The Therapeutic Potential of Targeting the Connexin43 as a New Approach to Reducing Post-Surgical Adhesion.

Post-surgical peritoneal adhesions are a serious problem causing complications, such as bowel obstruction, infertility, and pain. There are currently no effective ways of preventing post-surgical adhesions. Excess secretion of proinflammatory cytokines and profibrotic molecules by immune cells and adherent fibroblasts is the main mechanism thatpromotes post-operative fibrotic scars. Although many studies have been conducted on the pathological causes of this disorder, there are still many unknown facts in this matter, so assessment of the role of different molecules in causing inflammation and adhesion can lead to the creation of new treatment methods. Connexins are a group of proteins related to gap junctions that have a role in cell communication and transmitted signaling between adjacent cells. Between different types of connexin protein isoforms, connexin43 is known to be involved in pathological conditions related to inflammation and fibrosis. Recent studies have reported that inhibition of connexin43 has the potential to reduce inflammation and fibrosis by reducing the expression of molecules like α-SMA and plasminogen activator inhibitor (PAI) that are involved in the early stages of adhesion formation. Further, inhibition of connexin43 may have therapeutic potential as a target to prevent post-surgical peritoneal adhesions.

Lysyl Oxidase-like 2 Dysregulation Increases the Risk of Post-Operative Fibrotic Scars Formation in the Female Reproductive Tract: A Novel Therapeutic Target to Reduce Fibrogenesis.

The formation of fibrotic bands in female reproductive system, including the uterus, after abdominal and pelvic surgeries, is an important medical challenge associated with many complications, including infertility and pain. Investigating the role of different molecules involved in fibrosis and adhesion formation may help in the development of new drugs to prevent this disorder. Lysyl oxidase-like 2 (LoxL2) is a copper-dependent enzyme that catalyzes the cross-linking of collagen and elastin fibers in the extracellular matrix (ECM) to stabilize ECM. Dysregulation of LoxL2 activity resulting from tissue hypoxia and inflammation after gynecological surgeries in the female reproductive tract increases collagen fibers cross-linking and promotes fibrosis. It has been shown that targeting LoxL2 by Lox inhibitors may reduce fibrosis. Considering the expression of LoxL2 in female reproductive organs and its dysregulation in hypoxia and inflammation, it is possible that LoxL2 has therapeutic potential as a drug target in the prevention of adhesions. In this review, we discuss the role of LoxL2 in the promotion of fibrotic processes focusing on its link with inflammatory and hypoxic conditions. We also justify the use of anti- LoxL2 agents as a potential therapeutic strategy for the prevention of post-surgical scar formation.

Two Cases of COVID-Related Osteonecrosis of the Jaws: A New and Worrying Entity Is Emerging.

Many people were affected by COVID-19 in its severe form. Some intercurrences are still emerging. We here report two cases of COVID-related osteonecrosis of the jaws (CRONJ). Two retrospective cases were admitted into Imam Reza Hospital, Mashhad, Iran with suspected CRONJ. One patient escaped from hospital while the other showed a positive result after our proposed treatment. A new aftermath to COVID-19 infections is emerging. Maxillofacial and orthopedic surgeons should be aware of this situation. CRONJ should be on the suspect list in patients with COVID-19. Measures that are useful in the treatment carried out, as well as some measures recommended in the literature, were discussed. Surgical treatment of CRONJ appears to be an effective alternative, especially in the more aggressive cases.

A Young Woman with Common Variable Immunodeficiency: The Role of Thorough Medical History and Physical Examination in Accurate Diagnosis.

Common variable immunodeficiency (CVID) is a rare immunodeficiency syndrome which presents with wide manifestations leading to delayed diagnosis. A 34-year-old woman presented to our hospital complaining of dyspnea and productive cough. Lung CT scan revealed loculated right-sided pleural effusion with bronchiectasis and consolidation in right lower lobes. After taking medical history and physical examination, we suspected CVID and ordered serum immunoglobulin levels. The laboratory results were in line with CVID diagnosis and showed decreased levels of IgG, IgM, and IgA. The patient was started on intravenous immune globulin (IVIG) therapy every month. After 3-month follow-up, the patient reported no problem and felt better.

