Case Report: Postacute Rehabilitation of Guillain-Barré Syndrome and Cerebral Vasculitis-Like Pattern Accompanied by SARS-CoV-2 Infection.

Introduction: The main clinical manifestation of the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is respiratory issues. Neurological manifestations are being increasingly recognized, including febrile seizures, headache, dizziness, and myalgia, as well as encephalopathy, encephalitis, stroke, and acute peripheral nerve diseases. Cerebral vasculitis is rarely reported. We describe a case of SARS-CoV-2 interstitial pneumonia complicated by flaccid tetraplegia due to Guillain-Barré Syndrome (GBS) associated with a cerebral vasculitis-like pattern. Case description: A 62-year-old man was hospitalized for cough, fever, and severe respiratory failure requiring tracheal intubation and invasive ventilation. The chest Computerized Tomography (CT) showed images related to interstitial pneumonia and the subsequent nasopharyngeal swab confirmed the presence of SARS-CoV-2 infection. During the hospitalization, there was a progressive deterioration of the senses associated with areflexic flaccid tetraplegia. The treatment with high doses of immunoglobulin G (IgG) led to the immediate improvement of the general conditions and a partial response in terms of recovery of the upper limb and of the distal lower limb movements. Subsequently the patient was admitted to our Rehabilitation Unit, where he received an intensive rehabilitation treatment consisting of physiotherapy and occupational therapy. Two months later the patient was discharged at home and able to walk independently even for long distances thanks to the use of Ankle-Foot Orthosis (AFO). Conclusion: In this report, we present the case of a patient with peripheral and central neurological damage occurred later severe pneumonia induced by SARS-CoV-2. The Immunoglobulin G therapy allowed the patient to benefit considerably from early rehabilitation, reaching the walking, increasing the independence in daily living tasks, and enabling safe discharge from hospital to home. Related neurologic complications of SARS-CoV-2 infection suffer a lack of understanding and further investigations should be conducted.

Acute Generalized Exanthematous Pustulosis (AGEP) in 12 Patients Treated for SARS-CoV-2 Positive Pneumonia.

ABSTRACT: The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading throughout the world. The study describes 12 patients with SARS-CoV-2 pneumonia, who developed an acute erythematous rash with nonfollicular pinhead-sized pustules, without mucosal involvement. The clinical differential diagnosis was viral rash, acute generalized exanthematous pustulosis (AGEP), or multiform erythema. computed tomography with a diagnosis of interstitial pneumonia and a respiratory tract sample positive for SARS-CoV-2 in a reverse transcriptase polymerase chain reaction assay. Patients had signs of respiratory distress and were treated with hydroxychloroquine, darunavir, ritonavir, heparin, ceftriaxone, and azithromycin. Punch biopsies showed subcorneal pustules typical of AGEP. Dermal microvascular injury and thrombosis as described in skin damage by SARS-CoV-2 infection was not observed. The direct immunofluorescence for IgG, IgA, IgM, and C3 was negative in 8 patients investigated. A polymerase chain reaction for RNA SARS-CoV-2 performed on frozen skin was negative in 5 of 6 patients. Most of our patients were treated with systemic corticosteroids. After some days (4-10), the diffuse erythema and pustules had improved. AGEP is classified as a severe cutaneous adverse reaction, provoked by drugs and acute infections. Characteristically, removal of the offending agent leads to spontaneous resolution typically in less than 15 days. The recognition of AGEP is important, in order to avoid confusion with a systemic infection and consequently to avoid incorrect treatment. Cutaneous adverse reactions to drugs are common and are major health problems worldwide causing considerable costs for health care systems. We suggest that in the patients with AGEP during SARS-CoV-2 pneumonia, viral infection is a risk factor for developing drug reaction.

Lung Expression of Human Angiotensin-Converting Enzyme 2 Sensitizes the Mouse to SARS-CoV-2 Infection.

