The effectiveness of Covid-19 vaccinations is being impacted by the emergence of SARS-CoV-2 variants. This could become more problematic as the virus continues to spread, increasing its chance to mutate.

These variants could affect not only the effectiveness of the vaccines, but also the natural immunity that Covid-19 survivors have developed, making annual booster shots required for Covid-19 immunity.

Several natural variants have been identified, including the B.1.1.7 variant first identified in the UK, the B.1.351 variant first identified in South Africa and the P.1 variant first identified in Brazil.

The B.1.1.7 variant is currently thought to be about 50% more transmissible than the original SARS-CoV-2 strain, and possibly more deadly. However, there is no indication that B.1.1.7 reduces the effectiveness of Moderna or Pfizer Covid-19 vaccines.

This is supported by the fact that the B.1.1.7 variant is neutralised by the sera of Pfizer and Moderna vaccine recipients. Still, there is some laboratory evidence of reduced neutralisation of the B.1.1.7 variant by convalescent plasma of Covid-19 patients.

Novavax reported that its vaccine had 85% efficacy with the variant versus 89% with the non-variant strain and AstraZeneca/Oxford reported that their vaccine 74% efficacy with the variant versus 84% with the non-variant strain.

The B.1.351 variant is potentially more troubling. Clinical trials for the Pfizer and Moderna vaccines indicate a reduction in sera neutralisation of the B.1.351 variant and other studies have shown there could be a six to ten-fold lower binding affinity for antibodies to the variant.

Additionally, Johnson & Johnson’s vaccine had 57% efficacy in South Africa, where the variant is prevalent, versus 72% in the US, and Novavax’s vaccine had 49% efficacy in South Africa versus 90% in the UK.

However, World Health Organization director Kate O’Brien indicated that these results may have some uncertainty as they were based on a low number of cases in South Africa. The B.1.351 variant may have a higher chance of reinfecting people who were infected by earlier strains of the SARS-CoV-2 virus.

The P.1 variant has some of the same mutations as the B.1.351 variant and could have a higher chance of reinfecting people. More research needs to be conducted on this variant to monitor its effects.

Pfizer and Moderna are already working on developing booster shots for their vaccines to improve their effectiveness against the B.1.351 strain. As there is already some indication of Covid-19 reinfections and possible waning immunity from naturally recovered Covid-19 patients, yearly boosters may be required for Covid-19.

However, it is important to note that despite the presence of these variants in the population, the vaccines are still likely to prevent severe outcomes such as hospitalisation and death.

As such, naturally recovered Covid-19 patients should also consider getting vaccinated. Those who have a weak level of response to Covid-19 infection may have a shorter duration of immunity and weaker protection from reinfection.

Vaccines can offer a more consistent level of protection and a more robust immune response of neutralising antibodies. Single-dose boosters provided to patients who have naturally recovered from Covid-19 could increase and extend the duration of their immune response.

Myasthenia gravis (MG) is a rare autoimmune synaptopathy that is caused by the dysfunction of nerve cells and muscle fibres at the neuromuscular junction. The disease is characterised by pronounced muscle weakness and fatigue.

In the vast majority of MG patients, the disease is initially localised and limited to the eye muscles, causing drooping of the eyelid and double vision. Patients with untreated disease can experience severe weakness of respiratory muscles, leading to myasthenic crisis. In this situation, the patient can only survive through the use of mechanical ventilation and intubation.

Treatment of MG involves the administration of acetylcholinesterase inhibitors and corticosteroids. As it is an autoimmune condition, immunosuppressive therapies such as rituximab, tacrolimus and Alexion’s Soliris (eculizumab) have demonstrated efficacy in the management of patients with severe disease.

However, the high treatment-related costs associated with biologics mean that patients from underprivileged backgrounds can have difficulty accessing Soliris, despite the fact that the drug is approved in more than eight countries.

One potential solution to this issue is to encourage the use of drugs such as methotrexate, which has notable advantages over other widely available immunosuppressants, such as azathioprine and cyclosporine.

Methotrexate tablets are taken once weekly, while azathioprine and cyclosporine tablets are both administered once-daily. The potential teratogenicity of azathioprine is a subject of ongoing debate. Cyclosporine is associated with hypertension, gingivitis, renal dysfunction and impaired insulin metabolism.

Conversely, clinical trials have shown that methotrexate is a safe, effective drug that is well tolerated by young patients and in people with comorbidities such as rheumatoid arthritis and psoriasis. Another clinical advantage is the fact that methotrexate can be injected subcutaneously and intravitreally for ocular indications.

Methotrexate is an anti-neoplastic agent that prevents the proliferation of lymphocytes. In MG, these are responsible for the production of autoantibodies that inhibit the neurotransmission of acetylcholine, which is a key component of the autonomic nervous system.

Despite the widespread availability of generic methotrexate in countries such as the US, Italy, Germany and Switzerland, the lack of formal approval for MG restricts its use for this debilitating and potentially fatal condition.

Increasing the volume of clinical data to provide evidence of the drug’s efficacy and safety profile in people with MG could be an important step toward making the treatment more affordable for socioeconomically disadvantaged patients.

This is especially important for patients who are unable to be managed with non-pharmacotherapeutic strategies such as thymectomy and plasmapheresis.