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Effects of inactivated SARS‐CoV‐2 vaccination on male fertility: A retrospective cohort study
Abstract
Background:
Numerous studies have revealed severe damage to male fertility from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, raising concerns about the potential adverse impact on reproductive function of the coronavirus disease 2019 (COVID-19) vaccine developed based on the virus. Interestingly, there are several researchers who have studied the impact of the COVID-19 mRNA vaccine since then but have come up with conflicting results. As a near-ideal candidate for mass immunization programs, inactivated SARS-CoV-2 vaccine has been widely used in many countries, particularly in less wealthy nations. However, little is known about its effect on male fertility.
Methods:
Here, we conducted a retrospective cohort study at a single large center for reproductive medicine in China between December 2021 and August 2022. 519 fertile men with no history of laboratory-confirmed COVID-19 were included and categorized into four groups based on their vaccination status: unvaccinated group (n=168), one-dose vaccinated group (n=8), fully vaccinated group (n=183), and booster group (n=160). All of them underwent a semen analysis and most had serum sex hormone levels tested.
Results:
There were no significant differences in all semen parameters and sex hormone levels between the unvaccinated group and either vaccinated group. To account for possible vaccination-to-test interval-specific changes, sub-analyses were performed for two interval groups: ≤90 and >90 days. As expected, most of the semen parameters and sex hormone levels remained unchanged between the control and vaccinated groups. However, participants in vaccinated group (≤90 days) have decreased total sperm motility and increased FSH level compared with the ones in unvaccinated group. Moreover, some trends similar to those found during COVID-19 infection and recovery were observed in our study. Fortunately, all values are within the normal range. In addition, vaccinated participants reported few adverse reactions. No special medical intervention was required, and no serious adverse reactions happened.
Conclusion:
Our study suggests that inactivated SARS-CoV-2 vaccination does not impair male fertility, possibly due to the low frequency of adverse effects. This information reassures young male population who got this vaccine worldwide, and helps guide future vaccination efforts. This article is protected by copyright. All rights reserved.
... All the studies were of reasonable quality. Of 24 studies, 9 (38%) studies were conducted in the United States and Western European countries [34][35][36][37][38][39][40][41][42], 5 (21%) in China [43][44][45][46][47], 1 (4%) in Indonesia [48], and 9 (38%) in the Middle Eastern countries [49][50][51][52][53][54][55][56][57]. In total, 3 (12%) studies used inactivated COVID-19 vaccines, 4 (17%) studies used viral-vectored vaccines, 8 (33%) studies used mRNA vaccines, and 3 (12%) studies included a combined analysis of multiple types of vaccines. ...
... Therefore, male patients who experience fever after receiving the COVID-19 vaccine may experience fluctuations in their sperm parameters. However, this effect is similar to that caused by fever due to other registered vaccines [41,47,54]. ...
... Further persuasive evidence comes from ART and artificial insemination by partner outcomes in couples after receiving the COVID-19 vaccine [57,67]. In a prospective cohort study involving 735 infertile couples, Dong et al [47] demonstrated that the quality of the embryos and the pregnancy rate in IVF treatment were unaffected by the couples' vaccination status or vaccine type. Similarly, no differences in fertility or pregnancy outcomes were observed in the study by Orvieto et al [57]. ...
Background
The COVID-19 pandemic, caused by SARS-CoV-2, has triggered a global public health crisis of unprecedented proportions. SARS-CoV-2 vaccination is a highly effective strategy for preventing infections and severe COVID-19 outcomes. Although several studies have concluded that COVID-19 vaccines are unlikely to affect fertility, concerns have arisen regarding adverse events, including the potential impact on fertility; these concerns are plagued by limited and inconsistent evidence.
Objective
This review aims to provide a recent assessment of the literature on the impact of COVID-19 vaccines on male sperm quality. The possible impact of COVID-19 vaccines on fertility potential was also examined to draw a clearer picture and to evaluate the effects of COVID-19 on male reproductive health.
Methods
PubMed, Scopus, Web of Science, Embase, and Cochrane databases were searched from their inception to October 2023. Eligible studies included articles reporting SARS-CoV-2 vaccination and human semen quality and fertility, as well as the impact of vaccination on assisted reproductive technology treatment outcomes. The quality of cohort studies was assessed using the Newcastle-Ottawa Scale, and the quality of cross-sectional studies was assessed using the quality evaluation criteria recommended by the Agency for Healthcare Research and Quality. The systematic review followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.
Results
The initial literature search yielded 4691 records by searching 5 peer-reviewed databases (PubMed, Scopus, Web of Science, Embase, and Cochrane). Finally, 24 relevant studies were selected for our study. There were evident research inequalities at the regional level, with the United States and Western European countries contributing 38% (9/24) of the studies, Middle Eastern countries contributing 38% (9/24), China accounting for 21% (5/24), and Africa and South America accounting for none. Nonetheless, the overall quality of the included studies was generally good. Our results demonstrated that serious side effects of the COVID-19 vaccine are extremely rare, and men experience few problems with sperm parameters or reproductive potential after vaccination.
Conclusions
On the basis of the studies published so far, the COVID-19 vaccine is safe for male reproductive health. Obviously, vaccination is a wise option rather than experience serious adverse symptoms of viral infections. These instances of evidence may help reduce vaccine hesitancy and increase vaccination coverage, particularly among reproductive-age couples. As new controlled trials and prospective cohort studies with larger sample sizes emerge, the possibility of a negative effect of the COVID-19 vaccine on sperm quality must be further clarified.
... Six other retrospective studies examined various vaccine types (mRNA, inactivated, and viral vector vaccines) on sperm quality characteristics. Three studies investigated healthy men [163][164][165] and three individuals undergoing fertility treatments [166][167][168]. Overall, sperm characteristics were not influenced after vaccination, excluding a temporary decrease in concentration and motility in one study and decreased total sperm motility with increased FSH levels compared with the men in the unvaccinated group in another study; both studies focused on healthy donors [166,168]. ...
... Most of these studies were conducted among women undergoing assisted reproduction cycles. Similarly, studies on male fertility showed no adverse effects of the vaccines on parameters of semen specimens [158][159][160][161][162][163][164][165][166][167][168]. ...
The emergence of the COVID-19 pandemic has led to the rapid and worldwide devel-opment and investigation of multiple vaccines. While most side effects of these vaccines are mild and transient, potentially severe adverse events may occur and involve the endocrine system. This narrative review aims to explore the current knowledge on potential endocrine adverse effects following COVID-19 vaccination, with thyroid disorders being the most common. Data about pi-tuitary, adrenal, diabetes, and gonadal events will also be reviewed. This review also provides a comprehensive understanding of the pathogenesis of endocrine disorders associated with SARS-CoV-2 vaccines. A PubMed/MEDLINE, Embase database (Elsevier), and Google Scholar research were performed. Case reports case series, original studies, and reviews written in English and published online up to 31 August 2023 were selected and reviewed. Data on endocrine adverse events of SARS-CoV-2 vaccines is accumulating. However, their causal relationship with COVID-19 vaccines is not strong enough to make a definite conclusion, and further studies are needed to clarify the pathogenesis mechanisms of endocrine disorders linked to COVID-19 vac-cines.
... In this regard, Zhu et al. observed that there were no significant differences in semen parameters (volume, sperm concentration, progressive motility and total progressive motile count) before and after receiving first or second dose of the vaccine (14). Our previous study also showed similar results (15). However, these studies focused on evaluating the effect of each individual dose vaccination, while the influence of combined doses of vaccines on human fertility has not been assessed in detail. ...
... Although some studies have found a temporary decrease in sperm concentration and total sperm motility after 1 + 2 doses of mRNA vaccination compared to unvaccinated men, whether this conclusion applies to inactivated vaccines remains to be verified (16,17). Moreover, most of the participants included in previous studies on inactivated vaccines underwent semen analysis only once, making it difficult to use a pre and post control group design to eliminate confounding factors and selection bias (15,18,19). Therefore, we performed this study to comprehensively investigate the effect of inactivated COVID-19 vaccination on male fertility, hoping to provide more valuable information for future public health efforts. ...
Background
The inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine has made significant contributions to fighting the epidemic in the past three years. However, the rapid development and application raised concerns about its safety in reproductive health, especially after several studies had observed a decrease in semen parameters following two doses of mRNA SARS-CoV-2 vaccination. Thus, it is necessary to comprehensively evaluate the effect of inactivated SARS-CoV-2 vaccine on male fertility.
Methods
A retrospective cohort study was conducted in the Center for Reproductive Medicine of the Affiliated Hospital of Jining Medical University between July 2021 and March 2023. A total of 409 men with different vaccination status and no history of SARS-CoV-2 infection were included in this study. Their sex hormone levels and semen parameters were evaluated and compared separately.
Results
The levels of FSH and PRL in one-dose vaccinated group were higher than other groups, while there were no significant changes in other sex hormone levels between the control and inactivated SARS-CoV-2 vaccinated groups. Most semen parameters such as volume, sperm concentration, total sperm count, progressive motility and normal forms were similar before and after vaccination with any single dose or combination of doses (all P > 0.05). Nevertheless, the total motility was significantly decreased after receiving the 1 + 2 doses of vaccine compared to before vaccination (46.90 ± 2.40% vs. 58.62 ± 2.51%; P = 0.001). Fortunately, this parameter was still within the normal range.
Conclusion
Our study demonstrated that any single dose or different combined doses of inactivated SARS-CoV-2 vaccination was not detrimental to male fertility. This information could reassure men who want to conceive after vaccination and be incorporated into future fertility recommendations.
... Relatively little research on inactivated COVID-19 vaccine is available, mainly reported by scholars in China, who have the most applications for inactivated COVID-19 vaccine. Two retrospective studies included an unvaccinated population in the control group, and the results showed that the population vaccinated with inactivated COVID-19 vaccine had comparable semen parameters and pregnancy rates [24,86]. Like Gat et al. 's report on mRNA vaccine, Dong et al. also found a deterioration in semen parameters in the short term, the population within 90 days of vaccination displayed decreased total sperm motility compared to that in the unvaccinated population [24]. ...
