The picture theory of seven pathways associated with COVID-19 in the real world (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces immune-mediated diseases. Interactions between the host and virus govern induction, resulting in multiorgan impacts. In 2021, as normal life was challenging during the pandemic era, we analyzed SCI journals according to L. Wittgenstein's Tractatus Logi-co-Philosophicus. The pathophysiology of coronavirus disease 2019 (COVID-19) involves the following steps: 1) the angiotensin-converting enzyme (ACE2) and Toll-like receptor (TLR) pathways: 2) the neuropilin (NRP) pathway, with seven papers and continuing with twenty-four: 3) the sterile alpha motif (SAM) and histidine-aspartate domain (HD)-containing protein 1 (SAMHD1) tetramerization pathway, with two papers and continuing with twelve: 4) inflammasome activation pathways, with five papers and continuing with thirteen: 5) the cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) (cGAS–STING) signaling pathway, with six papers and successful with eleven: 6) the spike protein pathway, with fourteen and continuing with twenty-three: 7) the immunological memory engram pathway, with thirteen papers and successive with eighteen: 8) the excess acetylcholine pathway, with three papers and successful with nine. We reconfirmed that COVID-19 involves seven (1-7) pathways and a new pathway involving excess acetylcholine. Therefore, it is necessary to therapeutically alleviate and block the pathological course harmoniously with modulating innate lymphoid cells (ILCs) if diverse SARS-CoV-2 variants are subsequently encountered in the future.

Nachhaltigkeit im OP ­ korrelieren Sterilität, Sicherheit und Service auch mit einer ressourcenschonenden Verwendung von Medizinprodukten?

In times of an unprecedented energy crisis, sustainability is becoming increasingly important. This development does not stop at medicine and especially at the operating room, where a considerable amount of greenhouse gases is produced. Due to this development, the question arises whether sterility, safety and service can be reconciled with a resource-saving use of medical devices. One goal here must be to replace disposables, which offer a high degree of sterility, with safely reprocessable reusables. Due to rising energy costs as well as supply bottlenecks, reprocessing of products offers increasing independence for the hospital. Furthermore, the move towards renewable energy for reusable products is visibly improving the carbon footprint. The independence gained by clinics also offers greater safety for patients, as the risk of unavailable materials is reduced. In addition to the goal of increasing the use of reusable items, the recycling of disposable products will also play an increasing role. Life cycle assessments will increasingly guide the optimal choice of products in this regard. In summary, these options offer the possibility of implementing the increasing need for sustainability in the OR.

The bibliometric analysis of studies on intracytoplasmic sperm injection from 2002 to 2021.

Background: Infertility is estimated to occur in 1 out of every 4-7 couples. Intracytoplasmic sperm injection (ICSI), a type of assisted reproduction introduced in 1992, has been used across the world for almost all indications of infertility, yielding high pregnancy rates. There is a growing concern worldwide about ICSI since semen quality has declined in recent years, accompanied with the potential risks of this technology. This study aims to analyze the current status and hotspots of ICSI via a bibliometric analysis. Methods: We retrieved publications on ICSI from the Web of Science Core Collection database from 2002 to 2021. CiteSpace was used to summarize knowledge mapping of subject categories, keywords, and co-citation relationships with the strongest citation bursts. VOSviewer was used to explore co-citation and co-occurrence relationships for countries, organizations, references, authors, and keywords. Results: A total of 8271 publications were analyzed between 2002 and 2021. The major findings are as follows: the USA, China, Italy, Japan, and Belgium are the top five prolific countries. The Free University of Brussels, University of Copenhagen, University of Valencia, Ghent University, and the University of California San Francisco are the top five contributing organizations. Fertility and Sterility and Human Reproduction are the most productive and cited journals. The hotspot topics are risks of ICSI, oocyte preservation, live birth rate, infertile men, and embryo quality in the past two decades. Conclusion: This study presents a research overview of ICSI from different perspectives. These findings will contribute to a better understanding of the current status of ICSI research and provide hotspots and trends for future studies.

Acceptance of genetic editing and of whole genome sequencing of human embryos by patients with infertility before and after the onset of the COVID-19 pandemic.