Preclinical mouse models that recapitulate some characteristics of coronavirus disease (COVID-19) will facilitate focused study of pathogenesis and virus-host responses. Human agniotensin-converting enzyme 2 (hACE2) serves as an entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to infect people via binding to envelope spike proteins. Herein we report development and characterization of a rapidly deployable COVID-19 mouse model. C57BL/6J (B6) mice expressing hACE2 in the lung were transduced by oropharyngeal delivery of the recombinant human adenovirus type 5 that expresses hACE2 (Ad5-hACE2). Mice were infected with SARS-CoV-2 at Day 4 after transduction and developed interstitial pneumonia associated with perivascular inflammation, accompanied by significantly higher viral load in lungs at Days 3, 6, and 12 after infection compared with Ad5-empty control group. SARS-CoV-2 was detected in pneumocytes in alveolar septa. Transcriptomic analysis of lungs demonstrated that the infected Ad5-hACE mice had a significant increase in IFN-dependent chemokines Cxcl9 and Cxcl10, and genes associated with effector T-cell populations including Cd3 g, Cd8a, and Gzmb. Pathway analysis showed that several Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched in the data set, including cytokine-cytokine receptor interaction, the chemokine signaling pathway, the NOD-like receptor signaling pathway, the measles pathway, and the IL-17 signaling pathway. This response is correlative to clinical response in lungs of patients with COVID-19. These results demonstrate that expression of hACE2 via adenovirus delivery system sensitized the mouse to SARS-CoV-2 infection and resulted in the development of a mild COVID-19 phenotype, highlighting the immune and inflammatory host responses to SARS-CoV-2 infection. This rapidly deployable COVID-19 mouse model is useful for preclinical and pathogenesis studies of COVID-19.

A nontrivial differential diagnosis in COVID-19 pandemic: a case report and literary review of amiodarone-induced interstitial pneumonia.

Amiodarone is a drug commonly used to treat and prevent cardiac arrhythmias, but it is often associated with several adverse effects, the most serious of which is pulmonary toxicity. A 79-year-old man presented with respiratory failure due to interstitial pneumonia during the COVID-19 pandemic. The viral etiology was nevertheless excluded by repeated nasopharyngeal swabs and serological tests and the final diagnosis was amiodarone-induced organizing pneumonia. The clinical and computed tomography findings improved after amiodarone interruption and steroid therapy. Even during a pandemic, differential diagnosis should always be considered and pulmonary toxicity has to be taken into account in any patient taking amiodarone and who has new respiratory symptoms.

Haemodynamic characteristics of COVID-19 patients with acute respiratory distress syndrome requiring mechanical ventilation. An invasive assessment using right heart catheterization.

AIMS: Interstitial pneumonia due to coronavirus disease 2019 (COVID-19) is often complicated by severe respiratory failure. In addition to reduced lung compliance and ventilation/perfusion mismatch, a blunted hypoxic pulmonary vasoconstriction has been hypothesized, that could explain part of the peculiar pathophysiology of the COVID-19 cardiorespiratory syndrome. However, no invasive haemodynamic characterization of COVID-19 patients has been reported so far. METHODS AND RESULTS: Twenty-one mechanically-ventilated COVID-19 patients underwent right heart catheterization. Their data were compared both with those obtained from non-mechanically ventilated paired control subjects matched for age, sex and body mass index, and with pooled data of 1937 patients with 'typical' acute respiratory distress syndrome (ARDS) from a systematic literature review. Cardiac index was higher in COVID-19 patients than in controls [3.8 (2.7-4.5) vs. 2.4 (2.1-2.8) L/min/m2 , P < 0.001], but slightly lower than in ARDS patients (P = 0.024). Intrapulmonary shunt and lung compliance were inversely related in COVID-19 patients (r = -0.57, P = 0.011) and did not differ from ARDS patients. Despite this, pulmonary vascular resistance of COVID-19 patients was normal, similar to that of control subjects [1.6 (1.1-2.5) vs. 1.6 (0.9-2.0) WU, P = 0.343], and lower than reported in ARDS patients (P < 0.01). Pulmonary hypertension was present in 76% of COVID-19 patients and in 19% of control subjects (P < 0.001), and it was always post-capillary. Pulmonary artery wedge pressure was higher in COVID-19 than in ARDS patients, and inversely related to lung compliance (r = -0.46, P = 0.038). CONCLUSIONS: The haemodynamic profile of COVID-19 patients needing mechanical ventilation is characterized by combined cardiopulmonary alterations. Low pulmonary vascular resistance, coherent with a blunted hypoxic vasoconstriction, is associated with high cardiac output and post-capillary pulmonary hypertension, that could eventually contribute to lung stiffness and promote a vicious circle between the lung and the heart.

