Keywords
cancer - congregation - coronavirus disease 2019 - outcomes - RT-PCR negativity
Introduction
As novel coronavirus disease 2019 (COVID-19) pandemic is worsening, newer challenges
are also emerging. People living in congregations such as long-term care facilities
and dormitories are at increased risk of infection as norms of social distancing are
not executional.[1]
[2]
[3] Malignancy is a major risk factor for COVID-19-related mortality.[4]
[5] Congregation of large number of people on ships (e.g., Diamond Princess ship) face
difficulties in mobility and limited access to sanitation, drinking water, and food
supply makes them more vulnerable.[6]
[7] Cancer care during this pandemic is challenging.
Objective
Indian data on cancer patients with COVID-19 infection and its outcome are limited.
Infectivity and outcome among cancer patients staying in large congregations are not
known. We conducted this study to address this lacuna in literature and present our
experience in managing these patients who lived together and shared common areas of
sanitation and food. We analyzed the factors associated with mortality.
Methods
Study Design
This was a retrospective–prospective observational study conducted in a tertiary care
center at New Delhi after ethical approval.
Hospital Policy
After April 1, 2020, all patients were admitted to a separate screening (new admission)
ward. All such patients underwent screening for COVID-19. After negative results,
patients were shifted to specialty wards. Positive patients were shifted to designated
COVID-19 hospital.
Patient Population
In the 1st week of May 2020, one admitted cancer patient (who was initially negative
for COVID-19 in the screening ward) to the cancer ward was detected to have COVID-19
during evaluation for fever. Subsequently, screening was done for all admitted patients
and health-care workers (HCWs). Patients were congregated in one ward with three cubicles
and one common hall; they shared common areas of dining, wash rooms, and utility areas.
All patients were provided with triple layer face masks and regular briefing was done
for adherence. Patients were asked for compliance of use of face masks after the outbreak.
Details of the past treatment were assessed. Eastern Cooperative Oncology Group performance
status (PS) scale was used to assess the PS.
Investigations and Diagnosis
COVID-19 diagnosis was established by reverse transcription-polymerase chain reaction
(RT-PCR) of nasopharyngeal and oropharyngeal swabs. All basic investigations were
done on admission to COVID-19 ward (at designated hospital) that included complete
blood count, renal function test, liver function test, lactate dehydrogenase (LDH),
D-Dimer, C-reactive protein (CRP), ferritin, and chest X-ray. We analyzed the time
duration of RT-PCR positivity. Time was calculated from the date of the first positive
report till the date of negative report. RT-PCR was conducted weekly.
Prophylaxis and Treatment
Hydroxychloroquine (HCQ) prophylaxis was given to HCWs. All symptomatic COVID-19 cancer
patients were treated with HCQ and azithromycin as per the Indian Council of Medical
Research guidelines.[8]
[9] Grades 3 and 4 neutropenic patients were treated with granulocyte colony stimulating
factor (G-CSF) and prophylactic antibiotics as per institutional policy.
Health-Care Workers
As a policy and high-risk environment, HCWs used N-95 masks. None of them used complete
personal protective equipment (PPE) including hazmat suit and face shield (PPE). Preexposure
prophylaxis with HCQ was advocated to all HCWs.
Statistics
We analyzed clinical, laboratory parameters, and outcome of these patients. Demographics
and other variables were entered as per pro forma (Appendix). STATA version 16 (Texas,
United States) software was used to analyze the data. Descriptive statistics was used
for analysis of variables. Patients were grouped in curative and palliative intent
for analysis. Fisher’s exact test was applied for deriving association between variables.
Results
Baseline characteristics of patients are depicted in [Table 1]. Twenty-eight percent of patients had hematolymphoid malignancies. Three patients
were admitted in January 2020, 10 patients in March 2020, and remaining 19 were admitted
in April 2020. The last admission was done on April 30, 2020. Ten patients stayed
for 1 day and one patient stayed for 2 days in the screening ward before their transfer
to the oncology ward. They all were negative at the time of admission in the cancer
ward. One patient was admitted 1 day prior to the outbreak and became positive on
D+3 of admission.
