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Coronaviruses

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ISSN (Print): 2666-7967
ISSN (Online): 2666-7975

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Research Article

Polyherbal Syrup for Coronavirus Infection: Formulation and Evaluation

Author(s): Kranthi Kumar Kotta, Sunil Kumar Kadiri* and Sampath Ayyappa Gouru

Volume 5, Issue 1, 2024

Published on: 27 October, 2023

Article ID: e271023222886 Pages: 8

DOI: 10.2174/0126667975265630231025112858

Price: $65

Abstract

Background: SARS-CoV-2 emerged in Wuhan in December 2019, and after that, it spread quickly around the world. The virus could spread to millions of individuals since there were no particular treatments or preventative measures. The COVID-19 infection is often treated with current drugs such as Remdesivir, steroids, tocilizumab, favipiravir, and ivermectin. However, the immunosuppressive effects of these medicines might worsen COVID-19 symptoms and put the lives of immunocompromised individuals in peril. Thus, it is important to sustain a robust immune system when undergoing therapy for COVID-19. Herbal treatment has the potential to accomplish this objective.

Objective: The current investigation involves the preparation of polyherbal syrup containing various medicinal plants such as ephedra, diascorea, ginger, echinacea, garlic, rhubarb, and glycyrrhiza for the effective control of the COVID-19 infection.

Methods: All varieties of the individual plant powders (200 g) were treated to a 7 day maceration in aqueous ethanol (70:30) in a percolator at room temperature with intermittent vigorous shaking at room temperature and storage of the extract in a dark room. The mixture was run through a muslin cloth and then a Whatman qualitative grade 1 filter paper to produce the filtrate. The filtrate was evaporated to a thick paste-like consistency at 370°C under decreased pressure in a rota evaporator connected to a vacuum pump. After that, each individual extract was collected and kept in airtight jars at 4°C. According to the Indian Pharmacopoeia, simple syrup (66.67% w/v) of polyherbal extract was prepared. The oral administration of polyherbal syrup was carried out at varied doses of 0.5 ml, 1 ml, and 1.5 ml to infected golden Syrian hamsters from the 7th day for one week after infection reached its peak.

Results: When compared to the infection control group, the results revealed that the viral load was significantly reduced by 79.1% when treated with polyherbal syrup. A histological examination of the infected hamster lung on days 7, 10, and 13 demonstrated that polyherbal syrup significantly decreased viral load in a dose-dependent manner.

Conclusion: It is inferred that the polyherbal syrup formulation demonstrates efficacy in the prevention of COVID-19 infection during its first stages and may serve as a potential contender for SARSCoV- 2 due to its immunomodulatory properties.

