CORONA UPDATE-6

Compiled by Dr. Narendra Malhotra, Dr. Neharika Malhotra, Dr. Jaideep Malhotra, Dr. Keshav Malhotra

Special Inputs CORONA INDIA IN JULY by Prof. K. K. Aggarwal

SARS-COV-2 pandemic is still on the way of spreading. The curve has not flattened and the disease has not shown any signs of regression in numbers. The pandemic is predicted to worsen in India in the coming month. A major awareness drive needs to be undertaken and the hospital facilities need to be increased.
CASE RISE AS SEEN:

THE SEQUENCE OF SPREAD:

Ground Zero: Wuhan in live animal market or cafeteria for animal pathogens: 10th January; Total cases are based on RT PCR, 67% sensitivity
Doubling time India 15 days, USA 33 days, Brazil 13days, Russia 18 days, Spain 47 days, UK 35 days, Italy 55 days, France 49 days, Turkey 37 days,

Likely minimum deaths (540618 + 57979 x 15 == 8696) = 549314

Coronavirus Cases: 11,737,955
Deaths: 540,618
Recovered: 6,641,602
ACTIVE CASES 4,555,735
Currently Infected Patients 4,497,756 (99%) in Mild Condition 57,979 (1%) Serious or Critical

CLOSED CASES 7,182,220
Cases which had an outcome: 6,641,602 (92%) Recovered / Discharged 540,618 (8%) Deaths
India crosses Russia

Doubling Time

Country, Other

Total Cases

New Cases

Total Deaths

New Deaths

Total Recovered

Active Cases

Serious, Critical

Tot Cases/ 1M pop

Deaths/ 1M
pop

Total Tests

Tests/ 1M pop

Population

World

11,732,996

+171,508

540,137

+3,583

6,637,466

4,555,393

57,978

1,505

69.3

USA

3,040,833

+50,586

132,979

+378

1,324,947

1,582,907

15,198

9,186

402

38,217,640

115,449

331,034,037

Brazil

1,626,071

+21,486

65,556

+656

978,615

581,900

8,318

7,649

308

3,330,562

15,667

212,582,910

India

720,346

+22,510

20,174

+474

440,150

260,022

8,944

522

9,969,662

7,223

1,380,196,747

Russia

687,862

+6,611

10,296

+135

454,329

223,237

2,300

4,713

21,335,394

146,197

145,935,642

Peru

305,703

+2,985

10,772

+183

197,619

97,312

1,236

9,270

327

1,800,690

54,604

32,977,406

Date

Daily new cases

New Deaths

Total cases

Total Deaths

6th July

22510

474

720346

20174

5th July

23932

421

697836

19700

4th July

24015

610

673904

19279

3rd July

22721

444

649889

18669

2nd July

21948

377

627168

18225

1st July

19428

216

654405

17848

30th June

18256

506

585792

17410

29th June

18339

417

567536

16904

28th June

19620

384

549197

16487

27th June

20131

414

529577

16103

26th June 18276 381 509446 15689

25th June

18185

401

491170

15308 (3.11%)

24th June

16870

424

472985

14907

23rd June

15665

468

456115

14483

22nd June

13540

312

440450

14015

21st June

15183

426

426910

13703

20th June

13277

307

411727

13277

19th June

14721

366

395812

12970

18th June

13827

342

381091

12604

17th June

13103

341

367264

12262

India predictions

1. >90% of people are symptomatic within 2 weeks of infection

2. Death Rate is deaths today vs number of cases today

3. Corrected Death Rate is deaths today vs number of cases 14 days back

4. For one symptomatic test positive case there are 10-30 asymptomatic cases

5. Estimated Number of deaths = Reported deaths x 2

6. Number of deaths today should be 15% of the serious patients present 14 days back

7. Undocumented cases for each documented case [Iceland: 1: 2; German: 1: 5; New York City grocery store

shoppers: 1: 10; California 1.5%]
8. Amongst active 2.37% are serious, 1.82% need oxygen, and 0.41% need ventilator support. Extra Reading Background Material