Table 1
Baseline characteristics (n = 32)
|
Variable
|
n (%)
|
|
Abbreviations: CLL, chronic lymphocytic leukemia; CNS, central nervous system; COVID-19,
coronavirus disease 2019.
|
|
Age, median (range)
|
37.5 (16–64)
|
|
Sex
|
|
|
Male
|
32 (100)
|
|
COVID-19
|
|
|
Symptomatic
|
10 (31)
|
|
Asymptomatic
|
22 (69)
|
|
Cancer subtype
|
|
|
Hodgkin lymphoma
|
6 (18.75)
|
|
Sarcoma (bone and soft tissue)
|
6 (18.75)
|
|
Colon cancer
|
3 (9.37)
|
|
Germ cell tumor
|
3 (9.37)
|
|
Rectal cancer
|
2 (6.25)
|
|
Non-Hodgkin lymphoma
|
2 (6.25)
|
|
Lung cancer
|
2 (6.25)
|
|
Head and neck cancer
|
2 (6.25)
|
|
Stomach cancer
|
1 (3.12)
|
|
CNS tumor
|
1 (3.12
|
|
Gastrointestinal stromal tumor
|
1 (3.12)
|
|
Renal cell carcinoma
|
1 (3.12)
|
|
Periampullary region cancer
|
1 (3.12)
|
|
CLL (refractory to 3 lines)
|
1 (3.12)
|
|
Intent
|
|
|
Curative
|
18 (56)
|
|
Palliative
|
14 (44)
|
|
Type of palliative treatment (n = 14)
|
|
|
Chemotherapy
|
11 (78)
|
|
Best supportive care
|
5 (22)
|
All 32 admitted patients were tested positive for COVID-19 by RT-PCR. On the day of
the outbreak, 24 patients were positive and the rest became positive after 1 week.
The intent of treatment was curative and palliative in 18 (56%) and 14 (44%) patients,
respectively. About 60% of patients received their last chemotherapy within 10 days
prior to COVID-19 detection. Clinically, 10 (31%) patients had symptomatic COVID-19.
The most common symptom was fever (n = 7.70%). Cough, breathlessness, altered taste, and smell were present in three (30%)
patients each. Two (6.25%) patients had features of critical COVID-19.
Majority of the patients had hemoglobin levels of more than 10 g/dL (62.5%). Leukopenia
(total leukocyte count <4000/μL) was seen in 37.5% of cases; Grades 4, 3, 2 and 1
neutropenia were seen in 12.5% each. Grade 3 and 4 neutropenic patients received G-CSF
and prophylactic antibiotics. Lymphopenia (absolute lymphocyte count <1500/μL) was
found in 78% of cases. Other abnormal findings were high LDH (90%), high serum ferritin
(81%), and high CRP (25%). Two patients had typical radiological features of viral
pneumonia.
Eight patients received treatment with HCQ and azithromycin. They became asymptomatic
in 4 days with no cardiac toxicity. Total five patients died ([Table 2]). Three patients had features of progressive disease with poor PS lacking any definitive
evidence suggestive of severe or critical COVID-19 and one patient committed suicide
by hanging. Of 2 critical COVID-19 cases, one patient survived and one succumbed COVID-19.
Three fatal outcomes were observed in palliative/best supportive care patients ([Table 2]). When death was analyzed for intent of treatment, palliative intended patients
had more probability of death as compared with curative intended patients (4 vs. 0
deaths, p = 0. 027 Fisher’s exact) after excluding patient whose cause of death was suicide.
Table 2
Clinical and laboratorial parameters in patients with fatal outcome
|
Sr. no
|
Disease
|
Stage treatment received
|
ECOG PS
|
Age (y)
|
ALC (µ/dL)
|
NLR
|
Serum LDH (U/L)
|
Serum ferritin (µg/L)
|
Serum albumin (g/dL)
|
Cause of death
|
|
Abbreviations: ALC, absolute lymphocyte count; ASCT, autologous stem cell transplantation;
CLL, chronic lymphocytic leukemia; COVID-19, coronavirus disease 2019; CT-RT, chemotherapy
radiotherapy; ECOG PS, Eastern Cooperative Oncology Group performance status; LDH,
lactate dehydrogenase; NLR, neutrophil/lymphocyte ratio; NPC, nasopharyngeal carcinoma.
|
|
1
|
Refractory CLL
|
Relapsed/refractory post ibrutinib, R-CHOP
|
2
|
33
|
400
|
1.5
|
312
|
1,460
|
2.8
|
COVID-19
|
|
2
|
NPC
|
Stage IV post CT-RT, palliative chemotherapy
|
4
|
37
|
330
|
5.16
|
402
|
1,314
|
3.6
|
Not related to COVID-19
|
|
3
|
Hodgkin lymphoma
|
Relapse/refractory post two lines ASCT and nivolumab
|
4
|
25
|
816
|
3.1
|
459
|
1,496
|
2.6
|
Not related to COVID-19
|
|
4
|
Pancreatic cancer
|
Stage IV, post single agent
Gemcitabine (1 cycle)
|
4
|
53
|
760
|
1.5
|
356
|
1,631
|
2.9
|
Not related to COVID-19
|
|
5
|
Lung cancer
|
Stage IV, post multiple lines
|
2
|
31
|
550
|
–
|
272
|
1,287
|
3.7
|
Suicide
|
Median time for RT-PCR to become negative was 18.5 days (range: 9–40). Relationship
of time taken for RT-PCR negativity to duration (days) is depicted in [Fig. 1]. At day 30, patients with hematolymphoid malignancies had more RT-PCR positivity
as compared with solid tumors (n = 3/7 vs. 0/22, p = 0.02 Fisher’s exact). After excluding deaths, (n = 3/5 versus 0/19), p-value remained 0.01.