The Role of Local Angiotensin II/Angiotensin Type 1-receptor Mechanisms in Adipose Tissue Dysfunction to Promote Pancreatic Cancer.

Obesity and adipose tissue dysfunction are important risk factors for pancreatic cancer. Pancreatic cancer is one of the most lethal cancers globally. The renin-angiotensin system (RAS) is expressed in many tissues, including adipose tissue. Dysregulation of angiotensin II and angiotensin II receptors in adipose tissue through the activation of different signaling pathways leads to adipose tissue dysfunction, including insulin resistance, adipose tissue inflammation, adipocytokines secretion, and metabolic alterations. The pathogenesis of pancreatic cancer remains uncertain. However, there is evidence that dysregulation of local angiotensin II in adipose tissue that occurs in association with obesity is, in part, responsible for the initiation and progression of pancreatic cancer. Due to the role of local angiotensin II in the dysfunction of adipose tissue, angiotensin receptor blockers may be considered a new therapeutic strategy in the amelioration of the complications related to adipose tissue dysfunction and prevention of pancreatic cancer. This review aims to consider the biological roles of local angiotensin II and angiotensin II receptors in adipose tissue dysfunction to promote pancreatic cancer progression with a focus on adipose tissue inflammation and metabolic reprogramming.

Elucidating the Role of Pro-renin Receptors in Pancreatic Ductal Adenocarcinoma Progression: A Novel Therapeutic Target in Cancer Therapy.

Pancreatic cancer is a highly aggressive malignancy with a very poor prognosis. The 5- year survival in these patients is very low, and most patients develop drug resistance to current therapies, so additional studies are needed to identify the potential role of new drug targets for the treatment of pancreatic cancer. Recent investigations have been performed regarding the roles of pro-renin receptors (PRR) in the initiation and development of cancers. PRR is a component of the local renin-angiotensin system (RAS). Local tissue RAS has been known in diverse organ systems, including the pancreas. Various investigations have implicated that PRRs are associated with the upregulation of various signaling pathways, like the renin-angiotensin system pathway, PI3K/Akt/mTOR, and the Wnt-signaling pathways, to contribute to pathological conditions, including cancer. In this review, we presented an overview of the role of PRR in the progression of pancreatic adenocarcinoma.

Targeting Lysyl Oxidase as a Potential Therapeutic Approach to Reducing Fibrotic Scars Post-operatively: Its Biological Role in Post-Surgical Scar Development.

Abdominal and pelvic surgery, or any surgical injury of the peritoneum, often leads to chronic abdominal adhesions that may lead to bowel obstruction, infertility, and pain. Current therapeutic strategies are usually ineffective, and the pathological mechanisms of the disease are unclear. Excess collagen cross-linking is a key mediator for extra-cellular matrix deposition and fibrogenesis. Lysyl oxidase is a key enzyme that catalyzes the formation of stabilizing cross-links in collagen. Dysregulation of Lysyl oxidase (Lox) expressing upregulates collagen cross-linking, leading ECM deposition. Tissue hypoxia during surgery induces molecular mechanisms and active transcription factors to promote the expression of several genes related to inflammation, oxidative stress, and fibrosis, such as transforming growth factor beta, and Lox. Studies have shown that targeting Lox improves clinical outcomes and fibrotic parameters in liver, lung, and myocardial fibrosis, therefore, Lox may be a potential drug target in the prevention of postsurgical adhesion.

Review the Role of Metabolism Reprogramming in the Pathogenesis of Post-surgical Adhesion: A New Therapeutic Strategy.

