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.

[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.

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.

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)

Graft-versus-host disease and sialodacryoadenitis viral infection in bone marrow transplanted rats.

The effect of a localized viral infection on the occurrence of graft-vs.-host disease (GVHD) was examined in allogeneic rat bone marrow chimeras (ACI/LEW). Animals without clinical evidence of GVHD, 62 days after bone marrow transplant, were infected in salivary and lacrimal glands with sialodacryoadenitis virus (SDAV), and sacrificed 8-25 days postinfection. Using established histologic criteria, GVHD was found more frequently in salivary and lacrimal glands of SDAV-infected chimeras than uninfected chimeras. Skin and oral mucosa, tissues not infected by the virus, showed no differences in occurrence of GVHD, suggesting that the viral infection induced only local and not systemic GVHD. GVHD and SDAV infection, which are histologically similar, were differentiated by examining tissues for SDAV antigen using immunoperoxidase technique. Histologic changes were present for at least 1 week longer than viral antigen, suggesting they represented GVHD rather than viral infection. GVHD and SDAV infection were also differentiated by looking for a histologic feature characteristic of GVHD and not found in SDAV infection (periductal lymphocytic infiltrate). This was found in SDAV-infected chimeras more frequently than uninfected chimeras, suggesting that the viral infection somehow induced GVHD. Results showed a localized increase in the occurrence of GVHD subsequent to localized viral infection.

Association of coronavirus infection with neonatal necrotizing enterocolitis.

From the clustered occurrence of numerous cases of necrotizing enterocolitis in newborns, it was possible to associate this disease significantly with infection due to coronavirus-like agents. Prematurity or low birth weight did not seem to affect the development of the disease, at least during the present epidemic. However, associated gas-producing bacteria could influence its severity and play a role in the appearance of pneumatosis. In many aspects the human disease is reminiscent of experimental necrotizing enterocolitis obtained by infection of germ-free newborn animals, as reported in the literature.

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.

Nonfatal demyelinating encephalomyelitis induced by coronavirus (JHM strain) infection in mice.

C3H mice infected intravenously with the JHM strain of coronavirus showed high incidence of demyelination (44.8%) and low incidence of encephalitis-induced mortality (6.9%). High titers of virus were detectable in the brain and liver of mice only during the first 3 to 12 days of infection (10(3) and 10(4) PFU/g, respectively). Most of the animals recovered from the first phase of disease and some (11.1%) came down with paralysis 6 to 7 weeks after the infection, with no histological changes or virus detectable in their tissues.

Feline immunodeficiency virus infection in a population of pet cats from southeastern Florida.

Blood samples from 95 randomly selected pet cats that were brought to veterinarians in southeastern Florida were tested for antibodies to feline immunodeficiency virus (FIV). Virus-specific antibodies (indicative of virus infection) were found in 8 of the 95 (8.4%) cats tested. All of the virus-infected cats were males (statistically significant, P less than or equal to 0.016) and were at least 1 year of age. The 3 most severely ill cats infected with FIV were also infected with feline leukemia virus.

Influence of environment on airsacculitis: effects of relative humidity and air temperature on broilers infected with Mycoplasma synoviae and infectious bronchitis.

Mycoplasma synoviae (MS) obtained from broiler chickens condemned for airsacculitis was used to determine the influence of air temperature and relative humidity on the severity of airsacculitis produced experimentally. Infectious bronchitis virus was administered to 3-week-old broilers 5 days before aerosol exposure to MS broth cultures, producing extensive airsacculitis within 21-day study periods. High (31-32 C), medium (19-24 C), and low (7-10 C) air temperatures were studied in conjection with high (75-90%), medium (38-56%), and low (23-26%) relative humidities. Airsacculitis was most extensive (45%) at low temperatures regradless of high or medium humidity. The incidence of airsacculitis was greater (39%) at low humidity than at high humidity (17%) when air temperatures were medium. At high temperature, the trend was toward more airsacculitis (12%) at high humidity than (5%) at low humidity. However, the effect of cold air temperature was more dominant than the effect of relative humidity.

