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Investigating the Relationship Between Persisting ‘Long’ COVID-19 Symptoms and Mycoplasma Infection

The long-term effects of COVID-19 infection may have important implications.

Accordingly, characterising Long-COVID, the illness in those who have recovered or whose symptoms fair longer than expected, is of societal interest.

COVID-19 has short-term characteristics symptoms such as temperature, persistent cough and changes in one’s sense of smell or taste. Most of these symptoms recover in several weeks. However, Long-COVID symptoms appear to last longer, spanning from months to years. These long-term complications appear to extend beyond fatigue, headaches, dyspnoea and anosmia (Carfi et al., 2020), and to cognitive deficits as well (Zhao et al., 2021). Such symptoms need to be addressed


The Centers for Disease Control and Prevention (CDC), estimates 2 million cases of mycoplasma infections in the United States each year, although the actual number may be higher due to challenges in mycoplasma diagnosis. Reports of patients with pneumonia who were co-infected with COVID-19 and mycoplasma have raised questions of comorbidity (Gayam et al., 2020). The high prevalence and similarities in symptoms of COVID-19 and mycoplasma make the study of co-infection particularly relevant, especially as there may be a relationship with disease progression (Matsuda, 2015). Notably, mycoplasma infection which invades the respiratory tract and spreads throughout the body is known to cause symptoms similar to those of Long-COVID. Chronic fatigue has been associated with persistent mycoplasma infections (Endersen, 2003) as has Long-COVID.

Although mycoplasma infection itself has therapeutic drugs and is regarded as a treatable infectious disease, the diagnosis of mycoplasma infection has been challenging. M Bio Technology, a Japanese biotechnology venture company, has developed MID Prism®, a highly sensitive diagnostic tool that can detect mycoplasma infections with significantly higher specificity and sensitivity compared to conventional methods. Many clinics in Japan have used this technology for diagnosis and clinics.

Here, we propose a set of clinical studies investigating the relevance of mycoplasma infections on COVID-19 disease and its effects on long-lasting symptoms. We propose to characterise the state of mycoplasma infections using the MID platform technology (Matsuda, 2011) and aim to address the following points

1) What is the prevalence of mycoplasma in COVID-19 patients?

Screen serum samples of COVID-19 patients to assess the state of mycoplasma infection using the MID Prism®. We aim to assess how disease severity is associated with comorbidity.

2) Does mycoplasma infection increase the likelihood to have Long-Covid symptoms?

Screen serum samples of patients being treated for Long-COVID using MID Prism® test. Assess relationship with long covid symptoms such as fatigue, breathlessness

and cognitive measure of attention and memory.

3) Does treating mycoplasma infection alter improve long-covid symptoms?

Prescribe and treat patients with MID Prism®-confirmed diagnosis with drugs for mycoplasma infection.

4) Does mycoplasma infection alter the time course of COVD-19 symptom progression?

In addition to PCR and antigen testing for COVID-19 in patients, MID Prism® will be used to monitor mycoplasma infection longitudinally.


  • Carfì, A., Bernabei, R. and Landi, F., 2020. Persistent symptoms in patients after acute COVID-19. Jama, 324(6), pp.603-605.

  • Gayam, V., Konala, V.M., Naramala, S., Garlapati, P.R., Merghani, M.A., Regmi, N., Balla, M. and Adapa, S., 2020. Presenting characteristics, comorbidities, and outcomes of patients coinfected with COVID‐19 and Mycoplasma pneumoniae in the USA. Journal of medical virology, 92(10), pp.2181-2187.

  • Endresen, G.K., 2003. Mycoplasma blood infection in chronic fatigue and fibromyalgia syndromes. Rheumatology international, 23(5), pp.211-215.

  • Zhao, S., Shibata, K., Hellyer, P.J., Trender, W., Manohar, S., Hampshire, A. and Husain, M., 2021. Rapid vigilance and episodic memory decrements in COVID-19 survivors. medRxiv.

  • Matsuda, K. 2015. A novel therapeutic strategy for mycoplasma infectious diseases. Personalized Medicine Universe 4, 32-39.

  • Matsuda, K. 2011. Antigens: Lipids. Encyclopedia of Life Science. 3rd ed. John Wiley & Sons, Inc., 2.


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