Supervised by: Yuhui Zhou, BA (Hons). Yuhui is a 5th year medical student at the University of Cambridge. She gained a First class degree in her intercalated year studying Pathology. She has an interest in Cancer & Immunology and has been awarded a Wellcome Trust Biomedical Vacation Scholarship to study host responses to infection.
Severe Acute Respiratory Syndrome Coronavirus-2 or SARS-CoV-2 is a newly identified type of the coronavirus, which is responsible for the COVID-19 pandemic that began in 2019. Due to impaired immune systems triggered by cancer itself, as well as patients often having had antineoplastic immunotherapy, it was suggested that oncology patients are both at increased risk of developing COVID-19 than the general population and more likely to develop more severe symptoms associated with premature mortality. SARS-CoV-2 infection among HIV patients raises many concerns, not only about the risks of serious illness and vaccine safety, but also related to complex management—for example, the availability and effectiveness of antiretroviral agents.
Hence, the COVID-19 pandemic has fundamentally reshaped not only oncology but also the HIV/AIDS response worldwide, repositioning the significance of virtual consultations in light of these patients’ potential vulnerability, and reassessing the classification of critical versus non-critical planned cancer therapies and HIV/AIDS management. The current review underpins the relationship between SARS-CoV-2 infection and the pathobiology, screening, treatment, and outcomes for cancer patients, HIV/AIDS patients and disabled persons, as well as the impact of anti-SARS-CoV-2 vaccinations on these patient populations.
Keywords: COVID-19; SARS-CoV-2 infection; cancer; HIV/AIDS; disability persons
Severe Acute Respiratory Syndrome Coronavirus-2 or SARS-CoV-2 is a newly identified type of β-coronavirus which is responsible for the COVID-19 pandemic that began in early 2020 (1–6). Despite intensive research with antiviral drugs development and the occurrence of different types of vaccines, COVID-19 continues to spread globally at a worrying rate. This is especially true of the Delta variant, which is more than twice as contagious as earlier strains of the virus and holds important consequences on the quality of healthcare in chronic clinical settings.
Coronaviruses are a large family of viruses responsible for respiratory symptoms varying from mild upper respiratory tract infections to more serious lower respiratory infections, such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) (1–6). While anyone can become infected with SARS-CoV-2 and develop COVID-19, several categories of exposed people are at a higher risk of developing the disease and of having poor outcomes (1–6). It seems that the risk of severe disease is particularly high in the elderly and individuals with underlying chronic conditions, not only those which may impact the immune system’s competency—patients with cancer and systemic autoimmune conditions, for example—but also those with hypertension and other serious heart conditions, obesity, type II diabetes, and/or chronic kidney disease (1–6).
Due to an impaired immune system related to their cancer, as well as antineoplastic systemic immunotherapy such as chemotherapy that may expose patients to a higher risk of becoming infected, it was suggested that cancer patients are also at an increased risk of developing COVID-19 versus the general population and are also more likely to develop severe forms with higher subsequent mortality rates (1–6). Despite controversies regarding the true link between coronavirus infection and the outcomes of cancers, it is clear that the COVID-19 pandemic caused by the SARS-CoV-2 virus continues to have a critical impact on many individuals, including cancer patients, their families, and caregivers (1–6).
On the other hand, another significant infection that deeply affects the immune system and leads to a high risk of developing multiple infections, particularly opportunistic infections, is the final phase of HIV infection. Although there are many similarities between the ongoing HIV pandemic and the current COVID-19 pandemic, SARS-CoV-2 infection among HIV patients faces many concerns, not only about the risks of serious illness and vaccine safety, but also related to complex management (meaning the availability and effectiveness of antiretroviral agents).
COVID-19 has fundamentally reshaped oncology and HIV/AIDS practice, repositioning the significance of online consultations in light of the potential vulnerability of these categories of the patient population and reassessing the classification of critical versus non-critical planned cancer and HIV/AIDS therapies (1–6).
The current review underpins the relationship between SARS-CoV-2 infection and (i) oncology issues (such as the pathobiology, screening, treatment and outcomes, as well as the impact of anti-SARS-CoV-2 vaccinations on cancer patients); (ii) HIV/AIDS patients; and (iii) disabled persons.
