key: cord-0692393-edelrr0u
authors: Colpo, A.; Astolfi, L.; Tison, T.; De Silvestro, G.; Marson, P.
title: IMPACT OF COVID-19 PANDEMIC IN THE ACTIVITY OF A THERAPEUTIC APHERESIS UNIT IN ITALY
date: 2020-08-25
journal: Transfus Apher Sci
DOI: 10.1016/j.transci.2020.102925
sha: d2c3bc0cc8f91edac2346c47254587e5a2cbd154
doc_id: 692393
cord_uid: edelrr0u

Abstract Introduction The recent Coronavirus Disease 2019 (COVID-19) outbreak has led to profound and rapid changes in the Italian and Veneto Region Healthcare System. This context also includes the quick reorganization which the Apheresis Unit (AU) of the Padova University Hospital, i.e. the Regional Reference Center for Therapeutic Apheresis (TA), had to face. Material and Methods The study retrospectively evaluated the TA activity (procedures performed, patients treated and consultations) during the COVID-19 pandemic, from March to April 2020, comparing the activity in the same time period in 2018 and 2019. Results In the period analyzed, a significant reduction in both the total number of procedures performed and of patients treated, respectively by 17% and 16% for the procedures and by 19% and 20% for patients treated compared to the same period of 2018 and 2019, respectively, was observed. A concomitant reduction in requests for TA consultation for new patients (both outpatients and inpatients) was observed, equal to 32% and 21% compared to 2018 and 2019, respectively. Conclusion Many reasons determined the observed reduction in the TA activity during the recent COVID-19 outbreak. The AU itself was quickly reorganized in terms of location and supplies to allow for the appropriate COVID-19 patients care. Many non urgent cases, after multidisciplinary discussion between Clinicians and Apheresis Specialists, were deferred, maintaining close phone and e-mail contact with patients.

The ongoing outbreak of the Coronavirus Disease 2019 (COVID- 19) pandemic has deeply impacted the health systems around the world [1] . The Veneto region is one of the first and the most Italian regions where the COVID-19 outbreak started spreading at the end of February 2020. In order to contain the epidemic diffusion, strict measures were progressively implemented by the Italian National Health Service and the Regional Authorities. In the Veneto Region a dedicated emergency multidisciplinary network was promptly formed leading to a reorganization of the Regional Healthcare System: some Hospitals became "COVID Hospital", exclusively reserved for COVID- 19 patients, while in other Centers the activity of several Departments was reoriented, becoming sub-intensive or Intensive Care Units (ICU) [2] .

For the same reason the Apheresis Unit (AU) of the University Hospital of Padova was relocated and a new ICU was opened in the spaces previously occupied by the AU. The relocation of the equipment and furniture of the AU took place in just over 48 hours on March 5 th and the Therapeutic Apheresis (TA) activity was quickly rearranged. At the same time, the Regional Health Authorities decreed the suspension of the majority of non-urgent activities, including elective surgery and outpatient visits, with the exception of oncological and maternal and child health areas.

The Padova AU is the Regional Reference Center for TA. It has been active for over thirty years and covers the entire TA activity of the Province of Padova, including all the following procedures: and 2,006 procedures were performed, respectively, confirming the Padova AU among the mostly active in Italy [3] . The Apheresis team is composed by 3 physicians and 6 nurses highly specialized in apheretic technologies. The activity is usually carried out from Monday to Friday, from 8 am to 7 J o u r n a l P r e -p r o o f pm, both for outpatients and inpatients, and emergency treatments are also guaranteed, at nights and during the weekend through on call shifts.

We conducted a single center retrospective study aimed to evaluate the TA activity of the AU of Padova University Hospital throughout the COVID-19 outbreak, from March to April 2020. Data were collected from January to April in 2018, 2019 and 2020, recording the number of procedures and the number of patients treated per indication. Also the number of TA consultations for in and outpatients were collected. We used the GraphPad Prism version 6.04 for Windows, (GraphPad Software, San Diego, USA) for the basic statistics. The number of procedures and patients recorded at the AU are presented as absolute numbers and percentages. The odds ratios (OR) for retrospective analysis with 95% confidence interval (95% CI) were calculated to assess the differences between years and procedure groups, by Fisher's exact test were calculate the P values.

