❦ ‘We have recently demonstrated a causal link between loss of gonadotropin-releasing hormone ( GnRH ), the master molecule regulating reproduction , and cognitive deficits during pathological aging , including Down syndrome and Alzheimer’s disease. Olfactory and cognitive alterations , which persist in some COVID-19 patients, and long-term hypotestosteronaemia in SARS-CoV-2-infected men are also reminiscent of the consequences of deficient GnRH, suggesting that GnRH system neuroinvasion could underlie certain post-COVID symptoms and thus lead to accelerated or exacerbated cognitive decline . We explored the hormonal profile of COVID-19 patients and targets of SARS-CoV-2 infection in post-mortem patient brains and human fetal tissue. We found that persistent hypotestosteronaemia in some men could indeed be of hypothalamic origin , favouring post-COVID cognitive or neurological symptoms , and that changes in testosterone levels and body weight over time were inversely correlated. Infection of olfactory sensory neurons and multifunctional hypothalamic glia called tanycytes highlighted at least two viable neuroinvasion routes . Furthermore, GnRH neurons themselves were dying in all patient brains studied , dramatically reducing GnRH expression. Human fetal olfactory and vomeronasal epithelia , from which GnRH neurons arise, and fetal GnRH neurons also appeared susceptible to infection . Putative GnRH neuron and tanycyte dysfunction following SARS-CoV-2 neuroinvasion could be responsible for serious reproductive , metabolic , and mental health consequences in long-COVID and lead to an increased risk of neurodevelopmental and neurodegenerative pathologies over time in all age groups .’ ❂ 📖 (12 Sep 2023 ~ eBioMedicine: Lancet Discovery Science) Long-COVID cognitive impairments and reproductive hormone deficits in men may stem from GnRH neuronal death ➤ © 2023 eBioMedicine: Lancet Discovery Science .

❦ Strikingly, the [foetal brain] haemorrhages are predominantly found in the late first and early second trimester of gestation , a period of development in which the effect of the COVID-19 pandemic has not been thoroughly investigated. Specifically, the majority were between 12 and 14 PCW [post-conception week] , a critical window of human foetal brain development when the endothelial tight junctions increase to form the blood-brain barrier . Our observations of disrupted foetal cerebral vasculature are consistent with reports of damage to the microvasculature of the adult brain in SARS-CoV-2 infected patients . ❂ 📖 (16 Jan 2023 ~ Brain) Haemorrhage of human foetal cortex associated with SARS-CoV-2 infection ➤ © 2023 Massimo et al / Brain.

