Towards Neuro-CoViD-19.

CoViD-19 is the current pandemic caused by the Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2). Infection by SARS-CoV-2 occurs via the binding of its S protein to the angiotensin-converting enzyme-2 receptor (ACE2-R). S binding to ACE2-R leads to a drop in ACE2, a homolog of angiotensin converting enzyme (ACE). In the central nervous system (CNS), ACE mediates neuroinflammation, neurodegeneration and neurotoxicity responsible for several CNS disorders. ACE2 counteracts the damaging effects of ACE on CNS neurons. SARS-CoV-2 can directly access the CNS via the circulation or via cranial nerve I and the olfactory bulb. Inactivation of ACE2 following binding of SARS-CoV-2 S protein to ACE2-R in situ might blunt ACE2-moderating effects upon ACE CNS neurotoxicity and neurodegeneration. Here, we propose a neurobiological mechanism directly involving SARS-CoV-2 binding to ACE2-R in the etiology of putative Neuro-CoViD-19.

Toward a fractalomic idiotype/anti-idiotypic paradigm.

The CoViD-19 pandemic has demonstrated the need for future developments in anti-viral immunology. We propose that artificial intelligence (AI) and machine learning, and in particular fractal analysis could play a crucial role in that context. Fractals - never-ending repeats of self-similar shapes whose composite tend to resemble the whole - are found in most natural biological structures including immunoglobulin and antigenic epitopes. Increased knowledge of the fractalomic properties of the idiotype/anti-idiotypic paradigm should help develop a novel and improved simplified artificial model of the immune system. Case in point, the regulation and dampening of antibodies as well as the synergetic recognition of an antigen by multiple idiotypes are both immune mechanisms that require further analysis. An enhanced understanding of these complexities could lead to better data analysis for novel vaccines to improve their sensitivity and specificity as well as open other new doors in the field of immunology.

Four cases of Graves' disease following viral vector severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) vaccine.

Mass immunization has led to a decrease in the transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) worldwide. At the same time, awareness regarding possible adverse effects of newly developed vaccines is critical. The present study was undertaken to report the cases of Graves' disease occurring after administration of viral vector vaccine (ChAdox1nCoV-19) and describe the clinical profile, response to treatment, and effect of administration of a second dose in patients developing Graves' disease. Four cases of Graves' disease after administration of the vaccine were noted. Two of these had a mild thyroid eye disease. Three cases were female and had a family/self-history of autoimmune disease. All cases responded well to treatment and became euthyroid within two to four months. Two patients exhibited worsening thyrotoxicosis after receiving a second dose of the vaccine. We propose that the temporal relationship between administration of the vaccine and the onset of symptoms establishes Graves' disease as an adverse event after the SARS-CoV-2 viral vector vaccine. Close follow-up is advisable in individuals developing Graves' disease after SARS-CoV-2 vaccination.

Neuro-COVID-19 and the geriatric population: What particularities?

SARS-CoV-2 responsible for Covid-19, although having a primary pulmonary tropism, also causes variable neurological damage that it is important to know. In this narrative review, after briefly recalling the particularities of SARS-CoV-2 infection in the elderly, the authors present the main hypotheses that explain the neurotropism of SARS-CoV-2, the main types of neurological damage and the possible interactions with Parkinson's disease and Alzheimer's disease. © 2022 Elsevier Masson SAS

Neuro-Covid-19 et population gériatrique: quelles particularités?

Résumé Le SARS-CoV-2 responsable du Covid-19, bien qu'ayant un tropisme au premier plan pulmonaire, entraîne également des atteintes neurologiques diverses qu’il est important de connaître. Dans cette revue narrative, après avoir rappelé brièvement les particularités de l’infection à SARS-CoV-2 chez le sujet âgé, les auteurs présentent les hypothèses pouvant expliquer le neurotropisme du SARS-CoV-2, les principales atteintes neurologiques et les interactions possibles avec la maladie de Parkinson et la maladie d’Alzheimer. SARS-CoV-2 responsible for Covid-19, although having a primary pulmonary tropism, also causes variable neurological damage that it is important to know. In this narrative review, after briefly recalling the particularities of SARS-CoV-2 infection in the elderly, the authors present the main hypotheses that explain the neurotropism of SARS-CoV-2, the main types of neurological damage and the possible interactions with Parkinson's disease and Alzheimer's disease.

Optic Nerve Head Optical Coherence Tomography Angiography Findings after Coronavirus Disease.