1. China: Captured tiny droplets of viral genetic markers in 2 hospitals in Wuhan floating for > 2 hours. Infectivity? [Journal nature]
2. India: In states with average population density of 1185 /sk km the average number of cases were 2048. On the contrary in states with population density of 909/ sk km the number of cases were 56. (When Chandigarh and Pondicherry were taken out from this group) the Average Density of other states were 217 and the average number of cases were 35 [HCFI]

3. Revised COVID Sutras: It’s a COVID-19 Pandemic due to SARS 2 Beta Corona Viruses (different from SARS 1 where spread was only in serious cases); with three virus sequences floating (one similar to Wuhan, second similar to Iran and the third strain similar to USA – UK); has affected up to . 10% (5.7 % S Korea) of the population; Causes Mild or Asymptomatic Illness in 82%, Moderate to Severe Illness in 15%, Critical Illness in 3% and Death in 2.3% cases (15% of admitted serious cases, 71% with comorbidity< Male > Females); affects all ages but Predominantly Males (56%, 87% aged 30-79, 10% Aged < 20, 3% aged > 80); with Variable Incubation Period days (2-14; mean 5.2 days); Mean Time to Symptoms 5 days; Mean Time to Pneumonia 9 days, Mean Time to Death 14 days, Mean Time to CT changes 4 Days, Reproductive Number R0 1.5 to 3 (Flu 1.2 and SARS 2), Epidemic Doubling Time 7.5 days; Origin Possibly from Bats (Mammal); Spreads via Human to Human Transmission via Large and Small Droplets and Surface to Human Transmission via Viruses on Surfaces for up to three days. Enters through MM of eyes, nose or mouth and the spike protein gets attached to the ACE2 receptors. ACE2 receptors make a great target because they are found in organs throughout our bodies ( heart muscle, CNS, kidneys, blood vessels, liver) Once the virus enters, it turns the cell into a factory, making millions and millions of copies of itself — which can then be breathed or coughed out to infect others.

4. Prevalence: New York: 13.9%; New York City at 21.2%, S Korea 5.7%, world 5%; Ohio prison: 73% of inmates; New York: 21% mortality April 22 in JAMA.
5. Viral particles seen in tears, stool, kidneys, liver, pancreas, heart, semen, peritoneal fluid, CSF.
6. Thrombosis: University of Pennsylvania clots are seen in patients even on blood thinners. Netherlands study, 31% 7. Other human beta-coronaviruses has immunity lasting only for one year with no IMMUNITY PASSPORT.

8. In absence of interventions, prolonged or intermittent social distancing (till 2022-24)
9.Low levels of cross immunity from the other beta-coronaviruses against SARS-CoV-2 could make SARS-CoV-2 appear to die out, only to resurge after a few years. Surveillance till 2024.
10. During peak (trace and treat) and after the peak (trace and treat the close contacts)

11. Increased spread: close environment, crowded place with close physical contacts with no ventilation
12. Strategies: From community mitigation to individual containment; broader good over individual autonomy; perfect cannot be the enemy of the good; pandemics are fought on the grounds and not the hospitals., Treat the patient and not the test report, Consider every surface and every asymptomatic person as virus carrier
13. HCW: Direct patient exposure time < 30 minutes; 7 days work and 7 days holidays.
14. Italy mortality reduced when they were short of ventilators.
15. Hospital at HOME: CHF, mild pneumonia, exacerbations of asthma and COPD, cellulitis, and urinary tract infections.
16. Great Imitator (protean manifestation)
17. IgM can be false positive in pregnancy, immunological diseases); Pooled tests (< 5) when seroprevalence is < 2% 18. Early treatment to reduce the viral load and prevent cytokine storm using off label use of drugs like hydroxy chloroquine with azithromycin; ivermectin, remdesivir; Tocilizumab interleukin (IL)-6 receptor inhibitor; convalescent plasma therapy ( given early; bridge compassionate therapy, donor 14 days symptoms free, single donation can help 4 patients), Lopinavir-ritonavir and Favipiravir).

