COVID-19 is a biphasic illness. This implies it has two distinct phases which are chronologically separated. These two phases offer separate windows for the doctors to decide whether to initiate antiviral or immunomodulatory treatment. Initiating the right treatment at the right window of opportunity helps optimize the benefits of treatment and save a life.
The Two Phases of COVID-19 Disease:
Phase I: From Day 1 to Day 6 of Infection
This is the viral replication phase. The coronavirus multiplies and makes copies in the nose, throat, and maybe a little bit in the lungs. Chronologically, the initial 5-6 days of COVID-19 infection are crucial because a strong immune response comes into play. This helps stop the growth of the virus, improve symptoms and promote recovery.
Phase II: From Day 7 to Day 14 of Infection
This is the inflammatory response phase. The immune system may get dysregulated and cause the mild disease to turn into a moderate (or even a severe) disease.
Let’s Try to Understand This Biphasic Illness Phase by Phase:
PHASE I: Viral Replication Phase
(Intent of the medications: symptomatic relief and reduction in viral load)
Proposed medicines include:
2.Montelukast and Levocetirizine
Paracetamol is a Non-Steroidal Anti-inflammatory drug (NSAID). It is approved for the treatment of fever and mild to moderate pain relief in adults and children aged two months and over . The World Health Organisation (WHO) recommends using Paracetamol to relieve pain and reduce fever in COVID-19 . Usually, the lowest effective dose is recommended for the shortest time to relieve symptoms [1,3]. The maximum daily dose of Paracetamol for adults must not exceed 3000mg . It is advised not to take more than the recommended dose for fast relief as it can lead to side effects.
2. MONTELUKAST AND LEVOCETIRIZINE
A combination of anti-allergic medicines, namely, Montelukast and Levocetirizine may be effective against symptoms such as cough in COVID-19. While Montelukast was found to have some virus preventive role, levocetirizine may curb the inflammation seen in COVID-19 .
It is an oral antiviral medication. Its use has been approved for the treatment of mild to moderate COVID-19 cases [6,7]. Though it is considered to be an effective COVID-19 medicine, there is not enough evidence to support this. Misuse of this drug can lead to certain side effects. Hence, take this medicine only when advised by a doctor.
Other similar medicines such as Lopinavir and Ritonavir have not been found efficacious in treating COVID-19 .
Ivermectin is an antiparasitic medicine. This medicine has been seen to suppress the replication of novel coronavirus under laboratory conditions . Ministry of Health and Family Welfare (MoHFW) states in its guidelines for Home Isolation of mild/asymptomatic COVID-19 cases that Tablet Ivermectin (200 mcg/kg), once a day, on an empty stomach for a period of 3 to 5 days can be considered for treating the patient with mild/asymptomatic disease in home isolation .
However, in a recent tweet, Dr. Soumya Swaminathan, the WHOs chief scientist stated:
“Safety and efficacy are important when using any drug for a new indication. WHO recommends against the use of ‘ivermectin’ for COVID-19 except within clinical trials.”
This is WHO’s second warning against the usage of Ivermectin for coronavirus in the past two months .
WHO does not recommend using antibiotics in COVID-19, especially in mild cases . COVID-19 is caused by a virus and antibiotics work only against bacteria, not viruses. Therefore, antibiotics should not be used for prevention or treatment. However, it may be prescribed to cover bacterial superinfections .
PHASE II: Inflammatory Phase
(Intent of the medication: to halt the stage of Pneumonia and promote recovery)
Proposed medicines include:
6.Tocilizumab only to be given with steroids
Steroids such as Dexamethasone have anti-inflammatory benefits. This may help prevent or mitigate uncontrolled inflammation, which is responsible for causing lung damage and multisystem organ dysfunction in severe COVID-19. As per the RECOVERY trial and other studies, the incidence of death was lower in hospitalized COVID-19 patients who were given dexamethasone as compared to those who received standard care. Steroids, when used judiciously, are the only medicines to save lives in COVID-19 [14, 15, 16].
However, there is no evidence supporting the long-term use of steroids in patients with COVID-19. On the contrary, an extended course of steroids could be detrimental. Thus, while a short course of steroids may have therapeutic benefits, a long-lasting course may inadvertently lead to poor treatment outcomes .
Studies suggest that Tocilizumab, when given along with corticosteroids, may provide some benefit in severely ill COVID-19 patients. It is usually given to patients who are hospitalized, rapidly deteriorating with increasing oxygen needs, and have a significant inflammatory response [17,18].
