The 2019 novel coronavirus is another type of known coronaviruses; SARS-CoV-1 and MERS-CoV. The World Health Organization (WHO) has named the virus SARS-CoV-2 and its disease as coronavirus disease 2019 (abbreviated COVID-19). The first case of COVID-19 was reported in December 2019 in Wuhan, China. The epidemiological studies have shown that the disease is transmitted from animal to human, and the spread of the disease from person to person is rapidly expanding. Currently, the most important factor in preventing and controlling the spread of the disease is proper recognition, health care, and control measures. Given the importance of early detection and timely treatment of the disease, the use of nanoscale materials for the production of sensors and drug delivery system can be of great assistance to the researchers. In this context, we aimed to explain the effects of the prevalence of the disease worldwide and consider the different aspects of SARS-CoV-2.

Coronaviruses are a large family of viruses that usually cause mild to moderate upper respiratory tract illnesses. The newly emerged sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in late 2019 and causes coronavirus disease 2019 (COVID-19). Due to the novelty of the virus, new scientific evidence on various aspects of COVID-19 is reported in the literature continuously.Common symptoms of COVID-19 include fever, dry cough, fatigue, myalgia, arthralgia and Shortness of breath. Some articles have also reported on various manifestations of SARS-CoV-2 infection outside the respiratory tract. The affected organs are gastrointestinal tract, central nervous system, skin, olfactory system, cardiovascular system, liver, kidney and eye.The summary of extra pulmonary involvements by COVID-19 are anosmia, ageusia, erythematous rash, chickenpox-like blisters, acute cardiac injury with increased cardiac troponin levels, inflammation and edema of the renal parenchyma, gastrointestinal symptoms such as diarrhea and vomiting, abnormal liver function with increased levels of alanine and aspartateaminotransferase and neurologic symptoms ranging from headache to stroke. The hypothetical pathophysiologic mechanisms of systemic manifestations of COVID-19 are overproduction of cytokines (cytokine storm), hypoxemia, direct SARS-CoV-2 damage or combination of these mechanisms. Further studies are needed to demonstrate the relationship between outcome of COVID-19 and pathogenesis.

Background & Aims :

