models of this newly emergent viral respiratory disease focused initially on traditional nonhuman primate research species. Nonhuman primate models have previously been shown to be valuable in evaluation of emerging respiratory coronaviruses with pandemic potential (ie, SARS-CoV and Middle East respiratory syndrome coronavirus). In this article, we review the pulmonary histopathologic characteristics and immunohistochemical evaluation of experimental SARS-CoV-2 infection in the rhesus macaque, pigtail macaque, African green monkey, and squirrel monkey. Our results indicate that all evaluated nonhuman primate species developed variably severe histopathologic changes typical of coronavirus respiratory disease characterized by interstitial pneumonia with or without syncytial cell formation, alveolar fibrin, and pulmonary edema that progressed to type II pneumocyte hyperplasia. Lesion distribution was multifocal, frequently subpleural, and often more severe in lower lung lobes. However, squirrel monkeys showed the least severe and least consistent lesions of the evaluated nonhuman primates. Additionally, our results highlight the disparate physical relationship between viral antigen and foci of pulmonary lesions. While classic respiratory coronaviral lesions were observed in the lungs of all nonhuman primates evaluated, none of the primates exhibited severe lesions or evidence of diffuse alveolar damage and therefore are unlikely to represent the severe form of SARS-CoV-2 infection observed in fatal human cases.

Molecular dynamic simulation analysis of SARS-CoV-2 spike mutations and evaluation of ACE2 from pets and wild animals for infection risk.

Coronavirus Disease 2019 (COVID-19) is an ongoing global health emergency that has caused tremendous stress and loss of life worldwide. The viral spike glycoprotein is a critical molecule mediating transmission of SARS-CoV-2 by interacting with human ACE2. However, through the course of the pandemics, there has not been a thorough analysis of the spike protein mutations, and on how these mutants influence the transmission of SARS-CoV-2. Besides, cases of SARS-CoV-2 infection among pets and wild animals have been reported, so the susceptibility of these animals requires great attention to investigate, as they may also link to the renewed question of a possible intermediate host for SARS-CoV-2 before it was transmitted to humans. With over 226,000 SARS-CoV-2 sequences obtained, we found 1573 missense mutations in the spike gene, and 226 of them were within the receptor-binding domain (RBD) region that directly interacts with human ACE2. Modeling the interactions between SARS-CoV-2 spike mutants and ACE2 molecules showed that most of the 74 missense mutations in the RBD region of the interaction interface had little impact on spike binding to ACE2, whereas several within the spike RBD increased the binding affinity toward human ACE2 thus making the virus likely more contagious. On the other hand, modeling the interactions between animal ACE2 molecules and SARS-CoV-2 spike revealed that many pets and wild animals' ACE2 had a variable binding ability. Particularly, ACE2 of bamboo rat had stronger binding to SARS-CoV-2 spike protein, whereas that of mole, vole, Mus pahari, palm civet, and pangolin had a weaker binding compared to human ACE2. Our results provide structural insights into the impact on interactions of the SARS-CoV-2 spike mutants to human ACE2, and shed light on SARS-CoV-2 transmission in pets and wild animals, and possible clues to the intermediate host(s) for SARS-CoV-2.

Influence of SARS-CoV-2 on airway mucus production: A review and proposed model.

Coronavirus disease 2019 (COVID-19) is a worldwide pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has affected millions of lives. Individuals who survive severe COVID-19 can experience sustained respiratory symptoms that persist for months after initial infection. In other airway diseases, abnormal airway mucus contributes to sustained airway symptoms. However, the impact of SARS-CoV-2 on airway mucus has received limited attention. In the current review, we assess literature describing the impact of SARS-CoV-2 on airway pathophysiology with specific emphasis on mucus production. Accumulating evidence suggests that the 2 major secreted airway mucin glycoproteins, MUC5AC and MUC5B, are abnormal in some patients with COVID-19. Aberrations in MUC5AC or MUC5B in response to SARS-CoV-2 infection are likely due to inflammation, though the responsible mechanisms have yet to be determined. Thus, we also provide a proposed model highlighting mechanisms that can contribute to acute and sustained mucus abnormalities in SARS-CoV-2, with an emphasis on inflammatory cells and mediators, including mast cells and histamine. Last, we bring to light the challenges of studying abnormal mucus production in SARS-CoV-2 infections and discuss the strengths and limitations of model systems commonly used to study COVID-19. The evidence to date suggests that ferrets, nonhuman primates, and cats may have advantages over other models to investigate mucus in COVID-19.

First evidence of human-to-dog transmission of SARS-CoV-2 B.1.160 variant in France.