... Two retrospective studies included an unvaccinated population in the control group, and the results showed that the population vaccinated with inactivated COVID-19 vaccine had comparable semen parameters and pregnancy rates [24,86]. Like Gat et al. 's report on mRNA vaccine, Dong et al. also found a deterioration in semen parameters in the short term, the population within 90 days of vaccination displayed decreased total sperm motility compared to that in the unvaccinated population [24]. We speculate that the fever after vaccination may be the reason for the parameter deterioration, since researches had proved that fever can temporarily impair sperm count and quality [72]. ...
Although vaccination with the Coronavirus disease 2019 vaccine is important and effective in the prevention of SARS-CoV-2 infection, the public expressed concerns regarding the adverse effects of vaccine on fertility. Some reviews have focused on it, they have been unable to collect sufficient research data because of the earlier publication period. As relevant evidence has gradually increased, we reviewed these studies from the perspectives of males, females with or without pregnancy, and different vaccine types. The results suggest that although males may experience fluctuations in semen parameters within their physiological ranges after receiving the vaccine, it has not yet reached a level of influence on the partner’s pregnancy probability. As to female without pregnancy, it is believed that vaccination will not affect fertility; however, more research is needed to explore the short-term impact. Vaccination during any trimester is considered safe in pregnant women.
... These as well as our results support the safety of the SARS-CoV-2 vaccine regarding female reproductive health. The same has been reported for their male counterparts, where no association of male infertility with SARS-CoV-2 vaccination could be found [23,24]. ...
Background
There is debate about the causes of the recent birth rate decline in high‐income countries worldwide. During the pandemic, concern about the effects on reproductive health has caused vaccine hesitancy. We investigated the association of SARS‐CoV‐2 vaccination and infection with involuntary childlessness.
Methods
Females in fertility age within a prospective multicenter cohort of healthcare workers (HCW) were followed since August 2020. Data on baseline health, SARS‐CoV‐2‐infection, and vaccination were obtained and regularly updated, in which serum samples were collected repetitively and screened for anti‐nucleocapsid and anti‐spike antibodies. In October 2023, participants indicated the presence of involuntary childlessness with onset during the pandemic, whereas those indicating an onset before the pandemic were excluded. The association of involuntary childlessness and SARS‐CoV‐2‐vaccination and infection was investigated using univariable and multivariable analysis. Sensitivity analysis was performed to compare those reporting involuntary childlessness with those birthing a child since 2020.
Results
Of 798 participants, 26 (3.2%) reported involuntary childlessness starting since the pandemic. Of the involuntary childless women, 73.1% (19/26) were vaccinated compared to 86.0% (664/772) without involuntary childlessness (p = 0.73). SARS‐CoV‐2 infection was reported by 76.9% (20/26) compared to 72.4% (559/772) of controls (p = 0.64). Neither SARS‐CoV‐2 vaccination (aOR 0.91 per dose, 95%CI 0.67–1.26) nor infection (aOR per infection 1.05, 95%CI 0.62–1.71) was associated with involuntary childlessness. Sensitivity analysis confirmed these results.
Conclusions
Among female HCW of fertility age, 3.2% indicated involuntary childlessness, which is comparable to pre‐pandemic data. No association between involuntary childlessness and SARS‐CoV‐2 vaccination or infection was found.
... Some studies reported the effect of SARS-CoV-2 vaccination, and most did not find any statistical difference in the vaccination effect on semen parameters. 20,21 However, whether SARS-CoV-2 vaccination has a protective effect on semen quality has not been reported. Based on whether the SARS-CoV-2 three-dose inactivated vaccination booster was completed, we divided the population with normal sperm concentration before infection into two groups and observed the changes in the sperm parameters within 90 days of infection. ...
In this study, we aimed to assess the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on semen parameters. The study comprised 110 sperm volunteers who self-reported SARS-CoV-2 infection from the Human Sperm Bank of the Center for Reproductive Medicine, Shandong University (Jinan, China). The volunteers had normal sperm concentration before infection. Each volunteer provided semen samples before and after infection. We selected 90 days after infection as the cutoff point. Semen parameters within 90 days after infection of 109 volunteers (group A) were compared with semen parameters before infection. Moreover, semen parameters on or after 90 days after infection of 36 volunteers (group B) were compared with semen parameters before infection. Furthermore, based on whether the volunteers had completed the three-dose SARS-CoV-2 vaccination booster, volunteers in group A and B were further divided into two subgroups separately. Semen parameters were compared before and after infection in each subgroup. Our results showed that in this cohort population, the semen quality in volunteers with normal sperm concentrations before infection decreased after SARS-CoV-2 infection within 90 days, while the semen quality returned to preinfection levels after 90 days. The completion of a three-dose SARS-CoV-2 vaccination booster may exert a protective effect on semen quality after infection.
It has been over 4 years since the coronavirus disease 2019 outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As an effective response to coronavirus disease 2019, the SARS-CoV-2 vaccines have been widely used around the world. However, couples who are planning to conceive naturally or by assisted reproductive technology (ART) are concerned about the impact of SARS-CoV-2 vaccines on pregnancy and offspring safety. Furthermore, in the initial stage of the epidemic, opinions among physicians and healthcare providers on whether ART patients should be immunized are divided due to the lack of data regarding the impact of the SARS-CoV-2 vaccine on ART. This is not the first, nor will it be the last time humans confront pandemics. It is time to summarize the experience about the effect of the SARS-CoV-2 vaccine on the outcomes of ART, which can provide a reference for the future. This paper reviewed relevant research, and significant adverse effects of the SARS-CoV-2 vaccine on the outcome of ART have not been observed. Considering the increased risk of serious complications in pregnant women infected with SARS-CoV-2, timely vaccination may be a wiser choice.
The emergence of the COVID-19 pandemic has led to the rapid and worldwide development and investigation of multiple vaccines. While most side effects of these vaccines are mild and transient, potentially severe adverse events may occur and involve the endocrine system. This narrative review aimed to explore the current knowledge on potential adverse endocrine effects following COVID-19 vaccination, with thyroid disorders being the most common. Data about pituitary, adrenal, diabetes, and gonadal events are also reviewed. This review also provides a comprehensive understanding of the pathogenesis of endocrine disorders associated with SARS-CoV-2 vaccines. PubMed/MEDLINE, Embase database (Elsevier), and Google Scholar searches were performed. Case reports, case series, original studies, and reviews written in English and published online up to 31 August 2023 were selected and reviewed. Data on endocrine adverse events of SARS-CoV-2 vaccines are accumulating. However, their causal relationship with COVID-19 vaccines is not strong enough to make a definite conclusion, and further studies are needed to clarify the pathogenesis mechanisms of the endocrine disorders linked to COVID-19 vaccines.
Exposure to vaccine lipid nanoparticles, mRNA, adenoviral DNA, and or Spike protein from one of the approved Covid-19 vaccines, or through secondary exposure, as through blood transfusion, is a potential source of harm. Blood reactions are an acknowledged side-effect of Covid-19 vaccination, not limited to hemolysis, paroxysmal nocturnal hemoglobinuria, chronic cold agglutinin disease, immune thrombocytopenia, haemophagocytosis, hemophagocytic lymphohistiocytosis, and many other blood related conditions. The observation of adverse events has motivated investigation into the cardiovascular mechanisms of harm by Covid-19 vaccines, and the biodistribution of vaccine contents. Biodistribution may not be limited to the body of the vaccine recipient, as a growing body of evidence demonstrates the possibility of secondary exposure to vaccine particles. These can be via bodily fluids and include the following routes of exposure: blood transfusion, organ transplantation, breastfeeding, and possibly other means. As covid-19 vaccines are associated with an increased risk of stroke, the persistence of vaccine artifacts in the blood presents a possible threat to a recipient of a blood donation from a vaccinated donor who suffered from vaccine induced thrombosis or thrombocytopenia. (VITT) We assess the feasibility and significance of these risks through an overview of the case report literature of blood disorders in vaccinated individuals, pharmacovigilance reports from the US Vaccine Adverse Events Reporting System (VAERS) and a meta-analysis of the available literature on organ transplants from vaccinated organ donors. Our analysis establishes biological mechanistic plausibility, a coherent safety signal in pharmacovigilance databases for secondary vaccine contents exposure (for the cases of blood transfusion and breastfeeding) and also an elevated level of adverse events in organ transplants from VITT-deceased donors, echoing increases in organ transplantation related complications seen in national statistics for some countries. Secondary exposure to vaccine artifacts is a potential explanation for some of the cases put forth, and requires a deeper investigation.
Angiotensin converting enzyme‑2 (ACE-2) receptor and transmembrane serine protease 2 (TMPRSS2), which are essential for the infection of cells by SARS-CoV‑2, are present in cells of the male genital tract. Although coexpression of the ACE‑2 receptor and TMPRSS2 remains to be proven, effects of SARS-CoV‑2 infection on sperm quality and Leydig cell functions cannot be ruled out. Some men with COVID-19 showed clinical symptoms suspicious for orchitis or epididymitis during the acute phase of infection. SARS-CoV‑2 has been detected in semen and testicular tissue in early stages of infection. Nevertheless, cryopreservation of sperms is possible. Sperm quality may be reduced especially in severe cases of SARS-CoV‑2 infection. Fever and prolonged recovery from disease may have additional negative effects on spermatogenesis. Long-term damage to male fertility has not been demonstrated to date. In addition to spermatogenesis, Leydig cell function may be reduced during the initial phase of infection, resulting in lower serum testosterone levels. Further studies will show, whether these observations are short- or long-term effects. Vaccination against SARS-CoV‑2 does not impair spermatogenesis.
