[Neurological damage linked to coronaviruses : SARS-CoV-2 and other human coronaviruses]. / Les atteintes neurologiques liées au SARS-CoV-2 et autres coronavirus humains.

The recent emergence of a new coronavirus, SARS-CoV-2, responsible for COVID-19, is a new warning of the risk to public health represented by viral zoonoses and in particular by coronaviruses. Mainly described as being able to infect the upper and lower respiratory tract, coronaviruses can also infect the central and peripheral nervous systems as many other respiratory viruses, such as influenza or respiratory syncytial virus. Viral infections of the nervous system are a major public health concern as they can cause devastating illnesses up to death, especially when they occur in the elderly, who are more susceptible to these infections. Knowledge concerning the pathophysiology of recently emerging coronaviruses (MERS-CoV, SARS-CoV and SARS-CoV-2) and how they reach the central nervous system are very sketchy and the work in progress aims in particular to better understand their biology and the mechanisms associated with neurological damage. In this review we will discuss the current state of knowledge on the neurotropism of human coronaviruses and the associated mechanisms by developing in particular the latest data concerning SARS-CoV-2.

TITLE: Les atteintes neurologiques liées au SARS-CoV-2 et autres coronavirus humains. ABSTRACT: L'émergence récente d'un nouveau coronavirus, le SARS-CoV-2, responsable de la maladie appelée COVID-19, est un nouvel avertissement du risque pour la santé publique représenté par les zoonoses virales et notamment par les coronavirus. Principalement connus pour leur capacité à infecter les voies respiratoires supérieures et inférieures, les coronavirus peuvent également affecter le système nerveux central et périphérique, comme c'est le cas pour de nombreux virus respiratoires, tels que les virus influenza ou le virus respiratoire syncytial. Les infections du système nerveux sont un problème important de santé publique car elles peuvent provoquer des atteintes dévastatrices allant jusqu'au décès du patient, en particulier lorsqu'elles surviennent chez les personnes fragilisées ou âgées plus sensibles à ce type d'infection. Les connaissances de la physiopathologie des infections par les coronavirus émergents (MERS-CoV, SARS-CoV et SARS-CoV-2) et leurs moyens d'accéder au système nerveux central sont, pour l'heure, très sommaires. Les travaux en cours visent notamment à mieux appréhender les mécanismes associés aux atteintes neurologiques observées. Dans cette revue nous aborderons l'état des connaissances actuelles sur le neurotropisme des coronavirus humains et les mécanismes associés en développant tout particulièrement les dernières données concernant le SARS-CoV-2.

COVID-19 and anosmia in Tehran, Iran.

Patients with acute olfactory disorders typically present to the otolaryngologist with both acute hyposmia and less often with anosmia. With the onset of COVID-19 we have noticed an increase in the number of patients who have presented with new onset of complete smell loss to the senior author's practice in Tehran, Iran. This anosmia and the frequency with which patients present is highly unusual. Coronaviruses have been known to cause common cold symptoms. COVID-19 infections have been described as causing more severe respiratory infections and the symptoms reported by authors from Wuhan, China have not specifically included anosmia. We describe patients who have presented during a two-week period of the COVID-19 pandemic with complete loss of sense of smell. Most had either no symptoms or mild respiratory symptoms. Many had a normal otolaryngologic exam. A relationship between COVID-19 and anosmia should be considered during the pandemic. We hypothesize that the mechanism of injury is similar to that of other coronavirus infections that cause central and peripheral neurologic deficits.

Manifestações cutâneas relacionadas à COVID-19: uma revisão da literatura / Cutaneous manifestations related to COVID-19: a literature review

Neste artigo identificamos as manifestações de pele mais comuns relacionadas à doença do coronavírus 19 (COVID-19), a fim de facilitar o diagnóstico realizado pelos profissionais da saúde. Foram analisados um total de 524 pacientes, por meio de 20 artigos, sobre a relação entre o vírus e as lesões de pele. Os artigos considerados elegíveis para essa revisão preencheram critérios como descrição completa das lesões cutâneas e presença de foto. A prevalênciadas lesões de pele aumentou com a idade, sendo maiorno sexo feminino. Observou-se cinco principais tipos de manifestações, em ordem decrescente de prevalência: exantema maculopapular generalizado morbiforme, erupção cutânea papulovesicular, urticária, livedo reticular e placas eritematosas. Esses padrões aparecem em momentos diferentes da doença e estão associados a diferentes durações, gravidade e prognóstico. Vale destacar, que grande parte das lesões foram encontradas em tronco e extremidades. Além dessas manifestações, outros sintomas foram identificados, sendo febre o sintoma mais comum. Dessa forma, compreender as diversas apresentações do coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2) é de extrema importância no entendimento epidemiológico da doença. Portanto, profissionais da saúde devem atentar para as manifestações cutâneas nos pacientes pois, em conjunto com outros sinais e sintomas, ajudam a compor o quadro clínico da COVID-19, colaborando para um diagnóstico clínico e diferencial precoce. (AU)

