Emerging applications of phage therapy and fecal virome transplantation for treatment of Clostridioides difficile infection: challenges and perspectives.

Clostridioides difficile, which causes life-threatening diarrheal disease, is considered an urgent threat to healthcare setting worldwide. The current standards of care solely rely on conventional antibiotic treatment, however, there is a risk of promoting recurrent C. difficile infection (rCDI) because of the emergence of antibiotic-resistant strains. Globally, the alarming spread of antibiotic-resistant strains of C. difficile has resulted in a quest for alternative therapeutics. The use of fecal microbiota transplantation (FMT), which involves direct infusion of fecal suspension from a healthy donor into a diseased recipient, has been approved as a highly efficient therapeutic option for patients with rCDI. Bacteriophages or phages are a group of viruses that can infect and destroy bacterial hosts, and are recognized as the dominant viral component of the human gut microbiome. Accumulating data has demonstrated that phages play a vital role in microbial balance of the human gut microbiome. Recently, phage therapy and fecal virome transplantation (FVT) have been introduced as promising alternatives for the treatment of C. difficile -related infections, in particular drug-resistant CDI. Herein, we review the latest updates on C. difficile- specific phages, and phage-mediated treatments, and highlight the current and future prospects of phage therapy in the management of CDI.

Intestinal organoids: A versatile platform for modeling gastrointestinal diseases and monitoring epigenetic alterations.

Considering the significant limitations of conventional 2D cell cultures and tissue in vitro models, creating intestinal organoids has burgeoned as an ideal option to recapitulate the heterogeneity of the native intestinal epithelium. Intestinal organoids can be developed from either tissue-resident adult stem cells (ADSs) or pluripotent stem cells (PSCs) in both forms induced PSCs and embryonic stem cells. Here, we review current advances in the development of intestinal organoids that have led to a better recapitulation of the complexity, physiology, morphology, function, and microenvironment of the intestine. We discuss current applications of intestinal organoids with an emphasis on disease modeling. In particular, we point out recent studies on SARS-CoV-2 infection in human intestinal organoids. We also discuss the less explored application of intestinal organoids in epigenetics by highlighting the role of epigenetic modifications in intestinal development, homeostasis, and diseases, and subsequently the power of organoids in mirroring the regulatory role of epigenetic mechanisms in these conditions and introducing novel predictive/diagnostic biomarkers. Finally, we propose 3D organoid models to evaluate the effects of novel epigenetic drugs (epi-drugs) on the treatment of GI diseases where epigenetic mechanisms play a key role in disease development and progression, particularly in colorectal cancer treatment and epigenetically acquired drug resistance.

Detection of SARS-CoV-2 RNA in selected agricultural and food retail environments in Tehran, Iran.

The SARS-CoV-2 pandemic has and continues to impose a considerable public health burden. Although not likely foodborne, SARS-CoV-2 transmission has been well documented in agricultural and food retail environments in several countries, with transmission primarily thought to be worker-to-worker or through environmental high touch surfaces. However, the prevalence and degree to which SARS-CoV-2 contamination occurs in such settings in Iran has not been well documented. Furthermore, since SARS-CoV-2 has been observed to be shed in the feces of some infected individuals, wastewater has been utilized as a means of surveilling the occurrence of SARS-CoV-2 in some regions. This study aimed to investigate the presence of SARS-CoV-2 RNA along the food production and retail chain, from wastewater and irrigation water to vegetables in field and sold in retail. From September 2020 to January 2021, vegetables from different agricultural areas of Tehran province (n = 35), their irrigated agricultural water (n = 8), treated wastewater mixed into irrigated agricultural water (n = 8), and vegetables collected from markets in Tehran (n = 72) were tested for the presence of SARS-CoV-2 RNA. The vegetable samples were washed with TGBE buffer and concentrated with polyethylene glycol precipitation, while water samples were concentrated by an adsorption-elution method using an electronegative filter. RT-qPCR targeting the SARS-CoV-2 N and RdRp genes was then conducted. SARS-CoV-2 RNA was detected in 51/123 (41.5%) of the samples overall. The presence of SARS-CoV-2 RNA in treated wastewater, irrigation water, field vegetables, and market produce were 75, 37.5, 42.85, and 37.5%, respectively. These results indicate that SARS-CoV-2 RNA is present in food retail and may also suggest that produce can additionally be contaminated with SARS-CoV-2 RNA by agricultural water. This study demonstrates that SARS-CoV-2 RNA was detected in waste and irrigation water, as well as on produce both in field and at retail. However, more evidence is needed to understand if contaminated irrigation water causes SARS-CoV-2 RNA contamination of produce, and if there is a significant public health risk in consuming this produce.

