Does "COVID-19 sequelae" cause male infertility? Know these 7 points and no longer be afraid of "COVID-19 sequelae"!

As the COVID-19 pandemic continues to spread, many people are worried that even if they recover from the infection, they will still have "sequelae". In fact, there have been many rumors about the topic of "sequelae of COVID-19" on the Internet. Today, we will comprehensively sort out the topic of "sequelae of COVID-19" for everyone.

01

What is "post-COVID sequelae"?

"Post-COVID-19 Condition" is also called "Long COVID-19" or "Post COVID-19 Condition", commonly known as "Long COVID-19". It is worth noting that "Post-COVID-19 Condition" is actually very different from the "sequelae" that many ordinary people understand - irreversible and causing great physical and mental trauma. But for the convenience of everyone's understanding, it will still be called "Post-COVID-19 Condition" in the following text.

The current definition of "COVID-19 sequelae" by medical authorities refers to symptoms that persist for a long time after the infection is confirmed in patients with a history of COVID-19 infection. How long is this "long time"? The World Health Organization says it is 3 months[1], and the US Centers for Disease Control and Prevention says it is 4 weeks[2].

Generally speaking, COVID-19 infection can be cured within a few days to a few weeks. However, more and more reports show that 10%-20% of COVID-19 patients still have long-term symptoms after the virus turns negative, which will affect their daily life and work. The US Centers for Disease Control and Prevention gave a set of specific data: 13.3% of COVID-19 patients have "COVID-19 sequelae" for more than one month, 2.5% have more than three months, and more than 30% of hospitalized COVID-19 patients have "COVID-19 sequelae" for more than 6 months.

It seems scary that COVID-19 infection could have such long-term effects. So what are the symptoms of this "long-term" sequelae?

02

What are the symptoms of “post-COVID sequelae”?

The symptoms of post-COVID-19 syndrome are very broad and may include:

Fatigue

Shortness of breath or difficulty breathing

Problems with memory, concentration, or sleep, commonly known as "brain fog"

Persistent cough

Chest pain

Difficulty speaking

Muscle pain

Loss of smell or taste

Depression or anxiety

fever

These symptoms can last for weeks or even months, and may recur repeatedly, affecting the patient’s life and work to varying degrees. Studies have shown that long-term “post-COVID-19 sequelae” can lead to poor health, reduced quality of life, and psychological distress in patients [3].

03

Does “post-COVID-19 sequelae” include male infertility?

This is a question that many readers are concerned about. The various "new crown sequelae" mentioned above all come from authoritative organizations such as the World Health Organization and the U.S. Centers for Disease Control and Prevention. None of these organizations' reports mention male infertility.

In fact, there is currently no direct evidence in the scientific community that COVID-19 infection can cause male infertility. During the years of the epidemic, the medical community has indeed found that a considerable number of COVID-19 patients will experience difficulty with penile erection for a period of time after infection. A meta-analysis showed that the prevalence of penile erection difficulties in COVID-19 patients was 33%, while the prevalence in healthy people was only 9% [5]. However, penile erection difficulties are the result of a combination of complex mental, psychological, and physiological factors, and it is difficult to determine which factor will play a major role.

The scientific community has proposed various hypotheses[6], but from a physiological point of view, the new coronavirus is unlikely to affect the human reproductive system. The new coronavirus infection is mainly concentrated in the respiratory tract, especially the Omicron variant, which rarely enters the circulatory system and even less often invades other organs of the body. If a systemic inflammatory response is triggered, causing multiple organ damage other than the respiratory system, it will occur in severe patients. For asymptomatic or mild patients, the new coronavirus is unlikely to directly affect the male reproductive system.

Several studies have shown [5, 7, 8] that psychological and mental problems caused by COVID-19 infection are the most likely cause of erectile dysfunction. The new coronavirus has swept the world since the end of 2019, and various countries have experienced large-scale social lockdowns, mandatory social distancing, and economic depression caused by the epidemic. These social factors, combined with personal factors of the patients, have caused many patients to experience anxiety, despair and other emotions during the COVID-19 infection. Men who have sex with this negative psychological and mental state are more likely to suffer from erectile dysfunction.

However, there is no need to panic. This negative emotion will gradually ease as time goes by and the epidemic improves. Studies have shown that the prevalence of anxiety decreased by 12.3% three months after recovery from COVID-19 infection, and at the same time, the prevalence of erectile dysfunction also decreased by 14.4% in almost the same proportion [8]. This further proves that negative anxiety may be the direct cause of erectile dysfunction.

Although in theory, male spermatogonia carry ACE2, a target that the coronavirus can attack, studies have found that the most likely cause of the decline in sperm count and motility in coronavirus-infected individuals is high fever. Male reproductive capacity declines significantly within 72 to 90 days of coronavirus infection, due to the decline in sperm concentration and motility caused by high fever[9]. Fortunately, the human body has strong self-repair and sperm renewal capabilities, and the decline in reproductive capacity caused by high fever is only a one-time event, which can basically return to normal after three months.