❦ I’m so pro-mask and anti-infection that I started masking in 2019. Why? Because I was pregnant and working in healthcare. And in the before-times, it was normal to try your best to avoid contracting pathogens in pregnancy. We didn’t worry about the (illegitimately-termed) “generational immunity debt”. I was doing it wrong – intermittent masking with leaky, blue surgical masks, haha – but I was masking every day because I was pregnant during RSV/flu season, and I was acutely aware that both of those viruses (and several others) could put both myself and the baby at risk. Pregnancy is a state of relative immunosuppression, and there’s research associating fever, regardless of the pathogen, to neurodevelopmental disorders. Pathogens are always unwelcome, but especially so in pregnancy. I picked up the idea of masking while pregnant as a med student during my pediatrics rotation. One of my attendings (supervising physician) was pregnant, and she masked to protect herself. It really bothered me. Not the mask. It bothered me that she and her baby had to be in harm’s way at all. Where I live, women that work in childcare get preventative leave during pregnancy because of the risk of contracting viral illnesses. Not doctors, though. So here was this pediatrician working specifically with young children who have viral illnesses, while she was pregnant. It seemed so unfair. It left me upset. But she was doing what she could to protect herself. Gloves. Scrubs. Hand hygiene. And a mask all day. With every patient. Even with us. So years later, when I was pregnant, I masked at work, too. I actively tried to avoid viral illness. After all, if I had a job in childcare, I’d be on preventative leave right? So why would I expose my pregnant self to viruses in a healthcare setting, when doctors were taking women in other high-infectious-risk environments off work entirely? So anyway, imagine my utter shock when 2020 rolled around, and the “experts” started telling the population that masks don’t work. Remember that? — “Masks only protect others and not the wearer,” they said. That was the first lie in what we now know would be a long stream of lies. It was with that first lie that I understood that I needed to rely on myself, and not just the official messaging. That to keep my newborn safe, I would have to diligently double-check what we were being told. I knew I needed to find the truth-tellers among the “experts”. And this is not just about masks. Maybe the decision to mask in pregnancy wasn’t common pre-2020 – but looking out for each other absolutely was. In dermatology, we’d try to do the fever-plus-rash consults (and any other virus-risky consults) for pregnant colleagues. Why? Because why take unnecessary risks? Pathogens in pregnancy are bad. We’d often worry about the risk of the rash-plus-fever consult being measles or varicella. — “But aren’t you vaccinated?” Yes, and why take the risk? That was the mindset before the “vax and relax” lie. We got vaccinated against influenza in pregnancy as recommended because we didn’t want to catch it – not so that we could go out and expose ourselves to it. We didn’t “vax and relax”. We “vaxxed and continued to actively avoid” . It was an easier task with the flu than it is with Covid, given how much less contagious flu is. With Covid, individual effort is insufficient. For it to be avoidable with small individual efforts, there needs to be not much of it circulating. Which would require a big Public Health project. So the deciders decided that that was not going to happen. We were going to live with infinite, forever Covid. But that would endanger so many people. So that’s when the “pandemic of the unvaccinated” lie was born. And the “Omicron is mild” lie. And the “Long Covid is rare” lie. Honestly, there are just so many lies that I can’t keep them all straight. We’re just constantly being “nudged” with nonsense messaging to get us to accept unmitigated exposure to SARS and other pathogens as normal. And it’s working. People seem even less cautious than they were before. We had crushed RSV and the flu, emptied pediatric hospitals, and had negative pediatric excess mortality. And we took zero lessons from that time forward with us. We figured out how to dramatically lower infant / childhood morbidity / mortality, and they made sure we unlearned it ASAP. They didn’t marvel at that achievement, and strive to do the non-disruptive stuff like cleaning the air and normalizing masks during the winter viral season. Instead, the “let a SARS virus mass-infect kids”, and the lies to normalize all the suffering that we’re seeing just keep on coming. See, that’s the problem with siding with the disinformers. Maybe you let the lies go because you agreed that kids shouldn’t have to wear masks for the benefit of “the vulnerable”. But now the disinformers are saying that society shouldn’t have to mask up for the safety of your kids, either. Siding with people that openly devalue the lives and right to safety of other human beings, because you are not personally in the devalued group, rarely ever goes well. And that’s the point of this essay. We’ve slowly and tragically slid down a slippery slope. This is nothing like 2019. In 2019 we would have cared that pediatric ICUs were overflowing, and worn masks to flatten the curve for kids. We’ve fallen so far since 2019. And with each passing day that our society can be convinced not to wear a mask to work – or in the mall, or on the bus – to prevent others from dying, or to keep babies out of the ICU, we slip a little further down the slope. And the scary thought is that this is very unlikely to be rock bottom. We still have further to fall. © 2022 Dr. Lisa Iannattone ➲

❦ What are we going to tell young men in twenty years’ time if* they discover that they can’t ever have an erection in the usual manner due to repeated childhood COVID infections? * 📖 (12 Feb 2022 ~ International Journal of Impotence Research ~ Tip of the iceberg: erectile dysfunction and COVID-19 ➤ Have we thought about using vaccines and therapeutics in children to prevent this? What about protecting children with NPIs ( non-pharmaceutical interventions )? We all worry about kids missing out on fun stuff in this pandemic. What about their sexual health later in life? Is this not fun? Is this not important? Is this not for them ? Let’s not be squeamish. Let’s think this through properly. Our youth are being repeatedly infected with a pathogen that we know affects sexual and reproductive health in a myriad of ways. Due to the fact that I will likely be dead by the time you figure this out, I’m going to take the liberty of saying a few things now. 1) This is unacceptable. 2) I told you so. 3) I’m sorry future adults, I really tried. I hope that solutions come your way. © 2023 Dr. Noor Bari ➲