The development of the brain as the most complex structure of the human body is a long process that begins in the third week of pregnancy and continues until adulthood and even until the end of life (1). Human brain myelination begins one to two months before birth in the visual system and eventually lasts until the age of two in other sensory systems and then the motor systems (4). Processes associated with normal brain development involve a wide range of molecular events, including the expression of genes and environmental events (1). If the brain is exposed to some environmental factors, its normal development will be disrupted (2) because the fetus is very sensitive to physical and chemical disruptive factors in different stages (5). Generally, factors that upon exposure during pregnancy lead to changes in the growth or structure of the developing fetus and ultimately cause defects in the physical structure or abnormalities in fetal behavior are called teratogens (6). Some viral infections have devastating impacts on the developing fetal brain. Viruses like Zika and cytomegalovirus can pass directly through the placenta to the fetal brain. These viruses cross the blood-brain barrier of the developing fetus, infecting and damaging brain tissue (9,10). Other infections including the influenza virus that do not cross the placental barrier have been associated with adverse effects on neural growth in offspring, mainly through mechanisms involved in activating the immune system of the mother, placenta, and subsequently the fetus (11,12). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new type of coronavirus that emerged in late 2019 and its related disease is known as coronavirus disease 19 (COVID-19). Nowadays, great attention is paid to COVID-19 infection in pregnant women and possible damage to their offspring. Although studies on COVID-19 are progressing rapidly, the effects of SARS-CoV-2 on fetal growth are unclear (16). In this review, we discussed evidence on the impact of SARS-CoV-2 infection during pregnancy on neurodevelopmental outcomes. Moreover, potential mechanisms by which prenatal SARS-CoV-2 exposure might impact the developing fetal brain were explored. These mechanisms are as follows: (1) direct fetal infection of neurologic tissues via transplacental transmission of the virus (2) impaired placental function resulting in adverse pregnancy outcomes associated with an increased risk of neurologic harm (e.g. fetal growth restriction and preterm birth) (3) via MIA (maternal immune activation) during neurodevelopment in pregnancy (16,17,18). A growing body of evidence suggests that SARS-CoV-2 infection can cause acute and chronic neurological complications in adults and children (19,20,21). There is no definite link between prenatal SARS-CoV-2 exposure and developmental neurological disorders in offspring, which may be partly due to the fact that most children born to infected mothers, are still very young for diagnosis of many developmental neurological conditions. However, epidemiological and clinical data indicate the potential of SARS-CoV-2 exposure during pregnancy to influence early neurodevelopmental outcomes. Preliminary data on the immune and inflammatory response to SARS-CoV-2 in pregnancy showed proinflammatory cytokines in pregnant women with SARS-CoV-2 that IFN-γ and IL-6 play the most important role (33,34). Significant infiltration of maternal immune cells into the placenta has been observed in cases of severe maternal COVID-19 and high SARS-CoV-2 viral load in the placenta (38). In placental specimens without evidence of direct SARS-CoV-2 infection, upregulation of the inflammatory pathways of natural killer cells (NK cells), T cells in mothers infected with SARS-CoV-2, and interferon-stimulated genes (ISGs) in villi tissue of placenta were shown (35,36). The placenta is the primary source of serotonin for the developing fetal brain. Studies show that activation and inflammation of the maternal and placental immune systems alter placental serotonin signaling, which in turn affects fetal brain development through impaired synaptogenesis, neuronal migration, and axonal targeting (40,41). Activation of the maternal and placental immune systems is also associated with other changes in fetal brain neurotransmitter signaling, including dopaminergic, cholinergic, GABA, and glutamatergic systems, which affect fetal brain development conditions (42,43). Activation of the maternal and placental immune system is associated with mitochondrial dysfunction of the placenta and fetus, oxidative stress, and impaired protein homeostasis (44,45). Maternal and infant gut microbiome may also be important modulators of the effect of MIA on the developing brain. Given the extent of synapse formation in the fetus and infant, the microglial function is a critical goal for research to better understand the effect of SARS-CoV-2-induced immune activation on the developing fetal brain (46). Transmission of the virus through the placenta, which can infect neural tissue, can have lasting and devastating consequences for the developing fetus's brain. A key factor in understanding the risk of possible fetal infection is whether maternally acquired SARS-CoV-2 can be transmitted from the placenta (a primary physiological and immune barrier that prevents the virus from being transmitted from mother to fetus) (48). Most of the evidence to date shows that the negative effects of neurodevelopment of SARS-CoV-2 infection occur mostly through activation of the mother and placenta's immunity rather than direct fetal infection with SARS-CoV-2 in utero. The data showed that the rate of SARS-CoV-2 positivity in infants in pregnancies exposed to SARS-CoV-2 is between 1% and 3%, and placental infection is a relatively rare event. A meta-analysis of case reports and case series estimated the placental infection rate at 7% (49). Mechanisms of protection against placental infection include low maternal SARS-CoV-2 viremia, maintenance of immune defense at the syncytophoblast border, and failure to express the molecules required (ACE2 and TMPRSS2) to bind and enter SARS-CoV-2 into the syncytrophoblast (36,37). Due to the small number of cases of placental infection and vertical transmission, data on completed pregnancies exposed to SARS-CoV-2 are now available throughout the developmental period (first to third trimesters). To date, no specific congenital syndrome has emerged following prenatal SARS-CoV-2 exposure indicating direct fetal infection (50,51). All of these data point to the activation of the maternal and placental immune systems and the subsequent activation of the fetal nervous system as the primary stimuli of neurodevelopmental complications in children exposed to SARS-CoV-2. Instead, direct infection of the placenta and fetal brain with Zika virus or cytomegalovirus infection has been observed. The data presented demonstrated the potential for maternal SARS-CoV-2 infection to stimulate maternal, placental, and fetal immune activation. Future studies will need to evaluate whether the fetoplacental immune responses in maternal SARS-CoV-2 infection are associated with neurodevelopmental morbidity in offspring. The Effect of infection time, different strains of the virus, fetal gender, and prenatal status (eg, maternal cardiac metabolic status, substance use, stress, drug use) on offspring's neurodevelopment is important in the next generation for a comprehensive understanding of the potentially lasting impact of the COVID-19.

At the beginning of the 21st century, a new deadly infectious disease known as severe acute respiratory syndrome (SARS) was recognized as a global public health threat. Subsequently, ten years after the initial SARS cases occurred in 2002, new cases of another atypical respiratory disease caused worldwide concern. This disease became known as Middle East respiratory syndrome (MERS). Currently, history has repeated itself with the emergence of a new Chinese epidemic at the end of 2019.

