In China , in December 2019, a coronavirus (COVID-19) (SARS-CoV-2) appeared,  triggering a group of acute diseases in respiratory  [1,2]. SARS-CoV-2 as other viruses, change with time or mutate. The consequences of these changes and mutations result in a difference in the rates of disease spread and also the severity of the disease (3).  There were a number of challenges that happened during the COVID-19 pandemic to get rid of an infection and synthesis vaccine against these viral infections. To strengthen immunity and prevent infection, they developed vaccines taken as two doses [4,5]. 

Thyroid peroxidase (TPO) is an enzyme that is reliable for the iodination of tyrosyl residues incorporation in thyroglobulin [6]. It is known as the microsomal antigen due to its intracellular location. Its specific autoantigens are anti-thyroid peroxidase antibodies (anti-TPO) that present in autoimmune thyroid disease (AITD)  [7]. AITD can damage  thyroid cells and competitively inhibit enzymatic activity [8].

When the immune system doesn't recognize the auto antigens (self-antigens) from non autoantigens that are known as autoimmunity and are relatively more in women than men. The  dysfunction in any member in organ systems , autoimmune and reproductive system diseases,  neurologic manifestations, Several systemic illnesses, and any  severe illness can be affected in a woman's fertility [9, 10]. Anti-sperm antibodies (ASAs) (immunoglobulins of IgG, IgA, and/or IgM) are identified in males and females with unexplained subfertility [11].

Samples were taken of 30 women not infected and without vaccination (G1), 30 infected women without vaccination (G2) , and  30 women previously infected and vaccinated against COVID-19 (G3). All patients in G3 were positive for the SARS-CoV-2 virus RT-PCR test, while G1 and G2 were negative for the RT-PCR test. Biochemical measurements of thyroid hormone levels by AFIAS-10 . Anti-TPO by Maglumi 800 instrument and ASAs measured by ELISA kit from My Biosource. Statistical Analysis was done by XLSTAT statistical package software.

1. Thyroids hormones 

 The mean (±SD) of T3,T4,TSH and Anti-TPO IU/mL concentration in serum of G1, G2 and G3 groups are illustrated in table (1) . There was no significant difference (P>0.05) in T3 and T4 levels  . A high increase (P<0.001) in TSH and Anti-TPO levels in G3 compared with G1 and G2 , and a significant increase (P<0.01) in G2 compared with G1 .

Table (1) : The Mean of Thyroids hormones  for studied Groups

Virus entered into the cell by ACE2 receptors  , and all cells that express ACE2 receptors  are vulnerable to injury for this virus. As a result of the high presence of ACE2 receptors and its high expression in the thyroid gland, the thyroid gland is highly susceptible to this infection. The types of thyroid disorder are not yet fully expressed or described [12].

In a study conducted on 50 cases of people infected with Covid-19, it was found that there were thyroid gland imbalances in 60% of cases [13].

Several theories mechanism for the causing thyroid autoimmunity disorders caused by viruses: (1) the virus make changes in the expression of self-antigen, or by cryptic epitopes; (2) It can cause inflammation through several mechanisms, including cytokine release, which leads to the activation of autologous T cells, this mechanism is known as the bystander mechanism: (3)  leading mechanisms that were link between viral , thyroid and autoimmunity (molecular mimicry) ;and   (4) the effect of heat shock proteins [14,15].

Among the  pathogenic mechanisms in COVID-19 t :The Immune dysregulation  and increased pro-inflammatory agent like cytokines, which are similar to those of autoinflammatory diseases [16]. 

Also, COVID-19 vaccines may lead to thyroiditis [17]. In addition to infection with the virus, the vaccine against this virus also causes immune thyroid infections (autoimmune reactions) by the same mechanisms that occur in the case of infection. Also, a hypothesis has been put forward that the adjuvants in vaccines may cause inflammation of the thyroid gland, which contributes to the emergence of “autoimmune syndrome.” [18].

