COVID symptoms, testing, shielding impact on patient‐reported outcomes and early vaccine responses in individuals with multiple myeloma

Abstract

Patients with myeloma have been shielded and self-isolated since the start of the COVID-19 pandemic, due to the concern for and subsequent reports of higher risk of severe COVID-19 disease and mortality. In addition, guidelines have encouraged attenuation of myeloma therapeutics or a switch to oral therapies, ostensibly to reduce hospital footfall, facilitate shielding and potentially to limit further treatment-related immune suppression. Myeloma requires ongoing immune-suppressive chemotherapy, frequent medical visits and has previously demonstrated universally poor response to vaccinations. The protective titre of antibodies required to prevent reinfection is unclear, as is the ability to protect patients from SARS-CoV-2 virus variants of concern (VoC). Cycles of shielding and self-isolation can cause considerable physical and psychological distress for myeloma patients. High mortality rates with COVID-19 coupled with anticipated poor COVID-19 vaccine responses will increase isolation periods and be detrimental to their myeloma care. In order to address these evidence gaps, we initiated a national web-based prospective study of adults with multiple myeloma (MM) from December 2020 using patient co-developed measures of COVID symptoms, testing, vaccination, SARS-CoV-2 immunity acquired by infection or vaccination and quality-of-life (QoL) impact with standardised generic and disease-specific patient-reported outcome measures. Using the existing RUDYstudy.org platform (LREC 14/SC/ 0126 & RUDY LREC 17/SC/0501), informed online dynamic consent was obtained for all participants. Participants completed validated patient-reported questionnaires including the Hospital Anxiety and Depression (HADS) and Lubben Scales. A group of four adults with myeloma co-developed a RUDY COVID-19 consensus questionnaire (Data S1). Participants entered information about their myeloma diagnosis, current disease status and chemotherapy treatment. A serum sample collected from each patient; was tested for antibodies against SARS-CoV-2 nucleocapsid (N) or spike (S) protein. SARS-CoV-2 N protein antibodies were measured by turbidimetry (Abbott Labs, Abbott Park, IL, USA), with samples that produced values of >1 4 considered to be positive. SARS-CoV-2 S protein antibodies were measured by turbidimetry (Abbott; IgG serology only), with a cut-off value of 50 considered to be a positive result. Both of these assays are FDA-approved for use in clinical diagnostic settings. Between 5 February and 29 March 2021, when the UK was still in lockdown, 109 adults with myeloma completed the COVID-19 questionnaire with a returned blood sample. Patient characteristics are listed in Table I with 10% of recruited adults non-UK white. Although the majority of patients reported they were in remission, 20% of patients reported they had poorly controlled myeloma, either relapse or progressive disease. A minority of participants (6%) reported major symptoms of COVID-19 and only one patient reported a polymerase chain reaction (PCR)-positive result (Table SI). Almost all patients were either partially or fully shielded during both waves of the pandemic with fewer patients fully shielded in the second wave. The primary reason for shielding was due to current or recent immunosuppressive therapy (Table SII). Almost a third of respondents identified with making less healthy diet choices during the pandemic but few reported increases in alcohol, smoking or medical treatment for anxiety or depression. The reported impact of the pandemic on lifestyle and social activities varied considerably between participants (Figure S1). One in five respondents scored ‘at risk of social isolation’, with no differences by age but men significantly more likely to be at risk than women (P = 0 027). Using HADS, 23 1% of patients reported symptoms of mild to moderate anxiety or mild to moderate depression during this period (Table II). Out of the 107 patients suitable for serological analysis at the time of reporting, five were found to have positive levels of N protein antibodies, indicating that they had suffered a natural infection. Only one of these patients had a history of a PCR-positive result known at study entry, with the remaining patients having had asymptomatic infections. When looking at the timing of samples that were received from these patients, approximately 25% of them were taken from the patient >3 weeks post their first dose of vaccine (range 21–68 days). Approximatetly 50% of patients who received Astra-Zeneca/ Oxford (AZ) vaccination and 44% of patients who received Pfizer (P) vaccination produced a successful response >3 weeks post first dose [sample n = 14 (AZ) vs 9 (P)]. All patients who had had a previous infection had a robust antibody response to the first dose of COVID-19 vaccine and 60% of patients had an optimal immune response to the first dose of COVID-19 vaccination. There were no differences noted in humoral response after the first dose of either AZ (Adenoviral vector) or P mRNA based vaccination (Table SIII). correspondence