Cellular Landscaping of COVID-19 and Gynaecological Cancers: An Infrequent Correlation

Abstract

COVID-19 resulted in a mortality rate of 3-6% caused by SARS-CoV-2 and its variant leading to unprecedented consequences of acute respiratory distress septic shock and multiorgan failure. In such a situation, evaluation, diagnosis, treatment, and care for cancer patients are difficult tasks faced by medical staff. Moreover, patients with gynaecological cancer appear to be more prone to severe infection and mortality from COVID-19 due to immunosuppression by chemotherapy and coexisting medical disorders. To deal with such a circumtances oncologists have been obliged to reconsider the entire diagnostic, treatment, and management approach. This review will provide and discuss the molecular link with gynaecological cancer under COVID-19 infection, providing a novel bilateral relationship between the two infections. Moreover, the authors have provided insights to discuss the pathobiology of COVID-19 in gynaecological cancer and their risks associated with such comorbidity. Furthermore, we have depicted the overall impact of host immunity along with guidelines for the treatment of patients with gynaecological cancer under COVID-19 infection. We have also discussed the feasible scope for the management of COVID-19 and gynaecological cancer.

Figure 1

Schematic representation of the domain arrangement of a single spike protein of the SARS-CoV-2 S protein precursor. SS, signal peptide; NTD: N-terminal domain; RBD: receptor-binding domain; RBM: receptor-binding motif; SD1/2: subdomain 1 and 2; FP, fusion peptide; HR1, heptad repeat 1; CH, central helix; CD, connector domain; HR2, heptad repeat 2; TM, transmembrane domain; CT, cytoplasmic tail. The glycans were omitted for clarity. Below it is the 1D structure of the coronavirus spike. NTD, N-terminal domain. FP (fusion peptide), HR1 (heptad repeat 1), and HR2 (heptad repeat 2) are structural units in coronavirus S2 that function in membrane fusion. The sequence of the spike proteins from SARS-CoV-2 is mentioned based on genomic presentation.

Figure 2

Detailed illustration of structure and mechanism of auxiliary protein, namely, spike proteins inside the genome of SARS-CoV-2 for host-virus interaction. The domains of these glycosylated spike proteins, namely, S1 and S2 are elucidated here. The other membrane and surface proteins include D-dimer protein(D-dimer is one of the protein fragments produced when a blood clot gets dissolved in the body. It is normally undetectable or detectable at a very low level unless the body is forming and breaking down blood clots), haemagglutinin esterase (these are a family of viral envelope glycoproteins that mediate reversible attachment to O-acetylated sialic acids by acting both as lectins and as receptor-destroying enzymes (RDEs)) are also explained here. There is binding of ACE-2 receptor with type 2 pneumocytes for host-virus interaction on the membrane. The primary step involved coupling with the receptor in turn leads to (1) cleavage of SARS-CoV-2 Spike (S) protein, (2) thus causing activation of the S2 domain, and (3) finally leading to the fusion of viral and host membranes.

Figure 3

The schematic representation showing the influence of host immunity due to SARS-CoV-2 infection on the gynaecological malignancy. (a) The entry of viral pathogen inside the cell by the interaction of spike protein on the virus and ACE-2 receptor on the cell. The infection influences the breakdown of Ang II since the normal function of the ACE-2 receptor is blocked leading to the generation of ROS and enhanced inflammatory response. (b) IL-6 induces the release of more CRP, procalcitonin, and ferritin which facilitates the coinfection of COVID-19 and malignancy. IL-6 is the marker of immune suppression and influences cytokine storm which in turn reduces the haemoglobin in the blood. (c) Decreased haemoglobin leads to vaginal haemorrhage associated with gynaecological malignancy and indicates chronic anaemia.

Figure 4

The illustration indicating all the probable risks associated with COVID-19 and gynaecological cancer.

Figure 5

Schematic overview of a molecular link between COVID-19 coinfection with gynaecological cancer in patients. (A) The cascade of molecular macromolecules that is triggered by the host immune response upon entry of SARS-CoV-2 and responds to virus invasion by secreting proinflammatory cytokines and metalloprotease which include IL-7, IL-8, IL-9, and MCP-1. (B) This cascade of events causes caspase-1 to activate IL-1beta and IL-18 and upon activation it triggers an inflammatory response leading to cell pyroptosis. (C) Illustration of how coagulation in multiple organs reaches tumour microenvironment due to ACE-2 dysfunction and abnormal RAS activation by causing hypercoagulation.

Figure 6

The schematic representation showing different types of available treatments to fight against the coinfection of COVID-19 and gynaecological cancer. (a) Interferon-gamma alone or in combination with other drugs such as ribavidin, remdesivir, lopinavir, or ritonavir, and hydroxychloroquine can be a promising strategy to treat the coinfection. (b) TLR 9 agonists can be used to boost the circulating level of type 1 INF. (c) Tocilizumab is an antihuman IL-6R monoclonal antibody and can be used to reduce the pulmonary complications raised by SARS-CoV-2. (d) Androgen-deprived therapy has been used in the treatment of prostate cancer as well as COVID-19 infection in males. (e) Pathogen-associated molecular pattern (PAMP) agonists can enhance the systemic circulation of IFN type 1. (f) An anticancer drug, imatinib can be used to reduce the effect of COVID-19 as well as inhibit tumour cell proliferation. (g) Immunotherapy is a promising treatment for both COVID-19 infection and cancer. (h) Hydroxychloroquine is another drug that showed promising results in the treatment of coinfection.

Figure 7

The detailed guidelines provided by the European Society of Medical Oncology (ESMO), Society of European Robotic Gynaecological Surgery (SERGS), Society of Gynaecological Oncology (SGO), Gynaecological Cancer Society (BGCS), and National College of French Gynaecologists and Obstetrician (CNGOF) on the treatment and surgery of gynaecological malignancy under the influence of COVID-19.

Figure 8

The illustration showing the impact of COVID-19 on the diagnosis and treatment of different types of gynaecological cancers.