Safe administration of sotrovimab to a COVID-19 patient with acute phase type 1 diabetes mellitus

Abstract.

Type 1 diabetes mellitus (T1DM) and poor glycemic control are risk factors for severe coronavirus disease 2019 (COVID-19). Sotrovimab can treat mild-to-moderate COVID-19 in patients at a high risk of progression to severe COVID-19. However, its safety and efficacy in T1DM patients remain to be elucidated. We report the case of a 12-yr-old patient who was treated with sotrovimab for COVID-19 immediately after treatment for diabetic ketoacidosis (DKA) due to new-onset T1DM. He presented with nausea and sore throat and was diagnosed with severe DKA and COVID-19. A productive cough and sputum developed after admission. On the 3rd day of admission, the DKA resolved, and sotrovimab was administered to prevent exacerbation of COVID-19. Although the blood glucose levels increased after the administration of sotrobimab, there was no recurrence of DKA. Hyperglycemia may be a sotrovimab-related adverse event in T1DM patients. Nevertheless, the benefits of sotrovimab treatment may far outweigh the potential risks. Thus, sotrovimab was considered safe for patients with T1DM immediately after treatment of severe DKA.

Highlights

● Sotrovimab was safely administered to a COVID-19 patient with T1DM after DKA.

● Mild hyperglycemia may be one of the adverse effects of sotrovimab.

Introduction

Individuals with type 1 diabetes mellitus (T1DM) and poor glycemic control are at a greater risk of rapid progression and poor prognosis of coronavirus disease 2019 (COVID-19) (1, 2). Treatment with anti-SARS-CoV-2 monoclonal antibodies, including sotrovimab, should be considered for patients with mild-to-moderate COVID-19 who are at a high risk of progression to severe COVID-19 (3,4,5). Although T1DM is an indication for sotrovimab treatment (6, 7), there are no detailed case reports on the clinical course of patients with T1DM treated with sotrovimab for COVID-19. Therefore, the safety and efficacy of sotrovimab in patients with T1DM remain to be elucidated.

Herein, we describe the successful management of COVID-19 using sotrovimab in a 12-year-old boy with new-onset T1DM. In addition to hyperglycemia, no obvious adverse effects were observed. This case provides an important reference for the clinical course and management of COVID-19 using sotrovimab in patients with T1DM. We report the details of this case with the consent of the patient’s parents.

Patients and Methods

A 12-yr-old boy presented with a history of a sore throat for 4 days and vomiting for 1 day. He had lost weight and developed polydipsia and polyuria during the previous 1–2 mo. The patient’s medical history was unremarkable. Moreover, the patient had been vaccinated twice with COVID-19. On arrival at the referring hospital, his initial vital signs were as follows: body temperature, 36.7°C; heart rate, 142 beats/min; blood pressure, 94/73 mmHg; respiratory rate, 25 breaths/min; and SpO₂, 100% on room air. The Japan Coma Scale score was 1. SARS-CoV-2 was detected by loop-mediated isothermal amplification. The initial laboratory findings were as follows: plasma glucose, 902 mg/dL; venous blood, pH, 7.01; bicarbonate, 5.8 mmol/L; and urine ketones, 3+. Severe diabetic ketoacidosis (DKA) was diagnosed based on the 2018 ISPAD Clinical Practice Consensus Guidelines (8). Subsequently, the patient was transferred to our hospital with the intravenous administration of 0.9% saline, bicarbonate, and insulin.

Results

The patient’s posthospital clinical course is shown in Fig. 1. Fluid replacement and intravenous insulin therapy were continued after admission to the pediatric intensive care unit. We observed a gradual correction of acidosis, ketosis, and blood glucose levels. The DKA resolved on the 3rd day of admission, and the patient’s unconsciousness improved. Intravenous fluids were gradually reduced, and intravenous insulin infusion therapy with insulin aspart (90 units/d) was changed to multiple subcutaneous injections administered daily with insulin aspart (15 units/d) and insulin degludec (17 units/d). Productive cough and sputum that appeared on the 2nd day of hospitalization were considered signs of COVID-19 exacerbation. A 500 mg dose of sotrovimab was administered intravenously over 30 min on the 3rd day of hospitalization, concurrent with the resumption of food intake and initiation of subcutaneous insulin injection. Subsequently, the blood glucose level increased to 522 mg/dL; however, DKA did not recur. The total daily insulin dose was increased to a maximum of 93 units per day, and hyperglycemia > 200 mg/dL lasted for 7 days after sotrovimab administration. No major adverse events (diarrhea, redness, infusion-related reaction, or headache) were observed following sotrovimab administration. An improvement in sore throat and productive cough was observed 2 and 3 days after sotrovimab administration, respectively. On the 7th day of onset, the patient was transferred to the general ward. Additional blood test results were consistent with T1DM: glutamic acid decarboxylase antibody level, ≥ 2,000 U/mL, and islet antigen2 autoantibody, ≥ 30 U/mL. The patient was transferred to the referring hospital for T1DM education on the 14th day.

