Topic: COVID vaccination in Transplant Recipients

31^stJuly, 2021, Saturday

9.30am-10.30am

Key points from the discussion

#1. A presentation on “COVID-19 vaccines and the solid organ transplant population” was given by Dr Brahm Vasudev, Associate Professor, Transplant Nephrology Fellowship Program Director, Medical College of Wisconsin, USA.

• There are several different types of vaccine platforms -DNA based vaccines, viral vector vaccines, RNA vaccines, inactivated vaccines, live attenuated vaccines; different parts of the world have access to different types of vaccines. There are three vaccines approved for use in the US: Pfizer-BioNTech, Moderna and J&J, which have shown very good results in their secondary outcomes (preventing severe Covid) 83% to 100%. Pfizer and Moderna have shown 94-95% efficacy in primary outcomes of preventing symptomatic disease.
• No trial has yet compared efficacy between vaccines in the same study at the same time.
• All authorised Covid vaccines have shown efficacy ranging from 65% to 95% against symptomatic lab-confirmed Covid-19. They have also shown high efficacy against severe disease requiring hospitalisation.
• The pandemic has taught us quite many lessons with regard to prevention, symptoms, risk factors for developing severe disease, treatments, long haulers and vaccines. It has also brought to light the hidden morbidity and mortality due to delayed care for chronic medical conditions, overburdened health care systems. In the US, 37% of population has been fully vaccinated, while 47% have received one dose.
• A transplant organ is a foreign tissue; hence, it is recognised as non self and can generate an immune response.
• There are two types of immunosuppressants. Induction agents, which are T cell depleting agents and include monoclonal and polyclonal antibodies. The other types are the maintenance agents and include steroids, antiproliferative (azathioprine, mycophenolate), calcineurin inhibitors (cyclosporine, tacrolimus), calcium sparing drugs (sirolimus, everolimus) and the costimulator blocker (belatacept)
• The initial clinical presentation of COvid-19 in solid organ transplant recipients (SOTR) is fever, cough and diarrhea, which is similar to the general population. Acute kidney injury has been reported in kidney transplant patients more commonly in hospitalised SOTR vs non-SOTR.
• Hospitalizations in these patients have ranged from 32% to 78%. The ICU admissions have varied from 18-34%. Incidence of intubation or NIV is 30-39%. Intubation signals poor outcomes. The mortality in these patients is 4-46%.
• SARS-CoV-2 specific serologic responses in the form of IgG against the nucleocapsid protein of the virus and either IgM or IgG against SARS-CoV-2 recombinant nucleocapsid and spike antigens have been described in literature.
• Seven hospitalised patients developed IgG against the nucleocapsid protein between 5 and 27 days after the onset of symptoms. In a larger study, 35 kidney transplant recipients developed either positive IgM or IgG 14 days after onset of symptoms, which persisted through day 59.
• Study of vaccine safety and reactogenicity of the two doses of Covid-19 vaccines in SOTR has shown similar safety profile as individuals who participated in the clinical trials. At this time, there are no safety signals for increased risk of rejection or neurological problems.
• Literature has shown that transplant recipients do not have a good antibody response. Antimetabolite therapy and older transplant recipients are associated with lower response.
• mRNA vaccines have good safety profile in SOT recipients.
• SOTR may be at a higher risk for infection despite vaccination.
• The antibody response is at best a surrogate measure of protection from Covid-19, so the magnitude of loss is not clear.
• A latest JAMA study has suggested that a booster dose may be considered in kidney transplant recipients who show minimal serologic response to two doses of the mRNA vaccine
• The transplant specific literature is currently missing a consistent way to measure antibody titers, the threshold of a neutralizing antibody titer that provides protection, data to evaluate what happens to the antibodies over time, best approach to overcome the blunted response to the vaccine in SOTR – whether booster dose, high vaccine dose, optimise the time of administration, modify immunosuppression at the time of vaccine administration, vaccine efficacy against variants in SOTR and data on T-cell immunity and B-cell memory.
• If a SOTR develops symptoms of Covid-19 after the first dose of Pfizer or Moderna vaccine and tests positive on PCR, the second dose of the vaccine should be deferred until the patient recovers from acute illness and meets criteria to discontinue isolation.
• Covid-19 vaccine can be administered with other vaccines at a single visit. But administer each injection at a different site. Separate injection sites by ≥1 inch, if possible and administer Covid-19 vaccine and vaccines more likely to cause a local reaction in different limbs if possible.
• Patients who have received the first dose of Pfizer or Moderna prior to the transplant should delay the second dose 4 weeks after the transplant if no T or B cell depleting therapy is used at the time of transplant or after 12 weeks, if T or B cell depleting therapy is used at the time of transplant, as per International Society of Heart and Lung Transplantation (ISHLT) recommendations.
• If it is not feasible to adhere to the recommended interval between the two vaccine doses and a delay in vaccination is unavoidable, the second dose may be given up to 6 weeks after the first dose.
• Routine testing for antibody titers is not recommended as it will not alter the management.
• Vaccination is recommended for SOTRs. If possible, vaccine should be taken prior to the transplant.
• There is no specific vaccine recommended, but mRNA vaccine could be preferred in an immunocompromised patient, if it is available, as the response rate is better, they are tolerated well and there is enough data to show their safety in these patients.
• All live vaccines are contraindicated in transplant patients, but they can be given the attenuated vaccines or killed virus vaccines. Transplant patients may benefit from the mix and match vaccine booster dose, once it is approved.
• All household member and caregivers should take the vaccine, if eligible, to protect the patients.
• The immunosuppressant medications that the patient is taking should not be stopped for the vaccine. Organ rejection would be more difficult to manage.
• All transplant patients must continue to follow precautions such as social distancing, masks etc. even if they have taken both doses of the vaccine.
• Safety data shows that the benefit of the vaccine outweighs the risks, unless there is an apparent contraindication such as to the vaccine ingredients.
• There are ongoing studies looking at other vaccines (other than mRNA) and how transplant patients respond to them.
• The antibody response with J&J vaccine in transplant patients was around 20% whereas with Pfizer and Moderna, it was almost 54%. But most studies have only looked at antibody response and not T cell response, which could be different.
• Studies of vaccines have been done in dialysis patients and the response rate to vaccination in dialysis patients is better than in transplant patients. The response rate is 80-85%.
• The mortality due to COvid-19 in transplant patients varies from 20-30%.
• Currently, a booster dose is not approved by the US FDA.