Graphical Abstract

[1]
Gendrisch F, Haarhaus B, Krieger N, Quirin KW, Schempp CM, Wölfle U. The effect of herbal medicinal products on psoriasis-like keratinocytes. Biomolecules 2021; 11(3): 371.
[http://dx.doi.org/10.3390/biom11030371] [PMID: 33801280]
[2]
Pandarakalam JP. Interactions of quantum bioenergy fields. Neuroquantology 2020; 18(2): 157-72.
[http://dx.doi.org/10.14704/nq.2020.18.2.NQ20141]
[3]
Upton R. Traditional herbal medicine, pharmacognosy, and pharmacopoeial standards: A discussion at the crossroads in the age of COVID. In: Evidence-Based Validation of Herbal Medicine 2022; 109-48.
[http://dx.doi.org/10.1016/B978-0-323-85542-6.00003-2]
[4]
Spitzer O. Principles of herbal medicine. Clinical Naturopathic Medicine 2011; p. 21.
[5]
Jan JT, Cheng TJR, Juang YP, et al. Identification of existing pharmaceuticals and herbal medicines as inhibitors of SARS-CoV-2 infection. Proc Natl Acad Sci USA 2021; 118(5): e2021579118.
[http://dx.doi.org/10.1073/pnas.2021579118] [PMID: 33452205]
[6]
Rizvi ZA, Tripathy MR, Sharma N, et al. Effect of prophylactic use of intranasal oil formulations in the hamster model of COVID-19. Front Pharmacol 2021; 12: 746729.
[http://dx.doi.org/10.3389/fphar.2021.746729] [PMID: 34721035]
[7]
Kongratanapasert T, Kongsomros S, Arya N, et al. Pharmacological activities of fingerroot extract and its phytoconstituents against SARS-CoV-2 infection in golden syrian hamsters [Corrigendum]. J Exp Pharmacol 2023; 15(137): 137-8.
[http://dx.doi.org/10.2147/JEP.S411939] [PMID: 36941894]
[8]
Pattanayak S. Healthcare system using succulent parts of plants Volume II: Steps for production and marketing of some selected healthcare products. 1st ed. 2019.
[9]
Kim WR, Park EG, Kang KW, Lee SM, Kim B, Kim HS. Expression analyses of microRNAs in hamster lung tissues infected by SARS-CoV-2. Mol Cells 2020; 43(11): 953-63.
[http://dx.doi.org/10.14348/molcells.2020.0177] [PMID: 33199671]
[10]
Eng YS, Lee CH, Lee WC, Huang CC, Chang JS. Unraveling the molecular mechanism of traditional chinese medicine: Formulas against acute airway viral infections as examples. Molecules 2019; 24(19): 3505.
[http://dx.doi.org/10.3390/molecules24193505] [PMID: 31569633]
[11]
Ngwe Tun MM, Toume K, Luvai E, et al. The discovery of herbal drugs and natural compounds as inhibitors of SARS-CoV-2 infection in vitro. J Nat Med 2022; 76(2): 402-9.
[http://dx.doi.org/10.1007/s11418-021-01596-w] [PMID: 35006524]
[12]
Tang S, Ren J, Kong L, et al. Ephedrae Herba: A review of its phytochemistry, pharmacology, clinical application, and alkaloid toxicity. Molecules 2023; 28(2): 663.
[http://dx.doi.org/10.3390/molecules28020663] [PMID: 36677722]
[13]
Saleh MSM, Kamisah Y. Potential medicinal plants for the treatment of dengue fever and severe acute respiratory syndrome-coronavirus. Biomolecules 2020; 11(1): 42.
[http://dx.doi.org/10.3390/biom11010042] [PMID: 33396926]
[14]
Choonong R, Ruangdachsuwan S, Churod T, et al. Evaluating the in vitro efficacy of quassinoids from Eurycoma longifolia and Eurycoma harmandiana against common cold human coronavirus OC43 and SARS-CoV-2 using in-cell enzyme-linked immunosorbent assay. J Nat Prod 2022; 85(12): 2779-88.
[http://dx.doi.org/10.1021/acs.jnatprod.2c00736] [PMID: 36399766]
[15]
Chakravarti R, Singh R, Ghosh A, et al. A review on potential of natural products in the management of COVID-19. RSC Advances 2021; 11(27): 16711-35.
[http://dx.doi.org/10.1039/D1RA00644D] [PMID: 35479175]
[16]