Metabolic reprogramming is defined as the skill of cells to change their metabolism to support the induced energy demand due to continuous growth. Metabolic reprogramming is a well- known occurrence in the progression of neoplastic cells, although, evidence has shown that it is present in fibrotic disorders. Post-surgical adhesion as a fibrotic disorder is a medical challenge and is defined by fibrotic bands connected between organs with the abdominal wall. Despite many investigations carried out about the pathogenesis of the disorder but there are many unknowns, therefore, targeting special pathways may have the potential to prevent the formation of fibrotic bands post-operative. Glycolysis is a necessary metabolic pathway in living cells. In hypoxic conditions, it is the dominant pathway in the production of energy for different types of cells such as fibroblasts, immune cells, and endothelial cells. Also, glycolysis is a main downstream target for transforming growth factor ß (TGF-ß) and upregulates during fibrotic conditions. Furthermore, this is noteworthy that hypoxia induces factor 1 alpha (HIF-1α) as a transcription factor, elevated during the hypoxia condition stimulates different signaling pathways such as TGF-ß/SMAD, nuclear factor kappa B (NF-kB), and mTOR pathway to control glycolytic metabolism and T-cell trafficking for immune cell migration. Different evidence has indicated that the administration of glycolytic inhibitors has the potential to prevent the development of fibrotic markers. In this review, we pointed out the role of the glycolysis pathway and its connection to profibrotic cytokines to promote inflammatory and fibrotic pathways. Based on the results of studies related to fibrotic disorders we hypothesized that targeting glycolysis may have therapeutic potential in the prevention of postoperative adhesions.

The Association between Circulating Adipocytokine Omentin Levels and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver condition worldwide. NAFLD is often associated with features of Metabolic Syndrome such as obesity and insulin resistance. METHOD: The current comprehensive meta-analysis was performed to evaluate the association between circulating Omentin levels and NAFLD. A systematic search in Scopus, Web of Science, PubMed, and Google Scholar databases was conducted to identify relevant studies up until 5th May 2022. The standard mean difference (SMD) values and 95% confidence intervals (CIs) were computed for the association of Omentin levels with NAFLD risk in a random effect model. RESULT: The meta-analysis involved 6 case-control studies with a total of 371 cases and 269 controls. Pooled SMD showed no significant difference in serum Omentin between NAFLD and healthy groups (SMD= -0.047 and 95% CI -0.957_0.862 P=0.91). Subgroup analysis based on sample size showed that the average Omentin levels were significantly higher in NAFLD patients in studies with sample size ≥70 (SMD=0.356 CI 0.056_0.655 P=0.02). CONCLUSION: Additional well-designed studies with more sample sizes are essential to clarify the potential role of Omentin as a risk marker of NAFLD.

Efficacy and safety of an inactivated virus-particle vaccine for SARS-CoV-2, BIV1-CovIran: randomised, placebo controlled, double blind, multicentre, phase 3 clinical trial.