The COVID-19 pandemic and its social, economic, and health implications have generally reduced women's fertility intentions in different countries. In this article, we aimed to review studies of the impact of COVID-19 infection on women's fertility intentions and interventions to provide a theoretical basis and practical benchmark for the development of effective intervention strategies in China, which lifted its zero COVID system in early December 2022.
Vaccination remains the best prevention strategy against influenza. The MDCK-based influenza vaccine prompted the development of innovative cell culture manufacturing processes. In the present study, we report the effects of multiple administrations of a candidate, seasonal, MDCK-based, quadrivalent split influenza virus vaccine MDCK-QIV in Sprague-Dawley (SD) rats. Moreover, the effects of the vaccine were evaluated in terms of fertility and early embryonic development, embryo-fetal development, and perinatal toxicity in the SD rats and immunogenicity in Wistar rats and BALB/c mice. Regarding the safety profile, MDCK-QIV demonstrated tolerance in local stimulation with repeated dose administration and presented no significant effect on the development, growth, behavior, fertility, and reproductive performance of the adult male rats, maternal rats, and their offspring. MDCK-QIV elicited strong hemagglutination inhibition neutralizing antibody response and protection against the influenza virus in the mouse model. Thus, data supported that MDCK-QIV could be further evaluated in human clinical trial, which is currently underway.
Since Chinese were mainly inoculated with inactivated vaccine, Dong et al. concluded that inactivated COVID‐19 vaccine injection will not change on male fertility through a small retrospective study This article is protected by copyright. All rights reserved.
SARS coronavirus 2 (SARS-CoV-2) continues to evolve and new variants emerge. Using nationwide Danish data, we estimate the transmission dynamics of SARS-CoV-2 Omicron subvariants BA.1 and BA.2 within households. Among 22,678 primary cases, we identified 17,319 secondary infections among 50,588 household contacts during a 1–7 day follow-up. The secondary attack rate (SAR) was 29% and 39% in households infected with Omicron BA.1 and BA.2, respectively. BA.2 was associated with increased susceptibility of infection for unvaccinated household contacts (Odds Ratio (OR) 1.99; 95%–CI 1.72-2.31), fully vaccinated contacts (OR 2.26; 95%–CI 1.95–2.62) and booster-vaccinated contacts (OR 2.65; 95%–CI 2.29–3.08), compared to BA.1. We also found increased infectiousness from unvaccinated primary cases infected with BA.2 compared to BA.1 (OR 2.47; 95%–CI 2.15–2.84), but not for fully vaccinated (OR 0.66; 95%–CI 0.57–0.78) or booster-vaccinated primary cases (OR 0.69; 95%–CI 0.59–0.82). Omicron BA.2 is inherently more transmissible than BA.1. Its immune-evasive properties also reduce the protective effect of vaccination against infection, but do not increase infectiousness of breakthrough infections from vaccinated individuals.
Background:
The development of covid-19 vaccinations represents a notable scientific achievement. Nevertheless, concerns have been raised regarding their possible detrimental impact on male fertility OBJECTIVE: To investigate the effect of covid-19 BNT162b2 (Pfizer) vaccine on semen parameters among semen donors (SD).
Methods:
Thirty-seven SD from three sperm banks that provided 216 samples were included in that retrospective longitudinal multicenter cohort study. BNT162b2 vaccination included two doses, and vaccination completion was scheduled 7 days after the second dose. The study included four phases: T0 - pre-vaccination baseline control, which encompassed 1-2 initial samples per SD; T1, T2 and T3 - short, intermediate, and long terms evaluations, respectively. Each included 1-3 semen samples per donor provided 15-45, 75-125 and over 145 days after vaccination completion, respectively. The primary endpoints were semen parameters. Three statistical analyses were conducted: (1) generalized estimated equation model; (2) first sample and (3) samples' mean of each donor per period were compared to T0.
Results:
Repetitive measurements revealed -15.4% sperm concentration decrease on T2 (CI -25.5%-3.9%, p = 0.01) leading to total motile count 22.1% reduction (CI -35% - -6.6%, p = 0.007) compared to T0. Similarly, analysis of first semen sample only and samples' mean per donor resulted in concentration and total motile count (TMC) reductions on T2 compared to T0 - median decline of 12 million/ml and 31.2 million motile spermatozoa, respectively (p = 0.02 and 0.002 respectively) on first sample evaluation and median decline of 9.5 × 106 and 27.3 million motile spermatozoa (p = 0.004 and 0.003, respectively) on samples' mean examination. T3 evaluation demonstrated overall recovery without. Semen volume and sperm motility were not impaired.
Discussion:
This longitudinal study focused on SD demonstrates selective temporary sperm concentration and TMC deterioration 3 months after vaccination followed by later recovery verified by diverse statistical analyses.
Conclusions:
Systemic immune response after BNT162b2 vaccine is a reasonable cause for transient semen concentration and TMC decline. Long-term prognosis remains good.
The increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccination. We conducted a randomised, double-blinded, controlled, phase 2 trial to assess the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated COVID-19 vaccine (BBIBP-CorV) followed by a recombinant protein-based vaccine (NVSI-06-07), using homologous boost with BBIBP-CorV as control. Three groups of healthy adults (600 individuals per group) who had completed two-dose BBIBP-CorV vaccinations 1–3 months, 4–6 months and ≥6 months earlier, respectively, were randomly assigned in a 1:1 ratio to receive either NVSI-06-07 or BBIBP-CorV boost. Immunogenicity assays showed that in NVSI-06-07 groups, neutralizing antibody geometric mean titers (GMTs) against the prototype SARS-CoV-2 increased by 21.01–63.85 folds on day 28 after vaccination, whereas only 4.20–16.78 folds of increases were observed in control groups. For Omicron variant, the neutralizing antibody GMT elicited by homologous boost was 37.91 on day 14, however, a significantly higher neutralizing GMT of 292.53 was induced by heterologous booster. Similar results were obtained for other SARS-CoV-2 variants of concerns (VOCs), including Alpha, Beta and Delta. Both heterologous and homologous boosters have a good safety profile. Local and systemic adverse reactions were absent, mild or moderate in most participants, and the overall safety was quite similar between two booster schemes. Our findings indicated that NVSI-06-07 is safe and immunogenic as a heterologous booster in BBIBP-CorV recipients and was immunogenically superior to the homologous booster against not only SARS-CoV-2 prototype strain but also VOCs, including Omicron.
The current study included 80 people who were vaccinated with the COVID-19 vaccine, 40 males and 40 females, samples were drawn after the first and second doses, and 40 (20 males and 20 females) people as a control group in Thi-Qar province, southern Iraq, and for the period from November 2021 to January 2022, sex hormones were estimated for male and female and IL-10. Sex hormones were estimated by an automated CL device instrument, while IL-10 was measured by third-generation ELISA. The current study showed a significant decrease in FSH and testosterone levels after the second dose in the male group, while females showed a significant decrease in LH after the second dose, and IL-10 was decreased after the second dose in the male group. The LH, E2, and testosterone were significantly increased in both the first and second dose when compared with the control group, while non-significant in the level of FSH. In conclusion, the sex hormone effect of the COVID-19 vaccine and the vaccine induce hormone secretion in vaccinated people compared with non-vaccinated people, while FSH is not affected by the COVID-19 vaccine.
Since the reproductive toxicity of COVID‐19 vaccines have not been assessed in previous clinical trials, and studies have shown that SARS‐CoV‐2 is associated with a decrease in sperm parameters. Although it has been reported that the mRNA SARS‐CoV‐2 vaccines do not adversely affect semen parameters, whether this conclusion applies to inactivated vaccines remains unclear. Here, we conducted a study among patients who accepted in vitro fertilization (IVF) at the reproductive centre between June and August of 2021. In the enrolled cases, men who have completed two doses of COVID‐19 inactivated vaccine were included in “vaccine group” (N = 105), and those who were not vaccinated were included in “control group” (N = 155). In this study, we compare the sperm parameters and embryo quality between these two groups. Our data showed that the sperm parameters were similar in terms of volume, sperm concentration, sperm count, progressive motility, total motility and total motile sperm count between these two groups. Similarly, no significant differences were observed in IVF outcomes. The mean number of 2PN, cleavage‐stage embryos, blastocysts, and good‐quality blastocysts was 8.59 ± 4.47, 5.06 ± 3.17 and 2.08 ± 1.79 in vaccine group, 7.75 ± 4.14, 4.34 ± 3.06 and 1.74 ± 1.54 in control group, respectively. The high‐quality blastocyst rate was 41.05% (218 of 531) in vaccine group and 40.03% (269 of 672) in control group (p > 0.05). In addition, no differences were observed in biochemical and clinical pregnancy rates between the two groups. In summary, our results revealed that COVID‐19 inactivated vaccine administration exhibited no negative effect on sperm parameters and embryo quality in IVF.
Objective
Coronavirus disease 19 (COVID-19) has an increased risk of coagulopathy with high frequency of antiphospholipid antibodies (aPL). Recent reports of thrombosis associated with adenovirus-based vaccines raised concern that SARS-CoV-2 immunization in primary antiphospholipid syndrome (PAPS) patients may trigger clotting complications. Our objectives were to assess immunogenicity, safety, and aPL production in PAPS patients, after vaccinating with Sinovac-CoronaVac, an inactivated virus vaccine against COVID-19.
Methods
This prospective controlled phase-4 study of PAPS patients and a control group (CG) consisted of a two-dose Sinovac-CoronaVac (D0/D28) and blood collection before vaccination (D0), at D28 and 6 weeks after second dose (D69) for immunogenicity/aPL levels. Outcomes were seroconversion (SC) rates of anti-SARS-CoV-2 S1/S2 IgG and/or neutralizing antibodies (NAb) at D28/D69 in naïve participants. Safety and aPL production were also assessed.
