Keywords
Cancer - COVID-19 - novel coronavirus - oncology
Introduction
On March 11, 2020, the World Health Organization (WHO) characterized the novel coronavirus
(COVID-19) outbreak a global pandemic.[1] This was dated back to the advent of a mysterious outbreak of atypical pneumonia
in December 2019, which was traced to a seafood wholesale market in Wuhan of China.
Over the past 3 months, the COVID-19 has captured global media, political, as well
as scientific attention. There have been various publications on the epidemiological
and clinical features of the infection. This review article attempts to highlight
the latest update of the COVID-19 infection and explore any potential implications
with particular reference to cancer patients though the data have been limited and
fragmented.
Epidemiology
Four strains of coronaviruses (CoVs) are known to spread easily in humans, causing
generally mildly acute respiratory illnesses known as common cold.[2] A much larger number of CoVs have been detected in animals, particularly bats, but
have not been found in humans.[3]
On December 31, 2019, the Wuhan Municipal Health Commission announced a cluster of
cases of viral pneumonia of unexplained etiology. The Southern China Seafood Wholesale
Market in Wuhan was suspected to be related to the first 27 pneumonia patients without
identified pathogenic agents that were reported in the late December 2019.[4] Most of these early patients were reportedly either shop owners, largely in the
West District of Southern China Seafood Wholesale Market, or people who visited the
market before the symptom onset. This market is a large open complex of 50,000 sqm
including various sections with some selling a wide variety of live wild animals for
consumption. Environmental disinfection of the Southern China Seafood Wholesale Market
was initiated on December 30, 2019.
The novel CoV, known as 2019-nCoV at that time, was officially identified as the cause
of the disease outbreak in Wuhan on January 9, 2020. Following this official announcement
of genetic sequence of the virus, 41 laboratory-confirmed cases with pneumonia were
reported in Wuhan, among which the earliest known case had disease onset dated December
8, 2019.[5] At that time, approximately 70% of these first 41 confirmed patients were reported
to have exposure to the Southern China Seafood Wholesale Market.[6]
On January 13, 2020, Thai health authorities reported an imported case in a person
in his 60s who had traveled from Wuhan. This patient did not visit the Southern China
Seafood Wholesale Market but reported visiting another wet market in Wuhan. On January
16, 2020, Japanese health authorities reported a confirmed imported case in a person
in his 30s who had traveled from Wuhan and landed in Kanagawa on January 6, 2020.
This person had not visited any wet market in Wuhan but had visited a close relative
who was in hospital with pneumonia in Wuhan. Subsequently, an exported case to Seoul
in South Korea was reported on January 20, 2020, with no prior history of visiting
any wet markets in Wuhan or any contact with any confirmed patient. The lack of exposure
history to wet markets in the generally mild exported cases indicated that there might
be a larger number of undetected infections in Wuhan.[7] On January 18, 2020, the National Health Commission taskforce was established, and
while there was increasing number of new infections in Wuhan, there were travelers
coming from Wuhan, diagnosed as confirmed patients in Beijing, Shenzhen, with further
exported cases reported in Taiwan and the United States on January 21, 2020. Given
the cases reported outside Wuhan have mostly not been severe, it was inferred that
there might be a large number of undetected relatively mild infections in Wuhan.[7] The outbreak was declared a Public Health Emergency of International Concern on
January 30, 2020.[1] The WHO further announced a name for the new CoV disease: COVID-19 on February 11,
2020.[1]
Diagnostic Criteria and Clinical Features
Diagnostic Criteria and Clinical Features
While the case definition for the initial first batch of 41 laboratory-confirmed patients
was not officially published, it was understood that the initial case definition required
(i) fever, (ii) chest X-ray evidence of pneumonia, (iii) normal or low white cell
count or low lymphocyte count, (iv) antibiotic treatment for 3 days without improvement,
(v) history of recent visits to Wuhan with direct or indirect exposure to a wet market,
and (vi) a respiratory specimen positive for 2019-nCoV and confirmed as 2019-nCoV
by whole-genomic sequencing.[7]
In a study of a family cluster of six patients who traveled from Wuhan from Shenzhen
during December29, 2019, and January 4, 2020, five family members were identified
infected with the virus. In addition, one family member who did not travel to Wuhan
became infected with the virus after several days of contact with four of the family
members. None of the family members had contacts with Wuhan markets or animals, although