OBJECTIVE: To report the efficacy, safety, and exploratory immunogenicity findings of two 5 µg doses of the BIV1-CovIran vaccine. DESIGN: Randomised, placebo controlled, double blind, multicentre, phase 3 clinical trial. SETTING: In six cities of Iran, including Bushehr, Isfahan, Karaj, Mashhad, Shiraz, and Tehran. The first vaccine or placebo injection of the first participant was on 16 May 2021 in Tehran. The last vaccine or placebo injection of the last participant occurred on 15 July 2021 in Isfahan. PARTICIPANTS: 20 000 participants aged 18-75 years were randomly assigned to the intervention or placebo groups with a ratio of 2:1. INTERVENTION: 5 µg vaccine or placebo with the interval of 28 days. MAIN OUTCOME MEASURES: Vaccine efficacy for a 90 day follow-up period, safety and explanatory immunogenicity assessment, and variant detection during the trial. RESULTS: 20 000 participants were recruited and randomly assigned to receive BIV1-CovIran (n=13 335 (66.7%)) or placebo (n=6665 (33.3%)). Participants' mean age was 38.3 (standard deviation 11.2) years, and 6913 (34.6%) were female. Among vaccinated participants that had covid-19 reported during the follow-up (median 83 days), 758 (5.9%) had symptoms, 144 (1.1%) had severe infection, and seven (0.1%) were critical. Among participants who received placebo during the follow-up, 688 (10.7%) had symptoms, 221 (3.4%) had severe infection, and 19 (0.3%) were critical. Overall efficacy was 50.2% (95% confidence interval 44.7% to 55.0%) against symptomatic covid-19, 70.5% (63.7% to 76.1%) against severe disease, and 83.1% (61.2% to 93.5%) against critical cases. Two deaths were reported in the efficacy population in the placebo group, no deaths were from the intervention group. During follow-up, 41 922 adverse events were reported: 28 782 (68.7%) were adverse reactions, of which 19 363 (67.3%) were in the intervention group. Most adverse reactions were mild or moderate in severity (grade 1 or 2) and self-limiting. No serious adverse events were related to the injections. For variant investigation, of 119 participants positive for the SARS-CoV-2 variant, 106 (89.1%) were positive for the delta variant. CONCLUSIONS: A two dose regimen of the BIV1-CovIran vaccine conferred efficacy of 50.2% against symptomatic covid-19, 70.5% against severe disease, and 83.1% against critical disease. Vaccination was well tolerated, with no safety concerns raised. TRIAL REGISTRATION: Iranian Registry of Clinical Trials, IRCT20201202049567N3. FUNDING: Shifa-Pharmed Industrial Group.

Complications and Efficacy of Sinopharm Vaccine among Liver and Kidney Transplantation.

BACKGROUND: There are various vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, vaccination may lead to some complications. OBJECTIVE: This study aimed to investigate the complications of transplant recipients who received the Sinopharm COVID-19 vaccine. METHODS: This was a retrospective cross-sectional study conducted among 667 transplant recipients (211 liver transplant recipients and 456 kidney transplant recipients) who received the Sinopharm COVID-19 vaccine from March to August 2021 and had medical records in Montaserieh Hospital, affiliated to Mashhad University of Medical Sciences, Mashhad, Iran. The demographic and clinical information, as well as patient's symptoms after each dose of the vaccine, were recorded. RESULTS: Only 16.8% and 13.7% of the patients experienced some symptoms following the first and second doses of the Sinopharm vaccine, respectively. No significant difference was observed between patients younger than 50 years and those aged 50 years and over in terms of the complication rate of the Sinopharm vaccine (P>0.005). Vaccine failure was reported in 10% of the cases; however, the mortality rate due to infection with the Delta variant of COVID-19 in this population was reported to be 0.7%. CONCLUSION: Based on the obtained results, adverse reactions of the Sinopharm COVID-19 vaccine are generally mild, predictable, and non-life-threatening both in the first and second doses. Vaccine failure was reported in 10% of the cases; however, mortality due to infection with the Delta variant of COVID-19 was reported in less than 1% of the cases.

Efficacy of Sinopharm Vaccine Among Stem Cell Transplant Recipients During Two Peaks of Delta and Omicron variants of COVID-19.