CLASSIFICATION OF DISEASE
Group 0:
Mild disease/No risk for COVID/Throat swab not done Group 1:
Group 1x- Mild disease/Report Awaited
Group 1a- Mild disease /Report Negative
Group 1b- Mild disease / Report Positive
Group 2:
Group 2x- Moderate disease/ Report awaited
Group 2a- Moderate disease / Report Negative Group 2b- Moderate disease/ Report Positive
Group 3:
Group 3x- Severe disease/ Report Awaited
Group 3a- Severe disease/ Report Negative
Group 3b- Severe disease/ Report Positive

CASE DEFINITION Mild disease:

 Symptoms of URTI and fever with no breathlessness/ hypoxia and haemodynamically stable. Moderate disease: (If Any one of the following present)

 RR >24/min
 SpO2 ≤ 93% on Room air
 Confusion/drowsiness
 S.B.P <90mmHg and/or D.B.P <60mmHg

Severe Disease:

(Features of moderate disease plus any one of the following)

 SpO2/FiO2 <315
 PaO2/FiO2 <300
 Radiology(CT/CXR) showing bilateral opacities not fully explained by effusion/lung collapse/nodules  Worsening of underlying illness in the last 1 week despite adequate management

COVID19 TESTS AND SIGNIFICANCE

1) RT PCR
gold std
Highly expensive
Read ORF of proteins and E gene Result is in 3hrs

2) CBNAAT
detect E&N gene in one go
Both for screening and confirmation Less expensive than RTPCR
Result is in 2hrs
ICMR adviced for SARI&ICU patients

3) TRUENAT
Detect E gene in first level for screening suspected patients RDRP gene in next level for confirmation
Result is in 1hr
Highly economic with low maintenance cost
ICMR adviced it for screening

4) Rapid antigen test
Most economic
ICMR adviced it for containment zones Result in just 30mts
Moderate sensitivity and high specificity

5) Antibody tests
It is meant for seroprevalance survay
IgM starts from 3rd day and present till 22nd day

IgG starts from 7th day and persist till some good length of period E gene for screening
N gene, RDRP gene &ORF protein for confirmation

RADIOLOGICAL FINDINGS IN COVID

 Chest x-ray (CXR) is typically the first line imaging modality for patients with suspected Covid-19, although less sensitive than chest CT. It may be normal in early or mild disease. Even with serious disease, about 31% had normal CXR at the time of admission. Findings are most extensive about 10-12 days after onset of symptoms.

 Findings on CXR: most frequent are airspace opacities (described as consolidation or ground glass opacities), which are often bilateral, peripheral and mainly in the lower zone. Pleural effusion is very rare (if patient has pleural effusion, chances are that it may not be Covid).

 Oblique CXR is done when lesion (subpleural or close to chest cavity) is not seen on routine AP view but there may be some data on CT.

 Point of care ultrasound: It is useful to monitor disease progression in patients who have hypoxemia and hemodynamic failure. It is not a sensitive and specific modality, but its advantages are inexpensive, ease of use, repeatability and no exposure to radiation. However, there is high risk of exposure to the operator, so used less.

 Findings on USG:Multiple B-lines, subpleural consolidation, irregular thickened pleural line with scattered discontinuities, alveolar consolidation, reappearance of bilateral A-lines; return of normal A-lines from B-lines suggest that the patient is improving.

 CT chest: A systematic meta-analysis of 49 studies of CT features of Covid-19 by CARING showed that the commonest finding at all stages of the disease was diffuse bilateral ground glass opacity. The next common findings were consolidations and mixed density lesions. Around 78% of patients with RT-PCR positive had either ground-glass opacities or consolidation or both.

 There is a significant overlap of CT scan findings between Covid and non-Covid patients, who present as SARI or ILI.

 Common CT findings: Ground glass opacities, consolidation, mixed lesions, crazy paving pattern, reticulations, septal

thickening (can be inter- or intra-lobular; commonly seen in advanced disease)

 Specific CT findings: Halo sign, reverse Halo sign (focal rounded area of GGO surrounded by a complete ring of consolidation; one of the typical findings of Covid-19 as per RSNA), spider web sign, pulmonary vessel engorgement (prominent pulmonary vessels in relation to the lesions; it is a potential early predictor of lung impairment), vacuolar sign (vacuole-like transparent shadow <5mm in length observed in the lesion)

 Infrequent CT findings: Architectural distortion, lymph node enlargement and pleural effusion

 In initial stages, GGOs can be unilateral and patchy progressing to multifocal confluent lesions with advancing
disease.