Interrelation between COVID-19 and cancer
Susceptibility of COVID-19 in cancer patients
Overall, patients with cancer, especially those with active cancer, are at a higher risk of infections related to impaired, weakened immune response associated with the cancer itself and/or specific immunosuppressants and chemotherapy known to inhibit both the haematopoietic and immune systems. In addition, the immunocompromised status of cancer patients raises the question of whether such cases would have an increased susceptibility of contracting SARS-CoV-2 infection and would this then carry with it an excessive risk of severe illness, complications and death (1–6).
Nevertheless, patients with malignancies may also carry diverse comorbid conditions such as diabetes, hypertension, obesity, or cardiovascular disease—conditions consistently associated with poor outcomes for COVID-19, and which are known to enhance the chance of cancer patients contracting different types of infections, including coronavirus infections (1–6).
Whether cancer patients are at an increased risk of being infected with coronavirus and developing severe complications or, conversely, whether SARS-CoV-2 infection may prompt the progression of cancer is still debatable (1–6). Indeed, several authors (Lee et al., Jee et al., and Kong et al.) reported a high risk of severe COVID-19 and an increased rate of hospitalization and death in patients with haematological malignancies, especially those who have recently received chemotherapy, irrespective of age and gender (1–6). People with blood cancers may also be at higher risk of prolonged infection and death from COVID-19 than people with solid tumours since they have abnormal or depleted levels of immune cells producing anti-virus antibodies.
Importantly, COVID-19 is bidirectional, meaning cancer patients display worsening of their neoplastic status during and soon after infection. This was shown even in patients with a history of treated cancer. Moreover, the severity of cancer directly correlated with the severity of COVID-19 for both haematological malignancies and lung cancer, supporting the idea that immunosuppressive status (related to cancer severity and more aggressive medication) causes a high susceptibility to SARS-CoV-2 infection (1–6). It was suggested that the risk of having COVID-19 widely varied with the anatomopathological pattern of cancer; thus, lung adenocarcinoma is associated more frequently with COVID-19 than lung squamous cell carcinoma (1–6).
Conversely, more recent studies on larger cohorts of patients with cancer and COVID-19 reported similar outcomes of infection, irrespective of cancer subtype (solid cancers or haematological malignancies), severity (incipient or metastatic), type (chemotherapy or surgery) and timing of cancer treatment; thus, there was no higher risk of complications and death in cancer patients with coronavirus disease when compared to the general population. Indeed, the only common risk factor predictive of death in cancer patients with COVID-19 was smoking (1–6).
COVID-19 and the pathobiology of cancer
It is widely acknowledged that angiotensin-converting enzyme 2 (ACE2) acts as a receptor for the family of coronaviruses, including the novel SARS-CoV-2, which encourages the virus to enter the cells. In addition, the expression of ACE2 in different tissues has been shown to be critically linked to an individual’s risk of contracting the virus and the severity of the infection. Furthermore, it appears that, through binding to ACE2 receptors, SARS-CoV-2 is able to decrease the activity of these receptors, overriding their normal functioning (1–6).
Conversely, ACE2 is highly expressed in many cancer subtypes, including colon adenocarcinoma, renal papillary cell carcinoma, pancreatic adenocarcinoma, rectal adenocarcinoma, gastric adenocarcinoma and lung adenocarcinoma. Interestingly, the ACE2 promoter is hypomethylated in cancer patients; since hypomethylation can cause genome instability and DNA hypomethylation is related to gene activation during cancer progression, one may assume that ACE2 has a potentially protective effect on cancer progression (1–6).
Recent studies, however, have suggested that cancer patients are still at an increased risk of contracting a SARS-COV-2 infection as a result of their greater ACE2 expression in neoplastic tissues. Several authors have demonstrated that the hypomethylation of ACE2 promoters in patients with cancer and concomitant COVID-19 was at a significantly lower level compared to patients with cancer but without coronavirus infection. The tumour tissues infected with SARS-CoV-2 have decreased ACE2 expression, potentially leading to a decrease in immune infiltration and modified tumour microenvironment, contributing to a progression of cancer in infected patients (1–6).
