COVID-19

Brief summary on covid-19

 Covid-19(Coronavirus disease) is a infectious disease caused
by a new strain of corona virus i.e SARS-CoV2(Severe acute
respiratory syndrome-Corona virus 2 strain)

 Covid-19 term was named on 11 Feb 2020 by WHO.

 Previously
it was referred to as 2019 novel corona virus or
2019-nCoV.
 Cluster of unknown pneumonia cases was reported on 31st
December 2019 in wuhan city, hubei provience of china which was
eventually identified as 2019-nCoV.

 1st case was reported on 17/11/ 2019 in china.

 1st recorded case outside china- in Thailand on 13/1/2020.

 1st recorded case in India- in Kerala on 30/1/2020.

 WHO declared 2019 novel corona virus as PHEIC(Public health

emergency of International concern) on 30/1/2020.
 WHO declared COVID-19 as pandemic on 11/3/2020.

 Source of infection- not clear yet. Probably via consumption of raw, uncooked
animal product from meat market of wuhan city of china.

 Mode of transmission- a) Person to person transmission via direct contact by

breathing in a contaminated environment through respiratory droplets when infected
person coughs/sneezes/exhales (Direct spread) or by formite spread when droplets
land on objects and surfaces and people can catch covid-19 by touching these
objects/surfaces, then touching their eyes/nose/mouth. Droplets typically do not
travel more than 6 feet(2 m).
Other mode- b) Nosocomial transmission- Most common in healthcare
professionals during examination, transport, non invasive ventilation, intubation and
bronchoscopy of COVID patients.
 Incubation period- 2 to 14 days after exposure according to
CDC.

 Infectiousperiod- 1-2 days before appearance of symptoms

upto 7-12 days in mild to mod cases, upto 2 weeks in severe
cases. Most infectious during symptomatic period.

 Asymptomatic carriers play a major role in disease

transmission and spread.
 BRIEF NOTE ON CORONA VIRUS
 Family- Coronaviridae(ss RNA Virus)
 Genus- Corona virus
 Species- Human Corona virus(HCoV) and others
 Subspecies of HCoV- 1. SARS-CoV- identified in 2003
(7 subspecies) 2. HCoV- NL63 (alpha coronavirus)- identified in 2004
3. HCoV- HKU1 (beta coronavirus)- identified in 2005
4. MERS-CoV – identified in 2012 in Saudi arabia.
5. SARS- Cov2 – named on 11/2/2020 by ICTV(International
committee on taxonomy of viruses)
6.HCoV-OC43 (beta coronavirus)
7.HCoV-229E (alpha coronavirus)
BRIEF NOTE REGARDING
TREATMENT OF COVID-19
 CentralDrug Standard Control Organization(CDSCO)
approved 5 drugs for covid-19 in June 2020.
- 2 Anti virals (Remdesivir and Favipiravir)
-3 symptom easing drugs (Dexamethasone,
Tocilizumab, Itolizumab
 DRUGS COST Total cost of treatment

 1. Remdesivir Rs 5000/vial Rs 35000- 50000

 2. Favipiravir Rs 103/tablet Rs 12000- 15000

 3. Itolizumab Rs 8000/vial Rs 32000-50000

 4. Tocilizumab Rs 40k- 50k/vial

Remdesivir
 It
was approved for clinical use for both children and adults by
CDSCO as an injection on 1st June 2020.
 Itwas manufactured by Gilead Sciences Inc(US based pharma
company)
 Itwas approved following outcome of Randomized Control
Trial(2 done by Gilead company itself and 1 by US-
NIAID(National institute of Allergy and Infectious Diseases)
 It is FDA approved on 22/10/2020 for use in adults and pediatric patients
(12 years of age and older and weighing atieast 40 kg) for treatment of
covid-19 requiring hospitalization.