The mechanism by which the vaccine affects the thyroid gland (post-vaccination subacute thyroiditis) is still unclear. The possible mechanism for the vaccine's effect on the thyroid gland is a  cross-reaction between the spike protein of the Covid-19 vaccines and thyroid cell antigens [19].

A number of cases of inflammation of the thyroid gland (subacute thyroiditis) that happen after vaccination against COVID-19 have been found in recent research [20-25]. Şahin Tekin et al. [22] and Vera-Lastra O et al. [26] have also reported a case of subacute following CoronaVac vaccine, due to the effect of virus antigens and supporting proteins present in the vaccine .

1. Anti-sperm 

The mean (±SD) of Anti- sperm ng/mL concentration in serum of women control group and primary hypothyroidism in all groups are illustrated in table (2) . There was a highly significant increase (P<0.001) in G3 compared with G1 and G2.

Table (2) : The Mean of Anti- sperm for studied Groups

Another study showed presence of a pathogenic effect of virus on female Reproductive system, Follicular microvasculature, and ovarian antral folliculogenesis,  by altering the follicular fluid content and oocyte quality [27]. Also, correlation with the level of Immunoglobulin G to virus in the albuminous fluid in the follicular antrum and the number optimal numbers of mature oocytes leads to COVID-19 can negatively affect health  outcomes cryopreservation it looks like to have the protease system to be sensitive to virus [28,29].

According to a study by Sacchi M. C. et al., SARS-CoV-2 infection  is associated with autoantibodies [30].

 Some studies showed that COVID-19 vaccines cause irregular periods and induce period changes with unusual menstrual signs [31],  and other study found following vaccination retrospective disturbances occurred [32]. Some female have isoimmunity or autoimmunity against sperm, which cause infertility by production of ASAs [33,34]. ASAs, and other autoantibodies like antiphospholipid, are linked with infertility [35]. The effect of autoantibodies on reproduction was a reduction in spontaneous pregnancies [36,37].

The results indicate that the COVID-19 vaccine may have negative consequences on the immune and reproductive systems in women and that may explain the currently widespread cases of secondary infertility in future.

1. Kang, Shuntong, et al. "Recent progress in understanding 2019 novel coronavirus (SARS-CoV-2) associated with human respiratory disease: detection, mechanisms and treatment." International journal of antimicrobial agents 55.5 (2020): 105950. https://doi.org/10.1016/j.ijantimicag.2020.105950 

2. Shereen, Muhammad Adnan, et al. "COVID-19 infection: Emergence, transmission, and characteristics of human coronaviruses." Journal of advanced research 24 (2020): 91-98. https://doi.org/10.1016/j.jare.2020.03.005 

3. Peng, Xue-Liang, et al. "Advances in the design and development of SARS-CoV-2 vaccines." Military Medical Research 8.1 (2021): 67.https://link.springer.com/article/10.1186/s40779-021-00360-1 

4. Karampinis, Emmanouil, et al. "Serum vitamin D levels can be predictive of psoriasis flares up after COVID-19 vaccination: A retrospective case control study." Frontiers in Medicine 10 (2023): 1203426. https://doi.org/10.3389/fmed.2023.1203426 

5.  Tan, Chee-Wah, et al. "Pan-sarbecovirus neutralizing antibodies in BNT162b2-immunized SARS-CoV-1 survivors." New England Journal of Medicine 385.15 (2021): 1401-1406. https://www.nejm.org/doi/full/10.1056/NEJMoa2108453 

6. Shaker, Razan N., and Nawal Th Younis. "Biochemical study on anti thyroid peroxidase antibody enzyme in serum blood of women with thyroid disease." Research Journal of Pharmacy and Technology 16.1 (2023): 205-208. http://dx.doi.org/10.52711/0974-360X.2023.00038 

7.  Mahmood, Sara, and Chro Fattah. "ASSOCIATION BETWEEN ANTI-THYROID PEROXIDASE ANTIBODY AND RECURRENT MISCARRIAGE." JOURNAL OF SULAIMANI MEDICAL COLLEGE 13.2 (2023): 6-6. https://doi.org/10.17656/jsmc.10407 