two had visited a Wuhan hospital. Five family members (aged 36–66 years) presented
with fever, upper or lower respiratory tract symptoms, or diarrhea or a combination
of these 3–6 days after exposure. They presented to The University of Hong Kong -
Shenzhen Hospital 6–10 days after symptom onset. They and one asymptomatic child (aged
10 years) had radiological ground-glass lung opacities. Older patients (aged >60 years)
developed more systemic symptoms, extensive radiological ground-glass lung changes,
lymphopenia, thrombocytopenia, increased C-reactive protein, and lactate dehydrogenase
levels. The nasopharyngeal or throat swabs of these six patients were negative for
known respiratory microbes by point-of-care multiplex reverse transcription-polymerase-chain
reaction (RT-PCR), but five patients (four adults and the child) were RT-PCR positive
for genes encoding the internal RNA-dependent RNA polymerase and surface spike protein
of this novel CoV, which were confirmed by Sanger sequencing. Phylogenetic analysis
of these five patients' RT-PCR amplicons and two full genomes by next-generation sequencing
showed that this is a novel CoV, which is closest to the bat severe acute respiratory
syndrome (SARS)-related CoV found in Chinese horseshoe bats. This supports person-to-person
transmission of this novel CoV in hospital and family settings, and the reports of
infected travelers in other geographical regions.[8] Similar findings were supported by a study of 1099 patients with laboratory-confirmed
COVID-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities
in China through January 29, 2020. Ground-glass opacity was the most common radiological
finding on chest computed tomography (CT).[9]
Rapid Detection and Adequate Control
Rapid Detection and Adequate Control
Rapid and accurate detection of the COVID-19 is crucial in controlling the outbreak
in the community and hospitals. Nasopharyngeal and oropharyngeal swabs are recommended
upper respiratory tract specimen types for COVID-19 diagnostic testing. However, the
collection of these specimen types requires close contact between healthcare workers
and patients, which poses a risk of transmission of the virus to the healthcare workers.
Furthermore, the collection of nasopharyngeal or oropharyngeal specimen causes discomfort
and may cause bleeding, especially in patients with thrombocytopenia.[8] Thus, nasopharyngeal or oropharyngeal swabs are not desirable for serial monitoring
of viral load. Sputum is a noninvasive lower respiratory tract specimen, but only
28% of patients with COVID-19 in one case series could produce sputum for diagnostic
evaluation.[10]
Saliva specimens can be provided easily by asking patients to spit into a sterile
bottle. This noninvasive collection of the saliva can greatly minimize the risk of
exposing any healthcare workers to the COVID-19. In Hong Kong, the COVID-19 testing
was performed by Public Health Laboratory Services Branch in Hong Kong for patients
who fulfilled the reporting criteria or enhanced surveillance criteria.[11] Saliva was collected by asking the patients to cough out saliva from their throat
into a sterile container, and 2 ml of viral transport medium was added. The COVID-19
virus was detected in the self-collection saliva of 91.7% (11/12) of the patients
with the serial saliva viral load monitoring showing generally a decline trend.[12] This has allowed specimen collection outside the hospitals, where airborne-infection
isolation rooms are not available, and the elimination of waiting time for specimen
collection, thus leading to sooner availability of the results.
COVID-19 and Cancer
Like both SARS-CoV and MERS-CoV infections, the risk of severe disease increases substantially
with age and with the presence of underlying conditions.[7], [13], [14], [15] In the study of the family cluster treated in Shenzhen, the three oldest patients
in the family with comorbidities had more severe systemic symptoms of generalized
weakness and dry cough. As expected, they might have decreased total white blood cell,
lymphocyte, or platelet counts, with also extended activated thromboplastin time and
increased C-reactive protein level. Their lung involvement was also more diffuse and
extensive than those of the younger patients.[8] Higher mortality rate was also associated with baseline multiple comorbidities with
the first death from the COVID-19 in Hong Kong for a 39-year-old relatively young
man but known history of long-standing diabetes mellitus.[10], [16] While cancer is a prevalent disease and a global health challenge, little information
is available with regard to implications of COVID-19 for cancer patients. So far,
the data have been limited and fragmented.
Higher risk of complications and severe events of COVID-19
There was one relatively cancer-focused comment by Liang et al. in The Lancet Oncology; sharing of 1590 patients confirmed with COVID-19, 18 patients
had a history of cancer. Lung cancer was the most frequent type (28%, 5/18 patients).