High prevalence of SARS-Coronavirus-2 in patients with inflammatory bowel disease and the role of soluble angiotensin converting Enzyme2.

Context: Patients with inflammatory bowel disease (IBD) were found to have the higher intestinal expression of Angiotensin-Converting Enzyme2 (ACE2) that could consequently increase susceptibility to COVID-19 infection.Objective: This study reports the outcomes of COVID-19 infection in a large cohort of IBD patients. We compare levels of serum ACE and IFN-α between COVID19 patients with and without IBD. We performed a cross-sectional retrospective multicenter study.Methods: We enrolled patients with IBD screened for SARS-COV-2 in six medical centres in Iran from June to November 2020. The blood samples were drawn to measure COVID-19 IgM and IgG, and serum levels of sACE2, sACE1, and interferon-α, regardless of suspicious symptoms have done the molecular test.Results: A total of 534 IBD patients were included in the study. Of these, 109 (20.0%) cases had detectable IgG and IgM against SARS-CoV-2. sACE2 levels were higher in IBD patients than controls, whereas ACE1and IFN-α levels were similar among groups.

Serological response to SARS-CoV-2 is attenuated in patients with inflammatory bowel disease and can affect immunization.

In this study we indicated that impaired serological responses to SARS-CoV-2 infection among patients with IBD, could have significant implications for this group of patients and should be considered in vaccination program.

Association of SARS-CoV-2 presence in sewage with public adherence to precautionary measures and reported COVID-19 prevalence in Tehran.

Compared to the growing body of literature on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection and quantification in sewage, there are limited studies reporting on correlations between the viral loads in sewage and the prevalence of infected patients. The present work is a part of the regular monitoring effort for SARS-CoV-2 in wastewater influents from seven wastewater treatment plants (WWTPs) in Tehran, Iran, starting from late September 2020 until early April 2021. These facilities cover ~64% of the metropolis serving >5000,000 M individuals. The study set out to track the trends in the prevalence of COVID-19 in the community using wastewater based epidemiology (WBE) and to investigate whether these measurements correlate with officially reported infections in the population. Composite sewage samples collected over 16 h were enriched by polyethylene glycol precipitation and the corresponding threshold cycle (Ct) profiles for CDC 'N' and 'ORF1ab' assays were derived through real time RT-qPCR. Monte Carlo simulation model was employed to provide estimates of the disease prevalence in the study area. RNA from SARS-CoV-2 was detectable in 100% ('N' assay) and 81% ('ORF1ab' assay) of totally 91 sewage samples, with viral loads ranging from 40 to 45,000 gene copies/L. The outbreak of COVID-19 positively correlated (R2 = 0.80) with the measured viral load in sewage samples. Furthermore, sewage SARS-CoV-2 RNA loads preceded infections in the population by 1 to 2 days, which were in line with public adherence with and support for government instructions to contain the pandemic. Given the transient presence of human host-restricted infections such as SARS-CoV-2, these results provide evidence for assessment of the effectiveness of coordinated efforts that specifically address public health responses based on wastewater-based disease surveillance against not only COVID-19 but also for future infectious outbreaks.

Evaluation of miR-200c-3p and miR-421-5p levels during immune responses in the admitted and recovered COVID-19 subjects.

Angiotensin-converting enzyme 2 (ACE2) acts as a key receptor for the spike of SARS-CoV-2. Two main microRNAs (miRs), miR-200c-3p and miR-421-5p, are considered to modulate the expression of ACE2 gene and alterations in the expression of these miRNAs may influence the outcomes of COVID-19 infection. Accordingly, we examined whether miRNAs directing ACE2 expression altered in the SARS-CoV-2 infection. 30 patients with COVID-19 included in the study. At the time of admission and discharge, the expression of miR-200c-3p and miR-421-5p, inflammatory cytokine IL-6, and regulatory T cells' expression profiles (CD4, CD25, and Foxp3) were examined using quantitative real-time PCR method. At the time of admission, the expression levels of miR-200c-3p and miR-421-5p as well as CD4, CD25, and Foxp3 significantly decreased while IL-6 expression notably enhanced. However, by the time of discharge, the expression levels of the genes were opposite to the time of admission. Moreover, Pearson correlation analysis indicated that IL-6 expression negatively correlated with Foxp3 and miR-200c-3p expressions despite miR-421-5p and miR-200c-3p positively correlated at admission time. By manipulating miR-200c-3p and miR-421-5p expressions and controlling the ACE2 level, it is plausible to modulate the inflammation by reducing IL-6 and maintenance tolerance hemostasis during COVID-19 infection.