Values of p<0.05 were considered statistically significant.

In the period analyzed, we observed a significant reduction in both the total number of procedures performed and of patients treated, respectively by 17% and 16% (p-value<0,001; OR 0,503 95% CI 0,399-0,635; OR 0,516 95% CI 0,409-0,652) for the procedures and by 19% and 20% (p-value<0,01; OR 0,503 95% CI 0,399-0,635; OR 0,516 95% CI 0,409-0,652) for patients treated compared to the same period of 2018 and 2019, respectively ( Figure 1 ).

In Table 1 In Table 2 we reported, for each treatment indication, the respective ASFA 2019 categories, and the number of patients recorded at the beginning of outbreak accordingly to the decision about to continue, reduce or stop the apheretic procedure. 

The most relevant finding of the present study is the reduction of the number of TA procedures conducted, of patients treated and TA consultations performed during the COVID-19 outbreak guidelines [4] , but data in the medical literature, our previous experience and the discussion with Clinicians and Gynecologists justified the decision [5, 6] . Also, treatment of pediatric patients with HoFH and an adult with hyperLp(a) with advanced cardiovascular disease continued as scheduled, while frequency of treatment in 2 adult patient affected by HeFH and one adult patients with hyperLp(a) was reduced from biweekly to monthly. Our decisions agree with later issued recommendations for FH patients, stating that patients in regular LA treatment, including very highrisk HoFH patients, should be enabled to access this procedure and, where this is not possible, treatment might be postponed safely by as much as 2 months, maintaining maximal lipid lowering therapy and strict monitoring of symptoms [7] . Treatment was also guaranteed in 2 cases of NMOSD not responding to high-dose steroids, in accordance with a recent consensus paper [8] , and in a pediatric patient affected by FSGS recurrent after kidney transplant. For all the 9 patients affected by MG that were on maintenance treatment, TPE frequency was reduced and treatment was offered in case of flare-up of neurological symptoms. A recent Expert Panel paper suggested that MG patients in maintenance should continue treatment, but "extra precautions may need to be taken because of the need of travel to and from a healthcare facility" [9] . We believe that our clinical J o u r n a l P r e -p r o o f decisions have been in line with these recommendations. To note, we received request of consultation for 2 cases of respiratory failure secondary to COVID-19 in patients with MG. In accordance with Neurologists we decided not to proceed with TPE in order to avoid depletion of putative protective antibodies and patients received intravenous Immunoglobulins (IVIg). In the literature 5 more cases of COVID-19 in MG patients have been described until now, none treated with TPE [10] . At the beginning of the pandemic, 4 CIDP patients were on maintenance TPE treatment, with different schedules. Two cases of severely disabling CIDP continued treatments without changes; for the other 2 patients frequency was reduced and treatment schedule has been resumed at the end of the lockdown. This approach is consistent with recently issued treatment recommendations [11] . At March 1 st , 10 patients affected by severe and rapidly progressive SS were on biweekly long-term maintenance therapy, according to our experience [12] . In SS lung involvement, such as interstitial lung disease andpulmonary hypertension, is a common manifestation, and along with immunosuppressive therapy, it places SS patients at high risk of severe course in case of COVID-19 infection. A recent paper by the World Scleroderma Foundation recommended that SS patients should continued immunosuppressive treatments but should limit their visit to the hospital [13] . Nine of 10 SS patients suspended apheresis treatment, while one patient with a severe form continued treatment with a reduced frequency. We remained in close phone/email contact with them and TPE treatment was soon resumed at the end of the lockdown.

Decision about 3 patients with pemphigus vulgaris on maintenance TPE treatment was to suspend treatments. One of them had an exacerbation of symptoms and treatments were resumed. Expert recommendations about the management of autoimmune bullous disease during the COVID-19 pandemic suggest to weigh the risks about rituximab or apheresis treatments against conventional immunomodulatory regimens [14] . Maintenance TPE treatment in a case of Graves orbitopathy (not responding to antithyroid drugs) was suspended during the outbreak, in accordance with

Endocrinologists.

Surprisingly, we did not receive any request of consultation for application of TPE as a rescue therapy in severe COVID-19 patients, as recently published [15] .