Fig. 1.

The time course of events before transfer to the general ward. The horizontal axis lists the exact times of the day since the first day of visit to the emergency department of the referral hospital. The left and right vertical axes indicate the blood glucose levels (mg/dL) and pH levels, respectively. The patient initially received IVII therapy with 90 U/d of IAsp. After DKA resolved on the 3rd day of admission, the patient was switched to multiple daily injections of IAsp and IDeg with resumed food intake. After productive cough and sputum developed, sotrovimab was administered to prevent the exacerbation of COVID-19. Blood glucose levels increased after the administration of sotrobimab, and there was no recurrence of DKA. On the 7th day of admission, the patient was transferred to the general ward. Hosp., hospital; DKA, diabetic ketoacidosis; IVII, intravenous insulin infusion; IAsp, insulin aspart; IDeg, insulin degludec.

Discussion

Treatment with sotrovimab was safely administered to a COVID-19 patient in the acute phase of T1DM without any major adverse events other than hyperglycemia. Previous studies have reported adverse events in 17–22% of patients treated with sotrovimab (7, 9). The major adverse events included rash, diarrhea, nausea, headache, and infusion-related reactions. We did not observe any of these adverse events in this case. However, the elevation of blood glucose levels may be a sotrovimab-related adverse event. The Covid-19 Monoclonal Antibody Efficacy Trial–Intent to Care Early (COMET-ICE) trial reported one case of elevated blood glucose after administering sotrovimab in a COVID-19 patient with diabetes mellitus; however, there has been no report on the clinical course of the patient (10). This report illustrates the detailed clinical course of a COVID-19 patient with T1DM who was treated with sotrovimab. The increase in blood glucose level may be related to the change from intravenous to subcutaneous insulin injection and the reduction in insulin dosage before sotrovimab administration. Further studies are required to confirm the relationship between sotrovimab administration and hyperglycemia.

It is unclear whether the hyperglycemia observed after sotrovimab administration was caused by an imbalance between insulin and food intake or whether this was an adverse event with sotrovimab. Therefore, our findings should be cautiously interpreted. Nevertheless, no serious adverse events were observed following sotrovimab administration. Based on this, we suggest that sotrovimab be used as a treatment for COVID-19 in patients with acute-phase T1DM.

Sotrovimab administration is an option to prevent the progression of COVID-19, even in patients with new-onset T1DM, immediately after DKA treatment. In people with diabetes, hyperglycemia can lead to the rapid progression and poor prognosis of COVID-19, causing an altered immune response, cytokine dysregulation, enhanced inflammation, and promotion of a procoagulant state (11). Pediatric patients with COVID-19 generally have lower mortality rates than adult patients (12). Due to the lack of sufficient reference values for HbA1c in previous studies, the impact of sotrovimab on outcomes in children with T1DM is controversial. However, T1DM increases the hospitalization rate and severity of COVID-19, even in children (2, 13). Productive cough improved after sotrovimab administration, suggesting that sotrovimab prevented or alleviated the exacerbation of COVID-19. Thus, the administration of sotrovimab can be considered a therapeutic option to reduce the risk of severe COVID-19 in pediatric patients in the acute phase of T1DM.

This is the first report to describe the detailed clinical course of sotrovimab use in T1DM patients. Our report demonstrates the usefulness and safety of sotrovimab in patients with T1DM. Studies have reported increased DKA and severe DKA rates with new-onset T1DM during the COVID-19 pandemic (14, 15). The underlying reasons for this were presumed to be fear of accessing medical services and COVID-19-mediated cytokine activation, which may have delayed the diagnosis of new T1DM patients and increased insulin resistance, respectively (16, 17). A multicenter study in the USA reported that of 64 adults with T1DM with confirmed or suspected COVID-19, more than 50% reported hyperglycemia, and nearly one-third had DKA (18). Therefore, the COVID-19 pandemic may have increased the number of COVID-19 patients with T1DM and severe DKA in the emergency department. The administration of sotrovimab without major adverse events (other than hyperglycemia) or DKA recurrence can contribute to the treatment of COVID-19 in T1DM patients.

This study had some limitations. First, the reason for the elevated blood glucose level was unclear, as discussed above. Second, we did not identify any COVID-19 variants. Therefore, sotrovimab-resistant COVID-19 variants and omicron BA.2 variants could not be ruled out (19). However, when we encountered this case, the omicron BA.1 variant pandemic was in its early stages. Sotrovimab has been reported to be more active against omicron BA.1 than omicron BA.2 and can prevent the progression of COVID-19 (20).

Conclusion

We report the case of a COVID-19 patient who underwent treatment with sotrovimab in the acute phase of T1DM immediately after DKA. Sotrovimab may contribute to preventing the exacerbation of COVID-19 without any adverse effects (other than hyperglycemia) in T1DM patients. The number of COVID-19 patients with T1DM and DKA may increase, and our study serves as a guide for the administration of sotrovimab for the treatment of COVID-19 in patients with T1DM.

Conflict of interests

The authors declare no conflicts of interest.