RESEARCH QUESTION: Has acceptance of heritable genome editing (HGE) and whole genome sequencing for preimplantation genetic testing (PGT-WGS) of human embryos changed after the onset of COVID-19 among infertility patients? DESIGN: A written survey conducted between April and June 2018 and July and December 2021 among patients at a university-affiliated infertility practice. The questionnaire ascertained the acceptance of HGE for specific therapeutic or genetic 'enhancement' indications and of PGT-WGS to prevent adult disease. RESULTS: In 2021 and 2018, 172 patients and 469 patients (response rates: 90% and 91%, respectively) completed the questionnaire. In 2021, significantly more participants reported a positive attitude towards HGE, for therapeutic and enhancement indications. In 2021 compared with 2018, respondents were more likely to use HGE to have healthy children with their own gametes (85% versus 77%), to reduce disease risk for adult-onset polygenic disorders (78% versus 67%), to increase life expectancy (55% versus 40%), intelligence (34% versus 26%) and creativity (33% versus 24%). Fifteen per cent of the 2021 group reported a more positive attitude towards HGE because of COVID-19 and less than 1% a more negative attitude. In contrast, support for PGT-WGS was similar in 2021 and 2018. CONCLUSIONS: A significantly increased acceptance of HGE was observed, but not of PGT-WGS, after the onset of COVID-19. Although the pandemic may have contributed to this change, the exact reasons remain unknown and warrant further investigation. Whether increased acceptability of HGE may indicate an increase in acceptability of emerging biomedical technologies in general needs further investigation.

Detection of Some Causes of Feline Eye Infections in Baghdad City.

The current study aimed to determine the causes associated with ocular infection in cats received at Baghdad veterinary hospital from March 2020 to April 2021. Forty cats (22 females and 18 males) were examined at a small animal clinic in Baghdad veterinary hospital from March 2020 to April 2021. The cats suffered from severe eyes infection (inflammation, lacrimation, redness and other ocular signs). On the other hand, ten healthy cats were examined and prepared for bacterial isolation as a control group. For bacterial isolation, sterile cotton swabs with transport medium were taken gently from the corneal and conjunctiva area of infected eyes. The swabs were placed in an ice box within 24 hours for laboratory culture. Sterile swabs with transport media were used in our study; swabs passed directly on the inferior conjunctival sac of the compromised eye avoiding contact with eyelashes and skin of eyelids. All swabs were inoculated on the following media (5% Sheep blood agar, MacConkey agar and Nutrient agar) at 37ºC for 24 to 48 h.ImmunoChromatoGraphy assay (ICG) of FCV on samples. The results showed that 50%of Mixed bacterial and FCV were the significant cause of isolates; also, it showed that S. aureus was the most bacterial cause of eye infection; young females were mostly infected in February. In conclusion, the wide distribution of ocular infections in cats is due to different causes, especially with bacteria, including Staphylococcus spp. and virus (FCV). The seasonal variation between months plays a significant factor in the spreading of eye infections in the feline.

How to provide fertility treatment during COVID-19 pandemic.

PURPOSE OF REVIEW: The emergence of the novel coronavirus infection that arose in Wuhan, China in December 2019 has resulted in an epidemic that has quickly expanded to become one of the most significant public health threats in recent times. The objective of this review is to summarize how this pandemic has affected the activity of a Reproductive Medicine Center, which established a series of measures in parallel with governments decisions and scientific societies. RECENT FINDINGS: The control measures adopted for restarting the healthcare activity should be equitable and inclusive. Moreover, this pandemic has implied changes in treatments and strategies to be alert regarding the daily changing information. Finally, for ensuring a safe practice both for patients and staff, it is important to detect asymptomatic patients, so Reproductive Medicine centers must take special care with screening and testing procedures. SUMMARY: The pandemic has pushed up toward a new reality in terms of Assisted Reproductive treatments, where social distance and responsibility are protagonists. We face a new challenge of balancing between responding to the committed efforts of infertile couples to achieve pregnancy and safeguarding the health of the future parents and their children during this time of pandemic.

Association of laparoscopically-confirmed endometriosis with long COVID-19: a prospective cohort study.