 Initially it was authorized for use under Emergency(EUA) only for

suspected or laboratory confirmed covid-19 severe cases with low blood
oxygen levels or needing oxygen therapy or more intensive breathing
support such as mechanical ventilator. Later FDA revised EUA on 28th
August 2020 and was authorized for emergency use for treatment of
suspected or laboratory confirmed covid-19 in hospitalized adult and
pediatric population irrespective of severity of disease.

 It was developed to treat Ebola and presently repurposed to treat covid-

19.
 Dosage- 200 mg in 200 ml 0.9% NS over 30-120 min on day 1 f/b 100 mg in 100 ml 0.9%
NS over 30-120 min once daily IV from day 2-5 (can be extended for additional 5 days if
no clinical response) or 10 days in patients requiring mechanical ventilation and/ ECMO.

 Indications- Spo2 < 90% with clinico-radiological mod to severe cases.

Comorbidities with clinico-radiological mod to severe cases.
Isolated Mod to Severe CT scoring( mild, mod, severe- <8, 9-15, >15
respectively)

 Contraindications-ALT or AST> 5 times ULN

Cr clearance- < 30 ml/min. (Since Remdesivir contains
sulfobutylether beta cyclodextrin sodium(SBECD) which is renally cleared and gets
accumulated in patients with decreased renal function)
 Adverse events-
 COMMON – GI adverse events- nausea(5-10%), vomiting(3%), diarrhea(3%), constipation(6-14%)
Infusion related reactions- Hypotension, nausea, vomiting, diaphoresis, shivering.
Acute respiratory failure(6-11%)
Hypoalbuminemia(13%)
Hypokalemia(5-12%)
Anemia(8-12%)
Thrombocytopenia(10%)
Increased bilirubin(10%).

 Occasional-1. Elevated transaminases(4-7%)( Discontinue if patients develop ALT >= 5 ULN or ALT
elevation accompanied by signs and symptoms of liver inflammation or increasing conjugated
bilirubin, ALP or INR)
2. PT elevation without change in INR
3. Renal- AKI(2-8%)
4.Pyrexia(5%), Hypoglycemia(4%), Insomnia(5%),Rash(7%)
 MECHANISM OF ACTION- It is a adenosine nucleotide prodrug that is metabolized to
active form nucleoside triphosphate metabolite which acts as an analog of ATP and
competes with natural ATP substrate and binds to RNA dependent RNA polymerase and
thus inhibits this enzyme.

Inhibition of viral replication by terminating RNA transcription.

 Drug Interactions- HCQ- It decreases anti viral activity of Remdesivir. Hence co

administration not recommended.
No significant interactions with Oseltamivir, Dexamethasone.
 RCT regarding Remdesivir
 Gilead company CONDUCTED “ SIMPLE TRIAL” AT MORE THAN 180 SITES
ACROSS THE WORLD.
 Gilead company conducted 2 SIMPLE trials- one with Hospitalised moderate cases and
another with Hospitalised severe cases.
 In SIMPLE TRIAL with Hospitalised moderate cases- Safety and Efficacy of
Remdesivir in a 5 day and 10 day treatment duration is assessed.
 In SIMPLE TRIAL with Hospitalised severe cases- Again Safety and Efficacy of
Remdesivir in a 5 day and 10 day treatment duration is assessed.
 In SIMPLE TRIAL with Hospitalised moderate cases- 600 patients were enrolled in
1:1:1 ratio.(1 group were given remdesivir for 5 days along with standard of care,
another group were given remdesivir for 10 days along with standard of care and 3 rd
group were given standard of care alone)
 In SIMPLE TRIAL with Hospitalised severe cases- 397 patients were enrolled in 1:1 ratio(1 group were
given remdesivir for 5 days, another group were given remdesivir for 10 days)

 In both trials all patients received 200 mg of remdesivir on day 1 and 100 mg once daily IV on
subsequent days.

 Final outcome of SIMPLE trial Moderate cases study-

 65% patients have clinical improvement with 5 day Remdesivir treatment vs standard of care alone at
day 11 which is a primary end point of study assessed based on 7 point ordinal scale system ranging
from hospital discharge to increasing levels of oxygen and ventilatory support.

