Second symptomatic COVID-19 infections in patients with an underlying monoclonal gammopathy | Blood Cancer Journal – Nature.com

Out of the 101 patients, 13 (13%) developed a 2nd symptomatic COVID-19 infection. Details of the timeline for second infections in relation to vaccination, antibody testing and ongoing treatment are depicted in Fig. 1. The majority of 2nd COVID-19 were mild (11/13, 85%) and the 2 patients (15%) with a severe 2nd infection were both unvaccinated. The median time to 2nd infection was 6.3 months (range 1–19 months) from the 1st COVID-19 infection. Rate of 2nd infection was 21% (6/28) in unvaccinated patients compared to 9.6% (7/73) in patients after completion of initial vaccination series (p = 0.11). Six out of the 7 vaccinated patients had received a third dose of vaccination prior to the 2nd infection.

Fig. 1: Second COVID-19 infections.
figure 1

The figure demonstrates a timeline of second COVID-19 infection in patients with monoclonal gammopathy in relation to antibody status and treatment administered.

Of the 42 patients with MM/AL, 25 patients were in remission and 1 out of these 25 (4%) patients developed a 2nd COVID-19 infection. Compared to patients in remission, 5 (29%) of the 17 patients with MM/AL not in remission developed a 2nd infection (p = 0.03). Details of ongoing treatment for MM prior to the 2nd infection are depicted in Fig. 1. Among the 7 patients with MGUS/SMM, all 4 patients with immunoglobulin testing performed at the time of 2nd infection had immune paresis. Among the 382 patients in whom an antibody test was not performed, 22 (6%) patients developed a second infection out of which 3 (14%) were severe. Details of second infection in the of patients where an antibody test was not performed are depicted in Supplementary Fig. 2.

Patients with monoclonal gammopathy demonstrate an inferior seroconversion to COVID-19 vaccination but the rate and severity of 2nd infections in the context of prior seropositivity have not been described [8, 10]. To address this issue, we focused on patients who had an antibody test performed. Majority of the patients in our cohort demonstrate seropositivity after COVID-19 infection and/or vaccination. Despite this, the incidence of a second symptomatic COVID-19 infection was substantial and a short time to second COVID-19 infection (median of 6 months) points toward a rapidly waning immunity. Similarly, patients with a documented positive spike antibody before the 1st COVID-19 infection still went on to develop COVID-19, including severe infections. This further highlights the need for booster doses in this patient population.

In our study, the risk of a second infection was 9.6% in patients who had already experienced a COVID-19 infection and were fully vaccinated prior to the second infection. This occurred despite majority of the patients having received a 3rd dose of the mRNA vaccine. Even though recurrent infections were noted despite vaccination, there was a distinct trend towards a lower rate of 2nd infections in the vaccinated population. Notably, all severe 2nd COVID-19 infections occurred in patients that were unvaccinated at the time of the second infection, and this should serve as a reaffirmation of the importance of vaccination even in patients with a prior COVID-19 infection. These data continue to highlight the importance of vaccination even in patients who have had previous COVID-19 infection and a documented seropositivity.

This study has limitations, most prominent of which is the random nature in which patients underwent antibody testing, potentially leading to a selection bias. To ensure there was no systemic bias introduced while selecting this cohort, we compared the cohort of patients who had an antibody test performed versus those who did not undergo testing, and these were largely comparable. Another limitation is the type of antibody tested and the timing of testing in relation to the infection or vaccination. Despite these limitations, this study offers valuable information on rates and clinical characteristics of 2nd COVID-19 infections.

In conclusion, patients with an underlying MM, AL, or MGUS demonstrate a substantial risk for second symptomatic COVID-19 infections suggesting a rapidly waning immunity. Most of the 2nd COVID-19 infections were mild, with severe infections restricted to the unvaccinated population. Patients in whom underlying MM or AL was in remission was protective against a 2nd infection.

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