04

What is the cause of “post-COVID syndrome”?

At present, the scientific community is not clear about the cause of COVID-19 sequelae.

In fact, many patients with "post-COVID-19 syndrome" have normal test results. This is very important. Despite this, some researchers are trying to find possible causes of "post-COVID-19 syndrome".

There are currently some hypotheses about the causes and mechanisms of this disease:

1. Perhaps after the COVID-19 test turns negative, there are still undetectable amounts of the virus remaining in the human body, causing "COVID-19 sequelae". These people suffering from COVID-19 sequelae are similar to virus carriers. There is currently no evidence to support this hypothesis.

2. Perhaps the new coronavirus infection triggers a multi-organ inflammatory response and causes an immune system disorder. After the virus is cleared, this disorder is not completely corrected, which causes "new coronavirus sequelae."

3. Perhaps the "post-COVID-19 syndrome" is a post-traumatic stress disorder (PTSD) caused by the virus, which is more like a psychological disorder that only reflects on the body and causes physiological and pathological changes. This is the current mainstream hypothesis.

There are quite a few "COVID-19 sequelae" that have no causal relationship with COVID-19 infection, only a temporal correlation. When COVID-19 infection becomes widespread, there will always be various unrelated symptoms associated with it, similar to the various "side effects" and "coupling reactions" of vaccination that have attracted attention. In fact, the real cause of these symptoms may be other underlying diseases of the patient.

There is a very famous paper in the Journal of the American Medical Association (JAMA). The study attempted to explore the causes of COVID-19 sequelae[10]. A total of about 520,000 COVID-19 patients’ electronic health records were collected, and the scale of the study was very large. The results showed that hospitalized COVID-19 patients were more likely to suffer from shortness of breath, arrhythmia, and type 2 diabetes than healthy people, and COVID-19 patients over 20 years old were more likely to suffer from fatigue.

But this study did not balance the basic characteristics between the groups. For example, the body mass index of COVID-19 patients was significantly higher than that of healthy people, and they were also older. Obesity can cause many health problems, including shortness of breath, arrhythmia, and fatigue - so we don't know whether it is obesity that causes these problems or COVID-19 infection - the same is true for age.

The CDC also believes that severe COVID-19 patients are more likely to suffer from "COVID-19 sequelae." However, most severe patients have been admitted to intensive care units. In the past, non-COVID-19 patients who have been admitted to intensive care units also had similar "sequelae" after being discharged from the hospital. Therefore, it is not clear whether it is the new coronavirus itself or the stay in the intensive care unit that caused these "sequelae." At the same time, people with poor economic conditions, socially disadvantaged groups, and people with disabilities are also more likely to suffer from "COVID-19 sequelae."

Although the cause and pathogenesis are unclear, the "sequelae of COVID-19" are real. It is worth mentioning that some metabolic diseases, such as type 1 or type 2 diabetes, are more likely to occur in COVID-19 patients, which has been confirmed by many studies [10, 11]. The incidence of diabetes in COVID-19 patients increased by 1.31-2.66 times [11]. This requires great attention from the medical community.

05

What are the effective treatments for “post-COVID-19 syndrome”?

Currently, no research has been able to determine how long the sequelae of COVID-19 will last, but it is generally believed that most sequelae of COVID-19 will resolve themselves over time. Studies have shown that most patients can recover within 60 days of suffering from "sequelae of COVID-19", but some patients may suffer from it for 120-180 days or even longer [12].

Since the "new crown sequelae" has a large variability and varies from person to person, there is no unified and effective treatment measure. Studies have shown that active rehabilitation care can effectively alleviate the "new crown sequelae".

06

Vaccination can effectively reduce the incidence of "new crown sequelae"

The World Health Organization believes that the severity of COVID-19 infection has no relationship with sequelae, but vaccination with an effective COVID-19 vaccine can significantly reduce the incidence of COVID-19 sequelae.

The US Centers for Disease Control and Prevention also believes that people who have been vaccinated, even if they have a breakthrough infection, are less likely to suffer from "post-COVID sequelae" after recovery.

07

What warning does this give us?

After reading the full text, you will find that, in fact, "COVID-19 sequelae" is closer to a post-traumatic stress response, and as time goes by, the disease will gradually ease or even disappear. So for most individuals, "COVID-19 sequelae" is just a small trouble that can be faced.

However, at the social level, if there are many such individuals, then individual health problems will accumulate and become a serious group health problem. Facing the medical burden of a large number of COVID-19 sequelae, the medical community needs to be fully prepared, including research on the pathogenesis and treatment measures. Taking the UK as an example, the government has invested 50 million pounds this year to study "COVID-19 sequelae" [4].

