key: cord-0699613-ly2vlrnh authors: Dilip Pandkar, Prasad; Sachdeva, Vinay title: Pathophysiology of COVID-19 and Host centric approaches of Ayurveda date: 2020-12-02 journal: J Ayurveda Integr Med DOI: 10.1016/j.jaim.2020.11.010 sha: 13b9de21349425c1dde22a285c773d74927cf261 doc_id: 699613 cord_uid: ly2vlrnh The world is facing a global crisis and health emergency of COVID-19. Understanding of COVID-19 pathophysiology in ayurvedic host centric framework is prerequisite for apt use of Ayurveda. This paper reviews COVID-19 pathophysiology, clinical presentations and prognosis in ayurvedic perspective. Concept of exogenous pathogenic diseases can be traced in fever, microbes, toxins, epidemics and seasonal regimens chapters of Ayurveda. Such exogenous diseases later manifest multi-system presentation according to involvement of different ‘Dosha’ and derangement of ‘Agni’. The pathology of COVID-19 is primarily that of Sannipata Jwara (fever) with involvement of respiratory system. Secondary manifestations include coagulopathies, cardiovascular, neural, and renal complications. Gastrointestinal system is closely associated with respiratory mechanism in ayurvedic pathophysiological conceptualization of Srotas. Abnormal immune responses in COVID-19 are result of abnormalities of Tridosha, Rakta (blood) and Ojus (Vital nectar). The initial phase is Vata-Kapha dominant whereas later stage of aggravated immune response is Vata-Pitta dominant. Alveolar damage, coagulopathies indicate Rakta dhatu vitiation. This integrative understanding of COVID-19, we can propose novel strategies for therapeutics and prophylaxis. Measures for ‘Conservation of Agni-bala’, ‘Attainment of Rakta- Pitta-Prana homeostasis and ‘Protection of Tri-Marma i.e. vital organs’ can be important Host based strategies for reduction in the mortality in COVID-19 and for better clinical outcomes. This host centric approach can make paradigm shift in management of this epidemic. It affects type II pneumocytes (responsible for production of surfactant and are precursor for type I pneumocytes) than type I pneumocytes (responsible for gaseous exchange). Type II pneumocytes undergo apoptosis and die due to viral particles. [21] Aggravated immune response: Cytokine storm: lower lymphocyte counts and higher plasma concentrations of a number of inflammatory cytokines such as IL-6 and tumor necrosis factor (TNF). [22] DAD: Diffuse alveolar lung damage: This is most commonly seen histopathologic feature. [23] Histologically: Injury to the alveolar epithelial cells, Hyaline membrane formation, Hyperplasia of type II pneumocytes, Consolidation by fibroblastic proliferation with extracellular matrix and fibrin forming clusters in. [24] Crucial role of T cells: Another study reported that CD4+ T cells, CD8+ T cells, and natural killer cells were reduced in severely ill patients compared with those with mild disease symptoms. Moreover, a substantial reduction of CD4+ T cell and CD8+ T cell counts in the peripheral blood was also observed in a patient who died. [25] Alveolar macrophages affected: Alveolar macrophages expressing ACE2 are again target cells for SARS-CoV-2 infection. The 'Germ theory' received more importance and was followed by development of Medical Microbiology and anti-microbial medicines in last century. With these advances infectious diseases were treated far well. So far as Host-Germ approach is concerned 'virulence factor theory' was later followed by concept of 'Damage response framework'. DRF is an approach for incorporation of range of host responses to microbes with a parabolic curve in which host damage is plotted as a function of the host response. Importantly neither host nor microbial properties, are adequate to predict the outcome of host-microbe interaction because this outcome exhibits emergent properties. [45] In ayurvedic epistemology, microbe is viewed as nimitta karana (instrumental cause), contact of microbe with receptors as asamavayee karana (non-intimate cause) and host internal milieu as samavayee karana (intimate cause). As reviewed earlier the dynamic status of Dosha, Dhatu, mala and Agni the physiological elements of internal milieu are important in fate of exogenous and pathogenic diseases like COVID-19. The disease presentation is a dynamic phenomenon. Bala (body strength), Agni (digestive power) and Pradnya (mental ability) are as markers for prognosis, and Charaka has recommended continuous assessment of these three. [46] Thus it is host internal milieu in totality that is important for the prognosis. Bala is often considered as body strength but is inclusive of various activities such as immunomodulator, bulk promoting, nutritional etc. [47] Pathophysiology and Immune responses in COVID-19 are important to be discussed in Ayurveda perspectives. Immunity is popularly imitated as 'Vyadhikshmatwa' in Ayurveda which is an incomplete translation. Prana / vitality is an important consideration. Rakta (Blood), Shukra (Reproductive tissues, hormones and ability) and Ojus (Quintessence of the seven body tissues) are the body tissues responsible for immune functions and appropriate immune responses. In fact it is not only immunity but a holistic network of Bala, Agni, Dosha, DhatuBala, Vaya and many more factors that decide the immune responses and fate of disease progression. Other relevant measures for protection of Heart, Brain and kidney from relevant chapters like Visha Chikitsa. [49] Cytokine storm results in Inflammation and even necrotic changes in vital organs. [50] Basti is recommended as best measure for protection of vital organs. [51] Ayurveda Immunomodulator Herbs for arresting viral load in different