Multi-Center Study of COVID-19 Infection in Elderly Patients with Lymphoma: On Behalf of Jiangsu Cooperative Lymphoma Group (JCLG)
Authors: Shi Wenyu , Lu Xiao , Zhang Xiaoping , Hua Haiying , Zhang Jie , Miao Yuqing , Gu Weiying , Xu Min , Lu Xuzhang , Li Bingzong , Wang Chunling , Ni Haiwen , Qian Jun , Shi Jinning , Xu Maozhong , Wu Guangqi , Zhang Yunping , Shen Qiudan , Wang Zhi , Zhu Jianfeng , Cheng Zhen , Zhuang Wanchuan , Lin Guoqiang , Hu Yongjun , Shan Qiurong , Chen Yifei , Qiu Hongchun , Li Jianyong , Zhu Huayuan 
Published: December 2023

Objective: To survey the vaccination status, lymphoma status, characteristics and outcomes of COVID-19 infections in elderly patients with lymphoma in Jiangsu Province of China.

Methods: Elderly patients with lymphoma (age≥60 years) in Jiangsu Province was investigated by questionnaire and telephone follow-up during December 2022 to June 2023. Basic information, Lymphoma status, comorbidities, vaccination, severity and outcome of COVID-19 infection were collected.

Results: A total of 402 patients were followed up in this study, 364 were confirmed with COVID-19 infection during December 2022 to June 2023. Among these patients, median age was 70 years (range 60-92), Of which 50.25% (202/402) were over 70 years old. Most patients (85.9%,313/364) were symptomatic at COVID-19 diagnosis. 45.6% (166/364) and 54.4% (198/364) was defined as mild COVID-19 and severe COVID-19 infections according to Diagnosis and treatment plan for COVID -19（trial version 10）in China, all patients with severe COVID-19 infection were hospitalized. 56.0% (204 /364) of patients were aggressive lymphoma and 43.4%(158 /364) were indolent lymphoma. Only 43.9% of the patients had received two or more doses of SARS-CoV-2 vaccine at the onset of COVID-19. In univariable analysis, age &gt;70 years(OR 1.88;95% CI 1.24-2.85,p=0.003), the presence of comorbidities (OR 1.41;95% CI 1.41-1.11,p=0.005), active hematological disease(progressive disease or relapsed/refractory disease, OR 2.02;95% CI 1.53-2.67,P&lt;0.001), ≥2 prior treatment(OR 1.88,95% CI 1.42-2.47,p&lt;0.001), and time from anti-lymphoma treatment to COVID-19 (OR 1.90,95% CI 1.53-2.36,p&lt;0.001) were associated with severe COVID-19 infection in the entire cohort. For anti-lymphoma treatment, anti-CD20-based treatments within the last 6 months was associated with severe COVID-19 infection in the aggressive lymphoma patients (OR 2.17,95% CI 1.21-3.88, p=0.009) as well as in the indolent lymphoma patients (OR 5.67,95% CI 1.97-16.29, p=0.001). Of note, among the indolent lymphoma subsets, only anti-CD20-based maintenance therapy might be a risk factor for exacerbating COVID-19 infection (OR 4.42,95% CI 1.15-17.03,p=0.031), while continuous BTK inhibitors might be protective effect on the outcome when compared with other targeted drugs(OR 0.44,95% CI 0.20-0.97,p=0.043). Overall, 7.7% of patients (28/364) ceased，among them 57.4% (16/28) was due to COVID-19 infection,14.9% (4/28) was due to lymphoma deteriation, 17.9%(5/28) due to COVID-19 infection concurrent with lymphoma progression and 10.7%(3/28) with heart failure . Mortality rate increase by lymphoma status [ Controlled disease: 8.67%(15/173) ; Stable disease: 9.80%(5/51);Active disease:16,67%(6/36), p=0.006)], prior lines of anti-lymphoma therapy [1 prior: 7.14%(13/182)；2 prior: 5.26%(3/57);≥3 prior: 25%(9/36), p&lt;0.001] and anti-lymphoma therapy within one month of COVID-19 infection[&gt;1 months: 8.52%(11/129) ;&lt;1 months: 16.67%(17/102); p=0.002].

Conclusions: Elderly patients with lymphoma have a low rate of COVID-19 vaccination and a high rate of severe COVID-19 infection. Patients with active disease, multiple lines of prior therapy, advanced age, multiple comorbidities, and anti-CD20-based treatments within the last 6 months was associated with severe COVID-19 infection..