Guidance on Coronavirus Disease 2019 (COVID-19) for Transplant Clinicians
Updated 16 March 2020

Introduction

This is the third update of Coronavirus Disease 2019 (COVID-19) Guidance from the TID Section of TTS. It is important to note that  information about this disease and our understanding of this virus and its impact on transplantation is evolving rapidly so the guidance may change over time. We plan to regularly update the guidance as new information becomes available.

Since our initial guideline, COVID-19 has been declared a “public health emergency of international concern” and a pandemic by WHO. Further, the disease has been given the name Coronavirus Disease 2019 (COVID-19) and is caused by the virus named SARS CoV-2. As of 16 March 2020, there are 167,511 confirmed cases globally 151 countries (https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/). Ongoing community transmission has been noted in several countries in Europe, Asia and the United States.

As this is an emerging infection, we advise that, for decision making, careful attention to reports from local health authorities as well as review of updated data is essential.

Epidemiology

Initially limited to Wuhan, infection with COVID-19 is being reported from multiple Chinese cities

Recently, rates have been declining in China but increasing rapidly throughout Europe, Iran and the United States. Due to the change in locations experiencing local or national outbreaks, the relevant geographic exposure has expanded; the most up to date information can be found at relevant websites: https://www.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6.

Special consideration should be given to countries with under resourced healthcare systems and high rates of travel and trade with China, Japan, South Korea and Iran; they may not be reporting cases for lack of diagnostic capacity.

General comments on clinical features of relevance to transplant physicians

Initial case series have been published that provide a picture of the clinical spectrum of COVID-19 from centers in Wuhan.^2,3 Imaging demonstrates pneumonia in the majority of patients that are hospitalized (75-100%). Patients with less severe infections may have lower rates of abnormalities. Further, there may be differences in indication for hospitalization around the world (China appears to be admitting the more severely ill patients while other countries are admitting all that are diagnosed for public health containment purposes).⁴ Mortality appears to be age dependent, with the highest rates among older adults (Age 50-59: 1.3%, 60-69: 3.6%, 70-79: 8%, 80+: 14.8%).⁵ There is a paucity of data on mild and asymptomatic infections which will alter these estimates.

Although many patients had co-morbidities in the reported series, data on transplant patients is limited; patients with cancer are more likely to have more severe disease (HR 3.56, 95% CI 1.65-7.69).⁶ Hence a description of the disease in transplant recipients is still not available. Nevertheless the lymphocyte count was lower in those who required ICU care, and in those who perished.² It is not possible to tell if lymphopenia was a manifestation of a more severe form of disease, or if it predisposed to severe disease. Many transplant recipients have medication-induced lymphopenia. Particularly close attention should be paid to transplant patients with suspected or confirmed COVID-19 infection who are lymphopenic. Such attention may include admission (rather than care at home) and paying careful heed to oxygen saturation.

Among comorbidities of interest, more patients who required ICU care had cardiovascular diseases, compared with those who did not require ICU care.²

Patient-to-patient, and patient-to-healthcare worker infection were described and human-to-human transmission has been confirmed.^2,7 As such, strict infection prevention practices are essential.⁸

The mainstay of diagnostic testing is the use of PCR to detect presence of virus in samples collected from the respiratory tract of persons under investigation. Although viral load is generally highest early in the illness, an occasional case has been found with multiple initial negative swabs. Negative testing may occur early when patients are asymptomatic. (Personal communications, S Vasoo)

Transplant Specific Recommendations

Global COVID-19 Guidance

The NOTIFY Library has developed a compendium of guidelines relevant to transplantation (https://www.notifylibrary.org/background-documents#SARS-CoV-2). As these are PDF documents, careful review of the primary organization website is recommended as guidance may change quickly.

Deceased Donors

Persons who returned from countries with >10 infected patients or who have been exposed to a patient with confirmed or suspected COVID-19 within 14 days should not be accepted as a donor. Likewise donors with unexplained respiratory failure leading to death should be excluded.

