A Review of Special Considerations on Insulin Resistance Induced Hyperandrogenemia in Women with Polycystic Ovary Syndrome: A Prominent COVID-19 Risk Factor.

Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infecting mechanism depends on hosting angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) as essential components and androgens as regulators for inducing the expression of these components. Therefore, hyperandrogenism-related disease such as polycystic ovary syndrome (PCOS) in insulin resistant women in reproductive-age is a high-risk factor for SARS-CoV-2 infection. Here, we describe the signaling pathways that might increase the susceptibility and severity of this new pandemic in PCOS women with insulin resistance (IR). Luteinizing hormone and insulin increase the risk of SARS-CoV-2 infection in these patients via the induction of steroidogenic enzymes expression through cAMP-response element binding protein and Forkhead box protein O1 (FOXO1), respectively. TMPRSS2 expression is activated through phosphorylation of FOXO1 in ovaries. In other words, SARS-CoV-2 infection is associated with temporary IR by affecting ACE2 and disturbing ß-pancreatic function. Therefore, PCOS, IR, and SARS-CoV-2 infection are three corners of the triangle that have complicated relations, and their association might increase the risk of SARS-CoV-2 infection and severity.

Association between expression of ZBP1, AIM2, and MDA5 genes and severity of COVID-19.

Antiviral and inflammatory responses following the detection of the virus genome by nucleic acid sensors play a vital role in the pathogenesis and outcome of diseases. In this study, we investigated the ZBP1, AIM2, and MDA5 expression levels in COVID-19 patients with different intensities of the disease. 75 quantitative Real-Time PCR (qRT-PCR)-confirmed COVID-19 patients were included consecutively and divided into 3 groups of mild, severe, and critical based on the severity of the disease. Also, 25 healthy volunteer subjects were included. PBMCs were collected from the whole blood, and RNA was extracted using commercial kit. The expression of ZBP1, AIM2, and MDA5 genes was investigated using qRT-PCR technique. The mean age of the patients and healthy volunteers was 52.73±13.78 and 49.120±12.490, respectively. In each group, 13 out of 25 participants were male. The expression levels of ZBP1 (P=0.001), AIM2 (P=0.001), and MDA5 (P= 0.003) transcript were significantly higher in COVID-19 patients than the control group. The results also revealed that the expression levels of ZBP1, AIM2, and MDA5 were significantly higher in the critical and severe COVID-19 patients compared to those with mild disease (P<0.05). Moreover, regarding the gender, the expression levels of AIM2 and MDA5 were significantly elevated in male severe (P=0.04 and P=0.003, respectively) and critical (P=0.005 and P=0.0004, respectively) patients than the female ones. The results indicated that ZBP1, AIM2, and MDA5 genes might have an important role in the severity of COVID-19 disease. Moreover, the severity of COVID-19 disease in male and female patients might be related to AIM2, and MDA5 expression levels. More studies are recommended to be conducted to clarify this issue.

An Update on Protective Effectiveness of Immune Responses After Recovery From COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits variable immunity responses among hosts based on symptom severity. Whether immunity in recovered individuals is effective for avoiding reinfection is poorly understood. Determination of immune memory status against SARS-CoV-2 helps identify reinfection risk and vaccine efficacy. Hence, after recovery from COVID-19, evaluation of protective effectiveness and durable immunity of prior disease could be significant. Recent reports described the dynamics of SARS-CoV-2 -specific humoral and cellular responses for more than six months in convalescent SARS-CoV-2 individuals. Given the current evidence, NK cell subpopulations, especially the memory-like NK cell subset, indicate a significant role in determining COVID-19 severity. Still, the information on the long-term NK cell immunity conferred by SARS-CoV-2 infection is scant. The evidence from vaccine clinical trials and observational studies indicates that hybrid natural/vaccine immunity to SARS-CoV-2 seems to be notably potent protection. We suggested the combination of plasma therapy from recovered donors and vaccination could be effective. This focused review aims to update the current information regarding immune correlates of COVID-19 recovery to understand better the probability of reinfection in COVID-19 infected cases that may serve as guides for ongoing vaccine strategy improvement.