organs. This can be decided (from variety of Rasayana Herbs having efficacy on different systems and Organs) on basis of involvement of Organs and Tissues in the patient. Last few decades there is a good amount of research on virus-host interactions, particularly with approach of systems biology. Virus-host systems biology can make predictions on host responses and dynamic interactions between viruses and hosts by computational modelling. It is interesting to note that modelling are expected to be done at different levels of abstraction like genes, proteins, cells, and organisms. [52] Ayurvedic foundational framework of 'Dosha-Dhatu-Mala-Agni-Srotas' can serve as a model for these proposed studies. Ayurvedic foundational concepts have great potential and hence such studies can indeed make paradigm shift. Conservation of Agni-Bala and homeostasis of Prana-Rakta-Shukra-Ojus quadrant can be best host centric approach to improve clinical outcomes in COVID-19. 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Varanasi: ChaukhmbaSurbharatiPrakashana Bhavpraksh of Bhavmisra AshtangaHridaya (with the commentaries "SarvangaSundara" of Arunadatta and "Ayurveda rasayana" of Hemadri). 1st ed. Varanasi: ChaukhmbaSurbharatiPrakashana A comprehensive outlook of Sannipata. AYU (An Int Q Coronavirus Disease 2019 (COVID-19) as a Multi-Systemic Disease and its Impact in Low-and Middle-Income Countries (LMICs) Gastrointestinal symptoms associated with severity of coronavirus disease 2019 (COVID-19): a pooled analysis Neurologic Features in Severe SARS-CoV-2 Infection Estimates of the severity of coronavirus disease 2019: a model-based analysis The Science Underlying COVID-19 Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia Kidney disease is associated with in-hospital death of patients with COVID-19 Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China Liver injury in COVID-19: management and challenges Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis Varanasi: Chaukhambha Orientalia What Is a Host? Incorporating the Microbiota into the Damage-Response Framework: TABLE 1 A review on balya action mentioned in Ayurveda Charaka Samhita by Agnivesha. Varanasi: Chaukhambha Orientalia Varanasi: Chaukhambha Orientalia SARS-CoV-2 as potential cause of cardiac inflammation and heart failure Varanasi: Chaukhambha Orientalia Virus-host interactions: from systems biology to translational research COVID-19 pandemic: A pragmatic plan for ayurveda intervention Systems Science Methods in Public Health: Dynamics, Networks, and Agents Ayurveda Rasayana in prophylaxis of Covid19 Public Health Approach of Ayurveda and Yoga for COVID-19 Prophylaxis Analysis of the causes of "relapse" of patients with novel coronavirus pneumonia after discharge and treatment strategies Bridging Ayurveda with evidence-based scientific approaches in medicine Seasonality of Respiratory Viral Infections Varanasi: Chaukhambha Orientalia A Prospective Hospital-Based Study of the Clinical Impact of Non-Severe Acute Respiratory Syndrome (Non-SARS)-Related Human Coronavirus Infection Charaka Samhita of Agnivesa. 1 st. Varanasi: Choukhamba Surbharati Prakashan Charaka Samhita of Agnivesa. 1 st. Varanasi: ChaukhmbaSurbharatiPrakashana Airborne or Droplet Precautions for Health Workers Treating Coronavirus Disease Severe Acute Respiratory Syndrome Coronavirus Infection of Human Ciliated Airway Epithelia: Role of Ciliated Cells in Viral Spread in the Conducting Airways of the Lungs The pivotal link between ACE2 deficiency and SARS-CoV-2 infection TMPRSS2 Contributes to Virus Spread and Immunopathology in the Airways of Murine Models after Coronavirus Infection Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19 Innate Immune Response of Human Alveolar Type II Cells Infected with Severe Acute Respiratory Syndrome-Coronavirus Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China Pathological findings of COVID-19 associated with acute respiratory distress syndrome Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies Pulmonary pathological features in coronavirus associated severe acute respiratory syndrome (SARS) Charaka Samhita of Agnivesa. 1 st. Varanasi: ChaukhmbaSurbharatiPrakashana Bhavpraksh of Bhavmisra AshtangaHridaya (with the commentaries "SarvangaSundara" of Arunadatta and "Ayurveda rasayana" of Hemadri). 1st ed. Varanasi: ChaukhmbaSurbharatiPrakashana A comprehensive outlook of Sannipata. AYU (An Int Q Coronavirus Disease 2019 (COVID-19) as a Multi-Systemic Disease and its Impact in Low-and Middle-Income Countries (LMICs) Gastrointestinal symptoms associated with severity of coronavirus disease 2019 (COVID-19): a pooled analysis Neurologic Features in Severe SARS-CoV-2 Infection Estimates of the severity of coronavirus disease 2019: a model-based analysis The Science Underlying COVID-19 Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia Kidney disease is associated with in-hospital death of patients with COVID-19 Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China Liver injury in COVID-19: management and challenges Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis Varanasi: Chaukhambha Orientalia What Is a Host? Incorporating the Microbiota into the Damage-Response Framework: TABLE 1 A review on balya action mentioned in Ayurveda Charaka Samhita by Agnivesha. Varanasi: Chaukhambha Orientalia Varanasi: Chaukhambha Orientalia SARS-CoV-2 as potential cause of cardiac inflammation and heart failure Varanasi: Chaukhambha Orientalia Virus-host interactions: from systems biology to translational research Acknowledgement: Authors are thankful to Dr Supriya Bhalerao & Prof Asmita Wele for inputs on scientific writing.