key: cord-0998139-beya9xht
authors: Jazieh, Abdul Rahman; Alghamdi, Majed; Alkaiyat, Mohammad; Al Johani, Sameera M.; Damlaj, Moussab
title: A Retrospective Evaluation of the Value of COVID-19 Screening and Testing in Patients with Cancer: Aiming at a Moving Target
date: 2021-05-26
journal: J Infect Public Health
DOI: 10.1016/j.jiph.2021.05.005
sha: 4a75b2786374fb2af5eb9015a44641c54aeeb5e9
doc_id: 998139
cord_uid: beya9xht

BACKGROUND: Diagnosis of COVID-19 infection in cancer patients is critical to co-manage their underlying disease and infection appropriately. Our study aimed at evaluating the sensitivity and specificity of screening patients with cancer for COVID-19 infection. METHODS: All oncology patients receiving care at Department of Oncology at King Abdulaziz Medical City in Riyadh were screened using the acute respiratory infection (ARI) survey. Nasopharyngeal and throat swap for polymerase chain reaction (PCR) testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was performed on patients who have high ARI score (i.e. ≥ 4), or any patient requiring elective/emergency hospitalization, undergoing a procedure as well as screening asymptomatic patients receiving chemotherapy between April 1st and July 30, 2020. Institutional Review Board approval was obtained. Descriptive and inferential analyses were done and sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated considering the COVID-19 PCR as the gold standard. RESULTS: During the study period, a total of 473 patients were included with a median age was 56 years (14- 104), 51% were female, 73% had solid tumors, and 66% received treatment within the last 3 months. These patients underwent 688 PCR tests along with ARI survey screening. Testing was done in the outpatient, inpatient, and emergency department setting in 41%, 40% and 19% of the patients, respectively. Majority of tests were screening of asymptomatic patients and only 23% were tested for suspected infections with ARI ≥ 4. A total of 54 patients (8%) had positive PCR for COVID-19 infection. The prevalence of infection varied from month to month ranging from 1.09% in April up to 19.70% in June and correlated with the average daily and active case load at a national level. The diagnostic yield of the ARI score also correlated with infection burden nationally. The PPV and NPV of the ARI as a screening tool was 18.24% (0-31.8) and 95.6% (86.36-98.86%) with the PPN fluctuating considerably in parallel with the prevalence of COVID-19 result. Similarly, the sensitivity and specificity of the ARI were 55.77% (0-70.59) and 79.4 (69.19-92), respectively. CONCLUSION: The yield of screening asymptomatic patients with cancer varies based on the community burden of COVID-19 infection. As universal screening can cause delays to patient care, it should be tailored based on the individual patient risks and infection burden in the region.

requiring elective / emergency hospitalization, undergoing a procedure as well as screening asymptomatic patients receiving chemotherapy between April 1st and July 30, 2020. Institutional Review Board approval was obtained. Descriptive and inferential analyses were done and sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated considering the COVID-19 PCR as the gold standard.

During the study period, a total of 473 patients were included with a median age was 56 years (14- 104), 51% were female, 73% had solid tumors, and 66% received treatment within the last 3 months.

These patients underwent 688 PCR tests along with ARI survey screening. Testing was done in the outpatient, inpatient, and emergency department setting in 41%, 40% and 19% of the patients, respectively. Majority of tests were screening of asymptomatic patients and only 23% were tested for suspected infections with ARI ≥ 4. A total of 54 patients (8%) had positive PCR for COVID -19 infection. The prevalence of infection varied from month to month ranging from 1.09% in April up to 19 .70% in June and correlated with the average daily and active case load at a national level. The diagnostic yield of the ARI score also correlated with infection burden nationally. The PPV and NPV of the ARI as a screening tool was 18.24% (0-31.8) and 95.6% (86.36-98.86%) with the PPN fluctuating considerably in parallel with the prevalence of COVID-19 result. Similarly, the sensitivity and specificity of the ARI were 55.77% (0-70.59) and 79.4 (69.19-92), respectively.

