The second wave hits

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In the face of a second lock down Europe is waking up to the realization that COVID19 is now here to say. If something is here to say, the chances are that it would become the norm. For most this will mean wearing face masks, limiting social contact and being careful on a day to day based on background population infection rates. For those with MS and others on regular immunosuppressants, things will need to change.

  1. A real risk assessment of contracting COVID19. This is easier to do if you haven’t started on an MS therapy than if you’re already on one. Overall, the higher tier drugs have the greatest risk compared to platform treatments, followed by maintenance strategies versus induction strategies. This is a logical assumption, and explains the readout with HSCT (see below) and ocrelizumab.
  2. The existence of other co-morbidities increases the relative risk with the above, for example heart disease, asthma and diabetes; as does older age.
  3. Vaccinations will need to be given before start of immunosuppressive therapy, especially with highly active therapies to reduce the risk of other seasonal infections. Namely, the flu vaccine and pneumococcal vaccine (the commonest cause of community acquired pneumonia). The former will need to be given annually and the later 5-yearly. If your treatment affects the efficacy of vaccines speak to your neurologist.
  4. Risk reduction doesn’t stop with you, but includes your family as household contacts are the commonest mode of spread.
  5. It is important to maintain good mental health and physical health. Schedule in regular walks (via routes that are less crowded) and other fitness activities into your day.

ABSTRACT

Hematology. 2020 Dec;25(1):320. doi: 10.1080/16078454.2020.1802931.

Mélange intéressante: COVID-19, autologous transplants and multiple sclerosis

Juan Carlos Olivares Gazca David Gómez Almaguer Robert Peter Gale Guillermo José Ruiz Argüelles

The pandemic of coronavirus infectious disease-2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a threat to global health. During the pandemic changes in how hematopoietic cell transplant are done are suggested such as avoiding the use of immunosuppressive drugs. From June 2015 to March 2020, we autografted 894 persons with multiple sclerosis (MS) using a conditioning regimen of cyclophosphamide, 200 mg/kg and rituximab, 1 g. The first case of COVID-19 in México was diagnosed on 28 February 2020. To determine any interaction between SARS-CoV-2-infection and our program, we studied 13 subjects autografted 2–27 March 2020 during the initial part of the pandemic in México who had negative results of qualitative reverse transcription–polymerase chain reaction (qRT-PCR) tests for SARS-CoV-2 before and after their transplant. We also sent a questionnaire to 894 consecutive transplant recipients, 330 (37%) of whom responded. Four subjects indicated they were infected with the SARS-CoV-2 and developed COVID-19, 6–31 months posttransplant, only 1 of whom was hospitalized for 2 days, not in an intensive care unit. None were treated for COVID-19 (Table 1). Our data suggest, but do not prove, a low risk of developing COVID-19 in autotransplant recipients with MS. We cannot comment on the risk of SARS-CoV-2-infection as most respondents were not tested by qRT-PCR or for anti-SARS-CoV-2 antibodies. Also, there may be a selection bias of respondents.

Table 1: Characteristics of patients with COVID-19

Subject1234
Age (y)39454754
SexFFFM
Interval posttransplant (mo)3122226
Source of infectionFamily memberWorkFamily memberFamily member
Symptoms 
 Cough4
 Headaches3
 Fever3
 Shortness of breath3
 Diarrhea1
 Loss of smell0

About the author

Neuro Doc Gnanapavan

25 comments

    • The head of the HSCT clinic in Mexico has recently been inducted into the Royal College of Physicians in the UK. He is also an alum of the Mayo Clinic, USA. It may seem hard to believe, but the safety record of both the Clinica Ruiz, in Mexico and the AA Maximov
      Hospital in Moscow, are significantly superior to that of the UK clinics.

      • A sweeping statement that needs to be backed up with some (unbiased) data.For example you must ensure you are not comparing apples with oranges, for example the protocols of Russia and Mexico are even lower in intensity than what the EBMT refers to as “low intensity” protocols.

        • Perhaps I need to post this in November questions time section. But it’s relevant to this post and response above…
          I’ve read some discussion on this blog re Myeloablative vs non myeloablative HSCT for ms. Is it correct to say that in terms of longer term success, the higher intensity regime is favoured? However, if the intention is to reduce lymphocytes to almost nil, and if this is achieved with less intense regime; as per mexico or russia as mentioned, then why would a higher regime be required?

          • Most centers now only do the non-myeloablative procedure for MS, this is based on the risk:benefit analysis. The extra added benefit of a stricter conditioning regimen is not worth the increased risk mortality associated with it.

      • I worked at the Royal College of Surgeons but it doesn’t mean that you should let me loose with a scalpel. The RCP is a club for Doctors that costs a few grand a year membership, it give you access to…I could apply to be a member of the Royal College of Pathologists all I have to do is bung them a few quid.

        However thanks for the info
        COI: I suspect Mindy is a member of the HSCT fanclub
        https://multiple-sclerosis-research.org/2018/01/is-hsct-for-everyone-or-not/

        • “I worked at the Royal College of Surgeons but it doesn’t mean that you should let me lose with a scalpel.”…

          Huh..?..Scalpel..they don’t even allow you to give MS advice here…But if really looking for second career..here’s good advice on how to be a Fellow in Ireland Royal College of Physicians.

