key: cord-0836547-wddjb4i6
authors: Mukherjee, K. K.; Dam, A.; Chakrabarti, D.; Jatua, D.; Sengupta, S.; Dutta, R.; Majumdar, S.; Mandal, S. S.; Basu, B.; Bhattacharjee, P.; MUKHERJEE, D.; Chakrabarti, J.
title: Is Cancer significant Comorbid Condition in COVID 19 Infected Patients? -A Retrospective Analysis Experienced in a Tertiary Care Center in Eastern India
date: 2022-05-16
journal: nan
DOI: 10.1101/2022.05.14.22275079
sha: 310d6e5ef5e197a911e8e91250ae27e909c6bff0
doc_id: 836547
cord_uid: wddjb4i6

Objectives: Patients with a history of active malignancy were initially thought to be at a higher risk of having COVID-19, although available data are conflicting due to economic stress, malnutrition, fear of hospitalization or treatment discontinuation. A cohort-based study was undertaken in Indian regional cancer centre to understand cancer-covid link in patients. Study Design: A total of 1565 asymptomatic patients were admitted based on thermal screening and evaluation from the screening form. The COVID 19 has been checked by RT-PCR method and the COVID 19 positive patients were transferred to government allocated COVID 19 hospital. The COVID 19 negative patients were transferred to general ward for further cancer treatment. Method: Post COVID 19 testing, positive patients were transferred to COVID hospital and their outcomes were analyzed and correlated with patients age gender and cancer stages. Result: Out of 1565 patients, 54 patients (3.4%) tested positive. Most of the patients are in 45-59 years age group. As female patients admitted were more in number than males, so predominance of disease is higher in female. 3 patients were symptomatic after admission and 2 were severe and were admitted to the ICU with ventilations. 8 patients died in Cancer and one patient died in COVID 19. Conclusions: As only 3.4% patients tested positive and only one patient out of 54 had died, so cancer is found not to be a comorbid condition towards COVID 19 patients in the Indian population studied.

In late December 2019 first case of SARS-CoV-2 named by World Health Organization was reported in Wuhan, China. On January 31, 2020, World Health Organization (WHO) declared COVID-19 as a "Public Health Emergency of International Concern (PHEIC)" and on March 11, 2020 , it was propounded as a "pandemic". The rapid spread of SARS-CoV-2, combined with a near-complete global lockdown, has weakened the healthcare systems. Lack of adequate health care infrastructure and human resources, serious supply-chain disruptions, and widespread fear among patients and health care workers have resulted in patient care and safety being compromised.

The virus is transferred from person to person via respiratory droplets (coughing or sneezing) as well as through direct contact with an infected patient or fomites nearby (1, 2) . It is suspected that patients with comorbid illnesses are more susceptible viral infection complications (3) . Patients with a history of active malignancy, particularly in lung, were initially thought to be at a higher risk of having COVID-19 and experiencing COVID-19-related complications, according to early studies (4, 5, 6) .

In COVID-19 disease, it has been observed that the M1 macrophages are activated, which are associated with macrophage-activating syndrome (MAS), cytokine storm, lymphopenia, damage of the endothelium, and increase in intravascular blood coagulation. On the other hand, in cancer, M2 macrophages are activated that suppress the immune response and also simultaneously help in tumor progression. As a result of immunosuppression, the antiviral immune response is impaired that makes the cancer patients more susceptible to viral infections (7) .

Previous research gathered and studied COVID-19 cases from 575 hospitals in 31 Chinese region. 18 of the total patients have a history of cancer, which may indicate a higher cancer rate than the Chinese population as a whole (0.9 percent vs. 0.29 percent). It also revealed that patients who had undergone chemotherapy or surgery were at a higher risk of having clinically severe events compared to patients who were not receiving these treatments for cancer.

However, the interpretation of the findings in this study depended upon the small size of the cancer population (n=18), which acts as a limiting factor in drawing a conclusion (4).

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

A recent study of more than 1100 patients receiving treatment in oncology outpatient clinics in Germany reported that the vast majority of patients who tested positive for SARS-CoV-2 did not show any symptoms. Moreover, asymptomatic infections did not seem to impact the outcomes of further treatment such as chemotherapy. The findings -presented in a poster at the European potentially curable early tumors is a major conflict among the guidelines (9) . Some of the guidelines followed in India based government-funded cancer hospitals were the establishment of "screening camps" outside the hospital to reduce patient visits, stringent restriction of relatives and friends in outpatient clinics and inpatient wards, the establishment of a fever clinic, and creation of isolation wards, rotation of staff to ensure a fallback option in case of mass quarantine (10).