Nema NK, Mamdapur GM, Sarojam S, et al. Preventive medicinal plants and their phytoconstituents against SARS-CoV-2/COVID-19. Pharmacogn Rev 2021; 13(4)
[17]
Chao P-Y, Huang MY, Huang WD, Lin KHR, Chen S-Y, Yang CM. Study of chlorophyll-related compounds from dietary spinach in human blood. Not Bot Horti Agrobot Cluj-Napoca 2018; 46(2): 309-16.
[http://dx.doi.org/10.15835/nbha46210918]
[18]
Wang Z, Yang L. Post-acute sequelae of SARS-CoV-2 infection: A neglected public health issue. Front Public Health 1827; 2022(Jun): 17.
[PMID: 35784200]
[19]
Wang Z, Yang L, Zhao XE. Co-crystallization and structure determination: An effective direction for anti-SARS-CoV-2 drug discovery. Comput Struct Biotechnol J 2021; 19: 4684-701.
[http://dx.doi.org/10.1016/j.csbj.2021.08.029] [PMID: 34426762]
[20]
a) Agrawal AS, Garron T, Tao X, et al. Generation of a transgenic mouse model of Middle East respiratory syndrome coronavirus infection and disease. J Virol 2015; 89(7): 3659-70.
[http://dx.doi.org/10.1128/JVI.03427-14] [PMID: 25589660];
b) Roberts A, Vogel L, Guarner J, et al. Severe acute respiratory syndrome coronavirus infection of golden Syrian hamsters. J Virol 2005; 79(1): 503-11.
[http://dx.doi.org/10.1128/JVI.79.1.503-511.2005] [PMID: 15596843]
[21]
Lamirande EW, DeDiego ML, Roberts A, et al. A live attenuated severe acute respiratory syndrome coronavirus is immunogenic and efficacious in golden Syrian hamsters. J Virol 2008; 82(15): 7721-4.
[http://dx.doi.org/10.1128/JVI.00304-08] [PMID: 18463152]
[22]
Roberts A, Thomas WD, Guarner J, et al. Therapy with a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody reduces disease severity and viral burden in golden Syrian hamsters. J Infect Dis 2006; 193(5): 685-92.
[http://dx.doi.org/10.1086/500143] [PMID: 16453264]
[23]
Xu J, Yang W, Pan Y, et al. Lucidenic acid a inhibits the binding of hACE2 receptor with spike protein to prevent SARS-CoV-2 invasion. Food Chem Toxicol 2022; 169: 113438.
[http://dx.doi.org/10.1016/j.fct.2022.113438] [PMID: 36179993]
[24]
Furukawa R, Kitabatake M, Ouji-Sageshima N, et al. Antiviral effect of candies containing persimmon-derived tannin against SARS-CoV-2 delta strain. bioRxiv 2022.
[http://dx.doi.org/10.1101/2022.10.31.513793]
[25]
Gretebeck LM, Subbarao K. Animal models for SARS and MERS coronaviruses. Curr Opin Virol 2015; 13: 123-9.
[http://dx.doi.org/10.1016/j.coviro.2015.06.009] [PMID: 26184451]
[26]
Rizvi ZA, Babele P, Sadhu S, et al. Prophylactic treatment of Glycyrrhiza glabra mitigates COVID-19 pathology through inhibition of pro-inflammatory cytokines in the hamster model and NETosis. bioRxiv 2022.
[http://dx.doi.org/10.1101/2022.05.16.492112]
[27]
Gupta A, Ahmad R, Siddiqui S, et al. Flavonol morin targets host ACE2, IMP-α, PARP-1 and viral proteins of SARS-CoV-2, SARS-CoV and MERS-CoV critical for infection and survival: A computational analysis. J Biomol Struct Dyn 2022; 40(12): 5515-46.
[http://dx.doi.org/10.1080/07391102.2021.1871863] [PMID: 33526003]
[28]
Marmitt DJ, Goettert MI, Rempel C. Compounds of plants with activity against SARS-CoV-2 targets. Expert Rev Clin Pharmacol 2021; 14(5): 623-33.
[http://dx.doi.org/10.1080/17512433.2021.1903317] [PMID: 33706626]
[29]
Kim EH, Lee BW, Ryu B, et al. Inhibition of a broad range of SARS-CoV-2 variants by antiviral phytochemicals in hACE2 mice. Antiviral Res 2022; 204: 105371.
[http://dx.doi.org/10.1016/j.antiviral.2022.105371] [PMID: 35777669]
[30]
La Marca A, Capuzzo M, Paglia T, Roli L, Trenti T, Nelson SM. Testing for SARS-CoV-2 (COVID-19): a systematic review and clinical guide to molecular and serological in-vitro diagnostic assays. Reprod Biomed Online 2020; 41(3): 483-99.
