CMAAO: In susceptible high-risk (pro-inflammatory and/or pro-coagulative) individuals, reactogenic vaccines can trigger transient thrombo-inflammation lasting first few (up to four) days.

COVID Vaccine: non-replicative, non-repetitive dose, spike gene mRNA/spike gene DNA to mRNA/whole killed virus, reactogenic vaccine

Cases: 1M April 2, 2M April 15, 3M April 27, 4M May 8, 5M May 20, 6M May 30, 7M June 7, 8M June 15, 9M June 22, 10M June 29th, 11M July 4, 12M July 8, 13M July 13, 14M July 17, 15M July 23, 16M July 25, 17M July 29, 18M August 1, 19M August 6, 20M August 10, 21M August 16, 22M August 19, 23M August 21, 24M August 27, 25M August 30, 26M September 3, 27M September 7, 28M September 10, 29M September 14, 30M September 18, 31M September 21, 32M September 23, 33M September 28, 34M October 1, 35M October 4, 36M October 8, 37M October 11, 38M October 14, 39M October 17, 40M October 19, 41M October 22, 42M October 24, 43M October 26, 44M October 28, 45M October 30, 46M November 2, 47M November 4, 48M November 6, 49M November 7, 50M November 8, 51M November 10, 52M November 12, 53M November 14, 54M November 15, 55M November 17, 56M November 19, 57M November 20, 58M November 22, 59M November 24, 60M November 25, 61M November 27, 62M November 29, 63M December 1, 64M December 2, 65M December 4, 66M December 6, 67M December 7, 68M December 9, 69M December 10, 70M December 12, 71M December 13, 72M December 14, 73M December 15, 74M December 17, 75M December 19, 76M December 20, 77M December 22, 78M December 23, 79M December 26, 80M December 27, 81M December 29, 82M December 30, 83M December 31, 84M January 2, 85M January 4, 86M January 6, 87M January 7, 88M January 8, 89M January 9, 90M January 10, 91M January 12, 92M January 14, 93M January 15, 94M January 17, 95M January 18, 96M January 20, 97M January 21, 98M January 23, 99M January 25, 100M January 26, 101M January 29, 102M January 30, 103M February 1, 104M February 4, 105M February 6, 106M February 8, 107M February 11, 108M February 13, 109M February 16, 110M February 18, 111M February 21, 112M February 24, 113M February 28, 114M March 1, 115M March 4, 116M March 6, 117M March 9, 118M March 11, 119M March 13, 120M March16, 121M March 18, 122M March 19, 123M March 22, 124M March 24, 125M March 26, 126M March 27, 127M March 30, 128M March 31, 129M April 2, 130M April 3

Ground Zero: Wuhan - in live animal market or cafeteria for animal pathogens: 10^th January, 2020; Total cases are based on RT PCR, 67% sensitivity

Variants - B 1.1.7 UK, B.1.351 South Africa, P1 Brazil

B.1.1.7 lineage (20I/501Y.V1 VOC 202012/01): This variant carries a mutation in the receptor binding domain (RBD) of the spike protein at position 501; asparagine (N) has been replaced with tyrosine (Y) at this position. The mutation is also termed as N501Y. This variant also carries other mutations, including -

• 69/70 deletion: spontaneously occurred several times; possibly results in a conformational change in the spike protein;
• P681H: spontaneously occurred several times; near the S1/S2 furin cleavage site.

The variant is tied to heightened transmissibility (more efficient and rapid transmission). In January this year, scientists from Britain pointed that the B.1.1.7 variant may be linked with increased risk of death in comparison with other variants. Early reports do not indicate that the variant affects the severity of disease or vaccine efficacy.

B.1.351 lineage (20H/501Y.V2): This variant carries several mutations in the spike protein, which include K417N, E484K, N501Y. This variant does not carry the 69/70 deletion. The variant was first detected in South Africa, in samples as old as from the start of October last year. Cases have been identified outside of South Africa as well. E484K mutation in this variant may have an impact on neutralization by some polyclonal and monoclonal antibodies.