Where available, testing of upper and lower airway specimens by PCR/NAT of donors with concern for COVID-19 should be considered. Some national guidelines recommend routine testing of donors for SARS-CoV-2. Routine screening should only be performed in areas with significant ongoing community transmission to minimize the risk of false positive testing and organ wastage.

While the true risk of donor-derived transmission is unclear, RNAemia was reported in at least 15% in one case series.⁹

In a country with widespread community transmission, temporary suspension of the deceased donor program should be considered, especially when resources at the transplant center may be constrained.

A tiered suspension may also be considered (i.e. deferral of more elective transplants, i.e. kidney, pancreas and heart transplantation for patients with VADs).This was the approach in Toronto during the SARS outbreak in 2003.¹⁰

There is no clear reason to suspend deceased donor transplants in countries only experiencing sporadic cases of COVID-19 cases.

Living-related transplants

Living donation should not be performed on either a donor or recipient who has returned from countries with >10 infected patients or who have been exposed to a patient with confirmed or suspected COVID-19 within 14 days. Donors should not be utilized if they have fever and/or respiratory symptoms unless SARS-CoV-2 is excluded.

In countries with widespread community transmission, temporary suspension of the living-donor kidney and liver transplant programs should be considered when donation can safely be deferred to a later date.

Where available, testing of upper and lower airway specimens by PCR/NAT of donors with concern for COVID-19 should be considered. Some national guidelines recommend routine testing of donors for SARS-CoV-2.

If transplantation is required as a life-saving procedure, it can be conducted with appropriate assessment of infection in door and recipient and with appropriate informed consent.

Transplant Recipients

Like all persons, transplant recipients should adhere to travel advisories issued by their respective health authorities/government bodies. This may necessitate postponing travel to countries with >10 infected patients.

Recipients should avoid travel to all locations where SARS-CoV-2 is currently circulating.

Transplant recipients should avoid all cruise ship travel.

Transplant Recipients Returning from Abroad

There are two categories of patients here – those returning from a transplant performed abroad, and those returning from a holiday or work stint abroad. From an infection prevention viewpoint, both categories of patients may be managed similarly.

Teams should follow local health department guidelines for isolating, quarantining, testing, and monitoring returned travellers from endemic areas. Examples of such guidelines include (CDC: https://www.cdc.gov/coronavirus/2019-ncov/travelers/index.html; PHE: https://www.gov.uk/guidance/wuhan-novel-coronavirus-information-for-the-public#advice-for-travellers).

All patients who have returned from countries with >10 infected patients or have been exposed to a confirmed or suspected case of COVID-19 within the previous 14 days should avoid elective clinic visits and surgical procedures (including bronchoscopies in lung transplant patients). Plans should be in place to get required laboratory testing of such patients during the 14 days in such way as to avoid potential exposure of other patients.

Staff who have returned from countries with >10 infected patients or have been exposed to a confirmed or suspected case of COVID-19 within the last 14 days should follow hospital policies but should likely not care for transplant patients.

Transplant units should be prepared to receive patients who, for various reasons, have been abroad. They should be housed in single rooms with an attached bathroom, and all staff attending to them should be in full PPE, until infection with COVID-19 is ruled out. Close liaison is needed with other departments (eg, Radiology) whose services are likely needed. An effort to re-arrange schedules may be needed to permit spatial and temporal separation of patients awaiting COVID-19 “rule-out”. The incubation period, the asymptomatic shedder, negative PCRs early in the course of the disease combine to make “ruling out” a very difficult task.

Transplant patients with fever and/or respiratory symptoms should be instructed to call the transplant center and avoid presenting to the clinic without notifying the center in advance to avoid inadvertent exposures.

Transplant centers should develop guidelines for which symptomatic patients need evaluation, testing and management by the transplant center vs. which can remain at home with close telephonic follow-up.