[http://dx.doi.org/10.1016/j.rbmo.2020.06.001] [PMID: 32651106]
[31]
Zhou P, Tachedjian M, Wynne JW, et al. Contraction of the type I IFN locus and unusual constitutive expression of IFN-α in bats. Proc Natl Acad Sci USA 2016; 113(10): 2696-701.
[http://dx.doi.org/10.1073/pnas.1518240113] [PMID: 26903655]
[32]
Mukherjee PK, Nema NK, Bhadra S, Mukherjee D, Braga FC, Matsabisa MG. Immunomodulatory leads from medicinal plants. Indian J Tradit Knowl 2014; 13(2): 235-56.
[33]
Saha O, Shatadru RN, Rakhi NN, Islam I, Rahaman M. Temporal landscape of mutation accumulation in SARS-CoV-2 genomes from Bangladesh: Possible implications from the ongoing outbreak in Bangladesh. Preprint 2020.
[http://dx.doi.org/10.1101/2020.08.20.259721]
[34]
Vellingiri B, Jayaramayya K, Iyer M, et al. COVID-19: A promising cure for the global panic. Sci Total Environ 2020; 725: 138277.
[35]
Perlman S, Mcintosh K. Coronaviruses, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) 9th edi. Elsevier Inc 2020.
[36]
Zhou G, Zhao Q. Perspectives on therapeutic neutralizing antibodies against the Novel Coronavirus SARS-CoV-2. Int J Biol Sci 2020; 16(10): 1718-23.
[http://dx.doi.org/10.7150/ijbs.45123] [PMID: 32226289]
[37]
Mani JS, Johnson JB, Steel JC, et al. Natural product-derived phytochemicals as potential agents against coronaviruses: A review. Virus Res 2020; 284: 197989.
[http://dx.doi.org/10.1016/j.virusres.2020.197989]
[38]
Panyod S, Ho CT, Sheen LY. Dietary therapy and herbal medicine for COVID-19 prevention: A review and perspective. J Tradit Complement Med 2020; 10(4): 420-7.
[http://dx.doi.org/10.1016/j.jtcme.2020.05.004] [PMID: 32691006]
[39]
Ang L, Lee HW, Choi JY, Zhang J, Lee MS. Herbal medicine and pattern identification for treating COVID-19: A rapid review of guidelines. Integr Med Res 2020; 9(2): 100407.
[http://dx.doi.org/10.1016/j.imr.2020.100407] [PMID: 32289016]
[40]
Jahan I, Onay A. Potentials of plant-based substance to inhabit and probable cure for the COVID-19. Turk J Biol 2020; 44(3): 228-41.
[http://dx.doi.org/10.3906/biy-2005-114]
[41]
Shu YZ. Recent natural products based drug development: A pharmaceutical industry perspective. J Nat Prod 1998; 61(8): 1053-71.
[http://dx.doi.org/10.1021/np9800102] [PMID: 9722499]
[42]
Ramsay RR, Popovic-Nikolic MR, Nikolic K, Uliassi E, Bolognesi ML. A perspective on multi-target drug discovery and design for complex diseases. Clin Transl Med 2018; 7(1): e3.
[http://dx.doi.org/10.1186/s40169-017-0181-2] [PMID: 29340951]
[43]
Sahoo JP, Samal KC. World on alert: WHO designated South African new COVID strain (omicron/B. 1.1. 529) as a variant of concern. Biotica Res Today 2021; 3: 1086-8.
[44]
Schlottau K, Rissmann M, Graaf A, et al. SARS-CoV-2 in fruit bats, ferrets, pigs, and chickens: An experimental transmission study. Lancet Microbe 2020; 1(5): e218-25.
[http://dx.doi.org/10.1016/S2666-5247(20)30089-6] [PMID: 32838346]
[45]
Duan ZP, Jia ZH, Zhang J, et al. Natural herbal medicine Lianhuaqingwen capsule anti-influenza A (H1N1) trial: A randomized, double blind, positive controlled clinical trial. Chin Med J 2011; 124(18): 2925-33.
[PMID: 22040504]
[46]
Feng GZ, Zhou F, Huang M, Yao K. Inhibitory effects of Reduning injection on human rhinoviruses in vitro. Zhongguo Yaoke Daxue Xuebao 2008; 39: 262-6.
[47]
Zhang X, Gu J, Cao L, et al. Network pharmacology study on the mechanism of traditional Chinese medicine for upper respiratory tract infection. Mol Biosyst 2014; 10(10): 2517-25.