8. Terris, David J., et al. "American Thyroid Association statement on outpatient thyroidectomy." Thyroid 23.10 (2013): 1193-1202. https://www.liebertpub.com/doi/abs/10.1089/thy.2013.0049

9. Nagaria, Tripti, P. K. Patra, and Jai Prakash Sahu. "Evaluation of serum antisperm antibodies in infertility." The Journal of Obstetrics and Gynecology of India 61 (2011): 307-316. https://link.springer.com/article/10.1007/s13224-011-0034-7 

10.  Poppe, Kris, et al. "Thyroid dysfunction and autoimmunity in infertile women." Thyroid 12.11 (2002): 997-1001. https://doi.org/10.1089/105072502320908330 

11. Hassan, Muhjah Falah, and Ali M. Kadim Al-Tuma. "Female Autoimmune Disorders with Infertility: A Narrative Review." Al-Anbar Medical Journal 19.1 (2023): 3-9.  doi: 10.33091/amj.2023.138475.1022

12. Boaventura, Paula, et al. "Post-COVID-19 condition: where are we now?." Life 12.4 (2022): 517. , https://doi.org/10.3390/ life12040517.

13. Chen, Min, Weibin Zhou, and Weiwei Xu. "Thyroid function analysis in 50 patients with COVID-19: a retrospective study." Thyroid 31.1 (2021): 8-11. https://doi.org/10.1089/thy.2020.0363 .

14. Tomer, Yaron, and Terry F. Davies. "Infection, thyroid disease, and autoimmunity." Endocrine reviews 14.1 (1993): 107-120.https://academic.oup.com/edrv/article-abstract/14/1/107/2548405 

15. Tomer, Yaron, and Terry F. Davies. "Infections and autoimmune endocrine disease." Bailliere's clinical endocrinology and metabolism 9.1 (1995): 47-70.https://doi.org/10.1016/S0950-351X(95)80819-1 

16. Tanveer, Ayesha, et al. "Pathogenic role of cytokines in COVID-19, its association with contributing co-morbidities and possible therapeutic regimens." Inflammopharmacology 30.5 (2022): 1503-1516. https://link.springer.com/article/10.1007/s10787-022-01040-9 

17. WHO. mRNA vaccines against COVID-19: pfizer-BioNTech COVID-19 vaccine BNT162b2: prepared by the Strategic Advisory Group of Experts (SAGE) on immunization working group on COVID-19 vaccines. 2020. 

18. Watad, Abdulla, et al. "Autoimmune/inflammatory syndrome induced by adjuvants and thyroid autoimmunity." Frontiers in endocrinology 7 (2017): 150.https://www.frontiersin.org/articles/10.3389/fendo.2016.00150/full 

19. Vojdani, Aristo, and Datis Kharrazian. "Potential antigenic cross-reactivity between SARS-CoV-2 and human tissue with a possible link to an increase in autoimmune diseases." Clinical Immunology (Orlando, Fla.) 217 (2020): 108480.https://doi.org/10.1016%2Fj.clim.2020.108480 

20. Franquemont, Stephanie, and Juan Galvez. "Subacute thyroiditis after mRNA vaccine for Covid-19." Journal of the Endocrine Society 5.Suppl 1 (2021): A956. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089609/ 

21. İremli, Burçin Gönül, Süleyman Nahit Şendur, and Uğur Ünlütürk. "Three cases of subacute thyroiditis following SARS-CoV-2 vaccine: postvaccination ASIA syndrome." The Journal of Clinical Endocrinology & Metabolism 106.9 (2021): 2600-2605. https://academic.oup.com/jcem/article-abstract/106/9/2600/6287003 

22. Şahin Tekin, Melisa, Suzan Şaylısoy, and Göknur Yorulmaz. "Subacute thyroiditis following COVID-19 vaccination in a 67-year-old male patient: a case report." Human Vaccines & Immunotherapeutics 17.11 (2021): 4090-4092. https://www.tandfonline.com/doi/abs/10.1080/21645515.2021.1947102 