Since an effective drug against Covid-19 was not approved, researchers worldwide are trying to develop an effective vaccine against the disease to prevent related morbidity and mortality. According to the latest report of the World Health Organization, August 5, 2022, there are about 170 vaccine candidates for SARS-coronavirus-2 in the clinical and 198 vaccine candidates in the pre-clinical stage. In this review article, emphasis is placed on only 7 vaccines that have passed clinical phase IV. The mechanism of action of most of the proposed vaccines is the induction of a neutralizing antibody against the spike protein (glycoprotein S). These antibodies prevent the virus from entering the host cell by blocking the virus from attaching to its cell receptor (ACE-2). In this review, the role of SARS-coronavirus-2 proteins in the viral replication cycle and its pathogenic mechanism, and also the variants of SARS-coronavirus-2 are discussed to have an overview of the goals of designed vaccines. Then, the technology of producing various types of vaccines and the effectiveness of these vaccines against the virus variants are discussed.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pathogenic coronavirus that emerged in late 2019 and has caused a pandemic of acute respiratory disease, named ‘coronavirus disease 2019’ (COVID-19), which threatens human health and public safety. This virus has spread fast all over the world and declared a pandemic by the World Health Organization (WHO) (1). In early 2020 and recent literature has shown that co-infection of SARS-CoV-2 with other respiratory viruses might occur (2-4). The most common viral agents causing respiratory tract infection are influenza viruses (IFVs), adenoviruses (AdVs), parainfluenza viruses (PIVs), respiratory syncytial virus (RSV), and rhinoviruses (RVs). In addition, intensive investigations have led to the identification of new human respiratory viruses, including human metapneumovirus (hMPV) and human bocavirus (HBoV) (5). Therefore, identifying the epidemiological patterns of respiratory pathogens may be useful for stopping the epidemic spread of COVID-19, providing information for the development of optimal diagnosis (7). In this study, the presence of the respiratory syncytial virus, human metapneumovirus virus, adeno, boca, parainfluenza, influenza A and B, endemic coronaviruses including NL63, OC43, 229E, and HKU-1 among specimens with positive and negative SARS-CoV-2 tests was investigated.

This cross-sectional study was conducted at the beginning of the pandemic between December 2019 and March 2019. In this study, oropharyngeal/nasopharyngeal swab samples of patients suspected of COVID-19 were collected from the laboratory of Labafinejad Hospital in Tehran. A total of 197 samples (91 positive for SARS-CoV-2 and 106 negative) were included in the study. Total nucleic acids (DNA and RNA) were extracted from 200 µL oropharyngeal/nasopharyngeal swab specimens by GeneAll Ribospin vRD DNA/RNA Extraction Kit (Seoul, South Korea) according to the manufacturer’s instruction. The extracted specimens were tested by real-time reverse transcription PCR (rRT-PCR) with novel coronavirus (2019-nCoV) Nucleic Acid Diagnostic Kit (PCR-Fluorescence Probing) (Sansure Biotech Inc.) using the Rotor-Gene® Q instrument targeting the ORF1ab and N genes of SARSCoV-2 RNA. Internal control targeting the RNase P gene was used to monitor the sample collection and rRT-PCR process to avoid false-negative results. Afterward, the remaining total nucleic acids were stored at -80°C for analysis of viral respiratory pathogens. The residual total nucleic acids were subjected to the real-time PCR assay for the detection of respiratory viral pathogens using the real-time thermal cycler Mic qPCR instrument (BioMolecular Systems). In this study, Geneova HiTeq 17 Viro Respiratory Pathogen One-step RT-PCR Kit as a multiplex TaqMan one-step real-time PCR method was used. It can detect various respiratory viral pathogens including SARS-CoV-2, Flu/A, Flu/B, Flu H1N1, HCoV-NL63, HCoV-229E, HCoVHKU1, HCoV-229E, HCoV-OC43, PIV1/2/3, AdV, hRV, HBoV1/2/3, hMPV, and RSV. The reactions were named as an unknown sample, positive control, and negative control. Tube 1: Fam channel (SARS-CoV-2 virus), HEX channel (RNase P gene as internal control), Texas Red channel (Influenza A virus), and CY5 channel (Influenza B virus) were selected. Tube 2: channel FAM (influenza H1N1virus), channel HEX (HCoV-NL63 and HCov-229E viruses), channel Texas Red (metapneumovirus), and channel CY5 (respiratory syncytial virus) were selected. Tube 3: FAM channel (HKU-1 and OC-43 viruses), HEX channel (parainfluenza viruses 2, 1 and 3), Texas Red channel (bocavirus 2, 1 and 3), and CY5 channel (adenovirus) were selected.