The underlying immunosuppressive microenvironment due to dysfunctional immune cell production is a fundamental attribute of the malignancies that drives their pathogenesis (11) .

Comorbid conditions such as; Hypertension, Cardiovascular diseases, Chronic obstructive pulmonary diseases, Diabetes, Chronic kidney diseases, Cerebrovascular diseases are likely to . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted May 16, 2022. ; https://doi.org/10.1101/2022.05.14.22275079 doi: medRxiv preprint decrease immunity, impair macrophage and lymphocyte function, and are associated with the pathogenesis of SARS-CoV-2 (12) .

Previously reported observational studies showed hypertension (16-23%), cardiovascular disease (5-16.4%), diabetes (8) (9) (10) (11) .5%), cancer (3.9%), chronic kidney disease (2.4%), chronic obstructive pulmonary diseases (3.1%) and cerebrovascular diseases (3%) as the most frequently observed comorbidities among patients with SARS CoV-2. While hypertension (46.6%), diabetes mellitus (20.4%), cardiac disease (34.9%), cerebrovascular disease (9.1%), chronic liver disease (9.2 %), chronic kidney disease (10.8%) and chronic lung disease (14.7%) were reported as prevalent comorbidities among cancer patients (12) . Patients with chronic respiratory disorders like chronic obstructive pulmonary disease, are prone to developing ARDS because of their lower resistance to the virus. In diabetic patients it induces inflammatory infection by causing the accumulation of activated innate immune cells in metabolic tissues which leads to the release of inflammatory mediators, especially IL-1β and TNFα (12) .

From a systematic review of 31 studies and meta-analysis of 181,323 patients from 26 studies involving 23,736 cancer patients, it was observed that the most common type of cancer reported among COVID-19 patients were hematological malignancies (34.3%) followed by breast cancers (29.2%), lung cancers (23.7%), gastrointestinal malignancies (15.2%), prostate cancers (11.1%), gynecological cancers (9.6%), head and neck cancers (3.7%), brain tumors (3%) and other cancers (2.63%). Hematological malignancies had the highest pooled all-cause in-hospital mortality rate of (33.1%) followed by lung cancer at (28%), gastrointestinal malignancies at (19.8%), and breast cancer at (10.9%) (13) .

It was further reported that the most common treatment modality reported in cancer patients affected with COVID-19 was chemotherapy (30.3%), followed by hormonal therapy (17.4%), targeted therapy (15.4%), radiotherapy (13.8%), immunotherapy (9.1%) and surgery (7.3%) (13) .In response to the COVID-19 pandemic, the ASCO launched a Global Webinar emphasizing the need of protecting patients and health care teams from infections, delivery of timely and appropriate care, reduction of harm from the interruption of care, and preparation to handle a surge of new COVID-19 cases, complications, or comorbidities thereof (13) . In this hospital based retrospective study 1565 patients have been enrolled from June 2020 to November . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 16, 2022. ; https://doi.org/10.1101/2022.05.14.22275079 doi: medRxiv preprint 2020 out of which 54 (3.4%) patients were positive. During admission they were asymptomatic and it has been tried to make a correlation between COVID 19 and Cancer.

In a tertiary care hospital situated in eastern India, a total 1565 asymptomatic patients were . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) Assurance Program (EQAS) as provided to us by ICMR. All the samples for validation were in 100% concordance with the intra-laboratory report and the EQAS report. In general, sensitivity and specificity of the kits were not mentioned in the kit literature. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (Table-1 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 16, 2022. ; https://doi.org/10.1101/2022.05.14.22275079 doi: medRxiv preprint years. (Fig-IA) The ratio of male and female (Male: Female) was 1.0:3.6. Proportion of females (74.1%) was significantly higher than that of males (25.9%) (Z=6.78; p<0.0001). (Fig-IB) During admission more Female patient got admitted than male patient. (Table-1 )

Female p-value . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 16, 2022 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 16, 2022 94.4% of the cases were asymptomatic which was significantly higher than symptomatic cases (5.6%) (Z=12.44; p<0.0001). (Table-4 ), (Fig-IC) . In only 3.75 of the cases ITU admission was required. (Table-4 ). In only 3.7% of the cases ventilation was required as respiratory support.

( Table-4 ), (Fig-ID) .83.3%of the cases were discharged alive which was significantly higher than the patients died during treatments (16.7%) (Z=9.33; p<0.0001). A female patient aged 43 years died due to COVID-19. (Table-5 ), (Fig-IE) .