How Does COVID-19 Pandemic Impact on Incidence of Clostridioides difficile Infection and Exacerbation of Its Gastrointestinal Symptoms?

Coronavirus disease 2019 (COVID-19) has rapidly spread all over the world with a very high rate of mortality. Different symptoms developed by COVID-19 infection and its impacts on various organs of the human body have highlighted the importance of both coinfections and superinfections with other pathogens. The gastrointestinal (GI) tract is vulnerable to infection with COVID-19 and can be exploited as an alternative transmission route and target for virus entry and pathogenesis. The GI manifestations of COVID-19 disease are associated with severe disease outcomes and death in all age groups, in particular, elderly patients. Empiric antibiotic treatments for microbial infections in hospitalized patients with COVID-19 in addition to experimental antiviral and immunomodulatory drugs may increase the risk of antibiotic-associated diarrhea (AAD) and Clostridioides difficile infection (CDI). Alterations of gut microbiota are associated with depletion of beneficial commensals and enrichment of opportunistic pathogens such as C. difficile. Hence, the main purpose of this review is to explain the likely risk factors contributing to higher incidence of CDI in patients with COVID-19. In addition to lung involvement, common symptoms observed in COVID-19 and CDI such as diarrhea, highlight the significance of bacterial infections in COVID-19 patients. In particular, hospitalized elderly patients who are receiving antibiotics might be more prone to CDI. Indeed, widespread use of broad-spectrum antibiotics such as clindamycin, cephalosporins, penicillin, and fluoroquinolones can affect the composition and function of the gut microbiota of patients with COVID-19, leading to reduced colonization resistance capacity against opportunistic pathogens such as C. difficile, and subsequently develop CDI. Moreover, patients with CDI possibly may have facilitated the persistence of SARS-CoV-2 viral particles in their feces for approximately one month, even though the nasopharyngeal test turned negative. This coinfection may increase the potential transmissibility of both SARS-CoV-2 and C. difficile by fecal materials. Also, CDI can complicate the outcome of COVID-19 patients, especially in the presence of comorbidities or for those patients with prior exposure to the healthcare setting. Finally, physicians should remain vigilant for possible SARS-CoV-2 and CDI coinfection during the ongoing COVID-19 pandemic and the excessive use of antimicrobials and biocides.

Toward finding the difference between untreated celiac disease and COVID-19 infected patients in terms of CD4, CD25 (IL-2 Rα), FOXP3 and IL-6 expressions as genes affecting immune homeostasis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is defined as an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 and celiac disease (CD) is one of the autoimmune multiorgan diseases, which can be accompanied by an increased risk of viral infections. CD patients, especially untreated subjects, may be at greater risk of infections such as viral illnesses. Interleukin (IL)-6, CD4, CD25, and FOXP3 are known as genes affecting immune homeostasis and relate to the inflammation state. This study aimed to compare the expression levels of aforementioned genes in peripheral blood samples of CD and severe COVID-19 patients. METHODS: Sixty newly diagnosed CD patients with median age (mean ± SD) of 35.40 ± 24.12 years; thirty confirmed severe COVID-19 patients with median age (mean ± SD) of 59.67 ± 17.22, and 60 healthy subjects with median age (mean ± SD) of 35.6 ± 13.02 years; were recruited from March to September 2020. Fresh whole blood samples were collected, total RNA was obtained and cDNA synthesis was carried out. RNA expression levels of IL-6, CD4, CD25, and FOXP3 genes were assessed using real-time quantitative RT-PCR according to the 2-∆∆Ct formula. Statistical analysis was performed using SPSS (V.21) and GraphPad, Prism (V.6). RESULTS: While increased expression of CD4, CD25, and FOXP3 was observed in CD patients compared to the control group (p = 0.02, p = 0.03, and p < 0.0001 respectively) and COVID-19 patients group (p < 0.0001 for all of them), their expression levels in COVID-19 patients decreased compared to controls (p < 0.0001, p = 0.01, p = 0.007, respectively). Increased IL-6 expression was observed in both groups of patients compared to controls (p < 0.0001 for both of them). CONCLUSIONS: Although untreated CD patients may be at greater risk of developing into severe COVID-19 if they are infected by SARS-CoV-2 virus (due to their high expression of IL-6), increased expression of anti-inflammatory markers in these patients may be beneficial for them with the ability of reducing the severity of COVID-19 disease, which needs to be proven in future studies involving celiac patients infected with COVID-19.

