Is there a gender difference in the infection of people with the new coronavirus? One interesting topic in the outbreak is whether, based on gender differences between men and women, and the resulting huge differences in human structure and biology, there will be differential effects on infections with new coronary pneumonia.
In an earlier paper, the researchers disagreed on the incidence and mortality rates of new coronary pneumonia in different genders, with no difference, some saying women were more susceptible to infection and others saying that male patients had higher mortality rates than women. Now, there is a clearer and more persuasive answer to this question.
A meta-analysis of 77932 patients
On March 30, on the preprinted website ArXiv, an article entitled Sex Differences in Severity and Mortal Allingity Patients With COVID-19: Evidence PoOLEDFields Analysis and Insights from Integrated Bioinformatic Analysis.
This paper was published by professor Ren Shancheng from Shanghai Changhai Hospital, and the author (co-author) Wei Xiyi, Xiao Yutian, Wang Jian, Chen Rui, Zhang Wei, etc.
The paper attempts to explore gender differences in severity and mortality in patients with COVID-19 through a pooled literature analysis of evidence and insights from comprehensive bioinformatics analysis.
Arguably, this is the first large data analysis study on the gender-related correlation between the incidence/severeness/mortality of neo-coronary pneumonia, as required by meta-Analysis, a statistical method for quantitative synthesis of multiple studies and systematic review.
According to BioArtReports, the study searched a total of 1,561 documents, including pre-printed articles (march 19, 2020), and after independent screening, 39 studies resulted in a total of 77,932 patients, including 41,510 males, or 53.3%, all from China and Japan, South Korea, Singapore, Italy, and six other countries.
The results showed that in 39 overall studies of all cases, the incidence of new coronavirus esmogits was significantly higher in women (OR s 1.12), with 34 studies from Chinese groups supporting this conclusion (OR s 1.13).
At the same time, a total of 21 and 8 studies reported the number of severe cases (including ICU patients, ARDS patients, severe patients) and the number of deaths, meta-analysis results showed that the male population’s severe disease rate (OR?63; 95% Cl is 1.28-2.06) and the fatality rate (OR is 1.71; 95% CI is 1.51-1.93) is also significantly higher than in women.
Further subgroup analysis also found that there was no significant difference in the proportion of severe illness escloser in patients with an average age of less than 50 years of age (OR?45; 95% Cl?1.07-1.96) and that the incidence of severe illness in male patients with an average age of more than 50 was significantly higher than that of female patients (OR patients) 1.94; 95% Cl is 1.16-3.26).
Analysis from the above subgroup shows that, as patients get older, the higher the proportion of severe illness in men is higher than in women, thus suggesting that health care workers should pay more attention to the middle-aged and elderly male population in the process of treating patients with new coronary pneumonia.
Overall, the paper argues that the incidence, severe ity and mortality rate of the new coronavirus pneumonia in the male population are higher than that of the female population.
The biological reason why men and women are different
So why does the new coronal pneumonia have a “male and female” situation?
The researchers found that the key to the new coronavirus infection in human cells was the S protein of the coronavirus (Spike Glycoprotein, a stingy glycoprotein) and the ACE2 protein in the human body (Angiotensin-converted enzyme enzyme 2, Chinese the combination of the whole known as angiotensin conversion enzyme 2) – to be precise, is the virus’s S protein “hijack” the original control of blood pressure ACE2, by combining with it to invade the human body and induce infection.
However, according to a study published in Cell magazine in March, the new coronavirus (SARS-CoV-2) uses a protease in human cells, known as serine protease TMPRSS2, to activate its S protein.
The point here is that TMPRSS2, as a key molecule to promote the occurrence of prostate cancer in men, is regulated positively by androgens in the human body – thus, Professor Ren Shancheng’s team believes that the important factor that causes “male and female difference” in the new coronary pneumonia is the higher androgen levels in men androgens and their regulation of the key molecules of virus invasion.
The researchers identified several key lung ACE2 characteristics associated with SARS-CoV-2 virus infection by analyzing lung monocytosequencing data and other important databases.
1. Single-cell RNA-seq analysis showed that ace-type alveoli cells (AT2) that express ACE2 were significantly higher in the lungs of men than in women, meaning that the number of host cells that viruses could attack was higher in men than in women;
On March 12, the Hubei Provincial People’s Government’s website published a post entitled “Men of appropriate age infected with new coronary pneumonia should have fertility tests” for the same reason.
2, androgen receptors can directly regulate the expression of ACE2. The analysis found that androgen receptors (AR) and ACE2 were co-expression patterns, and further analysis found that androgen receptors were positively correlated with the expression of ACE2 and TMPRSS2, which were prevalent in multiple tissue organs of the human body, and that the expression of ACE2 and TMPRSS2 decreased after androgen deprivation. In addition, it is further suggested that androgen receptors may bind to the enhanced subregions upstream of ACE2 to promote the expression of ACE2.
3, analysis found that many pro-inflammatory cytokines and chemokines in the male population show superior expression, especially the “cytokine storm” of the core factor IL-6 receptor IL6ST in the male lung in multiple cells high expression, suggesting that men are more prone to “cytokine storm” leading to the deterioration of the new coronary pneumonia disease. Some cytokines such as CCL2, CCL3, and CCL4, which protect against viral infections, were highly expressed in the female population.
4, male lung microenvironment T cells (can play cell immunity and immunomodulation and other functions) than women’s ability to kill the virus is weaker. This difference in natural, gender-based immune responses has resulted in male lung cells being less resistant to viral attacks than women.
Combining these four points, the biological reasons for the morbidity and mortality of new coronary pneumonia in men are higher than those of women.
BioArtReports said the study was the first to clearly confirm that men had higher rates, rates of severe pneumonia, and mortality rates than women in terms of neo-coronary pneumonia. At the same time, it reveals the biological reasons behind the new coronavirus invasion of the key molecule ACE2 due to positive regulation of androgen receptors, in men’s lung cells expression and distribution is higher than women, and male lung cells when attacked by the virus less autoimmune response than women.
All this points to a simple conclusion: men are more vulnerable than women in the face of the new coronavirus.
In fact, before this paper, there has been research on the association between gender differences between men and women with new coronary pneumonia.
Among them, in mid-February, the Cdc released an outbreak statistics report showing that of the 44,672 confirmed cases of new coronary pneumonia nationwide as of February 11, 51.4% of the patients in the national data were male; New coronary pneumonia did not show significant gender orientation.
But at the same time, the CDC report shows that male patients have significantly higher mortality rates than women, with the former at 2.8 percent and women at just 1.7 percent.
In early March, a study published by the Wuhan University People’s Hospital team on the preprint platform SSRN gave new perspectives. Specifically, the researchers analyzed 6013 case data from January 1 to 29 and found that 55.9% of patients were male, compared with 58.8% of patients admitted to the intensive care unit.
In other words, men are not only more susceptible to the new coronavirus, but also appear to have more severe symptoms.
In addition, 47 of the 67 asymptomatic infections identified by the study were women, suggesting that women also accounted for a large proportion of asymptomatic infections – the researchers speculated that the gender differences in infected people may not be due to the virus’s preference for infecting men, but because men and women are less resistant to the virus.
Now, with the publication of the results of Professor Ren’s team’s paper, the relationship between the new coronapneumonia and the gender differencebetween between men and women seems to have a clearer and more argumentative interpretation.