 Treatment with 5 days of Remdesivir led to similar clinical improvement than standard of care alone as
a 10 day course.

 M/C adverse events encountered in more than 5% patients in both treatment groups during study-
Nausea, Diarrhea, Headache
 Final outcome of SIMPLE trial severe cases study-
- 64%, 54% patients have clinical improvement with 5 day, 10 day Remdesivir
treatment at day 14 respectively assessed on day 14 based on 7 point ordinal scale system
ranging from hospital discharge to increasing levels of oxygen and ventilatory support.

- M/c adverse events during treatment in both groups- nausea, worsening

respiratory failure ,elevated ALT and constipation.

Additional data was published on Remdesivir 0n July 10 2020 regarding clinical recovery
and mortality risk by enrolling 312 patients of treated severe cases group and a separate real
world retrospective cohort of 818 patients with similar baseline characteristics and disease
severity who received standard of care in the same time period as SIMPLE Severe study.
Results showed Improved clinical recovery and reduction in risk of mortality compared to
standard of care alone.(74% treated patients recovered by day 14 vs 59% patients receiving
standard of care alone, 62% reduction in mortality compared to standard of care alone)
 US-NIAID study showed Hospitalized patients with covid-19 recovered faster by an avg of 4
days(11 vs 15 days) when they were on remdesivir compared to placebo.

 However WHO found that remdesivir doesn’t help hospitalized patients with COVID-19
survive and doesn’t even shorten the recovery time of those who do survive as per WHO
sponsored study that was conducted from march 22 to oct 4 and involved 11,330 patients
from 405 hospitals in 30 countries.
Patients were given remdesivir and three other drugs singly or in combination. The
study concluded that neither remdesivir /hydroxychloroquine/ lopinavir/interferon regimens
appeared to have little or no effect on hospitalized covid patients, as indicated by overall
mortalty, initiation of ventilation and duration of hospital stay.
 FAVIPIRAVIR
 It is a oral drug approved by CDSCO to treat patients with mild to
moderate covid-19 disease on 19th June in India.

 It is a generic version of drug Avigan(developed by toyoma chemical

company, a japan based pharma company) which was marketed and
manufactured by Glenmark pharmaceuticals in India as favipiravir.

 Glenmark pharmaceuticals got approval from DCGI to conduct clinical

trials on May 12th 2020.
 It offers rapid reduction in viral load within 4 days and provides faster symptomatic and
radiological improvement. It has shown clinical improvement of upto 88% in mild to moderate
covid-19 cases.

 Its dosage for influenza 1600 mg on day 1 f/b 600 mg from day 2- 5.

 Its dosage in covid-19- 3600 mg(1800 mg BD) on day 1 f/b 1600 mg (800 mg BD) from day 2
for a total duration of 7-14 days.

 It is usually recommended in mild to mod covid-19 cases who have underlying diseases or
comorbidities like Diabetes or Cardiac disease.

 It is not safer (contraindicated) in - Pregnant women as it is teratogenic.

Severe liver and renal impairment.
Lactating women.
Cautiously used in patients with h/o abnormalities in metabolism of uric acid or having gout.
 MOA: It is a prodrug that undergoes phosphoribosylation to form favipiravir-RTP which
is a active form of this drug which acts as substrate for RNA dependent RNA
polymerase enzyme which is mistaken by enzyme as a purine nucleotide and thus
inhibits this enzyme.

Inhibition of viral replication by terminating RNA transcription.

 Spectrum of antiviral activity: Influenza A and B, Ebola, arenavirus, bunya virus,

filovirus, West Nile virus, yellow fever virus.

 Adverse events- Elevated liver enzymes, GI adverse events, increased uric acid levels,
increased triglycerides, decreased neutrophil and WBC.
 Metabolism: Liver by Aldehyde oxidase and partly by Xanthine oxidase but not by
cytochrome p450.