 If crazy paving pattern and vascular engorgement, the patient needs to be treated more aggressively.

 Pulmonary embolism is emerging as main pathogenesis in Covid-19, which can lead to pulmonary infarction. A contrast- enhanced CT pulmonary angiography is done when PE is suspected.

 CT severity score: it scores lung opacities in all 6 lung zones (3 on each side), the sum of scores from all 6 is the overall CT score (maximum score 24). The severity of lung involvement on CT correlates with disease severity.

 Extra-thoracic Covid manifestations: Covid-19-associated acute hemorrhagic necrotizing encephalopathy, multisystem inflammatory syndrome (airway inflammation and rapid development of pulmonary edema on thoracic imaging, coronary artery aneurysms and extensive right iliac fossa inflammatory changes on abdominal imaging)

 CT should not be used as initial screening or diagnostic tool. It can be used to identify early markers for lung impairment in symptomatic patient with RTPCR positive for Covid-19 or for patients with non-resolving symptoms to evaluate disease progression.

 The role of CT in stable pediatric patients is limited.

 X-ray should not be used as initial screening tool for Covid-19. In suspected patients with history of fever, dry cough, do
a RT PCR first instead of chest x-ray.

 All patients coming to Radiology with any respiratory symptoms should be considered a potential Covid-19 patient. Accordingly, all precautions should be taken. No mixing with other patients, maintain social distancing, sanitize equipment before using it for the next patient.

 Portable x-rays are used for temporal progression and resolution and also for serial follow-ups. Use a dedicated machine wherever logistically possible.

WHO says the virus may be surviving in air for 8 hours, so that makes the disease air borne spread and this makes it mandatory for all to wear masks and have good open ventilation and fan. Regular fogging of homes also becomes important.
Corona virus is here to stay with us for a long-long time various new treatments are being tried and trials are on for successful drug and vaccine. Until we have a definitive treatment and vaccine, prevention is the only core. So be safe.

Revised Management protocol for covid-19
Group 0:
Investigations: No investigations to be done unless recommended by COVID Physician Treatment:

 T.Desloratidine 5mg/ T.Levocetrizine 5mg 0-0-1

 T.Paracetamol 650mg (15mg/Kg/dose) SOS if fever

 100F/bodypain
 Salt water Gargle 1-1-1-1

Report for physician/pulmonologist’s consultation if worsening

Group 1:
Investigations: No investigations to be done unless recommended by COVID Physician Treatment:

 C.Oseltamivir 75mg 1-0-1 for 5 days

 T.Azithromycin 500mg 1-0-0 for 3 days

 T.Desloratidine 5mg OR T.Levocetrizine 5mg 0-0-1

 T.Paracetamol 650mg (15mg/Kg/dose) SOS if fever >100F/ body pain

 Salt water Gargle 1-1-1-1
Group 2:
Investigations:
Routine:
CBC, CRP, RFT, LFT, Procalcitonin, Blood culture, S.Ferritin, ABG, CXR, ECG, 2D ECHO, Urine Routine, Urine Culture.
Optional:
CK, CK-MB, Troponin-I, BNP as recommended by COVID Physician/ Cardiologist
Treatment:
Supportive :

 Oxygen therapy via nasal prongs/mask, titrated to achieve SPO2 >93%.

 C. Oseltamivir 75mg 1-0-1 for 5 days

 IV Antibiotics if infective parameters are high

 Inj.Ceftriaxone 1g IV Q 12H, or

 Inj.Amoxiclav 1.2g IV Q8H
(may be modified based on culture reports after 48-72hrs)

 T.Desloratidine 5mg/ T.Levocetrizine 5mg 0-0-1

 MDI. Duolin (Ipratropium 20mcg+Levosalbutamol 100mcg) 2 puffs Q8H via spacer

 MDI.Budesonide(200mcg) 2 puffs Q12H via spacer
COVID specific:

 IV Remdesivir 200mg on day1 F/B 100mg daily for 5 days

 IV Dexamethasone 6mg once daily for 10 days

 T. Hydroxychloroquine 400mg 1-0-1 on day 1, followed by
400mg 1-0-0 for 4 days OR

 T.Lopinavir+Ritonavir (200mg+50mg) 2-0-2 for 10 days
Note: HCQs/ Lopinavir+Ritonavir may be withdrawn once the COVID test report is Negative. Group 3:
Investigations:
Routine:CBC, CRP, RFT, LFT, Procalcitonin, Blood culture, S.Ferritin, ABG,
CXR, ECG, 2D ECHO, Urine Rouine, Urnie Culture.