Patients with suspected COVID-19 or who require testing to rule out COVID-19 should wear a surgical mask, be placed in isolation and have evaluation and testing coordinated with infection control or Transplant ID team, consistent with local policies.

Centers should develop testing algorithms for evaluation of patients with concern for SARS-CoV-2 infection. Examples of such algorithms are available (https://covid-19.uwmedicine.org/Screening%20and%20Testing%20Algorithms/4%20-%20Immunocompromised%20Patients%20-%20Protocol.pdf)
The situation is fluid, and all recommendations thus far are made on thin data. Preventing transmission from an infected patient to a healthcare worker is of essence. Careful attention to infection control precautions are essential. As more information becomes available, these guidelines will be updated.

HSCT Guidance

There have been a number of guidance documents developed for HSCT patients. These will be updated over time so would consult the most up-to-date guidance.

• ESBMT: https://www.ebmt.org/ebmt/news/coronavirus-disease-covid-19-ebmt-recommendations-update-march-16-2020
• ASBMT: https://www.astct.org/connect/astct-response-to-covid-19

Treatment of Cases

There is limited data on optimal treatment protocols and none have been clearly demonstrated to optimize outcomes. When considering potential therapies, it would be critical to recognize when there is drug-drug interactions (i.e. lopinavir-ritonavir) or may increase the risk of rejection (i.e. beta interferon).

Changes in immunosuppression are also not well studied in the transplant populations. Calibration of dose reduction has to balance consequences of rejection (i.e. easier to do with kidney transplants than heart transplantation).

Operational Considerations

All transplant-related teams should develop plans to address the following key issues to reduce burden on the healthcare system and mitigate against interruption in care of transplant patients:

• Have a plan for physician and staff absences or furlows due exposure to patients with or team member illness with COVID-19.
• Identify team members who may be impacted by school closures.
• Determine who can work remotely and ensure they have the resources to do so.
• Develop messaging for candidates and recipients about how and when to contact the transplant center in case of illness.
• Develop guidance for candidates and recipients about risk mitigation, including limiting exposure to large crowds, hand hygiene and avoidance of sick exposures.
• Implement procedures to screen patients coming to clinic for fever and respiratory symptoms.
• Determine approaches to minimize exposure to the healthcare setting
• Consider reduced frequencies of clinic visits and laboratory testing
• Consider deferral of elective procedures (i.e. protocol biopsies) in stable patients
• Consider delaying pre-transplant evaluations for patients who do not require immediate evaluation

KEY CHANGES since last update:

References

1. Wu JT, Leung K, Leung GM. Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study. Lancet 2020.
2. Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA 2020.
3. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020.
4. Rothe C, Schunk M, Sothmann P, et al. Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany. N Engl J Med 2020.
5. China CDC Weekly 2020:113-22.
6. Liang W, Guan W, Chen R, et al. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Lancet Oncol 2020;21:335-7.
7. Chan JF, Yuan S, Kok KH, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 2020.
8. Del Rio C, Malani PN. 2019 Novel Coronavirus-Important Information for Clinicians. JAMA 2020.
   
9. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020.
   
10. Kumar D, Tellier R, Draker R, Levy G, Humar A. Severe Acute Respiratory Syndrome (SARS) in a liver transplant recipient and guidelines for donor SARS screening. Am J Transplant 2003;3:977-81.
    
11. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020.
    