Results
We included 44 PAPS patients (31 naïve) and 132 CG (108 naïve) with comparable age (p=0.982) and sex (p>0.999). At D69, both groups had high and comparable SC (83.9% vs. 93.5%, p=0.092), as well as NAb positivity (77.4% vs. 78.7%, p=0.440), and NAb-activity (64.3% vs. 60.9%, p=0.689). Thrombotic events up to 6 months or other moderate/severe side effects were not observed. PAPS patients remained with stable aPL levels throughout the study at D0 vs. D28 vs. D69: anticardiolipin (aCL) IgG (p=0.058) and IgM (p=0.091); anti-beta-2 glycoprotein I (aβ2GPI) IgG (p=0.513) and IgM (p=0.468).
Conclusion
We provided novel evidence that Sinovac-CoronaVac has high immunogenicity and safety profile in PAPS. Furthermore, Sinovac-CoronaVac did not trigger thrombosis nor induced changes in aPL production.
During the coronavirus disease (COVID-19) epidemic, there have been concerns about the impact of vaccines on people's fertility, including the fertility of those who are currently preparing for pregnancy and those who might become pregnant in future. However, there is still a lack of research on the effect of the COVID-19 vaccine on male fertility, and it is not surprising that couples and donors have concerns regarding vaccination. In this study, a retrospective cohort study was conducted to examine semen quality before and after receipt of the inactivated COVID-19 vaccine. There were no statistically significant changes in semen parameters (volume, sperm concentration, progressive motility, and total progressive motile count) after two doses of vaccine (all P > 0.05). In summary, our study updates the most recent studies on the effects of the COVID-19 vaccine on male fertility, and the information from this study could be used to guide fertility recommendations for assisted reproductive technology (ART) patients and donors.
Background
The role of SARS-CoV-2 in the pathogenesis of testicular damage is uncertain.
Methods
We investigated the virological, pathological, and immunological changes in testes of hamsters challenged by SARS-CoV-2 wild-type and its variants by intranasal or direct testicular inoculation using influenza virus A(H1N1)pdm09 as control.
Results
Besides self-limiting respiratory tract infection, intranasal SARS-CoV-2 challenge caused acute decrease in sperm count, and serum testosterone and inhibin B at 4 to 7 days post-infection (dpi), and subsequently reduced testicular size and weight, and serum sex hormone level at 42 to 120 dpi. Acute histopathological damage with varying degree of testicular inflammation, haemorrhage, and necrosis, degeneration of seminiferous tubules and disruption of orderly spermatogenesis were seen with increasing virus inoculum. Degeneration and necrosis of Sertoli and Leydig cells were found. Though viral loads and SARS-CoV-2 nucleocapid (N) protein expression were markedly lower in testicular than lung tissues, direct intra-testicular injection showed N expressing interstitial cells and epididymal epithelial cells. Control intranasal or intra-testicular challenge by A(H1N1)pdm09 showed no testicular infection or damage. From 7 to 120 dpi, degeneration and apoptosis of seminiferous tubules, immune complex deposition and depletion of spermatogenic cell and spermatozoa persisted. Intranasal challenge with Omicron and Delta variants could also induce similar testicular changes. These testicular damages can be prevented by vaccination.
Conclusions
SARS-CoV-2 can cause acute testicular damage with subsequent chronic asymmetric testicular atrophy and associated hormonal changes despite a self-limiting pneumonia in hamsters. Awareness of possible hypogonadism and subfertility is important in managing convalescent COVID-19 males.
Objective
The gut microbiota plays a key role in modulating host immune response. We conducted a prospective, observational study to examine gut microbiota composition in association with immune responses and adverse events in adults who have received the inactivated vaccine (CoronaVac; Sinovac) or the mRNA vaccine (BNT162b2; BioNTech; Comirnaty).
Design
We performed shotgun metagenomic sequencing in stool samples of 138 COVID-19 vaccinees (37 CoronaVac and 101 BNT162b2 vaccinees) collected at baseline and 1 month after second dose of vaccination. Immune markers were measured by SARS-CoV-2 surrogate virus neutralisation test and spike receptor-binding domain IgG ELISA.
Results
We found a significantly lower immune response in recipients of CoronaVac than BNT162b2 vaccines (p<0.05). Bifidobacterium adolescentis was persistently higher in subjects with high neutralising antibodies to CoronaVac vaccine (p=0.023) and their baseline gut microbiome was enriched in pathways related to carbohydrate metabolism (linear discriminant analysis (LDA) scores >2 and p<0.05). Neutralising antibodies in BNT162b2 vaccinees showed a positive correlation with the total abundance of bacteria with flagella and fimbriae including Roseburia faecis (p=0.028). The abundance of Prevotella copri and two Megamonas species were enriched in individuals with fewer adverse events following either of the vaccines indicating that these bacteria may play an anti-inflammatory role in host immune response (LDA scores>3 and p<0.05).
Conclusion
Our study has identified specific gut microbiota markers in association with improved immune response and reduced adverse events following COVID-19 vaccines. Microbiota-targeted interventions have the potential to complement effectiveness of COVID-19 vaccines.
Age and gender disaggregated data on reports of adverse events following two or three doses of the Pfizer-BioNTech COVID-19 vaccine were obtained from four cross-sectional studies. The first was from reports submitted to the Israel Ministry of Health national adverse events database (for ages 16 and above). The second was from a national cross-sectional survey based on an internet panel (for ages 30 and above), and the third and fourth were from cross-sectional surveys among employees of a large company (for ages 20–65) using links to a self-completed questionnaire. Results: In all studies, the risks of adverse events were higher following the second dose and consistently higher in females at all ages. The increased risk among females at all ages included local events such as pain at the injection site, systemic events such as fever, and sensory events such as paresthesia in the hands and face. For the combined adverse reactions, for the panel survey the female-to-male risk ratios (RRs) were 1.89 for the first vaccine dose and 1.82 for the second dose. In the cross-sectional workplace studies, the female-to-male RRs for the first, second and third doses exceeded 3.0 for adverse events, such as shivering, muscle pain, fatigue and headaches. Conclusions: The consistent excess in adverse events among females for the mRNA COVID-19 vaccine indicates the need to assess and report vaccine adverse events by gender. Gender differences in adverse events should be taken into account when determining dosing schedules.
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the waning of vaccine-elicited neutralizing antibodies suggests that additional coronavirus disease 2019 (COVID-19) vaccine doses may be needed for individuals who initially received CoronaVac. We evaluated the safety and immunogenicity of the recombinant adenovirus type 5 (AD5)-vectored COVID-19 vaccine Convidecia as a heterologous booster versus those of CoronaVac as homologous booster in adults previously vaccinated with CoronaVac in an ongoing, randomized, observer-blinded, parallel-controlled phase 4 trial ( NCT04892459 ). Adults who had received two doses of CoronaVac in the past 3–6 months were vaccinated with Convidecia ( n = 96) or CoronaVac ( n = 102). Adults who had received one dose of CoronaVac in the past 1–3 months were also vaccinated with Convidecia ( n = 51) or CoronaVac ( n = 50). The co-primary endpoints were the occurrence of adverse reactions within 28 d after vaccination and geometric mean titers (GMTs) of neutralizing antibodies against live wild-type SARS-CoV-2 virus at 14 d after booster vaccination. Adverse reactions after vaccination were significantly more frequent in Convidecia recipients but were generally mild to moderate in all treatment groups. Heterologous boosting with Convidecia elicited significantly increased GMTs of neutralizing antibody against SARS-CoV-2 than homologous boosting with CoronaVac in participants who had previously received one or two doses of CoronaVac. These data suggest that heterologous boosting with Convidecia following initial vaccination with CoronaVac is safe and more immunogenic than homologous boosting.
Introduction
Coronavirus Disease (COVID-19) caused by Novel Coronavirus named as Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was declared Pandemic by The World Health Organization (WHO) and a Public Health Emergency of International Concern (PHEIC) on January 30, 2020. Many COVID-19 vaccines have been developed, including CoronaVac vaccines by Sinovac. Health care workers, along with medical clerkship students are the priority to receive the vaccine. However, the Adverse Events Following Immunization (AEFI) of the CoronaVac remains unclear. This study aims to describe and analyze the adverse events following immunization (AEFI) of COVID-19 vaccination in medical students in clerkship programs.
Method
We conducted a cross-sectional study using a questionnaire to assess AEFI after CoronaVac vaccination among medical clerkship students. A Chi-Square test with 95 % of CI was used to determine whether gender correlated with symptoms of AEFI.
Result
We identified 144 medical clerkship students. The most common AEFI of SARS-CoV-2 vaccinations was localized pain in the injection site during the first dose with 25 (45 %) reports and the booster dose with 34 (67 %) reports. Then followed by malaise, the first dose with 20 (36 %) reports and the booster dose with 21 (41 %) reports. Other symptoms like headache, fever, shivering, sleepiness, nausea, dysphagia, and cold were also reported.
Conclusions
CoronaVac SARS-COV-2 vaccine has several mild symptoms of AEFI and not correlated with gender. Nevertheless, follow-up after vaccination is needed to prevent immunologic responses that may occur in some patients.
Objective: We investigated whether there were sex differences in adverse reactions to an inactivated SARS-CoV-2 vaccine among medical staff in China.
Methods: From 24 February to 7 March 2021 an online cross-sectional survey was conducted with a self-administered COVID-19 vaccine questionnaire among medical staff in Taizhou, China. In total, 1397 interviewees (1,107 women and 290 men) participated in the survey.
Results: In our study, 178 (16.1%) women and 23 (7.9%) men reported adverse reactions following their first vaccination, and 169 (15.3%) women and 35 (12.1%) men reported adverse reactions following their second vaccination. After adjusting for confounding factors, adverse reactions to other vaccines, worry about adverse reactions, knowledge of the inactivated vaccine being used in the hospital, taking the vaccine for one's family proactively and receiving an influenza vaccination were significantly related to adverse reactions to both injections in women. In contrast, in men, concerns about adverse reactions independently increased the risk of adverse reactions following either vaccination, and a history of adverse reactions to other vaccines also increased the risk of adverse reactions to both injections.
