key: cord-268390-npuvodd4 authors: Rehman, Aziz ul; Qureshi, Shahzad Ahmad title: The role of primary and secondary bio-molecules in optical diagnosis of pandemic COVID-19 outbreak date: 2020-08-17 journal: Photodiagnosis Photodyn Ther DOI: 10.1016/j.pdpdt.2020.101953 sha: doc_id: 268390 cord_uid: npuvodd4 • Primary and secondary biomarkers for optical diagnosis in of COVID-19 infected patients for early diagnosis of disease. • Raman and fluorescence signature of ACE-2 specific proteins is the basis for real time detection of COVID-19. • Label free detection. • Portable optical devices for fast screening of COVID-19 patients. This letter to the editor aims to introduce primary and secondary biomarkers whose reflectance, transmittance and fluorescence signals can be used for optical diagnosis of COVID-19 to the scientific community and persuade to build portable, cost effective, label free and real time optical devices for its detection. Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS) and Severe belong to the family of coronaviruses which were considered to be mutated from bats through penguin's camels and civets respectively to humans. SARS-CoV-2 is responsible for COVID-19. WHO on March 2020 declared COVID-19 a pandemic, as it has effected approximately 7.4 million people till 11 th of June 2020. Still no one can say when this epidemic will be over because in some developing countries of Southeast Asia, like Pakistan and India, still its peak is not appearing. There is not only intra transmission but inter transmission across the globe of this deadly virus. It can transmit through direct routes including cough, sneeze, and droplet inhalation after touching with nose, mouth and eye mucous membranes. Secondary interaction with surfaces like plastic, hospital benches and air droplets for couple of hours and SARS-CoV-2 reaches to the lungs through respiratory track and angiotensin converting enzymes-2 (ACE-2) receptors existing inside the nose, mouth, tongue and lungs [1] [2] [3] . The patients on ACE inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) who are on long term immunotherapy are its soft target but the exact relationship between ACE-2 levels, severity of J o u r n a l P r e -p r o o f infection and viral infectivity are still uncleared. Once its spikes (S) make a bond with ACE-2 receptor, biological mechanisms triggered, results change in the biological activities of specific molecules that can be used directly or indirectly for the early diagnosis of COVID-19. The realtime reverse transcription polymerase chain reaction (rRT-PCR) is the gold standard method of diagnosis using nasopharyngeal swab but simultaneously it is time consuming, costly, susceptible to error and especially diagnosis devices are not easily portable. Second diagnostic technique is computed tomography (CT) that relies on symptom's like consolidation or ground glass opacities [4] [5] . Keeping in view the epidemic nature of COVID-19, we need early stage, cost effective, real time diagnosis and portable devices to detect this disease so that treatment can be started to save the vulnerable population. ACE-2 receptor exists on top of pneumocytes lung cells in the alveoli and have significant role in forming alveoli surfactant and maintaining enough surface tension to keep the sacs open for the exchange of oxygen and carbon dioxide [6] . The SARS-CoV-2 produces millions of copies during replication. It damages to the pneumocytes that activate specific inflammatory mediator to stimulate the macrophages to release specific Interleukin-6 (IL-6), tumor necrosis factor TNF-α and cytokine Interleukin-1 (IL-1). As some of the new proteins comes into play, immune response activates first defense IgG-type antibodies and specific neutralizing antibodies (IgM type). This whole cycle of biological activities ending in vasodilation of alveoli by increasing capillary permeability and goes towards alveoli's edema and finally alveolar collapse. So, consolidation (damaged pneumocytes type-1, 2 neutrophils, proteins and Reactive Oxygen Species (ROS)) and ground glass opacities produce that causes cough, hypoxia and increases breathing rate. Due to inflammatory response, patient becomes hypotensive and all of its multi-organ system like kidneys and liver start malfunctioning so Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and creatinine values are also rehabilitated. All the biomolecular level changes occurred during SARS-CoV-2 incubation period (4-14 days), alter the concentration of neutrophils, nucleic acids, cytokines (such as IL-1, IL-6)" [6] , blood components, proteins, Nucleic acids, lipids, carbohydrates, hormones, phosphate, carotenoids, electrolytes, IgG, IgM, Nicotinamide Adenine Dinucleotide (NADH), sputum components and Flavin Adenine Dinucleotide (FAD). So the above mentioned biomolecules containing biomarkers, vary their molar concentration during incubation period and can become a rich source of COVID-19 diagnosis. Some of them rely on optical method based detection system while the other depends on specific signatures. For example, IgG and IgM show very strong Raman signatures for dengue and COVID-19 detection [7] [8] . Nucleic acid based tests are most sensitive for early detection of COVID-19 [9] Cytokines such as IL-1 and IL-6 have specific antibody receptors that can be diagnosed using Enzyme-Linked Immunosorbent Assay (ELISA) [10] and calorimetric assays such as LAMP and RT-LAMP assay based techniques [11] . Some of the electrolytes also change their concentration level during this infection so bio fluid samples can be used in Micro-Electromechanical System (MEMS) that is the base of miniature portable diagnosis devices [12] to scan the mass on airports or even during flying. Similarly, nucleic acid and protein bound coenzymes molecules like NADH, FAD have their own specific fluorescence biomarkers when excited with UV-A light [13] and can be used for label free detection of COVID-19 on early stages employing portable optical detection systems. We would like to reinforce the potential of COVID-19 studies using the fluorescence, Raman signature and conductivity based techniques described in this letter for its diagnosis as current as well as futuristic in order to speed up the diagnostic process and contribute to the cure of this pandemic outbreak. COVID-19 Causative Virus (SARS-CoV-2) in Human Nasopharyngeal Swab Specimens Using Field-Effect Transistor-Based Biosensor High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa Sampaziotis, others, SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases Optical techniques, computed tomography and deep learning role in the diagnosis of COVID-19 pandemic towards increasing the survival rate of vulnerable populations Involvement of type II pneumocytes in the pathogenesis of chronic obstructive pulmonary disease Dengue blood analysis by raman spectroscopy Spectroscopy as a tool for detection and monitoring of Coronavirus (COVID-19) Overcoming the bottleneck to widespread testing: A rapid review of nucleic acid testing approaches for COVID-19 detection COVID-19: consider cytokine storm syndromes and immunosuppression Optical techniques for fast screening -Towards prevention of the coronavirus COVID-19 outbreak Fluorescence quenching of free and bound NADH in hela cells determined by hyperspectral imaging and unmixing of cell autofluorescence Medical Physics from PIEAS in 2007. He is an Assistant professor/Senior Scientist in Agri&Biophotics Division at NILOP-College, PIEAS. His area of research includes Light tissue Interaction, Optical Diagnosis, Hyperspectral autofluorescence imaging of biological tissues, Unsupervised Unmixing, Photodiagnosis and photodynamic therapy, Raman spectroscopy of biomolecules Islamabad. He received his MSc Computer Science degree from AK University, AJK and Post Graduate diploma in Computer Systems from CTC, PAEC, Pakistan. He received his BSc Engineering degree in Metallurgy and Materials from UET Lahore Pakistan. Most recently, he is an Associate Professor in the Department of Computer and Information Sciences at PIEAS. His research interests include Medical Image Analysis, Deep Learning, Biophotonics, Bioinformatics, Evolutionary Computing and Computer Vision on applications for solving problems related to Mammography, Mitosis Detection in Breast Cancer, Retinopathy, He-La Cervical Cancer Cells Investigation