In this article, we identified the most common skin manifestations related to coronavirus disease 2019 (COVID-19) to facilitate the diagnosis made by health professionals. A total of 524 patients were included by analyzing 20 articles regarding the relation between the virus and skin lesions. The articles considered eligible for this review met criteria such as complete description of the skin lesions and presence of a photograph. The prevalence of skin lesions increased with age, being higher in women. The following five main types of manifestations were observed, in descending order of prevalence: generalized morbilliform maculopapular rash, papulovesicular rash, urticaria, livedo reticularis and erythematous plaques. These patterns appeared at different times of the disease and were associated with different durations, severity and prognosis.It is worth noting that many lesions were found on the trunk and extremities. In addition to these manifestations, other symptoms were identified, with fever being the most common. Thus, understanding the various presentations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is extremely important in the epidemiological understanding of the disease. Therefore, health professionals should pay attention to skin manifestations in patients because, together with other signs and symptoms, they help formulate the clinical picture of COVID-19, contributing to an early clinical and differential diagnosis. (AU)

Cerebral pyogranuloma associated with systemic coronavirus infection in a ferret.

A 2-year-old male ferret was presented with central nervous system signs. Computed tomography (CT) of the brain revealed a well-defined contrast-enhancing lesion on the rostral forebrain that appeared extraparenchymal. Surgical excision of the mass was performed and the ferret was euthanised during the procedure. Histopathology of the excised mass showed multiple meningeal nodular lesions with infiltrates of epithelioid macrophages, occasionally centred on degenerated neutrophils and surrounded by a broad rim of plasma cells, features consistent with pyogranulomatous meningitis. The histopathological features in this ferret were similar to those in cats with feline infectious peritonitis. Definitive diagnosis was assessed by immunohistochemistry, confirming a ferret systemic coronavirus (FSCV) associated disease. This is the first case of coronavirus granuloma described on CT-scan in the central nervous system of a ferret.

MERS CoV infection in two renal transplant recipients: case report.

Middle East Respiratory Syndrome Coronavirus (MERS CoV) infection has recently emerged as a cause of severe potentially fatal pneumonia. The clinical presentation ranges from asymptomatic infection to severe pneumonia and acute renal failure. Data on the clinical presentation in solid organ transplant recipients are lacking. We report two cases of MERS CoV infections in two renal transplant recipients with variable clinical presentations and outcomes. The first patient presented with progressive respiratory symptoms, acute renal failure and died. While the second patient presented with respiratory tract symptoms, remained stable and had an excellent clinical recovery despite recent reception of thymoglobulin induction. This is a rare report of MERS CoV infection in renal transplant recipients. Further data are needed to gain better understanding of the impact of anti-rejection immunosuppressive therapy on the clinical presentation, severity and outcome of MERS CoV infections in solid organ transplant recipients.

Possible involvement of infection with human coronavirus 229E, but not NL63, in Kawasaki disease.

Although human coronavirus (HCoV)-NL63 was once considered a possible causative agent of Kawasaki disease based on RT-PCR analyses, subsequent studies could not confirm the result. In this study, this possibility was explored using serological tests. To evaluate the role of HCoV infection in patients with Kawasaki disease, immunofluorescence assays and virus neutralizing tests were performed. Paired serum samples were obtained from patients with Kawasaki disease who had not been treated with γ-globulin. HCoV-NL63 and two antigenically different isolates of HCoV-229E (ATCC-VR740 and a new isolate, Sendai-H) were examined as controls. Immunofluorescence assays detected no difference in HCoV-NL63 antibody positivity between the patients with Kawasaki disease and controls, whereas the rate of HCoV-229E antibody positivity was higher in the patients with Kawasaki disease than that in controls. The neutralizing tests revealed no difference in seropositivity between the acute and recovery phases of patients with Kawasaki disease for the two HCoV-229Es. However, the Kawasaki disease specimens obtained from patients in recovery phase displayed significantly higher positivity for Sendai-H, but not for ATCC-VR740, as compared to the controls. The serological test supported no involvement of HCoV-NL63 but suggested the possible involvement of HCoV-229E in the development of Kawasaki disease.