BACKGROUND: Considering the dearth of research on the complications of Sinopharm coronavirus disease 2019 (COVID-19) vaccine in immunocompromised individuals and the lack of available data on COVID-19 vaccination from Iran. OBJECTIVE: This study aimed to investigate the efficacy of vaccine of Sinopharm COVID-19 vaccine and its complications in bone marrow transplant (BMT) recipients. METHODS: This was a retrospective cross-sectional study conducted on 250 patients with BMT who were referred to Montaserieh Hospital, Mashhad, Iran. Among them, 53 cases who received at least two doses of Sinopharm COVID-19 vaccine from March to January 2021 were entered in this study. The data were extracted from a student dissertation (Code:4000370). RESULTS: Sinopharm vaccine side effects were reported only in 7.7% of the patients, and shingles was the only serious side effect of the Sinopharm vaccine, which was observed only in one case. The results also revealed that Sinopharm COVID-19 vaccine side effects were not related to age or gender. Infection with the Delta variant of COVID-19 was reported in 7.5% (n=4) and no mortality was reported among them. Vaccine failure was reported in 39.6% of the cases; however, no mortality was reported among patients infected with the Omicron variant of COVID-19. CONCLUSION: In summary, it seems that Sinopharm COVID-19 vaccine adverse effects were not serious among stem cell transplant recipients. However, it may lead to some severe complications in the population. Vaccine failure against the Delta and Omicron variants of COVID-19 has been reported among more than one-third of BMT patients; however, no mortality was observed among BMT patients infected with the new variants of COVID-19.

The relationship between cumulative dose of immunosuppressive agents and COVID-19-associated mucormycosis: A multicenter cross-sectional study.

Background and Aims: Immunosuppressive therapy has a key role in developing coronavirus disease-2019 (COVID-19)-associated mucormycosis. In this study, we investigated the effect of the type and cumulative dose of immunosuppressive agents on COVID-19-associated mucormycosis. Methods: We designed a descriptive cross-sectional study involving three COVID-19 hospitals in Iran. Clinical and demographic data were gathered from the medical records and checked by two independent researchers to minimize errors in data collection. Results: Seventy-three patients were included in the study. The mean age of cases was 57.41 (SD = 12.64) and 43.8% were female. Among patients, 20.5% were admitted to the intensive care unit (ICU) during COVID-19. Furthermore, 17 patients (23.29%) had a history of diabetes mellitus. Sixty-nine patients (94.52%) had a history of receiving corticosteroids (dexamethasone) during treatment of COVID-19, and of those, five patients (6.85%) received Tocilizumab beside. The mean cumulative dose of corticosteroids prescribed was 185.22 mg (SD = 114.738). The average cumulative dosage of tocilizumab was 720 mg (SD = 178.89). All of the included patients received amphotericin B for mucormycosis treatment, and 42 survived (57.53%). Also, there was a significant relationship between hospitalization in ICU for COVID-19 and the mucormycosis outcome (p = 0.007). However, there weren't any significant associations between cumulative doses of immunosuppressive drugs and mucormycosis outcome (p = 0.52). Conclusion: The prevalence of COVID-19-associated mucormycosis is increasing and should be considered in the treatment protocols of COVID-19. Controlling risk factors such as diabetes, malignancy and the administration of immunosuppressive agents based on recommended dosage in validated guidelines are ways to prevent mucormycosis.

Simultaneous occurrence of knee septic arthritis and coronavirus disease 2019 (COVID-19): A case report.

Background: Coronavirus disease 2019 (COVID-19) pandemic is increasingly recognized as a serious, worldwide public health concern. Most of the patients with COVID-19 are asymptomatic or show mild symptoms. It is important to identify the unusual manifestations and their long-term complication. Case presentation: A case of COVID-19 in 45 years old man with septic arthritis due to Staphylococcus aureus is presented. COVID-19 was diagnosed using real-time polymerase chain reaction without obvious clinical manifestation. The patient had no history of trauma or inflammatory arthritis and had progressive left knee pain and limitation of movement. Knee X-ray was normal. Aspiration of the knee joint fluid showed a cloudy and purulent appearance. The patient was admitted to hospital and immediately treated with vancomycin 1gr/12 hr. A polymerized chain reaction (PCR) test for COVID-19 was performed, which was positive 24 h after hospitalization. Staphylococcus aureus was reported in synovial fluid culture which was sensitive to vancomycin and ciprofloxacin, thus vancomycin was continued. On the 4th day of hospitalization the patient had cough, therefore underwent CT scan lungs and ground-glass opacities (GGO) characteristic of COVID-19 were noticed. Favipiravir and interferon were started. Patient's knee aspiration was performed for 5 consecutive days. On the 6th day of hospitalization, joint fluid markedly decreased and the patient's oxygen saturation was 96%. One week after hospitalization, the patient was discharged and a month later knee examination was completely normal. Conclusions: Septic arthritis should be considered in the manifestations or co-morbidity of COVID-19 patients with joint pain, swelling or redness.

