Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Background
During the COVID-19 pandemic general medical complications have received the most attention, whereas only few studies address the potential direct effect on mental health of SARS-CoV-2 and the neurotropic potential. Furthermore, the indirect effects of the pandemic on general mental health are of increasing concern, particularly since the SARS-CoV-1 epidemic (2002–2003) was associated with psychiatric complications.

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COVID-19 pandemic and mental health consequences: Systematic review of the current evidence.

The coronavirus disease 19 (COVID-19) pandemic is a significant psychological stressor in addition to its tremendous impact on every facet of individuals' lives and organizations in virtually all social and economic sectors worldwide. Fear of illness and uncertainty about the future precipitate anxiety- and stress-related disorders, and several groups have rightfully called for the creation and dissemination of robust mental health screening and treatment programs for the general public and front-line healthcare workers. However, in addition to pandemic-associated psychological distress, the direct effects of the virus itself (several acute respiratory syndrome coronavirus; SARS-CoV-2), and the subsequent host immunologic response, on the human central nervous system (CNS) and related outcomes are unknown. We discuss currently available evidence of COVID-19 related neuropsychiatric sequelae while drawing parallels to past viral pandemic-related outcomes. Past pandemics have demonstrated that diverse types of neuropsychiatric symptoms, such as encephalopathy, mood changes, psychosis, neuromuscular dysfunction, or demyelinating processes, may accompany acute viral infection, or may follow infection by weeks, months, or longer in recovered patients. The potential mechanisms are also discussed, including viral and immunological underpinnings. Therefore, prospective neuropsychiatric monitoring of individuals exposed to SARS-CoV-2 at various points in the life course, as well as their neuroimmune status, are needed to fully understand the long-term impact of COVID-19, and to establish a framework for integrating psychoneuroimmunology into epidemiologic studies of pandemics.

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Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms.

Background: The COVID-19 pandemic, caused by SARS-CoV-2, is of a scale not seen since the 1918 influenza pandemic. Although the predominant clinical presentation is with respiratory disease, neurological manifestations are being recognised increasingly. Based on knowledge of other coronaviruses, especially those that caused the SARS and MERS epidemics, we might expect to see rare cases of central nervous system (CNS) and peripheral nervous system (PNS) disease caused by SARS-CoV-2.

Recent developments: A growing number of case reports and series describe a wide array of neurological manifestations, but many lack detail, reflecting the challenge of studying such patients. Encephalopathy is relatively common, being reported for 93 patients in total, including 16 (7.5%) of 214 hospitalised COVID-19 patients in Wuhan, China, and 40 (69%) of 58 in intensive care with COVID-19 in France. Encephalitis has been described in 8 patients to date, and Guillain-Barre syndrome in 19 patients. SARS-CoV-2 is detected in the cerebrospinal fluid of some patients. Anosmia and ageusia are common and may occur in the absence of other clinical features. Unexpectedly, acute cerebrovascular disease is also emerging as an important complication, with cohort studies reporting stroke in 1.6-6% of hospitalised COVID-19 cases. So far, 88 patients have been described, mostly with ischaemic stroke, who frequently have vascular events in the context of a pro-inflammatory hypercoagulable state with elevated CRP, D-dimer, and ferritin.

Where next?: Careful clinical, diagnostic and epidemiological studies are needed to help define the manifestations and burden of neurological disease caused by SARS-CoV-2. Precise case definitions must be used to distinguish non-specific complications of severe disease, such as hypoxic encephalopathy and critical care neuropathy, from those caused directly or indirectly by the virus; these include infectious, para- and post-infectious encephalitis, hypercoagulable states leading to stroke, and acute neuropathies such as Guillain-Barre syndrome. Recognising SARS-CoV-2 neurological disease in patients whose respiratory infection is mild or asymptomatic may prove challenging, especially if the primary COVID-19 illness occurred weeks earlier. The proportion of infections leading to neurological disease will remain small. However, these patients may be left with severe neurological sequelae. With so much of the population infected, the overall number of neurological patients, and their associated health, social and economic costs, may be large. Healthcare planners and policymakers must prepare for this eventuality. The many ongoing studies investigating the neurological association will increase our knowledge base.

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Neurological Associations of COVID-19

Effects of COVID-19 on the Nervous System.

The discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the outbreak of coronavirus disease 2019 (COVID-19) are causing public health emergencies. A handful pieces of literature have summarized its clinical and radiologic features, whereas therapies for COVID-19 are rather limited. To evaluate the efficacy of convalescent plasma therapy in COVID-19 patients, we did this timely descriptive study. Six laboratory-confirmed COVID-19 patients were enrolled and received the transfusion of ABO-compatible convalescent plasma. The efficacy of this intervention was determined by the alleviation of symptoms, changes in radiologic abnormalities and laboratory tests. No obvious adverse effect observed during the treatment. Transfusion of convalescent plasma led to a resolution of ground-glass opacities and consolidation in patients #1, #2, #3, #4, and #6. In patients #1 and #5 who presented with SARS-CoV-2 in throat swab, convalescent plasma therapy elicited an elimination of the virus. Serologic analysis indicated an immediate increase in anti-SARS-CoV-2 antibody titers in patients #2 and #3, but not in patient #1. This study indicates that convalescent plasma therapy is effective and specific for COVID-19. This intervention has a special significance for eliminating SARS-CoV-2 and is believed to be a promising state-of-the-art therapy during COVID-19 pandemic crisis.

https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.25882

Treatment with convalescent plasma for COVID-19 patients in Wuhan, China.

With great interest, we read the paper “Nervous system involvement after infection with COVID-19 and other coronaviruses”. The authors speculated that SARS-CoV-2 may cause neurological damages (Wu et al., 2020). Herein, we provided clinical evidence showing the central nervous system (CNS) involvement for SARS-CoV-2. A Wuhan male had fever, shortness of breath, and myalgia since Jan 28. On Feb 10, his disease deteriorated and his consciousness suddenly progressed to confusion. Laboratory test indicated low WBC count (3.3 × 10/L) and lymphopenia (0.8 × 10/L). Skull computer tomography (CT) was normal (Fig. 1A), while chest CT showed multiple subpleural ground glass opacities (GGOs) (Fig. 1B). The patient was positive for SARS-CoV-2 and sent to our institution. On physical examination, vital signs were stable without altered consciousness. Meningeal irritation signs (including nuchal rigidity, Kernig sign and Brudzinski sign) and extensor plantar response were present. Arterial blood gas analysis indicted PO2/FiO2 ratio of 240 mmHg. This COVID19 patient was treated with arbidol and oxygen therapy, whereas his consciousness was not improved. Lumbar puncture was performed on Feb 16, and the cerebrospinal fluid (CSF) pressure was 220 mmHg. Laboratory tests with CSF showed WBC (0.001 × 10/L), protein (0.27 g/L), ADA (0.17 U/L) and sugar (3.14 mmol/L) contents within normal limits. The CSF specimen was further tested for SARS-CoV-2 but the result was negative. This patient did not have evidence of bacterial or tuberculous infection of the CNS. After careful evaluation by neurologic experts, encephalitis associated with SARS-CoV-2 infection was concluded. Treatment at this moment was largely supportive, including mannitol infusion. Intriguingly, the patient’s consciousness generally ameliorated since Feb 20, and chest CT suggested a resolution of GGOs (Fig. 1B). His consciousness was completely clear on Feb 24. Two consecutive throat swab tests were negative for SARS-CoV-2. The patient was discharged from hospital on Feb 27. This letter describes a COVID-19 case who presented as encephalitis. To the best of our knowledge, this is an unusual manifestation of COVID-19. Fortunately, encephalitic associate with SARS-CoV-2 is selflimited. Although the definitive diagnosis of viral encephalitis largely depends on virus isolation, this is difficult for COVID-19 because SARSCoV-2 dissemination is transient and its CSF titer may be extremely low. Consistently, anti-SARS-CoV-2 IgM and IgG were not detectable in the patient’s CSF sample (unpublished data). Therefore, physical evaluation of neurological symptom is important to lead a presumptive diagnosis, as we have mentioned in this case. The pathophysiological characteristic of SARS-CoV-2 associated encephalitis is not fully understood. In agreement with Wu and colleagues (Wu et al., 2020), we speculate that SARS-CoV-2-induced immunologic response may cause inflammatory injury and edema, as a consequence, leading to alterations in consciousness. With the clearance of virus and the use of mannitol, the CSF pressure gradually reduces and the patient’s consciousness gradually improves. This might be a rational explanation for the self-limited property of SARS-CoV-2 associated encephalitis. Collectively, this report indicated that CNS may be involved in COVID-19 and highlights the diagnostic and therapeutic approaches to SARS-CoV-2 associated encephalitis.

Yi Ren

Papers

Treatment with convalescent plasma for COVID-19 patients in Wuhan, China.

Encephalitis as a clinical manifestation of COVID-19.