Conclusions: Sex differences in the frequency of reported adverse reactions to an inactivated SARS-CoV-2 vaccine and potential factors were demonstrated in a sample of medical staff.
Objectives
: Vaccines are one of the best interventions developed for eradicating COVID-19,. The aim of this study to provide evidence on Sinopharm COVID-19 vaccine side effects.
Methods
: A cross-sectional survey study was conducted between January and April 2021 to collect data on the effects of COVID-19 vaccine among individuals in the UAE.
Demographic data. vaccination, and the response of people not willing to take COVID-19 vaccine were reported.
Results
: The most common side effects of post 1st dose (≤49 years old vs >49 years) were normal injection site pain, fatigue, and headache, while pain at the vaccination site, fatigue, lethargy, headache, and tenderness were the most side effects of the post 2nd dose in both groups. All the side effects in both doses were more prevalent among the participants ≤ 49-year-old group.
Among female's vs males, side effects were more common in females compared with males in both doses. . The most common reason of not willing to take the COVID-19 vaccine were the vaccines are not effective.
Conclusion
: The 1st and 2nd dose post-vaccination side effects were mild, predictable, and there were no hospitalization cases, this data will help to reduce the vaccine hesitancy.
CoronaVac, an inactivated SARS-CoV-2 vaccine, has been approved for emergency use in several countries. However, its immunogenicity in immunocompromised individuals has not been well established. We initiated a prospective phase 4 controlled trial (no. NCT04754698, CoronavRheum) in 910 adults with autoimmune rheumatic diseases (ARD) and 182 age- and sex-frequency-matched healthy adults (control group, CG), who received two doses of CoronaVac. The primary outcomes were reduction of ≥15% in both anti-SARS-CoV-2 IgG seroconversion (SC) and neutralizing antibody (NAb) positivity 6 weeks (day 69 (D69)) after the second dose in the ARD group compared with that in the CG. Secondary outcomes were IgG SC and NAb positivity at D28, IgG titers and neutralizing activity at D28 and D69 and vaccine safety. Prespecified endpoints were met, with lower anti-SARS-Cov-2 IgG SC (70.4 versus 95.5%, P < 0.001) and NAb positivity (56.3 versus 79.3%, P < 0.001) at D69 in the ARD group than in the CG. Moreover, IgG titers (12.1 versus 29.7, P < 0.001) and median neutralization activity (58.7 versus 64.5%, P = 0.013) were also lower at D69 in patients with ARD. At D28, patients with ARD presented with lower IgG frequency (18.7 versus 34.6%, P < 0.001) and NAb positivity (20.6 versus 36.3%, P < 0.001) than that of the CG. There were no moderate/severe adverse events. These data support the use of CoronaVac in patients with ARD, suggesting reduced but acceptable short-term immunogenicity. The trial is still ongoing to evaluate the long-term effectiveness/immunogenicity. In a large prospective phase 4 trial, vaccination with CoronaVac, an inactivated SARS-CoV-2 vaccine, elicited significantly lower virus-specific IgG antibodies and neutralizing antibodies in patients with autoimmune rheumatic diseases than in age- and sex-matched healthy control trial participants.
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.
To evaluate the testicular damage caused by COVID‐19, we prospectively evaluated 44 patients who applied to the COVID‐19 outpatient clinic between March 2020 and July 2020. Patients' ages, COVID‐19 PCR results, presence of pneumonia, total testosterone, luteinising hormone (LH) and follicle‐stimulating hormone (FSH) values were recorded. It was evaluated whether there were significant differences between people who were positive for COVID‐19 and those who were not. Any differences between those who had COVID‐19 pneumonia and those who did not were also recorded. There was no difference between the FSH, LH and testosterone values of the COVID‐19 PCR positive and negative patients (p = 0.80, vp = 0.62, p = 0.56 respectively). However when LH values were separated as low, normal and high, LH values were statistically significantly higher in the COVID‐19 PCR positive group (p = 0.04). Thoracic computed tomography was performed in 42 patients. Testosterone levels were significantly lower in patients with COVID‐19 pneumonia (p = 0.01). When FSH, LH and testosterone values were separated as low, normal and high, there was no difference in FSH and LH values (p = 1, p = 0.2). Testosterone levels were found significantly lower in patients with COVID‐19 pneumonia (p < .001). Testosterone levels seem to decrease during acute COVID‐19 infection, especially in the patient group with viral pneumonia.
Background: The current study aimed to determine the impact of SARS-CoV-2 infection on male fertility.
Methods: This is a single-center, hospital-based observational study that included autopsied testicular and epididymal specimens of deceased COVID-19 male patients (n=6) and recruited recovering COVID-19 inpa-tients (n=23) with an equal number of age-matched controls, respectively. We performed histopathological examinations on testicular and epididymal specimens, and also performed TUNEL assay and immunohis-tochemistry. Whereas, we investigated the semen specimen for sperm parameters and immune factors.
Findings: Autopsied testicular and epididymal specimens of COVID-19 showed the presence of interstitial edema, congestion, red blood cell exudation in testes, and epididymides. Thinning of seminiferous tubules was observed. The number of apoptotic cells within seminiferous tubules was significantly higher in COVID-19 compared to control cases. It also showed an increased concentration of CD3+ and CD68+ in the interstitial cells of testicular tissue and the presence of IgG within seminiferous tubules. Semen from COVID-19 inpa-tients showed that 39.1% (n=9) of them have oligozoospermia, and 60.9% (n=14) showed a significant increase in leucocytes in semen. Decreased sperm concentration, and increased seminal levels of IL-6, TNF-a, and MCP-1 compared to control males were observed.
Interpretation: Impairment of spermatogenesis was observed in COVID-19 patients, which could be partially explained as a result of an elevated immune response in testis. Additionally, autoimmune orchitis occurred in some COVID-19 patients. Further research on the reversibility of impairment and developing treatment are warranted.
Objectives
The purpose of this study is to assess the prevalence of overweight/obesity, abdominal obesity and obesity-related risk factors in southern China.
Methods
A cross-sectional survey of 15,364 participants aged 15 years and older was conducted from November 2013 to August 2014 in Jiangxi Province, China, using questionnaire forms and physical measurements. The physical measurements included body height, weight, waist circumference (WC), body fat percentage (BFP) and visceral adipose index (VAI). Multivariate logistic regression analysis was performed to evaluate the risk factors for overweight/obesity and abdominal obesity.
Results
The prevalence of overweight was 25.8% (25.9% in males and 25.7% in females), while that of obesity was 7.9% (8.4% in males and 7.6% in females). The prevalence of abdominal obesity was 10.2% (8.6% in males and 11.3% in females). The prevalence of overweight/obesity was 37.1% in urban residents and 30.2% in rural residents, and this difference was significant (P < 0.001). Urban residents had a significantly higher prevalence of abdominal obesity than rural residents (11.6% vs 8.7%, P < 0.001). Among the participants with an underweight/normal body mass index (BMI), 1.3% still had abdominal obesity, 16.1% had a high BFP and 1.0% had a high VAI. Moreover, among obese participants, 9.7% had a low /normal WC, 0.8% had a normal BFP and 15.9% had a normal VAI. Meanwhile, the partial correlation analysis indicated that the correlation coefficients between VAI and BMI, VAI and WC, and BMI and WC were 0.700, 0.666, and 0.721, respectively. A multivariate logistic regression analysis indicated that being female and having a high BFP and a high VAI were significantly associated with an increased risk of overweight/obesity and abdominal obesity. In addition, living in an urban area and older age correlated with overweight/obesity.
Conclusion
This study revealed that obesity and abdominal obesity, which differed by gender and age, are epidemic in southern China. Moreover, there was a very high, significant, positive correlation between WC, BMI and VAI. However, further studies are needed to explore which indicator of body fat could be used as the best marker to indirectly reflect cardiometabolic risk.
Objectives
This study aims to estimate the prevalence of overweight and obesity and determine potential influencing factors among adults in northeast China.
Methods
A cross-sectional survey was conducted in Jilin Province, northeast China, in 2012. A total of 9873 men and 10 966 women aged 18–79 years from the general population were included using a multistage stratified random cluster sampling design. Data were obtained from face-to-face interview and physical examination. After being weighted according to a complex sampling scheme, the sample was used to estimate the prevalence of overweight (body mass index (BMI) 24–27.9 kg/m2) and obesity (BMI >28 kg/m2) in Jilin Province, and analyse influencing factors through corresponding statistical methods based on complex sampling design behaviours.
Results
The overall prevalence of overweight was 32.3% (male 34.3%; female 30.2%), and the prevalence of obesity was 14.6% (male 16.3%; female 12.8%) in Jilin Province. The prevalence of both overweight and obesity were higher in men than women (p<0.001). Influencing factors included sex, age, marriage status, occupation, smoking, drinking, diet and hours of sleep (p<0.05).
Conclusions
This study estimated that the prevalence of overweight and obesity among adult residents of Jilin Province, northeast China, were high. The results of this study will be submitted to the Health Department of Jilin Province and other relevant departments as a reference, which should inform policy makers in developing education and publicity to prevent and control the occurrence of overweight and obesity.