12. Tay JY, Lim PL, Marimuthu K, Sadarangani SP, Ling LM, Ang BSP, Chan M, Leo YS, Vasoo S. De-isolating COVID-19 Suspect Cases: A Continuing Challenge. Clin Infect Dis. 2020 Feb 26. pii: ciaa179. doi: 10.1093/cid/ciaa179. [Epub ahead of print]
    
13. Zou L et al. SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. N Engl J Med 2020; DOI: 10.1056/NEJMc2001737
14. Sun X and Yin D (translators). Reporter's Notebook: Life and death in a Wuhan coronavirus ICU. The Straits Times 8 February 2020. Also accessible from: https://www.straitstimes.com/asia/east-asia/reporters-notebook-life-and-death-in-a-wuhan-coronavirus-icu
15. Personal communications. S Vasoo MD, National Centre for Infectious Diseases, Singapore.
16. Novel Coronavirus (COVID-19). WHO Thailand Situation Report – 8 February 2020
17. Soy A. Coronavirus: Are African countries ready? From: https://www.bbc.com/news/world-africa-51403865, accessed on 09022020 @1501hrs.
18. Wuhan virus: Three Japanese evacuated from China infected; 13 other evacuees show symptoms of fever, cough. From: https://www.straitstimes.com/asia/east-asia/wuhan-virus-three-japanese-evacuated-from-china-infected-nine-evacuees-show-symptoms (accessed on 09022020@2129hrs)

Guidance on Coronavirus Disease 2019 (COVID-19) for Transplant Clinicians
Updated 27 February 2020

Introduction

This is the second update of Coronavirus Disease 2019 (COVID-19). It is important to note that information about this disease and our understanding of this virus and its impact on transplantation is evolving rapidly so the guidance may change over time. We plan to regularly update the guidance as new information becomes available.

Since our initial guideline, COVID-19 has been declared a “public health emergency of international concern” by WHO. (https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200131-sitrep-11-ncov.pdf?sfvrsn=de7c0f7_4) Further, the disease has been given the name Coronavirus Disease 2019 (COVID-19) and is caused by the virus named SARS CoV-2. As of 26 February 2020, there are 81,109 confirmed cases globally in China, Iran, Italy, Japan, South Korea and 33 other countries (https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/). Several countries are also reporting community transmission. As this is an emerging infection, we advise that, for decision making, careful attention to reports from local health authorities as well as review of updated data is essential.

Epidemiology

Recently, increases in rates in Japan, Korea, Iraq and Italy have heightened concerns that further spread is likely. In fact, there have been new cases identified outside these countries linked to exposure to them. Due to the change in locations experiencing local or national outbreaks, the relevant geographic exposure has expanded; the most up to date information can be found at relevant websites: https://www.gov.uk/guidance/wuhan-novel-coronavirus-information-for-the-public.

In countries experiencing community transmission, the case definition may have to be wider still. As such, it would be prudent consult updates from your country’s public health authority.

General comments on clinical features of relevance to transplant physicians

Initial case series have been published that provide a picture of the clinical spectrum of COVID-19 from centers in Wuhan.2,3 Imaging demonstrates pneumonia in the majority of patients that are hospitalized (75-100%). Patients with less severe infections may have lower rates of abnormalities. Further, there may be differences in indication for hospitalization around the world (China appears to be admitting the more severely ill patients while other countries are admitting all that are diagnosed for public health containment purposes).4 The current mortality rate in China is 2.9% of laboratory-confirmed cases (https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200213-sitrep-24-covid-19.pdf?sfvrsn=9a7406a4_4). There is a paucity of data on mild and asymptomatic infections which will alter these estimates.

Although many patients had co-morbidities in the reported series, none has been a transplant recipient to date. Hence a description of the disease in transplant recipients is still not available. Nevertheless the lymphocyte count was lower in those who required ICU care, and in those who perished.2 It is not possible to tell if lymphopenia was a manifestation of a more severe form of disease, or if it predisposed to severe disease. Many transplant recipients have medication-induced lymphopenia. Particularly close attention should be paid to transplant patients with suspected or confirmed COVID-19 infection who are lymphopenic. Such attention may include admission (rather than care at home) and paying careful heed to oxygen saturation.

