High ACE2 Expression Research Articles

COVID-19 and the Cardiovascular System: Requiem for a Medical Minotaur.

COVID-19 and the Cardiovascular System: Requiem for a Medical Minotaur.

Targeting ACE2-BRD4 crosstalk in colorectal cancer and the deregulation of DNA repair and apoptosis

ACE2 overexpression in colorectal cancer patients might increase susceptibility to SARS-CoV-2 infection. We report that knockdown, forced overexpression, and pharmacologic inhibition in human colon cancer cells targeted ACE2-BRD4 crosstalk to mediate marked changes in DNA damage/repair and apoptosis. In colorectal cancer patients for whom high ACE2 plus high BRD4 expression is predictive of poor survival, pan-BET inhibition would need to consider proviral/antiviral actions of different BET proteins during SARS-CoV-2 infection.

Male infertility along with the era of coronavirus infection SARS-CoV-2

Russian and foreign epidemiological data suggest that males may have an increased risk of morbidity and mortality associated with COVID‑19. It is known that due to the high expression of ACE2 in spermatogonia, Leydig and Sertoli cells, the testicle, as an organ producing male germ cells, is a potential target for the COVID‑19 virus, which directly affects the reproductive health of men. To date, several factors of the influence of the SARS-CoV‑2 virus on the male reproductive system are known. To begin with, when infected, the virus has a direct damaging effect on the testicle itself with the provocation of orchitis. In addition to the previous statement, high body temperature during inflammation contributes to an increase in testicular temperature, which can lead to a deterioration in the quality of sperm. Furthermore, a pronounced inflammatory reaction promotes the circulation of a large number of cytokines and damage to the hemato-testicular barrier. Also, the increased activity of immunocytes leads to an imbalance of the antioxidant system of men, an increase in the level of reactive oxygen species and the formation of oxidative stress. In a Nutshell, Leydig cell dystrophy provokes the development of secondary hypogonadism. Thus, COVID‑19, like a “multifaceted Janus”, has a polysymptomatic manifestation, but at the same time has a multifactorial effect on the reproductive function of a man. All these factors of the impact of the SARS-CoV‑2 virus on the testicle must be considered when rehabilitating the patient. It should be kept in mind that the deterioration of sperm quality is observed both during the acute period of coronavirus infection and during recovery period. Therefore, laboratory evaluation of the ejaculate in dynamics and its correction is necessary for males, especially those who plan to realize their reproductive potential.Conclusion. COVID‑19 generally has a negative impact on spermatogenesis and male fertility. To date, the timing and degree of restoration of a man’s reproductive function after a coronavirus infection remains completely unknown. Therefore, both in the early and late rehabilitation period, men of reproductive age need the supervision of an andrologist.

Receptor-Binding Domain (RBD) Antibodies Contribute More to SARS-CoV-2 Neutralization When Target Cells Express High Levels of ACE2.

Neutralization assays are experimental surrogates for the effectiveness of infection- or vaccine-elicited polyclonal antibodies and therapeutic monoclonal antibodies targeting SARS-CoV-2. However, the measured neutralization can depend on the details of the experimental assay. Here, we systematically assess how ACE2 expression in target cells affects neutralization by antibodies to different spike epitopes in lentivirus pseudovirus neutralization assays. For high ACE2-expressing target cells, receptor-binding domain (RBD) antibodies account for nearly all neutralizing activity in polyclonal human sera. However, for lower ACE2-expressing target cells, antibodies targeting regions outside the RBD make a larger (although still modest) contribution to serum neutralization. These serum-level results are mirrored for monoclonal antibodies: N-terminal domain (NTD) antibodies and RBD antibodies that do not compete for ACE2 binding incompletely neutralize on high ACE2-expressing target cells, but completely neutralize on cells with lower ACE2 expression. Our results show that the ACE2 expression level in the target cells is an important experimental variable, and that high ACE2 expression emphasizes the role of a subset of RBD-directed antibodies.

Multisystem screening reveals SARS-CoV-2 in neurons of the myenteric plexus and in megakaryocytes.