Prognostic Factors Associated with Survival in Patients Infected with COVID-19: A Retrospective Study on 214 Patients from Iran.

BACKGROUND: Decision-making on allocating scarce medical resources is crucial in the context of a strong health system reaction to the coronavirus disease 2019 (COVID-19) pandemic. Therefore, understanding the risk factors related to a high mortality rate can enable the physicians for a better decision-making process. METHODS: Information was collected regarding clinical, demographic, and epidemiological features of the definite COVID-19 cases. Through Cox regression and statistical analysis, the risk factors related to mortality were determined. The Kaplan-Meier curve was used to estimate survival function and measure the mean length of living time in the patients. RESULTS: Among about 3000 patients admitted in the Taleghani hospital as outpatients with suspicious signs and symptoms of COVID-19 in 2 months, 214 people were confirmed positive for this virus using the polymerase chain reaction (PCR) technique. Median time to death was 30 days. In this population, 24.29% of the patients died and 24.76% of them were admitted to the ICU (intensive care unit) during hospitalization. The results of Multivariate Cox regression Analysis showed that factors including age (HR, 1.031; 95% CI, 1.001-1.062; P value=0.04), and C-reactive protein (CRP) (HR, 1.007; 95% CI, 1.000-1.015; P value=0.04) could independently predict mortality. Furthermore, the results showed that age above 59 years directly increased mortality rate and decreased survival among our study population. CONCLUSION: Predictor factors play an important role in decisions on public health policy-making. Our findings suggested that advanced age and CRP were independent mortality rate predictors in the admitted patients.

Cross-talk between immune system and microbiota in COVID-19.

INTRODUCTION: Human gut microbiota plays a crucial role in providing protective responses against pathogens, particularly by regulating immune system homeostasis. There is a reciprocal interaction between the gut and lung microbiota, called the gut-lung axis (GLA). Any alteration in the gut microbiota or their metabolites can cause immune dysregulation, which can impair the antiviral activity of the immune system against respiratory viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. AREAS COVERED: This narrative review mainly outlines emerging data on the mechanisms underlying the interactions between the immune system and intestinal microbial dysbiosis, which is caused by an imbalance in the levels of essential metabolites. The authors will also discuss the role of probiotics in restoring the balance of the gut microbiota and modulation of cytokine storm. EXPERT OPINION: Microbiota-derived signals regulate the immune system and protect different tissues during severe viral respiratory infections. The GLA's equilibration could help manage the mortality and morbidity rates associated with SARS-CoV-2 infection.

The first detection of SARS-CoV-2 RNA in the wastewater of Tehran, Iran.

Following the official announcement of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide pandemic spread by WHO on March 11, 2020, more than 300,000 COVID-19 cases reported in Iran resulting in approximately 17,000 deaths as of August 2, 2020. In the present survey, we investigated the presence of SARS-CoV-2 RNA in raw and treated wastewater samples in Tehran, Iran. Untreated and treated wastewater samples were gathered from four wastewater treatment plants over a month period from June to July 2020. Firstly, an adsorption-elution concentration method was tested using an avian coronavirus (infectious bronchitis virus, IBV). Then, the method was effectively employed to survey the presence of SARS-CoV-2 genome in influent and effluent wastewater samples. SARS-CoV-2 RNA was found in 8 out of 10 treated wastewater samples utilizing a reverse transcription-quantitative polymerase chain reaction (RT-qPCR) test to detect ORF1ab and N genes. Moreover, the rate of positivity in wastewater samples increased in last sample collection that shows circulation of SARS-CoV-2 was increased among the population. In addition, the high values detected in effluent wastewater from local wastewater treatment plants have several implications in health and ecology that should be further assessed.

The characteristics of cancerous patients infected with COVID-19 in hospital setting.