The yield of screening asymptomatic patients with cancer varies based on the community burden of COVID-19 infection. As universal screening can cause delays to patient care, it should be tailored based on the individual patient risks and infection burden in the region. During the period of March to July 2020, consecutive patients seen at the department whom underwent a COVID-19 RT-PCR test were eligible for inclusion. Nasopharyngeal and throat swabs for COVID-19 real time PCTR were obtained from all patients using appropriate personal protective equipment including N95 respirators within a negative pressure room. All patient and disease related variables were retrospectively collected from the electronic medical records.

All patients were contacted via phone call prior to their appointment in the outpatient infusion suite by a health care professional to ensure they were symptom free. In case COVID-19 related symptoms were present, patients were advised not to attend to their scheduled visit and the most responsible physician (MRP) of the patient was contacted to arrange for an alternative and appropriate medical plan. Patients planned for outpatient chemotherapy administration, procedure or an elective admission underwent COVID-19 RT-PCR screening prior. Patients admitted from the emergency department also underwent PCR screening regardless of the reason for admission.

Furthermore, all patients underwent ARI form screening at the time of initial contact with the health care professional (table 1) . This is a locally developed screening tool aiming to identify patients with risk factors of COVID-19 infection, such as symptoms of infection and suspected or confirmed exposure to a positive case. In the outpatient setting, patients scoring ≥ 4 points were placed in an isolation room and COVID-19 RT-PCR swab was done, the MRP was contacted for patients scoring J o u r n a l P r e -p r o o f > 0 but < 4 for appropriate disposition whereas patients with score of 0 proceeded to receive their scheduled treatment.

This was a retrospective study including oncology patients whom were served at our center between March and July 2020. Data were collected retrospectively which included age, gender, diagnosis, systemic therapy used over the last three months, ARI score, indication for RT-PCR testing, location of testing and result. Baseline characteristics were reported using descriptive statistics (numbers, medians and percentage). For inferential statistics, the relationship between the categorical and continuous variables with the study variables will be analyzed using the Pearson's Chi-square and and Wilcoxon / Kruskal-Wallis as appropriate. Calculation of sensitivity, specificity, positive and negative predictive values were performed considering the COVID-19 RT-PCR as the gold standard.

During the study period, a total of 473 patients were included with a median age of 56 years (14-104), 51% of whom were female. Underlying diagnosis was solid malignancy in 73%, 92 (19%) had a hematological malignancy while 8 (2%) underwent a hematopoietic stem cell transplantation. About two thirds of patients received treatment within the last three months. Most common types of treatment was chemotherapy in 230 (73%) patients followed by targeted therapy (oral or intravenous) in 45 (14%) of patients followed by immunotherapy in 17 (5%) of patients. Stratified by ARI score (high vs. low), patient gender, underlying diagnosis and treatment received were similar between the two cohorts. High ARI score was significantly associated with swabs taken in the emergency department (39% vs. 13%, p < 0.0001), having a suspected case (53% vs. 14%, p < 0.0001) and having a positive COVID-19 PCR result (18% vs. 4%, p < 0.0001). These results are shown further in table 4.

Over the study period, the performance of the ARI as a screening tool was examined on a monthly basis. Overall, the prevalence of COVID-19 infection was 7.61% ranging from 1% in April to 19.7% in at its peak in June. Considering COVID-19 PCR as the gold standard for diagnosis, the PPN and NPV of the ARI as a screening tool was 18.24% 

The COVID-19 pandemic presented considerable challenges in delivering optimal cancer care to patients. A number of societies including the European Society of Medical Oncology (ESMO) as well as ASCO recommended to screen patients prior to cancer treatment but additional factors such as laboratory capacity with PCR turnaround time must be considered at each institution as it can further cause delays to care delivery. The ESMO reported the utility of a pre-screening tool for COVID-19 infection using a patient-reported platform. 11 Using this tool, COVID-19 related symptoms are monitored and uploaded in the patient's electronic records, with an alarm triggered in such cases to advise the patient to report for PCR testing.