Among comorbidities of interest, more patients who required ICU care had cardiovascular diseases, compared with those who did not require ICU care.2

Patient-to-patient, and patient-to-healthcare worker infection were described and human-to-human transmission has been confirmed.2,5 As such, strict infection prevention practices are essential.6

The mainstay of diagnostic testing is the use of PCR to detect presence of virus in samples collected from the respiratory tract of persons under investigation. Negative testing may occur early when patients are asymptomatic. (Personal communications, S Vasoo) One Thai person evacuated from Wuhan was negative for COVID-19 two days in a row; he then developed a mild flu-like illness 4 days after return at which point their swab confirmed infection.( https://www.who.int/docs/default-source/searo/thailand/20200208-tha-sitrep-03-ncov-final.pdf?sfvrsn=f2aa5c07_0)

Transplant Specific Recommendations

Current Regions Experiencing Local/Regional Transmission

• China
• Iran
• Northern Italy, especially
• Lombardy: Codogno, Castiglione d’Adda, Casalpusterlengo, Fombio, Maleo, Somaglia, Bertonico, Terranova dei Passerini, Castelgerundo and San Fiorano
• Veneto: Vo’ Euganeo
• Special Care Zones of South Korea: Daegu and Cheongdo
• Vietnam
• Cambodia
• Laos
• Myanmar
• Updated at: https://www.gov.uk/guidance/wuhan-novel-coronavirus-information-for-the-public

Deceased Donors

Persons who returned from China, Iran, Italy, South Korea, Vietnam, Cambodia, Laos or Myanmar (See above regions of concern) or been exposed to a patient with confirmed or suspected COVID-19 within 14 days should not be accepted as a donor.

While the true risk of donor-derived transmission is unclear, RNAemia was reported in at least 15% in one case series.7

In a country with widespread community transmission, temporary suspension of the deceased donor program should be considered.

A tiered suspension may also be considered (i.e. deferral of more elective transplants, i.e. kidney, pancreas and heart transplantation for patients with VADs).This was the approach in Toronto during the SARS outbreak in 2003.8

There is no clear reason to suspend deceased donor transplants in countries only experiencing sporadic cases of COVID-19 cases.

Ongoing transmission of COVID-19 has been demonstrated in several countries including China, Iran, Italy, South Korea; updated data, available from WHO (https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/) should be consulted regularly for updated decision making about donors with relevant exposures.1 “Community” cases in Singapore and Japan are being investigated for links with Chinese tourists/returnees.

Special consideration should be given to countries with under resourced healthcare systems and those with high rates of travel and trade with China, Japan, South Korea and Iran; they may not be reporting cases for lack of diagnostic capacity.

When diagnostic testing becomes more widely available, approaches to testing of potential at risk donors could be considered. Such approaches are not currently recommended.

Living-related transplants

Living donation should not be performed on either a donor or recipient who has returned from China, Iran, Italy, South Korea, Vietnam, Cambodia, Laos or Myanmar (See above regions of concern) or been exposed to a patient with confirmed or suspected COVID-19 within 14 days.

In countries with widespread community transmission, temporary suspension of the living-donor kidney and liver transplant programs should be considered.

When diagnostic testing becomes more widely available, approaches to testing of potential at risk donors could be considered. Such approaches are not currently recommended.

If transplantation is required as a life-saving procedure, it can be conducted with appropriate assessment of infection in donor and recipient and with appropriate informed consent.

Transplant Recipients

Like all persons, transplant recipients should adhere to travel advisories issued by their respective health authorities/government bodies. This may necessitate postponing travel to China, Iran, Italy, Japan and South Korea.

Transplant Recipients Returning from Abroad

There are two categories of patients here – those returning from a transplant performed abroad, and those returning from a holiday or work stint abroad. From an infection prevention viewpoint, both categories of patients may be managed similarly.

Teams should follow local health department guidelines for isolating, quarantining, testing, and monitoring returned travellers from endemic areas. Examples of such guidelines include (CDC: https://www.cdc.gov/coronavirus/2019-ncov/travelers/index.html; PHE: https://www.gov.uk/guidance/wuhan-novel-coronavirus-information-for-the-public#advice-for-travellers).

