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.

Expression of the SARS-CoV-2 receptorACE2 in human heart is associated with uncontrolled diabetes, obesity, and activation of the renin angiotensin system.

BACKGROUND: Diabetic and obese patients are at higher risk of severe disease and cardiac injury in corona virus 2 (SARS-CoV-2) infections. Cellular entry of SARS-CoV-2 is mainly via the angiotensin-converting enzyme 2 (ACE2) receptor, which is highly expressed in normal hearts. There is a disagreement regarding the effect of factors such as obesity and diabetes on ACE2 expression in the human heart and whether treatment with renin-angiotensin system inhibitors or anti-diabetic medications increases ACE2 expression and subsequently the susceptibility to infection. We designed this study to elucidate factors that control ACE2 expression in human serum, human heart biopsies, and mice. METHODS: Right atrial appendage biopsies were collected from 79 patients that underwent coronary artery bypass graft (CABG) surgery. We investigated the alteration in ACE2 mRNA and protein expression in heart tissue and serum. ACE2 expression was compared with clinical risk factors: diabetes, obesity and different anti-hypertensive or anti-diabetic therapies. WT or db/db mice were infused with Angiotensin II (ATII), treated with different anti-diabetic drugs (Metformin, GLP1A and SGLT2i) were also tested. RESULTS: ACE2 gene expression was increased in diabetic hearts compared to non-diabetic hearts and was positively correlated with glycosylated hemoglobin (HbA1c), body mass index (BMI), and activation of the renin angiotensin system (RAS), and negatively correlated with ejection fraction. ACE2 was not differentially expressed in patients who were on angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) prior to the operation. We found no correlation between plasma free ACE2 and cardiac tissue ACE2 expression. Transmembrane serine protease 2 (TMPRSS2), metalloprotease ADAM10 and ADAM17 that facilitate viral-ACE2 complex entry and degradation were increased in diabetic hearts. ACE2 expression in mice was increased with ATII infusion and attenuated following anti-diabetic drugs treatment. CONCLUSION: Patients with uncontrolled diabetes or obesity with RAS activation have higher ACE2 expressions therefore are at higher risk for severe infection. Since ACEi or ARBs show no effect on ACE2 expression in the heart further support their safety.

The outcomes of COVID-19 and acute pancreatitis: a systematic review and meta-analysis.

Background: Coronavirus disease 2019 (COVID-19) was first reported in China at the end of 2019. Several case studies have documented a probable association between infection with severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) and acute pancreatitis (AP). The objective of this study was to provide a complete analysis of existing literature that compares the clinical outcomes of AP in patients with COVID-19 and those without COVID-19. The intention was to further our understanding of the involvement of SARS-CoV-2 in the development of pancreatitis. Methods: Between January 2019 and December 2022, we searched PubMed, Embase, Cochrane Library, Web of Science, and Scopus. Nine studies (3,160 patients) were included. In this meta-analysis, Stata 12.0. was utilized. The information provided in this study is presented following the MOOSE reporting checklist. Results: Mortality [odds ratio (OR) =3.95, 95% confidence interval (CI): 2.87, 5.43, P<0.001], intensive care unit (ICU) administration (OR =3.74, 95% CI: 2.26, 6.20, P<0.001), mechanical ventilation (OR =4.84, 95% CI: 2.14, 10.96, P<0.001), severe pancreatitis (OR =2.71, 95% CI: 1.04, 7.04, P=0.042), etiology of idiopathic and unknown (OR =4.75, 95% CI: 1.80, 12.56, P=0.002), necrotizing pancreatitis (OR =1.88, 95% CI: 1.28, 2.76, P=0.001), and length of hospital stay [weighted mean difference (WMD) =5.10, 95% CI: 2.79, 7.41, P<0.001] were more significantly increased in AP cases with COVID-19 than those without it. Conclusions: In conclusion, the findings of this study indicate a potential worsening of AP outcomes in patients affected by COVID-19.

Colliding Pandemics and CoViD-19.

Cases of the respiratory syncytial virus (RSV), monkeypox virus (MPXV), and avian influenza A Virus (IAV) have increased during our current prolonged Corona Virus Disease 2019 (CoViD-19) pandemic. The rise of these viral infectious diseases may be associated or even inter-dependent with acute, latent or recurrent infection with Systemic Acute Respiratory Syndrome Corona virus-2 (SARS-CoV2). The nonsensical neologism 'tripledemic' was tentatively introduced to describe the confluent nature of these trends (epidemic comes from two Greek words: epi=on, about, demos=people; pandemic is also derived from Ancient Greek: pan=all, demos=people; but 'tripledemic' would derive from Latin triplus=three, Greek demos=people, and would at best signify 'three countries, three peoples', but certainly not the current threat of confluence of three, or perhaps more pandemics). Emerging evidence suggests that monkey pox and CoViD-19, among several other viral diseases, produce significant observable manifestations in the oral cavity. From a clinical standpoint, dentists and dental personnel may be among the first health professionals to encounter and diagnose clinical signs of converging infections. From the immune surveillance viewpoint, viral recombination and viral interference among these infectious diseases must be examined to determine the potential threat of these colliding pandemics.

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.

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.

Virus interference in CoViD-19.

Virus interference is one of the oldest concepts in immunology. Recent findings indicate that it may depend on the host's anti-viral cellular immune surveillance processes, as well as on sequence-specific gene silencing mechanism guided by double-stranded RNA. Other biological events, unrelated to some degree at least from immune-dependent IFN or RNA-dependent viral interference may be at play as well. We discuss these biological mechanisms in the context of of the Systemic Acute Respiratory Syndrome Corona virus2 (SARS-CoV2) virus responsible for Corona Virus Disease 2019 (CoViD-19).