❦ ‘SARS-CoV-2 enters the human body through the ACE2 receptor and exerts different effects on various systems of the human body. Regarding the impact of COVID-19 on the reproductive system, ACE2 is highly expressed in the testis of the male reproductive system. A study of scRNA-seq data in adult human testes showed that male gonads may be infected with SARS-CoV-2, which may cause male reproductive dysfunction. The increase in pro-inflammatory cells and decrease in androgens in men infected with SARS-CoV-2 may lead to a decreased gonadal function. SARS-CoV-2 may also infect the ovaries, uterus, vagina, and placenta in the female reproductive system through the expression of ACE2 receptors, leading to infertility, menstrual disorders, and fetal distress. Pregnant women infected with SARS-CoV-2 have a lower incidence of vertical transmission of the virus to newborns, which may be related to the lower expression of ACE2 and TMPRSS2 in the placenta and an increase in SARS-CoV-2-specific antibodies and IgG during pregnancy; however, it may cause inflammation of the placenta, which increases the risk of pre-eclampsia and placental abruption during pregnancy. ACE2 is expressed at a high level in testicular tissues compared to that in the ovaries and uterus. Therefore, male patients may be slightly more affected by SARS-CoV-2 infection than females.’ ❂ 📖 (20 Sep 2022 ~ Frontiers in Cellular and Infection Microbiology) Therapeutic prospects of ceRNAs in COVID-19 ➤ © 2022 Lin Liu et al / Frontiers in Cellular and Infection Microbiology.

❦ ‘Statistics are significant regarding the link between COVID-19 and impotence. In the largest study to date on this topic, Dr. Ranjith Ramasamy, director of male reproductive medicine and surgery for the University of Miami Health System, says: “We found the risk of getting diagnosed with erectile dysfunction (ED) was about 20% higher in men who had COVID versus those who did not.” Survey studies in China and Italy, among multiple others, support the notion of a link between ejaculation difficulty and the virus – a study of nearly half a million adults published in Nature* identified ejaculation difficulty and reduced libido as Long COVID symptoms in men. * 📖 (25 Jul 2022 ~ Nature: Medicine) Symptoms and risk factors for long COVID in non-hospitalized adults ➤ “We know that COVID infection, especially with high fever, can significantly drop sperm counts and motility (the number of sperm moving),” says Raevti Bole, a Cleveland Clinic fellow in male fertility and andrology. A University of Florida Health study* found reports of impotence were three times as likely after an infection. * 📖 (14 Mar 2022 ~ Miami Herald) Can COVID cause sexual dysfunction? Here's what experts know – and what they don’t ➤ “Men are generally reluctant to report sexual dysfunction, suggesting that the problem may be greater than we know.” COVID-19 can adversely affect endothelial cell function, which is a significant clue. These cells release substances that modulate vascular relaxation and contraction, so damage to them is likely to impair a wide range of functions, including the body’s ability to get proper blood flow to the penis when it’s most urgently needed. Ramasamy and his researchers have found evidence of the virus remaining within the endothelial cells of penile tissue as much as seven months after infection, which suggests that direct damage to cavernosal endothelium may affect erectile function. A non-peer-reviewed, pre-print study conducted on COVID-infected monkeys by researchers at Northwestern Medicine found that multiple sites within the male genital tract, including the prostate, penis and testicles, were infected with SARS-CoV-2. Ramasamy described it as “probably the best evidence we have that the virus can remain within these organs and can replicate”.’ ❂ 📖 (17 Aug 2022 ~ Fortune) Long COVID could be leading to a wave of erectile dysfunction as the pandemic invades our sex lives ➤ 📖 (15 Dec 2021 ~ Sexual Medicine) COVID-19 Infection Is Associated With New Onset Erectile Dysfunction: Insights From a National Registry ➤ © 2023 Carolyn Barber / Fortune.

