Acute infections and fever under chemotherapy are an important cause of morbidity and mortality in hematologic malignancies [1,2,3,4,5,6,7,8]. For patients with advanced-stage Hodgkin lymphoma (HL) in particular, treatment-related morbidity rates of up to 66% can be observed, depending on the chemotherapy’s intensity [3, 4, 9, 10]: treatment-related Common Terminology Criteria for Adverse Events (CTCAE) Grade 3/4 infections are documented in up to 17% of the patients and febrile neutropenia in 33% of the patients [10]. Therefore, prophylactic anti-infective medication is prescribed frequently, although evidence for positive effects in patients with lymphatic malignancies is limited [5, 8]. Another measure to decrease the rate of infections might be prophylactic self-isolation and avoiding contact to potential sources of infection. In addition, wearing face masks in case of unavoidable contacts might protect against infectious diseases. However, it is still an unanswered question, if these measures are actually effective in this regard. Accordingly, current guidelines do not cover them so far [5, 8].
On January 27, 2020, the first case of an infection with SARS-CoV-2 in Germany was reported. Subsequently, infection rates for SARS-CoV-2 increased rapidly throughout the country so that the German government implemented several protection measures to slow down the spreading of the virus, following recommendations by the World Health Organization (WHO) [11,12,13]. These measures included closing non-essential businesses, schools, universities and gastronomy, implementing the obligation to wear facemasks in public spaces and most importantly, prophylactic social distancing [11, 14]. Possibly due to the generally high acceptance of these measures, the infection rates continuously dropped over the following months from a maximum of approximately 6500 new infections per day in the beginning of April to around 500 new infections per day in Mid of June 2020 [15]. The protection measures in the public health system apparently had an impact on reducing the rate of infection with SARS-CoV-2 in Germany [16].
This observation raises the question whether these measures would generally prevent the spreading and transmission of respiratory viruses causing influenza and other infections through droplets or direct contact and thereby also reduce the incidence of various infectious complications in cancer patients treated with chemotherapy.
Between July 2016 and August 2020, thus covering periods before and during lockdown measures, we have conducted a controlled, prospective, randomized study in adults with newly diagnosed, advanced-stage Hodgkin lymphoma (GHSG HD21, NCT02661503). Patients in the standard group were treated with eBEACOPP (dose-escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisolone), an intensive outpatient polychemotherapy regimen. Fever and infections are the most frequent and clinically relevant complications of this treatment [3]. Consequently, the HD21 trial provides a uniformly treated and well-documented patient cohort, which might allow describing differences between the periods before and during lockdown in the incidence of infections or fever and possibly to derive recommendations from these observations.
We thus aimed to evaluate whether the occurrence of acute infections during chemotherapy for advanced-stage HL decreased since the Corona Virus Disease 2019 (COVID-19) protection measures have been in effect in this well-defined and controlled study population being at high risk for infectious complications.