BACKGROUND: Women are at greater risk than men of developing chronic inflammatory conditions and "long COVID." However, few gynecologic health risk factors for long COVID-19 have been identified. Endometriosis is a common gynecologic disorder associated with chronic inflammation, immune dysregulation, and comorbid presentation with autoimmune and clotting disorders, all of which are pathophysiological mechanisms proposed for long COVID-19. Therefore, we hypothesized that women with a history of endometriosis may be at greater risk of developing long COVID-19. OBJECTIVE: This study aimed to investigate the association between history of endometriosis before SARS-CoV-2 infection and risk of long COVID-19. STUDY DESIGN: We followed 46,579 women from 2 ongoing prospective cohort studies-the Nurses' Health Study II and the Nurses' Health Study 3-who participated in a series of COVID-19-related surveys administered from April 2020 to November 2022. Laparoscopic diagnosis of endometriosis was documented prospectively in main cohort questionnaires before the pandemic (1993-2020) with high validity. SARS-CoV-2 infection (confirmed by antigen, polymerase chain reaction, or antibody test) and long-term COVID-19 symptoms (≥4 weeks) defined by the Centers for Disease Control and Prevention were self-reported during follow-up. Among individuals with SARS-CoV-2 infection, we fit Poisson regression models to assess the associations between endometriosis and risk of long COVID-19 symptoms, with adjustment for potential confounding variables (demographics, body mass index, smoking status, history of infertility, and history of chronic diseases). RESULTS: Among 3650 women in our sample with self-reported SARS-CoV-2 infections during follow-up, 386 (10.6%) had a history of endometriosis with laparoscopic confirmation, and 1598 (43.8%) reported experiencing long COVID-19 symptoms. Most women were non-Hispanic White (95.4%), with a median age of 59 years (interquartile range, 44-65). Women with a history of laparoscopically-confirmed endometriosis had a 22% greater risk of developing long COVID-19 (adjusted risk ratio, 1.22; 95% confidence interval, 1.05-1.42) compared with those who had never been diagnosed with endometriosis. The association was stronger when we defined long COVID-19 as having symptoms for ≥8 weeks (risk ratio, 1.28; 95% confidence interval, 1.09-1.50). We observed no statistically significant differences in the relationship between endometriosis and long COVID-19 by age, infertility history, or comorbidity with uterine fibroids, although there was a suggestive trend indicating that the association may be stronger in women aged <50 years (<50 years: risk ratio, 1.37; 95% confidence interval, 1.00-1.88; ≥50 years: risk ratio, 1.19; 95% confidence interval, 1.01-1.41). Among persons who developed long COVID-19, women with endometriosis reported on average 1 additional long-term symptom compared with women without endometriosis. CONCLUSION: Our findings suggest that those with a history of endometriosis may be at modestly increased risk for long COVID-19. Healthcare providers should be aware of endometriosis history when treating patients for signs of persisting symptoms after SARS-CoV-2 infection. Future studies should investigate the potential biological pathways underlying these associations.

Rescuing fertility during COVID-19 infection: exploring potential pharmacological and natural therapeutic approaches for comorbidity, by focusing on NLRP3 inflammasome mechanism.

The respiratory system was primarily considered the only organ affected by Coronavirus disease 2019 (COVID-19). As the pandemic continues, there is an increasing concern from the scientific community about the future effects of the virus on male and female reproductive organs, infertility, and, most significantly, its impact on the future generation. The general presumption is that if the primary clinical symptoms of COVID-19 are not controlled, we will face several challenges, including compromised infertility, infection-exposed cryopreserved germ cells or embryos, and health complications in future generations, likely connected to the COVID-19 infections of parents and ancestors. In this review article, we dedicatedly studied severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) virology, its receptors, and the effect of the virus to induce the activation of inflammasome as the main arm of the innate immune response. Among inflammasomes, nucleotide oligomerization domain-like receptor protein, pyrin domain containing 3 (NLRP3) inflammasome pathway activation is partly responsible for the inflicted damages in both COVID-19 infection and some reproductive disorders, so the main focus of the discussion is on NLRP3 inflammasome in the pathogenesis of COVID-19 infection alongside in the reproductive biology. In addition, the potential effects of the virus on male and female gonad functions were discussed, and we further explored the potential natural and pharmacological therapeutic approaches for comorbidity via NLRP3 inflammasome neutralization to develop a hypothesis for averting the long-term repercussions of COVID-19. Since activation of the NLRP3 inflammasome pathway contributes to the damage caused by COVID-19 infection and some reproductive disorders, NLRP3 inflammasome inhibitors have a great potential to be considered candidates for alleviating the pathological effects of the COVID-19 infection on the germ cells and reproductive tissues. This would impede the subsequent massive wave of infertility that may threaten the patients.