[http://dx.doi.org/10.1039/C4MB00164H] [PMID: 25000319]
[48]
Tang LP, He RR, Li YF, et al. Study on antipyretic effect of Reduning injection on lipopolysaccharide-induced fever rats. Zhongguo Zhongyao Zazhi 2013; 38(14): 2374-7.
[PMID: 24199575]
[49]
Liu Y, Huang Y, Wei B, et al. Efficacy and safety of clearing heat and detoxifying injection in the treatment of influenza: A randomized, double-blinded, placebo-controlled trial. Evid Based Complement Alternat Med 2014; 2014: 1-8.
[http://dx.doi.org/10.1155/2014/151235] [PMID: 25506380]
[50]
Li YR, Sun SG. Revaluating the rationality and safety of Reduning injections in clinical use: An integrated approach. Chinese Journal of Clinical Pharmacology 2015; 31: 569-72.
[51]
Balamurugan V, Sen A, Saravanan P, et al. Potential effect of Acacia arabica. on Peste des Petits Ruminants. virus replication. Pharm Biol 2008; 46(3): 171-9.
[http://dx.doi.org/10.1080/13880200701585865]
[52]
Orhan İE, Özçelik B, Kartal M, Kan Y. Antimicrobial and antiviral effects of essential oils from selected Umbelliferae and Labiatae plants and individual essential oil components. Turk J Biol 2012; 36(3): 239-46.
[http://dx.doi.org/10.3906/biy-0912-30]
[53]
Orhan DD, Özçelik B, Özgen S, Ergun F. Antibacterial, antifungal, and antiviral activities of some flavonoids. Microbiol Res 2010; 165(6): 496-504.
[http://dx.doi.org/10.1016/j.micres.2009.09.002] [PMID: 19840899]
[54]
Choi HJ. Evaluation of antiviral activity of Zanthoxylum species against picornaviruses. Osong Public Health Res Perspect 2016; 7(6): 400-3.
[http://dx.doi.org/10.1016/j.phrp.2016.11.003] [PMID: 28053847]
[55]
Trong Le N, Viet Ho D, Quoc Doan T, et al. Biological activities of essential oils from leaves of Paramignya trimera (Oliv.) guillaum and Limnocitrus littoralis (miq.) swingle. Antibiotics 2020; 9(4): 207.
[http://dx.doi.org/10.3390/antibiotics9040207] [PMID: 32344551]
[56]
Kelley N, Jeltema D, Duan Y, He Y. The NLRP3 inflammasome: An overview of mechanisms of activation and regulation. Int J Mol Sci 2019; 20(13): 3328.
[http://dx.doi.org/10.3390/ijms20133328] [PMID: 31284572]
[57]
Xie J, Li Y, Shen X, et al. Dampened STING-dependent interferon activation in bats. Cell Host Microbe 2018; 23(3): 297-301.e4.
[http://dx.doi.org/10.1016/j.chom.2018.01.006] [PMID: 29478775]
[58]
Ahn M, Anderson DE, Zhang Q, et al. Dampened NLRP3-mediated inflammation in bats and implications for a special viral reservoir host. Nat Microbiol 2019; 4(5): 789-99.
[http://dx.doi.org/10.1038/s41564-019-0371-3] [PMID: 30804542]
[59]
Tőzsér J, Benkő S. Natural compounds as regulators of NLRP3 inflammasome-mediated IL-1β production. Mediators Inflamm 2016; 2016: 1-16.
[http://dx.doi.org/10.1155/2016/5460302] [PMID: 27672241]
[60]
He Y, Hara H, Núñez G. Mechanism and regulation of NLRP3 inflammasome activation. Trends Biochem Sci 2016; 41(12): 1012-21.
[http://dx.doi.org/10.1016/j.tibs.2016.09.002]
[61]
Jahan S, Kumar D, Chaturvedi S, et al. Therapeutic targeting of NLRP3 Inflammasomes by natural products and pharmaceuticals: A novel mechanistic approach for inflammatory diseases. Curr Med Chem 2017; 24(16): 1645-70.
[http://dx.doi.org/10.2174/0929867324666170227121619] [PMID: 28245768]
[62]
Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. Cytokine release syndrome in severe COVID-19: Interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents 2020; 55(5): 105954.
[63]
Grimes JM, Grimes KV. p38 MAPK inhibition: A promising therapeutic approach for COVID-19. J Mol Cell Cardiol 2020; 144: 63-5.
