Thursday, May 28, 2020

CMAAO CORONA FACTS and MYTH BUSTER 107 Strategic Lessons

CMAAO CORONA FACTS and MYTH BUSTER 107 Strategic Lessons

929:  Lessons learnt from coronavirus strategies
Dr K K Aggarwal
President CMAAO

With inputs from Dr Monica Vasudev

1.     Italy reached nearly 100,000 Covid-19 cases and more than 10,000 deaths by March 29, becoming the deadliest epicentre in the pandemic. They were slow to implement strict social distancing measures and, even once officials began to institute social distancing as Covid-19 cases began to spike, the public did not seem to respond to government directives with urgency. Italy suffered from “a systematic failure to absorb and act upon existing information rapidly and effectively rather than a complete lack of knowledge of what ought to be done.”

2.     In early days it was common to see officials sceptical of the Covid-19 threat pointing to low fatality numbers and asking why there was panic, given how many people die of the seasonal flu every year. But the coronavirus spreads stealthily, with those who contract it not showing symptoms for days, and the full gravity of their illness not becoming clear until a week or two after infection.

Most political leaders of the world who have not faced the taste of SARS and MERS earlier did not act pre-emptively despite evidence suggesting such delays could increase the number of cases. State-of-emergency declarations were shrugged off by the public and political leaders.

3.     Threats such as pandemics that evolve in a non-linear fashion (they start small but exponentially intensify) are especially tricky to confront because of the challenges of rapidly interpreting what is happening in real time. The most effective time to take strong action is extremely early, when the threat appears to be small — or even before there are any cases. But if the intervention actually works, it will appear in retrospect as if the strong actions were an overreaction. This is a game many politicians don’t want to play. The first step to a better pandemic response is acknowledging the current situation.

When three cases appeared in Kerala India between 31st January and 2nd February, even India did not close the International boarders thinking it to be a Kerala local [problem. They only acted on 22nd March.

4.     Ignoring and not anticipating the problem of migrants: Italy started small with its coronavirus containment and only expanded it as the scale of the problem revealed itself. The country started with a targeted strategy: Certain areas with a lot of infections were designated as “red zones.” Within the red zones, there were progressive lockdowns depending on the severity of the outbreak in the area. The restrictions were only broadened to the whole country when these measures did not stop the virus’s spread.

In fact, these limited lockdowns made it worse. Because the coronavirus transmits so silently, the “facts on the ground” (number of cases, deaths, etc.) didn’t actually capture the full scale of the problem. Once partial lockdowns went into effect, people fled to less restricted parts of the country — and they may have unwittingly taken the virus with them.

The selective approach might have inadvertently facilitated the spread of the virus. Consider the decision to initially lock down some regions but not others. When the decree announcing the closing of northern Italy became public, it touched off a massive exodus to southern Italy, undoubtedly spreading the virus to regions where it had not been present.

Even in India after the 3rd lock down was partially lifted the migrants caused a surge in the cases.  Between 3.5 to 7% of them became positive and carried the infection to other states.

5.     There will be a surge after the lockdown is lifted: The disease will continue to spread with no lockdown, social distancing, or other intervention with no change in transmission rate. R0= 2.66

If there is moderate lockdown, it will reduce transmission to R0 of 2 during lockdown period, then transmission will resume at R0 of 2.4.

In Hard Lockdown, there will be reduced to R0 of 1.5 during lockdown period, then transmission will resume at R0 of 2.4.

And with Hard Lockdown and Continued Social Distancing/Isolating Cases there will be reduced transmission to R0 of 1.5 during lockdown period, then, through social distancing regulations and isolation of symptomatic individuals will resume at R0 of 2.

6.     Uniform national policy vs state policies: Both India and USA did not declare a public health national emergency and had asked states to take care of the problem. Trump did issue his recommendation that people stay home for 15 days to stop the Covid-19 spread, but he did not renew the call. States took different approaches: some, like New York, California, and Washington locked down completely. Others, like Florida, were reluctant to take the same step.

7.     Lockdown will only postpone the worse: Italy’s experience indicates that truncated social distancing periods and a mishmash of social distancing policies across different interlocked areas only prolonged and deepened the problem.

8.     Public ignorance: The message that personal social distancing and masking will never be lifted for the next few years has not been understood by the masses as yet.

9.     Having two strategies in the same country: The experiences of Lombardy and Veneto, two neighbouring Italian regions that took two different strategies for their coronavirus response and saw two different results, are instructive. Lombardy has 10 million people, and it has endured 35,000 Covid-19 cases and about 5,000 deaths; Veneto is home to 5 million people, but it has seen just 7,000 cases and fewer than 300 deaths. Its outbreak is a fraction the size of its neighbour’s.

This is what Veneto did to successfully control the outbreak:
Extensive testing: People with symptoms and people who were asymptomatic were tested whenever possible.