❦ ‘Babies whose mothers were infected with the coronavirus during pregnancy may face a higher risk of brain development disorders such as autism and bipolar disorder, a new study that examined more than 7,500 births suggests. Other viruses, such as influenza and measles, are thought to make babies more vulnerable to conditions such as autism, schizophrenia and depression if they are exposed in utero. After the researchers accounted for other factors that could affect a child’s risk for a neurodevelopmental issue — such as pre-term births, the mother’s age and the baby’s gender — they calculated that babies with prenatal exposure to SARS-CoV-2 were 86% more likely to be diagnosed in their first year compared with babies who weren’t exposed before they were born. “Unfortunately, it is very possible that asymptomatic or mild infections might also be linked to neurodevelopmental disorders in the child.” The medical advice for pregnant women remains unchanged. “This should be another wake-up call for pregnant women to get vaccinated, and boosted, and stay masked and take as many precautions as they can.” ❂ 📖 (10 Jun 2022 ~ LA Times) Coronavirus infection during pregnancy linked to brain development problems in babies ➤ 📖 (9 June 2022 ~ JAMA Network Open) Neurodevelopmental Outcomes at 1 Year in Infants of Mothers Who Tested Positive for SARS-CoV-2 During Pregnancy ➤ © 2022 Sumeet Kulkarni / LA Times

❦ ‘In this analysis of 222 offspring of mothers infected with SARS-CoV-2, compared with the offspring of 7550 mothers in the control group (not infected) delivered during the same period, we observed neurodevelopmental diagnoses to be significantly more common among exposed offspring, particularly those exposed to third-trimester maternal infection . The majority of these diagnoses reflected developmental disorders of motor function or speech and language .’ ❂ 📖 (9 Jun 2022 ~ JAMA: Pediatrics) Neurodevelopmental Outcomes at 1 Year in Infants of Mothers Who Tested Positive for SARS-CoV-2 During Pregnancy ➤ © 2022 Edlow et al / JAMA: Pediatrics.

❦ The effects of SARS-CoV-2 infection during pregnancy on fetal lung development have been largely understudied throughout the COVID-19 pandemic. To our knowledge, this is the first study showing reduced fetal lung volume in otherwise healthy pregnant women with SARS-CoV-2 infection. This reduction was dependent on the timepoint of infection, indicating that the most significant results occurred in the third trimester. ❂ 📖 (10 Apr 2022 ~ The Lancet / Respiratory Medicine) Effects of SARS-CoV-2 on prenatal lung growth assessed by fetal MRI ➤ © 2022 Stoecklein et al / The Lancet: Respiratory Medicine.

❦ We describe a severe form of SARS-CoV-2 placentitis with thrombohematomas occurring primarily in stillbirths from pregnancies complicated by SARS-CoV-2 infection during the 2021 pandemic wave. This pathology is distinctive and grossly identifiable, representing a change in the spectrum of SARS-CoV-2 pregnancy complications. The thrombohematomas are likely a result of severe viral placental damage. Our findings suggest a pathogenetic mechanism for the reported increased risk of stillbirth associated with SARS-CoV-2 infection in 2021. ❂ 📖 (21 Mar 2022 ~ JAMA Network Open / Research Letter / Infectious Diseases) SARS-CoV-2 Placentitis and Intraparenchymal Thrombohematomas Among COVID-19 Infections in Pregnancy ➤ © 2022 Huynh et al / JAMA Network Open: Infectious Diseases.