SARS‐CoV‐2, the causative agent of COVID‐19, typically manifests as a respiratory illness, although extrapulmonary involvement, such as in the gastrointestinal tract and nervous system, as well as frequent thrombotic events, are increasingly recognised. How this maps onto SARS‐CoV‐2 organ tropism at the histological level, however, remains unclear. Here, we perform a comprehensive validation of a monoclonal antibody against the SARS‐CoV‐2 nucleocapsid protein (NP) followed by systematic multisystem organ immunohistochemistry analysis of the viral cellular tropism in tissue from 36 patients, 16 postmortem cases and 16 biopsies with polymerase chain reaction (PCR)‐confirmed SARS‐CoV‐2 status from the peaks of the pandemic in 2020 and four pre‐COVID postmortem controls. SARS‐CoV‐2 anti‐NP staining in the postmortem cases revealed broad multiorgan involvement of the respiratory, digestive, haematopoietic, genitourinary and nervous systems, with a typical pattern of staining characterised by punctate paranuclear and apical cytoplasmic labelling. The average time from symptom onset to time of death was shorter in positively versus negatively stained postmortem cases (mean = 10.3 days versus mean = 20.3 days, p = 0.0416, with no cases showing definitive staining if the interval exceeded 15 days). One striking finding was the widespread presence of SARS‐CoV‐2 NP in neurons of the myenteric plexus, a site of high ACE2 expression, the entry receptor for SARS‐CoV‐2, and one of the earliest affected cells in Parkinson's disease. In the bone marrow, we observed viral SARS‐CoV‐2 NP within megakaryocytes, key cells in platelet production and thrombus formation. In 15 tracheal biopsies performed in patients requiring ventilation, there was a near complete concordance between immunohistochemistry and PCR swab results. Going forward, our findings have relevance to correlating clinical symptoms with the organ tropism of SARS‐CoV‐2 in contemporary cases as well as providing insights into potential long‐term complications of COVID‐19. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

EXPRESSION PROFILE OF SARS-COV-2 ENTRY RECEPTOR ACE2 IN THE HEPATOCELLULAR CARCINOMA AND ITS IMPACT ON COVID-19 PATIENTS

The SARS-CoV-2 infection leads to liver injury and promotes other viral infections such as hepatitis B virus (HBV) in COVID-19 patients. Obesity is involved with an increased risk of mortality in hepatocellular carcinoma (HCC) patients. In the current study, we analyzed the SARS-CoV-2 entry receptor ACE2 expression patterns in various HCC patients using different public databases on cancer. We found that the ACE2 and TMPRSS2 mRNA expressions are significantly downregulated in HCC tissues compared with the healthy population. Interestingly, high ACE2 expression is positively associated with HCC patient’s obesity and age of 61 to 80 years old. A significantly lower survivability rate is revealed in extremely obese and obese HCC patients with high expression of ACE2. In addition, the expression of important innate immune-related genes such as IKBKB, MAVS, IRF3, and RELA are found to be significantly increased in HCC patients. Therefore, it might be suggested that obesity and age of the HCC patient along with the involvement of innate immune genes, might be the important triggers for COVID-19 pathogenesis.

Neutrophils predominate the immune signature of cerebral thrombi in COVID-19 stroke patients

