Differentially Expressed Inflammatory Cell Death-Related Genes and the Serum Levels of IL-6 are Determinants for Severity of Coronaviruses Diseases-2019 (COVID-19).

Background: Inflammatory cell death, PANoptosis, has been suggested to orchestrate the lymphocyte decrement among coronavirus disease-2019 (COVID-19) patients. The main aim of this study was to examine the differences in the expression of key genes related to inflammatory cell death and their correlation with lymphopenia in the mild and severe types of COVID-19 patients. Materials and Methods: Eighty-eight patients (36 to 60 years old) with mild (n = 44) and severe (n = 44) types of COVID-19 were enrolled. The expression of key genes related to apoptosis (FAS-associated death domain protein, FADD), pyroptosis (ASC (apoptosis-associated speck-like protein containing caspase activation and recruitment domains (CARD)), the adapter protein ASC binds directly to caspase-1 and is critical for caspase-1 activation in response to a broad range of stimuli), and necroptosis (mixed lineage kinase domain-like, MLKL) genes were examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay, and compared between the groups. The serum levels of interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay (ELISA) assay. Results: A major increase in the expression of FADD, ASC, and MLKL-related genes in the severe type of patients was compared to the mild type of patients. The serum levels of IL-6 similarly indicated a significant increase in the severe type of the patients. A significant negative correlation was detected between the three genes' expression and the levels of IL-6 with the lymphocyte counts in both types of COVID-19 patients. Conclusion: Overall, the main regulated cell-death pathways are likely to be involved in lymphopenia in COVID-19 patients, and the expression levels of these genes could potentially predict the patients' outcome.

Risk Factors of COVID-19 Associated Mucormycosis (CAM) in Iranian Patients: A Single-Center Retrospective Study.

BACKGROUND: COVID-19 associated mucormycosis (CAM) has been known as one of the most severe post-COVID morbidities. OBJECTIVES: To describe CAM cases, identify possible risk factors, and report outcomes of patients. METHODS: This retrospective study was performed in Amir-Alam Hospital, Tehran, Iran between February 2020 and September 2021. Patients with mucormycosis who had an active or previous diagnosis of COVID-19 have been included. RESULTS: Of 94 patients with mucormycosis, 52 (33 men and 19 women; mean age: 57.0 ± 11.82 years) were identified with an active or history of COVID-19. Rhino-orbital, rhino maxillary, rhino-orbito cerebral subtypes of mucormycosis were detected in 6 (11.5%), 18(34.6%), and 28(53.8%) patients. As a control group, 130 (69 men and 61 women; mean age: 53.10 ± 14.49 years) random RT-PCR-confirmed COVID-19 patients without mucormycosis have been included. The mean interval between COVID-19 diagnosis and initial mucormycosis symptoms was 16.63 ± 8.4 days (range 0-51). Those in the CAM group had a significantly more severe course of COVID-19 (OR = 3.60, P-value < 0.01). Known history of previous diabetes mellitus (OR = 7.37, P-value < 0.01), smoking (OR = 4.55, P-value < 0.01), and history of receiving high-dose corticosteroid pulse therapy because of more severe COVID-19 (P-value = 0.022) were found as risk factors. New-onset post-COVID hyperglycemia was lower in the CAM group (46.2% vs. 63.8%; OR = 0.485, P-value = 0.028). After treatment of the CAM group, 41(78.8%) of patients recovered from mucormycosis. The mean ages of the expired patients in the CAM group were significantly higher than those who recovered from mucormycosis (66.18 ± 9.56 vs. 54.56 ± 11.22 years; P < 0.01); and COVID-19 disease was more severe (P = 0.046). CONCLUSION: Either active or history of COVID-19 can cause an increase in the risk of mucormycosis development. Some of the most important risk factors are the medical history of diabetes mellitus, smoking, and high-dose corticosteroid therapy. CAM is important possible comorbidity related to COVID-19, which could make the post-COVID conditions more complicated. More research and studies with greater sample sizes among different ethnicities are needed to explore the association between COVID-19 and mucormycosis.

The Value of Spiral Chest Computed Tomography Scan in the Diagnosis of Asymptomatic Coronavirus Carriers among Paranasal Sinus and Pharynx Surgery Candidates.

