Management of COVID-19 outbreak on transplant wards

The Lymphoma Hub, Multiple Myeloma Hub, AML Hub, and GvHD Hub present an article based on a webinar arranged by the European Society for Blood and Marrow Transplantation (EBMT) and American Society for Transplantation and Cellular Therapy titled “Strategies to prevent and handle outbreak of COVID-19 on transplant wards”. This web call was a moderated by Pavan Reddy, University of Michigan, US and Nicolaus Kroeger, University Hospital Hamburg-Eppendorf, DE, and had speakers from COVID-19 hotspots around the world (China, Spain and US) sharing experiences and recommendations from their respective clinics.

Preliminary results from the EBMT registry

Dr Per Ljungman, Karolinska University Hospital, SE, presented the data from the EBMT registry.

The EBMT registry, in collaboration with the Spanish group (GETH), set-up a multicenter registry using a three-step data collection (at registration, after two weeks and a later follow-up) which analyzed data from COVID-19 infected transplant patients collected between February 28 to April 14, 2020.

• 130 patients had been registered, 98 with allogenic hematopoietic stem cell transplantation (allo-HSCT), 29 with autologous (auto)-HSCT, one had CAR T-cell treatment, and two were unknown
• Median time from transplant to COVID-19 infection
  • in patients with allo-HSCT: 10 months (range, 0–241)
  • in patients with auto-HSCT: 13 months (range, 0–203)
• Median age of patients at COVID-19 diagnosis
  • Patient with allo-HSCT: 54 years (range, 0–79), included 14 patients < 18 years
  • patients with auto-HSCT: 59 years (range, 41–72)
• Symptoms of COVID-19 diagnosis
  • Asymptomatic: 7/130 (5.4%)
  • Upper respiratory tract symptoms: 51/130 (39.2%)
  • Lower respiratory tract symptoms: 47/130 (36.2%)
  • Other (mostly fever alone): 25/130 (19.2%)
• The registry has follow-up data on 55 out of 130 patients
  • Of the 44 patients from the cohort that received allo-HSCT, 10 had died (22.7%)
  • Of the 11 from patients who received auto-HSCT, 1 patient had died (9%)
  • In 9/11 patients the cause of death was COVID-19
  • Median time to death was 10 days (range, 1–26)

 Preventive measures before transplantation

China

Dr He Huang, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, CH, presented the Chinese COVID-19 recommendations. This hospital also has a handbook called “COVID-19 prevention and treatment” to ensure understanding of new administrative processes and policies

• Provide negative-pressure ambulances and personal protective equipment (PPE) to ambulance attendants
• Keep each area divided into COVID-19+ and COVID-19-, e.g. wards, transplant units and labs
• Patients made to wear masks—frequency and duration of visit to be reduced to a minimum
• Defer planned non-urgent transplants for patients from communities with high COVID-19 prevalence
• For urgent transplants and transplants for patients from communities with low COVID-19 prevalence, screen patients and donors for SARS-CoV-2 with chest CT, RT-PCR/ genomic sequencing and serum antibody
  • If patient is negative, perform transplant in COVID-19- area
  • If patient is positive, perform transplant in COVID-19+ area
  • If donor is positive, identify alternative stem cell source
• Recommendation for patients undergoing unrelated donor HSCT
  • Cryopreserve donor stem cells within local laboratory prior to conditioning
  • Prepare alternative haploidentical related donor as back-up
  • Collect and preserve cryopreserve autologous stem cells
• Related donor HSCT
  • Prepare alternative haploidentical related donor as back-up
  • Collect and preserve cryopreserve autologous stem cells
• Autologous HSCT
  • G-CSF ± plerixafor-based mobilization was the preferred treatment

Spain

Dr Rafael de la Camara, Hospital Universitario de la Princesa, ES, reported the Spanish COVID-19 recommendations

• Divide hematology ward into COVID+ and COVID-
• Split staff were into those caring for patients with COVID- or COVID+
• Disconnect high-efficiency particulate air filter and ventilate normal rooms once per shift
• Suspend non-urgent transplant programs
• Test all patients for SARS-CoV-2 before they enter the ward
• Test negative patients weekly
• Recommendations from experience
  • Anticipate shortage of PPE, diagnostic tests, and healthcare workers
  • Devise a plan for testing healthcare workers and how to manage positive cases
  • Make use of telemedicine for outpatients
• Transplant plan: ship and cryopreserve donor stem cells to the hospital labs prior to conditioning

US

Dr Steven Pergam, Fred Hutchinson Cancer Research, US, reported the US experience and presented a set of recommendations