Coronavirus disease 2019 (COVID-19) is associated with an increased risk of thrombotic events. Ischemic stroke in COVID-19 patients entails high severity and mortality rates. Here we aimed to analyze cerebral thrombi of COVID-19 patients with large vessel occlusion (LVO) acute ischemic stroke to expose molecular evidence for SARS-CoV-2 in the thrombus and to unravel any peculiar immune-thrombotic features. We conducted a systematic pathological analysis of cerebral thrombi retrieved by endovascular thrombectomy in patients with LVO stroke infected with COVID-19 (n = 7 patients) and non-covid LVO controls (n = 23). In thrombi of COVID-19 patients, the SARS-CoV-2 docking receptor ACE2 was mainly expressed in monocytes/macrophages and showed higher expression levels compared to controls. Using polymerase chain reaction and sequencing, we detected SARS-CoV-2 Clade20A, in the thrombus of one COVID-19 patient. Comparing thrombus composition of COVID-19 and control patients, we noted no overt differences in terms of red blood cells, fibrin, neutrophil extracellular traps (NETs), von Willebrand Factor (vWF), platelets and complement complex C5b-9. However, thrombi of COVID-19 patients showed increased neutrophil density (MPO+ cells) and a three-fold higher Neutrophil-to-Lymphocyte Ratio (tNLR). In the ROC analysis both neutrophils and tNLR had a good discriminative ability to differentiate thrombi of COVID-19 patients from controls. In summary, cerebral thrombi of COVID-19 patients can harbor SARS-CoV2 and are characterized by an increased neutrophil number and tNLR and higher ACE2 expression. These findings suggest neutrophils as the possible culprit in COVID-19-related thrombosis.Graphical

Comorbidity between lung cancer and COVID-19 pneumonia: role of immunoregulatory gene transcripts in high ACE2-expressing normal lung.

SARS-CoV-2 (COVID-19) elicits a T-cell antigen-mediated immune response of variable efficacy. To understand this variability, we explored transcriptomic expression of angiotensin-converting enzyme 2 (ACE2, the SARS-CoV-2 receptor) and of immunoregulatory genes in normal lung tissues from patients with non-small cell lung cancer (NSCLC). This study used the transcriptomic and the clinical data for NSCLC patients generated during the CHEMORES study [n = 123 primary resected (early-stage) NSCLC] and the WINTHER clinical trial (n = 32 metastatic NSCLC). We identified patient subgroups with high and low ACE2 expression (p = 1.55 × 10-19) in normal lung tissue, presumed to be at higher and lower risk, respectively, of developing severe COVID-19 should they become infected. ACE2 transcript expression in normal lung tissues (but not in tumor tissue) of patients with NSCLC was higher in individuals with more advanced disease. High-ACE2 expressors had significantly higher levels of CD8+ cytotoxic T lymphocytes and natural killer cells but with presumably impaired function by high Thymocyte Selection-Associated High Mobility Group Box Protein TOX (TOX) expression. In addition, immune checkpoint-related molecules - PD-L1, CTLA-4, PD-1, and TIGIT - are more highly expressed in normal (but not tumor) lung tissues; these molecules might dampen immune response to either viruses or cancer. Importantly, however, high inducible T-cell co-stimulator (ICOS), which can amplify immune and cytokine reactivity, significantly correlated with high ACE2 expression in univariable analysis of normal lung (but not lung tumor tissue). We report a normal lung immune-tolerant state that may explain a potential comorbidity risk between two diseases - NSCLC and susceptibility to COVID-19 pneumonia. Further, a NSCLC patient subgroup has normal lung tissue expressing high ACE2 and high ICOS transcripts, the latter potentially promoting a hyperimmune response, and possibly leading to severe COVID-19 pulmonary compromise.

COMPARATIVE ANALYSIS OF THE FREQUENCY OF RS1801133 POLYMORPHISM OF THE MTHFR GENE IN THE GROUP OF PATIENTS WITH POSTCOVID COMPLICATIONS OF MAXILLOFACIAL AREA

In the article of genetic studies of patients with post-covid maxillofacial complications. The condition after COVID-19 is considered a life-threatening disease, ranging from mild symptoms to serious complications. Candidiasis is the most common type of superficial purulent infection. The Candida species is a frequent inhabitant of the oral mucosa, but its growth is inhibited by other organisms in the body, which prevents any pathological change in the mucous membrane of this fungus. Candida albicans is the most common yeast, followed by Candida glabrata, Candida krusei, Candida tropicalis and Candida stellatoidea. According to this systematic review, 57 cases of oral candidiasis and one case of retinitis candidiasis were reported in patients undergoing treatment for COVID-19. Single-cell RNA-seq analysis of angiotensin-converting enzyme II (ACE2) expression and serologic examination of samples indicates that ACE2 may be the cellular receptor for SARS-CoV-2, suggesting that ACE2-expressing cells are likely to be the main target cell type that vulnerable to SARS-CoV-2 infection. As a rule, there is a high expression of ACE2 r on the epithelial cells of the oral mucosa, enrichment is enriched in epithelial cells of the tongue. There were few reports prior to this study.