          • Lol not at all helpful. I can tell you that the Royal College of Physicians has only appointed 38,000 fellows worldwide in the UK over the history of the college ~500years. I was given a fellowship this year after being nominated – apparently the nominees remain anonymous (so thanks who ever did that!). All hush, hush.

    • “I can believe anything coming from that clinic that offers “transplants” for money.”

      As opposed to what..all the world’s free MS clinics..? Russia/Mexico do turn away money. Your post fits in here as it tends to be a source of hsct hate/fake news.

      “not accepted for HSCT?…My brother after year of waiting, finally went to Moscow, underwent the tests and the results were bad , his brain is too damaged and there is high risk he could die during the treatment.”

      Mexico..”..said she is too far advanced for the treatment, and yet she has fully functioning cognition, bladder and bowel control, can eat regular food, but cannot move her arms or legs.”

  • https://www.news-medical.net/news/20200925/D614G-mutation-now-the-dominant-variant-in-the-global-COVID-19-pandemic.aspx

    It seems an amino acid mutation in the spike protein may be key in the second wave of COVID-19. The reproductive number and transmissibility may be increasing but in regards to disease severity and morbidity it is still unknown. From an evolutionary perspective it would make sense that the virus would increase its fitness by mutating, cause a less severe disease and lead to fewer deaths. But that is conjecture at this point and public health vigilance is the only way to reduce morbidity and mortality. Lastly, the mutation may have significance when developing an effective vaccine.

  • I don’t understand how this paper really says anything at all. Only 4 people actually contracted COVID-19? That’s a very small sample size. And 330 didn’t respond to the questionnaire?

    • I know! This requires a bit of lateral thinking. The start of the pandemic was March but really it may have been Mexico from the end of the year before. Since they stopped transplants everywhere after the start in March, the cases they’ve reported if some of these were 6months post transplant will still make it roughly a third. But that’s a lot of lateral thinking.
      Most places sensibly halted transplants during the pandemic, as haematologists who have a lot of experience with transplant associated infections felt the risk was too high.

    • From the abstract “330 responded from the last 894 transplants”. Only 4 of the 330 responders indicated they tested positive for COVID-19. The authors put out the caveat that most respondents wer not tested by the standard RT-PCR. To test 6-31 months after transplant and draw conclusions on the risk of infection after transplant is a stretch.

      • This is entirely observational, what I’m interested is to know how many of the March transplants contracted COVID? But, like I said you don’t need COVID to tell you about the increased risk of infection post-transplant. It was sensible that they didn’t continue their transplants through to June/July (the peak of COVID19 infection in Mexico).

    • Yeah, that is a bit of a pattern with stuff from the Mexican HSCT places: the results in the data they present are almost always good, but the proportion of patients covered in followup is usually tiny, making it really hard to interpret.

      • Big question : how much does reinfection play a role in second wave? And if antibodies wane quickly, what does that mean for possible vaccines? Under reported news here in US is that states are observing possible reinfections and there is no guidance by CDC to states on how to monitor reinfections (I.e. Gene sequencing) . South Dakota believes it has 28 cases of reinfection over 90 days apart but hasn’t gene sequenced per last weeks news conference, at 28 min mark on video in middle of page. Heads up. https://www.dakotanewsnow.com/2020/10/28/south-dakota-health-officials-investigating-28-possible-covid-19-reinfections/

        • This will be a very expensive environmental/public health intervention. What I suspect most Department of Health’s would do is test for new mutations in silos where there is an outbreak.

          Re- vaccines, look to influenza every year there’s a new one. Hopefully, COVID settles into this. That’s why its very important to pick the correct DMT.

          • Doc, I know that Covid is a factor in DMT selection but surely the primary consideration is still efficacy at treating MS. For instance, Ocrevus is the only first line highly effective treatment. Anti CD20 can put you more at risk of severe covid though not necessarily death. Does this make it an incorrect choice? Surely not. MS trump’s Covid 9/10

        • There are lots of options for RRMS in the highly active group, Ocrelizumab isn’t at the top-it is in the order of HSCT, natalizumab, Alemtuzumab, Ocrelizumab. All highly active immunosuppressants increase risk of infections, the reason why in my opinion Ocrelizumab has taken the placard as the worst of them for COVID19 is the amount of people started on it ( it’s a numbers game the more people who are on it the more likely you’ll have a side effect— that’s why the risk is small but still exists). Remember severe COVID means hospital admission/ITU admission; no one wants an ITU admission in a pandemic.

          It’s important that you don’t misunderstand risks and benefits. It’s also a glass half full concept, until you’re in it you won’t know. Doctors try and make educated assessments based on this, but we get it wrong sometimes. MS is nasty for some of you and we try to put a risk to benefit to this. We’re also swayed by what the person wants, but when the risks are listed and agreement is reached it is a contract of agreement in both yours and the doctors mind. I don’t say this to frighten any of you, but these are the dilemmas that we grapple with every time.

          • Doc Gnanapavan, the UK shielding guidelines advise those who have undergone HSCT in the last 6 months to shield. The NICE guidelines advise those who have undergone hsct in the last year to shield. Do you have any view on how long post transplant one remains in the ‘clinically extremely vulnerable’ group, assuming no other co morbidity

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