Airsacculitis induced in broilers with a combination of Mycoplasma gallinarum and respiratory viruses.

Mycoplasma gallinarum was isolated from tracheas and air-sac lesions from broilers in flocks having higher than normal condemnations due to airsacculitis. A representative M. gallinarum isolant, given by aerosol or by air-sac inoculation, produced air-sac lesions in young chickens when given in combination with a vaccine combining Newcastle disease and infectious bronchitis or with a field strain of infectious bronchitis virus.

Increased incidence of airsacculitis in broilers infected with mycoplasma synoviae and chicken-passaged infectious bronchitis vaccine virus.

Infectious bronchitis vaccine virus is thought to cycle (i.e., pass from vaccine-virus-infected to susceptible chickens) in commercial broiler and pullet flocks. To simulate the effect of this cycling, mild infectious bronchitis vaccine virus was passaged in chickens serially six times. This sixth passage virus was used to infect chickens, which were then exposed to a moderately cold environment of 10 +/- 2 C and to Mycoplasma synoviae. In two separate experiments, the chicken-passaged vaccine virus resulted in a marked increase in the incidence of airsacculitis compared with nonpassaged vaccine virus. Intermediate passage levels also increased airsacculitis incidence but not as much as the sixth passage virus. In another experiment, virus chicken-passaged by contact transmission also caused increased airsacculitis incidence.

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.

Studies of avian urolithiasis associated with an infectious bronchitis virus.

Avian urolithiasis syndrome was diagnosed in 14-to-25-week-old chickens from a multiple-age caged-layer complex housing more than 2.5 million chickens. Losses from this syndrome ranged from 0.5 to 1.0% per week. Seven-to-14-week-old pullets from this facility had multifocal renal tubular necrosis leading to interstitial fibrosis, tophus formation, and tubular dilation. A coronavirus was isolated in embryos inoculated with pooled samples of trachea, kidney, and cecal tonsil of 4-week-old pullets. This virus, identified as 85-209, was related to infectious bronchitis virus strain Florida 88 by hemagglutination-inhibition assay. Day-old specific-pathogen-free chicks were inoculated with fifth-embryo-passage amnioallantoic fluid containing this virus. These chicks developed histologic lesions of tracheitis at 5 to 7 days postinoculation. Half the chicks inoculated by eyedrop developed renal tubular necrosis after 7 days. Urolithiasis in the flock investigated was attributed to renal damage by this strain of infectious bronchitis virus occurring in 4-to-7-week-old pullets and progressing to segmental atrophy, hyperplasia, and ureteral stone formation in 14-to-25-week-old chickens.

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.

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.

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.

Evaluation of antithrombin-III activity as a coindicator of disseminated intravascular coagulation in cats with induced feline infectious peritonitis virus infection.

Six adult specific-pathogen-free cats were inoculated intraperitoneally with a cell culture-adapted strain of feline infectious peritonitis virus. Plasma samples were evaluated for antithrombin-III (AT-III) activities at post-inoculation days (PID) 0, 4, and 11 and at termination on PID 16 (1 cat) or 21 (5 cats). Other hemostatic values evaluated were activated partial thromboplastin times, prothrombin times, thrombin times, fibrinogen, platelet counts, and fibrin/fibrinogen degradation products. Antithrombin-III activity remained within normal or above normal range (89 to 246%) in all cats, with the exception of one cat on PID 4 (AT-III, 70%). Mean baseline AT-III activity for 6 cats at PID 0 was 123%. Mean AT-III activity on PID 4, 11, and 16 or 21 was 98, 162, and 130%, respectively. On PID 4 and 16 or 21, results of coagulation screening tests indicated that all cats had disseminated intravascular coagulation. Histologically, cats also had severe fibrinonecrotizing thrombovasculitis.