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 16, 2022. ; https://doi.org/10.1101/2022.05.14.22275079 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 16, 2022. ; https://doi.org/10.1101/2022.05.14.22275079 doi: medRxiv preprint Percentage of patients having CT value below or 25 and above 25 signifies the viral load. In the study it was see that percentage of patients having CT value above 25 was more. (Fig-IIB) ( F .

G .

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The copyright holder for this preprint this version posted May 16, 2022. ;  https://doi.org/10.1101/2022.05.14.22275079 doi: medRxiv preprint

COVID-19 is strongly related with an inflammatory outburst, oxidative stress, and other pathophysiological abnormalities, which can exert enormous influence on the evaluation of cancer and treatment choices (14, 15, 16, 17) . In mild cases of COVID-19, there were substantial elevations in levels of numerous blood cancer indicators when compared to normal control participants, according to retrospective research. These cancer indicators were elevated even more in severe COVID-19 patients. (15) . These changes might impact the positive and negative predictive values of a number of tumor-related biomarkers, making it more difficult to correctly assess and identify cancer diagnosis, disease progression, and treatment choices (18) .

In our study, the 1565 patients were admitted in the hospital 40 bedded isolation ward through a screening process. In the isolation ward, COVID 19 testing was done in CNCI Rajarhat Campus and 54 patients (3.4%) were tested COVID 19 positive. All the patients were asymptomatic during admission.

COVID-19 testing prior to systemic treatment offers several advantages. To begin, the diagnosed patient can be spared potentially hazardous immunosuppressive therapy (chemotherapy, biologics, and immunotherapy). Secondly, for assessment, care, and isolation, the patient might be sent to an infectious disease expert. Third, contact tracing of the COVID-19-positive patient can be done and all the primary contacts can undergo COVID-19 testing to rule out asymptomatic COVID-19 infection. Contact tracing and isolation have both been found to be useful in breaking down chain transmission and fattening curves (19) .

A Chinese retrospective analysis of 205 cancer patients with COVID-19 infection found that those who received treatment within four weeks after the beginning of symptoms had a high case fatality rate (20) . The mortality was unrelated to cytotoxic chemotherapy or anticancer treatment in prospective observational research conducted in the United Kingdom on 800 individuals with cancer and symptomatic COVID-19 infection (21) . Systematic strategizing, an environment that . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 16, 2022. allows healthy disagreements, rapid multipronged implementation, willingness to change decisions on short notice, effective communication, and teamwork are all required to manage this pandemic, according to the Tata Memorial Hospital-COVID-19 working group (22) . This is one of the first study in India in a Government Setup where a large number of asymptomatic patients had undergone COVID 19 testing. This study has shown that only 3.6% of patients were COVID 19 positive. Testing adds to the workload of staff collecting specimens, increases the cost of personal protective equipment, creates a psychological burden for patients and their families if they test positive due to the delay in cancer treatment and the stigma associated with quarantine, and puts pressure on patients to be tested before each systemic therapy.

According to our study, this can be stated easily that Cancer is not a comorbid situation towards COVID 19 affected patients. Only 3.4% patients were tested positive and only 3 patients out of 54 were symptomatic, 2 patients were severely symptomatic and those patients had been admitted to ITU with ventilation support. Out of 54 patients, only one patient died in COVID 19.

Another Indian Study have also shown similar scenario where 1.45% patients were COVID 19 positive. So, it can be stated that in Indian genetics and environment, COVID 19 is not a Comorbid situation.

Our retrospective single center study in regional cancer center showed the following outcomes in Majority of patients (94.4%) where asymptomatic and 5.6% patients were symptomatic after the admission ITU admission was not needed for 96.3% patients and ITU admission was done in 3.75% patients. These 3.75% patients were in ventilation.

83.3% patients were discharged alive, 14.8% patients died due to cancer and 1.9% patients died due to COVID 19 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted May 16, 2022. ; https://doi.org/10.1101/2022.05.14.22275079 doi: medRxiv preprint Limitations of our study may be -most of the patients admitted in the age group of 40-60 years and female patients admitted were more in number than male patients. Our single center study has limitations of small cohort, so this study may be undertaken in larger cohort considering different demographic locations of East India and pooled data may be generated. Our study cohort represented that cancer is not a comorbid condition in COVID-19 infected patients where other comorbid conditions remaining almost same.

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Declaration: We are sincerely thankful to everyone who have helped us in this study. We are also thankful to patients and their family members for their cooperation.