SARS-CoV-2 infection (COVID-19) and male fertility: Something we should be worried about?

Zeginiadou, Theodosia; Symeonidis, Evangelos N.; Symeonidis, Asterios; Vakalopoulos, Ioannis

doi:10.1177/03915603231175941

Cited by 3 publications

(2 citation statements)

References 82 publications

(162 reference statements)

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“…TMPRSS2 expression is high in human prostate gland and this enzyme regulates sperm function in the seminal prostasome 357 . Increasing evidence suggests that COVID-19 could inflict detrimental effects on spermatogenesis and hormonal regulation in male patients 369 . Abnormal serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) levels were also reported, which suggests a dysfunctional hypothalamic-pituitary-gonadal (HPG) axis in COVID-19 patients 370 .…”

Section: Pasc: Viral-hijacked Host Cellular Factors and Consequencesmentioning

confidence: 99%

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

Naidu,

Wang,

Rao

et al. 2024

npj Sci Food

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SARS‐CoV‐2, the etiological agent of COVID-19, is devoid of any metabolic capacity; therefore, it is critical for the viral pathogen to hijack host cellular metabolic machinery for its replication and propagation. This single-stranded RNA virus with a 29.9 kb genome encodes 14 open reading frames (ORFs) and initiates a plethora of virus–host protein–protein interactions in the human body. These extensive viral protein interactions with host-specific cellular targets could trigger severe human metabolic reprogramming/dysregulation (HMRD), a rewiring of sugar-, amino acid-, lipid-, and nucleotide-metabolism(s), as well as altered or impaired bioenergetics, immune dysfunction, and redox imbalance in the body. In the infectious process, the viral pathogen hijacks two major human receptors, angiotensin-converting enzyme (ACE)-2 and/or neuropilin (NRP)-1, for initial adhesion to cell surface; then utilizes two major host proteases, TMPRSS2 and/or furin, to gain cellular entry; and finally employs an endosomal enzyme, cathepsin L (CTSL) for fusogenic release of its viral genome. The virus-induced HMRD results in 5 possible infectious outcomes: asymptomatic, mild, moderate, severe to fatal episodes; while the symptomatic acute COVID-19 condition could manifest into 3 clinical phases: (i) hypoxia and hypoxemia (Warburg effect), (ii) hyperferritinemia (‘cytokine storm’), and (iii) thrombocytosis (coagulopathy). The mean incubation period for COVID-19 onset was estimated to be 5.1 days, and most cases develop symptoms after 14 days. The mean viral clearance times were 24, 30, and 39 days for acute, severe, and ICU-admitted COVID-19 patients, respectively. However, about 25–70% of virus-free COVID-19 survivors continue to sustain virus-induced HMRD and exhibit a wide range of symptoms that are persistent, exacerbated, or new ‘onset’ clinical incidents, collectively termed as post-acute sequelae of COVID-19 (PASC) or long COVID. PASC patients experience several debilitating clinical condition(s) with >200 different and overlapping symptoms that may last for weeks to months. Chronic PASC is a cumulative outcome of at least 10 different HMRD-related pathophysiological mechanisms involving both virus-derived virulence factors and a multitude of innate host responses. Based on HMRD and virus-free clinical impairments of different human organs/systems, PASC patients can be categorized into 4 different clusters or sub-phenotypes: sub-phenotype-1 (33.8%) with cardiac and renal manifestations; sub-phenotype-2 (32.8%) with respiratory, sleep and anxiety disorders; sub-phenotype-3 (23.4%) with skeleto-muscular and nervous disorders; and sub-phenotype-4 (10.1%) with digestive and pulmonary dysfunctions. This narrative review elucidates the effects of viral hijack on host cellular machinery during SARS-CoV-2 infection, ensuing detrimental effect(s) of virus-induced HMRD on human metabolism, consequential symptomatic clinical implications, and damage to multiple organ systems; as well as chronic pathophysiological sequelae in virus-free PASC patients. We have also provided a few evidence-based, human randomized controlled trial (RCT)-tested, precision nutrients to reset HMRD for health recovery of PASC patients.

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Section: Pasc: Viral-hijacked Host Cellular Factors and Consequencesmentioning

confidence: 99%

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

Naidu,

Wang,

Rao

et al. 2024

npj Sci Food

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“…COVID-19 pathophysiology is closely related to OS and semen quality deterioration observed in men after COVID-19 [ 43 ]. Antioxidants seem to be a promising adjuvant treatment against the disease progression with a simultaneous protective role to male fertility.…”

Section: Could Antioxidants Play a Role In Counteracting Covid-19 Os-...mentioning

confidence: 99%

COVID-19 and Male Infertility: Is There a Role for Antioxidants?

Kalfas,

Kaltsas,

Symeonidis

et al. 2023

Antioxidants

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Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), jeopardizes male fertility because of the vulnerability of the male reproductive system, especially the testes. This study evaluates the effects of the virus on testicular function and examines the potential role of antioxidants in mitigating the damage caused by oxidative stress (OS). A comprehensive PubMed search examined exocrine and endocrine testicular function alteration, the interplay between OS and COVID-19-induced defects, and the potential benefit of antioxidants. Although the virus is rarely directly detectable in sperm and testicular tissue, semen quality and hormonal balance are affected in patients, with some changes persisting throughout a spermatogenesis cycle. Testicular pathology in deceased patients shows defects in spermatogenesis, vascular changes, and inflammation. Acute primary hypogonadism is observed mainly in severely infected cases. Elevated OS and sperm DNA fragmentation markers suggest redox imbalance as a possible mechanism behind the fertility changes. COVID-19 vaccines appear to be safe for male fertility, but the efficacy of antioxidants to improve sperm quality after infection remains unproven due to limited research. Given the limited and inconclusive evidence, careful evaluation of men recovering from COVID-19 seeking fertility improvement is strongly recommended.

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Update on known and emergent viruses affecting human male genital tract and fertility

Dabizzi,

Maggi,

Torcia

2024

Basic Clin. Androl.

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Many viruses infect the male genital tract with harmful consequences at individual and population levels. In fact, viral infections may induce damage to different organs of the male genital tract (MGT), therefore compromising male fertility. The oxidative stress, induced during viral-mediated local and systemic inflammation, is responsible for testicular damage, compromising germinal and endocrine cell functions. A reduction in sperm count, motility, number of normal sperm and an increase in DNA fragmentation are all common findings in the course of viral infections that, however, generally regress after infection clearance. In some cases, however, viral shedding persists for a long time leading to unexpected sexual transmission, even after the disappearance of the viral load from the blood.The recent outbreak of Zika and Ebola Virus evidenced how the MGT could represent a reservoir of dangerous emergent viruses and how new modalities of surveillance of survivors are strongly needed to limit viral transmission among the general population.Here we reviewed the evidence concerning the presence of relevant viruses, including emergent and re-emergent, on the male genital tract, their route of entry, their adverse effects on male fertility and the pattern of viral shedding in the semen.We also described laboratory strategies to reduce the risk of horizontal or vertical cross-infection in serodiscordant couples undergoing assisted reproductive technologies.

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SARS-CoV-2 infection (COVID-19) and male fertility: Something we should be worried about?

Cited by 3 publications

References 82 publications

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

COVID-19 and Male Infertility: Is There a Role for Antioxidants?

Update on known and emergent viruses affecting human male genital tract and fertility

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