Since the start of the coronavirus disease of 2019 (COVID-19) pandemic, several episodes of human-to-animal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission have been described in different countries. The role of pets, especially domestic dogs, in the COVID-19 epidemiology is highly questionable and needs further investigation. In this study, we report a case of COVID-19 in a French dog living in close contact with its owners who were COVID-19 patients. The dog presented rhinitis and was sampled 1 week after its owners (a man and a woman) were tested positive for COVID-19. The nasal swabs for the dog tested remained positive for SARS-CoV-2 by reverse transcription quantitative real-time PCR (RT-qPCR) 1 month following the first diagnosis. Specific anti-SARS-CoV-2 antibodies were detectable 12 days after the first diagnosis and persisted for at least 5 months as tested using enzyme-linked immunoassay (ELISA) and automated western blotting. The whole-genome sequences from the dog and its owners were 99%-100% identical (with the man and the woman's sequences, respectively) and matched the B.1.160 variant of concern (Marseille-4 variant), the most widespread in France at the time the dog was infected. This study documents the first detection of B.1.160 in pets (a dog) in France, and the first canine genome recovery of the B.1.160 variant of global concern. Moreover, given the enhanced infectivity and transmissibility of the Marseille-4 variant for humans, this case also highlights the risk that pets may potentially play a significant role in SARS-CoV-2 outbreaks and may transmit the infection to humans. We have evidence of human-to-dog transmission of the Marseille-4 variant since the owners were first to be infected. Finally, owners and veterinarians must be vigilent for canine COVID-19 when dogs are presented with respiratory clinical signs.

Transmission dynamics and susceptibility patterns of SARS-CoV-2 in domestic, farmed and wild animals: Sustainable One Health surveillance for conservation and public health to prevent future epidemics and pandemics.

The exact origin of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and source of introduction into humans has not been established yet, though it might be originated from animals. Therefore, we conducted a study to understand the putative reservoirs, transmission dynamics, and susceptibility patterns of SARS-CoV-2 in animals. Rhinolophus bats are presumed to be natural progenitors of SARS-CoV-2-related viruses. Initially, pangolin was thought to be the source of spillover to humans, but they might be infected by human or other animal species. So, the virus spillover pathways to humans remain unknown. Human-to-animal transmission has been testified in pet, farmed, zoo and free-ranging wild animals. Infected animals can transmit the virus to other animals in natural settings like mink-to-mink and mink-to-cat transmission. Animal-to-human transmission is not a persistent pathway, while mink-to-human transmission continues to be illuminated. Multiple companions and captive wild animals were infected by an emerging alpha variant of concern (B.1.1.7 lineage) whereas Asiatic lions were infected by delta variant, (B.1.617.2). To date, multiple animal species - cat, ferrets, non-human primates, hamsters and bats - showed high susceptibility to SARS-CoV-2 in the experimental condition, while swine, poultry, cattle showed no susceptibility. The founding of SARS-CoV-2 in wild animal reservoirs can confront the control of the virus in humans and might carry a risk to the welfare and conservation of wildlife as well. We suggest vaccinating pets and captive animals to stop spillovers and spillback events. We recommend sustainable One Health surveillance at the animal-human-environmental interface to detect and prevent future epidemics and pandemics by Disease X.

First Reported Cases of SARS-CoV-2 Infection in Companion Animals - New York, March-April 2020.

On April 22, CDC and the U.S. Department of Agriculture (USDA) reported cases of two domestic cats with confirmed infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). These are the first reported companion animals (including pets and service animals) with SARS-CoV-2 infection in the United States, and among the first findings of SARS-CoV-2 symptomatic companion animals reported worldwide. These feline cases originated from separate households and were epidemiologically linked to suspected or confirmed human COVID-19 cases in their respective households. Notification of presumptive positive animal test results triggered a One Health* investigation by state and federal partners, who determined that no further transmission events to other animals or persons had occurred. Both cats fully recovered. Although there is currently no evidence that animals play a substantial role in spreading COVID-19, CDC advises persons with suspected or confirmed COVID-19 to restrict contact with animals during their illness and to monitor any animals with confirmed SARS-CoV-2 infection and separate them from other persons and animals at home (1).

Natural infection of Delta mutant of SARS-CoV-2 in Asiatic lions of India.

The current pandemic caused by a novel coronavirus (SARS-CoV-2) has underlined the importance of emerging diseases of zoonotic importance. Along with human beings, several species of wild and pet animals have been demonstrated to be infected by SARS-CoV-2, both naturally and experimentally. In addition, with constant emergence of new variants, the species susceptibility might further change which warrants intensified screening efforts. India is a vast and second most populated country, with a habitat of a very diverse range of animal species. In this study we place on record of SARS-CoV-2 infections in three captive Asiatic lions. Detailed genomic characterization revealed involvement of Delta mutant (Pango lineage B.1.617.2) of SARS-CoV-2 at two different locations. Interestingly, no other feline species enclosed in the zoo/park were found infected. The epidemiological and molecular analysis will contribute to the understanding of the emerging mutants of SARS-CoV-2 in wild and domestic animals.