 Excretion: Kidney

 Drug interactions: Precaution to be used while administering favipiravir with below

mentioned drugs
1.Pyrazinamide:Blood uric acid level increases.
2.Repaglinide: inhibits metabolism and thus increases exposure to repaglinide
causing hypoglycemia.
3.Theophylline:Theophylline increases blood levels of favipiravir and adverse
events to favipiravir increases.
4.Famciclovir,sulindac:efficacy of these drugs are reduced when co administered
with favipiravir.
 Glenmark pharmaceuticals conducted a RCT across 7 sites in India.

 This study enrolled 150 patients (90 mild covid-19 cases and 50 moderate covid-19 cases) in a
1:1 ratio. i.e 75 covid-19 patients were given favipiravir along with standard of care and 75
covid-19 patients were given standard of care alone.

 Patients were given 3600 mg(1800 mg BD) on day 1 f/b 1600 mg (800 mg BD) from day 2-14.

 Safety and efficacy of favipiravir plus standard of care vs standard of care alone is assessed
during the study.

 Results- 40% faster achievement of clinical cure ( 3 vs 5 days) and 69% patients achieved
clinical cure by day 4 compared to 45% in control group.
Among patients who clinically deteriorated and required oxygen support, those
receiving favipiravir had a longer median time to 1 st time use of oxygen.(5 vs 2 days)
Regarding A/E- M/c A/E- Transient elevation in uric acid levels
GI A/E.
The adverse events are well tolerated during the study and
doesn’t necessitate the need to discontinue the drug.

Jichi Medical University of Japan conducted a study on favipiravir- Data showed it is not
efficacious against covid-19.
ITOLIZUMAB
 It was approved on 11th July 2020 by Indian drug regulatory agency for restricted emergency use for
treatment of cytokine release syndrome(CRS) in moderate to severe ARDS due to covid-19.

 It is a immune modulating drug to decrease cytokine storm.

 It is a IgG1 monoclonal antibody against CD6 receptor.

 Biocon India Limited got approval from DCGI for a study on Itolizumab for which a multicentric, open
label, two arm RCT was conducted across 4 sites in India with just 30 patients. (20 patients were
randomized to receive Itolizumab plus standard of care in case group while 10 patients received standard
of care alone in control group)

 Primary end point was to assess mortality at end of 1 month.

 Secondary key point was to assess inflammatory markers status at end of 1 month.
 Results-
All patients on drug arm recovered fully and were discharged from hospital
whereas 3 out of 10 patients in control arm died.
All patients on drug arm were weaned off oxygen by day 30 and none needed
ventilator support unlike control arm.
79% of severely ill patients were discharged from ICU after 14 days of treatment
while moderately ill patients showed a reduction in rate of disease progression.

Secondary end points of clinical markers of inflammation such as IL-6, TNF-alpha, serum
ferritin, d-dimer, LDH, CRP showed significant suppression post Itolizumab and corelated
well with clinical improvement in symptoms and chest x ray images.
TOCILIZUMAB
 It is a monoclonal antibody against IL-6 receptor.

 It is recommended by ICMR for emergency use in treating covid-19 patients as a investigational therapy
(off label use)

 It is indicated in patients with below all criteria are met-

moderate to severe disease with progressively increasing oxygen requirements and in
mechanically ventilated patients, not improving despite the use of steroids, significantly raised
inflammatory markers( CRP and or IL-6)

 It is mainly used for treatment of Rheumatoid Arthritis and systemic juvenile idiopathic arthritis as an
immunosuppressive drug.

 DOSAGE- >=30 kg:4-8 mg/kg upto max of 800 mg iv in 100 ml 0.9% NS over 1 hr Dose can be
repeated after 12 hrs and 24 hrs if needed.(A total of 3 doses if needed)
< 30 kg:12 mg/kg upto max of 800 mg iv in 100 ml 0.9% NS over 1 hr
 MOA: Tocilizumab binds to both soluble and membrane bound IL-6 receptor and
inhibits IL-6 mediated signaling. IL-6 is a proinflammatory cytokine that is elevated in
cytokine release syndrome.