P.1 lineage (20J/501Y.V3): This variant is a branch off the B.1.1.28 lineage, first identified by the National Institute of Infectious Diseases (NIID) in Japan among four travelers from Brazil. The samples were tested during routine screening at Haneda airport. This variant has three mutations in the spike protein RBD, including K417T, E484K, and N501Y. Evidence indicates that some of the mutations in this variant may have an impact on its transmissibility and antigenic profile, thus affecting the potential of antibodies produced by a natural infection or vaccine to identify and neutralize the virus.

Some consequences of emerging variants:

• Potential for quicker spread: D614G mutation increases the ability of the virus to spread more quickly compared to the wild-type virus. Laboratory experiments have shown that 614G variants propagate more quickly in human respiratory epithelial cells, and outperform the 614D viruses. Data also suggest that the 614G variant spreads more quickly than viruses without the mutation.
• Potential to cause milder or more severe disease in people: The 1.1.7 variant may be tied to a heightened risk of death compared to other variants.
• Potential to evade detection by viral diagnostic tests: 1.1.7 has S gene target failure
• Diminished susceptibility to therapeutic agents like monoclonal antibodies: 1.1.28
• Potential to evade natural or vaccine-induced immunity: 1.1.28

Once a large population receives vaccination, immune pressure would likely facilitate and speed up the emergence of such variants by selecting for escape mutants.

[CDC]

Coronavirus Cases:

132,402,668

Deaths:

2,873,247

Recovered:

106,686,437

ACTIVE CASES

22,842,984

Currently Infected Patients 22,744,652 (99.6%) in Mild Condition

98,332 (0.4%)

Serious or Critical

CLOSED CASES

109,559,684

Cases which had an outcome: 106,686,437 (97%) Recovered / Discharged

2,873,247 (3%)

Deaths

 (Source: https://www.worldometers.info/coronavirus/)

India

5^th April: New Cases 96557, New Deaths 445, Total Cases 12684477, Total Deaths 165577, Active Cases 788855

4^th April: New Cases 103793, New Deaths 477, Total Cases 12587920, Total Deaths 165132, Active Cases 742830

3^rd April: New Cases 92998, New Deaths 514, Total Cases 12484127, Total Deaths 164655, Active Cases 177638

2^nd April: New cases 89019, New Deaths 713, Total Cases 12391129 Total Deaths 164141, Active Cases 659928

1^st April: New Cases 81441, New Deaths 468, Total Cases 12302110, Total Deaths 163428, Active cases 615798

31^st March: New Cases 72182, New Deaths 458, Total Cases 12220669, Total Deaths 162960, Active Cases 585215

30^th March: New Cases 53158, New Deaths 355, Total Cases 12148487, Total Deaths 162502, Active Cases 553933

29^th March: New Cases 56119, New Deaths 266, Total Cases 12095329, Total Deaths 162147, Active Cases 54235328^th March: New Cases 68206, New Deaths 295, Total Cases 12039210, Total Deaths 161881, Active Cases 523602

27^th March: New cases 62631, New deaths 311, Total Cases 11971004, Total Deaths 161586, Active Cases 487840

26^th March: New cases 62291, New Deaths 292, Total Cases 11908373, Total Deaths 161275, Active Cases 454249

25^th March: New Cases 59069, New Deaths 257, Total Cases 11846082, Total Deaths 160983, Active Cases 422596

24^th March: New Cases 53419, New Deaths 249, Total Cases 11787013, Total Deaths 160726, Active Cases 396696

23^rd March: New Cases 47264, New Deaths 277, Total Cases 11733594, Total Deaths 160477, Active Cases 370101

22^nd March: New cases 40611, New Deaths 197, Total Cases 11686330, Total Deaths 160200, Active Cases 347071

21^st March: New Cases 47009, New Deaths 213, Total Cases 11645719, Total Deaths 160003, Active Cases 336392

20^th March: New Cases 43815, New deaths 196, Total Cases 11598710, Total Deaths 159790, Active cases 310801

19^th March: New cases 40950, New Deaths 189, Total Cases 11554895, Total Deaths 159594, Active Cases 290154

18^th March: New Cases 39643, New Deaths 155, Total Cases 11513945, Total Deaths 159405, Active Cases 273062