Association Between COVID-19 Vaccination and Artificial Insemination Outcomes for Couples Experiencing Infertility.

This cohort study investigates the association between COVID-19 vaccination status and artificial insemination by partner outcomes among couples experiencing infertility in China.

Impact of COVID-19 on fertility and assisted reproductive technology (ART): a systematic review.

The appearance of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a major obstacle for the performing of current medical activities throughout the world. COVID-19 has affected humanity in many ways, thus causing a great medical, social, economic, and political instability. The aim of this study was to make an analysis of the scientific data obtained by so far to highlight the impact that COVID-19 has had on fertility and assisted reproductive technology (ART). Infection with SARS-CoV-2 alters the normal immune response by local and systemic damage to tissues and organs. After the virus enters the body, the first lesions are produced in the respiratory tract. Extrapulmonary lesions specific to COVID-19 include acute renal lesions/acute kidney damage, hepatocellular lesions, neurological diseases, myocardial dysfunction and arrhythmia, gastrointestinal diseases but also genital impairment. The possible impairment of the male reproductive system is because angiotensin-converting enzyme 2 (ACE2) receptors are in an increased number in the testes, seminiferous duct cells, spermatogonia, Leydig cells and Sertoli cells. Many published studies to date have pointed out that COVID-19 could also affect female fertility and disrupt the functions of the female reproductive system. The theory that this virus can also be transmitted sexually and can cause infertility or testicular damage is supported by the fact that the virus can be isolated in the semen of COVID-19 patients but only during the disease. Choosing the best method of treating infertility during the COVID-19 pandemic is multifactorial, but the risk of infection and compliance with specific ART hygiene protocols must always be considered. Currently, there is no scientific basis regarding the fact that the COVID-19 vaccination would influence fertility.

COVID-19 vaccine hesitancy and associated factors among infertile couples undergoing assisted reproductive treatment.

Although periconception vaccination is important to maternal and neonatal health, little is known about the COVID-19 vaccine hesitancy among infertile couples seeking fertility treatment. Thus, we conducted this survey among infertile patients in a reproductive medicine center, between September 2021 and December 2021, to estimate the prevalence of COVID-19 vaccine hesitancy and its influencing factors. Information was collected through face-to-face interviews among volunteers. Among the 987 included interviewees, 17.33% reported hesitancy in primary vaccination, 25.63% reported hesitancy in booster vaccination, and 32.32% delayed the primary vaccination. Hesitancy in primary vaccination was associated with unexplained infertility (OR: 1.77, 95% CI: 1.05-2.98), ongoing IVF treatment (OR: 2.17, 95% CI: 1.22-3.89), concerns for vaccine safety (OR: 4.13, 95% CI: 2.66-6.42), effectiveness (OR: 1.62, 95% CI: 1.15-2.28), and influence on pregnancy (OR: 2.80, 95% CI: 1.68-4.67). These factors were also associated with hesitancy in booster vaccination. Delay of the primary vaccination was inversely associated with a college or above degree (OR: 0.49, 95% CI: 0.27-0.87), previous history of influenza vaccination (OR: 0.67, 95% CI: 0.46-0.98), and was positively associated with concerns for the influence on pregnancy (OR: 7.78, 95% CI: 5.01-12.07). It is necessary to carry out targeted education program by health professionals to publicize the benefits of periconception vaccination, and to reduce the resistance to COVID-19 vaccine among infertile couples.

Satisfaction with new patient telehealth visits for reproductive endocrinology patients in the era of COVID-19.