Cancer management during COVID-19 pandemic
COVID-19 has drastically changed the healthcare industry, especially the standard care for patients with malignancies. At the onset of the COVID-19 pandemic in early 2020, different international and national professional societies and organizations recognized that cancer patients are a distinctly vulnerable population for experiencing COVID-19 and recommended a delay to routine oncologic screenings as well as elective medical and surgical procedures due to the massive involvement of physicians and healthcare providers in resolving the urgent medical needs of COVID-19 patients and decreasing the spread of infections (1–6). Reduced access to healthcare (due to a range of factors such as lockdowns, fear of COVID-19 infection, unemployment with subsequent financial insecurity, reallocation of healthcare resources); delayed routine care; a higher rate of advanced-stage diagnoses; and delayed or modified cancer treatments have dramatically impacted the oncological landscape, leading to increased mortality according to the American Cancer Society’s 2021 surveillance report. Furthermore, a cumulative excess death from colorectal and breast cancers in the following ten years (2020-2030) is anticipated in the US, due to the COVID-19 pandemic preventing routine screenings (1–6).
As our knowledge about COVID-19 and its management has improved, oncologists have issued special reports on cancer care during the pandemic, emphasizing guidance around adjusting cancer treatment. Thus, newly published guidelines advance recommendations for a wide range of clinical settings, mostly focused on the vulnerable, and point towards a limited frequency of on-site monitoring visits when appropriate (1–6).
Antiviral therapy and cancer
Early on in the pandemic, several immunomodulatory anti-inflammatory treatments commonly used in people with rheumatic conditions were proposed as possible options for people with severe COVID-19 infections. Thereafter, specific, effective antiviral agents were developed and proved their efficacy in treating COVID-19 patients.
The therapeutic algorithm for COVID-19 essentially relies on antivirals (ribavirin and arbidol hydrochloride), immunotherapy (convalescent plasma, intravenous injection of COVID-19 human immunoglobulin, biological drugs such as tocilizumab, and, potentially, targeted synthetic drugs such as baricitinib) and glucocorticoids. A holistic approach towards patients with SARS-CoV-2 infections is mandatory and depends on multiple factors, including the stage of the disease and complications, recognized risk factors, comorbidities and chronic-specific medications (1–6).
A closer look at the coexistence of cancer and COVID-19 should emphasize the potential interactions of anti-cancer drugs with anti-COVID therapies in this vulnerable population. Although there is still limited data, it seems that different antiviral drugs may also potentially act as anti-cancer agents. The most relevant information on this comes from the excessive synthesis of proinflammatory interleukin-6 (IL-6), a key regulator of immune response and cytokine storm in the pathobiology of SARS-CoV-2 infection. IL-6 is also involved in tumorigenesis and anti-apoptotic signals and is recognized as a key diagnostic and prognostic biomarker in malignancies (1–6).
Indeed, the dual role of IL-6 in the pathogenetic mechanisms of coronavirus infection and cancers promoted the significance of IL-6 inhibitors such as tocilizumab (an IL-6 receptor inhibitor primarily approved for the management of systemic immune-mediated rheumatic conditions)—not only in improving inflammatory damage caused by COVID-19, but also in treating various forms of cancer. Further studies are required in order to correctly identify which clinical scenarios exactly benefit from IL-6 inhibition, however (1–6).
COVID-19 vaccine in cancer patients
The latest information about COVID-19 vaccines focuses not only on effectiveness and safety across the exposed population, but also on the different categories of population and disorders which should be considered high risk for severe outcomes of coronavirus infection and, therefore, should be on priority lists for vaccination (1–6).
Three COVID-19 vaccines are currently approved for use in the EU and USA. Their rollout has not only meaningly reduced the risk of coronavirus infection in these regions, but also significantly protected vulnerable individuals against severe disease, hospitalization and fatal outcomes due to COVID-19. Of these three vaccine options, two are messenger RNA (mRNA) vaccines (Pfizer-BioNTech and Moderna), in which the mRNA enters cells of the body following vaccination and stimulates the immune system to make copies of the COVID-19 virus’s “spike” protein (1–6). On the other hand, the Johnson & Johnson vaccine contains a laboratory-modified adenovirus (which is different from the coronavirus). The injected adenovirus holds the gene that codes for the spike protein specifically found on the SARS-CoV-2 virus and promotes a specific immune response responsible for copying the coronavirus spike protein. Hence, irrespective of the vaccine, the immune system of the vaccinated individual, when exposed to coronavirus infection, will recognize and attack the virus (1–6).