PURPOSE: To quantify the microvasculature density of the optic nerve head (ONH) using optical coherence tomography angiography (OCTA) analysis in patients recovered from Coronavirus Disease 2019 (COVID-19). METHODS: In a comparative cross-sectional, observational study, patients recovered from COVID-19 whose initial diagnosis was confirmed by a rRT-PCR of a nasopharyngeal sample were included in this study. OCTA of ONH was performed in included patients and normal controls. Vascular density (VD) of the all vessels (AV) and small vessels (SV) inside the disc and radial peripapillary capillary (RPC) network density were measured in COVID-19 recovered patients and compared with similar parameters in an age-matched group of normal controls. RESULTS: Twenty-five COVID-19 patients and twenty-two age-matched normal controls were enrolled in the study and one eye per participant was evaluated. The mean whole image SV VD in the COVID-19 group (49.31 ± 1.93) was not statistically significantly different from that in the control group (49.94 ± . 2.22; P = 0.308). A decrease in RPC VD was found in all AV and SV VD measured, which became statistically significant in whole peripapillary SV VD, peripapillary inferior nasal SV VD, peripapillary inferior temporal SV VD, peripapillary superior nasal SV VD, and grid-based AV VD inferior sector (P < 0.05). Inside disc SV VD in the COVID-19 group (49.43 ± 4.96) was higher than in the control group (45.46 ± 6.22) which was statistically significant (P = 0.021). CONCLUSION: Unremarkable decrease was found in ONH microvasculature in patients who had recovered from COVID-19. These patients may be at risk of ONH vascular complications. Increase in inner disc SV VD may be an indicator of ONH hyperemia and edema.

Impairment of olfactory and gustatory sensations in severe acute respiratory syndrome corona virus 2 (SARS-CoV-2 virus) disease.

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2 virus) disease had first appeared in December 2019 in Wuhan, China, and since then, it has emerged as a global threat to humanity. An early diagnosis and isolation are the most significant measures required to prevent its spread. Recent anecdotal evidence has suggested impairment of olfactory and gustatory sensations associated with corona virus disease (COVID-19). Angiotensin-converting enzyme-2 is an important aspect for the manifestations seen in this deadly viral disease. The associated olfactory and gustatory dysfunction can also lead to partial and/or complete loss of the ability to smell and taste in the early stages of disease onset. Evidence has also suggested that the presence of SARS-CoV-2 nucleic acid in human saliva makes it the carrier of the infectious viral disease and aids in its diagnosis. The present review focuses on the listed clinical manifestations in the form of olfactory and gustatory impairment in SARS-CoV-2 virus disease.

Autoantibodies to heat shock protein 60, 70, and 90 are not altered in the anti-SARS-CoV-2 IgG-seropositive humans without or with mild symptoms.

Highly conserved heat shock proteins (Hsps) are localized in the cytoplasm and cellular organelles, and act as molecular chaperones or proteases. Members of Hsp families are released into the extracellular milieu under both normal and stress conditions. It is hypothesized that the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) has the potential to elicit autoimmunity due to molecular mimicry between human extracellular Hsps and immunogenic proteins of the virus. To confirm the above hypothesis, levels of circulating autoantibodies directed to the key human chaperones i.e., Hsp60, Hsp70, and Hsp90 in the anti-SARS-CoV-2 IgG-seropositive participants have been evaluated. Twenty-six healthy volunteers who got two doses of the mRNA vaccine encoding the viral spike protein, anti-SARS-CoV-2 IgG-positive participants (n = 15), and healthy naïve (anti-SARS-CoV-2 IgG-negative) volunteers (n = 51) have been included in this study. We found that the serum levels of anti-Hsp60, anti-Hsp70, and anti-Hsp90 autoantibodies of the IgG, IgM, or IgA isotype remained unchanged in either the anti-COVID-19-immunized humans or the anti-SARS-CoV-2 IgG-positive participants when compared to healthy naïve volunteers, as measured by enzyme-linked immunosorbent assay. Our results showing that the humoral immune response to SARS-CoV-2 did not include the production of anti-SARS-CoV-2 antibodies that also recognized extracellular heat shock protein 60, 70, and 90 represent a partial evaluation of the autoimmunity hypothesis stated above. Further testing for cell-based immunity will be necessary to fully evaluate this hypothesis.

Literature Review of COVID-19, Pulmonary and Extrapulmonary Disease.

In December 2019 novel coronavirus-Severe Acute Respiratory Syndrome-Corona Virus2 (SARS-CoV2)-originated from Wuhan, China, and spread rapidly around the world. This literature review highlights the dynamic nature of COVID-19 transmission and presentation. Analyzing 59 relevant articles up to May 1st, 2020 reflects that the main reported clinical manifestation of COVID-19 pandemic is fever and respiratory involvement. Also, current literature demonstrates a wide spectrum of different and atypical presentation(s) of COVID-19. The definite route of SARS-CoV2 transmission is respiratory droplets, however, virus nucleic acid has been detected in the stool and urine specimens as well. The severity of symptoms and outcomes of COVID-19 vary based on the patient's medical background, age, sex, and concurrent medical conditions (e.g. pregnancy). This is the first review that classifies all essential points regarding COVID-19 manifestations at a glance to improve the outcome of the patients by a better insight into diagnosis and management.

Optic Nerve Head Parameters and Peripapillary Retinal Nerve Fiber Layer Thickness in Patients with Coronavirus Disease 2019.