❦ SARS-CoV-2 infection in pregnancy is known to confer a risk of increased morbidity and mortality for the mother. Placental and fetal infection with SARS-CoV-2 have been rare to date; SARS-CoV-2 infection in pregnancy appears most likely to impact fetal brain development via maternal and placental immune activation. Maternal and placental immune activation may impact the placenta and developing fetal brain via induction of immune activation and proinflammatory cytokine production, dysregulation of serotonin/other neurotransmitter signaling, and increased oxidative stress. ❂ 📖 (13 Feb 2022 ~ Trends in Molecular Medicine) COVID-19 in pregnancy: implications for fetal brain development ➤ © 2022 Shook et al / Trends in Molecular Medicine.

❦ Most data support the role of COVID-19 in erectile dysfunction (ED) . Although the exact pathophysiology is not fully elucidated, we strove to gather the most probable reasons around this topic and elaborate on related mechanisms. In summary, COVID-19 infection could affect male sexual function through endothelial damage in erectile tissue, testicular damage, and psychological alterations. ❂ 📖 (12 Feb 2022 ~ International Journal of Impotence Research) Tip of the iceberg: erectile dysfunction and COVID-19 ➤ © 2022 Kaynar et al / International Journal of Impotence Research.

❦ ‘Researchers in 12 countries, including the United States, analyzed placental and autopsy tissue from 64 stillbirths and four newborns who died shortly after birth. The cases all involved unvaccinated women who had COVID-19 during their pregnancy. The study bolsters evidence from small case reports and confirms that placenta damage – rather than an infection of the fetus – is the likely cause of many COVID-19-related stillbirths. Previous evidence suggests the chances of stillbirth are higher than usual for pregnant women with COVID-19, particularly if infected with the Delta variant. Vaccination recommendations include pregnant women and note their higher risk for complications when infected. Dr. David Schwartz, an Atlanta pathologist who led the study, said other infections can infiltrate the placenta and cause stillbirth, typically by infecting and damaging the fetus. (A recent example of this is the Zika virus.) Schwartz and his colleagues wanted to see if that was the case with stillbirths in women with COVID-19. But what they found was almost the opposite: it was the placenta that was infected and extensively destroyed. "Many of these cases had over 90% of the placenta destroyed – very scary," said Schwartz. Normal placenta tissue is a healthy reddish hue and spongy. The specimens they studied were stiff, with dark discolorations of dead tissue. While other infections can sometimes damage the placenta, Schwartz said he’d never seen them cause such consistent, extensive destruction.’ ❂ 📖 (10 Feb 2022 ~ AP / Los Angeles Times) Coronavirus can destroy the placenta and lead to stillbirths ➤ 📖 (10 Feb 2022 ~ Archives of Pathology & Laboratory Medicine) Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury: A Study of 68 Cases With SARS-CoV-2 Placentitis From 12 Countries ➤ © 2022 Lindsey Tanner / AP / LA Times.

❦ SARS-CoV-2 is speculated to affect the ovary’s follicular membrane and granular cells, influence the growth of follicles and the quality of oocytes, lessen the ovarian reserve function, and cause infertility or pregnancy loss . It can also damage the endometrial epithelial cells that affect early embryo implantation. Several studies have suggested that SARS-CoV-2 can indirectly affect fetal growth in pregnant women. Studies have reported that all SARS-CoV-2 infected males had orchitis at autopsy. The testis has a risk of COVID-19 infection but the mechanism of infection is still not clear. Studies also suggest that the expression of ACE2 in testicular cells is associated with age. The highest expression was reported in the 30-year-old age group, while the lowest was reported in the 60-year-old group. COVID-19 infection could result in more severe testicular damage in young men than older men. SARS-CoV-2 infections in males have also been associated with a higher risk of male sterility . Semen analysis also reported that patients with moderate infection showed lower sperm concentration , a lower total number of sperm per ejaculate, motile sperm, and progressively motile sperm than healthy individuals. ❂ 📖 (19 Jan 2022 ~ News Medical Life Sciences) Impact of COVID-19 on male and female reproductive health ➤ © 2022 Suchandrima Bhowmik / News Medical Life Sciences.