23. Oyibo, Samson O. "Subacute thyroiditis after receiving the adenovirus-vectored vaccine for coronavirus disease (COVID-19)." Cureus 13.6 (2021). https://www.cureus.com/articles/63134-subacute-thyroiditis-after-receiving-the-adenovirus-vectored-vaccine-for-coronavirus-disease-covid-19.pdf 

24. Bornemann, Catherine, Katharina Woyk, and Caroline Bouter. "Case report: two cases of subacute thyroiditis following SARS-CoV-2 vaccination." Frontiers in Medicine 8 (2021): 737142. https://www.frontiersin.org/articles/10.3389/fmed.2021.737142/full 

25. Ratnayake, Gowri M., Dorota Dworakowska, and Ashley B. Grossman. "Can COVID‐19 immunisation cause subacute thyroiditis?." Clinical Endocrinology 97.1 (2022): 140. 

26. Vera-Lastra O, Ordinola Navarro A, Cruz Domiguez MP, Medina G, Sánchez Valadez TI, Jara LJ. Two cases of Graves’ disease following SARS-CoV-2 vaccination: an autoimmune/inflammatory syndrome induced by adjuvants. Thyroid 2021 31 1436–1439.  https://doi.org/10.1111%2Fcen.14555 

27. Herrero, Yamila, et al. "SARS-CoV-2 infection negatively affects ovarian function in ART patients." Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 1868.1 (2022): 166295. https://doi.org/10.1016/j.bbadis.2021.166295 

28. Caso, Francesco, et al. "Could Sars-coronavirus-2 trigger autoimmune and/or autoinflammatory mechanisms in genetically predisposed subjects?." Autoimmunity reviews 19.5 (2020): 102524. https://doi.org/10.1016%2Fj.autrev.2020.102524 

29. Dolgushina, Nataliya V., et al. "The effect of COVID-19 severity, associated serum autoantibodies and time interval after the disease on the outcomes of fresh oocyte ART cycles in non-vaccinated patients." Journal of Clinical Medicine 12.13 (2023): 4370. https://www.mdpi.com/2077-0383/12/13/4370 

30. Sacchi, Maria C., et al. "SARS‐CoV‐2 infection as a trigger of autoimmune response." Clinical and translational science 14.3 (2021): 898-907. https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1111/cts.12953 

31. Alvergne, Alexandra, et al. "COVID-19 vaccination and menstrual cycle changes: A United Kingdom (UK) retrospective case-control study." MedRXiv (2021): 2021-11.https://www.medrxiv.org/content/10.1101/2021.11.23.21266709.abstract 

32. Male, Victoria. "Menstrual changes after covid-19 vaccination." Bmj 374 (2021).https://doi.org/10.1136/bmj.n2211 

33. Adams, Judith M., et al. "Polycystic ovarian morphology with regular ovulatory cycles: insights into the pathophysiology of polycystic ovarian syndrome." The Journal of Clinical Endocrinology & Metabolism 89.9 (2004): 4343-4350.https://academic.oup.com/jcem/article-abstract/89/9/4343/2844382 

34. Morin-Papunen, Laure C., et al. "Chlamydia antibodies and self-reported symptoms of oligo-amenorrhea and hirsutism: A new etiologic factor in polycystic ovary syndrome?." Fertility and sterility 94.5 (2010): 1799-1804.https://doi.org/10.1016/j.fertnstert.2009.10.021

35. Malinowski, A., et al. "Antiphospholipid autoantibodies in women treated for infertility." Ginekologia Polska 71.9 (2000): 1011-1016.https://europepmc.org/article/med/11082966 

36. Heng, Boon Chin, et al. "Roles of antiphospholipid antibodies, antithyroid antibodies and antisperm antibodies in female reproductive health." Integrative Medicine International 2.1-2 (2015): 21-31. https://karger.com/imi/article-abstract/2/1-2/21/181784 

37. Robertson, Sarah A., and David J. Sharkey. "Seminal fluid and fertility in women." Fertility and sterility 106.3 (2016): 511-519. https://doi.org/10.1016/j.fertnstert.2016.07.1101