Why Urgent COVID19 Vaccination Prioritization is necessary for those with Primary & Secondary Immunodeficiencies; and for those with recent cancer diagnoses.
My letter to the Ontario COVID19 Vaccine Distribution Task Force is below:
This is by no means intended to be an exhaustive literature review, or an end all list of who is vulnerable to COVID19. There are so many people with chronic illness who are at greater risk of poorer outcomes. However, immunodeficiency appears to be the common denominator for extremely poor outcomes, whether from primary or secondary causes. The CDC has recognized the threats posed by COVID19 to those with chronic illness. Our Ontario task force and Federal task force (NACI) must continue to review the literature and adjust vaccination schemes as necessary, to protect the most vulnerable as quickly as possible. I cannot imagine the number of special interest groups who have recently sent advocacy letters. However, as physicians, we have to advocate as best we can.
LETTER:
13 January 2020
TO: MEMBERS OF ONTARIO COVID-19 VACCINE DISTRIBUTION TASK FORCE
General Rick Hillier, Chair
Hon. Minister of Health, Christine Elliott
Hon. Dr. David Williams, Chief Medical Officer of Health
Dr. Isaac Bogoch, Assoc. Professor and Infectious Disease Consultant
Dr. Dirk Huyer, Ontario Chief Coroner
Dr. Maxwell Smith, Bioethicist and Asst. Professor, Western University
RoseAnne Archibald of Taykwa Tagamou Nation
Linda Hasenfratz, CEO, Linamar Corporation
Angela Mondou, President and CEO, TECHNATION
Mark Saunders, former Toronto Police Chief
RE: PRIORITIZATION OF PERSONS WITH IMMUNODEFICIENCY AND THOSE WITH RECENT CANCER DIAGNOSES/ACTIVE CANCER TREATMENT
Dear Task Force Members,
I would like to thank each of you for your time and commitment to ensure the vaccine roll out in Ontario is done in a manner that protects the most vulnerable citizens, as soon as possible.
The comments I make here are my own.
Introduction:
The Herculean task of vaccinating > 70% of Ontarians cannot be understated. It is easy to be critical, as I am too often, though I remain confident that all provincial governments are working toward the same goal. The apparent community transmission of the B117 Sars-CoV-2 UK variant in Ontario heightens the importance of vaccine triage for the most vulnerable among us.
Soon, the vast majority of vulnerable seniors in long term care and retirement homes, and high risk healthcare workers will be vaccinated. The next tier of persons will include “home care patients with chronic conditions” and other healthcare workers. As you continually revisit the ethical order in which to vaccinate vulnerable persons, as the science evolves, I wish to highlight the importance of vaccinating those who are immunocompromised, especially from primary immunodeficiencies (such as Combined Immunodeficiency or Common Variable Immunodeficiency), and secondary immunodeficiencies. These individuals are most probably in a greater risk category than those “in receipt of homecare with a chronic condition” of the phase 1 vaccination group. All indications are that both morbidity (severity of illness) and mortality are much greater in this patient population.
Cancer patients with more recent diagnoses are also much more likely to contract COVID19. Mortality is significantly higher among this patient group. Other vulnerable populations have been identified (5,6).
I have reviewed the literature, and would like to share these few important references with you.
Immunodeficiency
AM Shields et al., from the UK PIN COVID-19 consortium, published the largest peer reviewed paper to date, on the experience of COVID19 patients with pre-existing primary and secondary immunodeficiency. (1)
Of the 60 patients with primary immunodeficiency (CVID — common variable immunodeficiency 23 patients), over half were hospitalized (n=32) and the case fatality rate was 32% (n=12). Of those hospitalized, 38% died (n=12). This is a very significant risk of COVID19 related death above what we would normally expect in group with a median age of 42, i.e. at least 28x fold increase. This risk posed is greater than seniors in the highest age cohort. I note the CFR among CVID patients was 50% — CVID is the most common primary immunodeficiency in Ontario.
Patients with secondary immunodeficiency had a CFR of 39% (11/28) (1).
See Ontario Case Fatality rates by age group below from the Public Health Ontario January 12, 2021, Daily Epidemiological Summary, in comparison :
Malignancy
A number of publications have identified malignancy as a risk factor for more severe COVID19 outcome.
W. Liang et al reported on the experience in China on comorbidity and severe outcomes with COVID19 (2). Over 1500 patients were analyzed. Those at risk of critical illness included cancer patients, with an Odds Ratio of 4.07. (i.e risk 4 x greater than baseline risk).
A multi-cohort study by Harvard researchers and others, the STOP-COVID working group, identified a recent diagnosis of cancer as an independent risk factor for increased mortality (OR 2.5) among those diagnosed with critical COVID19 illness. (3). See Figure 1.