 A/E- General- Hypersensitivity reactions

Risk of infections and reactivation of latent infections.
Occasional- neutropenia, thrombocytopenia, elevated liver enzymes.

 Dosage modifications- Cr clearance- >30 ml/min- No dosage reduction

<30 ml/min- not been studied in patients.
 STUDIES REGARDING TOCILIZUMAB-

ROCHE company (Swiss pharma company) conducted COVACTA Study( 1st

global, randomized, double blind, placebo controlled phase 3 study) on Tocilizumab-
Results were disappointing as it doesn’t met its primary end point of improved clinical
status that is assessed by 7 point ordinal scale in hospitalized adult patients with severe
covid-19 associated pneumonia. Infact secondary endpoint was also not met which included
difference in patient mortality at week 4.( Results published on July 29 th)

ROCHE company conducted yet another study EMPACTA trial which met primary end
point showing that patients with covid-19 pneumonia who received tocilizumab plus
standard of care were 44% less likely to progress to mechanical ventilation or death
compared to patients who received standard of care alone. (Results published on sept 18 th)
 On Oct 21st , New England journal of Medicine published a study on 243 patients that found
tocilizumab was not effective in preventing death in moderately ill hospitalized covid-19 patients. At
end of 14 days, those given tocilizumab had no significant clinical improvement except fewer severe
infections compared to those not administered the drug. While 18% of patients in tocilizumab group
had worsening of disease against 15% in placebo group,25% were still on oxygen support against 21%
in other group.

 On Oct 20th,JAMA published a study on 126 patients (60 to tocilizumab group, 66 to control group) that
no difference in mortality of two groups at 4 weeks was observed. However drug reduced the likelihood
of patients needing ventilation or dying as of two weeks compared to those who didn’t receive the drug.

 One of the main concern with the use of tocilizumab is the risk of reactivation of Tb along with other
latent and bacterial, fungal and viral infections. It is expected to decrease mortality in severe covid-19
patients. One of the study showed it reduced mortality only by 3.8% which becomes even more less
impressive when adverse effects listed by manufacturer are accounted for.

 Amid to the disappointing results, yet the drug is recommended as an investigational therapy for
treating covid-19. Some experts recommend its use for treatment of severe or life threatening
cytokine release syndrome(CRS) due to covid-19.
DEXAMETHASONE
 Trials showed reduced death rates by around 1/3 rd among severely ill covid-19 patients on
ventilators and by 1/5th for patients requiring oxygen only. That is reduced mortality
among patients with covid-19 who needed ventilator support (by around 33%) or oxygen
( by around 20%)
 No evidence of benefit for patients who doesn’t require oxygen. Infact being an anti
inflammatory drug with immune suppressive ability, it increases healthy persons risk of
developing covid-19 infection.
 In addition being a steroid and its indiscriminate use leads to adverse effect with zero
benefit.
 DOSE- 6 mg dexamethasone once daily for 7 to 10 days=40 mg prednisone=8 mg methyl
prednisone every 6 hrs=100 mg hydrocortisone every 12 hrly or 50 mg every 8 hrly.
 Current recommendations for use of corticosteroids includes – Refractory shock(since it
hampers host immune response to bacterial toxin release), mechanical ventilated patients
with ARDS.
AZITHROMYCIN AND HCQ IN
COVID-19
 HCQ dosage- 400 mg twice a day on day 1 followed by 200 mg twice a day for 4 days.
 Azithromycin dosage- 500 mg once a day for 5 days.