Covid-19 pathogenesis in prostatic cancer and TMPRSS2-ERG regulatory genetic pathway.

Members of Coronaviridae family have been the source of respiratory illnesses. The outbreak of SARS-CoV-2 that produced a severe lung disease in afflicted patients in China and other countries was the reason for the incredible attention paid toward this viral infection. It is known that SARS-CoV-2 is dependent on TMPRSS2 activity for entrance and subsequent infection of the host cells and TMPRSS2 is a host cell molecule that is important for the spread of viruses such as coronaviruses. Different factors can increase the risk of prostate cancer, including older age, a family history of the disease. Androgen receptor (AR) initiates a transcriptional cascade which plays a serious role in both normal and malignant prostate tissues. TMPRSS2 protein is highly expressed in prostate secretory epithelial cells, and its expression is dependent on androgen signals. One of the molecular signs of prostate cancer is TMPRSS2-ERG gene fusion. In TMPRSS2-ERG-positive prostate cancers different patterns of changed gene expression can be detected. The possible molecular relation between fusion positive prostate cancer patients and the increased risk of lethal respiratory viral infections especially SARS-CoV-2 can candidate TMPRSS2 as an attractive drug target. The studies show that some molecules such as nicotinamide, PARP1, ETS and IL-1R can be studied deeper in order to control SARS-CoV-2 infection especially in prostate cancer patients. This review attempts to investigate the possible relation between the gene expression pattern that is produced through TMPRSS2-ERG fusion positive prostate cancer and the possible influence of these fluctuations on the pathogenesis and development of viral infections such as SARS-CoV-2.

Harnessing Memory NK Cell to Protect Against COVID-19.

The worldwide struggle against the coronavirus disease 2019 (COVID-19) as a public health crisis continues to sweep across the globe. Up to now, effective antiviral treatment against COVID-19 is not available. Therefore, throughout virus infections, a thorough clarification of the virus-host immune system interactions will be most probably helpful to encounter these challenges. Emerging evidence suggests that just like SARS and MERS, COVID-19 primarily suppresses the innate immune system, enabling its stable propagation during the early stage of infection. Consequently, proinflammatory cytokines and chemokines have been increasing during infection progression associated with severe lung pathology. It is imperative to consider hyper inflammation in vaccine designing, as vaccine-induced immune responses must have a protective role against infection without leading to immunopathology. Among the front-line responders to viral infections, Natural Killer (NK) cells have immense therapeutic potential, forming a bridge between innate and adaptive responses. A subset of NK cells exhibits putatively increased effector functions against viruses following pathogen-specific and immunization. Memory NK cells have higher cytotoxicity and effector activity, compared with the conventional NK cells. As a pioneering strategy, prompt accumulation and long-term maintenance of these memory NK cells could be an efficacious viral treatment. According to the high prevalence of human cytomegalovirus (HCMV) infection in the world, it remains to be determined whether HCMV adaptive NK cells could play a protective role against this new emerging virus. In addition, the new adaptive-like KIR+NKG2C+ NK cell subset (the adaptive-like lung tissue residue [tr]NK cell) in the context of the respiratory infection at this site could specifically exhibit the expansion upon COVID-19. Another aspect of NK cells we should note, utilizing modified NK cells such as allogeneic off-the-shelf CAR-NK cells as a state-of-the-art strategy for the treatment of COVID-19. In this line, we speculate introducing NKG2C into chimeric antigen receptors in NK cells might be a potential approach in future viral immunotherapy for emerging viruses. In this contribution, we will briefly discuss the current status and future perspective of NK cells, which provide to successfully exploit NK cell-mediated antiviral activity that may offer important new tools in COVID-19 treatment.