The Experience of the Cooperation in Science and Technology European Network for Innovative Diagnosis and Treatment of Chronic Neutropenias (COST EuNet-INNOCHRON) Action and the Sweden Experience in the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Era

Background-Aim: Infection from SARS-CoV-2 has emerged as new pathological entity within the global medical community. One of the earliest questions was in relation to the ability of the immunocompromised patients to clear the infection. In COST EuNet-INNOCHRON we were interested in the impact of SARS-CoV-2 infection in patients with different types of chronic neutropenia (CNP). The aim of the current study is to understand the impact of SARS-CoV-2 infection and to identify any possible characteristic patterns of the clinical course in patients with CNP.

Patients and Methods: The COST EuNet-INNOCHRON Action in collaboration with the European Haematology Association - Scientific Working Group (EHA-SWG) on Granulocytes and Constitutional Marrow Failure Syndromes has conducted an online survey on SARS-CoV-2 infection in patients with CNP. The EuNet-INNOCHRON participants from different countries got access to an on-line platform fulfilling the General Data Protection Regulation (GDPR) and could register adult and paediatric CNP patients who had been infected by SARS-CoV-2 from March 2020 to June 2021. Data on demographic characteristics, type of CNP, patients' background and SARS-CoV-2 infection history (symptoms, laboratory features, radiological appearance, therapeutic approach and outcome) were collected.

Results: Twenty-six patients with diagnosis of CNP, 7 males and 19 females were registered. Patient age distribution as follows: 16 patients >18 years old (y.o.)5 patients 5-18 y.o, 4 patients < 5 y.o whereas age was not available for one of the patients. Nine of the patients were diagnosed with idiopathic CNP, 7 patients with congenital neutropenia (6 of them with severe congenital neutropenia), 3 with secondary CNP, 2 with suspected autoimmune neutropenia of infancy (although antineutrophil Ab were negative), one with autoimmune neutropenia, one with drug induced neutropenia and 3 with other types of CNP. Twelve patients were on treatment with G-CSF and 6 patients had a history of previous viral or bacterial infections. Clonal Cytopenia(s) of Undetermined Significance (CCUS) was excluded in the eight patients who were investigated.

Twenty-four out of 26 patients had positive PCR and one was found incidentally with positive antibodies for SARS-CoV-2. One more patient was symptomatic with history of close contact with SARS-CoV-2 infected family members. The commonest observed symptoms were fever >38 ^oC (19 patients), cough (10 patients), rhinorrhoea (10 patients), sore throat (6 patients), musculoskeletal pains (7 patients), taste/smell loss (5 patients), headache (5 patients), dyspnoea (4 patients), chest pain (one patient) and none of them had gastrointestinal symptoms. No other associated respiratory viral or bacterial infections were reported.

Four patients who had one or more underlying conditions (immune deficiency, heart/respiratory/kidney disease) were admitted in hospital and needed anti SARS-CoV-2 treatment. Two of them had non-invasive ventilation and one of them needed admission in intensive care unit (ICU); both recovered. Another patient with Fallot's tetralogy needed mechanical ventilation in ICU and sadly passed away. No other deaths were observed. Deterioration of the pre-existing neutropenia was seen in two patients, two patients developed thrombocytopenia, one patient developed worsening lymphopenia and one anaemia. Twelve patients had chest X-ray and consolidation was found in two of them. All three patients who had chest CT scans were found with ground-glass changes. During the observation period (up to two months), no re-infection from SARS-CoV-2 was found.

The Stockholm, Sweden experience is similar to the above data. One hundred fifty-four patients with CNP were followed up, for 10 months (March 1 to December 31, 2020) for SARS-CoV-2. Seventeen of these (i.e. 11 %) were infected. None needed hospitalization and there were no fatalities.

Conclusion: Although the relative susceptibility of neutropenic patients to contract SARS-CoV-2 needs to be assessed with further studies, the clinical course and severity of SARS-CoV-2 infection doesn't seem to be worse in CNP patients (regardless the type of neutropenia and the need for GCSF treatment) compared to the general population. Also, like what has been observed in non-neutropenic patients, underlying comorbidities is a significant risk factor for severe disease and adverse outcome.