A rare case of acute motor axonal neuropathy and myelitis related to SARS-CoV-2 infection.

We describe a rare case of post-infective Acute Motor Axonal Neuropathy (AMAN) variant of Guillain-Barrè Syndrome (GBS) associated with myelitis and anti-GD1b positivity after SARS-CoV-2 infection. The patient referred to the hospital reporting a history of ten days lasting moderate fever, myalgia and anosmia, with the onset of progressive quadriparesis and ascending paraesthesias in the four limbs since five days from defervescence. A chest computed tomography demonstrated interstitial pneumonia with "ground glass opacities", suggesting Coronavirus disease (COVID-19). The patient exhibited three negative reverse-transcription polymerase chain reaction (RT-PCR) nasopharyngeal swabs, while SARS-CoV-2 IgG was found in plasma. The electrophysiological examination demonstrated an AMAN and the spinal cord Magnetic Resonance Imaging (MRI) showed a T2-weighted hyperintense lesion in the posterior part of the spinal cord at the C7-D1 levels. Furthermore, anti-GD1b IgM was detected. GBS and myelitis could exceptionally develop simultaneously. Our findings reasonably support a causality link between COVID-19 and the neurological symptoms, suggesting a post-infective autoimmune reaction.

Platypnea-orthodeoxia after fibrotic evolution of SARS-CoV-2 interstitial pneumonia. A case report.

Platypnea-orthodeoxia syndrome (POS) is a clinical entity characterized by positional dyspnoea (platypnea) and arterial desaturation (orthodeoxia) that occurs when sitting or standing up and usually resolves by lying down. POS may result from some cardiopulmonary disorders or from other miscellaneous aetiologies. We report a case of POS in a patient after fibrotic evolution of SARS-CoV-2 interstitial pneumonia associated with pulmonary embolism. The patient did not have any evidence of an intracardiac/intrapulmonary shunt.

Inappropriate risk perception for SARS-CoV-2 infection among Italian HCWs in the eve of COVID-19 pandemic.