Introduction The nasopharynx and oropharynx are the main colonization sites of coronavirus. Therefore, patients with paranasal sinuses and pharyngeal problems (ear, nose, and throat [ENT] patients) predispose coronavirus infection. Ear, nose, and throat patients with concomitant asymptomatic coronavirus infection may develop severe pneumonia following surgical procedures. As a result, presurgical screening for coronavirus infection is a substantial concern. Objective We evaluated the usefulness of a spiral chest computed tomography (CT) scan in the diagnosis of asymptomatic coronavirus infection in the presurgical assessment of ENT patients Methods In this study, candidates of paranasal sinus or pharyngeal surgery were evaluated for coronavirus infection. Patients with neither history of coronavirus disease 2019 (COVID-19) nor compatible symptoms and signs were screened for asymptomatic coronavirus infection. These patients composed two groups: the first group underwent a reverse transcription polymerase chain reaction (RT-PCR) test of nasopharyngeal sample and spiral chest CT scan, but for the second one, only the latter was performed. Results In the first group, which consisted of 106 patients, 11 (10.4%) cases had positive RT-PCR test results, and 17 (16%) patients showed positive findings in favor of coronavirus infection in the spiral chest CT scan. In the second group, which consisted of 173 patients, 34 (19.7%) cases had positive chest CT scan results. Conclusion The chest CT scan has a valuable role in the early diagnosis of asymptomatic coronavirus carriers in patients highly predisposed to infection, especially in low resource areas, where the RT-PCR test is unavailable.

Distinguishing Characteristics of COVID-19-Associated Mucormycosis; a Case Series.

Introduction: Since the emergence of COVID-19 pandemic, several articles have reported the co-existence of mucormycosis and COVID-19. This study aimed to distinguish the characteristics of COVID-19-associated rhinocerebral mucormycosis. Methods: In this case series, 18 patients with COVID-19-associated rhinocerebral mucormycosis and unique clinical manifestations and outcomes, who were referred to Amiralam Hospital, a tertiary otorhinolaryngology center, Tehran, Iran, during the COVID-19 era, were reported. Results: Eighteen patients with the mean age of 62.0 ± 11.6 (range: 42 - 83) years were studied (50% males). The mean time interval between diagnosis of COVID-19 and first manifestation of mucormycosis was 15.5 ± 9.7 days. The most common presenting symptom was facial paresthesia (72.2%). Fifty percent of patients developed frozen eye. Palatal necrosis was seen in 7 cases (38.8%). Remarkably, facial paralysis was observed in 5 (27.7%) patients. Another notable clinical picture was cavernous sinus thrombosis, seen in 7 patients. We also had two cases of carotid artery occlusion. Three patients, unfortunately, passed away. Conclusion: Rhinocerebral mucormycosis is one of the most important complications of COVID-19 patients, especially those with underlying diseases. It seems that the key to proper management of mucormycosis is early diagnosis and timely intervention, which could give a patient a chance to live more.

Type-I interferons in the immunopathogenesis and treatment of Coronavirus disease 2019.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is currently the major global health problem. Still, it continues to infect people globally and up to the end of February 2022, over 436 million confirmed cases of COVID-19, including 5.95 million deaths, were reported to the world health organization (WHO). No specific treatment is currently available for COVID-19, and the discovery of effective therapeutics requires understanding the effective immunologic and immunopathologic mechanisms behind this infection. Type-I interferons (IFN-Is), as the critical elements of the immediate immune response against viral infections, can inhibit the replication and spread of the viruses. However, the available evidence shows that the antiviral IFN-I response is impaired in patients with the severe form of COVID-19. Moreover, the administration of exogenous IFN-I in different phases of the disease can lead to various outcomes. Therefore, understanding the role of IFN-I molecules in COVID-19 development and its severity can provide valuable information for better management of this disease. This review summarizes the role of IFN-Is in the pathogenesis of COIVD-19 and discusses the importance of autoantibodies against this cytokine in the spreading of SARS-CoV-2 and control of the subsequent excessive inflammation.

Dysregulation of RNA interference components in COVID-19 patients.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the novel coronavirus causing severe respiratory illness (COVID-19). This virus was initially identified in Wuhan city, a populated area of the Hubei province in China, and still remains one of the major global health challenges. RNA interference (RNAi) is a mechanism of post-transcriptional gene silencing that plays a crucial role in innate viral defense mechanisms by inhibiting the virus replication as well as expression of various viral proteins. Dicer, Drosha, Ago2, and DGCR8 are essential components of the RNAi system, which is supposed to be dysregulated in COVID-19 patients. This study aimed to assess the expression level of the mentioned mRNAs in COVID-19patients compared to healthy individuals. RESULTS: Our findings demonstrated that the expression of Dicer, Drosha, and Ago2 was statistically altered in COVID-19 patients compared to healthy subjects. Ultimately, the RNA interference mechanism as a crucial antiviral defense system was suggested to be dysregulated in COVID-19 patients.

