Does being immunocompromised present particular risks once infected with COVID-19?

Summary

The following is a short summary of the best available evidence on the increased risk of a COVID-19 infection for immunocompromised individuals. The secondary question that this summary will answer is if individuals who are immunocompromised, are at an increased risk of severe complications. Four meta-analyses, three systematic reviews, four guidance documents and two rapid reviews were identified to answer this question and were used in this REAL Summary. For additional information about each of the sources, see the Table below.

Alberta Health Services states in its Is being immunosuppressed (in its various forms) associated with increased likelihood of recognized COVID-19 and/or increased disease severity? (September 2020) review that it remains unclear if immunosuppressed patients are at an increased risk of developing COVID-19 [13]. However, the risk of infection may be underestimated in this group because patients of higher risk of severe illness likely adopted protective measures earlier and more rigorously [13]. In the Comorbidity and its Impact on Patients with COVID-19 (June 2020) review it was stated that based on current information and clinical experience, older individuals and people with underlying medical conditions are at a greater risk of getting a COVID-19 infection [12].   
 
The Government of Canada states in its Vulnerable populations and COVID-19 guidance (October 2020) that vulnerable populations (i.e., groups at greater risk of getting an infection and developing severe complications due to their health, social, and economic circumstances) include individuals who have underlying medical conditions or who have comprised immune systems from a medical condition or treatment [11]. There were differences in the main conclusions from two systematic reviews regarding health outcomes of immunosuppressed patients who were infected with COVID-19. A review and meta-analysis (August 2020) found that immunosuppression and immunodeficiency were associated with increased risk of severe COVID-19 disease [3]. However, another review on How immunosuppressive status is affecting children and adults in SARS-CoV-2 infection (July 2020), found that, among both adults and children, immunosuppressed patients without other comorbidities had overall better outcomes compared to patients with other comorbidities and that these immunosuppressed patients appeared to have no increased risk for severe disease than the general population [4]. 
 
Numerous studies agree that other potential risk factors for more severe disease outcomes include elderly age, male sex, and smoking, as well as having hypertension, diabetes, obesity, respiratory disease, cardiovascular disease, cerebrovascular disease or a malignancy [1,2,4,5,7]. The authors of a review of COVID-19 in 7,780 pediatric patients (July 2020) noted that 65% of children in intensive care unit (ICU) observation reported an underlying medical condition (i.e., immunosuppression, a history of respiratory or cardiac conditions) [6]. Another systematic review, Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China (May 2020), including both pediatric and adult patients, found incidences of  hypertension and diabetes were twice as high as those not in the ICU, while there were three times the number of patients with cardia-cerebrovascular diseases in ICUs as compared to those not in the ICUs [7].  
 
The World Health Organization (WHO) and the Government of Canada recommend high risk individuals minimize trips outside their homes unless medically necessary [8,9]. In its If you are at higher risk of severe COVID-19, prepare now guidance (March 2020), the WHO recommends these individuals have sufficient quantities of regular medications to reduce outdoor trips, as well as recommends scheduling appointments during off-peak hours [8]. The Centers for Disease Control and Prevention (CDC) recommends in its If You Are Immunocompromised, Protect Yourself From COVID-19 guidance (update December 2020) that individuals on immunosuppressants or other medications should not change or stop taking their medicines without talking to their doctor, as this may cause serious health problems [10]. The CDC also explains that immunosuppressed individuals are at an increased risk of severe infection due to their decreased ability to fight infections [10]. 

Evidence

What‘s Trending on Social Media and Media

Millions of tweets have been published explaining different methods to prevent the spread of COVID-19. Many of the tweets focus on the workplace and preventative measures that can be put in place to protect immunocompromised employees.  
 
YouTube videos from @VICENews @CTVnews surface averaging millions of views and instructing individuals on how to best prevent spreading COVID19 in hopes of containing the virus and ensuring those who are immunocompromised remain healthy, well and not at risk. The most suggested method is mask to mask interaction and keeping six feet apart in all public areas.  