The NIH COVID treatment guidelines clearly state that Tocilizumab should only be given in hospital settings and in combination with a course of dexamethasone therapy (or an alternative corticosteroid at a dose equivalency). It should be with caution as this medicine has its share of side effects.
WHO suggests using low-dose anticoagulants to prevent blood clot formation in hospitalized COVID-19 patients . Preventive doses of anticoagulants, preferably Low molecular weight heparin (LMWH) can be given unless there is a contraindication .
As per the Adaptive COVID-19 Treatment Trial (ACTT-2), the combination of baricitinib (an anti-inflammatory drug) and remedesivir (an antiviral) reduced the time of recovery among individuals hospitalized with COVID-19 
What’s new (updated 27 May 2021) by the National Institute of Health (NIH)
It was reported that baricitinib had an additional survival benefit when given along with corticosteroids (with or without remedesivir) . This observation was based on the results of COV-BARRIER, a trial of baricitinib in hospitalized adults.
The SOLIDARITY Trial on Remdesivir conducted by WHO, showed no evidence to suggest that this medicine can reduce the length of hospital stay or save the life of a COVID-19 patient .
What’s new (updated 15 Oct 2020) by World Health Organisation (WHO)
WHO suspended Remedesivir from their pre-qualified list of medicines as it showed no mortality benefit .
While antibiotics are not needed during the first phase of illness, hospitalized patients may be prescribed antibiotics to overcome bacterial co-infections. Antibiotics may be indicated in patients with COVID-19 due to suspected or confirmed bacterial superinfection/secondary infection [12,13].
Convalescent Plasma Therapy (CPT) benefits are dependent on the concentration of specific antibodies in convalescent plasma that could neutralize the effects of novel coronavirus. As per the PLACID trial  conducted by ICMR, “CPT didn’t lead to a reduction in progression to severe COVID-19 or all-cause mortality.”
What’s new (updated 17th May 2021) by AIIMS & ICMR COVID-19 National Taskforce group
Plasma therapy was dropped from the treatment guidelines of COVID-19 .
In case you notice any symptoms of COVID-19, get tested. Isolate yourself while waiting for the report as this will help curb spreading it to your loved ones. In the meanwhile, make sure to get in touch with a doctor. Adhere to your doctor’s advice and never take any medication without consulting your doctor.
*Disclaimer: This content is for informational purposes only and does not replace a qualified doctor’s advice. This content must not be considered as a substitute to any of the Government of India’s Guidelines on COVID-19 around similar and/or dissimilar context(s). The sole purpose of this content is to help our readers better understand their health and their diagnosed medical problems. 1mg encourages all the readers to always consult a doctor before the intake of any medicine.
Links to all e-books: https://www.1mg.com/coronavirus-covid19
With inputs from Dr. Varun Gupta, MBBS, MD (Pharmacology)
(The article is written by Dr. Lipika Khurana, Medical Writer and reviewed by Dr. Sakshi Jain, Health Content Manager and Dr. Swati Mishra, Medical Editor)
1. GSK. What you should know about paracetamol and COVID-19. In: Webinars & News. 2021. Available at:.https://www.gskhealthpartner.com/en-gb/news-events/covid-19/ib-covid19-update/#:~:text=Paracetamol%20is%20currently%20recommended%20by,reduce%20fever%20in%20COVID%2D19.
2. Russell FM, Shann F, Curtis N, Mulholland K. Evidence on the use of paracetamol in febrile children. Bull World Health Organ. 2003;81(5):367-72. Epub 2003 Jul 7. PMID: 12856055; PMCID: PMC2572451. https://www.who.int/bulletin/volumes/81/5/Russell0503.pdf
3. National Institute for Health and Care Excellence (NICE). COVID-19 rapid guideline:managing COVID-19.NICE Guideline [NG191].Published 23 March 2021. Last updated 03 June 2021.Available at: https://www.nice.org.uk/guidance/ng191/resources/fully-accessible-version-of-the-guideline-pdf-pdf-9078468301
