Mycoplasma hominis & Ureaplasma urealyticum Cause Septic Arthritis in Subjects with Hypogammaglobulinemia

 If you have a subject with hypogamma, either due to CVID or other "constitutional" causes, such XLA, or acquired, due to immunosuppression, usually with Rituximab, who present with a picture of inflammatory arthritis, either monoarthritis or oligoarthritis, suspect infection by either Mycoplasma hominis or Ureaplasma urealyticum, particularly if usual cultures are negative and the usual antibiotics do not work.

Both organisms are overrepresented in subjects with septic arthritis developing against a background of hypogamma, particularly on Rituximab. The most commonly affected joints are hip, knee, shoulder, elbow, ankle and PIP. Prosthetic joint infections, particularly affecting the hip have been reported several times.

These fastidious organisms will not grow on routine cultures. M.hominis may show up on anaerobic culture plates after 5 days, but is best cultured on PPLO (pleuropneumonia like organism) broth or looked for by 16S RNA. Similarly, U.urealyticum is best cultured on Ureaplasma differential agar, Ureaplasma broth, or A7B agar. Fortunately, the last 3 will also grow M.hominis. U.urealyticum can also be identified on 16S RNA analysis.

If a person with hypogamma and putative inflammatory arthritis has proven culture negative on synovial fluid and blood culture, do ask for these special media or 16S RNA to isolate these 2 organisms. 

Ureaplasma requires urea in its culture medium for growth. It produces urease with breaks down urea into ammonia, and can thus change the colour of phenol red to pink. M.hominis metabolises arginine, but not glucose. Ureaplasma ferments neither, but produces a "managanese reaction" in culture.

If the usual antibiotics have not worked, there would be a natural tendency to attribute the inflamed joint(s) to the underlying disorder such as RA or Lupus, or make a new diagnosis of one of the above two, and treat with steroids. This may lead to a worsening of such arthritis, so special caution is warranted in subjects with hypogamma.

A course of doxycycline may be indicated if the usual antibiotics which target cell walls (which these organisms lack) have not worked. Resolution of fever/arthritis with doxycycline supports the likelihood of infection by one of the above two.

Is Re-infection By COVID-19 Possible?

Once you have had COVID19, can you be reinfected with the same virus?

This article in JAMA may provide some reassurance, although it's understandably based on very little data.

https://jamanetwork.com/journals/jama/fullarticle/2766097

If you wanted a summary, it's halfway down the article, in this line here:

To date, no human reinfections with SARS-CoV-2 have been confirmed.

However, as with everything COVID, answers may not be forthcoming for a very long time. Hence, you look at the literature to see if there are predictors of long term immunity after infections, and a couple of facts begin to emerge.

In general viruses (excluding Influenza, which is prone to antigenic shift and drift) tend to cause long lasting immunity- the half life for antibody levels is between 50-200 years, from a 26 year long study of subjects following infections by 6 viruses- Vaccinia (the virus used for small pox vaccine), measles, mumps, rubella, Varicella zoster (chicken pox), and EBV. This may explain why there has never been a sustained second epidemic by a non-influenza virus, i.e. SARS, MERS, Marburg, Zika, Lassa Fever etc (don't misinterpret this as meaning that these viruses cannot infect naive subjects).

https://www.nejm.org/doi/full/10.1056/NEJMoa066092

The same does not apply to antibody responses to protein antigens, specifically for bacteria. For example, the half life for antibodies to Tetanus and Diphtheria is only 11 years-a fifth of that to the virus with shortest lived immunity.

Thirdly, women tend to have longer lasting protection than men.

https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-018-0568-8

Fourth, if you have low antibody levels to start with, for example in a condition called Common Variable Immunodeficiency, a predominantly IgM response to the infective agent would suggest that the response will not be long lived. This may sound strange, but is intuitive, as IgM is the first antibody isotype produced for any sort of humoral (antibody mediated) response. It is then gradually followed by an IgG response. If IgG (particularly IgG1- there are 4 subclasses of IgG-1, 2, 3 and 4) levels do not increase appreciably, the response will not be long lived. Therefore in general, a high IgM level and a low IgG level- particularly that for the IgG1 component- is a worrisome feature.

https://www.jacionline.org/article/S0091-6749(18)30560-8/fulltext

And finally, some people use memory B cells as a surrogate marker for long lasting immunity. This is not a correct assumption. Long lasting humoral immunity can be memory B cell dependent and memory B cell independent, and each exists independently of the other.

If you wanted a straight yes or no answer to the question as to whether infection with COVID-19 is likely to lead to long lasting immunity- I would say, based on the available evidence, the answer is "Yes".