Role of regulatory T cells in coronavirus-induced acute encephalitis.

C57BL/6 mice infected with mouse hepatitis virus, strain JHM (JHMV) develop a rapidly fatal acute encephalitis. Previously, we showed that this disease is partially CD4 T cell-mediated since infection with a recombinant JHMV (rJ) mutated in only a single immunodominant CD4 T cell epitope (epitope M133, rJ.M(Y135Q)) results in a nonlethal disease. Increased mortality correlated with a greater number of JHMV-specific CD4 T cells in the brains of rJ compared to rJ.M(Y135Q)-infected mice. Here, we extend these results to show that the diminished number of virus-specific T cells correlates with a reduced cytokine/chemokine response in the infected brain. We also show that regulatory CD4 T cells (Tregs) are critical for mild disease in rJ.M(Y135Q)-infected mice because their depletion results in increased mortality. Further, a relative paucity of Tregs characterizes lethal infection because adoptive transfer of Tregs into rJ-infected mice increases survival from 0% to 50%. These results support the notion that clinical disease in coronavirus-induced acute encephalitis results from a balance between factors critical for virus clearance, such as virus-specific effector T cells and anti-inflammatory elements, such as Tregs. These findings also show that unlike chronic infections, in which an excessive number of Tregs contributes to pathogen persistence, Tregs in the setting of acute encephalitis may help to limit immunopathological disease without delaying virus clearance.

Persistence of viruses in upper respiratory tract of children with asthma.

OBJECTIVES: Nasopharyngeal swabs of 50 asthmatic children in the symptom-free period were examined for the presence of adenoviruses, rhinoviruses and coronaviruses. A control group of 20 healthy individuals was included in this study. METHODS: A polymerase chain reaction was used to detect adenovirus DNA and rhinovirus and coronavirus complementary DNA. The fragments of amplified genetic material were visualized with the use of agarose gel electrophoresis. RESULTS: Adenovirus DNA was found in 78.4% of asthmatic children, rhinovirus RNA in 32.4% and coronavirus RNA in 2.7%. Adenovirus DNA was detected in one of the 20 nasopharyngeal swabs of healthy controls; the rest of the control samples were negative. CONCLUSIONS: The persistent presence of viruses in the upper respiratory tract of asthmatic children shows a possible connection between viral infections and asthma.

Pathogenicity of concurrent infection of pigs with porcine respiratory coronavirus and swine influenza virus.

Combinations of porcine respiratory coronavirus (PRCV) and either of two swine influenza viruses (H1N1 or H3N2) were administered intranasally and by aerosol to six- to eight-week-old specific pathogen-free pigs. The clinical responses, gross respiratory lesions and growth performances of these pigs were studied and compared with those of single (PRCV, H1N1 or H3N2) and mock-infected animals. PRCV infection caused fever, growth retardation and lung lesions, but no respiratory symptoms. Infection with swine influenza viruses caused rather similar, mild symptoms of disease, with H1N1 infection being the least severe. Combined infections with influenza viruses and PRCV did not appear to enhance the pathogenicity of these viruses. Furthermore, viruses were isolated more frequently from tissues and nasal swabs taken from 'single' than 'dual' infected animals, suggesting a possible in vivo interference between replication of PRCV and swine influenza virus.

Escherichia coli multiplication and lesions in the respiratory tract of chickens inoculated with infectious bronchitis virus and/or E. coli.