#2. Country Updates

• Bangladesh Update: Cases and deaths are high particularly near the borders; the country is in a lockdown, it will open for the export industries. Vaccination has improved as vaccines are now available, the government plans to give 10 million doses per month.
• India Update: The second wave has plateaued. Almost 30% of the population has been immunised; 45 crore people have been immunised and the vaccination program is picking up. There are regional variations in lockdown, most locally confined lockdown. Phase 1 trial for evaluating the anti-helminitic drug, niclosamide as treatment for Covid is ongoing. A clinical trial of mixing the two vaccines available in India (Covaxin and Covishield) to be conducted at CMC Vellore has been approved by regulatory authority.
• Pakistan Update: The numbers are gradually increasing all over the country. Almost 80% of cases are delta variant. The positivity rate in Karachi in Sindh Province is 35-40%; here almost 85% have not been vaccinated. Partial lockdown has been implemented in the city and a vaccine certificate is needed for movement in the city.
• Malaysia Update: The situation is grim as the number of cases is increasing. There are around 16,000-17,000 cases daily with more than 100 daily deaths. There is total lockdown and the cases are rising despite the lockdown. Essential services are functioning. 19 million people have been vaccinated so far; of these, 6 million have got two doses. The vaccines available are Sinovac and Pfizer mainly, though AstraZeneca is also available.
• South Africa Update: Total number of positive cases is 2.5 million; 2.2 million have recovered and there have been 71,000 deaths. The third wave is proving to be more deadly than the first and the second waves. Breakthrough infections, especially among doctors, are a cause for concern. There are more than 13,000 daily cases on an average; around 1.5 million people have been vaccinated with J&J vaccine since February; around 5.9 million have received the Pfizer vaccine; 4.5 million have taken the first dose and 1.4 million have taken both doses.
• Australia Update: There have been around 200 cases in Sydney; the state of Victoria has come out of it as it implemented short lockdowns to deal with the new delta variant.
• Singapore Update: There are around 2000 cases of delta since July; the cases are 130 per day since the last few days. Oxygen needs have increased with the delta variant in the country; 4.6% patients who are not vaccinated need oxygen, whereas only 0.1% patients need oxygen if they are fully vaccinated. 76% of the population is vaccinated with one dose at least and 57% have received both doses. About 22% of those who are above 70 years are not vaccinated yet. The ICU capacity is alright.

Participants

Member National Medical Associations

Dr Yeh Woei Chong, Singapore, Chair CMAAO

Dr Ravi Naidu, Malaysia, Immediate Past President CMAAO

Prof Ashraf Nizami, Pakistan, First Vice President CMAAO

Dr Marthanda Pillai, India Member World Medical Council

Dr Angelique Coetzee, South Africa

Dr Akhtar Hussain, South Africa

Dr Qaiser Sajjad, Pakistan

Dr Marie Uzawa Urabe, Japan

Dr Md Jamaluddin Chowdhury, Bangladesh

Invitees

Dr Brahm Vasudev, USA

Dr Russell D’Souza, Australia UNESCO Chair in Bioethics

Dr Shashank Joshi, Mumbai, India

Dr Rahul Pandit

Dr Monica Vasudev, USA

Dr Mulazim Hussain Bukhari, Pakistan

Dr Ahmet Murt, Turkey

Dr S Sharma, Editor IJCP Group

Moderator

Mr Saurabh Aggarwal

Dr Veena Aggarwal

Consultant Womens’ Health

Trustee, Dr KK’s Heart Care Foundation of India

CMD and Editor-in-Chief, IJCP Group & Medtalks