Organizational Scan

The Government of Ontario states that at-risk groups have a higher risk of getting COVID-19. Their  list for at-risk groups includes (but is not limited to) the following those who: 1) are 70 years old or older; 2) are getting treatment that compromises their immune system; 3) have a condition that compromises their immune system; 4) have a chronic health condition; and/or 5) regularly go to a hospital or health care setting for a treatment.[14] 

The Canadian Medical Association states that people with underlying conditions are not necessarily more susceptible to COVID-19. However, if an immunocompromised individual is infected with the virus, their symptoms may be more severe.[15] 

Review of Evidence

Resource	Type/Source of Evidence	Last Updated
Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis — Yang et al.	Meta-Analysis	Study design: systematic review & meta-analysis.   Methods: authors focused on studies describing epidemiological, clinical features of COVID-19, and the prevalence of chronic diseases in COVID-19 patients.  Risk factors such as hypertension, respiratory system disease and cardiovascular disease may be associated with more severe disease outcomes.   Patients with cardiovascular diseases were more likely to have a severe outcome compared to those with hypertension and respiratory system disease.   Last Updated: April 30, 2020
Does comorbidity increase the risk of patients with COVID-19: evidence from meta-analysis — Wang et al.	Meta-Analysis	Study design: meta-analysis.  Methods: focused on COVID-19 patients with comorbidities.  Methods: authors assessed the quality of included studies using the Newcastle-Ottawa scale.   This study found that there was no increased risk of adverse outcomes related to COVID-19 in those with liver disease or renal disease.   Hypertension, diabetes, COPD, cardiovascular disease and cerebrovascular disease are major risk factors for patients with COVID-19.   Last Updated: April 7, 2020
Impacts of immunosuppression and immunodeficiency on COVID-19: A systematic review and meta-analysis — Gao et al.	Meta-Analysis	Study design: systematic review and meta-analysis.  Methods: authors included English and Chinese studies with patients that have a laboratory-confirmed diagnosis of COVID-19, that focused on immunosuppression, immunodeficiency, or human immunodeficiency virus (HIV) between patients with severe or non-severe disease or between non-survivors and survivors.  This meta-analysis showed that immunosuppression and immunodeficiency were associated with an increased risk of severe COVID-19 clinical presentation.   Special preventative and protective measures should be provided to patients who are immunosuppressed.  More high-quality studies are needed to provide robust evidence of the association.   Last Updated: July 31, 2020
How is immunosuppressive status affecting children and adults in SARS-CoV-2 infection? A systematic review — Minotti et al.	Systematic Review	Study design: systematic review.  Methods: authors included English studies that focused on immunosuppressed adults and children with SARS-CoV-2.    This review noted that immunosuppressed patients showed an overall better outcome as compared to other comorbidities, and these results were consistent among adults and children.   Immunosuppressed patients without other comorbidities appear to have no increased risk or a more severe disease than the general population.   The major risk factors for a worse outcome appear to be elderly age, obesity, diabetes, cardiovascular problems and the male sex.   Last Updated: June 30, 2020
Cancer patients and research during COVID-19 pandemic: A systematic review of current evidence — Moujaess et al.	Systematic Review	Study design: systematic review.  Methods: authors included English and French studies focused on adult patients with cancer and COVID-19.    This review notes that cancer patients with severe COVID-19 were more likely to have a malignancy compared to non-severe cases.   Cancer status did not appear to be as great of a risk factor as compared to smoking status and age.   Last Updated: May 31, 2020
COVID-19 in 7780 pediatric patients: A systematic review — Hoang et al.	Systematic Review	Study design: systematic review.  Methods: authors included studies focused on clinical, laboratory, imaging, and hospital course of pediatric patients including neonates, children, and young adults up to 21 years of age.  Methods: authors assessed risk of bias for observational studies using the National Institutes of Health quality assessment tool.  This review notes that among children who were in the intensive care unit, the majority (65%) of the children reported an underlying medical condition.   These children were either immunosuppressed or had a history of respiratory or a cardiac condition.  Last Updated: June 30, 2020
Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China — Li et al.	Systematic Review	Study design: meta-analysis.  Methods: authors included studies that focus on pediatric cases of confirmed COVID-19.  Methods: authors conducted a quality assessment using the Cochrane Collaboration’s tool was followed to assess the risk of bias.  This review describes how patients with previous cardiovascular metabolic diseases face a greater risk of developing a severe condition of COVID-19.   Among patients admitted to ICUs, incidence for hypertension and diabetes were twice as high as those not in the ICU, while there were three times the number of patients with cardia-cerebrovascular diseases in ICUs as compared to those not in the ICU.    Last Updated: April 30, 2020
If you are at higher risk of severe COVID-19, prepare now — WHO: World Health Organization	International Guidance	The WHO recommends to those who are at a higher risk to: 1) talk to a doctor about seeking routine care during off-peak hours and about what to do if someone is sick; 2) make sure they are up to date on vaccinations; 3) have sufficient quantities of their regular medication and other supplies to minimize the number of trips outside the home; and 4) limit in-home services and visitors to what is essential.   Last Updated: March 24, 2020
People who are at high risk for severe illness from COVID-19 — Government of Canada	National Guidance	The Government of Canada recommends that those who are immunocompromised or older should do the following things to reduce their risk of COVID-19: 1) if possible, don’t leave the house too often but attend all medically necessary appointments; 2) stay away from people who are sick; 3) practice physical distancing and wash hands frequently; and 4) avoid touching their face or food with their hands.   Last Updated: September 29, 2020
If You Are Immunocompromised, Protect Yourself From COVID-19 — CDC: Centers for Disease Control and Prevention	National Guidance	The CDC recommends that individuals who are on immunosuppressants or other medications for their specific conditions should not change or stop taking their medicines without talking to their doctor as this may cause serious health problems.   The CDC also explains that immunosuppressed individuals are at an increased risk of severe infection due to their decreased ability to fight infections.  Last Updated: May 13, 2020
Vulnerable populations and COVID-19 — Government of Canada	National Guidance	The Government of Canada states that those who have underlying medical conditions or who have compromised immune systems from a medical condition or treatment are more at risk for severe outcomes and make up part of Canada’s “vulnerable population.”   Vulnerable populations are more at risk of getting an infection and developing severe complications due to their health, social and economic circumstances.  Last Updated: September 30, 2020
Comorbidity and its Impact on Patients with COVID-19 — Sanyaolu et al.	Review	Study design: review.  Methods: authors reviewed literature that focused on COVID-19 in patients with comorbidities.   It was observed that comorbidities increase the chances of a COVID-19 infection.   Based on current information and clinical experience, older individuals and people of any age with serious underlying medical conditions are at greater risk of getting COVID-19.   Last Updated: June 24, 2020
Is being immunosuppressed (in its various forms) associated with increased likelihood of recognized COVID-19 and/or increased disease severity? — AHS: Alberta Health Services	Rapid Review	Study design: rapid review.  Methods: the review focused on COVID-19 patients with immunosuppressive conditions from Europe and North America.  Methods: authors assessed quality using an adapted Mixed Methods Appraisal Tool.   It remains unclear if immunosuppressed patients are at an increased risk of developing COVID-19, however, may be underestimated because patients of higher risk of severe illness likely adopted protective measures earlier and more rigorously.    Last Updated: September 8, 2020
Re-opening your practice during COVID-19 — Canadian Medical Association	Organizational Scan	Last Updated: June 24, 2020
COVID-19: Stop the spread — Government of Ontario	Organizational Scan	Last Updated: July 12, 2020
Disclaimer: The summaries provided are distillations of reviews that have synthesized many individual studies. As such, summarized information may not always be applicable to every context. Each piece of evidence is hyperlinked to the original source.