Invasive cryptococcal disease in COVID-19: systematic review of the literature and analysis

SUMMARY During the Coronavirus Disease 2019 (COVID-19) pandemic, an increasing number of fungal infections associated with SARS-CoV-2 infection have been reported. Among them, cryptococcosis could be a life-threatening disease. We performed a Systematic Review (PRISMA Statement) of cryptococcosis and COVID-19 co-infection, case report/series were included: a total of 34 cases were found, then we added our case report. We collected patients' data and performed a statistical analysis comparing two groups of patients sorted by outcome: "dead” and "alive”. Three cases were excluded for lack of information. To compare categorical data, we used a Fisher-exact test (α=0.05). To compare quantitative variables a U Mann-Whitney test was used (α=0.05), with a 95% Confidence Interval. A total of 32 co-infected patients were included in the statistical analysis. Mortality rate was 17/32 (53.1%): these patients were included in "dead” group, and 15/32 (46.9%) patients survived and were included in "alive” group. Overall, males were 25/32 (78.1%), the median age was 60 years (IQR 53–70) with non-statistically significant difference between groups (p=0.149 and p=0.911, respectively). Three variables were associated with mortality: ARDS, ICU admission and inadequate treatment. Overall, 21 out of 24 (87.5%) patients were in ARDS with a statistically significant difference among two groups (p=0.028). ICU admission for COVID-19 was observed in 18/26 (69.2%), more frequently among dead group (p=0.034). Finally, 15/32 (46.9%) patients had adequate treatment (amphotericin B + flucytosine for invasive cryptococcosis) mostly among alive patients (p=0.039). In conclusion, mortality due to cryptococcal infection among COVID-19 patients remains high but an early diagnosis and appropriate treatment could reduce mortality.

Invasive cryptococcal disease in COVID-19: systematic review of the literature and analysis.

During the Coronavirus Disease 2019 (COVID-19) pandemic, an increasing number of fungal infections associated with SARS-CoV-2 infection have been reported. Among them, cryptococcosis could be a life-threatening disease. We performed a Systematic Review (PRISMA Statement) of cryptococcosis and COVID-19 co-infection, case report/series were included: a total of 34 cases were found, then we added our case report. We collected patients' data and performed a statistical analysis comparing two groups of patients sorted by outcome: "dead" and "alive". Three cases were excluded for lack of information. To compare categorical data, we used a Fisher-exact test (α=0.05). To compare quantitative variables a U Mann-Whitney test was used (α=0.05), with a 95% Confidence Interval. A total of 32 co-infected patients were included in the statistical analysis. Mortality rate was 17/32 (53.1%): these patients were included in "dead" group, and 15/32 (46.9%) patients survived and were included in "alive" group. Overall, males were 25/32 (78.1%), the median age was 60 years (IQR 53-70) with non-statistically significant difference between groups (p=0.149 and p=0.911, respectively). Three variables were associated with mortality: ARDS, ICU admission and inadequate treatment. Overall, 21 out of 24 (87.5%) patients were in ARDS with a statistically significant difference among two groups (p=0.028). ICU admission for COVID-19 was observed in 18/26 (69.2%), more frequently among dead group (p=0.034). Finally, 15/32 (46.9%) patients had adequate treatment (amphotericin B + flucytosine for invasive cryptococcosis) mostly among alive patients (p=0.039). In conclusion, mortality due to cryptococcal infection among COVID-19 patients remains high but an early diagnosis and appropriate treatment could reduce mortality.

The future of neurology after the COVID-19 pandemic according to neurology residents.

BACKGROUND: The ongoing COVID-19 pandemic has resulted in significant changes in the delivery of neurological disease care and in neurology training in academic departments. OBJECTIVE: We aimed to investigate how neurology residents viewed the future of neurology after the COVID-19 pandemic with regard to three main aspects: (i) organization of neurological activity, (ii) patient care, and (iii) funding availability for neurological diseases. METHODS: We surveyed Italian neurology residents in order to investigate how they viewed the future of neurology after the COVID-19 pandemic. RESULTS: Responses were collected from 254 residents who reported: a high risk of reduction of hospital neurological beds, of worsening of the quality of neurological patient management, and of lack of funding for neurological care and research. CONCLUSION: The survey results demonstrate the views of future neurologists regarding the direction of neurology after the COVID-19 emergency. It is important to focus on these aspects in order to adapt neurology training to the societal changes introduced by the pandemic, and to safeguard the essential role of neurology in the management and prevention of chronic degenerative illnesses and emergencies.

Alveolar-Arterial Gradient Is an Early Marker to Predict Severe Pneumonia in COVID-19 Patients.