Four (25%) of 16 patients (2/18 having unknown treatment status) with cancer and COVID-19
had received chemotherapy or surgery within the past month at the time of diagnosis,
and the other 12 (75%) patients were cancer survivors in routine follow-up after primary
definitive surgery. In this relatively small sample of cancer patients with COVID-19,
compared with patients without any cancer, those COVID-19 patients with cancer were
older (mean age 63.1 vs. 48.7 years), more likely to have a smoking history (22% 4/18
patients vs. 7% 107/1572 patients), and more severe baseline CT manifestation (94%
17/18 patients vs. 71% 1113/1572 patients). Furthermore, cancer patients with COVID-19
were observed to have a higher risk of severe events (a composite endpoint defined
as the percentage of patients being admitted to the intensive care unit requiring
invasive ventilation, or death) compared with patients without cancer (39% 7/18 patients
vs. 8% 124/1572 patients; Fisher's exact P = 0.0003).[17] Indeed, this sample size is relatively small with much heterogeneity within the
cancer population with COVID-19 in the cohort as different primary cancer types will
have different biological behaviors with highly variable disease courses (0–16 years)
and diverse treatment strategies. This will not be an ideal representation of the
whole cancer population with COVID-19 confirmation. Thus, any conclusions that generalize
to all cancer patients with respect to COVID-19 should be interpreted with caution
until we have sufficient prospective data with in-depth study of this subset of population.[18]
Greater challenge for prompt diagnosis of cancer, especially lung cancer
While the current data seemed to echo patients with underlying diseases including
background of cancer would have higher risk of a protracted course of the COVID-19
and higher risk of severe events, the background radiological features of COVID-19
may also be a confounding factor making diagnosis of cancer, especially lung cancer
more difficult and challenging. The diagnosis and treatment of lung cancer patients
have been challenged greatly because of extraordinary public health measures since
the lung cancer patients are part of the high-risk population during the COVID-19
outbreak period.[19] Vigilant protection for lung cancer patients is needed to avoid infection. In the
background of COVID-19, lung cancer patients are difficult to differentiate from the
patients with COVID-19 in terms of clinical symptoms, which may bring extra challenge
to the clinical diagnosis and management of lung cancer patients, with potential additional
physical and psychosocial unmet needs of the lung cancer patients.
The dilemma to treat or not to treat or wait and see
While Liang et al. have demonstrated that cancer patients are prone to have increased risk of severe
infection,[17] many cancer patients or even their carers may prefer to delay their cancer treatment
during the time of the COVID-19 epidemic in line with social distancing and to reduce
the exposure to high-risk area such as clinics and hospitals. Some may opt to withhold
or delay their treatment with the fear and anxiety for COVID-19 and its complications,
while the risk of disease progression with no timely treatment or dose intensity of
treatment being compromise in the course of anticancer treatment will make the issue
more complicated and controversial. Though the current data is limited, there has
been a case report published by our Chinese colleagues recently on a patient with
advanced adenocarcinoma of the lung progressed after gefitinib and EGFR T790M detected
with osimertinib started since September, 2017, was also diagnosed with COVID-19 confirmed
with throat swab for COVID-19 on real time reverse transcription-polymerase-chain
reaction (RT-PCR) on 26th January, 2020, he was treated with cocktail therapy for
his COVID-19 with cefoselis, oseltamivir, meropenem, teicoplanin and moxifloxacin
while continuing his lung cancer treatment with osimertinib. Follow-up CT showed stable
disease for both the lung cancer and radiological improvement for the COVID-19.[20] Of course, this is an illustration demonstrating continuation of anti-cancer treatment
in a patient with good performance status and good baseline clinical condition at
the diagnosis of COVID-19, yet in the era of personalize cancer medicine and precision
oncology, further prospective studies are in urgent need to see if this can be generally
applied to all cancer patients with all clinical subtypes or that there are potential
specific predictive, prognostic clinical factors or biomarkers to help us to make
an informed personalised clinical decision for the best benefit of the patients.
Same should be applied with patient-oriented clinical strategies for treating pediatric
cancer during the outbreak of COVID-19 as children with cancer are assumed to be more
susceptible to COVID-19. A reasonable treatment strategy between epidemic prevention
and anticancer therapy under the current epidemic conditions needs to be well planned
with multidisciplinary approach. Strict implementation of prevention and protective
measures for both healthcare workers and patients, the engagement of hand hygiene,
medical waste management, and other hospital infection control work should be enforced.[21]
Stepping up infection control measures to prepare for potential community outbreak
and to ensure continuity of quality cancer care
While the outbreak of COVID-19 is spreading rapidly, public health experts have been
advising for “social distancing” and strengthening the control of “personnel mobility.”