Many expert medical groups recommend that most patients with cancer or a history of cancer should get a COVID-19 vaccine; however, data on vaccination rates in patients with active cancer is still limited and controversial. Although people with cancer or with a history of cancer are encouraged to vaccinate, the benefit-risk ratio of doing so should be judged based on many factors, such as the type of vaccine, the type of cancer a person has or has had (solid or haematological cancer), the stage of cancer (“in situ”, incipient or metastatic), the management (patient still being treated for cancer or a past treatment; surgical treatment, chemotherapy or irradiation) and the potential impairment of immune response (1–6).
It seems that patients with certain cancers may have a weaker response to COVID-19 vaccines. The Center for Disease Control (CDC) recommends that people with malignancies such as blood cancers (leukaemia, lymphoma or multiple myeloma) get an additional vaccine dose to improve their response to a primary vaccine series and to ensure adequate protection against COVID-19 (1–7).
COVID-19 and changed care delivery in cancer patients
Despite the challenges experienced during the pandemic, the global oncology community has promptly responded and changed care delivery for cancer patients. The reorganization prompted by hospital visit restrictions, delayed screenings and delayed diagnostic appointments reinforced the role of virtual consultations. Thus, in early 2020, telehealth became popular inpatient care in a variety of different areas—particularly in oncology—with high overall satisfaction (3, 8).
In addition, the rapid development of COVID-19 registries allowed an increased understanding of the medical history, risk factors, and outcomes of patients with cancer who were then diagnosed with COVID-19 (3, 8). 14 major registries, including up to 28,500 patients with cancer and COVID-19 exist, providing new insights into the management of oncology patients (7). Among the first registries developed for cancer and COVID-19 patients, COVID-19 and Cancer Consortium (CCC19) stands out due to it being a public initiative that originated on Twitter, aiming to analyze different factors associated with short-term and long-term clinical decision-making and outcomes of COVID-19 and cancer treatment modifications related to coronavirus infection (7).
Impact of COVID-19 on people with HIV/AIDS
In 2018, there were 175 million people living with HIV worldwide (9, 10). COVID-19 has made it difficult for these people to access the necessary treatments. Key resources, including diagnostic platforms, community outreach programs, medical care access and research infrastructure have been built up over decades for the control of HIV but have now been redirected to control COVID-19 (8).
About 28,000 HIV community health workers were deployed to assist with COVID screening and testing referrals. HIV outreach, therefore, had to be halted in 993 vulnerable, high-density, poor communities (8).
In many countries in Africa, medication is not being received. In South Africa, 10,950 HIV patients in one province have not collected their medications on schedule since the start of the national lockdown (8). In Zimbabwe in 2020, roughly 19% of HIV patients trying to get a refill of antiretroviral medication either could not get a refill or could only get a partial refill. In Kenya and Nigeria in 2020, 14% weren’t able to get their medication (9). In May 2020, the World Health Organization (WHO) surveyed 5 out of 13 sub-Saharan African countries and found that antiretroviral therapy (ART) stock availability for major first-line drugs was 3 months or less. One major reason for this was the inability of suppliers to deliver on time (9). The WHO estimated that a 6-month-long disruption of ART could lead to 500,000 more AIDS-related deaths in 2021 (8). An interruption across 50% of the population of HIV patients would most likely lead to a 63 times increase in HIV-related deaths in a 1-year period, compared with HIV-related death without disruption. This interruption could also potentially lead to an increase in mother-to-child transmission by 6 times (9). These mortality rates would completely reverse the 33% reduction in AIDS-related deaths from 2010 to 2018 (8). In addition to this, interruptions to the supply of other drugs like co-trimoxazole and the suspension of HIV testing would increase HIV-related deaths by 6 times (9). Overall, COVID-19 and HIV both demonstrate a disproportionate burden on already vulnerable populations experiencing poverty and other systemic stressors (10).