All patients who have returned from China, Iran, Italy, South Korea, Vietnam, Cambodia, Laos or Myanmar (See above regions of concern) or have been exposed to a confirmed or suspected case of COVID-19 within the previous 14 days should avoid elective clinic visits and surgical procedures (including bronchoscopies in lung transplant patients). Plans should be in place to get required laboratory testing of such patients during the 14 days in such way as to avoid potential exposure of other patients.

Staff who have returned from China, Iran, Italy, South Korea, Vietnam, Cambodia, Laos or Myanmar (See above regions of concern) or have been exposed to a confirmed or suspected case of COVID-19 within the last 14 days should follow hospital policies but should likely not care for transplant patients.

Transplant units should be prepared to receive patients who, for various reasons, have been abroad. They should be housed in single rooms with an attached bathroom, and all staff attending to them should be in full PPE, until infection with COVID-19 is ruled out. Close liaison is needed with other departments (eg, Radiology) whose services are likely needed. An effort to re-arrange schedules may be needed to permit spatial and temporal separation of patients awaiting COVID-19 “rule-out”. The incubation period, the asymptomatic shedder, negative PCRs early in the course of the disease combine to make “ruling out” a very difficult task.

The situation is fluid, and all recommendations thus far are made on thin data. Preventing transmission from an infected patient to a healthcare worker is of essence. Careful attention to infection control precautions are essential. As more information becomes available, these guidelines will be updated.

References

• Wu JT, Leung K, Leung GM. Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study. Lancet 2020.
• Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA 2020.
  
• Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020.
• Rothe C, Schunk M, Sothmann P, et al. Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany. N Engl J Med 2020.
• Chan JF, Yuan S, Kok KH, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 2020.
• Del Rio C, Malani PN. 2019 Novel Coronavirus-Important Information for Clinicians. JAMA 2020.
• Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020.
• Kumar D, Tellier R, Draker R, Levy G, Humar A. Severe Acute Respiratory Syndrome (SARS) in a liver transplant recipient and guidelines for donor SARS screening. Am J Transplant 2003;3:977-81.
• Sun X and Yin D (translators). Reporter's Notebook: Life and death in a Wuhan coronavirus ICU. The Straits Times 8 February 2020. Also accessible from: https://www.straitstimes.com/asia/east-asia/reporters-notebook-life-and-death-in-a-wuhan-coronavirus-icu
• Personal communications. S Vasoo MD, National Centre for Infectious Diseases, Singapore.
• Novel Coronavirus (COVID-19). WHO Thailand Situation Report – 8 February 2020
  Soy A. Coronavirus: Are African countries ready? From: https://www.bbc.com/news/world-africa-51403865, accessed on 09022020 @1501hrs.
• Wuhan virus: Three Japanese evacuated from China infected; 13 other evacuees show symptoms of fever, cough. From: https://www.straitstimes.com/asia/east-asia/wuhan-virus-three-japanese-evacuated-from-china-infected-nine-evacuees-show-symptoms (accessed on 09022020@2129hrs)

An Update and Guidance on 2019 Novel Coronavirus (2019-nCov) for Transplant ID Clinicians
Updated 27 January 2020

We have prepared the following Update for Transplant Infectious Diseases Clinicians about the novel 2019 Coronavirus associated with viral pneumonia from Wuhan, China. As this is a rapidly changing topic, consult your local public health authority for the most up to date data. We will continue to update this document over time.

Background and Timeline

On 31 December 2019, the World Health Organization received reports from Chinese authorities about a cluster of pneumonia cases at a hospital in Wuhan, China. All patients seemed to be epidemiologically linked to a fresh seafood market that also sold live animals like snakes and marmots. It appeared that common respiratory viruses like influenza and adenovirus had been excluded, as had SARS Co-V and MERS Co-V. (eCDC)

On 9 January 2020, WHO revealed that Chinese scientists had found a novel coronavirus from respiratory samples of one of the patients involved in the cluster. (WHO 0901) The full sequence was subsequently shared with WHO and the GISAID website. (WHO lab guidance 17 January 2020) This virus has been named the 2019 novel coronavirus (2019-nCoV).