The issue of screening asymptomatic cancer patients is subject to debate. Lee et al., reported on 1,989 tests in 1,226 patients at the UK Birmingham chemotherapy cancer center and observed an infection prevalence of 0.6% among asymptomatic patients. 12 On the other hand, Al-Shamsi et al., 109 asymptomatic cancer patients underwent serial screening swabs totaling 384 specimens and noted that 25 out of 32 patients (78.1%) were diagnosed while asymptomatic. 13 From these reports and our own observations, such numerical quantitation is variable based on the community status of the pandemic at a given time point. Therefore, giving a percentage of prevalence among this population is inaccurate as it is time-bound and correlates with external variables. Herein, we noted that the overall prevalence of infection during the study period was 7.61%, however, it varied considerably with time correlating with the proportion of active cases at a national level. The predictive value of the ARI screening tool varied with the prevalence of the infection over time. Specifically, the PPV performance of the ARI was poor ranging from 0-31% indicating that this screening tool is not ideal for ruling in infection. On the other hand, the NPV ranged from 86-98% indicating that it would be a helpful tool in ruling out infection. Furthermore, even the value of ARI screening correlated with the disease burden in the community and when the case load was low, there was an overestimation of the suspected cases among cancer patients leading to performing of more tests. Collectively, the ARI would be most helpful to rule out infection in a time of low infection burden nationally.

This analysis carries a number of limitations that should be highlighted. First, the attributes of the ARI screening tool were compared to the PCR test which is considered to be the gold standard. However, false negative PCR samples are possible particular due to the nasopharyngeal swab acquisition technique and other limitations of the techniques itself may lead to underestimation of the ARI value. 14 15 16 17 18 Second, approximately 10% of the cohort did not have ARI results and it was unclear whether it was due to lack of administration or documentation in the medical records. Lastly, it is possible but less likely that patients may not report their infection symptoms due to fears of delaying their planned oncology treatments.

In conclusion, these findings challenge the application of universal recommendations of screening all Oncology patients prior to treatment without consideration of the status of the pandemic in the community. Furthermore, there are variations in the type of treatments, procedures, type of underlying malignancies, patients' general condition and underlining comorbidities. 19 Screening at the surge of the pandemic for patients with certain malignancies (hematologic malignancies, lung cancer or metastatic cancers), or procedure (particularly aerosol generating procedures) is probably justifiable.

However, universal screening when the prevalence in the community is low may not be cost effective or practical as it may cause unnecessary delays to treatments and inconvenience to the patients.

Adapting the recommendations for local setting and situations is required similar to what was suggested for testing asymptomatic healthcare workers. 20 Conflict of Interest Non Acknowledgement: Authors would like thank Nursing team and laboratory team for the help in collecting the data. 

Managing cancer patients during the COVID-19 pandemic: an ESMO multidisciplinary expert consensus

Cancer care during the COVID-19 pandemic: a perspective from Saudi Arabia

Impact of COVID-19 on Cancer Care Delivery in Africa: A Cross-Sectional Survey of Oncology Providers in Africa

The impact of the COVID-19 pandemic on cancer care

Impact of the COVID-19 Pandemic on Cancer Care: A Global Collaborative Study

A War on Two Fronts: Cancer Care in the Time of COVID-19

Cancer patients in covid-19 era: swimming against the tide

The official French guidelines to protect patients with cancer against SARS-CoV-2 infection

A Practical Approach to the Management of Cancer Patients During the Novel Coronavirus Disease 2019 ( COVID -19) Pandemic: An International Collaborative Group

Prescreening for COVID-19 in patients receiving cancer treatment using a patient-reported outcome platform

Utility of COVID-19 Screening in Cancer Patients

Serial Screening for COVID-19 in Asymptomatic Patients Receiving Anticancer Therapy in the United Arab Emirates

Correlation of Chest CT and RT-PCR Testing for Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases

Sensitivity of Chest CT for COVID-19: Comparison to RT-PCR

Should RT-PCR be considered a gold standard in the diagnosis of COVID-19?

Stability issues of RT-PCR testing of SARS-CoV-2 for hospitalized patients clinically diagnosed with COVID-19

Overview of COVID-19 testing and implications for otolaryngologists

COVID-19 Testing in Patients with Cancer: Does One Size Fit All?

COVID-19: PCR screening of asymptomatic healthcare workers at London hospital

We would like to acknowledge all members of the health care team of physicians, nurses, nurse specialists, coordinators and administrators who provide excellent care to our patients. We would also acknowledge our clinic nurse manager Ms. Noridayu Rashid and nurse specialist Nadine Mabsout for data collection.

J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f