At the time of the SARS-CoV-2 outbreak 7 SCD patients were on chronic RBCEx program for stroke prophylaxis and recurrent vaso-occlusive crisis (VOC) or acute chest syndrome (ACS). In accordance with Hematologists, we decided to lengthen the interval between RBCEx procedures and we did not observe any change in the clinical course. Patients with SCD are at high risk of COVID-19 pulmonary severe course and hypoxia can cause VOC and/or ACS. Frequent hospital access, needed for cross-matching and RBCEx procedures, have been discouraged during the outbreak and regular treatments have been resumed at the end of the lockdown. This policy has been in line with the UK National Haemoglobinopathy Panel recent report [16] .

ECP treatment in a patient with acute GVHD was stopped because the patient was in complete remission at the beginning of the outbreak and therapeutic cycle was considered completed. ECP procedures performed in patients affected by chronic GVHD were conducted with a reduced frequency. Despite the absence of specific recommendation about management of chronic GVHD in the COVID-19 era, chronic GVHD patients generally are severely immunosuppressed and are probably at higher risk of a severe COVID-19 course. The same decision was made in patients affected by CTCL. All patients were in partial remission or stable disease and they were treated with ECP as maintenance therapy. Our decisions were made in accordance with Dermatologists and we believe that they are in line with a EORTC CLTF guidelines [17] . Moreover, ECP maintenance treatment was suspended in a DA patients. Even if European Task Force on Atopic Dermatitis (ETFAD) recommended to continue all immune-modulating treatments [18] , we preferred to avoid access in hospital during the pandemic and the disease was well controlled with the adjustment of steroid treatment. In accordance with Gastroenterologists, adsorptive cytapheresis treatments were stopped or postponed in patients affected by mildly active IBD (ulcerative colitis) in maintenance treatment. The patients continued their oral and topic medications [19] and we have not observed an exacerbation of the disease. Even if there is no available evidence that supports discontinuation of J o u r n a l P r e -p r o o f immune-modulating treatments in cutaneous immune-mediated disease because of the risk of COVID-19 [20] , we decided to stop adsorptive cytapheresis treatments in all Hidradenitis Suppurativa patients.

We did not observe a reduction in the autologous PBSCC collection in the period analyzed.

Oncohematologic adult and pediatric patients candidated to high dose therapy and autologous transplantation continued their treatment programs. In addition to the exams required by the National regulations and the FACT-JACIE Standards, all patients have been tested for SARS-CoV-2 before the mobilization regimen and the collection, as recently stated in the EBMT recommendations [21] . During the COVID-19 outbreak we did not perform any PBSCC in related and unrelated allogeneic donors, probably due to travel and logistic restrictions.

Many of the efforts and hospital resources during the COVID-19 pandemic have been oriented in the fight against COVID-19 spread and in the caring of COVID-19 patients. All the hospital activity, including TA and Transfusion Medicine in general have been quickly reorganized to face an unparalleled health emergency, with impact in blood donations and supply [22] and with great effort in the field of convalescent plasma [23] [24] [25] 

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Application of plasma exchange in patients with history of unexplained recurrent abortion: a Case series

Therapeutic apheresis during pregnancy: A single center experience

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Management challenges for chronic dysimmune neuropathies during the COVID-19 pandemic

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Impact of COVID-19 on Blood Centres in Zhejiang Province China

Collecting and evaluating convalescent plasma for COVID-19 treatment: why and how? Vox Sang

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Convalescent Plasma, an Apheresis Research Project by Targeting and Motivating the Fully Recovered COVID 19 patients: A Rousing Message of Clinical Benefits To Both Donors /Recipients Alike

Thrombotic microangiopathy I 1

Graves orbitopathy --1

Pemphigus vulgaris III 1 2

Transplantation, renal -Antibody mediated rejection I 1

Antiphospholipid syndrome during pregnancy --1

I 1

Graft Versus Host Disease -Acute II 1 §

Cutaneous T cell lymphoma -Erythrodermic I 3Atopic Dermatitis III 1

Sickle cell disease -non acute (stroke prohylaxis/recurrent vaso-occlusive crisis)

Hidradenitis suppurativa --4