Enhanced apoptosis as a possible mechanism to self-limit SARS-CoV-2 replication in porcine primary respiratory epithelial cells in contrast to human cells

The ability of SARS-CoV to infect different species, including humans, dogs, cats, minks, ferrets, hamsters, tigers, and deer, pose a continuous threat to human and animal health. Pigs, though closely related to humans, seem to be less susceptible to SARS-CoV-2. Former in vivo studies failed to demonstrate clinical signs and transmission between pigs, while later attempts using a higher infectious dose reported viral shedding and seroconversion. This study investigated species-specific cell susceptibility, virus dose-dependent infectivity, and infection kinetics, using primary human (HRECs) and porcine (PRECs) respiratory epithelial cells. Despite higher ACE2 expression in HRECs compared to PRECs, SARS-CoV-2 infected, and replicated in both PRECs and HRECs in a dose-dependent manner. Cytopathic effect was particularly more evident in PRECs than HRECs, showing the hallmark morphological signs of apoptosis. Further analysis confirmed an early and enhanced apoptotic mechanism driven through caspase 3/7 activation, limiting SARS-CoV-2 propagation in PRECs compared to HRECs. Our findings shed light on a possible mechanism of resistance of pigs to SARS-CoV-2 infection, and it may hold therapeutic value for the treatment of COVID-19.

Infection of Brain Pericytes Underlying Neuropathology of COVID-19 Patients.

A wide range of neurological manifestations have been associated with the development of COVID-19 following SARS-CoV-2 infection. However, the etiology of the neurological symptomatology is still largely unexplored. Here, we used state-of-the-art multiplexed immunostaining of human brains (n = 6 COVID-19, median age = 69.5 years; n = 7 control, median age = 68 years) and demonstrated that expression of the SARS-CoV-2 receptor ACE2 is restricted to a subset of neurovascular pericytes. Strikingly, neurological symptoms were exclusive to, and ubiquitous in, patients that exhibited moderate to high ACE2 expression in perivascular cells. Viral dsRNA was identified in the vascular wall and paralleled by perivascular inflammation, as signified by T cell and macrophage infiltration. Furthermore, fibrinogen leakage indicated compromised integrity of the blood–brain barrier. Notably, cerebrospinal fluid from additional 16 individuals (n = 8 COVID-19, median age = 67 years; n = 8 control, median age = 69.5 years) exhibited significantly lower levels of the pericyte marker PDGFRβ in SARS-CoV-2-infected cases, indicative of disrupted pericyte homeostasis. We conclude that pericyte infection by SARS-CoV-2 underlies virus entry into the privileged central nervous system space, as well as neurological symptomatology due to perivascular inflammation and a locally compromised blood–brain barrier.

Persistent chemosensory dysfunction in a young patient with mild COVID-19 with partial recovery 15months after the onset.

ObjectiveIt is reported that recovery from COVID-19 chemosensory deficit generally occurs in a few weeks, although olfactory dysfunction may persist longer. Here, we provide a detailed follow-up clinical investigation in a very young female patient (17-year-old) with a long-lasting anosmia after a mild infection, with partial recovery 15 months after the onset.MethodsNeuroimaging and neurophysiologic assessments as well as olfactory mucosa swabbing for microbiological and immunocytochemical analyses were performed. Olfactory and gustatory evaluations were conducted through validated tests.ResultsChemosensory evaluations were consistent with anosmia associated with parosmia phenomena and gustatory impairment, the latter less persistent. Brain MRI (3.0 T) showed no microvascular injury in olfactory bulbs and brain albeit we cannot rule out slight structural abnormalities during the acute phase, and a high-density EEG was negative. Immunocytochemistry of olfactory mucosa swabs showed high expression of ACE2 in sustentacular cells and lower dot-like cytoplasmic positivity in neuronal-shaped cells.DiscussionThe occurrence of long-term persistent olfactory deficit in spite of the absence of structural brain and olfactory bulb involvement supports the view of a possible persistent dysfunction of both sustentacular cells and olfactory neurons. The gustatory dysfunction even if less persisting for the described features could be related to a primary gustatory system involvement. Future longitudinal studies are needed to investigate the persistence of chemosensory impairment, which could have a relevant impact on the daily life.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10072-021-05635-y.

