Partners in crime: Autoantibodies complicit in COVID-19 pathogenesis.

Autoantibodies (AABs) play a critical role in the pathogenesis of autoimmune diseases (AIDs) and serve as a diagnostic and prognostic tool in assessing these complex disorders. Viral infections have long been recognized as a principal environmental factor affecting the production of AABs and the development of autoimmunity. COVID-19 has primarily been considered a hyperinflammatory syndrome triggered by a cytokine storm. In the following, the role of maladaptive B cell response and AABs became more apparent in COVID-19 pathogenesis. The current review will primarily focus on the role of extrafollicular B cell response, Toll-like receptor-7 (TLR-7) activation, and neutrophil extracellular traps (NETs) formation in the development of AABs following SARS-CoV-2 infection. In the following, this review will clarify how these AABs dysregulate immune response to SARS-CoV-2 by disrupting cytokine function and triggering neutrophil hyper-reactivity. Finally, the pathologic effects of these AABs will be further described in COVID-19 associate clinical manifestations, including venous and arterial thrombosis, a multisystem inflammatory syndrome in children (MIS-C), acute respiratory distress syndrome (ARDS), and recently described post-acute sequelae of COVID-19 (PASC) or long-COVID.

SARS-CoV-2 in municipal wastewater treatment plant, collection network, and hospital wastewater.

The current outbreak of coronavirus disease (COVID-19) has led to creating a public health emergency conditions since 2019. COVID-19, which is caused by SARS-CoV-2, is spread via human-to-human transmission by direct contact or droplets. Through conducting this study, we were looking for detecting SARS-CoV-2 in wastewater produced in Iran country (Ardabil, Nir, Khalkhal, and Kowsar) (wastewater collection network, wastewater treatment plant, and hospital wastewater). In this research, samples (n=76) were collected from influent and effluent of municipal and hospital wastewater treatment plants, and some samples were also collected from Ardabil municipal wastewater manholes. The sampling duration included the white (lower risk of COVID-19) and red (high risk of COVID-19) conditions. Samples were stored at -20 °C for further diagnostic tests. The specific primer and probe real-time reverse transcriptase-polymerase chain reaction (real-time PCR) targeting ORF1ab and N genes (nucleoprotein gene) were applied to detect viral genomes of the SARS-CoV-2 virus in the wastewater samples. Out of 76 samples, a total of 15 samples (19.73%) collected from wastewater in Ardabil province (Ardabil, Nir, Khalkhal, and Kowsar), were positive in terms of SARS-CoV-2. Wastewater epidemiology can facilitate detection of the incidence of pathogens through metropolises, measurement of population prevalence without direct testing, and provision of information to the public health system about the efficiency of intervening efforts. Graphical abstract.

Serum Brain-Derived Neurotrophic Factor (BDNF) in COVID-19 Patients and its Association with the COVID-19 Manifestations.

COVID-19 is a systematic disease that frequently implies neurological and non-neurological manifestations, predominantly by inducing hypoxia. Brain-derived neurotrophic factor (BDNF) is a key factor in regulating functions of nervous and respiratory systems and has been strongly related to hypoxia. Therefore, this study planned to investigate BDNF association with the COVID-19 manifestations especially neurological impairments and the infection-induced hypoxia. We enrolled sixty-four COVID-19 patients and twenty-four healthy individuals in this study. Patients were divided into two groups, with and without neurological manifestations, and their serum BDNF levels were measured by enzyme-linked immunosorbent assay (ELISA). COVID-19 patients had significantly lower BDNF levels than healthy individuals (p = 0.023). BDNF levels were significantly lower in patients with neurological manifestations compared to healthy individuals (p = 0.010). However, we did not observe a statistically significant difference in BDNF levels between patients with and without neurological manifestations (p = 0.175). BDNF's levels were significantly lower in patients with CNS manifestations (p = 0.039) and higher in patients with fever (p = 0.03) and dyspnea (p = 0.006). Secondly, BDNF levels have a significant negative association with oxygen therapy requirement (p = 0.015). These results strongly suggest the critical association between dysregulated BDNF and hypoxia in promoting COVID-19 manifestations, particularly neurological impairments.