Proactive tracing: If somebody tested positive, everybody they live with was tested or, if tests weren’t available, they were required to self-quarantine.
Emphasis on home diagnosis and care: Health care providers would actually go to the homes of people with suspected Covid-19 cases to collect samples so they could be tested, keeping them from being exposed or exposing other people by visiting a hospital or doctor’s office.

Monitoring of medical personnel and other vulnerable workers: Doctors, nurses, caregivers at nursing homes, and even grocery store cashiers and pharmacists were monitored closely for possible infection and given ample protective gear to limit exposure.

Lombardy, on the other hand, was much less aggressive on all of those fronts: testing, proactive tracing, home care, and monitoring workers. Hospitals there were overwhelmed, while Veneto’s have been comparatively spared. And yet it took weeks upon weeks for Lombardy to adopt the same strategies that were already working next door in Veneto:

10.  Not reporting the proper data or underreporting the data for political gains: Importance of good data — the raw numbers themselves — which were lacking in the early days of Italy’s outbreak. These figures should focus on the important metrics like tests conducted and hospitalizations. The data is often downplayed by most countries. Every one wants gto show that they have the best results. .

Wuhan Update: In two weeks, the Chinese health authorities managed to administer 6.5 million tests for the coronavirus in Wuhan, the city where the pandemic began and where six new infections detected two weeks ago raised fears of a second wave of contagion.  200 cases were found, mostly people who showed no symptoms. This study demonstrates that for every, one symptomatic case there are 33 asymptomatic cases.

Actual Cases (1.7 million: 10 times the number of confirmed cases)
New York State conducted an antibody testing study
12.3% of the population COVID-19 antibodies as of May 1, 2020.
The survey developed a baseline infection rate by testing 15,103 people at grocery stores and community centers across the state over the preceding two weeks. The study provides a breakdown by county, race (White 7%, Asian 11.1%, multi/none/other 14.4%, Black 17.4%, Latino/Hispanic 25.4%), and age, among other variables. 
19.9% of the population of New York City had COVID-19 antibodies.
With a population of 8,398,748 people in NYC, this percentage would indicate that 1,671,351 people had been infected with SARS-CoV-2 and had recovered as of May 1 in New York City. The number of confirmed cases reported as of May 1 by New York City was 166,883, more than 10 times less.

11. Actual deaths are twice the number of reported deaths

As of May 1, New York City reported 13,156 confirmed deaths and 5,126 probable deaths (deaths with COVID-19 on the death certificate but no laboratory test performed), for a total of 18,282 deaths

The CDC on May 11 released its "Preliminary Estimate of Excess Mortality During the COVID-19 Outbreak — New York City, March 11–May 2, 2020" in which it calculated an estimate of actual COVID-19 deaths in NYC by analyzing the "excess deaths" (defined as "the number of deaths above expected seasonal baseline levels, regardless of the reported cause of death") and found that, in addition to the confirmed and probable deaths reported by the city, there were an estimated 5,293 more deaths to be attributed. After adjusting for the previous day (May 1), we get 5,148 additional deaths, for a total of actual deaths of 13,156 confirmed + 5,126 probable + 5,148 additional excess deaths calculated by CDC = 23,430 actual COVID-19 deaths as of May 1, 2020 in New York City.

Mortality Rate (23k / 8.4M = 0.28% CMR to date) and Probability of Dying

As of May 1, 23,430 people are estimated to have died out of a total population of 8,398,748 in New York City. This corresponds to a 0.28% crude mortality rate to date, or 279 deaths per 100,000 population, or 1 death every 358 people.

Infection Fatality Rate (23k / 1.7M = 1.4% IFR)

Actual Cases with an outcome as of May 1 = estimated actual recovered (1,671,351) + estimated actual deaths (23,430) = 1,694,781.
Infection Fatality Rate (IFR) = Deaths / Cases = 23,430 / 1,694,781 = 1.4% (1.4% of people infected with SARS-CoV-2 have a fatal outcome, while 98.6% recover).

12.  Admitting covid patients in non covid hospitals instead of managing them at home: Home admissions: Coronavirus can hit "like a tsunami". In one hospital in Italy more than 100 out of 120 people admitted with the virus developed pneumonia. Doctors became  patients. Opening separate COVID-19 blocks to admit and treat the infected patients made the hospital hot spots. Delhi is doing the same mistake that Italy made.

Do not allow hospitals becoming “the main” source of Covid-19 transmission. The related coronavirus illness MERS also has high transmission rates within hospitals, as did SARS during its 2003 epidemic.
Major hospitals in Italy such as Bergamo’s themselves became sources of [coronavirus] infection with Covid-19 patients indirectly transmitting infections to non-Covid-19 patients. Ambulances and infected personnel, especially those without symptoms, carry the contagion both to other patients and back into the community.

Covid-19 patients started arriving and the rate of infection in other patients soared. That is one thing that probably led to the disaster in Italy.
Western health care systems have been built around the concept of patient-cantered care. But a pandemic requires “community-cantered care.”. Broader good overrules over the individual good.

