Genetic analysis of ACE2 peptidase domain in SARS-CoV-2-positive and SARS-CoV-2-negative individuals from Pakistan.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has emerged as a serious public health emergency of global concern. Angiotensin converting enzyme 2 (ACE2) peptidase domain is important for the cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Germline variants in ACE2 peptidase domain may influence the susceptibility for SARS-CoV-2 infection and disease severity in the host population. ACE2 genetic analysis among Caucasians showed inconclusive results. This is the first Asian study investigating the contribution of ACE2 germline variants to SARS-CoV-2 infection in Pakistani population. METHODS: In total, 442 individuals, including SARS-CoV-2-positive (n = 225) and SARS-CoV-2-negative (n = 217) were screened for germline variants in ACE2 peptidase domain (exons 2, 3, 9, and 10) using high resolution melting and denaturing high-performance liquid chromatography analyses followed by DNA sequencing of variant fragments. The identified variant was analyzed by in silico tools for potential effect on ACE2 protein. RESULTS: A missense variant, p.Lys26Arg, was identified in one SARS-CoV-2-positive (1/225; 0.4%) and three SARS-CoV-2-negative (3/217; 1.4%) individuals. No significant difference in the minor allele frequency of this variant was found among SARS-CoV-2-positive and SARS-CoV-2-negative individuals (1/313; 0.3% versus 3/328; 0.9%; P = 0.624), respectively. The SARS-CoV-2-positive patient carrying p.Lys26Arg showed mild COVID-19 disease symptoms. It was predicted as benign variant by in silico tool. No variant was detected in ACE2 residues important for binding of SARS-CoV-2 spike protein. CONCLUSION: The p.Lys26Arg variant may have no association with SARS-CoV-2 susceptibility in Pakistani population. Whole ACE2 gene screening is warranted to clarify its role in SARS-CoV-2 infection.

Clinical Characteristics of COVID-19-Infected Cancer Patients in Pakistan: Differences Between Survivors and Non-Survivors.

BACKGROUND: Cancer patients are considered as highly vulnerable individuals in the current COVID-19 pandemic. We studied the clinical characteristics of survivor and non-survivor COVID-19-infected cancer patients in Pakistan. PATIENTS AND METHODS: We did a retrospective study of 70 cancer patients with PCR-confirmed COVID-19 infection from Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore and Peshawar, Pakistan between April 13 and July 09, 2020. These patients were discharged from the hospital or had died by July 09, 2020. Clinical, pathological and radiological characteristics were compared between survivors and non-survivors by fisher's exact test and chi-square test. Univariable and multivariable logistic regression models were performed to explore the risk factors of mortality. RESULTS: Seventy cancer patients with SARS-CoV-2 infection were enrolled and the majority were males 38 (54.3%). 57 (81.4%) had solid tumors and 13 (18.6%) had hematological malignancies. Dyspnea (44 cases) was the most common symptom (62.9%). Complications were reported in 51 (72.9%) patients during the course of disease. 19 (27.1%) patients were admitted to an intensive care unit (ICU). A significant increase in the C-reactive protein level and neutrophil count was observed in the deceased patients as compared to the surviving patients. D-dimer values of ≥0.2 mg/L were significantly associated with mortality (P=0.01). We identified two independent risk factors associated with death, ICU admission (P=0.007) and D-dimer (P=0.003). CONCLUSION: Pakistani cancer patients with COVID-19 infection reported poor prognosis. Intensive surveillance of clinicopathological characteristics of cancer patients infected with COVID-19 especially D-dimer values may play a pivotal role in the outcome of the disease.

SARS-COV-2 infection and lung tumor microenvironment.

Coronavirus Disease 2019 (COVID-19) is an acute respiratory syndrome, reported at the end of 2019 in China originally and immediately spread affecting over ten million world population to date. This pandemic is more lethal for the older population and those who previously suffered from other ailments such as cardiovascular diseases, respiratory disorders, and other immune system affecting abnormalities including cancers. Lung cancer is an important comorbidity of COVID-19. In this review, we emphasized the impact of lung tumor microenvironment (TME) on the possibility of enhanced severity of infection caused by the SARS-Co-V2. The compromised lung TME is further susceptible to the attack of viruses. The lung cells are also abundant in the virus entry receptors. Several SARS-Co-V2 proteins can modulate the lung TME by disrupting the fragile immune mechanisms contributing to cytokine storming and cellular metabolic variations. We also discussed the impact of medication used for lung cancer in the scenario of this infection. Since other respiratory infections can be a risk factor for lung cancer, COVID-19 recovered patients should be monitored for tumor development, especially if there is genetic susceptibility or it involves exposure to other risk factors.