Association of HScore Parameters with Severe COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: Several reports have associated the severe Coronavirus disease-2019 (sCOVID-19) with secondary-hemophagocytic lymphohistiocytosis (sHLH) and proposed utilizing the hemophagocytic syndrome diagnostic score (HScore) for sCOVID-19 patients. We conducted a systematic review and meta-analysis to find the possible association of HScore parameters with severity in COVID-19 patients. METHODS: A systematic search was performed in Medline via PubMed, EMBASE, and Cochrane databases using all HScore and COVID-19 keywords. The studies were all from 2020, and the study language was limited to English. The records were screened based on inclusion/exclusion criteria. Random/fixed-effect models were employed for meta-analysis, based on the I2 index of parameters. The pooled mean differences were estimated for continuous parameters. The pooled odds-ratio was estimated for fever. The level of significance was set at 0.05. RESULTS: Eighteen studies (comprising 2459 patients) out of 26151 screened studies were included in this meta-analysis. The results showed that the level of leukocyte, neutrophil, aspartate transaminase (AST), ferritin, and fibrinogen were significantly higher in sCOVID-19 patients than in non-severe ones. Significant lower levels of lymphocyte, platelet, and hemoglobin were also found in sCOVID-19 patients than non-severe patients. Fever was nearly associated with two times increased odds of sCOVID-19 (P=0.051). CONCLUSION: Lymphopenia, thrombocytopenia, hypohemoglobinemia, hyperferritinemia, high levels of AST, and fever are common features of both sCOVID-19 and HLH. However, the leukocytosis, neutrophilia, and hyperfibrinogenemia found in sCOVID-19 are in contrast with HScore. Conclusively, HScore parameters could be risk factors for sCOVID-19. However, some parameters' roles are contradictory, suggesting the need for further investigation and a new way of HScore interpretation in sCOVID-19 patients.A preprint of this study was published at https://www.researchsquare.com/article/rs-54490/v2.

Erythrodermic flare‐up of psoriasis with COVID‐19 infection: A report of two cases and a comprehensive review of literature focusing on the mutual effect of psoriasis and COVID‐19 on each other along with the special challenges of the pandemic

The COVID‐19 pandemic has been extra challenging for patients with chronic diseases. Psoriasis is one of the chronic conditions that its treatment mostly relies on immunosuppressants. In this study, we report two cases with a long history of psoriasis that COVID‐19 infection caused them to undergo erythrodermic psoriasis. In psoriatic patients, the administration of glucocorticoids during the course of COVID‐19 infection might affect patient's psoriasis presentation, as in some cases early after administrating steroids, psoriatic lesions seem to be mitigated, and after finishing the course of treatment, some patients have reported to experience certain degrees of psoriasis flare‐up.

Erythrodermic flare-up of psoriasis with COVID-19 infection: A report of two cases and a comprehensive review of literature focusing on the mutual effect of psoriasis and COVID-19 on each other along with the special challenges of the pandemic.

The COVID-19 pandemic has been extra challenging for patients with chronic diseases. Psoriasis is one of the chronic conditions that its treatment mostly relies on immunosuppressants. In this study, we report two cases with a long history of psoriasis that COVID-19 infection caused them to undergo erythrodermic psoriasis.

An experimental in silico study on COVID-19: Response of neutrophil-related genes to antibiotics.

Background and Aims: All components of the immune system are involved in alleviating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Further research is required to provide detailed insights into COVID-19-related immune compartments and pathways. In addition, a significant percentage of hospitalized COVID-19 patients suspect bacterial infections and antimicrobial resistance occurs following antibiotics treatment. The aim of this study was to evaluate the possible effects of antibiotics on the response of neutrophil-related genes in SARS-CoV-2 patients by an experimental in silico study. Methods: The two data sets GSE1739 and GSE21802 including 10 SARS positive patients and 35 influenza A (H1N1) patients were analyzed, respectively. Differentially expressed genes (DEGs) between these two data sets were determined by GEO2R analysis and the Venn diagram online tool. After determining the hub genes involved in immune responses, the expression of these genes in 30 COVID-19 patients and 30 healthy individuals was analyzed by real-time polymerase chain reaction (PCR). All patients received antibiotics, including levofloxacin, colistin, meropenem, and ceftazidime. Results: GEO2R analysis detected 240 and 120 DEGs in GSE21802 and GSE1739, respectively. Twenty DEGs were considered as enriched hub genes involved in immune processes such as neutrophil degranulation, neutrophil activation, and antimicrobial humoral response. The central nodes were attributed to the genes of neutrophil elastase (ELANE), arginase 1 (ARG-1), lipocalin 2 (LCN2), and defensin 4 (DEFA4). Compared to the healthy subjects, the expression of LCN2 and DEFA4 were significantly reduced in COVID-19 patients. However, no significant differences were observed in the ELANE and AGR-1 levels between COVID-19 subjects and the control group. Conclusions: Activation and degranulation of neutrophils were observed mainly in SARS, and H1N1 infection processes and antibiotics administration could affect neutrophil activity during viral infection. It can be suggested that antibiotics can decrease inflammation by restoring the expression of neutrophil-related genes in COVID-19 patients.