INTRODUCTION: Recently, Covid 19 as a fatal virus has been known as the cause of the pandemic. Different number of the mortality rate in various societies have been reported. However, it seems the underlying comorbidities increase the risk of mortality and the severity of presentation. In this study we evaluated the pattern of presentation of COVID-19 among cancerous patients in terms of severity. METHOD: between 20th February to 22nd April of 2020, among 214 hospitalized patients because of COVID-19. 41 patients revealed the cancer as a synchronous comorbidity. These patients based on the severity of COVID-19 infection presentation were divided to mild and severe groups. Then, the demographic characteristics, manifestation and laboratory data between these groups were compared. RESULT: about 19 (46.34%) of 41 cases were categorized as severe forms of COVID-19 with malignancy. The mean age of severe groups was significantly higher (P=0.00). Dyspnea (48.78%), cough (46.34%) and myalgia (24.39%) were the most common clinical features among cancerous patients with COVID-19.  diarrhea and nearly cough caused significant effects on severe form of presentation of COVID-19 infection (P=0.05, P=0.06, respectively). Hematological cancers were the most frequent types of cancer among these patients (46.34%). White Blood Cell counts were significantly lower in severe groups (P=0.03, P=.0.06, respectively). C-reactive protein is another item that nearly significantly was higher in severe groups of cancerous patients (P=0.06). CONCLUSION: The elderly age, the positive chemotherapy history, diarrhea, cough, declined WBC, PLT and elevated CRP correlated with a severe form of this infection in malignant cases.

Risk factors related to liver injury in non-Intensive Care Unit admitted patients infected with COVID-19: A retrospective study of 102 patients.

BACKGROUND: COVID-19 targets the liver and there is no available data about liver injury due to mild to moderate form of COVID-19. In this study, we evaluated the risk factors associated with liver injury in NON-ICU admitted COVID-19 patients. METHODS: in this retrospective study, 102 eligible adult participants admitted in the ward were included. The patients with previous history of liver disease were excluded. The patients with AST or ALT or bilirubin more than normal ranges were allocated in liver injury group and patients with normal ranges of them were categorized in non-liver injury. Characteristics and laboratory data were analyzed between these two groups. RESULTS: The mean age of the population was 55.13± 17.02 years old. The most common symptom was fever (45.8%). The most frequent co-morbidity was hypertension (25%). 65 patients had liver injury (63.72%). CRP were significantly higher in liver injury group (P=0.01). Univariate analysis reported ALKP, and CRP was associated significantly with liver injury (P=0.04, OR= 1.003, Cl 95%= 1.000-1.007; P=0.03, OR= 1.009, Cl 95%= 1.000- 1.017, respectively). No independent factor was detected in multivariate analysis. Based on the Spearman's rank correlation coefficients CRP correlated significantly with AST (r=0.22, P=0.00). Moreover, neutrophil and CRP, correlated with ALT (r=0.01, P=0.90; r=0.23, P=0.02, respectively). CONCLUSION: No independent factor was detected to predict liver injury chance due to COVID-19. However, CRP had a significant association with it. It appears that the role of inflammatory pathways in liver damage was due to COVID-19.

Lethal outcome of Covid-19 pneumonia in a new liver recipient with neurological manifestation.

COVID-19 is a new contagious viral pneumonia with various signs and symptoms, including loss of consciousness, liver injury, and cerebrovascular accident; however, there is little data on the manifestation and outcome of COVID-19 in liver transplant patients. Moreover, because transplant units in Iran were closed from the first day of the COVID-19 pandemic, accurate data about nosocomial COVID-19 and the liver transplant setting is not available. In this article, we introduce a liver transplant recipient with a final fatal outcome, who had had neurological manifestations, and whose COVID-19 manifestations began in the hospital within 2 days of transplant surgery.

COVID-19 prognosis: what we know of the significance and prognostic value of liver-related laboratory parameters in SARS-CoV-2 infection.