 ICMR recommendations-
On March 31st 2020 - Recommends the use of this combination as an off label indication in severe cases
requiring ICU management.
Latest recommendation as per new guideline published on 13 th June 2020-
HCQ may be considered in patients with mild cases(URTI) with high risk features which include-
Age: 60 years or more.
HTN or DM or other immunocomprimised states.
Chronic lung/liver/kidney disease.
Cerebrovascular Disease.
Obesity( BMI>25 Kg/m2)
 HCQ can be recommended in moderate cases(Pneumonia with no signs of respiratory distress, RR- 24 to <30/min,
Spo2- 90-94%) after ECG assessment.

 No longer recommended in severe cases(Pneumonia with signs of respiratory distress, RR- >30/min, Spo2- <90%)

 No longer recommends the use of Azithromycin in any cases of Covid-19.

 This combination was avoided since both drugs causes QT prolongation which can lead to adverse cardiac events
like arrythmias(Torsades de pointes)

 Contraindications to HCQ- k/c/o Retinopathy

k/c/o hypersensitivity to HCQ
G6PD deficiency.
Pre existing cardiomyopathy and cardiac rhythm disorders.
Children under 15 years of age.
Suggested monitoring of ECG during treatment as per ICMR task force- Acquire ECG 2-3 hrs after 1 st dose of HCQ
and then at 48 and 96 hrs thereafter and if QT prolongation (>500 ms or >60 ms increase from baseline) is seen stop
azithromycin(if used) and reassess benefit vs risk of continuing HCQ therapy.
 Before Initiating the therapy obtain a baseline ECG-
If QT interval <470 ms- HCQ can be given
470-500 ms- To be given with caution after removing correctable risk
factors like electrolyte imbalance(Na, K, Ca) and withholding QT prolonging drugs.
>500 ms- In patients with lower risk of COVID-19 complications,
HCQ can be avoided or cautiously used.
In patients with higher risk of COVID-19 complications,
HCQ may be cautiously used with close daily monitoring.

MOA of HCQ in covid-19- It interferes with pH dependent endosome mediated entry of

enveloped viruses like SARS- COV2 .The viral and endosomal membranes fuse together
leading to the release of viral genome into cytosol which can be inhibited.
Another mechanism could be due to its ability to increase lysosomal pH which modulates the
cellular metabolism of iron thereby decreasing its intracellular concentration which in turn
inactivates glycosyltransferases and glycosylating enzymes further suppressing glycosylation
of SARS coronavirus. This results in virus losing its ability to bind to lysosomal membrane(no
fusion) which prevents the virus to enter into host cell cytoplasm.
 Azithromycin exhibited a synergistic antiviral effect against SARS-COV-2 when
combined with HCQ both in vitro and in clinical setting.

 Azithromycin appears to decrease virus entry into cells. In Addition, it can enhance
immune response against viruses by several actions like it upregulates the production
of IFN- beta and gamma and genes involved in virus recognition such as MDA5 and
RIG-1. These mechanisms are involved in innate response against infectious agents and
potentially against SARS-COV-2.

 Azithromycin has an immunomodulatory effect by inhibiting several cytokines

involved in covid-19 severe respiratory syndrome. It decreases production of IL-1b,IL-
2, IL-6, IL-17, IL-22, IFN-alpha, TNF.

 Note- IL-2 is a key cytokine involved in host immune response to bacterial or viral
pathogens by inducing T cell proliferation and differentiation.
DOXYCYCLINE AND IVERMECTIN
COMBINATION IN COVID-19
 Doxycycline is a broad spectrum tetracycline antimicrobial agent which exhibits anti
inflammatory effect. In vitro it had exhibited anti viral effect against several RNA viruses.

 Doxycycline inhibits IL-6, IL-8,TNF-alpha and MMP(especially MMP-9) which are the key
regulators of the cytokine storm which is often associated with severe viral pneumonitis. Since
it inhibits MMP’s it thus may help repair the damaged lung tissue and enhance recovery.

 Clinical studies have also concluded that it is effective against dengue and chickungunya
infections.