Fig. 1 Coronavirus disease 2019 negativity rate in relation to days by reverse transcription-polymerase
chain reaction.
Two medical oncologists, four resident doctors, six nurses, and four paramedical staff
were working in the cancer ward on rotational duties. They were using N-95 masks and
none of them wore Hazmat suits and face shields during the patient care. Among HCWs,
those who had close and prolonged contact had contracted infection (5 out of 16).
On subsequent screening, all doctors remained negative, two nursing staff were positive,
and three out of four paramedical staff became positive. All RT-PCR-positive HCWs
were asymptomatic. Only two HCWs used HCQ preexposure prophylaxis.
In the cancer ward, patients shared a common wash room and sanitation area. Dining
room was common for all these patients. Twenty-four-hour consistent use of face masks
was not practiced by any patient. Twenty-one (81%) and six (19%) patients used cotton
cloth masks and surgical masks, respectively.
Discussion
This study clearly brought out the high infectivity rate among patients who are sharing
common areas. This finding is of paramount importance for establishments such as armed
forces, police departments, prolonged health-care facilities, and other institutions.
One hundred percent infection rate among patients in the ward might be due to multiple
factors such as viral infectivity, viral load, type and duration of exposure, immunocompromised
state, lack of social distancing, and inconsistent use of masks. The 30% infection
rate among HCWs further emphasized the national and international priority of protecting
HCWs.[10]
[11] Epidemiological investigation of one COVID-19 patient in the general ward revealed
protection from transmission with surgical mask, hand hygiene, and basic infection
control.[12] However, surgical masks or triple layer masks may be not adequate for HCWs in cancer
wards in pandemic situations. Ministry of Health, Government of India, recommends
use of PPE while performing duty in a COVID-19 zone or during an aerosol-generating
procedure.[13]
Sixty percent of patients received their last chemotherapy within 10 days prior to
COVID-19 infection; even though they had Grades 3 or 4 neutropenia, we did not find
increased morbidity for patients receiving chemotherapy.
The role of RT-PCR in asymptomatic COVID-19 patients is not studied.[14] Our patients were negative on the day of admission; repeated testing for a span
of 2 to 3 weeks is suggested. Two weeks of quarantine period need to be explored in
future studies.
Hematological cancers have the worst outcomes with COVID-19.[1]
[15]
[16] The time for RT-PCR negativity in our study was significantly more in hematological
malignancies as compared with nonhematological malignancies (p = 0.02). Only death directly attributed to COVID-19 in our study suggests augmenting
the strategies to save these patients.
COVID-19 infection is associated with profound psychological and social effects. Higher
suicidal rates were also observed in patients with advanced malignancies especially
lungs as the primary site.[17]
[18]
[19] We had one patient with metastatic lung cancer who committed suicide. Psychological
counseling and measures to reduce stress among these patients are equally important.
Transfer of oncology patients from peripheral hospitals and stagnation at this hospital
led to more congregations of patients and remained the same after national lock down.
Telemedicine and digital platforms of communication may help curb these issues to
some extent.[20]
Cancer patients are more susceptible to COVID-19, so we recommend that oncology departments,
wards, and day care centers should remain in a COVID-free zone. As most of the cancer
patients with good PS and nonmetastatic disease had a comparable COVID-19-related
mortality with the general population and delay in cancer treatment can worsen the
disease outcome, their cancer directed therapy should not be delayed. Patients with
metastatic disease and poor PS had an increased COVID-19-related mortality and their
treatment with increased toxicities should be preferably avoided during the pandemic.
Patients on chemotherapy should be closely monitored for cytopenias and prophylactic
growth factors may be given to prevent prolonged and profound cytopenia in these patients.
To the best of our knowledge, only limited data are available in the management of
cancer patients with COVID-19 and this is the first Indian study conducted exclusively
in cancer patients with COVID-19. However, our study has a few limitations. Even though
this study included patients with a wide spectrum of malignancies, the number of patients
was limited to 32.
Conclusion
Cancer patients living in congregation areas are more susceptible to COVID-19. However,
COVID-19-specific mortality was low. Recent chemotherapy and associated cytopenia
may not pose increased risk. Palliative intended patients are at increased risk of
death. RT-PCR clearance is delayed in patients with hematological malignancies. N-95,
PPE, and adherence to infection control measures should be encouraged in cancer wards.
Telemedicine and digital platforms of communications must be utilized to avoid congregation.