In this study, the presence of several respiratory viruses on 197 nasopharyngeal/oropharyngeal swab samples collected from suspected COVID-19 patients was investigated. Among the 197 people who entered the study, 88 people (45%) were women and 109 people (55%) were men. The average age of the subjects was 58 ± 13 years. The most common clinical symptoms found in these patients were fever in 169 people (86%), cough in 133 people (68%), sore throat in 111 people (56%), shortness of breath in 51 people (26%), headache in 47 people (24%), diarrhea in 38 people (19%), and asthma in 18 people (9.1%). Among 197 patients, 64 (32%) had diabetes, 70 (36%) had high blood pressure, 49 (25%) had kidney disease, 24 (12%) had heart disease, and 9.1% had asthma. Therefore, high blood pressure was considered as the most common underlying disease. In general, there was no difference in basic characteristics including age, gender, underlying disease, and clinical manifestations between the two groups. Among 197 patients, 14 people (7.1 percent) were infected with human metapneumovirus, 4 people (2 percent) with RSV infection, 3 people (1.5 percent) with influenza A, B, 2 people (1 percent) with parainfluenza virus, 8 people (1 NL63,229E infection, 3 people (5.1%) had HKU1, OC43 infection, 2 people (1%) had adenovirus infection, and 1 person (0.5%) had bocavirus infection. In this study, a total of 37 viruses (18.78%) were detected in oropharyngeal/nasopharyngeal swab samples from 197 subjects suspected of COVID-19. The results showed that human metapneumovirus was the most common cause of the disease in both groups of SARS-CoV-2 positive people [7 (7.7%)] and SARS-CoV-2 negative people [7 (6.6%)]. In addition, the rate of viral co-infection in SARS-CoV-2 positive (18.68%) and SARS-CoV-2 negative (18.86%) patients was almost the same. In 91 people with positive SARS-CoV-2 test, the infection with other viral infections was in the following order: 7 people (7.7%) infection with metapneumovirus, 2 people (2.2%) with RSV, 1 person (1.1%) influenza A/B, 1 person (1.1%) parainfluenza, 3 people (3.3 NL-63,229E, 1 person (1.1%) HKU1, OC43, 1 person (1.1%) adenovirus, and 1 person (1.1%) also had co-infection with bocavirus.

The data presented in this study strengthened our understanding of the epidemiology of different types of viral respiratory pathogens in suspected patients with COVID-19 during the fall and winter of 2019 in Iran. Using the multiplex PCR method, we reported the rate of simultaneous viral respiratory infections of 18.78%, which was mainly human metapneumovirus. Therefore, simultaneous screening of other viral respiratory pathogens will be useful for clinicians and researchers interested in the treatment and control of viral respiratory tract infections. It seems that the reduction of the prevalence of the respiratory syncytial virus, influenza virus, and other respiratory viruses during the COVID-19 pandemic in Iran happened due to public health measures, maintaining social distancing, and wearing masks.

Coronaviruses, enveloped positive single-stranded RNA viruses, have become significant pathogens for humans and other vertebrates since the outbreak of SARS (severe acute respiratory syndrome) in 2002 in China. These viruses could infect the respiratory tract of humans and other animals. The outbreaks of SARS and MERS (Middle East respiratory syndrome), which Bats are thought to be the origin of both viruses, have demonstrated that these viruses could be transmitted from animal to human and human to human. The rapid and widespread outbreak of pneumonia caused by SARS-CoV-2, since December 2019 worldwide, and its 2 to 3 percent mortality, indicates the serious threat of coronavirus to global health. Some coronaviruses also cause great economic loss by infecting domestic animals. At the current time, there is no definitive treatment or effective vaccine for COVID-19, a disease caused by SARS-CoV-2. So it is necessary to develop effective treatment and prevention methods to combat coronaviruses.

COVID-19 is a novel coronavirus with an outbreak of unusual viral pneumonia in Wuhan, China, and then pandemic. Based on its phylogenetic relationships and genomic structures the COVID-19 belongs to genera Betacoronavirus. Human Betacoronaviruses (SARS-CoV-2, SARS-CoV, and MERS-CoV) have many similarities, but also have differences in their genomic and phenotypic structure that can influence their pathogenesis. COVID-19 is containing single-stranded (positive-sense) RNA associated with a nucleoprotein within a capsid comprised of matrix protein. A typical CoV contains at least six ORFs in its genome. All the structural and accessory proteins are translated from the sgRNAs of CoVs. Four main structural proteins are encoded by ORFs 10, 11 on the one-third of the genome near the 3′-terminus. The genetic and phenotypic structure of COVID-19 in pathogenesis is important. This article highlights the most important of these features compared to other Betacoronaviruses.

Since the beginning of the 21st century, coronaviruses that originated from animals to human have been the cause of several deadly pneumonia epidemics including SARS, MERS disease, and now COVID-19 which has become a worldwide pandemic. The emergence of these acute respiratory syndromes emphasizes the cross-species transmission of coronaviruses and their prevalence in humans. Coronaviruses contain a surface- spike protein (S) that initiates infection by recognizing its receptor and attaching to the membrane, which is a key step in the host specificity and intergenerational transmission. To date, no specific treatment or vaccine against any of the seven human coronaviruses has been approved. This underscores the importance of exploring the mechanisms governing the virus entry and intergenerational transmission. This review article discuss the mechanism of infection used by coronaviruses by focusing on the features of the S protein and its receptor binding characteristics in different species. In addition, protease processes involved in the onset of infection was considered to provide a complete picture of their role in the coronavirus replication cycle. Finally, treatments based on the interaction of S-protein and ACE2 receptor were described.