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OBJECTIVES: During the COVID-19 pandemic in Qatar, many patients who were severely ill were colonized and infected by Candida auris, an invasive multidrug-resistant yeast pathogen that spreads through nosocomial transmission within healthcare facilities. Here, we investigated the molecular epidemiology of these C. auris isolates and the mechanisms associated with antifungal drug resistance. METHODS: Whole genomes of 76 clinical C. auris isolates, including 65 from patients with COVID-19 collected from March 2020 to June 2021, from nine major hospitals were sequenced on Illumina NextSeq. Single nucleotide polymorphisms were used to determine their epidemiological patterns and mechanisms for antifungal resistance. The data were compared with those published prior to the COVID-19 pandemic from 2018 to 2020 in Qatar. RESULTS: Genomic analysis revealed low genetic variability among the isolates from patients with and without COVID-19, confirming a clonal outbreak and ongoing dissemination of C. auris among various healthcare facilities. Based on antifungal susceptibility profiles, more than 70% (22/28) of isolates were resistant to both fluconazole and amphotericin B. Variant analysis revealed the presence of multi-antifungal resistant isolates with prominent amino acid substitutions: Y132F in ERG11 and V704L in CDR1 linked to reduced azole susceptibility and the emergence of echinocandin resistance samples bearing mutations in FKS1 in comparison with pre-COVID-19 pandemic samples. One sample (CAS109) was resistant to three classes of antifungal drugs with a unique premature stop codon in ERG3 and novel mutations in CDR2, which may be associated with elevated amphotericin B and azole resistance. DISCUSSION: Candida auris isolates from patients with COVID-19 and from most patient samples without COVID-19 in Qatar were highly clonal. The data demonstrated the emergence of multidrug-resistant strains that carry novel mutations linked to enhanced resistance to azoles, echinocandins, and amphotericin B. Understanding the epidemiology and drug resistance will inform the infection control strategy and drug therapy.
ABSTRACT
Objectives During the COVID-19 pandemic in Qatar, many severely ill patients were colonized and infected by Candida auris, an invasive multidrug-resistant yeast pathogen that spreads through nosocomial transmission within healthcare facilities. Herein, we investigated the molecular epidemiology of these C. auris isolates and the mechanisms associated with antifungal drugs resistance. Methods Whole genomes of 76 clinical C. auris isolates, including 65 from COVID-19 patients collected from Mar 2020 - Jun 2021, from nine major hospitals were sequenced on Illumina NextSeq. SNPs were used to determine their epidemiological patterns and mechanisms for antifungal resistance. The data was compared to those published prior to COVID-19 pandemic from 2018-2020 in Qatar. Results Genomic analysis revealed low genetic variability among the isolates from COVID-19 and non-COVID-19 patients, confirming a clonal outbreak and ongoing dissemination of C. auris among various healthcare facilities. Based on antifungal susceptibility profiles, over 70% (22/28) of isolates were resistant to both fluconazole and amphotericin B. Variant analysis revealed the presence of multi-antifungal resistant isolates with prominent amino acid substitutions;Y132F in ERG11 and V704L in CDR1 linked to reduced azole susceptibility, and the emergence of echinocandin resistance samples bearing mutations in FKS1 in comparison to pre-COVID pandemic samples. One sample (CAS109) was resistant to three classes of antifungal drugs with a unique premature stop codon in ERG3 and novel mutations in CDR2, which may be associated with elevated amphotericin B and azole resistance. Conclusion C. auris isolates from COVID-19 patients, and from most non-covid patient samples in Qatar were highly clonal. The data demonstrated the emergence of multidrug-resistant strains that carry novel mutations linked to enhanced resistance to azoles, echinocandins and amphotericin B. Understanding the epidemiology and drug resistance will inform infection control strategy and drug therapy.