EXPRESSION PROFILE OF SARS-COV-2 ENTRY RECEPTOR ACE2 IN THE HEPATOCELLULAR CARCINOMA AND ITS IMPACT ON COVID-19 PATIENTS

The SARS-CoV-2 infection leads to liver injury and promotes other viral infections such as hepatitis B virus (HBV) in COVID-19 patients. Obesity is involved with an increased risk of mortality in hepatocellular carcinoma (HCC) patients. In the current study, we analyzed the SARS-CoV-2 entry receptor ACE2 expression patterns in various HCC patients using different public databases on cancer. We found that the ACE2 and TMPRSS2 mRNA expressions are significantly downregulated in HCC tissues compared with the healthy population. Interestingly, high ACE2 expression is positively associated with HCC patient’s obesity and age of 61 to 80 years old. A significantly lower survivability rate is revealed in extremely obese and obese HCC patients with high expression of ACE2. In addition, the expression of important innate immune-related genes such as IKBKB, MAVS, IRF3, and RELA are found to be significantly increased in HCC patients. Therefore, it might be suggested that obesity and age of the HCC patient along with the involvement of innate immune genes, might be the important triggers for COVID-19 pathogenesis.

Angiotensin-Converting Enzyme 2 in the Pathogenesis of Renal Abnormalities Observed in COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) was first reported in late December 2019 in Wuhan, China. The etiological agent of this disease is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the high transmissibility of the virus led to its rapid global spread and a major pandemic (ongoing at the time of writing this review). The clinical manifestations of COVID-19 can vary widely from non-evident or minor symptoms to severe acute respiratory syndrome and multi-organ damage, causing death. Acute kidney injury (AKI) has been recognized as a common complication of COVID-19 and in many cases, kidney replacement therapy (KRT) is required. The presence of kidney abnormalities on hospital admission and the development of AKI are related to a more severe presentation of COVID-19 with higher mortality rate. The high transmissibility and the broad spectrum of clinical manifestations of COVID-19 are in part due to the high affinity of SARS-CoV-2 for its receptor, angiotensin (Ang)-converting enzyme 2 (ACE2), which is widely expressed in human organs and is especially abundant in the kidneys. A debate on the role of ACE2 in the infectivity and pathogenesis of COVID-19 has emerged: Does the high expression of ACE2 promotes higher infectivity and more severe clinical manifestations or does the interaction of SARS-CoV-2 with ACE2 reduce the bioavailability of the enzyme, depleting its biological activity, which is closely related to two important physiological systems, the renin-angiotensin system (RAS) and the kallikrein-kinin system (KKS), thereby further contributing to pathogenesis. In this review, we discuss the dual role of ACE2 in the infectivity and pathogenesis of COVID-19, highlighting the effects of COVID-19-induced ACE2 depletion in the renal physiology and how it may lead to kidney injury. The ACE2 downstream regulation of KKS, that usually receives less attention, is discussed. Also, a detailed discussion on how the triad of symptoms (respiratory, inflammatory, and coagulation symptoms) of COVID-19 can indirectly promote renal injury is primary aborded.

Spike in pollution to ignite the bursting of COVID-19 second wave is more dangerous than spike of SAR-CoV-2 under environmental ignorance in long term: a review.