PURPOSE: To study patient satisfaction with new patient telehealth visits in a reproductive endocrinology and infertility (REI) office. METHODS: A cross-sectional study in a university-based fertility clinic was completed including all new patients seen via telehealth between March 1, 2021, and August 19, 2021. Primary outcomes were perceived patient satisfaction, access, and preferences to telehealth visits. RESULTS: A total of 351 participants were contacted, 61.8% (n = 217) agreed to participate in the study, and 28.8% (n = 101) completed the survey. There were no significant differences in age, BMI, distance from clinic, or length of infertility with response to survey. Ninety-three percent of responders would use telehealth services again and were satisfied with the telehealth system. Telehealth improved access to healthcare for 88% and travel time for 96%. The median distance from clinic was 24 miles, and there was no significance difference in preference for telehealth visits over in person visits (p = 0.696). CONCLUSIONS: In the era of COVID-19, healthcare implementation has dramatically changed with a drastic increase in telehealth services. Based on our survey, majority of patients were satisfied with telehealth visits and believed it saved travel time while improving access to REI care. Despite no differences in patient preference for in person versus telehealth depending on their distance from clinic, this is reassuring because patients are satisfied with telehealth for reasons other than distance from clinic.

Rates of COVID-19 infection among in vitro fertilization patients undergoing treatment at a university reproductive health center.

BACKGROUND: The coronavirus disease 2019 (COVID-19) caused an unprecedented challenge for in-vitro fertilization (IVF) patients. The incidence of COVID-19 infection among this population is a fundamental knowledge gap. OBJECTIVE: The purpose of this study was to determine the rate of COVID-19 infection among IVF patients compared to other gynecologic surgery patients. MATERIALS AND METHODS: This retrospective study evaluated the incidence of COVID-19 infection among patients undergoing IVF, female fertility-related surgeries (FRS) and other gynecologic surgeries at a single academic institution in Los Angeles, California. All patients underwent routine COVID-19 polymerase chain reaction (PCR) screening prior to treatment. RESULT: A total of 2742 patients underwent asymptomatic COVID-19 screening before a surgical procedure or IVF between March 1, 2020, and April 5, 2021. The rate of COVID-19 infection among patients who underwent preoperative testing for a non-fertility-related gynecologic procedure was 1.74% (28/1612). In comparison, the positive test results for those who underwent either FRS or IVF were 0.56% (1/180) and 0.34% (1/290), respectively, representing 6.70% (2/30) of positive tests for the whole cohort. The infertility patients had a significantly lower positivity rate compared to the other gynecologic patients during preoperative COVID-19 testing (0.43% vs 1.74%, p = 0.03). CONCLUSION(S): Our study demonstrated that there was a significantly lower incidence of COVID-19 infections in infertility patients undergoing IVF or FRS compared to other gynecologic surgery patients. Future studies should evaluate the cost-effectiveness of routine screening in both the gynecology and infertility patient population, especially in the setting of different variant surges and vaccination rates.

Telehealth provider experience in reproductive endocrinology and infertility clinics during the COVID-19 pandemic and beyond.

PURPOSE: To assess telehealth services offered by reproductive endocrinology and infertility specialists and to gauge provider experiences with incorporating telehealth into their practices. METHODS: A 16-question web-based survey on use of telehealth was distributed to Society for Assisted Reproductive Technology (SART) clinics and to Society for Reproductive Endocrinology and Infertility (SREI) members. Clinic demographic data, telehealth descriptive data, and provider satisfaction with use of telehealth were assessed. Results were collected via Survey Monkey. RESULTS: A total of 1160 individuals (330 SART clinic contacts and 830 SREI members) were reached via email with an 18.6% (216) survey response rate. All respondents indicated that they offer telehealth visits. Several telehealth platforms were used, with Zoom (62.7%) and telehealth through the clinic's electronic medical record platform (34.8%) being the most common. The majority of participants (87.0%) anticipate they will offer telehealth visits after the COVID-19 pandemic. Roughly two-thirds (64.4%) of respondents anticipate fewer telehealth visits after the pandemic because of logistics, cost, and patient/provider preference. Nearly all providers are either "very satisfied" (66.2%) or "somewhat satisfied" (31.0%) with telehealth overall. CONCLUSION: Telehealth enabled safe patient-provider interactions throughout the COVID-19 pandemic. While only one-third of survey respondents offered telehealth services before the pandemic, nearly all providers express satisfaction with telehealth and anticipate they will offer telehealth services henceforth.