BACKGROUND: One of the main challenges in the management of COVID-19 patients is to early assess and stratify them according to their risk of developing severe pneumonia. The alveolar-arterial oxygen gradient (D(A-a)O2) is defined as the difference between the alveolar and arteriolar concentration of oxygen, an accurate index of the ventilatory function. The aim of this study is to evaluate D(A-a)O2 as a marker for predicting severe pneumonia in COVID-19 patients, in comparison to the PaO2/FiO2. METHODS: This retrospective, multicentric cohort study included COVID-19 patients admitted to two Italian hospitals between April and July 2020. Clinical and laboratory data were retrospectively collected at the time of hospital admission and during hospitalization. The presence of severe COVID-19 pneumonia was evaluated, as defined by the Infectious Diseases Society of America (IDSA) criteria for community-acquired pneumonia (CAP). Patients were divided in severe and non-severe groups. RESULTS: Overall, 53 COVID-19 patients were included in the study: male were 30/53 (57%), and 10/53 (19%) had severe pneumonia. Patients with severe pneumonia reported dyspnea more often than non-severe patients (90% vs. 39.5%; p = 0.031). A history of chronic obstructive pulmonary disease (COPD) was recalled by 5/10 (50%) patients with severe pneumonia, and only in 6/43 (1.4%) of non-severe cases (p = 0.023). A ROC curve, for D(A-a)O2 >60 mmHg in detecting severe pneumonia, showed an area under the curve (AUC) of 0.877 (95% CI: 0.675-1), while the AUC of PaO2/FiO2 < 263 mmHg resulted 0.802 (95% CI: 0.544-1). D(A-a)O2 in comparison to PaO2/FiO2 had a higher sensibility (77.8% vs. 66.7%), positive predictive value (75% vs. 71.4%), negative predictive value (94% vs. 91%), and similar specificity (94.4% vs. 95.5%). CONCLUSIONS: Our study suggests that the D(A-a)O2 is more appropriate than PaO2/FiO2 to identify COVID-19 patients at risk of developing severe pneumonia early.

Telemedicine application to headache: a critical review

Background Migraine affects more than a billion people all over the world and requires critical employment of healthcare resources. Telemedicine could be a reasonable tool to manage people suffering from headaches, and it received a big push from the COVID-19 pandemic. Objective This review aims to propose a practical approach for the virtual management of these patients. Methods To do this, we conducted a literature search, including 32 articles relevant to the topic treated in this review. Results The most challenging step in telemedicine applied to practical neurology remains the clinical assessment, but through a careful headache history and a recently proposed entirely virtual neurological assessment, this hitch can be easily overcome. Electronic diary compilations and virtual administration of disability-measuring scales, conversely, are the key features of effective long-term follow-up although we do not have apps that met the criteria of scientific reliability. Furthermore, tele-rehabilitation seems to be effective and has demonstrated to be a solution to alternatively treat chronic patients at home, and can be considered part of the remote management of headache patients. Moreover, virtual management of headaches finds an application in specific communities of patients, as pediatric patients and for rural communities of low- and middle-income countries suffer from health disparities, with inadequate resources and knowledge gaps. Conclusion Telemedicine could be promising for patients with no regular or convenient access to headache specialists and seems to be a priority in managing migraine patients to avoid non-urgent hospitalizations

Evaluation of the 2020 European Academy of Neurology virtual congress: transition from a face-to-face to a virtual meeting.

BACKGROUND AND PURPOSE: Due to the COVID-19 pandemic, scientific congresses are increasingly being organized as virtual congresses (VCs). In May 2020, the European Academy of Neurology (EAN) held a VC, free of charge. In the absence of systematic studies on this topic, the aim of this study is to evaluate the attendance and perceived quality of the 2020 EAN VC compared to the 2019 EAN face-to-face congress (FFC). METHODS: An analysis of the demographic data of participants obtained from the online registration was done. A comparison of the two congresses based on a survey with questions on the perception of speakers' performance, quality of networking and other aspects was made. RESULTS: Of 43,596 registered participants, 20,694 active participants attended the VC. Compared to 2019, the number of participants tripled (6916 in 2019) and the cumulated number of participants attending the sessions was five times higher (169,334 in 2020 vs. 33,024 in 2019). Out of active participants 55% were from outside Europe, 42% were board-certified neurologists (FFC 80%) and 21% were students (FFC 0.6%). The content of the congress was evaluated as 'above expectation' by 56% of the attendees (FFC 41%). Of the respondents who had been exposed to earlier EAN congresses 73% preferred the FFC compared to the VC (17%). CONCLUSION: The VC fulfilled the main mission of organizing high quality EAN congresses despite the restrictions of the impersonal format. The geographical distribution of the participants proves the expected higher inclusivity of a VC. The large participation of students and neurologists in training opens new educational potentials for the EAN.

Dementia and COVID-19, a Bidirectional Liaison: Risk Factors, Biomarkers, and Optimal Health Care.