17^th March: New Cases 35838, New deaths 171, Total Cases 11474302, Total Deaths 159250, Active Cases 1128238

16^th March: New cases 28869, New Deaths 187, Total Cases 11438464, Total Deaths 159079, Active cases 236008

15^th March: New Cases 24437, New Deaths 130, Total Cases 11409595, Total Deaths 158892, Active Cases 225139

14^th March: New Cases 26514, New Deaths 120, Total Cases 11385158, Total Deaths 158762, Active Cases 220951

13^th March: New Cases 25153, New Deaths 159, Total Cases 11358644, Total Deaths 158642, Active Cases 212147

12^th March: New Cases 27512, New Deaths 157, Total Cases 11333491 Total Deaths 158483, Active Cases 203661

11^th March: New Cases 21668, New Deaths 113, Total cases 11305979, Total Deaths 158326, Active Cases 200401

10^th March: New Cases 22841, New Deaths 134, Total Cases 11284311, Total Deaths 158213, Active Cases 190295

9^th March: New Cases 16846, New Deaths 113, Total cases 11261470, Total Deaths 158079, Active Cases 185767

8^th March: New Cases 15353, New Deaths 76, Total Cases 11244624, Total Deaths 157966, Active Cases 189172

7^th March: New Cases 18691, New Deaths 99, Total Cases 11229271, Total Deaths 157890, Active Cases 190501

6^th March: New Cases 18716, New Deaths 98, Total Cases 11210580, Total Deaths 157791, Active Cases 186253

5th March: New Cases 18292, New Deaths 109, Total Cases 11191864, Total Deaths 157693, Active Cases 181997

4^th March: New Cases 16824, New Deaths 113, Total Cases 11173572, Total Deaths 157584, Active Cases 177967

3^rd March: New Cases 17425, New Deaths 86, Total Cases 11156748, Total Deaths 157471, Active Cases 175044

2^nd March: New Cases 15704, New Deaths 110, Total Cases 11139323, Total Deaths 157385, Active Cases 171776

1^st March: New Cases 11563, New Deaths 80, Total Cases 11123619, Total Deaths 157275, Active Cases 169786

28^th February: New Cases 15616, New Deaths 108, Total Cases 11112056, Total Deaths 157195, Active Cases 170293

27^th February: New Cases 17346, New Deaths 117, Total Cases 11096440, Total Deaths 157087, Active Cases 166079

26^th February: New cases 16056, New Deaths 109, Total Cases 11079094, Total Deaths 156970, Active Cases 160985

25^th February: New Cases 16568, New deaths 119, Total Cases 11063038, Total Deaths 156861, Active Cases 15741824^th February: New Cases 17144, New Deaths 144, Total Cases 11046470, Total Deaths 156742, Active Cases 153257

23^rd February: New Cases 13463, New Deaths 100, Total Cases 11029326, Total Deaths 156598, Active Cases 148584

22^nd February: New Cases 10792, New Deaths 80, Total Cases 11015863. Total Deaths 156498, Active Cases 148882

21^st February: New Cases 13980, New Deaths 79, Total Cases 11005071, Total Deaths 156418, Active Cases 151639

20^th February: New Cases 14315, New Deaths 99, Total Cases 10991091, Total Deaths 156339, Active Cases 147214

19^th February: New Cases 14587, New Deaths 117, Total Cases 10976776, Total Deaths 156240,

18^th February: New cases 12643, New Deaths 85, Total Cases 10962189, Total Deaths 156123, Active Cases 140998

17^th February: New Cases 12440, New Deaths 89, Total Cases 10949546, Total Deaths 156038, Active Cases 138802

16^th February: New Cases 11795, New Deaths 109, Total Cases 10937106, Total Deaths 155949, Active Cases 138254

15^th February: New Cases 9139, New Deaths 76, Total Cases 10925311, Total Deaths 155840, Active Cases 138579

India predictions

1. Death rate is deaths today vs number of cases today.
2. Corrected death rate is deaths today vs number of cases 14 days back.
3. For one symptomatic test positive case, there are 10-30 asymptomatic cases and 20 untested cases.
4. Estimated number of deaths = Reported deaths x 2.
5. Number of deaths today should be 15% of the serious patients present 14 days back.
6. Amongst active cases, 2.37% are serious, 1.82% need oxygen, and 0.41% need ventilator support.