AIM: The present study aims to evaluate the prognostic value of liver-related laboratory parameters in COVID-19. BACKGROUND: This is not the first nor will it be the last time that a member of the ß-coronaviruses wages a full-scale war against human health. Notwithstanding atypical pneumonia being the primary symptom, the emergence of severe disease mainly resulting from the injury of non-pulmonary organs leaves no alternative, in some cases, other than a dreadful death. METHODS: To provide a well-conceptualized viewpoint representing the prognostic values of liver-related laboratory parameters in COVID-19, a meta-analysis was performed with the calculation of mean difference and 95% confidence intervals of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Bili), and albumin (Alb) in severe and non-severe COVID-19 patients. RESULTS: While severe COVID-19 cases displayed higher values of ALT, AST, and Bili compared to non-severe patients (mean differences of 7.48, 12.07, and 3.07, respectively), the value of Alb was significantly lower in severe cases (mean differences of -6.15). There was also a correlation between alterations in all of the parameters; however, only correlations between ALT and Bili (R=0.98, p=0.0031), and Bili and Alb (R=-1, p=0.0012) were significant. CONCLUSION: Abnormal values of liver-related examinations outwardly contribute to reflect the progression of the disease toward an unfavorable outcome. Therefore, careful scrutiny of these parameters will provide clinicians with invaluable information regarding SARS-CoV-2 infection, at least in terms of liver injury.

Antimicrobial Resistance as a Hidden Menace Lurking Behind the COVID-19 Outbreak: The Global Impacts of Too Much Hygiene on AMR.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new coronavirus that was recently discovered in 2019. While the world is working hard to overcome and control the coronavirus disease 2019 (COVID-19) pandemic, it is also crucial to be prepared for the great impacts of this outbreak on the development of antimicrobial resistance (AMR). It is predicted that inappropriate and too much use of antibiotics, biocides, and disinfectants during this pandemic may raise disastrous effects on antibiotic stewardship programs and AMR control all around the world. Furthermore, the use of certain antibiotics alone or in combination with antiviral agents or other medications for the treatment of secondary bacterial infections among COVID-19 patients may be regarded as a major factor that negatively affects host immune response by disrupting mitochondrial function and activity. Herein, we suggest that the current management strategies to control AMR and prioritize antibiotic stewardship schemes should be extremely highlighted in relation to the COVID-19 outbreak. The rising concerns about excessive use of antimicrobials and biocides and taking too much hygiene also need to be addressed during this pandemic due to their impacts on AMR, public health, and the environment.

Fecal microbiota transplantation for COVID-19; a potential emerging treatment strategy.

At the end of 2019, an emerging outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that first reported from Wuhan, China. The first manifestations of patients infected with SARS-CoV-2 was flu-like symptoms, while other type of manifestations, especially gastrointestinal manifestations were discovered recently. As of June 2020, there is no specific drug or treatment strategy for COVID-19, a disease caused by SARS-CoV-2, so different combination of antiviral drugs is currently being used. Gut microbiota mostly consists of four phyla, including Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. The interaction between gut microbiota and immune system through releasing some cytokines such as IL-1ß, IL-2, IL-10, TNF-α, and IFN-γ that play roles in the severity of COVID-19. In this article, a new potential treatment for COVID-19 by fecal microbiota transplantation (FMT) is described. FMT revealed promising results in different diseases, especially recurrent clostridium difficile infection, and it might reduce length of hospital admission and severity of the disease by modification of gut microbiota composition.

Presence of SARS-CoV-2 in the air of public places and transportation.

This study investigated the presence of SARS-CoV-2 in air of public places such as shopping centers, a post office, banks, governmental offices, and public transportation facilities including an airport, subways, and buses in Tehran, Iran. A total of 28 air samples were collected from the eight groups of public and transportation locations. The airborne particle samples were collected on PTFE or glass fiber filters using two types of samplers with flow rates of 40 and 3.5 L/min, respectively. The viral samples were leached and concentrated, and RNA was extracted from each. The presence of viral RNA was evaluated using novel coronavirus nucleic acid diagnostic real time PCR kits. In 64% of the samples, SARS-CoV-2 RNA (62% and 67% from the public places and transportation, respectively) was detected. Positive samples were detected in banks (33%), shopping centers (100%), governmental offices (50%), the airport (80%), subway stations (50%), subway trains (100%), and buses (50%). Logistic regression showed that number of people present during the sampling and the sampled air volume were positively associated with presence of SARS-CoV-2; while the percentage of people with masks, air temperature, and sampling site's volume were negatively related to SARS-CoV-2's presence. However, none of these associations were statistically significant. This study showed that most public places and transportation vehicles were contaminated with SARS-CoV-2. Thus, strategies to control the spread of COVID-19 should include reducing the number of people in indoor spaces, more intense disinfection of transport vehicles, and requiring people to wear masks.