PURPOSE: To quantify the optic nerve head (ONH) and peripapillary retinal nerve fiber layer (pRNFL) thickness in patients with Coronavirus Disease-2019 (COVID-19) and compare the measurements with a healthy control group. METHODS: In a comparative cross-sectional observational study, ONH and pRNFL thickness were evaluated in patients with a history of COVID-19, at least 2 weeks after recovery from the systemic disease, and compared with an age-matched, normal control group. RESULTS: Thirty COVID-19 patients along with 60 age- and gender-matched healthy controls were studied. Mean average pRNFL thickness was 105.0 ± 16.3 µm in the COVID-19 patients, compared to 99.0 ± 9.0 µm in the controls (p = .31). The pRNFL thicknesses in all sectors was higher in patients with a history of COVID-19; however, this did not reach statistical significance. Similarly, ONH parameters were not significantly different between the groups. CONCLUSION: Patients recovered from COVID-19 had unremarkable alterations in the peripapillary RNFL thickness. ABBREVIATIONS: ONH: Optic Nerve HeadRNFL: Retinal Nerve Fiber LayerSD-OCT: Spectral-Domain Optical Coherence TomographyCOVID-19: Coronavirus Disease 2019SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2CNS: Central Nervous SystemACE: Angiotensin-Converting EnzymeRT-PCR: Reverse Transcription-Polymerase Chain Reaction.

The challenges in colorectal cancer management during COVID-19 epidemic.

It has been over 2 months since the start of the Coronavirus disease 2019 (COVID-19) outbreak. The epidemic stage of COVID-19 has brought great challenges to the diagnosis and management of colorectal cancer (CRC) patients. Symptoms, such as fever and cough caused by cancer, and the therapeutic process (including chemotherapy and surgery) should be differentiated from some COVID-19 related characteristics. Besides, clinical workers should not only consider the therapeutic strategy for cancer, but also emphasize COVID-19's prevention. Moreover, the detailed therapeutic regimens of CRC patients may be different from the usual. Also, treatment principles may various for CRC patients with or without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as well as patients with or without an emergency presentation. In this paper, we want to discuss the above-mentioned problems based on previous guidelines, the current working status and our experiences, to provide a reference for medical personnel.

Putative Natural History of CoViD-19.

The Severe Acute Respiratory Syndrome Corona Virus2 (SARS-CoV2) is responsible for Corona Virus Disease 2019 (CoViD-19), the pandemic that has afflicted close to two million people worldwide, and has taken the lives of over 120,000 patients since its first report in late December 2019. Per million people globally, the infection rate is close to 250 with a death rate of close to 14 (death rate average global death rate: 6.06%; for comparison, revised estimate of the 1918 influenza pandemic had an average global death rate of 5.4% [1]). About 400,000 SARS-CoV2-positive patients have been declared 'recovered', although it is not clear to date what exactly that entails. To be clear, the natural history of SARS-CoV2 infection and of the patho-physiology of CoViD-19 remains shrouded in relative confusion, in part due to the exceedingly virulent nature of the virus, as manifest by its elevated morbidity and mortality, and the fast accumulation of clinical observations and research evidence. Many pieces of a complex puzzle are emerging all at once and their organization into a coherent and cogent picture of the natural history of CoViD-19 is arduous and still wanting. Here, we discuss the recent findings in the context of the available evidence. We propose a putative prediction model of the natural history of CoViD-19. We highlight putative loci and modes of therapeutic intervention that may become beneficial preventive and treatment modalities for individuals at risk of SARS-CoV2 infection and CoViD-19 patients.

Increased Serum Aminotransferase Activity and Clinical Outcomes in Coronavirus Disease 2019.

AIM: Elevation of hepatic aminotransferases (aspartate aminotransferase [AST]/alanine aminotransferase [ALT]) is commonly noted among COVID-19 patients. It is unclear if they can predict the clinical outcomes among hospitalized COVID-19 patients. We aim to assess if elevations in AST/ALT were associated with poor outcomes in hospitalized COVID-19 patients. METHODS: We retrospectively evaluated hospitalized COVID-19 patients with clinically significant elevated aminotransferases (defined as >2 times upper limit of normal) and compared them with COVID-19 patients without an elevation in aminotransferases. RESULTS: The prevalence of elevation in AST/ALT was found to be 13.7% (20/145). The two groups were similar in baseline demographics, comorbidities, and the majority of laboratory tests. There was no difference in the mortality (50% vs. 36.8%, P = 0.32) and median hospital stay (7 days vs. 7 days, P = 0.78). However, there was a statistically significant increase in the rates of mechanical ventilation among elevated aminotransferases group compared with individuals without elevation (50% vs. 24%, P = 0.028). However, this difference was not observed after adjusting for inflammatory markers such as ferritin, lactate dehydrogenase, and lactic acid levels. CONCLUSION: Elevated aminotransferases among hospitalized COVID-19 patients is associated with higher rates of mechanical ventilation but did not achieve statistical significance after controlling for inflammatory markers. Also, patients with elevated aminotransferases did not have higher rates of mortality or prolonged length of stay.