Impact of COVID-19 on people with disabilities
15% of the world’s population has at least one form of disability. Of that 15%, 80% are in developing countries. In 2020, the SARS-CoV-2 virus caused a pandemic that resulted in many countries needing a response plan and resources to mitigate the effects. As of 30 June 2020, the WHO had listed 63 countries that needed technical and financial support in implementing their response plan. All these countries are developing countries, which have the greatest percentage of people with disabilities (PWD) in the world. It wasn’t a surprise that a lot of minority groups, including PWD, would be disadvantaged by the pandemic, especially because the virus seemed initially to be most deadly to the elderly, so priority in communication, treatment and general response was given to the elderly.
Responses to a survey conducted in the early stages of the pandemic highlight the public’s view on this matter. ‘While knowledge of COVID-19 was generally low at the time of the survey, people with disabilities felt there had been little effort from governments and the media to consider or meet their specific needs, based on the information that was available. Families expressed the sentiment that, although there had been attention paid to the provision of information about the risks to older people, people with disability had been overlooked. There was a general feeling within respondents’ comments that people with disabilities are a low priority in public responses to crises, a sentiment borne out by the federal government’s demonstrable lack of attention to the intersection of disability and pandemic planning’ (10).
People with disabilities suffer social injustice and discrimination that has only been heightened by the pandemic and its subsequent response. A study done in four South American countries to measure the degree of disability inclusiveness in government responses show us the various inadequacies in considering this minority group. For instance, the Explicit Guarantees in Health (GES) programme in Chile, which removes financial barriers of access to health for people diagnosed with certain chronic conditions, was suspended for one month, without a strategy to ensure continued access to healthcare (12).
The suspension of this programme, no matter for how long, shows the level of consideration given to PWD. This is shown by the fact that some weren’t financially able to access healthcare and even those who were financially capable had appointments postponed or ultimately cancelled. ‘Furthermore, none of these four countries acknowledged the extra costs associated with disability, and how these might be further increased as a result of the pandemic (for example, due to the need to buy antiseptic products and face masks, or due to the inability to access usual ways of support)’ (12).
A further example is the way in which Australia failed to even include people with disabilities in their initial response plan, and a disability-specific COVID-19 response plan was not implemented in Australia until April 2020 (11).
These are just a few instances that show the injustice faced by PWD during the COVID-19 pandemic. Although this shows the discrimination against people with disabilities, it limits the examples to a few countries out of possibly more than 180 affected by the virus
and, therefore, does not give an appropriate measure of discrimination faced by PWD globally.
Another impact of COVID-19 on PWD was job loss. ‘Fewer USUS persons with a disability were employed in 2020 with a total employment rate of 17.9%, down from 19.3% in 2019, according to data from the US Bureau of Labor Statistics (BLS). That translated to an unemployment rate of 12.6% for persons with a disability, the highest such mark in seven years. The decline amounts to a 5.3 percentage point increase year over year, compared to a 4.4 percentage point increase year over year for persons without a disability, who experienced an unemployment rate of 7.9% last year, up from 3.5% in 2019’ (13). The growth in unemployment rate for PWD contrasted against that for people without disabilities not only shows the impact COVID-19 had on their employment status but also shows further discrimination, possibly due to unfounded and ignorant assumptions made about their capability or usefulness in the workplace. Organizations were then more likely to lay them off first. Losses in jobs would also cause a reduction in income and standard of living for PWD.
Looking more closely at younger PWD and all those still involved in the education sector, we see that again PWD were left at a disadvantage when it came to schooling. The lockdown pushed schools to learn online. Students without disabilities found it hard to learn, but students with disabilities, especially intellectual disabilities, were further disadvantaged because the educational support they needed was reduced or completely stopped.
A survey conducted in Australia showing the feelings of people with disabilities and their families provides proof of earlier claims (14). However, this survey only shows responses by a few families in Australia and does not include a more diverse group. Furthermore, the survey produced qualitative responses by family members, with no empirical evidence to support it. It is important to note that people with disabilities, across all spectrums of ages, were impacted by the COVID-19 pandemic in more ways than mentioned above.
The COVID-19 pandemic has dramatically changed the healthcare landscape worldwide. It encouraged a timely shift from routine emergency care to chronic care and demanded a massive mobilization of resources to inform the management of and research into SARS-CoV-2 infection, particularly with a view to the ways it has affected the treatment of chronic conditions such as cancers.