Facts

DENSITY: India: In states with average population density of 1185/sq km, the average number of cases were 2048. On the contrary, in states with population density of 909/sq 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] 

COVID Sutra: COVID-19 pandemic is due to SARS 2 Beta-coronavirus (different from SARS 1 where spread was only in serious cases); with over eleven virus sequences floating; Causes Mild or Atypical 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 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 of copies of itself, which are then breathed or coughed out and infect others.

The most important

1. Masking is THE prevention
2. RT PCR Ct is THE test for diagnosis
3. Zinc is THE Vitamin
4. Day 5 is THE day in COVID phase for mortality prevention
5. Day 90 is THE day after which the word COVID ends
6. Home Isolation is THE modality of Treatment
7. 12 years is THE age when the mortality starts
8. CRP is THE lab test for seriousness
9. Loss of Smell is THE symptom equal to RT PCR test
10. 15 minutes is THE time to get the infection.

Numbers to remember

1. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2770945: RDW at admission 14.5%

Other Sutras

1. Viral particles are seen in tears, stool, kidneys, liver, pancreas, heart, semen, peritoneal fluid, CSF.
2. Thrombosis: University of Pennsylvania has reported that clots are seen in patients even on blood thinners.
3. Other human beta-coronaviruses have immunity lasting only for one year with no IMMUNITY PASSPORT.
4. In absence of interventions, prolonged or intermittent social distancing (till 2022-24) is the key.
5. Due to low levels of cross immunity from other beta-coronaviruses against SARS-CoV-2, the virus may appear to fade away, only to show resurgence after a few years. Surveillance till 2024.
6. During peak, trace and treat, and after the peak, trace and treat the close contacts.
7. Increased spread: Close environment, crowded place with close physical contacts with no ventilation.
8. 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.
9. HCW: Direct patient exposure time < 30 minutes; 7 days work and 7 days holidays.
10. Italy: mortality reduced when they were short of ventilators.
11. Hospital at HOME: CHF, mild pneumonia, exacerbations of asthma and COPD, cellulitis, and urinary tract infections.
12. Great Imitator (protean manifestation).
13. IgM can be false positive in pregnancy, immunological diseases; Pooled tests when seroprevalence is <2%.
14. Early treatment, day 3-5, to reduce the viral load and prevent cytokine storm.
15. Hypoxia: Low flow oxygen <6l/mt, titrated to high flow oxygen using non rebreathing mask, Venturi mask, HFNC and helmet CPAP, NIV in supine or prone position.
16. Early intubation with prone ventilation only if progressive. Hypoxia (walking dead) have capillary problem and not alveoli.

Formulas and Predictions

Deaths

1. The goal is to save lives. Monitoring deaths is important, especially when testing is limited.
2. Daily deaths are the best indicator of the progression of the pandemic, although there is generally a 17- to 21-day lag between infection and deaths.
3. Deaths in symptomatic cases: Less than one percent (best of the care).
4. Therefore, Deaths X 100 = expected number of symptomatic cases
5. Some may count probable or presumptive COVID-19 deaths when cases are not confirmed with a positive test but on the basis of symptoms and medical history. In New York, 3,700 presumptive deaths were added in one day in April when testing was limited.
6. Case fatality rate: Number of total deaths as on date/number of total RT PCR positive cases as on today
7. Infection fatality rate: Number of total deaths as on date/number of total calculated cases as on today
8. Number of reported deaths = Number of confirmed deaths x 2

Prediction Metrics

1. The University of Washingtons Institute for Health Metrics and Evaluation (IHME):

Is based on what is known about a disease and how peoples actions may affect that.

Forecasts are not fixed but change depending on public behavior. When people learn that new cases are rising, they start wearing masks and using social distancing again; and when they realize that fresh cases are dropping, they tend to drop their guard.  IHME makes use of real-time infection data from Johns Hopkins Universitys Coronavirus Resource Center to represent disease transmission and estimate how many Americans will die. The researchers then estimate how many Americans are wearing masks or using social distancing, which can modulate the final model.