With the limited resources of personal protective equipment and the ever-increasing
demand by all healthcare workers across all countries, various healthcare organizations
have been trying to postpone elective or nonurgent follow-up appointments for cancer
patients, especially the cancer survivors, to space out the human flow. This has also
been seen in other nononcology departments and clinics, and this may delay diagnosis
of some newly presented cancer patients or missing to address to active complaints
of those who have been stable, including cancer survivors.
Yet, to balance equal access to treatment and to minimize the unnecessary human-to-human
transmission, and with the understanding that the COVID-19 has rapidly emerged as
a global health threat which will remain as a global health challenge to all of us
for a while, the initiative to step up infection control measures in individual departments
or clinics, especially for those serving high-risk patients such as cancer centers,
should be seriously considered. This has been started in nononcology departments such
as the stepping up of infection control in ophthalmology to minimize COVID-19 infection
of both healthcare workers and patients.[22] We hope through the stepping up infection control measures for COVID-19 infection
in all cancer centers could help all oncologists locally and globally to prepare for
any potential community outbreak in the current fight of the global pandemic. Furthermore,
all medical oncologists should work closely with all disciplines, especially the local
infection control teams to implement the most optimal infection control measures appropriate
for individual clinical setting through our conventional “multidisciplinary team approach”
(MDT).
Relieving distress for cancer patients and their carers
Distress is the sixth vital sign for all cancer patients and their carers. While screening
for distress is one way to measure psychological dimensions of cancer patients' experiences,
and doing so is increasingly part of standard operations,[23] addressing the extra distress among cancer patients in the era of COVID-19 pandemic
is of paramount importance. Indeed, since appearance of COVID-19 which has now progressed
to a global pandemic, there has been flurry of scientific activity and publication
surrounding this novel agent, further igniting serious cross-cutting media, as well
as scientific and political debate as the more we know, the more we know how much
we do not know. Reporting of the situation in real time from the public on social
media could lead to more accurate collating of information by the media. Yet, the
rapid pace of developments, increasing case detection rates, along with increasing
diversity of information with information overload, may make the general public, especially
cancer patients and their carers who understand they are of higher health risk, difficult
to assimilate all these information, or difficult to make any meaningful interpretations
from all the resources. The inability to validate information in a timely manner can
fuel speculation and making the audience, especially the cancer patients more anxious
with more media and public concern. It is recommended that the media should focus
on having altruistic intentions and develop dialog with the appropriate experts and
authorities to protect global heath security through effective amiable partnership
and collaboration.
Perhaps, on top of social distancing and the advocacy of continuous vigilance, seamless
communication with compassion and care is equally important for our cancer patients,
especially this time of the year with the challenge of COVID-19. While hospital or
clinic visits are delayed for some of the patients due to the COVID-19, additional
psychosocial support or psychological counseling through the cyberspace or telephone
calls dedicated for cancer patients should be considered.[24] This would certainly help to maintain the general well-being of our cancer patients
and their carers, physically, mentally, psychosocially, and spiritually.
Combating COVID-19 With “COVID”
Combating COVID-19 With “COVID”
While much work needs to be done to study the specific unmet needs of cancer patients
with the challenge of the COVID-19, be it at the patient level or at the healthcare
management level, from diagnosis to treatment and follow-up, prevention is always
better than cure. Prevention of the COVID-19 is equally important as cancer prevention.
With that, vigilant infection control measures should be enforced continuously, and
public health education and engagement should be highly recommended. At the time of
writing of this manuscript, the WHO has just declared the COVID-19 as a global pandemic;
we anticipate second and even third wave of the infection may come if we lose our
vigilance. We propose to join hands together to combat against COVID-19 with some
simple tips for our cancer patients raise their awareness of this public health challenge
– combating against COVID-19 with “COVID:”
-
Continue “social distancing”
-
Omit unnecessary face-to-face meeting or meal gathering or mass event, make use of
cyber meeting and bring one's own lunch box to work
-
Visage protection, i.e. universal precaution with surgical masks when going out in
a large crowd such as public transport or any close contact in high risk area
-
Infection control of the hands with hand hygiene at all times and
-
Diet, lifestyle, and exercise continue to be balanced and healthy.