On 14 January 2020, Thai authorities reported that a Chinese tourist from Wuhan had been admitted for fever and had been found to have the novel coronavirus, 2019-nCoV. (CIDRAP 13 Jan) The history of contact with the seafood market was not initially available, but it was subsequently reported that she had not had such contact. (CIDRAP 14 Jan 2020)

As more countries reported cases of 2019-nCoV among persons who had been to Wuhan, the suspicion that there was human-to-human transmission increased. On 20 January 2020, reports emerged that healthcare workers were infected with the novel coronavirus (CIDRAP 20 Jan 2020). It was unclear if these workers had had contact with the initial cohort of patients reported on 31 December 2019, or if they were from one or several healthcare facilities. Nevertheless this report heightened already increasing concerns about human-to-human transmission. Using sequences publicly shared by laboratories from China and Thailand, preliminary phylogenetic analysis has been performed, with results suggesting limited diversity thus far. (virological.org) A recent report of intra-family transmission (Family cluster Lancet, Lancet 24 Jan 2020) confirmed human-to-human transmission of the virus.

Most worrying is the statement made by the Chairman of China’s National Health Commission that the asymptomatic may also be infectious. (Anon, weixin.qq.com) There is as yet no published data to support this. It is also difficult to dismiss this, as this statement was made at a press conference held by a government body. One patient in the Shenzhen family cluster was asymptomatic, but it is not possible to determine the direction of transmission as all patients were part of the same family. (Shenzhen)

Transplant physicians are likely to encounter transplant candidates, transplant recipients, and potential donors who have travelled to or are planning to travel to Wuhan, or more generally, China. This document provides preliminary guidance on the approach to this new infection in the transplant setting. As the situation is fluid, we advise transplant physicians to work closely with their Transplant Infectious Diseases (TID) colleagues, and we urge TID specialists to keep abreast of developments by referring regularly to reputable websites such as those of US CDC (https://www.cdc.gov/coronavirus/2019-ncov/index.html), WHO (www.who.int) and Public Health England (PHE) (www.gov.uk/government/organisations/public-health-england).

2019-nCoV

To date, data on modes of transmission, incubation period, and degree or duration of infectiousness is preliminary. The incubation period of SARS was estimated to range from 2 to 11 days (Tsang). The median incubation period of MERS was calculated to be 5.2 days (Assiri). Based on one family cluster, the authors concluded that the incubation period of 2019-nCoV was similar to that of SARS. (Shenzhen cluster)

In a case definition advocated by PHE, an acute respiratory illness in a person who had been to Wuhan or confirmed to be infected with the 2019-nCoV in the previous 14 days constituted a possible case; the US CDC gives almost identical case definitions. (PHE guidance, CDC guidance) Interim guidance from WHO also uses a 14-day time period between last contact with a case or travel to China/Wuhan and symptom onset. (WHO interim guidance 21012020). While most patients had fever and cough, patients may be asymptomatic initially. Contact with a known or suspected case of 2019-nCoV should be a flag.

General Measures

It is presumed that hospitals receiving and managing transplant candidates and recipients have put themselves and their staff on the alert for this novel coronavirus. Protocols should be in place for frontline staff (those in clinic or Emergency) to perform questionnaire-based screening for respiratory symptoms and a travel history. US CDC recommends that persons who fit the criteria should immediately be given a surgical mask and evaluated in a private room with the door closed. (CDC IPC guide)

As authoritative bodies have already published guidance on case definitions, testing, and infection prevention precautions, this document will highlight mainly issues pertinent to transplantation. It is also obvious that information is lacking on many aspects of the virus and the disease. As more information become available, these guidelines will likely require modification.