Sir, Italy has been recently involved in the outbreak of severe interstitial pneumonia associated with the previously unknown Coronavirus SARS-CoV-2 (1,2). Even before the notification of the first autochthonous cases, the SARS-CoV-2 associated syndrome (COVID-19) had raised an intense attention in the public opinion (3), with a counterproductive over-abundance of mixed quality information. As even Italian healthcare workers (HCWs) were not spared by subsequent misunderstandings and knowledge gaps during the previous influenza pandemic of 2009 (4), we performed a web-based survey (Google® Modules), specifically aimed to characterize knowledge status and risk perceptions in a sample from participating to 6 Facebook discussion groups (181,684 total unique members at the time of the study). The questionnaire was made available between February 1st and 7th, 2020, i.e. around 2 weeks before the first COVID-19 was officially diagnosed in Italian residents.   Overall, the sampled population included 2106 respondents (Table 1), and 39.3% were HCWs. Even though HCWs were more likely to exhibit a better understanding of SARS-CoV-2/COVID-19 related issues (aOR 2.195, 95%CI 1.809 to 2.664), they were not exempt for misunderstandings, particularly on actual incidence and lethality of COVID-19. Interestingly, most of respondents were aware of the main clinical features of COVID-19, with HCWs more frequently acknowledging that the COVID-19 may run pauci- or even asymptomatic (86.3% vs. 79.1%), resembling an Influenza-Like Illness (i.e. fever, cough, headache, etc.), with a potential latency up to 14 days (85·9% vs· 80·3%), eventually spreading by droplets (98.5% vs. 92.7%) rather through running water (92.3% vs· 79.8%), or blood/body fluids (88.0% vs. 70.4%).   Retrospectively, the assessment of preventive measures and risk perception appears somewhat worrisome. For instance, while HCWs were more likely to acknowledge as an appropriate preventive measure wearing a filtering mask (i.e. N95/FFP2/3 mask; aOR 2.296, 95%CI 1.507 to 3.946), around » of HCWs failed to recognize the importance of such personal protective equipment, while 7.4% felt as appropriate the wearing of a surgical mask. Moreover, not only COVID-19 was appropriately acknowledged as a severe disease by only 62.0% of respondents, with no differences between HCWs and non-HCWs, but an even smaller share (i.e. 8.0%) reported any concern for being infected by SARS-CoV-2 in Italy. In fact, at the time of the survey SARS-CoV-2 was more properly associated with international travelers (26.7%).   Our results are therefore of certain interests for several reasons. First at all, early epidemiological reports on the Italian cases of COVID-19 hint towards some failures in the initial management of incident cases (5-6). In fact, in our survey a large share of respondents substantially overlooked the risk to interact with SARS-CoV-2 positive subjects, that was otherwise perceived as a not-so-severe disease (i.e. "nothing more than a seasonal flu", as often described in some social media) (7). Moreover, around a 1/3 of HCWs participating to the study presumptively did not use proper personal protective equipment for the airways interacting with possible COVID-19 cases, either underestimating the infection risk or being unable to recognize early symptoms. Actually, the base of evidence shared by participants at the time of the study substantially ignored that COVID-19 may be characterized by dermatologic and gastro-intestinal symptoms (8-9). As most of infections may be actually pauci- or asymptomatic, such early exposure in the healthcare settings may have contributed to the quick spreading of SARS-CoV-2 epidemic in Northern Italy.   Therefore, despite the intrinsic limits of a convenience sampling, web-based survey (10), our study stresses the importance to improve the overall quality of information on COVID-19 conveyed not only in HCWs, but also in the general population. Moreover, our data may contribute to clarify the early stages of SARS-CoV-2 pandemic in Italy.

Acute myocardial infarction and large coronary thrombosis in a patient with COVID-19.

This is a case report of a 60-year-old male, without any cardiovascular risk factor and no cardiac history admitted to hospital with a diagnosis of interstitial pneumonia caused by coronavirus disease 2019 (COVID-19). After 7 days, the blood tests showed a significant rise of inflammatory and procoagulant markers, along with a relevant elevation of high-sensitivity Troponin I. Electrocardiogram and transthoracic echocardiogram (TTE) were consistent with a diagnosis of infero-posterolateral acute myocardial infarction and the patient was transferred to the isolated Cath Lab for primary percutaneous coronary intervention (PCI). The angiography showed an acute massive thrombosis of a dominant right coronary artery without clear evidence of atherosclerosis. Despite the optimal pharmacological therapies and different PCI techniques, the final TIMI flow was 0/1 and after 3 hr the clinical condition evolved in cardiac arrest for pulseless electric activity. Acute coronary syndrome-ST-elevation myocardial infarction is a relevant complication of COVID-19. Due to high levels of proinflammatory mediators, diffuse coronary thrombosis could occur even in patients without cardiac history or comorbidities. This clinical case suggests that coronary thrombosis in COVID-19 patients may be unresponsive to optimal pharmacological (GP IIb-IIIa infusion) and mechanical treatment (PCI).