Escherichia coli numbers and histopathological changes were studied in the respiratory tract of line 151 chickens intranasally inoculated with infectious bronchitis virus (IBV) and/or virulent E. coli; this line is highly susceptible to IBV. Chickens inoculated with IBV alone showed increased numbers of E. coli in the trachea and had tracheitis, airsacculitis, and bronchiolitis. One of 17 chickens inoculated with IBV alone died with fibrinopurulent serositis. Chickens inoculated with IBV and E. coli had more severe and persistent respiratory lesions than those inoculated with IBV alone. E. coli was isolated from tracheas of chickens inoculated with IBV and E. coli more frequently than from chickens inoculated with IBV alone. In this group, 14 of 27 chickens died with tracheal plugs or with fibrinopurulent serositis. There was neither increased numbers of E. coli nor significant lesions in the respiratory tract of the group inoculated with E. coli alone. These results suggest that IBV may facilitate E. coli invasion into the lower respiratory tract of the chicken.

Serologic prevalence of selected infectious diseases in cats with uveitis.

Serologic evidence of infection by Toxoplasma gondii, feline leukemia virus, feline coronaviruses, or feline immunodeficiency virus (FIV) is commonly found in cats with uveitis. Serum samples from 124 cats with uveitis were assayed by use of ELISA for the detection of T gondii-specific immunoglobulin M (IgM), IgG, and circulating antigens (Ag), as well as an ELISA for feline leukemia virus Ag, an ELISA for antibodies to FIV, and an indirect fluorescent antibody assay for antibodies to feline coronaviruses. Serologic evidence of infection by 1 or more of the infectious agents was detected in 83.1% of the samples. Serologic evidence of T gondii infection, defined as the detection of T gondii-specific IgM, IgG, or Ag in serum, was found in 74.2% of the samples. The seroprevalence of T gondii infection was significantly greater in cats with uveitis than in healthy cats from a similar geographic area. Serum samples from cats with serologic evidence of both T gondii and FIV infections were more likely to contain T gondii-specific IgM without IgG than samples from cats with serologic evidence of T gondii infection alone. Cats with serologic evidence of FIV and T gondii coinfection had a higher T gondii-specific IgM titer geometric mean and a lower T gondii-specific IgG titer geometric mean than did cats with serologic evidence of T gondii infection alone. Serologic evaluation for T gondii infection should include assays that detect IgM, IgG, and Ag, particularly in cats coinfected with FIV.

Induction and enhancement of feline infectious peritonitis by canine coronavirus.

Preexisting antibody to feline infectious peritonitis virus (FIPV) causes acceleration and enhancement of disease on subsequent infection of cats with FIPV. Other workers have shown that canine coronavirus (CCV) can infect cats subclinically, but have found no evidence of enhancement of, or protection against, subsequent FIPV infection. With various isolates of CCV, we determined that 1 strain of CCV can induce transient mild diarrhea in cats and, furthermore, that previous infection with CCV causes acceleration and enhancement of subsequent infection with FIPV. In addition, sequential inoculation of cats with another strain of CCV caused lesions indistinguishable from those of FIP, without exposure at any time to FIPV.

Concurrent experimentally induced infection with Eimeria bovis and coronavirus in unweaned dairy calves.

Over a period of 3 summers, 21 colostrum-fed Holstein bull calves, 1 to 3 days old, were assigned to 7 replicates, each consisting of 3 calves. Within each replicate of 3 calves, 2 were selected at random, to be given 100,000 to 146,000 sporulated coccidia oocysts (principally Eimeria bovis) orally 60 hours after arrival at the college research farm. On the thirteenth day after coccidia inoculation, 1 of the 2 calves that had been given coccidia and the third calf that had not been inoculated, were given coronavirus by intranasal and oral routes. Calves were observed daily, and consistency of feces was scored visually. Nasal swab specimens for indirect immunofluorescent antibody testing for coronavirus and fecal samples for oocyst determination were obtained approximately every third day. Of 7 calves that were given only coronavirus, 3 developed diarrhea of short duration. Of 7 calves that were given only coccidia oocysts, 6 developed diarrhea. All 7 calves inoculated initially with coccidia and subsequently with coronavirus developed diarrhea. For 5 of 7 replicates, calves that were given coccidia and coronavirus developed diarrhea first. When overall severity, measured by fecal score and by blood in the feces, was compared, calves inoculated with coccidia followed by coronavirus were more severely affected (P less than 0.05) than were calves that were given only coronavirus. Calves that were given only coccidia oocysts appeared more severely affected than calves that were given only coronavirus, but differences were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

A study of naturally occurring feline coronavirus infections in kittens.