Wang, Q et al of Case Reserve University carried out an extensive case-control analysis of cancer patients from over 73 million electronic patient records. Their analysis examined: 1) the risk of specific cancers and risk of acquiring COVID19 infection, and 2) The outcome of COVID19 infection and a recent malignant diagnosis. Their results revealed a 7 fold increased risk of contracting COVID19 among cancer patients with a diagnosis within the last year (aOR 7.14 95% CI 6.91–7.39). The greatest risk was among recently diagnosed leukaemia (aOR 12.16, P<0.01), non-Hodgkin’s Lymphoma (aOR, 8.54, P< .001), and lung cancer (aOR, 7.66, P < .001).
Patients with cancer and COVID-19 had significantly worse outcomes (hospitalization, 47.46%; death, 14.93%) than patients with COVID-19 without cancer (hospitalization, 24.26%; death, 5.26%) (P < .001) and patients with cancer without COVID-19 (hospitalization, 12.39%; death, 4.03%) (P < .001).
Cancer Patients on Treatment
Hospitals have been the site of serious COVID19 outbreaks, especially in Windsor and in London, Ontario. Both have busy cancer programs. We are presently vaccinating custodial and clerical staff in hospitals presumably because of their regular exposures in a high risk environment.
Cancer patients treated with radiotherapy normally complete a 5–6 week treatment course where they spend an hour or two in the hospital daily, Monday through Friday. This places them at a perilous risk of COVID19 infection, especially in their immunocompromised state.
Obviously, chemotherapy patients make frequent visits to outpatient programs where they may receive infusions over many hours and visit on a weekly to monthly basis. They are more immunosuppressed than radiotherapy patients, on average.
These unique circumstances should also prioritize recently diagnosed cancer patients and those on active treatment.
Other Significant At-Risk Populations
Finally, I would raise attention to the CDC guidelines recently published, recommending “People with Certain Medical Conditions” who are at risk of severe COVID19 illness be considered for vaccination (5). Specifically, they have identified the following conditions placing people at severe risk:
Cancer
Chronic Kidney Disease
COPD
Down’s Syndrome
Heart conditions (Cardiomyopathy, Congestive heart failure, coronary artery disease)
Immunocompromised state from solid organ transplant
Severe Obesity
Pregnancy
Sickle Cell Disease
Smoking
Type 2 Diabetes Mellitus
A second list was provided which included a list of conditions that may be at risk of severe COVID19 illness (including asthma, Cystic Fibrosis, HIV etc) noting that additional data is lacking.
However, I would note a recent UK population based analysis (N=27,480) revealed people living with HIV had a higher risk of COVID-19 death, than those without HIV, after adjusting for age and sex: hazard ratio (HR) 2·90 (95% CI 1·96–4·30; p<0·0001) (6).
Any patient with a chronic respiratory condition such as Cystic Fibrosis or COPD should be also considered for early vaccination, given their limited functional reserve. A significant respiratory infection would pose a risk of a serious negative outcome.
Recommendations:
- Prioritize vaccinations for those with primary immunodeficiency, and secondary immunodeficiency, and those with recent diagnoses of cancer/or with active cancer therapy as soon as possible.
- Allow other at risk individuals, with autoimmunity, on renal dialysis, underlying lung disease, with HIV, or on immunosuppressants for reasons such as organ transplantation, to be vaccinated at the direction of their treating physicians, at least with the age 80+ cohort. A medical form could be devised to identify these individuals if necessary
I remain most grateful for your consideration. Thank you for your efforts on behalf of all Ontarians.
Sincerely,
Christopher Leighton MD, FRCPC
Radiation Oncologist
(home address deleted)
DISCLOSURE: I have Common Variable Immunodeficiency and an autoimmune neurological condition that resulted in relapsing transverse myelitis and spinal cord injury at T4.
Cc Hon. Andrea Horwath, Leader Official Opposition, NDP
References:
1. Adrian M. Shields, Siobhan O. Burns, Sinisa Savic, et al. COVID-19 in patients with primary and secondary immunodeficiency: the United Kingdom experience. J Allergy Clin Immun. https://doi.org/10.1016/j.jaci.2020.12.620
2. Liang W, Liang H, Ou L, et al. Development and Validation of a Clinical Risk Score to Predict the Occurrence of Critical Illness in Hospitalized Patients With COVID-19. JAMA Intern Med. 2020;180(8):1081–1089. doi:10.1001/jamainternmed.2020.2033
3. Gupta S, Hayek S, Wang W, et al. Factors Associated with Death in Critically Ill Patients with Coronavirus Disease in 2019 in the US. JAMA Intern Med. 2020;180(11):1436–1446. doi:10.1001/jamainternmed.2020.3596
4. Wang Q, Berger N, Xu R. Analyses of Risk, Racial Disparity, and Outcomes Among US Patients With Cancer and COVID-19 Infection. JAMA Oncol. doi:10.1001/jamaoncol.2020.6178
5. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html
6. Bhaskaran K, Rentsch C, MacKenna B, et al. HIV infection and COVID-19 death: a population-based cohort analysis of UK primary care data and linked national death registrations within the OpenSAFELY platform. The Lancet HIV. Vol. 8, Issue 1, E24-E32, January 01, 2021. https://doi.org/10.1016/S2352-3018(20)30305-2
