Synergistic Action of Immunotherapy and Nanotherapy against Cancer Patients Infected with SARS-CoV-2 and the Use of Artificial Intelligence

Abstract

Since 2019, the SARS-CoV-2 pandemic has caused a huge chaos throughout the world and the major threat has been possessed by the immune-compromised individuals involving the cancer patients; their weakened immune response makes them vulnerable and susceptible to the virus. The oncologists as well as their patients are facing many problems for their treatment sessions as they need to postpone their surgery, chemotherapy, or radiotherapy. The approach that could be adopted especially for the cancer patients is the amalgamation of immunotherapy and nanotherapy which can reduce the burden on the healthcare at this peak time of the infection. There is also a need to predict or analyze the data of cancer patients who are at a severe risk of being exposed to an infection in order to reduce the mortality rate. The use of artificial intelligence (AI) could be incorporated where the real time data will be available to the physicians according to the different patient's clinical characteristics and their past treatments. With this data, it will become easier for them to modify or replace the treatment to increase the efficacy against the infection. The combination of an immunotherapy and nanotherapy will be targeted to treat the cancer patients diagnosed with SARS-CoV-2 and the AI will act as icing on the cake to monitor, predict and analyze the data of the patients to improve the treatment regime for the most vulnerable patients.

Keywords: artificial intelligence; cancer; immunotherapy; nanotherapy.

Figure 1

Overview of the SARS-CoV-2 in the cancer patients. The entry of SARS-CoV-2 is mediated by binding of the spike protein to the angiotensin-converting enzyme II (ACE2) receptor (abundantly expressed on alveolar epithelial cells) with a subsequent membrane fusion leading to the down regulation of the ACE2 receptor. This in turn leads to the activation of angiotensin type 1 receptor (AT1R) through up regulation of angiotensin (ANG II). ANG II is also produced from ANG I through the renin-angiotensin system regulated by the angiotensin-converting enzyme (ACE). Up regulation of ANG II leads to respiratory failure and ANG II interferes with the adaptive immunity by activation of immune cells and increases the production of inflammatory cytokines to promote acute respiratory distress syndrome (ARDS). Viral infected patients also show widespread complement activation that leads to accumulation of macrophages, along with lymphopenia as an indicator of the seriousness and hospitalization in the infected patients.

Figure 2

Illustration of scheme for SARS-CoV-2 in cancer patients. Common symptoms observed for the cancer patients with SARS-CoV-2 are fever, dry cough, fatigue, dyspnea. In diagnosis, (A) sample has been collected from throat or nasopharynx using sterile swabs followed by gene amplification and genetic analysis through RT-PCR or rapid diagnostic test (RDT), (B) abnormal liver function tests result in elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), (C) bronchoscopy is performed to avoid complications. In the management, cancer patients need to be more cautious compared to the normal people by restricting social meetings, maintaining good hygiene and self- isolation to avoid becoming infected and intake of medicines as prescribed by doctors.

Figure 3

Typical patterns of COVID-19 at CT imaging. (a) Ground glass shadows (early stage), (b) Ground glass opacities, (c) Ground glass nodules and subpleural consolidation, (d) Focal consolidation, (e) Multifocal consolidation, (f) Multifocal consolidation with honeycomb (end stage). Reproduced with permission. Ref. [1] Journal of Internal Medicine © 2022 John Wiley and Sons, Inc.

Figure 4

Patterns of COVID-19 at chest ultrasound. (a) Early bilateral multifocal areas of interstitial syndrome, (b) Interstitial pneumonia characterized by interstitial syndrome with B lines and preserved sliding sign, (c) Advanced, and organized pneumonia with interstitial syndrome associated with multiple subpleural consolidations and reduced sliding sign. Reproduced with permission. Ref. [1] Journal of Internal Medicine © 2022 John Wiley and Sons, Inc.

Figure 5

Monitoring of cancer patients to mitigate the severity risk. (A) Immunotherapy or radiotherapy considered for the treatment of cancer patients, (B) they usually have weak immune response, (C) follow-ups after the therapy, (D) cancer patients are more susceptible to SARS-CoV-2, (E) multiple complications includes septic shock, acute myocardial infarction (AMI) and acute respiratory distress syndrome (ARDS), (F) avoid visits to hospitals and opt for telecommunications.

Figure 6

Role of action by immune checkpoint inhibitors for blockage cancer patients having solid tumors infected with SARS-CoV-2 can opt for the treatment by the use of immune checkpoint inhibitors such as anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibodies which can increase the CD8+ T cell response and viral clearance.

Figure 7

Incorporation of machine learning algorithm for the prediction and analysis On the top and left panel involves the input data whereas on the bottom and right panel involves the output data after the training of machine. The topmost input data involving (A) basic information—age, sex, race and common symptoms, (B) lab tests—WBCs, lymphocyte, neutrophil, platelet count, C-reactive protein level, lactate dehydrogenase, D-dimer level, IL-6 level and so on, (C) cancer type—lung, breast, prostate, gastric, ovarian, leukemia or others, (D) cancer stage—I, II, III, IV, (E) treatment—radiotherapy, chemotherapy, immunotherapy, surgery or targeted therapy or others. The output data can help in the prediction of the severity level—low, moderate or high. The left input data involves the ongoing treatments of the patients could be radiotherapy, chemotherapy, immunotherapy and the output data could help the oncologists to recommend their patients; whether the treatment needs to be modified, altered or additional changes required.