COVID-19 cases, hospitalizations and deaths after vaccination: a cohort event monitoring study, Islamic Republic of Iran.

Objective: To investigate the incidence of coronavirus disease 2019 (COVID-19) cases, hospitalizations and deaths in Iranians vaccinated with either AZD1222 Vaxzevria, CovIran® vaccine, SARS-CoV-2 Vaccine (Vero Cell), Inactivated (lnCoV) or Sputnik V. Methods: We enrolled individuals 18 years or older receiving their first COVID-19 vaccine dose between April 2021 and January 2022 in seven Iranian cities. Participants completed weekly follow-up surveys for 17 weeks (25 weeks for AZD1222) to report their COVID-19 status and hospitalization. We used Cox regression models to assess risk factors for contracting COVID-19, hospitalization and death. Findings: Of 89 783 participants enrolled, incidence rates per 1 000 000 person-days were: 528.2 (95% confidence interval, CI: 514.0-542.7) for contracting COVID-19; 55.8 (95% CI: 51.4-60.5) for hospitalization; and 4.1 (95% CI: 3.0-5.5) for death. Compared with SARS-CoV-2 Vaccine (Vero Cell), hazard ratios (HR) for contracting COVID-19 were: 0.70 (95% CI: 0.61-0.80) with AZD1222; 0.73 (95% CI: 0.62-0.86) with Sputnik V; and 0.73 (95% CI: 0.63-0.86) with CovIran®. For hospitalization and death, all vaccines provided similar protection 14 days after the second dose. History of COVID-19 protected against contracting COVID-19 again (HR: 0.76; 95% CI: 0.69-0.84). Diabetes and respiratory, cardiac and renal disease were associated with higher risks of contracting COVID-19 after vaccination. Conclusion: The rates of contracting COVID-19 after vaccination were relatively high. SARS-CoV-2 Vaccine (Vero Cell) provided lower protection against COVID-19 than other vaccines. People with comorbidities had higher risks of contracting COVID-19 and hospitalization and should be prioritized for preventive interventions.

Cytomegalovirus pneumonia in an immunosuppressed sarcoidosis patient; a rare case of cytomegalovirus infection in a sarcoidosis patient.

BACKGROUND: Sarcoidosis is a multisystemic granulomatosis disease that is mostly treated with immunosuppressive regimens. Studies demonstrated that these patients are prone to develop various infections. However, some infections including viral severe pneumonia is rare complications in sarcoidosis patients. In the present report, we described for cytomegalovirus (CMV) pneumonia in a female patient with sarcoidosis which has been successfully managed by ganciclovir. CASE PRESENTATION: Herein, we present a known case of sarcoidosis admitted to the emergency department because of fever, dyspnea, and productive cough. The patient was receiving prednisolone and methotrexate for months. The primary chest x-ray imaging revealed bilateral infiltration, especially in the upper lobes and hilar lymphadenopathy. The lung high resolution computed tomography showed a bilateral diffuse nodular pattern. After 72 hours of antimicrobial treatment, the fever was still present and the patient became a candidate for fiberoptic bronchoscopy. The gram staining of the bronchial fluid, polymerase chain reaction for tuberculosis, and PCP was also unremarkable. However, the PCR-CMV was positive. The quantitative PCR for CMV form blood sample was taken and the result came back as 3.6*103. With the impression of CMV pneumonia, a daily dose of 5mg of ganciclovir was prescribed. After 3 weeks of receiving 5mg/kg of ganciclovir twice daily (600mg daily), clinical symptoms, and dyspnea improved. Also, the radiological findings improved. CONCLUSION: In the present report, we demonstrated that sarcoidosis patients' receiving immunosuppressives are prone to develop CMV pneumonia, and fever and dyspnea were the alarm signs of CMV pneumonia is our patient which was successfully managed by ganciclovir.