For ordinary people like us, on the one hand, we don’t need to be overly afraid - if we let go of our fear, we have already overcome the "new crown sequelae" to a certain extent. On the other hand, we need to get an effective new crown vaccine and booster shot in time - various medical authorities believe that vaccination can effectively reduce the incidence of "new crown sequelae".

If you have friends and family who have not yet been fully vaccinated, please be sure to forward this article to them.

References:

[1] World Health Organization. Coronavirus disease (COVID-19): Post COVID-19 condition. https://www.who.int/news-room/questions-and-answers/item/coronavirus-disease-(covid-19)-post-covid-19-condition

[2] Centers of Disease Control and Prevention. Long COVID or Post-COVID Conditions. https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/index.html

[3] Han JH, Womack KN, Tenforde MW, et al. Influenza and Other Viruses in the Acutely Ill (IVY) Network. Associations between persistent symptoms after mild COVID-19 and long-term health status, quality of life, and psychological distress. Influenza Other Respir Viruses. 2022 Jul;16(4):680-689. doi: 10.1111/irv.12980. Epub 2022 Mar 28. PMID: 35347854; PMCID: PMC9111447.

[4] Office for National Statistics. Prevalence of ongoing symptoms following coronavirus (COVID-19) infection in the UK: 7 April 2022. https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/prevalenceofongoingsymptomsfollowingcoronaviruscovid19infectionintheuk/7april2022

[5] Zhang J, Shi W, Zou M, et al. Prevalence and risk factors of erectile dysfunction in COVID-19 patients: a systematic review and meta-analysis. J Endocrinol Invest. 2022 Oct 28:1–10. doi: 10.1007/s40618-022-01945-w. Epub ahead of print. PMID: 36307637; PMCID: PMC9616422.

[6] Kaynar M, Gomes ALQ, Sokolakis I, et al. Tip of the iceberg: erectile dysfunction and COVID-19. Int J Impot Res. 2022 Mar;34(2):152-157. doi: 10.1038/s41443-022-00540-0. Epub 2022 Feb 12. PMID: 35152276; PMCID: PMC8853253.

[7] Sevim M, Alkis O, Kartal İG, Telli S, Aras B. A factor not to be ignored in post-COVID-19 erectile dysfunction; psychological effect, a prospective study. Andrologia. 2022 Aug;54(7):e14443. doi: 10.1111/and.14443. Epub 2022 Apr 21. PMID: 35445425; PMCID: PMC9111346.

[8] Harirugsakul K, Wainipitapong S, Phannajit J, et al. Erectile dysfunction after COVID-19 recovery: A follow-up study. PLoS One. 2022 Oct 20;17(10):e0276429. doi: 10.1371/journal.pone.0276429. PMID: 36264947; PMCID: PMC9584530.

[9] Malki MI. COVID-19 and male infertility: An overview of the disease. Medicine (Baltimore). 2022 Jul 8;101(27):e29401. doi: 10.1097/MD.0000000000029401. PMID: 35801743; PMCID: PMC9258969.

[10] Hernandez-Romieu AC, Carton TW, Saydah S, et al. Prevalence of Select New Symptoms and Conditions Among Persons Aged Younger Than 20 Years and 20 Years or Older at 31 to 150 Days After Testing Positive or Negative for SARS-CoV-2. JAMA Netw Open. 2022;5(2):e2147053.

[11] Barrett CE, Koyama AK, Alvarez P, et al. Risk for Newly Diagnosed Diabetes >30 Days After SARS-CoV-2 Infection Among Persons Aged<18 Years - United States, March 1, 2020-June 28, 2021. MMWR Morb Mortal Wkly Rep. 2022 Jan 14;71(2):59-65. doi: 10.15585/mmwr.mm7102e2. PMID: 35025851; PMCID: PMC8757617.

[12] Hernandez-Romieu AC, Leung S, Mbanya A, et al. Health Care Utilization and Clinical Characteristics of Nonhospitalized Adults in an Integrated Health Care System 28-180 Days After COVID-19 Diagnosis - Georgia, May 2020-March 2021. MMWR Morb Mortal Wkly Rep. 2021 Apr 30;70(17):644-650. doi: 10.15585/mmwr.mm7017e3. PMID: 33914727; PMCID: PMC8084119.

Author: Ding Chao, Physician at the Cancer Hospital of University of Chinese Academy of Sciences

Reviewer: Li Yongsheng Director of the Department of Oncology, Chongqing University Cancer Hospital

Jin Dong, Associate Researcher, Institute of Infectious Diseases, Chinese Center for Disease Control and Prevention

Produced by: Science Popularization China-Starry Sky Project (Creation and Cultivation)