Specific areas in many countries such as Italy, India, China, Brazil, Germany and the USA have witnessed that air pollution increases the risk of COVID-19 severity as particulate matters transmit the virus SARS-CoV-2 and causes high expression of ACE2, the receptor for spike protein of the virus, especially under exposure to NO2, SO2 and NOx emissions. Wastewater-based epidemiology of COVID-19 is also noticed in many countries such as the Netherlands, the USA, Paris, France, Australia, Spain, Italy, Switzerland China, India and Hungary. Soil is also found to be contaminated by the RNA of SARS-CoV-2. Activities including defecation and urination by infected people contribute to the source for soil contamination, while release of wastewater containing cough, urine and stool of infected people from hospitals and home isolation contributes to the source of SARS-CoV-2 RNA in both water and soil. Detection of the virus early before the outbreak of the disease supports this fact. Based on this information, spike in pollution is found to be more dangerous in long-term than the spike protein of SARS-CoV-2. It is because the later one may be controlled in future within months or few years by vaccination and with specific drugs, but the former one provides base for many diseases including the current and any future pandemics. Although such predictions and the positive effects of SARS-CoV-2 on environment was already forecasted after the first wave of COVID-19, the learnt lesson as spotlight was not considered as one of the measures for which 2nd wave has quickly hit the world.

Interactions of Spike-RBD of SARS-CoV-2 and Platelet Factor 4: New Insights in the Etiopathogenesis of Thrombosis.

The rare but dangerous adverse events evidenced after massive vaccination against SARS-CoV-2 are represented by thrombosis and thrombocytopenia. The patients diagnosed with severe COVID-19 may develop a pro-thrombotic state with a much higher frequency, thus we decided to investigate the role of Spike protein (the only common product of the two conditions) or the anti-Spike antibodies in the etiopathogenesis of thrombosis. A pathogenic Platelet Factor 4 (PF4)-dependent syndrome, unrelated to the use of heparin therapy, has been reported after the administration of vaccines in the patients manifesting acute thrombocytopenia and thrombosis. Thus, we aimed at shedding light on the structural similarities of Spike of SARS-CoV-2 and PF4 on their eventual biochemical interactions and on the role of their specific antibodies. The similarities between PF4 and Spike-RBD proteins were evaluated by a comparison of the structures and by testing the cross-reactivity of their specific antibodies by ELISA assays. We found that the anti-Spike antibodies do not recognize PF4, on the contrary, the anti-PF4 antibodies show some cross-reactivity for Spike-RBD. More interestingly, we report for the first time that the PF4 and Spike-RBD proteins can bind each other. These data suggest that the interaction of the two proteins could be involved in the generation of anti-PF4 antibodies, their binding to Spike-RBD, which could lead to platelets aggregation due also to their high expression of ACE2.

Th2/Th1 Cytokine Imbalance Is Associated With Higher COVID-19 Risk Mortality.

A major component of COVID-19 severe respiratory syndrome is the patient’s immune response to the SARS-CoV-2 virus and the consequential multi-organ inflammatory response. Several studies suggested a potential role of CD4+ T cells in COVID-19 severe respiratory syndrome. We first hypothesized that there is a type 2 helper (Th2)/type 1 helper (Th1) imbalance in older age, male, asthma, smokers, and high ACE2 expression phenotype in the airway of non-infected patients. Next, we hypothesized that a Th2/Th1 imbalance may predict higher mortality in COVID-19 infected hospitalized patients with and without patient reported current asthma. We first analyzed publicly available gene expression from the sputum of 118 moderate-to-severe asthma patients and 21 healthy controls, and from nasal epithelium of 26 healthy current smokers and 21 healthy never smokers. Secondly, we profiled 288 new serum proteomics samples measured at admission from patients hospitalized within the Mount Sinai Health System with positive SARS-CoV-2 infection. We first computed Th1 and Th2 pathway enrichment scores by gene set variation analysis and then compared the differences in Th2 and Th1 pathway scores between patients that died compared to those that survived, by linear regression. The level of Th2/Th1 imbalance, as determined by the enrichment score, was associated with age, sex, and ACE2 expression in sputum, and with active smoking status in nasal epithelium (p < 0.05). Th2/Th1 imbalance at hospital admission in sera of patients was not significantly associated with death from COVID-19 (p = 0.11), unless evaluated in the asthmatic strata (p = 0.01). Using a similar approach we also observed a higher Th17/Th1 cytokine imbalance in all deceased patients compared to those that survived (p < 0.001), as well as in the asthmatic strata only (p < 0.01). Th2/Th1 imbalance is higher in the sera of asthma patients at admission that do not survive COVID-19, suggesting that the Th2/Th1 interplay may affect patient outcomes in SARS-CoV2 infection. In addition, we report that Th17/Th1 imbalance is increased in all patients that die of COVID-19.

