COVID-19 pandemic: is a gender-defined dosage effect responsible for the high mortality rate among males?

Groot, Natasja G. de; Bontrop, Ronald E.

doi:10.1007/s00251-020-01165-7

Cited by 41 publications

(41 citation statements)

References 29 publications

(31 reference statements)

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“…One should take into account though that the percentages of patients with systemic autoimmune disease who receive immunosuppressives may be lower within the elderly population which is more vulnerable to severe outcomes. Moreover, since males seem to have higher death rates than females [ 54 ], the female preponderance in systemic autoimmunity could be a protective factor.…”

Section: Discussionmentioning

confidence: 99%

Systemic autoimmune diseases, anti-rheumatic therapies, COVID-19 infection risk and patient outcomes

et al. 2020

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As of June 10th 2020 about 7.2 million individuals have tested positive for, and more than 410,000 have died due to COVID-19. In this review we outline the pathophysiology that underpins the potential use of anti-rheumatic therapies for severe COVID-19 infection and summarize the current evidence regarding the risk and outcome of COVID-19 in patients with systemic autoimmune diseases. Thus far there is no convincing evidence that any disease-modifying anti-rheumatic drug (conventional synthetic, biologic or targeted synthetic) including hydroxychloroquine, may protect against severe COVID-19 infection; answers about their possible usefulness in the management of the cytokine storm associated with severe COVID-9 infection will only arise from ongoing randomized controlled trials. Evidence on COVID-19 risk and outcome in patients with systemic autoimmune diseases is extremely limited; thus, any conclusions would be unsafe and should be seen with great caution. At present, the risk and severity (hospitalization, intensive care unit admission and death) of COVID-19 infection in people with autoimmune diseases do not appear particularly dissimilar to the general population, with the possible exception of hospitalization in patients exposed to high glucocorticoid doses. At this stage it is impossible to draw any conclusions for differences in COVID-19 risk and outcome between different autoimmune diseases and between the various immunomodulatory therapies used for them. More research in the field is obviously required, including as a minimum careful and systematic epidemiology and appropriately controlled clinical trials.

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Section: Discussionmentioning

confidence: 99%

Systemic autoimmune diseases, anti-rheumatic therapies, COVID-19 infection risk and patient outcomes

et al. 2020

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“…How the disease affects the body is affected by the physiological environment of the individual this includes the underlying pathway the virus takes to invade the host cells, the reaction of the host to the virus, and comorbidities that influence the impact of the disease -all of which can be seen to have marked biological sex differences [12]. These have been well described elsewhere [13,14,15,16,17,18,19] Beyond the biological risk the epidemiological evidence of the spread of the disease is demonstrating that this is not an equal playing field, with marked intersectional differences seen in its impact based on different population groups [20]. Men's risk of developing and dying from SARS-CoV2 is markedly increased depending on their socio-economic status.…”

Section: Men's Risk Of Sars-cov2mentioning

confidence: 99%

Men and COVID-19: the aftermath

White

2020

Postgraduate Medicine

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The global pandemic as a result of the SARS-CoV2 virus has seen over 16 m people infected and over 650,000 deaths, with men at double the risk of both developing the severe form of the disease and mortality. There are both biological (sex) and socio-cultural (gender) factors, compounded by socioeconomic factors and ethnicity, that impact on the aftermath of what has occurred over the short time that this novel coronavirus has been circulating the world. The potential lifelong morbidity as a result of the infection and as a consequence of highly invasive critical care treatment needs to be factored into the rehabilitation of survivors. There are also many men whose lives will have been severely affected both physically and emotionally by the pandemic without ever contracting the disease, with the widespread disruption to normal existence and its impact on their social world and the economy. The implications of the closure of many healthcare services over the initial lockdown will also have both a shorter-and longer-term impact on other diseases due to missed early diagnosis and disrupted treatment regimes. Getting effective public health messages out to the population is critical and this current pandemic is demonstrating that there needs to be a more focused view on men's health behavior. Without effective public support for preventative action, the more likely the disease will continue its path unabated. This review explores the wider ramifications of the disease both for those men who have survived the disease and those that have been affected by the wider social effects of the pandemic. The pandemic should be a wake-up call for all involved in the planning and delivery of health and social care for the greater attention to the central role of sex and gender.

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“… 97 , 98 Human studies of SARS-CoV-1 and SARS-CoV-2 suggest a correlation between sex and certain clinical parameters, perhaps rooted in sex-based or related immunologic differences or gene dosage effects. 94 , 99 However, separating biological differences from sex-related cultural practices (e.g., different rates of social distancing) and body habitus (i.e., potential correlations of body mass index with sex separate from strict genetic correlations) may be difficult.…”

Section: Introductionmentioning

confidence: 99%

The Role of Host Genetic Factors in Coronavirus Susceptibility: Review of Animal and Systematic Review of Human Literature

LoPresti

Beck

Duggal

et al. 2020

The American Journal of Human Genetics

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Summary The SARS-CoV-2 pandemic raises many scientific and clinical questions. These include how host genetic factors affect disease susceptibility and pathogenesis. New work is emerging related to SARS-CoV-2; previous work has been conducted on other coronaviruses that affect different species. We reviewed the literature on host genetic factors related to coronaviruses, systematically focusing on human studies. We identified 1,832 articles of potential relevance. Seventy-five involved human host genetic factors, 36 of which involved analysis of specific genes or loci; aside from one meta-analysis, all were candidate-driven studies, typically investigating small numbers of research subjects and loci. Three additional case reports were described. Multiple significant loci were identified, including 16 related to susceptibility (seven of which identified protective alleles) and 16 related to outcomes (three of which identified protective alleles). The types of cases and controls used varied considerably; four studies used traditional replication/validation cohorts. Among other studies, 30 involved both human and non-human host genetic factors related to coronavirus, 178 involved study of non-human (animal) host genetic factors related to coronavirus, and 984 involved study of non-genetic host factors related to coronavirus, including involving immunopathogenesis. Previous human studies have been limited by issues that may be less impactful now, including low numbers of eligible participants and limited availability of advanced genomic methods; however, these may raise additional considerations. We outline key genes and loci from animal and human host genetic studies that may bear investigation in the study of COVID-19. We also discuss how previous studies may direct current lines of inquiry.

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COVID-19 pandemic: is a gender-defined dosage effect responsible for the high mortality rate among males?

Cited by 41 publications

References 29 publications

Systemic autoimmune diseases, anti-rheumatic therapies, COVID-19 infection risk and patient outcomes

Systemic autoimmune diseases, anti-rheumatic therapies, COVID-19 infection risk and patient outcomes

Men and COVID-19: the aftermath

The Role of Host Genetic Factors in Coronavirus Susceptibility: Review of Animal and Systematic Review of Human Literature

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