Optional: CK, CK-MB, Troponin-I, BNP as recommended by COVID Physician/Cardiologist
Treatment:
Supportive :

 Oxygen Therapy & Ventilatory management as per ICU Team

 C. Oseltamivir 75mg 1-0-1 for 5 days

 Prophylactic UFH or LMWH( Enoxaparin 0.5mg/kg SC twice daily

 IV Antibiotics if infective parameters are high

 Inj.Ceftriaxone 1g IV Q 12H, or

 Inj.Amoxiclav 1.2g IV Q8H
(may be modified based on culture reports after 48-72hrs)

 T. Desloratidine 5mg/ T.Levocetrizine 5mg 0-0-1

 MDI. Duolin (Ipratropium 20mcg+Levosalbutamol 100mcg) 2puffs Q6H via spacer

 MDI. Budesonide(200mcg) 2 puffs Q12H via spacer
COVID specific:

 IV Remdesivir 200mg on day1 F/B 100mg daily for 5 days

 IV Dexamethasone 6mg once daily for 10 days

 T.Hydroxychloroquine 400mg 1-0-1 on day 1, followed by
200mg 1-0-1 for 5 days OR

 T.Lopinavir+Ritonavir (200mg+50mg) 2-0-2 for 10 days Special considerations:

 Inj.Azithromycin 500mg Q24H for 5 days can be added, Monitor QTc especially if it is combined with HCQs. Guided by the following score:

 Tocilizumab 400mg single dose IV infusion over 60mins (for rising ferritin/cytopenia/H score >170 (https://www.mdcalc.com/hscorereactive-hemophagocytic-syndrome#evidence)

Not to be given if

 Absolute Neutrophil count(ANC) <2000/cu mm

 Platelet count <100000/cu mm

 ALT or AST > 1.5 times the upper limit of normal

 IVIg: 0.3- 0.5 g/Kg/day for 5 days

 Convalescent Plasma

 Systemic Corticosteroid ≤ 0.5-1.0 mg/Kg/day of Methyl prednisolone OR
Equivalent for < 1 week

(Disclaimer: All the interventions in special consideration are off-label uses, no evidence for any of these treatments. To be decided on individual case basis).

RECOVERY IS THE RULE (SOURCE UNKNOWN)

 Timely action can save lives as most cases are mild; few are moderate and less than 5% are serious.

 Death rate is reducing as we are now able to better manage cases.

 In all patients who have loss of smell/taste, recovery is the rule and mortality is an exception. Analysis of 100 patients
with loss of smell/taste showed that none needed oxygen or ventilator or hospitalization. Occurred more often in
males, at any age and recovery is the rule within 4 weeks.

 Recovery if the rule means that the disease is salvageable at every step. It does not mean that mortality is zero.

 After 9 days, the virus becomes non-replicative and after 9 days, the illness is a post-Covid complication.

 Day 1 is the day when any of the symptom/s recognized by the CDC/MOHFW guidelines such as fever, throat irritation,
subconjuctival hemorrhage, rash, diarrhea, headache, calf pain etc.; test may or may not be positive.

 Post-Covid inflammation is very common. It can be in the form of persistent fever/sore
throat/bronchitis/diarrhea/cystitis/ exertional tachycardia.

 Doctors have high viral load because of repeated exposure and they have more hypercoagulable state. So, if all HCWs
are given anticoagulant + short course of steroids, even in mild cases, recovery is the rule.

 In non-HCW group of patients, if there are signs of chest congestion on Day 3-4, do an immediate chest CT scan and
give 10-day course of steroids, antiviral and anticoagulant, then recovery should be the rule and death an exception.

 RT PCR may be positive for up to 40 days; this does not mean that the virus is culturable. The virus is culturable for only 9 days, after 9 days, the virus is present but is non-culturable. This data is available for patients who are not on ventilator.