Post acute CoViD-19 syndrome (PACS) - Long CoViD.

Patients sero-positive for the Systemic Acute Respiratory Syndrome Corona virus2 (SARS-CoV2) virus develop the Corona Virus Disease 2019 (CoViD-19). CoViD-19 may be asymptomatic in some individuals, proffer mild symptoms in other patients, and can be a serious and even lethal disease in a sub-group of the population. The variables that determine the severity of CoViD-19 have not been fully characterized. What is clear is that the patients who survive CoViD-19 return to a state of sero-negativity for SARS-CoV2 generally within 3-5 weeks. However, several cases of repeated infection have been reported, and a large proportion of CoViD-19-recovered patients manifest multi-system and multi-organ symptomatic pathologies several weeks-to-months after resuming sero-negativity for SARS-CoV2. This new pathological condition, originally termed Long Covid, is now recognized as the Post Acute CoViD-19 Syndrome (PACS). The original principal clusters of signs and symptoms of PACS: likelihood of relapse and reinfection, physical fatigue and cognitive slowdown, may actually be broadened to include immune deregulation, cardiovascular disease and coagulation abnormalities. The development and evaluation of new and improved clinical interventions for PACS are critical and timely.

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.

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.

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.

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.

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.

Challenges and countermeasures of thoracic oncology in the epidemic of COVID-19.

Since December, 2019, a 2019 novel coronavirus disease (COVID-19) infected by the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) emerged in Wuhan, Hubei province, and the epidemic situation has continued to spread globally. The epidemic spread of COVID-19 has brought great challenges to the clinical practice of thoracic oncology. Outpatient clinics need to strengthen the differential diagnosis of initial symptoms, pulmonary ground-glass opacity (GGO), consolidation, interstitial and/or interlobular septal thickening, and crazy paving appearance. In the routine of oncology, the differential diagnosis of adverse events from COVID-19 is also significant, including radiation pneumonitis, checkpoint inhibitor pneumonitis (CIP), neutropenic fever, and so on. During the epidemic, indications of transbronchial biopsy (TBB) and CT-guided percutaneous thoracic biopsy are strictly controlled. For patients who are planning to undergo biopsy operation, screening to exclude the possibility of COVID-19 should be carried out. For confirmed or suspected patients, three-level protection should be performed during the operation. Disinfection and isolation measures should be strictly carried out during the operation. At last, more attention to the protection of cancer patients and give priority to the treatment of infected cancer patients.

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.

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.

Manifestaciones orales y disfunción olfativa y gustativa en el síndrome respiratorio agudo severo por corona virus 2 (VIRUS SARS-COV-2): una revisión sistemáticaA / Oral Manifestations and Olfactory and Gustatory Dysfunction in Severe Acute Respiratory Syndrome Corona Virus 2 (SARSCov-2 Virus) Disease: A Systematic Review

La enfermedad del corona virus 2 del síndrome respiratorio agudo severo (virus SARS-CoV-2) apareció por primera vez en diciembre de 2019 en Wuhan, China, y desde entonces se ha extendido rápidamente por todo el mundo. Desde entonces, el brote de esta grave enfermedad viral se ha convertido en una amenaza global para la humanidad. El diagnóstico precoz y el aislamiento son las medidas más importantes necesarias para prevenir su propagación. La evidencia anecdótica reciente ha sugerido manifestaciones orales con o sin deterioro olfativo y gustativo en asociación con la enfermedad por coronavirus (COVID-19). La enzima convertidora de angiotensina-2 (ECA-2) se expresa en la mucosa oral en grandes cantidades y, por tanto, puede contribuir a las primeras manifestaciones de esta enfermedad viral mortal. Las manifestaciones bucales de la enfermedad por coronavirus pueden presentarse en forma de lesiones ulcerativas irregulares en relación con diferentes partes de la cavidad oral y, en particular, en relación con la mucosa adherida en la región del paladar duro, así como inflamación y posterior atrofia de las diversas papilas de la lengua. La disfunción olfativa y gustativa asociada también puede conducir a una pérdida parcial y / o incluso completa de la capacidad para oler y saborear en las primeras etapas del inicio de la enfermedad. La evidencia también ha sugerido la presencia de ácido nucleico del SARS-CoV-2 en la saliva humana, lo que la convierte en portadora de la enfermedad viral infecciosa y ayuda en su diagnóstico. Hemos buscado sistemáticamente la base de datos médica para el mismo y hemos revisado toda la literatura disponible hasta el 29 de junio de 2020

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2 virus) disease had first appeared in December 2019 in Wuhan, China and has been spreading quickly throughout the world since then. Since then, the outbreak of this severe viral disease has become 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 oral manifestations with or, without olfactory and gustatory impairment in association with corona virus disease (COVID-19). Angiotensin converting enzyme-2 (ACE-2) is expressed in oral mucosa in large amounts and can, thus, contribute in the early manifestations of this deadly viral disease. The oral manifestations of corona virus disease can occur in the form of irregular ulcerative lesions in relation to different parts of the oral cavity and particularly, in relation to the attached mucosa in the hard palate region as well as inflammation and subsequent, atrophy of the various tongue papilla. The associated olfactory and gustatory dysfunction can, also, lead to partial and/or, even a complete loss of the ability to smell and taste in the early stages of the disease onset. Evidence has, also, suggested the presence of SARS-CoV-2 nucleic acid in human saliva making it the carrier of the infectious viral disease as well as aiding in its diagnosis. We have systemically searched medical database for the same and have reviewed all the literature available up to 29th of June 2020.