COVID-19 and celiac disease: A pathogenetic hypothesis for a celiac outbreak.

BackgroundA growing body of evidence supports the intestinal trophism of SARS‐CoV‐2, with ciliated cells and intestinal enterocytes being target cells because of the high expression of ACE2 and TMPRSS2. Indeed, COVID‐19 promotes a “cytokine storm” in the intestinal mucosa: the resulting epithelial damage leads to increased barrier permeability, allowing the passage of gliadin in the intestinal lamina.MethodsBased on current literature, we hypothesize the role of COVID‐19 as a potential trigger factor for celiac disease in predisposed patients.ConclusionsGenetically predisposed patients could be more likely to develop celiac disease following SARS‐CoV‐2 infection, making COVID‐19 a candidate culprit for a potential outbreak of celiac disease in the forthcoming future.

Alterations of the male and female reproductive systems induced by COVID-19.

A variety of pneumonia cases of unknown cause emerged in China in December 2019. A new virus belonging to the Coronaviridae family, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). Within a few days, COVID-19 became a pandemic disease. This review aimed to investigate the possible implications of COVID-19 for human reproductive systems, as in previous studies ACE2 was highly expressed in some organs of these systems, such as the testicles. A total of 41 publications were found in the specialized databases and, after selection, 7 articles were used to build this study. Our results showed that the fever caused by COVID-19 has a negative effect on spermatogenesis, there is high expression of ACE2 in the testicles and in the uterine tubes and there is a higher level of transmembrane protease serine 2 (TMPRSS2), which is also responsible for the entry of the virus into the cell. Moreover, it was noted that there was viral genetic material in the semen and an increase in the serum concentration of luteinizing hormone (LH) in men and women, which could cause hypogonadism. Thus, we conclude that there is the possibility of infection and malfunction in the reproductive organs as well as the plausibility of sexual transmission of this disease. Further analysis must be carried out to prove the effects of COVID-19 on the human reproductive systems.

VARICELLA LIKE DERMATOLOGICAL MANIFESTATION FOLLOWING SARSCOVID-19 INFECTION :A DIAGNOSTIC DILEMMA

The infection caused by the novel SARS-CoV-2 is a public health emergency of international concern. Although, COVID-19, mainly affects the lungs, the infection can spread to extrapulmonary tissues, causing multiorgan involvement in severely ill patients. The infectivity of SARS-CoV-2 is related to the pattern of expression of the viral entry factors ACE2 and TMPRSS2 in human tissues. As such, the respiratory and gastrointestinal tracts are at high risk for SARS-CoV-2 infection due to their high expression of ACE2 and TMPRSS2, which explains the clinical phenotype described in the vast majority of infected patients that includes pneumonia and diarrhea. Recently, concern regarding virus to infect the skin has been raised by dermatologists due to the increasing observations of cutaneous manifestations in patients with SARS-CoV-2 infection. Although there is little evidence of the expression of ACE2 and TMPRSS2 in the normal skin, the dermatological ndings observed among COVID-19 patients warrants further investigation to delineate the mechanisms of skin affection after SARS-CoV-2 infection[1]. The frequency of skin lesions in these patients varies between 1.8 % and 20.4 % . The major dermatologic morphologies described in CoVID-19 cases were morbilliform, pernio-like, urticaria, macular erythema, vesicle, papulosquamous and retiform purpura