COVID-19 vaccine and corticosteroids: A challenging issue

To the editor,

In the pandemic era of COVID-19 and its vaccines, patients on immunosuppressive medications need special considerations. Immunosuppression can disturb the effectiveness of the vaccine responses. Thus, establishing a proper recommendation for timing of vaccination in these patients would be challenging. The immunosuppressive effects of corticosteroids (CS) vary and depend on its duration of use and doses. Doses > 40 mg/day prednisone or equivalent for more than 1 week or ≥ 20 mg of prednisone or equivalent for 2 weeks or more induce immunosuppression.^1,2 The current recommendations for COVID-19 vaccines and CS administration are mostly based on the available evidences for inactivated vaccines (e.g. influenza).

Choosing the best time to increase the efficacy of vaccination is important in immunosuppressed patients. Also, each country’s vaccine policy is important to set out vaccination times in these specific groups. In some countries, especially developing countries, the COVID-19 vaccination schedule is not adjustable by the patients or physicians, and selecting a particular time window for the best efficacy of immunization is impossible. However, if the vaccination schedule is not adjustable, it is recommended to receive the vaccine without delay. ³ If the schedules are adjustable, the following issues can be considered to improve the vaccine response:

Evidence showed that with the dose of up to 20 mg/day prednisone or equivalents, the response to inactivated vaccines could not be suppressed, and these patients can receive vaccines safely. Patients treated with prednisone at a dose of less than 20 mg/day are not immunocompromised and have sufficient immune response.^1,2

The immunosuppressive doses of CS are prednisone or equivalent ≥ 20 mg/day for ≥ 2 weeks, or > 40 mg prednisone or equivalent for > 1 week. The ideal time for vaccination in this group is 1 month after discontinuation of the CS treatment to elicit an adequate immune response. ¹ If it was not possible to end the CS treatment, it is better to prescribe the vaccine when receiving the lowest dose of CS. For example, the dose of CS can be reduced to less than 20 mg with or without the addition of steroids sparing drugs (e.g. azathioprine), and then at least 2 weeks after vaccination, the dose of the drug returns to the previous state. ⁴

Suppose the patient is a candidate for CS therapy with doses of ≥ 20 mg prednisone for ≥ 2 weeks or > 40 mg prednisone for > 1 week. In this case, it is suggested that vaccine be administered at least 2 weeks before immunosuppression initiation because 2 weeks are required to develop an immune response. ² But if the CS administration cannot be withheld after vaccination because of disease flare or if the patient may not have access to the vaccine with the recommended interval, we suggest ordering the vaccine considering a suboptimal response to the vaccine. Corticosteroid pulse therapy per se does not cause immunodeficiency, and the vaccine need not be delayed. ⁵

If a country’s vaccination policy is such that the clinicians can choose the type of vaccine, it is better to choose a vaccine based on the underlying disease and the number of days that they can reduce the steroid dose. When we want to reduce the dose of corticosteroids over a period of time and there is a possibility of worsening symptoms and disease flare, then it makes sense to return the dose of corticosteroids to the previous dose sooner. Hence, it is better to use vaccines with less interval time between two doses.

The immunogenicity of a single dose of some vaccines is likely to be acceptable in patients who have natural antibodies and were infected before. In the future, only one dose of the vaccine may be sufficient in these patients.^6,7 Sometimes, we cannot change the dose of the corticosteroid due to risk of disease flare. Therefore, in order to increase the effectiveness of the vaccine, it is better for the patient to adjust the vaccine time for receiving at least one of the two vaccine doses at a time when it can be more effective. For patients under CS therapy who are immunocompromised, we suggest using a highly effective vaccine. The best vaccines with the best efficacy in this group of patients are not determined. These vaccines may be with mRNA or vector-based vaccines. Further clinical trial studies are required in this topic.