Comparison of the effects of etomidate, ketamine, sodium thiopental, and midazolam on the mortality of patients with COVID-19 requiring intubation.

Background: Among the medications administered for the management of COVID-19 patients, the induction drugs used for intubation have received little attention. The aim of this study was to compare the effect of induction drugs on the mortality of patients with COVID-19 requiring intubation. Methods: In this retrospective study, all patients who were admitted to Shahid Sadoughi and Shahid Rahnemoun hospitals in Yazd from February to March 2020 with definitive diagnosis of COVID-19 and needed intubation were enrolled. Patients were divided into 4 groups based on the type of drugs used in intubation, and mortality rate was assessed at the end of the first, second, fourth, and seventh days of the study. Statistical analyses were performed using SPSS 20 and P values <.05 was considered significant. Results: In this study, 76 patients were examined. Patients were divided into 4 groups, of which 21 were in etomidate group, 8 in ketamine group, 21 in sodium thiopental group, and 35 in midazolam group. Mortality rate in these 4 groups was 25%, 12.5%, 14.3%, and 14.3% (p=0.822), respectively at the end of the first day after intubation; it was 83.3%, 12.5%, 28.6%, and 25.7% (p=0.001), respectively, at the end of the second day; it was 83.3%, 12.5%, 42.9%, and 42.9% (p=0.015), respectively, until the end of the fourth day; it was 100%, 25%, 61.9%, and 65.7% (p=0.007), respectively, until the end of the seventh day. Admission to intubation time interval was 0.91±0.99, 3.12±1.95, 4.09±2.44, and 4.74±2.62 days, respectively (p<0.001). Conclusion: The results of this study suggest that the use of etomidate may be associated with higher mortality in COVID-19 patients. Further studies are needed to verify the results of this study.

Implications of Sex Difference in CT Scan Findings and Outcome of Patients with COVID-19 Pneumonia.

PURPOSE: The novel coronavirus pandemic has caused significant morbidity and mortality since December 2019. Although the role of chest CT for diagnosing coronavirus disease 2019 (COVID-19) pneumonia is still debatable, the modality has been used in scenarios of constrained reverse-transcription polymerase chain reaction (RT-PCR) testing. The epidemiologic reports indicate an unexplored difference between men and women in disease severity. We aimed to study the role of sex on disease severity and its correlation with CT findings. MATERIALS AND METHODS: Authors retrospectively studied all confirmed cases of COVID-19 with thoracic CT scans obtained at three hospitals from February 25, 2020, to March 15, 2020, in Tehran, Iran. CT involvement patterns of COVID-19 were analyzed based on sex and age of patients. RESULTS: One hundred fifteen patients (64.3% [74/115] men) were enrolled, with a median age of 57 years (age range, 21-89). Thirty patients were admitted to the intensive care unit, and 30 patients died during the hospital stay. Seventy-seven percent (37/48) of patients with unfavorable prognosis were male. Peripheral distribution of opacities was more common in men than women. When grouped by an age cut-off of 60 years, the women in the elder group had a peribronchovascular distribution pattern, and younger men showed an anterior distribution of opacities. Women younger than 60 years had significantly lower severity scores (CT-scores) (7.5 ± 6.8). Receiver operating characteristic (ROC) curve analysis demonstrated a CT-score cut-off of 14.5 to have 100% sensitivity and 91.9% specificity for predicting poor prognosis in women younger than 60 years. CONCLUSION: Opacity patterns on chest CT scans in COVID-19 are different based on sex and age, and men are at higher risk of disease severity and death.© RSNA, 2020.

Immunopathological similarities between COVID-19 and influenza: Investigating the consequences of Co-infection.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a global public health emergency since December 2019, and so far, more than 980,000 people (until September 24, 2020) around the world have died. SARS-CoV-2 mimics the influenza virus regarding methods and modes of transmission, clinical features, related immune responses, and seasonal coincidence. Accordingly, co-infection by these viruses is imaginable because some studies have reported several cases with SARS-CoV-2 and influenza virus co-infection. Given the importance of the mentioned co-infection and the coming influenza season, it is essential to recognize the similarities and differences between the symptoms, immunopathogenesis and treatment of SARS-CoV-2 and influenza virus. Therefore, we reviewed the virology, clinical features, and immunopathogenesis of both influenza virus and SARS-CoV-2 and evaluated outcomes in cases with SARS-CoV-2 and influenza virus co-infection.