Absence of SARS-CoV-2 RNA and anti-SARS-CoV-2 antibodies in stray cats.

SARS-CoV-2 positive or seropositive owned cats have been reported worldwide. The detection of seropositive stray cats in the proximity of farms of infected minks, coupled with the demonstration of cat-to-cat transmission in experimental settings, raise the question whether stray cats may have an epidemiological role in the COVID-19 pandemic and may act as sentinel for the circulation of SARS-CoV-2. The aim of this study was to evaluate the presence of SARS-CoV-2 RNA and anti-SARS-CoV-2 antibodies in free roaming cats belonging to colonies located in an area highly affected by the COVID-19 pandemic and to correlate the results with the positivity rate in people sharing the same area. Interdigital, cutaneous, oropharyngeal, nasal and rectal swabs, as well as blood samples, were collected from 99 cats living in colonies and admitted to our hospital for neutering. This caseload corresponds to the 24.2% of the feline population living in the 25 sampled colonies and to the 5.6% of all the free-roaming registered cats. The presence of SARS-CoV-2 RNA in swabs was assessed using real time RT-PCR. Anti-SARS-CoV-2 serum antibodies were assessed using commercially available ELISA kits and confirmed by serum virus neutralization. In people, the SARS-CoV-2 positivity rate ranged from 3.0% to 5.1% (mean rate: 4.1%) and the seropositive rate from 12.1% to 16.3% (mean rate: 14.2%). Most of the colonies were in urban areas and resident cats had frequent contacts with external cats or people. A COVID-19 positive caretaker was found, whereas all the cats were negative for SARS-CoV-2 RNA and seronegative. Although the negative results cannot exclude previous infections followed by decrease of antibodies, this study suggests that colony cats do not have an important epidemiological role in SARS-CoV-2 transmission dynamics. Further studies on larger caseloads are warranted, also in the light of the emerging new viral variants, on a One Health perspective.

Preliminary report of an outbreak of SARS-CoV-2 in mink and mink farmers associated with community spread, Denmark, June to November 2020.

In June-November 2020, SARS-CoV-2-infected mink were detected in 290 of 1,147 Danish mink farms. In North Denmark Region, 30% (324/1,092) of people found connected to mink farms tested SARS-CoV-2-PCR-positive and approximately 27% (95% confidence interval (CI): 25-30) of SARS-CoV-2-strains from humans in the community were mink-associated. Measures proved insufficient to mitigate spread. On 4 November, the government ordered culling of all Danish mink. Farmed mink constitute a potential virus reservoir challenging pandemic control.

Current status on treatment options for feline infectious peritonitis and SARS-CoV-2 positive cats.

Feline infectious peritonitis (FIP) is a viral-induced, immune-mediated disease of cats caused by virulent biotypes of feline coronaviruses (FCoV), known as the feline infectious peritonitis virus (FIPV). Historically, three major pharmacological approaches have been employed to treat FIP: (1) immunomodulators to stimulate the patient's immune system non-specifically to reduce the clinical effects of the virus through a robust immune response, (2) immunosuppressive agents to dampen clinical signs temporarily, and (3) re-purposed human antiviral drugs, all of which have been unsuccessful to date in providing reliable efficacious treatment options for FIPV. Recently, antiviral studies investigating the broad-spectrum coronavirus protease inhibitor, GC376, and the adenosine nucleoside analogue GS-441524, have resulted in increased survival rates and clinical cure in many patients. However, prescriber access to these antiviral therapies is currently problematic as they have not yet obtained registration for veterinary use. Consequently, FIP remains challenging to treat. The purpose of this review is to provide an update on the current status of therapeutics for FIP. Additionally, due to interest in coronaviruses resulting from the current human pandemic, this review provides information on domesticated cats identified as SARS-CoV-2 positive.

Comparative ACE2 variation and primate COVID-19 risk.

The emergence of SARS-CoV-2 has caused over a million human deaths and massive global disruption. The viral infection may also represent a threat to our closest living relatives, nonhuman primates. The contact surface of the host cell receptor, ACE2, displays amino acid residues that are critical for virus recognition, and variations at these critical residues modulate infection susceptibility. Infection studies have shown that some primate species develop COVID-19-like symptoms; however, the susceptibility of most primates is unknown. Here, we show that all apes and African and Asian monkeys (catarrhines), exhibit the same set of twelve key amino acid residues as human ACE2. Monkeys in the Americas, and some tarsiers, lemurs and lorisoids, differ at critical contact residues, and protein modeling predicts that these differences should greatly reduce SARS-CoV-2 binding affinity. Other lemurs are predicted to be closer to catarrhines in their susceptibility. Our study suggests that apes and African and Asian monkeys, and some lemurs, are likely to be highly susceptible to SARS-CoV-2. Urgent actions have been undertaken to limit the exposure of great apes to humans, and similar efforts may be necessary for many other primate species.