Rift Valley fever (RVF) is an arthropod-borne viral disease of importance in livestock and humans. Epidemics occur periodically in domestic ruminants. People in contact with infected livestock may develop disease that varies from mild flu-like symptoms to fatal viraemia. Livestock vaccination may assist in disease control. Rift Valley fever virus (RVFV) Clone 13 is a relatively new vaccine against RVF, derived from an avirulent natural mutant strain of RVFV, and has been shown to confer protective immunity against experimental infection with RVFV. The hypothesis tested in the current trial was that rams vaccinated with RVFV Clone 13 vaccine would not experience a reduction in semen quality (measured by evaluating the percentage progressively motile and percentage morphologically normal spermatozoa in successive ejaculates) relative to unvaccinated control animals. Ram lambs were screened for antibodies to RVFV using a serum neutralisation test. Animals without detectable antibodies (n = 23) were randomly allocated to either a test group (n = 12) or a control group (n = 11). Animals in the test group were vaccinated with RVFV Clone 13 vaccine. Daily rectal temperature measurements and weekly semen and blood samples were taken from all animals. Seven animals were eliminated from the statistical analysis because of potential confounding factors. Logistic regression analysis was performed on data gathered from the remaining animals to determine whether an association existed between animal group, rectal temperature and semen quality parameters. No correlation existed between the treatment group and values obtained for the semen quality parameters measured. There was no statistically significant post-vaccination decline in the percentage of live morphologically normal spermatozoa, or the percentage of progressively motile spermatozoa, either when assessed amongst all animals or when assessed within individual groups. A repeat study with a larger sample size and a more comprehensive pre-screening process may be indicated to avoid the inclusion of unsuitable animals.
The process of spermatogenesis is temperature-dependent and occurs optimally at temperatures slightly lower than that of the body. Adequate thermoregulation is imperative to maintain testicular temperatures at levels lower than that of the body core. Raised testicular temperature has a detrimental effect on mammalian spermatogenesis and the resultant spermatozoa. Therefore, thermoregulatory failure leading to heat stress can compromise sperm quality and increase the risk of infertility. In this paper, several different types of external and internal factors that may contribute towards testicular heat stress are reviewed. The effects of heat stress on the process of spermatogenesis, the resultant epididymal spermatozoa and on germ cells, and the consequent changes in the testis are elaborated upon. We also discuss the molecular response of germ cells to heat exposure and the possible mechanisms involved in heat-induced germ cell damage, including apoptosis, DNA damage and autophagy. Further, the intrinsic and extrinsic pathways that are involved in the intricate mechanism of germ cell apoptosis are explained. Ultimately, these complex mechanisms of apoptosis lead to germ cell death.
Objective
To assess the effect of foot and mouth disease (FMD) vaccination on seminal and biochemical profiles of semen of mithun at pre and post vaccinated stage.
Methods
The breeding bulls were maintained at Semen Collection Centre, National Research Centre on Mithun, Jharnapani, Nagaland. A total of 160 ejaculates were collected from eight mithun bulls twice a week at about 4 weeks in pre vaccinated stage and 12 weeks post vaccinated stage to know the effect of vaccine stress on seminal and biochemical profiles of mithun semen. The vaccine was given at the end of 4th week of experimental period and semen was collected and evaluated upto the 16th weeks of experimental period.
Results
It revealed that FMD vaccination affected the sperm functional and biochemical parameters significantly (P<0.05) upto 10th weeks of vaccination. But the animal recovered slowly in both physical health and spermiogram.
Conclusions
The adverse effect of vaccination on seminal parameters suggest that the semen collection and preservation should be suspended till 10th weeks of vaccination to get normal fertility of sperm to avoid the failure of conception from artificial insemination using such semen in this precious species.
MicroRNAs target specific mRNA(s) to silence its expression and thereby regulate various cellular processes. We have investigated miRNA gene counts in chromosomes for 20 different species and observed wide variation. Certain chromosomes have extremely high number of miRNA gene compared with others in all the species. For example, high number of miRNA gene in X chromosome and the least or absence of miRNA gene in Y chromosome was observed in all species. To search the criteria governing such variation of miRNA gene counts in chromosomes, we have selected three parameters- length, number of non-coding and coding genes in a chromosome. We have calculated Pearson's correlation coefficient of miRNA gene counts with length, number of non-coding and coding genes in a chromosome for all 20 species. Major number of species showed that number of miRNA gene was not correlated with chromosome length. Eighty five percent of species under study showed strong positive correlation coefficient (r ≥ 0.5) between the numbers of miRNA gene vs. non-coding gene in chromosomes as expected because miRNA is a sub-set of non-coding genes. 55% species under study showed strong positive correlation coefficient (r ≥ 0.5) between numbers of miRNA gene vs. coding gene. We hypothesize biogenesis of miRNA largely depends on coding genes, an evolutionary conserved process. Chromosomes having higher number of miRNA genes will be most likely playing regulatory roles in several cellular processes including different disorders. In humans, cancer and cardiovascular disease associated miRNAs are mostly intergenic and located in Chromosome 19, X, 14, and 1.
Sex steroid hormones play important physiological roles in reproductive and nonreproductive tissues, including immune cells. These hormones exert their functions by binding to either specific intracellular receptors that act as ligand-dependent transcription factors or membrane receptors that stimulate several signal transduction pathways. The elevated susceptibility of males to bacterial infections can be related to the usually lower immune responses presented in males as compared to females. This dimorphic sex difference is mainly due to the differential modulation of the immune system by sex steroid hormones through the control of proinflammatory and anti-inflammatory cytokines expression, as well as Toll-like receptors (TLRs) expression and antibody production. Besides, sex hormones can also affect the metabolism, growth, or virulence of pathogenic bacteria. In turn, pathogenic, microbiota, and environmental bacteria are able to metabolize and degrade steroid hormones and their related compounds. All these data suggest that sex steroid hormones play a key role in the modulation of bacterial-host interactions.
Sperm DNA fragmentation was analysed in 113 semen samples obtained from different rams over a period of one year. Semen samples were collected from: unvaccinated rams between January and June (Control group 1; CG1); vaccinated rams at least 70 days after vaccination between October and December (Control group 2; CG2); vaccinated rams 20 days after vaccination (Vaccinated group 1; VG1); and vaccinated rams 40 days after vaccination (Vaccinated group 2; VG2). Results show Miloxan, the vaccine of interest in this study, increased the percentage of sperm cells with fragmented DNA by 10-fold on average (from 6.5±7.9 to 63.4±24.2). However, the negative impact of vaccination on sperm DNA fragmentation appeared to reversible; near normal levels of sperm DNA fragmentation had been restored 40 days after vaccination (21.7±10.6). On the basis of these data, the use of semen samples from vaccinated animals should be avoided until at least one month after vaccination.
Traditionally, biomedical research in the field of pain has been conducted with male animals and subjects. Over the past 20-30 yr, it has been increasingly recognized that this narrow approach has missed an important variable: sex. An ever-increasing number of studies have established sex differences in response to pain and analgesics. These studies have demonstrated that the differences between the sexes appear to have a biological and psychological basis. We will provide brief review of the epidemiology, rodent, and human experimental findings. The controversies and widespread disagreement in the literature highlight the need for a progressive approach to the questions involving collaborative efforts between those trained in the basic and clinical biomedical sciences and those in the epidemiological and social sciences. In order for patients suffering from acute and/or chronic pain to benefit from this work, the approach has to involve the use or development of clinically relevant models of nociception or pain to answer the basic, but complex, question. The present state of the literature allows no translation of the work to our clinical decision-making.
The measurement or evaluation and clinical significance of human sperm morphology has always been and still is a controversial aspect of the semen analysis for the determination of a male's fertility potential. In this review the background of the development of the evaluation criteria for sperm morphology will be discussed. Aspects of criticism on the strict criteria definition and use of the criteria for sperm morphology evaluation will be discussed as well as possible reasons for the decline in normal sperm morphology values and how we can compromise for this phenomenon resulting in the very low normal reference value as published in the 2010 WHO manual for the Examination and Processing of Human Semen. One of the possible solutions may be to give more attention to a limited number of abnormal sperm morphology categories and the inclusion of sperm morphology patterns. It is concluded in this review that if done correctly and with care and with strict application of existing guidelines as outlined in the 2010 WHO manual, sperm morphology measurement still has a very important role to play in the clinical evaluation of male fertility potential.
Background
Impaired semen quality and reproductive hormone levels were observed in patients during and after recovery from coronavirus disease 2019 (COVID-19), which raised concerns about negative effects on male fertility. Therefore, this study systematically reviews available data on semen parameters and sex hormones in patients with COVID-19.
Methods
Systematic search was performed on PubMed and Google Scholar until July 18, 2022. We identified relevant articles that discussed the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on male fertility.
Results
A total number of 1684 articles were identified by using a suitable keyword search strategy. After screening, 26 articles were considered eligible for inclusion in this study. These articles included a total of 1960 controls and 2106 patients. When all studies were considered, the results showed that the semen parameters and sex hormone levels of patients infected with SARS-CoV-2 exhibited some significant differences compared with controls. Fortunately, these differences gradually disappear as patients recover from COVID-19.
Conclusion
While present data show the negative effects of SARS-CoV-2 infection on male fertility, this does not appear to be long-term. Semen quality and hormone levels will gradually increase to normal as patients recover.
Introduction:
There is no study specifically focused on SARS-CoV-2 vaccine in primary Sjögren's syndrome (pSS).
Objectives:
To assess the immunogenicity, safety, possible effects on disease activity, and autoantibody profile of the Sinovac-CoronaVac vaccine in pSS.
Methods:
Fifty-one pSS patients and 102 sex- and age-balanced controls without autoimmune diseases were included in a prospective phase 4 trial of the Sinovac-CoronaVac vaccine (two doses 28 days apart, D0/D28). Participants were assessed in three face-to-face visits (D0/D28 and six weeks after the 2nd dose (D69)) regarding adverse effects; clinical EULAR Sjögren's Syndrome Disease Activity Index (clinESSDAI); anti-SARS-CoV-2 S1/S2 IgG (seroconversion (SC) and geometric mean titers (GMT)); neutralizing antibodies (NAb); and pSS autoantibody profile.