Cognitive impairment following SARS-CoV-2 infection is being increasingly recognized as an acute and possibly also long-term sequela of the disease. Direct viral entry as well as systemic mechanisms such as cytokine storm are thought to contribute to neuroinflammation in these patients. Biomarkers of COVID-19-induced cognitive impairment are currently lacking, but there is some limited evidence that SARS-CoV-2 could preferentially target the frontal lobes, as suggested by behavioral and dysexecutive symptoms, fronto-temporal hypoperfusion on MRI, EEG slowing in frontal regions, and frontal hypometabolism on 18F-FDG-PET. Possible confounders include cognitive impairment due to hypoxia and mechanical ventilation and post-traumatic stress disorder. Conversely, patients already suffering from dementia, as well as their caregivers, have been greatly impacted by the disruption of their care caused by COVID-19. Patients with dementia have experienced worsening of cognitive, behavioral, and psychological symptoms, and the rate of COVID-19-related deaths is disproportionately high among cognitively impaired people. Multiple factors, such as difficulties in remembering and executing safeguarding procedures, age, comorbidities, residing in care homes, and poorer access to hospital standard of care play a role in the increased morbidity and mortality. Non-pharmacological interventions and new technologies have shown a potential for the management of patients with dementia, and for the support of their caregivers.

Is the Frontal Lobe the Primary Target of SARS-CoV-2?

Acute delirium and other neuropsychiatric symptoms have frequently been reported in COVID-19 patients and are variably referred to as acute encephalopathy, COVID-19 encephalopathy, SARS-CoV-2 encephalitis, or steroid-responsive encephalitis. COVID-19 specific biomarkers of cognitive impairment are currently lacking, but there is some evidence that SARS-CoV-2 could preferentially and directly target the frontal lobes, as suggested by behavioral and dysexecutive symptoms, fronto-temporal hypoperfusion on MRI, EEG slowing in frontal regions, and frontal hypometabolism on 18F-FDG-PET imaging. We suggest that an inflammatory parainfectious process targeting preferentially the frontal lobes (and/or frontal networks) could be the underlying cause of these shared clinical, neurophysiological, and imaging findings in COVID-19 patients. We explore the biological mechanisms and the clinical biomarkers that might underlie such disruption of frontal circuits and highlight the need of standardized diagnostic procedures to be applied when investigating patients with these clinical findings. We also suggest the use of a unique label, to increase comparability across studies.

COVID-19 impact on neurology training program in Italy.

The ongoing COVID-19 pandemic is having a huge impact on clinical activity of all hospitals, including the ones involved in training of residents. In addition, neurology residents underwent substantial modifications of their training program. Aim of our investigation was to evaluate the impact of COVID-19 pandemic on the educational activities of Italian neurology residents through an online questionnaire delivered to neurology residents. The results obtained showed that almost 30% of the respondents were redistributed to COVID-19 units. Neurology departments underwent substantial modifications of their organization influencing clinical educational activities; lessons and seminars were rescheduled online and research protocols were stopped and transferred to remote working, when feasible. There was a relevant use of telemedicine approach even if most of the respondents had never been trained before. Some of the changes had a North-South gradient, following the epidemiology of the pandemic. The data obtained from our survey highlight those points to address to be prepared for possible future emergencies.

COVID-19 and neurological training in Europe: from early challenges to future perspectives.

The worldwide SARS-CoV-2 pandemic is dramatically affecting health systems with consequences also for neurological residency training. Here we report early experiences and challenges that European neurologists and residents faced. The breadth of the pandemic and the social restrictions induced substantial modifications in both inpatient and outpatient clinical care and academic activities as well, adversely affecting our residency training. On the other hand we see also opportunities, such as gaining more clinical and professional skills. All these drastic and sudden changes lead us to reconsider some educational aspects of our training program that need to be improved in order to better prepare the neurologists of the future to manage unexpected and large emergency situations like the one we are living in these days. A reconsideration of the neurological training program could be beneficial to guarantee high standard level of the residency training in this period and beyond.

COVID-19 Impact on Neurology Training Program in Italy (preprint)

The ongoing COVID-19 pandemic is having a huge impact on clinical activity of all hospitals, including the ones involved in training of residents. In addition, neurology residents underwent substantial modifications of their training program.Aim of our investigation was to evaluate the impact of COVID-19 pandemic on the educational activities of Italian neurology residents through an online questionnaire delivered to neurology residents.The results obtained showed that almost 30% of the respondents were redistributed to COVID-19 units. Neurology departments underwent substantial modifications of their organization influencing clinical educational activities; lessons and seminars were rescheduled online and research protocols were stopped and transferred to remote working, when feasible. There was a relevant use of telemedicine approach even if most of the respondents had never been trained before. Some of the changes had a North-South gradient, following the epidemiology of the pandemic.The data obtained from our survey highlight those points to address to be prepared for possible future emergencies.

Dementia care and COVID-19 pandemic: a necessary digital revolution.

Due to the COVID-19 pandemic, most memory clinics have had to suspend their activities. On the other hand, international dementia experts have recommended to provide urgently worldwide support for people living with dementia. This situation urges to play out new strategies to guarantee adequate care. Telemedicine and digital technology (DT) devices, such as smartphones, can be very helpful in remote monitoring and care. Technological devices such as videoconference or smartphone apps might be used for follow-up visits and support to patients and caregivers and to acquire digital markers of clinical progression. Hopefully, this dramatic situation would facilitate the process of progressive familiarization of neurologists with telemedicine and DT approach.