4. Paracetamol [EMC Patient Leaflet]. Ruislip, UK: Aurobindo Pharma – Milpharm Ltd.
; 2020. [Accessed 03 June. 2021] (online) Available from: https://www.medicines.org.uk/emc/product/10817/smpc#gref
5. Bhattacharyya, D. Reposition of montelukast either alone or in combination with levocetirizine against SARS-CoV-2. Med Hypotheses. 2020 Nov;144:110046. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321662/
6. Glenmark becomes the first pharmaceutical company in India to receive
regulatory approval for oral antiviral Favipiravir, for the treatment of mild
to moderate COVID-19. Glenmark Pharmaceuticals Press Release. https://www.glenmarkpharma.com/sites/default/files/Glenmark-becomes-the-first-pharmaceut-cal-company-in-India-to-receive.pdf
7. Standard Operating Procedures. AIIMS Bhubaneswar. https://aiimsbhubaneswar.nic.in/writereaddata/upload/Documents/COVID.pdf
8. Lopinavir–ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.Lancet. 2020; 396: 1345-1352
9. Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020 Jun;178:104787. https://www.sciencedirect.com/science/article/pii/S0166354220302011
10. Revised guidelines for Home Isolation of mild /asymptomatic COVID19cases. Ministry of Health & Family Welfare( MOHFW) Government of India. 28th April 2021. https://www.mohfw.gov.in/pdf/RevisedguidelinesforHomeIsolationofmildasymptomaticCOVID19cases.pdf
11. Soumya Swaminathan (@doctorsoumya). Chief Scientist, World Health Organization. Twitter. https://twitter.com/doctorsoumya?lang=en
12. Episode #11 – Antibiotics & COVID-19. Science in 5. World Health Organization (WHO). https://www.who.int/emergencies/diseases/novel-coronavirus-2019/media-resources/science-in-5/episode-11—antibiotics-covid-19
13. Beović B, Doušak M, Ferreira-Coimbra J, Nadrah K, Rubulotta F, Belliato M, Berger-Estilita J, Ayoade F, Rello J, Erdem H. Antibiotic use in patients with COVID-19: a ‘snapshot’ Infectious Diseases International Research Initiative (ID-IRI) survey. J Antimicrob Chemother. 2020 Nov 1;75(11):3386-3390. https://pubmed.ncbi.nlm.nih.gov/32766706/
14. RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. https://www.nejm.org/doi/full/10.1056/NEJMoa2021436
15. NIH. Table: Corticosteroids Clinical Data | COVID-19 Treatment Guidelines. National Institute of Health (NIH). https://www.covid19treatmentguidelines.nih.gov/tables/table-4a/
16. Mishra GP, Mulani J. Corticosteroids for COVID-19: the search for an optimum duration of therapy. Lancet Respir Med. 2021 Jan;9(1):e8. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30530-0/fulltext
17. NIH. Interleukin-6 Inhibitors | COVID-19 Treatment Guidelines. National Institute of Health (NIH).https://www.covid19treatmentguidelines.nih.gov/immunomodulators/interleukin-6-inhibitors/
18.Therapeutic Management | COVID-19 Treatment Guidelines.National Institute of Health(NIH). https://www.covid19treatmentguidelines.nih.gov/therapeutic-management/
19. WHO. Follow-up care, low-dose anticoagulants for COVID-19 patients. World Health Organisation (WHO). 26 January 2021.
20. COAGULOPATHY IN COVID-19: REVIEW AND RECOMMENDATIONS. American College of Surgeons (FACS).
21. NIH. Baricitinib plus remdesivir shows promise for treating COVID-19. National Institute of Health
22. NIH. What’s new | COVID-19 Treatment Guidelines.National Institute of Health (NIH). https://www.covid19treatmentguidelines.nih.gov/whats-new/
23. WHO. WHO recommends against the use of remdesivir in COVID-19 patients. World Health Organisation (WHO). 20 November 2020.
24. WHO – Prequalification of Medical Products (IVDs, Medicines, Vaccines and Immunization Devices, Vector Control). WHO. https://extranet.who.int/pqweb/medicines/prequalified-lists/finished-pharmaceutical-products?label=&field_medicine_applicant=&field_medicine_fpp_site_value=&search_api_aggregation_1=&field_medicine_pq_date%5Bdate%5D=&field_medicine_pq_date_1%5Bdate%5D=&field_therapeutic_area=81&field_medicine_status=Suspended&field_basis_of_listing=43&field_single_fixed_dose_list%5B%5D=1&field_co_packed_list%5B%5D=2
25. AIIMS Covid Portal. CLINICAL GUIDANCE FOR MANAGEMENT OF ADULT COVID-19 PATIENTS.https://covid.aiims.edu/clinical-guidance-for-management-of-adult-covid-19-patients/
26. ICMR. Evidence-based Advisory in the time of COVID-19 (Screening, Diagnosis & Management of Mucormycosis). https://www.icmr.gov.in/pdf/covid/techdoc/Mucormycosis_ADVISORY_FROM_ICMR_In_COVID19_time.pdf