Results:
Patients and controls had comparable female sex frequency (98.0% vs. 98.0%, p = 1.000) and mean age (53.5 ± 11.7 vs. 53.4 ± 11.4 years, p = 0.924), respectively. On D69, pSS patients presented moderate SC (67.5% vs. 93.0%, p < 0.001) and GMT (22.5 (95% CI 14.6-34.5) vs. 59.6 (95% CI 51.1-69.4) AU/mL, p < 0.001) of anti-SARS-CoV-2 S1/S2 IgG but lower than controls, and also, moderate NAb frequency (52.5% vs. 73.3%, p = 0.021) but lower than controls. Median neutralizing activity on D69 was comparable in pSS (58.6% (IQR 43.7-63.6)) and controls (64% (IQR 46.4-81.1)) (p = 0.219). Adverse events were mild. clinESSDAI and anti-Ro(SS-A)/anti-La(SS-B) levels were stable throughout the study (p > 0.05).
Conclusion:
Sinovac-CoronaVac vaccine is safe in pSS, without a deleterious impact on disease activity, and has a moderate short-term humoral response, though lower than controls. Thus, a booster dose needs to be studied in these patients.
Trial registration:
ClinicalTrials.gov Identifier: NCT04754698. Key Points • Sinovac-CoronaVac vaccine is safe in pSS, without a detrimental effect on systemic disease activity, and has a moderate short-term humoral response • A booster dose should be considered in these patients.
Research Question
We aimed to investigate the effect of the BNT162b2 COVID-19 vaccine on sperm parameters of patients with a normal and abnormal semen analysis.
Design
We collected data of male patients undergoing in vitro fertilization (IVF) treatment after vaccination completion between February and June 2021 (POST vaccine). For comparison, we reviewed records of the same patients before the vaccination (PRE vaccine) up to January 2017. Azoospermia patients were excluded. Sperm parameters were compared between PRE and POST vaccine groups. Each patient served as self-control.
Results
Seventy-two patients were included in the study (mean age 38.1±6.7 years), of whom 57 had a normal semen analysis. The mean time between the first vaccine and the POST vaccine sperm analysis was 66.3±44.0 days. The median [IQR] of the sperm parameters before and after the vaccination were: sperm volume before 3.0 [2.0-4.0] and after 3.0 [1.6-3.9] ml, p=0.02; sperm concentration: before 26.5 [14.0-64.7] and after 31.0 [14.2-80.0] 10⁶/ml, p=0.35; and total motile count: before 33.7 [9.0-66.0] and after 29 [6.0-97.5] 10⁶, p=0.96. Sub-group analyses were performed for patients with male infertility and patients with a normal semen analysis. Neither of the sub-groups showed significant changes post-vaccination.
Conclusion
Sperm parameters showed no significant changes following vaccination among men with a normal and abnormal semen analysis. Therefore, the BNT162b2 vaccine appears not to affect sperm parameters. The preliminary results are reassuring for the entire global population, currently undergoing intense vaccination campaigns against COVID-19.
Background
Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older.
Methods
In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18–59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574.
Findings
540 (90%) of 600 participants aged 18–59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1–5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2–8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9–190·4) for cohort 1b-14d-8m and 143·1 (110·8–184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3–27·6) on day 28 after the second dose to 45·8 (35·7–58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4–51·1) to 49·7 (39·9–61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1–12·0) in cohort 1a-14d-2m and 10·0 (7·3–13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0–59·4) on day 28 after the second dose to 158·5 (96·6–259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m.
Interpretation
A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses.
Funding
National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China.
Translation
For the Mandarin translation of the abstract see Supplementary Materials section.
The coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has precipitated a global health crisis of unprecedented proportions. Because of its severe impact, multiple COVID-19 vaccines are being rapidly developed, approved and manufactured. Among them, mRNA vaccines are considered as ideal candidates with special advantages to meet this challenge. However, some serious adverse events have been reported after their application, significantly increasing concerns about the safety and efficacy of the vaccines and doubts about the necessity of vaccination. Although several fertility societies have announced that COVID-19 mRNA vaccines are unlikely to affect fertility, there is no denying that the current evidence is very limited, which is one of the reasons for vaccine hesitancy in the population, especially in pregnant women. Herein, we provide an in-depth discussion on the involvement of the male and female reproductive systems during SARS-CoV-2 infection or after vaccination. On one hand, despite the low risk of infection in the male reproductive system or fetus, COVID-19 could pose an enormous threat to human reproductive health. On the other hand, our review indicates that both men and women, especially pregnant women, have no fertility problems or increased adverse pregnancy outcomes after vaccination, and, in particular, the benefits of maternal antibodies transferred through the placenta outweigh any known or potential risks. Thus, in the case of the rapid spread of COVID-19, although further research is still required, especially a larger population-based longitudinal study, it is obviously a wise option to be vaccinated instead of suffering from serious adverse symptoms of virus infection.
Research question
Does Pfizer's Covid-19 vaccination detrimentally affect semen analysis parameters?
Design
We conducted a prospective cohort study in a single large tertiary center in Israel between February and March of 2021. Semen samples of 75 fertile men were analyzed 1-2 months following the second dose of Pfizer's covid-19 vaccine. The semen parameters were compared to the WHO reference ranges. The primary outcome was the percentage of abnormal semen parameters in those vaccinated, i.e. the rates of oligozoospermia, reduced percentage of motile sperm and abnormal sperm morphology.
Results
The interval from the time of the second vaccine to the date of participation was on average 37 days, with most subjects describing either mild or no side effects after the first or second dose. The mean sperm concentration was 63.2±33.6 10^6 ml with only a single subject (1.3%) with sperm count of 12.5 10^6 ml, considered by the WHO as oligozoospermic. The mean sperm motility percentage was 64.5%±16.7 with only a single subject (1.3%) displaying reduced motility. No significant morphological abnormalities were observed. This constituted a significantly lower percentage of abnormal semen parameters compared with the 5% rates reported in fertile men by the WHO.
Conclusions
The semen parameters following Covid-19 vaccination were predominantly within normal reference ranges as set by the WHO and do not reflect any causative detrimental effect from COVID-19 vaccination. Our results strengthen the notion that the Pfizer's SARS-CoV-2 vaccine is safe and should be recommended to fertility seeking men.
ClinicalTrials.gov number, NCT04778033.
To address vaccine hesitancy based on concerns about fertility, this study assesses sperm parameters before and after mRNA vaccine administration.
Background
With the unprecedented morbidity and mortality associated with the COVID-19 pandemic, a vaccine against COVID-19 is urgently needed. We investigated CoronaVac (Sinovac Life Sciences, Beijing, China), an inactivated vaccine candidate against COVID-19, containing inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for its safety, tolerability and immunogenicity.
Methods
In this randomised, double-blind, placebo-controlled, phase 1/2 clinical trial, healthy adults aged 18–59 years were recruited from the community in Suining County of Jiangsu province, China. Adults with SARS-CoV-2 exposure or infection history, with axillary temperature above 37·0°C, or an allergic reaction to any vaccine component were excluded. The experimental vaccine for the phase 1 trial was manufactured using a cell factory process (CellSTACK Cell Culture Chamber 10, Corning, Wujiang, China), whereas those for the phase 2 trial were produced through a bioreactor process (ReadyToProcess WAVE 25, GE, Umea, Sweden). The phase 1 trial was done in a dose-escalating manner. At screening, participants were initially separated (1:1), with no specific randomisation, into two vaccination schedule cohorts, the days 0 and 14 vaccination cohort and the days 0 and 28 vaccination cohort, and within each cohort the first 36 participants were assigned to block 1 (low dose CoronaVac [3 μg per 0·5 mL of aluminium hydroxide diluent per dose) then another 36 were assigned to block 2 (high-dose Coronavc [6 μg per 0·5 mL of aluminium hydroxide diluent per dse]). Within each block, participants were randomly assigned (2:1), using block randomisation with a block size of six, to either two doses of CoronaVac or two doses of placebo. In the phase 2 trial, at screening, participants were initially separated (1:1), with no specific randomisation, into the days 0 and 14 vaccination cohort and the days 0 and 28 vaccination cohort, and participants were randomly assigned (2:2:1), using block randomisation with a block size of five, to receive two doses of either low-dose CoronaVac, high-dose CoronaVac, or placebo. Participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was adverse reactions within 28 days after injection in all participants who were given at least one dose of study drug (safety population). The primary immunogenic outcome was seroconversion rates of neutralising antibodies to live SARS-CoV-2 at day 14 after the last dose in the days 0 and 14 cohort, and at day 28 after the last dose in the days 0 and 28 cohort in participants who completed their allocated two-dose vaccination schedule (per-protocol population). This trial is registered with ClinicalTrials.gov, NCT04352608, and is closed to accrual.
Findings
Between April 16 and April 25, 2020, 144 participants were enrolled in the phase 1 trial, and between May 3 and May 5, 2020, 600 participants were enrolled in the phase 2 trial. 743 participants received at least one dose of investigational product (n=143 for phase 1 and n=600 for phase 2; safety population). In the phase 1 trial, the incidence of adverse reactions for the days 0 and 14 cohort was seven (29%) of 24 participants in the 3 ug group, nine (38%) of 24 in the 6 μg group, and two (8%) of 24 in the placebo group, and for the days 0 and 28 cohort was three (13%) of 24 in the 3 μg group, four (17%) of 24 in the 6 μg group, and three (13%) of 23 in the placebo group. The seroconversion of neutralising antibodies on day 14 after the days 0 and 14 vaccination schedule was seen in 11 (46%) of 24 participants in the 3 μg group, 12 (50%) of 24 in the 6 μg group, and none (0%) of 24 in the placebo group; whereas at day 28 after the days 0 and 28 vaccination schedule, seroconversion was seen in 20 (83%) of 24 in the 3 μg group, 19 (79%) of 24 in the 6 μg group, and one (4%) of 24 in the placebo group. In the phase 2 trial, the incidence of adverse reactions for the days 0 and 14 cohort was 40 (33%) of 120 participants in the 3 μg group, 42 (35%) of 120 in the 6 μg group, and 13 (22%) of 60 in the placebo group, and for the days 0 and 28 cohort was 23 (19%) of 120 in the 3 μg group, 23 (19%) of 120 in the 6 μg group, and 11 (18%) of 60 for the placebo group. Seroconversion of neutralising antibodies was seen for 109 (92%) of 118 participants in the 3 μg group, 117 (98%) of 119 in the 6 μg group, and two (3%) of 60 in the placebo group at day 14 after the days 0 and 14 schedule; whereas at day 28 after the days 0 and 28 schedule, seroconversion was seen in 114 (97%) of 117 in the 3 μg group, 118 (100%) of 118 in the 6 μg group, and none (0%) of 59 in the placebo group.