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Objective: To determine whether the COVID-19 mRNA vaccines can negatively impact the semen parameters of young healthy men in the long-term. Design: We conducted semen analyses on 12 men before, 3 and 9 months after achieving fully vaccinated status. Individuals who admitted a history of infertility or previous azoospermia were excluded from study participation. Subjects: Healthy male volunteers between the ages of 18-50 years old were recruited between September 2021 - March 2022. Main Outcome Measures: Semen analyses were performed and evaluated volume, sperm concentration, total motility, and total motile sperm count (TMSC). The primary outcome was median change in the TMSC at baseline, 3 months, and at least 9 months following vaccination. Results: A total of 12 men volunteered in our study (median age 26 [25 - 30] years). Subjects provided follow-up semen samples at a median of 10 months following the second vaccine dose. There were no significant changes in any semen parameters between baseline, 3 months, and 10 months following vaccination. Baseline samples demonstrated median sperm concentrations and TMSC of 29.5 million/cc [9.3 - 49] and 31 million [4-51.3], respectively. At 9-month follow-up, sperm concentration and TMSC were 43 [20.5 - 63.5] (P=.351) and 37.5 [8.5 - 117.8] (P=.519), respectively. Of note, there were no significant changes in semen volume nor total motility (%) for participants at follow-up. Conclusion: COVID-19 mRNA vaccines and the booster dose does not appear to negatively impact the semen parameters of healthy males up to 10 months following vaccination.
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The identification of Candida auris fungemia in critically ill COVID-19 patients is detrimental, with huge implications on patient mortality and infectious control measures.
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Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by a novel coronavirus (SARS-CoV-2), which demonstrates the ability to invade endothelial cells and cause systemic inflammation. Many possible long-term sequelae of COVID-19 remain unidentified. We describe a case of a man who developed Peyronie's disease after a resolved COVID-19 infection. Erectile dysfunction was confirmed by the International Index of Erectile Function-15(IIEF) and Sexual Health Inventory for Men(SHIM) scores. A diagnosis was Peyronie's disease was confirmed on ultrasound. Furthermore, he was found to have low endothelial progenitor cells colony-forming units and low brachial artery flow-mediated vasodilation, both of that are indicative of endothelial dysfunction. This case suggests Peyronie's disease should be considered as a possible sequela of COVID-19 infection and providers should inquire about a history of COVID-19 infection in patients presenting with Peyronie's disease.
Subject(s)
COVID-19 , Erectile Dysfunction , Penile Induration , Endothelial Cells , Erectile Dysfunction/etiology , Humans , Male , Penile Induration/diagnosis , SARS-CoV-2ABSTRACT
PURPOSE: A pilot study to describe histopathological features of penile tissue of patients who recovered from symptomatic COVID-19 infection and subsequently developed severe erectile dysfunction (ED). MATERIALS AND METHODS: Penile tissue was collected from patients undergoing surgery for penile prosthesis for severe ED. Specimens were obtained from two men with a history of COVID-19 infection and two men with no history of infection. Specimens were imaged with TEM and H&E staining. RT-PCR was performed from corpus cavernosum biopsies. The tissues collected were analyzed for endothelial Nitric Oxide Synthase (eNOS, a marker of endothelial function) and COVID-19 spike-protein expression. Endothelial progenitor cell (EPC) function was assessed from blood samples collected from COVID-19 (+) and COVID-19 (-) men. RESULTS: TEM showed extracellular viral particles ~100 nm in diameter with peplomers (spikes) near penile vascular endothelial cells of the COVID-19 (+) patients and absence of viral particles in controls. PCR showed presence of viral RNA in COVID-19 (+) specimens. eNOS expression in the corpus cavernosum of COVID-19 (+) men was decreased compared to COVID-19 (-) men. Mean EPC levels from the COVID-19 (+) patients were substantially lower compared to mean EPCs from men with severe ED and no history of COVID-19. CONCLUSIONS: Our study is the first to demonstrate the presence of the COVID-19 virus in the penis long after the initial infection in humans. Our results also suggest that widespread endothelial cell dysfunction from COVID-19 infection can contribute to ED. Future studies will evaluate novel molecular mechanisms of how COVID-19 infection leads to ED.
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PURPOSE: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created a surge of research to help better understand the breadth of possible sequelae. However, little is known regarding the impact on semen parameters and fertility potential. We sought to investigate for presence of viral RNA in semen of men with SARS-CoV-2 infection and to evaluate its effect on semen parameters in ejaculate. MATERIALS AND METHODS: We prospectively recruited thirty men diagnosed with acute SARS-CoV-2 infection using real-time reverse transcriptase polymerase chain reaction (RT-PCR) of pharyngeal swab specimens. Semen samples were collected from each individual using mailed kits. Follow-up semen samples were done with mailed kits or in-person in office setting. Semen analysis and PCR was performed after samples were received. RESULTS: Thirty semen samples from recovered men were obtained 11-64 days after testing positive for SAR-CoV-2 infection. The median duration between positive SAR-CoV-2 test and semen collection was 37 days (interquartile range [IQR]=23). The median total sperm number (TSN) in ejaculate was 12.5 million (IQR=52.1). When compared with age-matched SARS-CoV-2(-) men, TSN was lower among SARS-CoV-2(+) men (p=0.0024). Five men completed a follow-up sperm analysis (median 3 months) and had a median TSN of 18 million (IQR=21.6). No RNA was detected by means of RT-PCR in the semen in 16 samples tested. CONCLUSIONS: SARS-CoV-2 infection, though not detected in semen of recovered men, can affect TSN in ejaculate in the acute setting. Whether SARS-CoV-2 can affect spermatogenic function long-term remains to be evaluated.
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BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a virus that is present in most bodily fluids. However, whether SARS-CoV-2 is present in the semen remains underexplored. Thus, we systematically reviewed the existing studies on the presence of SARS-CoV-2 in semen. METHODS: A literature search of the PubMed, Embase, Cochrane, Web of Science, Google Scholar, and Ovid databases was performed for articles from the dates of their inception to August 2020 using the following keywords: COVID-19, SARS-CoV2, seminal, semen, and sperm. After excluding non-human studies and articles that were not in the English language, we identified 19 relevant studies. The full text of the articles were reviewed and a total of eight articles remained after applying our selection criteria. RESULTS: After reviewing the presence of SARS-CoV-2 in the eight different studies using semen samples, only one reported the presence of the virus. Six out of 160 total semen samples with SARS-CoV-2 positive demonstrated the presence of viral RNA, of which 2 were from males in the recovery phase and 4 from the acute phase of the infection. CONCLUSION: The novel nature of SARS-CoV-2 has limited the number and size of studies on semen. Nevertheless, the current literature, while limited, has confirmed the presence of SARS-CoV-2 in semen in one out of the eight reported studies and totaling 4.3% of the population screened. Taken together, the risk of the presence of SARS-CoV-2 in semen appears to be extremely low and likely negligible in recovered men. Future studies need to focus on whether complete viral particles can be seen in semen and the possibility of sexual transmission.
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PURPOSE: To evaluate the presence and analyze the pathological changes within the testes of patients who died or recovered from severe acute respiratory syndrome coronavirus 2 (COVID-19) complications. MATERIALS AND METHODS: Testis tissue was collected from autopsies of COVID-19 positive (n=6) and negative men (n=3). Formalin-fixed paraffin-embedded tissues were stained with hematoxylin and eosin (H&E) and subjected to immunofluorescence for angiotensin-converting enzyme 2 (ACE-2) expression. Fluorescent-labeled tissue slides were imaged on a quantitative pathology scope with various zoom levels allowing for qualitative and quantitative interpretation. Tissue from four COVID-19 positive autopsy cases and a live seroconverted patient was imaged with transmission electron microscopy (TEM). RESULTS: H&E histomorphology showed three of the six COVID-19 biopsies had normal spermatogenesis while the remaining three had impaired spermatogenesis. TEM showed the COVID-19 virus in testis tissue of one COVID-19 positive autopsy case and the live biopsy, H&E stain on the same autopsy case demonstrated interstitial macrophage and leukocyte infiltration. Immunofluorescent stained slides from six COVID-19 positive men demonstrated a direct association between increased quantitative ACE-2 levels and impairment of spermatogenesis. CONCLUSIONS: The novel COVID-19 has an affinity for ACE-2 receptors. Since ACE-2 receptor expression is high in the testes, we hypothesized that COVID-19 is prevalent in testes tissue of infected patients. This study suggests the male reproductive tract, specifically the testes, may be targets of COVID-19 infection. We found an inverse association between ACE-2 receptor levels and spermatogenesis, suggesting a possible mechanism of how COVID-19 can cause infertility.