Feline coronavirus is a common infection in cats, as indicated by the high prevalence of antibodies against the virus, especially in multicat households. Approximately 5 to 12 per cent of seropositive cats develop classical feline infectious peritonitis. A survey of kittens born into households of seropositive cats demonstrated the existence of healthy coronavirus carriers. Seronegative animals did not appear to excrete virus. No specific antibody titre could be linked to carrier status and some carrier cats subsequently became seronegative. The management of the kittens strongly influenced whether they became infected, and some degree of protection appeared to be conferred by maternally derived antibody. At present, feline infectious peritonitis virus and feline enteric coronavirus can only be differentiated by their different clinical histories in infected catteries. In this survey, cases of feline infectious peritonitis occurred in kittens from households where the initial presentation had been enteritis and vice versa. Therefore no difference in epidemiology could be found.

An experimental model for myocarditis and congestive heart failure after rabbit coronavirus infection.

In a model for virus-induced myocarditis and congestive heart failure, rabbit coronavirus infection was divided into acute (days 2-5) and subacute (days 6-12) phases on the basis of day of death and pathologic findings. During the acute phase, the principal histologic lesions were degeneration and necrosis of myocytes, myocytolysis, interstitial edema, and hemorrhage. The severity of these changes increased in the subacute phase. Pleural effusion and congestion of the lungs and liver were also present at this time. Myocarditis was detected by day 9 and peaked by day 12. Heart weights and heart weight-to-body weight ratios were increased, and dilation of the right ventricular cavity became prominent early in infection and persisted. In contrast, dilation of the left ventricle occurred late in the subacute stage. Virus was isolated from infected hearts between days 2 and 12. These data suggest that rabbit coronavirus infection progresses to myocarditis and congestive heart failure.

Concomitant cryptosporidia, coronavirus and parvovirus infection in a raccoon (Procyon lotor).

A juvenile raccoon (Procyon lotor) was found moribund near Fort Collins, Colorado (USA). Upon examination, the raccoon was dehydrated, had a mucopurulent oculonasal discharge and diarrhea, and was euthanized. Postmortem examination revealed emaciation, severe fibrinous gastroenteritis and a small, firm liver. Histopathological findings included blunting of villi, infiltration of lamina propria with neutrophils and plasma cells, and mild bronchopneumonia. Cryptosporidium sp. was demonstrated on intestinal villi and coronavirus and parvovirus were identified in feces. Fluorescent antibody test for rabies was negative and no evidence of canine distemper was found.

Pathobiology of cryptosporidiosis (C. baileyi) in broiler chickens.

Pathologic and clinicopathologic changes were examined in broiler chickens inoculated with Cryptosporidium baileyi (Cb) alone or in combination with infectious bronchitis virus (IBV), infectious bursal disease virus (IBDV) or Escherichia coli (Ec). Concurrent infections with Cb and either IBV or Ec resulted in a greater respiratory inflammatory response than either agent given alone. Concurrent Cb, IBV or Ec infections resulted in a decreased density of respiratory cryptosporidial stages. No interactions between Cb and IBDV were observed. Clinicopathologic results in broiler chicks exhibiting signs of respiratory cryptosporidiosis indicated that pO2 decreased, pCO2 increased, HCO3 increased and CO2 increased. Changes in blood gases and serum electrolyte values correlated with signs of acute respiratory disease. Blood gases and serum electrolyte values were unchanged in birds with bursal and cloacal infections only. Results of these studies clarified pathogenetic events associated with avian respiratory cryptosporidiosis, and demonstrated that cryptosporidiosis may enhance the severity of respiratory disease caused by other avian pathogens.

Canine coronavirus infection in the dog following oronasal inoculation.

The pathogenesis of canine coronavirus (CCV) infection in 10-week-old puppies was studied up to 14 days after oronasal inoculation. Mild diarrhoea was seen from three to 11 days after inoculation, approximately coincident with faecal virus shedding. Virus was initially isolated from the tonsils on day 3, and then from both small and large intestinal tissues up to 14 days after inoculation. Virus was also isolated from liver and lung. Histological changes were not seen in any tissues, but CCV antigen was detected, using a peroxidase antiperoxidase staining technique, mainly in epithelium overlying gut-associated lymphoid tissue. Virus neutralising antibody was first detected on day 10. Specific anti-CCV IgM was first detected in plasma three days after inoculation and IgG on days 4 to 7. Small amounts of anti-CCV IgG, IgM and IgA were detected in duodenal secretion, but none in bile.