Interpretation
Taking safety, immunogenicity, and production capacity into account, the 3 μg dose of CoronaVac is the suggested dose for efficacy assessment in future phase 3 trials.
Funding
Chinese National Key Research and Development Program and Beijing Science and Technology Program.
Both sex (i.e., biological differences) and gender (i.e., social or cultural influences) impact vaccine acceptance, responses, and outcomes. Clinical data illustrate that among children, young adults, and aged individuals, males and females differ in vaccine-induced immune responses, adverse events, and protection. Although males are more likely to receive vaccines, following vaccination, females typically develop higher antibody responses and report more adverse effects of vaccination than do males. Human, nonhuman animal, and in vitro studies reveal numerous immunological, genetic, hormonal, and environmental factors that differ between males and females and contribute to sex- and gender-specific vaccine responses and outcomes. Herein, we address the impact of sex and gender variables that should be considered in preclinical and clinical studies of vaccines.
An outbred mouse model was used to determine if antibody response to immunization with whole-virus trivalent inactivated influenza vaccine (TIV) differs between the sexes. The antibody response was examined one (serum titer of IgM antibodies), and three and six weeks post-immunization (serum titer of neutralizing and total IgG antibodies and IgG subclass profile). Compared with male in female mice was found (i) the more robust IgM response against all influenza strains included in TIV and (ii) more vigorous neutralizing antibody and total IgG responses against H1N1 influenza virus at both the examined time points post-immunization. The total IgG antibody response against H3N2 and B influenza viruses was comparable between female and male mice three weeks post-immunization, but significantly greater in female mice six weeks post-immunization. The neutralizing antibody response against H3N2 and B influenza viruses did not significantly differ between sexes at both the examined points post-immunization. Finally, three weeks post-immunization subclass profile of IgG specific to the influenza strains included in TIV differed between female and male mice, reflecting the lower titer of IgG1 antibodies in female ones, so that IgG2a (contributing mainly to the total IgG) to IgG1 ratio in mice of this sex was shifted toward the former. In agreement with this shift, compared with male mice, Th1/Th2 balance in female mice was shifted toward Th1, as shown by ELISPOT. Collectively, the results showed influenza virus strain-dependent sexual dimorphism in the magnitude, dynamics and characteristics of antibody response in outbred mice immunized with TIV.
Estrogen has long been reported to show immunomodulatory effects on immune responses, yet, its specific anti-inflammatory mechanism is not clear.
In this study, we analyzed the effects of beta-estradiol (E2), at its contraceptive dose, on both T cell-independent and T cell-dependent inflammations, and the associated immune mechanism, in female mice. The T cell-independent inflammation was locally induced either with an intradermal injection of olive oil in the footpad, or by an intraperitoneal injection of proteose peptone (PP). The T cell-dependent inflammation was induced by an intraperitoneal injection of the purified protein derivatives (PPD).
While E2 inhibited olive oil-induced inflammation as monitored by the decrease in footpad swelling, it did not affect the gene expression of monocyte chemoattractant protein-1 and IL-6 by cells at the inflammatory locus. E2 also inhibited PP-induced inflammation as monitored by the decrease in the number of inflammatory peritoneal exudate cells (PEC) coinciding with a marked decrease in the number of macrophages and granulocytes (Gr. 1+). While E2 did not affect the gene expression of monocyte chemoattractant protein-1 and IL-6 by PP-elicited PEC, it decreased both gene expression and production of TNF-alpha. E2 also decreased the number of cells expressing the lymphocyte function-activated protein-1 in PP-elicited PEC, but not for CD62L. In purified protein derivative-induced T cell-dependent inflammation, E2 decreased the total cellularity of PEC and the relative numbers of CD3+ and CD4+ T cells, and the number of cells expressing the lymphocyte activation markers CD40, CD44, CD69 and IL-2Ralpha in PEC. Furthermore, while E2 did not affect the gene expression of the early T lymphocyte activation protein-1 by PEC, it decreased the gene expression of INF-gamma.
Collectively, the results suggest that E2-mediated inhibition of inflammatory responses may be due to a combination of suppression of homing and activation of inflammatory cells and their production of TNF-alpha and IFN-gamma.
Background:
Previous studies suggest pain sensitivity may be decreased in obesity, but it is unknown whether this is a global or a site-specific phenomenon related to the amount of excess fat.
Methods:
Design:
a cross-sectional study comparing obese and non-obese participants on body sites with much and little excess subcutaneous fat in obesity. Hot and cold sensory detection thresholds, pain thresholds, pain tolerance and subjective ratings for a cold (0 °C) and hot (48 °C) stimulus were assessed using a 16 × 16 mm thermode (Medoc, Israel) on the forehead and abdomen. Pressure pain thresholds were measured on the hand. Cold water immersion tolerance duration and subjective ratings were assessed on the hand. Two indices of central pain processing, i.e., temporal summation and heterotopic noxious stimulation, were assessed.
Results:
A total of 20 obese participants [10M/10F, BMI mean (SD) =41.5 kg/m(2) (9.4 kg/m(2) )] and 20 age- and gender-matched non-obese controls [10M/10F, BMI mean (SD) =23.5 kg/m(2) (2.9 kg/m(2) )] were studied. Compared with non-obese, obese participants had higher thresholds and lower subjective ratings, indexing decreased sensitivity, for painful and non-painful thermal stimuli on the abdomen, an area with much excess subcutaneous fat. Decreases in abdominal sensitivity correlated with measures of adiposity (i.e., waist-to-hip ratio and subcutaneous fat thickness). On areas with little excess subcutaneous fat (forehead and hand), obese and non-obese groups did not differ in measures of thermal or pressure sensitivity, nor for indices of central pain processing.
Conclusion:
Obese participants are less sensitive than non-obese individuals, but only on areas with excess subcutaneous fat.
MicroRNAs (miRNAs) are newly discovered, small, noncoding ribonucleic acids (RNAs) that play critical roles in the regulation of host genome expression at the posttranscriptional level. During last 20 years, miRNAs have emerged as key regulators of various biological processes including immune cell lineage commitment, differentiation, maturation, and maintenance of immune homeostasis and normal function. Thus, it is not surprising that dysregulated miRNA expression patterns now have been documented in a broad range of diseases including cancer as well as inflammatory and autoimmune diseases. This rapidly emerging field has revolutionized our understanding of normal immunoregulation and breakdown of self-tolerance. This review focuses on the current understanding of miRNA biogenesis, the role of miRNAs in the regulation of innate and adaptive immunity, and the association of miRNAs with autoimmune diseases. We have discussed miRNA dysregulation and the potential role of miRNAs in systemic lupus erythematosus (SLE), rheumatoid arthritis, and multiple sclerosis. Given that most autoimmune diseases are female-predominant, we also have discussed sex hormone regulation of miRNAs in inflammatory responses, with an emphasis on estrogen, which now has been shown to regulate miRNAs in the immune system. The field of miRNA regulation of mammalian genes has tremendous potential. The identification of specific miRNA expression patterns in autoimmune diseases as well as a comprehensive understanding of the role of miRNA in disease pathogenesis offers promise of not only novel molecular diagnostic markers but also new gene therapy strategies for treating SLE and other inflammatory autoimmune diseases.
The objective of this research was to determine the effect of vaccination against porcine circovirus type 2 (PCV2) on ejaculate characteristics, PCV2-specific antibody titers in serum, viremia, and viral shedding in the semen of PCV2-positive boars. Before vaccination, all boars were confirmed by PCR to be naturally infected with PCV2. The boars were vaccinated with a commercial killed vaccine against PCV2 (n = 5) or served as controls and received 2 mL of 0.9% saline (n = 5). Semen and blood samples were collected before vaccination at wk 0 and at 7-d intervals thereafter until wk 8. Sperm concentration and characteristics of sperm motility were assessed using a computer-assisted sperm analysis system, and sperm morphology was evaluated using light microscopy after staining. The PCV2 antibody titers were determined in serum using an ELISA, and the genomic copy numbers of PCV2 DNA in serum and semen were determined by real-time PCR. In general, there were no effects of treatment or treatment × week on semen or sperm characteristics (P > 0.10). An effect of treatment × week was detected for serum antibody titers (P < 0.01). Compared with controls, PCV2 antibody titers in vaccinated boars were less (P < 0.01) at wk 7 (1.01 ± 0.05 titer/mL vs. 1.23 ± 0.05 titer/mL) and tended (P = 0.07) to be less at wk 8 (1.05 ± 0.05 titer/mL vs. 1.17 ± 0.05 titer/mL). There were no effects of treatment or treatment × week for serum and semen genomic copy numbers of PCV2 DNA (P > 0.10). There was a tendency (P = 0.09) for an effect of week on serum viral load. It was evident that during this experiment, boars experienced reoccurring PCV2 infection, and the detection of an increased PCV2 DNA load in serum preceded that in semen; the duration of reoccurring infection appeared to be less in vaccinated boars compared with controls. In summary, vaccination against PCV2 can reduce antibody titers when given postinfection and has no dramatic effect on indicators of semen quality. Vaccination against PCV2 in naturally infected boars can also decrease the length of reoccurring infection and decrease the duration of viral shedding in semen.