Case Definition

A case definition should be developed - using one promulgated by the local government or by the hospital’s ID team or published by reputable bodies may simplify preparations. Patients fulfilling the case definition should be managed in respiratory isolation rooms, with one guideline stating that both negative-pressure and neutral pressure rooms are acceptable. (PHE infection control guidance) US CDC notes that an airborne infection isolation room is ideal (US CDC). As transplant patients should not be placed in negative pressure rooms, neutral pressure rooms are an option. The WHO recommends “adequately ventilated single rooms”. (WHO IPC guide 25 Jan) It is important that the room has an attached bathroom. (PHE)

Case definitions available thus far combine a travel and/or a contact history (with Wuhan/China/patients hospitalised in Wuhan) with respiratory symptoms. (PHE, WHO interim guidance) Prominent among symptoms highlighted is fever. Indeed the first available case series from Wuhan noted that fever was present in 98% of the patients. (Huang first case series) The presence of fever in a case series does not mean every patient presents with fever. Two of the patients in the Shenzhen family cluster were actually afebrile at presentation – they had diarrhoea and upper respiratory symptoms. (Shenzhen family cluster) It is well known that immunocompromised patients may have atypical or muted presentations. Therefore transplant physicians may want to have a low threshold to isolate and test patients with mild symptoms but the relevant epidemiological exposures.

Patients can experience non-respiratory symptoms (TTT paper in EID). Although largely thought of as a respiratory illness, 35% of MERS CoV patients had gastrointestinal symptoms. (Assiri) A small percentage of patients with 2019-nCoV have diarrhoea, though it is unclear from available reports if this may be the presenting symptom. (Huang, First case series, Shenzhen family cluster)

Transplant Specific Recommendations

Deceased Donors
As little is known about the virus, persons dying of or with 2019-coV should not be eligible for deceased donation.

Living Donors
Living donation should not be performed within 14 days of return from China/Wuhan.

Transplant Candidates
Transplant candidates should not undergo a transplant within 14 days of return from China/Wuhan. This will allow sufficient time for symptoms to develop.

Transplant Recipients
Like all persons, transplant recipients should adhere to travel advisories issued by their respective health authorities/government bodies. This may necessitate postponing non-essential travel to Wuhan and Hubei province, and depending on how the situation evolves, China.

An intra-departmental guide should be developed for transplant patients who are within 14 days of return from China/Wuhan, or who have had contact with a patient infected with the 2019-nCoV, and who need a surgical procedure, e.g., scheduled BAL in a lung transplant recipient. Re-scheduling an elective procedure is prudent. If the procedure is urgent, then full infection prevention precautions should be applied. It is also prudent for transplant patients with the relevant epidemiological exposures who get admitted for intercurrent illnesses like appendicitis to be managed under full infection prevention precautions. The development of fever or dyspnoea post-operatively will be a particularly challenging and difficult situation, but prudence would indicate that efforts to rule out the 2019-nCoV should be undertaken.

Staff
This outbreak is occurring across the Chinese New Year, a time when many native Chinese go back to their home cities/villages to celebrate with families. As the festive period winds down, many will return to their places of residence. Programs should develop policies related to handling of staff returning to work after potential exposure to areas with active transmission of nCoV 2019. Policy should include requirement for patients who become ill to not report to work but to instead report to their occupational health clinic. Such potentially ill staff should call the clinic to alert them that they were exposed and are sick so that appropriate preparations can be made.

Summary

We have proposed rather strict guidelines for the safety of the transplant patients in our care. As this is a rapidly evolving situation, new data will emerge that may render these recommendations outdated. Uncertainties may well persist for some time into the future, and prudence might dictate the need to practise under stringent infection prevention precautions for a longer period than necessary. The importance of strict adherence to good hand hygiene, the most important of infection prevention precautions, cannot be over-emphasized.

References

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