[64]
Schumacher N, Rose-John S. Adam17 activity and IL-6 trans-signaling in inflammation and cancer. Cancers 2019; 11(11): 1736.
[http://dx.doi.org/10.3390/cancers11111736] [PMID: 31694340]
[65]
Kono M, Tatsumi K, Imai AM, Saito K, Kuriyama T, Shirasawa H. Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by chloroquine: Involvement of p38 MAPK and ERK. Antiviral Res 2008; 77(2): 150-2.
[http://dx.doi.org/10.1016/j.antiviral.2007.10.011] [PMID: 18055026]
[66]
Nair A, Chattopadhyay D, Saha B. Plant-derived immunomodulators. Elsevier Inc 2018.
[http://dx.doi.org/10.1016/B978-0-12-814619-4.00018-5]
[67]
Kumar D, Arya V, Kaur R, Bhat ZA, Gupta VK, Kumar V. A review of immunomodulators in the Indian traditional health care system. J Microbiol Immunol Infect 2012; 45(3): 165-84.
[http://dx.doi.org/10.1016/j.jmii.2011.09.030] [PMID: 22154993]
[68]
Lin L, Lu L, Cao W, Li T. Hypothesis for potential pathogenesis of SARS-CoV-2 infection–a review of immune changes in patients with viral pneumonia. Emerg Microbes Infect 2020; 9(1): 727-32.
[http://dx.doi.org/10.1080/22221751.2020.1746199] [PMID: 32196410]
[69]
Tikellis C, Thomas MC. Angiotensin-converting enzyme 2 (ACE2) is a key modulator of the renin angiotensin system in health and disease. Int J Pept 2012; 2012: 1-8.
[http://dx.doi.org/10.1155/2012/256294] [PMID: 22536270]
[70]
Wang N, Shi X, Jiang L, et al. Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4. Cell Res 2013; 23(8): 986-93.
[http://dx.doi.org/10.1038/cr.2013.92] [PMID: 23835475]
[71]
Angeletti S, Benvenuto D, Bianchi M, Giovanetti M, Pascarella S, Ciccozzi M. COVID-2019: The role of the nsp2 and nsp3 in its pathogenesis. J Med Virol 2020; 92(6): 584-8.
[http://dx.doi.org/10.1002/jmv.25719] [PMID: 32083328]
[72]
Seif F, Aazami H, Khoshmirsafa M, et al. JAK inhibition as a new treatment strategy for patients with COVID-19. Int Arch Allergy Immunol 2020; 181(6): 467-75.
[http://dx.doi.org/10.1159/000508247] [PMID: 32392562]
[73]
Baruah C, Devi P, Sharma DK. In silico proteome analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). bioRxiv 2020.
[http://dx.doi.org/10.1101/2020.05.23.104919]
[74]
Banerjee A, Baker ML, Kulcsar K, Misra V, Plowright R, Mossman K. Novel insights into immune systems of bats. Front Immunol 2020; 11(January): 26.
[http://dx.doi.org/10.3389/fimmu.2020.00026] [PMID: 32117225]
[75]
Li F. Structure, function, and evolution of coronavirus spike proteinS. Annu Rev Virol 2016; 3(1): 237-61.
[http://dx.doi.org/10.1146/annurev-virology-110615-042301] [PMID: 27578435]
[76]
Grief SN. Upper respiratory infections. Prim Care 2013; 40(3): 757-70.
[http://dx.doi.org/10.1016/j.pop.2013.06.004] [PMID: 23958368]
[77]
Lin CW, Tsai FJ, Tsai CH, et al. Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds. Antiviral Res 2005; 68(1): 36-42.
[78]
Eccles R, Wilkinson JE. Exposure to cold and acute upper respiratory tract infection. Rhinology 2015; 53(2): 99-106.
[http://dx.doi.org/10.4193/Rhino14.239] [PMID: 26030031]
[79]
Agarwal R, Handa A, Dhooria S, Sehgal IS. Primary cavitary sarcoidosis: A case report, systematic review, and proposal of new diagnostic criteria. Lung India 2018; 35(1): 41-6.
[http://dx.doi.org/10.4103/lungindia.lungindia_225_17] [PMID: 29319033]
[80]
Isaacs D, Flowers D, Clarke JR, Valman HB, MacNaughton MR. Epidemiology of coronavirus respiratory infections. Arch Dis Child 1983; 58(7): 500-3.
[http://dx.doi.org/10.1136/adc.58.7.500] [PMID: 6307189]

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