The rate of infection in a population is based on the "R0," or reproduction number. R0 represents the average number of people who will contract the infection from a single infected person, in a population thats never been witness to the disease before. If R0 is 3, it suggests that one case will create an average of three new cases. When that transmission rate of infection occurs at a specific time, its called an "effective R," or "Rt."  R0 less than 1 means the epidemic is under control; and when its higher than 1, it is still spreading.

IHME found the "effective R over 1 in Oklahoma. In all other states the effective R was found to be less than 1.”

2. CDC: Relies on positive tests results. CDCs report these as confirmed cases. The positivity rate suggests how tough or easy it is to find a case, which is an indicator of both the spread of COVID-19 and how widespread testing is. If the rate of positive tests is 20%, one doesn’t have to look hard to find a case, compared to 1%, which means that one has to do a lot of tests to get a positive one. The more COVID-19 spreads, the higher the positivity rate. A 60% positivity rate may suggest that testing is only being done in a nursing home during an outbreak or a hospital where the most apparent cases are and not the general population where cases may be milder.
3. Marylands COVID-19 dashboard: It reports the daily positivity percentage (percentage of positive tests and total testing volume since March). While looking at testing, one wants to know how many tests were done historically with the ability to compare and understand if the number has increased or declined or is stable and the percentage that is positive. Maryland and Pennsylvania report a 7-day rolling average of the daily positivity percentages. The 7-day average rate better indicates a trend as compared to daily numbers.
4. The testing numbers often fluctuate, depending on where testing is done and when the labs report test results. A sudden surge in testing numbers may point to a large number of tests done in a group setting such as a nursing home or prison on a single day. Laboratories and hospitals report test results on weekdays, so the numbers can decline on weekends.
5. A major goal during the coronavirus epidemic has been to flatten the curve to maintain local hospital capacity. After expected COVID-19 surges, many hospitals limited surgeries and admissions to preserve their resources, including hospital beds, ventilators, and healthcare personnel. [WebMD]

Infrastructure Capacity

1. If hospital capacity reaches 80%, we may have to stop admitting patients to prevent the hospital from being overwhelmed.
2. In order to plan for surges and increase capacity: It is required to know the number of people who tested positive and were admitted to the hospital with symptoms of COVID-19.
3. Pennsylvanias COVID-19 dashboard: has a hospital preparedness page that shows the number of hospitalized COVID-19 patients and the number and percentage of available beds by unit, including intensive care, medical/surgical, and airborne isolation.
4. Pennsylvania: Reports the number of ventilators COVID-19 patients and non-COVID-19 patients use every day.
5. Illinois lists the recovery rate: In Illinois, the recovery rate of 95% has been calculated as recovered cases divided by recovered cases plus confirmed deaths. This indicates the quality of medical care and the severity of disease.[WebMD]

Some more numbers

1. Cases will double after the average doubling time of the country at that time
2. Cases expected in the community: Get number of deaths occurring in a five-day period

Estimate the number of infections required to generate these deaths based on the country or area case fatality rate

Compare that to the number of new cases actually detected in the five-day period.

This can then give us an estimate of the total number of cases, confirmed and unconfirmed

3. Lock down effect: Reduction in cases after average incubation period (5 days)
4. Lock down effect in reduction in deaths: Reduction in number of deaths on day 14 (average time to death of that country)
5. Requirement of ventilators on day 9: 1-3% of number of new cases detected
6. Requirement of future oxygen on day 7: 10% of total cases detected today
7. Number of people which can be managed at home care: 90% of number of cases today
8. Requirement of ventilators: 1-3% of number of cases admitted 7-9 days back
9. Requirement of oxygen beds today: 10% of total cases admitted seven days back
10. Number of unreported or untested cases: Number of reported cases x 10-30 (depending on the country, New York 10, Delhi 23.8, Pakistan 30)
11. Number of asymptomatic cases: For 6 symptomatic cases, 200 asymptomatic cases (CHINA); (1.78 M tests in Hong Kong, 32 asymptomatic cases, 10 symptomatic cases)
12. Oxygen requirement on that day in the hospital at 6am: Number of cases detected to have hypoxia on six minutes walk test.

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA