Sex differences in mortality in the intensive care unit patients with severe COVID-19

Moiseev, Sergey; Brovko, Michail; Tao, E.; Bulanov, Nikolay; Akulkina, Larisa; Fоmin, Victоr

doi:10.1016/j.jinf.2020.09.031

Cited by 9 publications

(10 citation statements)

References 6 publications

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“…Looking at mortality according to gender, it seems the effect of fluvoxamine was more significant among female COVID‐19 ICU patients. Gender differences in mortality in ICU COVID‐19 patients have been described before, with significantly lower mortality rates among women 28 . Also, gender‐specific differences in fluvoxamine pharmacokinetics have been described in the published literature, 29 as well as gender differences in CYP2D6 30 and CYP1A2 31 enzyme activity.…”

Section: Discussionmentioning

confidence: 77%

“…Gender differences in mortality in ICU COVID‐19 patients have been described before, with significantly lower mortality rates among women. 28 Also, gender‐specific differences in fluvoxamine pharmacokinetics have been described in the published literature, 29 as well as gender differences in CYP2D6 30 and CYP1A2 31 enzyme activity. Whether the same gender‐specific differences which impact COVID‐19 mortality also play a role in the response to fluvoxamine treatment, or whether biological sex‐specific differences in cytochrome P450 enzymes CYP2D6 and/or CYP1A2 could be responsible for improved efficacy in female patients and consequently better outcomes remains to be investigated in additional studies.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Safety and efficacy of fluvoxamine in COVID‐19 ICU patients: An open label, prospective cohort trial with matched controls

Čalušić

Marčec

Luksa

et al. 2021

Brit J Clinical Pharma

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Aims Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) and sigma‐1 receptor agonist, has so far shown promise in the prevention of COVID‐19 progression as an early treatment option in three trials. The aim of this study was to evaluate the safety and efficacy of fluvoxamine in COVID‐19 patients if administered later in the course of the disease. Methods The study was designed as an open‐label, prospective cohort trial with matched controls. In April and May 2021, 51 ICU COVID‐19 patients hospitalised in the University Hospital Dubrava and University Hospital Centre Zagreb, Croatia, were treated with fluvoxamine 100 mg three times daily for 15 days in addition to standard therapy and they were prospectively matched for age, gender, vaccination against COVID‐19, disease severity and comorbidities with 51 ICU controls. Results No statistically significant differences between groups were observed regarding the number of days on ventilator support, duration of ICU or total hospital stay. However, overall mortality was lower in the fluvoxamine group, 58.8% ( n = 30/51), than in the control group, 76.5% ( n = 39/51), HR 0.58, 95% CI (0.36–0.94, P = .027). Conclusion Fluvoxamine treatment in addition to the standard therapy in hospitalised ICU COVID‐19 patients could have a positive impact on patient survival. Further studies on the effects of fluvoxamine in COVID‐19 patients are urgently required.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of fluvoxamine in COVID‐19 ICU patients: An open label, prospective cohort trial with matched controls

Čalušić

Marčec

Luksa

et al. 2021

Brit J Clinical Pharma

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“…Recently in this Journal, Sergey Moiseev et al reported that the mortality rate in intensive care unit patients with severe COVID-19 was higher in males older than 50 years old in contrast to females of similar age based on a nationwide cohort study [1] . The sex differences between mortality rates cannot be explained by comorbidities, given the increased occurrence of chronic illnesses in females that may worsen survival in COVID-19 patients.…”

mentioning

confidence: 99%

“…A null causal relationship was observed for TT or SHBG levels with COVID-19 outcomes in females and males. The relationships between gender difference, sex hormone difference and COVID-19 outcomes have been reported based on several observational studies [ 1 , 4 ] and various hypotheses have been postulated to explain the relationships, including a sex-dependent difference in immune responses, sex-related expression difference of angiotensin-converting enzyme 2 and transmembrane protease serine 2 [5] , [6] , [7] . Our study demonstrated a direct causal effect of BAT levels and COVID-19 hospitalization and severe disease in females based on MR analysis.…”

mentioning

confidence: 99%

Bioavailable testosterone level is associated with COVID-19 severity in female: A sex-stratified Mendelian randomization study

Liu

Fan

Guan

et al. 2022

Journal of Infection

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“…In particular, several key genes have been reported from pathological pathway of both diseases, such as angiotensin-converting enzyme 2 (ACE2), A disintegrin and metalloproteinase domain 17 (ADAM17), transmembrane serine protease 2 (TMPRSS2), and melanoma adhesion molecule (CD146/MCAM). In addition, mortality caused by COVID-19 has a sex difference, with a worse rate in men [ 8 , 9 ]. Evidently, it has been known that sex difference exists in CKD.…”

Section: Introductionmentioning

confidence: 99%

Potential Similarities in Sex Difference in Key Genes and Their Expression, Network, EQTL and Pathways between COVID-19 and Chronic Kidney Disease Based on Mouse Model

Yu¹,

Zhan

Dong

et al. 2022

JPM

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COVID-19 and chronic kidney disease (CKD) share similarity in sex bias and key genes in the disease pathway of sex difference. We investigated the sex difference of molecular pathways of four key players of these two diseases using an existing large set of whole genome expression profiles from the kidneys of female and male mouse models. Our data show that there is little to no correlation at the whole genome expression level between female and male mice among these four genes. There are considerable sex differences among genes in upstream regulation, Ace2 complex interaction, and downstream pathways. Snap25 and Plcb4 may play important roles in the regulation of the expression level of Adam17, Tmprss2, and Cd146 in females. In males, Adh4 is a candidate gene for the regulation of Adam17, while Asl, Auts2, and Rabger1 are candidates for Tmprss2. Within the Ace2 complex, Cd146 directly influences the expression level of Adam17 and Ace2 in the female, while in the male Adam potentially has a stronger influence on Ace2 than that of Tmprss2. Among the top 100 most related genes, only one or two genes from four key genes and 11 from the control B-Actin were found to be the same between sexes. Among the top 10 sets of genes in the downstream pathway of Ace2, only two sets are the same between the sexes. We concluded that these known key genes and novel genes in CKD may play significant roles in the sex difference in the CKD and COVID-19 disease pathways.

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Sex differences in mortality in the intensive care unit patients with severe COVID-19

Cited by 9 publications

References 6 publications

Safety and efficacy of fluvoxamine in COVID‐19 ICU patients: An open label, prospective cohort trial with matched controls

Safety and efficacy of fluvoxamine in COVID‐19 ICU patients: An open label, prospective cohort trial with matched controls

Bioavailable testosterone level is associated with COVID-19 severity in female: A sex-stratified Mendelian randomization study

Potential Similarities in Sex Difference in Key Genes and Their Expression, Network, EQTL and Pathways between COVID-19 and Chronic Kidney Disease Based on Mouse Model

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