Interferences between COVID-19 and cancers are extensively documented across the literature on multifaceted cancer management and encompass postponed screenings, delayed diagnoses, overdue treatments, delayed routine monitoring appointments, and limited access to psychosocial resources. The concerted efforts of healthcare providers, international cancer societies and professional associations are essential in improving the management of cancer outcomes during the ongoing pandemic.
It is more than evident that COVID-19 has also negatively affected patients suffering from other illnesses globally due to varied factors. In order to reduce this impact, it is necessary to ensure continued progression as a society and to better prepare for any other occurrences that could potentially shut down vital global activities.
The world has progressed so much over the past century with medical care, but COVID-19 threatens to reverse that progress. It would be detrimental to the treatment of other diseases to continue to place COVID-19 needs above all others. While it’s understandable for some nurses and doctors to focus on COVID-19, other diseases and their care should not be neglected. Non-COVID patients should have staff dedicated to their wellbeing.
- Li Y, Wang X, Wang W. The Impact of COVID-19 on Cancer. Infect Drug Resist. 2021;14:3809-3816; https://doi.org/10.2147/IDR.S324569
- Richards M, Anderson M, Carter P et al. The impact of the COVID-19 pandemic on cancer care. Nat Cancer 1, 565–567 (2020). https://doi.org/10.1038/s43018-020-0074-y
- Edge R, Meyers J, Tiernan G, Li Z, Schiavuzzi A, Chan P, et al. (2021) Cancer care disruption and reorganization during the COVID-19 pandemic in Australia: A patient, carer and healthcare worker perspective. PLoS ONE 16(9): e0257420. doi.org/10.1371/journal.pone.0257420
- Broom A, Kenny K, Page A, et al. The Paradoxical Effects of COVID-19 on Cancer Care: Current Context and Potential Lasting Impacts; Clin Cancer Res November 15 2020 (26) (22) 5809-5813; DOI: 10.1158/1078-0432.CCR-20-2989
- Kuderer NM, Choueiri TK, Shah DP, et al. Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study. Lancet. 2020;395(10241):1907-1918.
- Sharpless NE. COVID-19 and cancer. Science. 2020;368(6497):1290.
- Desai A, Mohammed TJ, Duma N, Garassino MC, Hicks LK, Kuderer NM, Lyman GH, Mishra S, Pinato DJ, Rini BI, Peters S, Warner JL, Whisenant JG, Wood WA, Thompson MA. COVID-19 and Cancer: A Review of the Registry-Based Pandemic Response. JAMA Oncol. 2021 Sep 2. doi: 10.1001/jamaoncol.2021.4083. Epub ahead of print. PMID: 34473192.
- Chenneville, Tiffany, et al. “The Impact of Covid-19 on HIV Treatment and Research: A Call to Action.” MDPI, Multidisciplinary Digital Publishing Institute, 24 June 2020, https://www.mdpi.com/1660-4601/17/12/4548/htm
- Jewell, Britta L, et al. “Potential Effects of Disruption to HIV Programmes in Sub-Saharan Africa Caused by Covid-19: Results from Multiple Mathematical Models.” The Lancet HIV, Elsevier, 6 Aug. 2020, https://www.sciencedirect.com/science/article/pii/S2352301820302113.
- Karim, Quarraisha Abdool, et al. “Covid-19 Affects HIV and Tuberculosis Care.” Science, 24 July 2020, https://www.science.org/doi/full/10.1126/science.abd1072.
- Dickinson, H., Smith, C., Yates, S., & Tani, M. (2021). The importance of social support in education: survey findings from students with disability and their families during COVID-19. Taylor and Francis Online, 1.
- Sakellariou, D., Malfitano, A. P., & Rotarou, E. S. (2020). Disability inclusiveness of government responses to COVID-19 in South America: a framework analysis study. International Journal for Equity in Health, 7.
- Golden, R. (2021, March 2). 2020 marked a 7-year high unemployment rate for people with disabilities. Retrieved from hrdive: https://www.hrdive.com/news/2020-marked-7-year-high-unemployment-rate-for-peopl e-with-disabilities/595959
- Yates, S., & Dickinson, H. (2021). Navigating Complexity in a Global Pandemic: The Effects of COVID-19 on Children and Young People with Disability and Their Families in Australia. Public Administration Review, 2.