The role of IL-1 family of cytokines and receptors in pathogenesis of COVID-19.

A global pandemic has erupted as a result of the new brand coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic has been consociated with widespread mortality worldwide. The antiviral immune response is an imperative factor in confronting the recent coronavirus disease 2019 (COVID-19) infections. Meantime, cytokines recognize as crucial components in guiding the appropriate immune pathways in the restraining and eradication of the virus. Moreover, SARS-CoV-2 can induce uncontrolled inflammatory responses characterized by hyper-inflammatory cytokine production, which causes cytokine storm and acute respiratory distress syndrome (ARDS). As excessive inflammatory responses are contributed to the severe stage of the COVID-19 disease, therefore, the pro-inflammatory cytokines are regarded as the Achilles heel during COVID-19 infection. Among these cytokines, interleukin (IL-) 1 family cytokines (IL-1, IL-18, IL-33, IL-36, IL-37, and IL-38) appear to have a strong inflammatory role in severe COVID-19. Hence, understanding the underlying inflammatory mechanism of these cytokines during infection is critical for reducing the symptoms and severity of the disease. Here, the possible mechanisms and pathways involved in inflammatory immune responses are discussed.

Can anti-parasitic drugs help control COVID-19?

Novel COVID-19 is a public health emergency that poses a serious threat to people worldwide. Given the virus spreading so quickly, novel antiviral medications are desperately needed. Repurposing existing drugs is the first strategy. Anti-parasitic drugs were among the first to be considered as a potential treatment option for this disease. Even though many papers have discussed the efficacy of various anti-parasitic drugs in treating COVID-19 separately, so far, no single study comprehensively discussed these drugs. This study reviews some anti-parasitic recommended drugs to treat COVID-19, in terms of function and in vitro as well as clinical results. Finally, we briefly review the advanced techniques, such as artificial intelligence, that have been used to find effective drugs for the treatment of COVID-19.

The sufficient vitamin D and albumin level have a protective effect on COVID-19 infection.

There is limited information regarding the protective factors of SARS-CoV-2 infection. This research is focused on analyzing the role of vitamin D and albumin in the severity, progression, or possible prevention of COVID-19 infection. In this case-control study, 191 patients and 203 healthy individuals were enrolled. Blood samples were taken to test the albumin and vitamin D levels of both groups. Our results show a direct association of vitamin D deficiency with the infection of COVID-19 and severity. According to our findings, 84.4% of patients with COVID-19 in this study had vitamin D deficiency. Moreover, the average level of albumin was significantly decreased in those infected patients who had respiratory symptoms. In the present study, a considerable negative correlation was established between the levels of vitamin D and the severity of COVID-19 infection. This reflects on the immunomodulatory and inhibitory nature of vitamin D to the viral replication.

The immune response and immune evasion characteristics in SARS-CoV, MERS-CoV, and SARS-CoV-2: Vaccine design strategies.

The worldwide outbreak of SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 as a novel human coronavirus, was the worrying news at the beginning of 2020. Since its emergence complicated more than 870,000 individuals and led to more than 43,000 deaths worldwide. Considering to the potential threat of a pandemic and transmission severity of it, there is an urgent need to evaluate and realize this new virus's structure and behavior and the immunopathology of this disease to find potential therapeutic protocols and to design and develop effective vaccines. This disease is able to agitate the response of the immune system in the infected patients, so ARDS, as a common consequence of immunopathological events for infections with Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and SARS-CoV-2, could be the main reason for death. Here, we summarized the immune response and immune evasion characteristics in SARS-CoV, MERS-CoV, and SARS-CoV-2 and therapeutic and prophylactic strategies with a focus on vaccine development and its challenges.