 If any illness is developed during the 9 days, then the post-Covid illness (post-Covid inflammatory state) may last for up to 6 weeks.

 A delayed cytokine storm, which occurs between Day 14 and18, has been observed in Mumbai. A 6-minute walk test is now mandatory at the time of discharge to look for drop in oxygen saturation. This is a valid marker for delayed cytokine storm. Give 5-10 days of LMWH/oral anticoagulant and small dose of statin at the time of discharge, especially to those who have been in hospital for >28 days and are >55 years age. This can reduce mortality.

 Initially steroids were given only in serious cases, but now their indication has also shifted to moderately severe cases. And the time may well come when steroid may become mandatory in all patients starting from Day 3. Timely steroids can prevent secondary cytokine crisis.

 Capacity building not just of HCWs but also RWAs etc. as many patients are in home care; issues like stigma and discrimination also need to be addressed. The word “contact” needs to be eliminated as it is a type of stigma.

 Indian vaccine is a live attenuated vaccine (Bharat Biotech); Moderna vaccine is mRNA vaccine; all vaccines have different technologies. Three things to be detected when a vaccine is given: Cellular antibodies, humoral protection and non-specific immunity building (innate immunity). By 15th August, we may only be able to tell whether antibodies are produced or not. Since this is a live attenuated virus, will there be a delayed response (cytokine crisis), we do not know.

 Isolate for 9 days, quarantine for 5 days and then monitoring with rest for next 2 weeks. Monitoring means that the person is not contagious, but is still likely to get secondary complications.

 Plasma therapy is effective if given within first 7 days of illness; plasma should be donated between 28 and 40 days.

Need some clarifications with surgeons including gynecologists

1. How you are dealing with elective cases, If you are postponing, how long to postpone.
2. Regarding delivery cases: do we need to send COVID testing of all pregnant women, If yes, when to send, & what to do if it’s positive.
3. What personal protective measures you are using in your OT and LABOR ROOMS, and based on what recommendations.
I realize you folks are seeing lot of sick Covid patients: Here some tips that I wanted to share with you about precautions during the Covid times. I and some of close friends are following. See if these are applicable, please do consider.

 If you are in direct care of Covid patients, you are at high risk of getting infected. please try to isolate yourself or minimize your close contact with your family as much as possible . I have separate room for me in my home, since I do deal with patients in the hospital. (You be solution to the problem, not the problem ( spreader) in your home

 Keep your car separate and don’t let your family commute in that.

 Wear scrubs (no watches and no fancy rings)

 Once you come home, make sure you keep your scrubs in the laundry bin, before entering home.

 Don’t take your work shoes inside the home. One set of shoes in the hospital, Other shoes stay in the garage.

 Your nutrition (water and food) is carried from home daily in plastic bag, and it does not touch anything until you keep
on your designated place in your office.

 Forget about hangout or food in the cafeteria for some time.

 Shower as soon as you enter your home.
In the hospital

 Minimize face 2 face visits

 Try to do as many tele visits or video options( thanks to Doximity)

 Before you meet your pt, you should’ve already gathered all the possible information about your patient (no surprises)

 Your encounter should not be more than quick focused exam.

 Tell your Pt that you will call them on their phone.

 Ask your staff to be meticulous about enquiring about Covid related questions and respiratory symptoms.

 Your work station to complete the notes for the visit is separate from your exam room (this is must)

 Your office is yours, don’t let anyone come in (not your friendly staff or colleagues)

 Don’t travel in crowded elevators. Carry the wipe to press the button on your elevator. Don’t touch any surfaces or lean
on the wall.

 Avoid extended conversation with your friends in the hospital.

 If you are seeing any sick patients, make sure you wear appropriate PPE including eye glasses.

 Try not to use the public restrooms

 If you are doing procedures, plan for electives. If you anticipate risk, do the Covid testing on everyone. If
urgent/emergent, you have to use full PPE.

 Spend less time in the hospital. This is not the time for face to face teaching. You can face time with your friends.

 Get good sleep, meditate and hydrate, stay away from crowd, isolate, and lesser TV.
Corona is here to stay with humans for long time Take care. You all be safe!! Good luck.