• Prevention protocol: dedicated units for patients with COVID-19, and assign a dedicated team
• Provide masks and hard plastic face shields for all staff
• Decrease patient volume by deferring non-essential visits
• Mask all symptomatic patients and enforce compulsory eye protection
• Review supplies of PPE and diagnostic tests weekly
• Screening at hospital entry and entry to inpatient wards
  • Enforce face-to-face screening for all healthcare workers upon entry to clinics/units
  • Staff who are sick are not allowed in any unit/research area
  • Screening for caregivers, and accompanying caregivers, visitation was limited
• Ensure aggressive environmental cleaning on transplant units, and droplet/ contact precautions for symptomatic patients
• Use negative pressure machines in the inpatient rooms
• Plan for cancer and transplant units
  • Early triage of patients with severe symptoms to intensive care if they present with acute shortness of breath or hypoxia

Recommendations on preventive measures after transplantation

China

• Educate patients and caregivers on isolation procedures and preventative measure tactics
• Encourage self-isolation at home and minimize visitation
• Healthcare workers to practice telemedicine/online visits
• Explore ways for patients to avoid busy areas in the hospital when having blood tests

Spain

• If possible, continue to divide the hematology unit into COVID+ and COVID-
• Organize telemedicine for outpatients

US

• Organize telemedicine
• Defer survivorship and routine follow-ups to a later date
• Only essential staff in clinics
• Restrict visitation
• Re-train staff to take up alternative roles
• Educate patients, caregivers, and staff
• Maintain consistent communication to staff and patients (e.g. townhalls)

Testing for infections

China

Diagnosis

• The gold standard for COVID-19 diagnosis is a positive result for the presence of nucleic acid of SARS-CoV-2 in the upper respiratory area
• Suspected cases with clinical manifestations in chest CT scans are treated as confirmed cases—even if nucleic acid of SARS-CoV-2 is negative  
• Serum antibody testing for IgM and IgG against SARS-CoV-2 are also treated as a confirmed case

Classification

• Mild: mild symptoms without pneumonia at CT
• Moderate: fever and respiratory symptoms; pneumonia at CT
• Severe: respiratory rate, ≥ 30; oxygen saturation, ≤ 93%; oxygen index, ≤ 300; 50% in CT results within 48 hours 
• Critically severe: respiratory failure with mechanical ventilation, shock, and organ failures

US

• Enhance and amplify testing options and testing locations
  • Test at admission
  • Test before each procedure
  • Perform weekly testing in transplant patients
  • Perform weekly testing of patients in on-campus housing
  • Provide testing stations outside of the hospital
  • Conduct pre-admission screening calls to identify symptomatic patients early

 Treating patients with COVID-19

China

• Reduced-intensity conditioning as the preferred treatment for transplant patients
• Antiviral treatment
  • Standard regimen: 200/100 mg of oral lopinavir/ritonavir every 12 hours combined with 200 mg arbidol
• Alternatives treatments
  • Chloroquine phosphate: weight ≥ 50 kg, 500 mg; weight ≤ 50 kg, 500 mg twice a day for two days followed by 500 mg once a day for five days
  • Interferon nebulization
  • Darunavir/cabicistat: 800/150 mg
  • Favipiravir: 1,600 mg starting dose followed by 600 mg
• The combination of ≥ 3 medications is not recommended
• Average course of treatment was two weeks
• Patients with COVID-19 have been reported to have coagulopathies (thrombosis was experienced by 4% of Chinese patients. Also disseminated intravascular coagulation, acro-ischemia, and cerebral infarction was seen)
• Patients are discharged if
  • they were afebrile for more than two days
  • had reduced respiratory symptoms
  • tested negative for SARS-CoV-2 on two consecutive counts
  • had visible improvements in CT scans
  • had spO₂ at > 93% without respiratory aid
• Self-isolation at home
  • Patients are advised to self-isolate for two weeks following hospital discharge
  • Patients are advised to wear masks and avoid people
  • Symptoms and temperature of patients need to be monitored
• Follow-up in Weeks 1, 2 and 4
  • CT scans
  • routine blood test
  • analysis of renal and hepatic function
  • nucleic acid detection of SARS-CoV-2

Spain

• The COVID-19 experience in Spain was reported differently to what was described in China
  • There was a high incidence of vascular events. Therefore, all HSCT patients received prophylactic heparin at the hospital and when discharged
  • Immunocompromised patients with COVID-19 got worse in Week 3 or 4 after infection compared to normal patients who deteriorated in the second week. Therefore, prolonged follow-up is recommended for these patients
• Treatment recommendation
  • Offer antiviral treatment as soon as the diagnosis is made
  • Try to include patients in COVID-19 clinical trials
  • Manage cytokine storms with tocilizumab, anakinra, corticosteroids, and consider immunoglobins
  • To manage endothelial damage, perform D-dimer testing and administer prophylactic heparin as thrombosis prophylaxis

 Conclusion

The speakers from around the world gave an account of their experience with COVID-19 in the transplant wards and provided recommendations. As COVID-19 is an evolving pandemic, the global experience slightly differs but there are many reoccurring similarities and recommendations from the speakers. Please note guidelines are also changing as more data are released which may supersede the data in this article.