 It also provides coverage against atypical bacterial pneumonia such as mycoplasma

pneumoniae, Legionella pneumophillia.
 How Doxycycline works in covid-19?
The antiviral action of doxycycline may be secondary to upregulation of
intracellular zinc finger antiviral protein(ZAP), an encoding gene of host cell. These
proteins binds to viral mRNA and inhibits RNA transcription and thus prevents viral
replication.

 Dose- 200 mg stat on day 1 followed by 100 mg bd from day 2 to 5.

IVERMECTIN
It is included in some countries both for prophylaxis and therapeutic use but NOT
INCLUDED IN ICMR guideline.
It is a wide spectrum anti parasitic agent that has known to exert antiviral property
against a host of viruses that cause dengue, Japanese encephalitis, tick born encephalitis,
chikungunya and even more recently COVID-19.
 How Ivermectin works in covid-19?
Its antiviral potential against SARS-COV2 may be attributed to its inhibition of importin
transporter that mediates the nucleo- cytoplasmic transport of viral proteins which leads to
inhibition of virus entry into host nucleus. So there will be no virus replication.

Dosage-
For treatment of mild to moderate cases-
Tab Ivermectin 12 mg once daily for 5 days along with doxycycline.
Ivermectin should be taken with a fatty meal.

For Prophylaxis- Tab Ivermectin 12 mg once daily on day 1,day 7 and followed by 12 mg
once every 30 days.

Note: Both Ivermectin and HCQ ideally should not be used together.
 Evidences
1. Several observational studies in Bangladesh showed encouraging results in mild
to moderate cases and showed increased recovery rate using ivermectin along with
doxycycline. [Chowdhury et al, 2020]
2. In Latin American countries, Ivermectin has been approved in mild cases of
Covid 19.
3. Australian study showed that Ivermectin, zinc and doxycycline can be taken as a
preventive treatment by high risk individuals or by those who test positive to minimize need
for hospitalization [Borody et al, 2020]
4. In retrospective cohort study in USA, Ivermectin showed significantly lowered
mortality rates when used in severe hospitalized cases. [Cennimo et al, 2020]
5. In an observational registry based study from 169 hospitals across different
continents established the survival benefit of Ivermectin and it reduced the duration of
hospital stay.[Patel et al, 2020]
6. Ivermectin and Doxycycline combination have already been recommended in
several Indian states.
 A/E- Usually well tolerated. Decreased leukocyte count (3%), eosinophilia (3%), and
increased hemoglobin (1%) have been reported with the systemic use of systemic
Ivermectin.

 Caution: Hepatic impairment, allergic disorders, HIV infection. Avoid in Pregnancy and
children below 2 years. (Monitor LFT, hypersensitivity reaction etc.
CONVALSCENT PLASMA THERAPY
IN COVID PATIENTS
 It is not FDA approved but it can be administered as an EUA( Emergency Use Authorization)
for covid-19 convalescent plasma for treatment of hospitalized patients with covid-19.

 It may be considered when following are met- Early moderate disease, increasing oxygen
requirements.

 It is done to lessen the severity or shorten the length of the disease.

 Regimen- 200 mi of convalscent plasma transfused 24 hrs apart

 Risks- Allergic reactions, transfusion-associated circulatory overload (TACO), and transfusion-

associated acute lung injury (TRALI), Infections like HIV, HBV and HCV.
 What is the evidence that convalescent plasma might be beneficial in
COVID-19?
Results from small case series during the prior MERS and
SARS coronavirus outbreaks suggested that CP is safe and may confer
clinical benefits, including faster viral clearance, particularly when
administered early in the disease course. The vast majority of patients who
recover from COVID-19 illness developed circulating antibodies to various
SARS-CoV-2 proteins 2-3 weeks following infection, which are detectable
by ELISA or other quantitative assays and often correlate with the presence
of neutralizing antibodies. These antibodies appear to be protective, based
on several primate studies showing animals could not be re-infected with
SARS-CoV-2 weeks to months later.
PLACID( PLAsma Convalscent India) trial conducted by ICMR concluded
that use of convalescent plasma did not forestall progression to severe
disease or mortality.