Subcutaneous tocilizumab in adults with severe and critical COVID-19: A prospective open-label uncontrolled multicenter trial.

Potential therapeutic approaches in coronavirus disease 2019 (COVID-19) comprise antiviral and immunomodulatory agents; however, no immunomodulator drug has been approved. This multicenter, prospective, open-label, uncontrolled study aimed to assess the use of subcutaneous tocilizumab in adult patients with severe and critical COVID-19. Tocilizumab was added to the standard care of therapy at a dose of 324 mg (<100 kg bodyweight) or 486 mg (≥100 kg bodyweight). The study endpoints were all-cause mortality rate, changes in oxygen-support level, oxygen saturation, body temperature, respiratory rate, and laboratory variables during the study, and drug safety. Of 126 patients enrolled, 86 had severe and 40 had critical disease. Most patients were male (63.49%) and aged below 65 (78.57%). By day 14 of the study, 4.65% (4/86) of severe patients and 50.00% (20/40) of critical patients died. By the end, 6.98% (6/86) of severe patients and 60.00% (24/40) of critical patients died.Outcomes concerning three additional endpoints (oral temperature, oxygen saturation, and respiratory rate)were significantly improved as early as three days after tocilizumab administration in both groups of subjects, more considerably in severe patients. Significant improvement in the required level of oxygenation was reported in severe patients seven days after tocilizumab administration. No tocilizumab-related serious adverse event occurred in this study. Subcutaneous tocilizumab might improve some clinical parameters and reduce the risk of death in COVID-19 patients, particularly if used in the early stages of respiratory failure.

Ocular Manifestations of Hospitalized Patients with COVID-19 in Northeast of Iran.

PURPOSE: To evaluate ocular findings in patients with Coronavirus Disease 2019 (COVID-19) in the Northeast of Iran. METHODS: In a cross-sectional, observational study all consecutive patients with confirmed COVID-19 diagnosis at the central referral center of these patients in northeast of Iran were included. Ocular examinations (external and slit) were randomly performed for the patients who were admitted to the Intensive Care Unit (ICU) and six COVID wards of the hospital. Moreover, Chart records and serum chemistry results were collected. RESULTS: A total of 142 patients with the mean age of 62.6 ± 15 years (range: 23-96 years) and almost equal gender distribution (male: N = 77, 54.2%) were included in the study. During the initial external examination by the ophthalmologist, 44 (31%) patients were found to have conjunctival hyperemia and 22 (15.5%) patients had chemosis. Consecutive slit examination showed 41 (28.9%) conjunctival hyperemia, 22 (15.5%) chemosis, 11 (7.7%) cataract, and 9 (6.3%) diabetic retinopathy. The patients with at least one ocular manifestation had significantly higher blood urea levels at the time of admission compared to those with no obvious ocular involvement (median: 41.5, IQR: 28-66.3 vs. median: 33, IQR: 23.8-51.8, P = .023). Moreover, a significant difference was observed in the total white blood cell count, lymphocyte percent, neutrophil count, Erythrocyte Sedimentation Rate (ESR), and blood urea level between patients with positive and negative Polymerase Chain Reaction (PCR) for SARS-CoV-2 virus. None of the patients reported ocular symptoms prior to systemic involvement. The proportion of patients with at least one ocular manifestation was significantly higher in those admitted in the ICU compared to the non-ICU wards. wards. While conjunctival hyperemia was the most prevalent ocular finding in all patients, chemosis was the most common ocular manifestation in ICU admitted patients. CONCLUSION: Ocular manifestation was observed in more than half of our COVID-19 patients. Hence, it seems important to involve ophthalmologist in the diagnosis and management of these patients.