Effects of COVID-19 vaccination status, vaccine type, and vaccination interval on IVF pregnancy outcomes in infertile couples.

PURPOSE: This study aimed to explore whether the coronavirus disease (COVID-19) vaccination of both partners in infertile couples, different types of COVID-19 vaccines, and the interval between complete vaccination and oocyte retrieval or embryo transfer (ET) affect the quality of embryos and pregnancy rates in in vitro fertilization (IVF). METHODS: This was a prospective cohort study, comprising 735 infertile couples conducted between December 6, 2021, and March 31, 2022, in a single university hospital-based IVF center. The patients were divided into different groups according to the vaccination status of both partners in infertile couples, type of vaccine, and interval between complete vaccination and IVF treatment. The embryo quality and pregnancy rates were compared among different groups. RESULTS: The results showed that embryo quality and pregnancy rates had no significant differences among different groups. The multivariate regression model showed that the vaccination status of both infertile couples, types of vaccines, and intervals had no significant effects on the clinical pregnancy rate. CONCLUSIONS: The vaccination status of both partners in infertile couples, different types of vaccines, and time intervals have no effect on embryo quality and pregnancy rates in IVF. This is the first study to compare the vaccination status of both partners in infertile couples and the impact of different vaccine types on pregnancy rates and embryo quality in detail. Our findings provide evidence of vaccine safety for infertile couples wishing to undergo IVF treatment. This evidence is crucial for decision-making by clinicians and policymakers involved in IVF cycles.

SARS-CoV-2 the ASIA virus (Autoimmune/autoinflammatory Syndrome Induced by Adjuvants), the risk of infertility and vaccine hesitancy.

INTRODUCTION: COVID-19 has had a catastrophic impact on the world. The current death toll far exceeds 6 million and large numbers of patients are experiencing long-term medical and psychiatric morbidity from the infection. The immunopathology of severe COVID-19 is now better understood. In severely affected patients, there is a chaotic, destructive immune response triggered by SARS-CoV-2, where autoimmunity features prominently. AREAS COVERED: COVID-19 vaccines ensure a coordinated, balanced immune response to future SARS-CoV-2 infection. The rapid global deployment of effective COVID-19 vaccines has been hindered by financial, logistical and political barriers. Of concern is increasing vaccine hesitancy caused by unfounded conspiracy theories of vaccine adverse effects, often fueled by misinformation and disinformation on social media. EXPERT OPINION: This perspective discusses the potential impact of the so-called Autoimmune/autoinflammatory Syndrome Induced by Adjuvants (ASIA) on COVID-19 vaccine uptake. Proponents of the ASIA syndrome have inappropriately linked infertility to HPV vaccines and have recently suggested antigenic cross-reactivity between SARS-CoV-2 and ovarian follicles. COVID-19 vaccines have also been linked to ASIA and unfounded fear of infertility is a leading cause of vaccine hesitancy. Vaccine hesitancy caused by spurious disorders such as ASIA are likely to harm individuals and delay global vaccination efforts leading to emergence of vaccine and monoclonal antibody-resistant SARS-CoV-2 variants, thereby prolonging the COVID-19 pandemic.

Impact of Protocol Adjustments Due to the COVID-19 Pandemic on Infertility Treatment Outcomes.

As a result of the COVID-19 pandemic, our centre made adjustments that reduced the number of patient visits, ultrasound scans, laboratory investigations, and face-to face instructions. The objective of this study was to evaluate whether these changes had any effect on the pregnancy rate for patients undergoing infertility treatment. The primary outcome was clinical pregnancy rates from intrauterine insemination and frozen embryo transfer. Clinical pregnancy rates were not statistically different between patients who underwent either procedure before and after the protocols were put in place. It is reassuring to know our pandemic protocol adjustments did not have a negative impact on infertility treatment outcomes.