Wednesday, May 27, 2020

CMAAO CORONA FACTS and MYTH BUSTER 106 Lessons Learned So far from COVID

CMAAO CORONA FACTS and MYTH BUSTER 106 Lessons Learned So far from COVID

Dr K K Aggarwal
President Confederation of Medical Associations of Asia and Oceania, HCFI, Past National President IMA, Chief Editor Medtalks

Round Table Expert Zoom Meeting on Lessons learnt from Covid-19

23rd May, 2020


Dr KK Aggarwal
Dr Alok Roy
Dr AK Agarwal
Dr Narottam Puri
Dr Suneela Garg
Dr Girdhar Gyani
Dr Atul Pandey
Dr Ashok Gupta
Dr Jayakrishnan Alapet
Dr Alex Thomas
Dr K Kalra
Dr Major Prachi Garg
Ms Ira Gupta
Dr Sanchita Sharma

·        Do not miss the first case in the country or your state. A first case of a new disease is a potential epidemic.
·        We should have permanent Arogya Setu App for all notifiable communicable diseases, specifically MDR TB and other highly infectious diseases. Personal privacy does not apply in cases of notifiable diseases. The concept of “broader good” comes into play here.
·        Elderly are at risk. We must have a national program for the protection of health of the elderly. There is a need to set up separate geriatric medicine departments in all medical colleges. It is also important to establish a group of doctors aged ≥65years. Their rich experience can be tapped into in times of crisis.
·        Contact time: we must know the contact time for every disease. For TB, the contact time is 8 hours. For Covid-19, the contact time is between 10 and 30 minutes. A casual contact time of less than 10 minutes has low risk of transmission (monitoring). If the contact time is more than 30 minutes, the risk of transmission is high (quarantine).
·        A virus may have several different types of presentations/manifestations in different countries or population groups and the treatment will be according to the presentation. Identify the presentation in different communities. Covid-10 has so far shown the following 7 characteristics.
1.    It is a viral illness, so it is self-limiting disease; antiviral drugs like remdesivir may work
2.    It has bacterial activity as in some cases, procalcitonin is high, neutrophilia is also seen; antibiotics like doxycycline, azithromycin may work.
3.    It has some HIV like properties, as there is lymphopenia (viruses usually cause lymphocytosis), decrease in CD4 cell count; anti-HIV drugs may be effective.
4.    It causes immuno-inflammation: Viruses do not cause immunoinflammation. But, increase in ESR (>100), CRP, ferritin (acute phase reactants) is seen in Covid-19. Hydroxychloroquine may be effective. Immunoinflammation is being seen much more in European countries than in Asian countries.
5.    It causes thrombo-inflammation: Increase in d-dimer and fibrinogen (usually if d-dimer is high, fibrinogen is low); anticoagulation may be important.
6.    Silent hypoxia (walking dead phenomenon): Patients have low oxygen but are conscious. Usually, people with hypoxia are drowsy, irritable.
7.    Cytokine storm: ARDS
·        We have learnt three terms: Home isolation, home quarantine and monitoring.
·        The pandemic has focused on different populations e.g. migrants, factory workers, private sector
·        The problem of migrants should be anticipated timely and planned properly. Positivity rate in India is 3.5-7%
·        Random testing rate of people reaching Bihar is 8% and for those reaching UP is 5%.
·        Living with fear: Manage fear by being well-prepared.
·        Treat the patient, not the report. About 30% of tests may be false-negative.
·        There should be a worldwide ban on wet markets.
·        Vaccine may or may not come. We may be over-relying on a vaccine.
·        Health infrastructure will change. Now, new hospitals will be airy, roomier, more ventilated; there will be no central AC, no attached bathroom with every room.
·        Standard precautions: We did not learn social distancing from the 2009 H1N1 flu. Face to face meeting is more risky than side to side meeting.
·        Never ignore nature.
·        Never ignore essential health services.
·        Super spreader: A latest study from Israel says that 5% people are responsible for the remaining 95% of transmission. This is similar to the 80/20 rule, which has been the standard teaching in PSM, where approximately 20% of infected individuals are responsible for 80% of transmissions. The first known super spreader was in South Korea (patient #31) and then there have been super spreaders in different countries.
·        We have learnt how to sustain the improved pollution. If pollution levels are very high, then a lockdown of 1-2 days may help.
·        Terms like R0 (R naught; reproduction number), herd immunity have been revisited.
·        Create more awareness in the society.
·        Transparent communication and dissemination of accurate information to promote community engagement is important to allay the fears, stigma. We need to be consistent in data projections.
·        Be a realist rather than being an optimist when presenting data”
·        This pandemic has highlighted the inadequacy in testing and testing facilities, the importance of investment in health and more focus on research and indigenous health technologies.
·        We must keep a watch on every situation happening in the world. Be prepared in advance.
·        The disease has focused on the need of Epidemic Intelligence services, which can forecast epidemics. A training program can be started on pilot basis in few medical colleges.
·        Learn to live with Corona is the new buzzword.
·        A change in lifestyle with new norms is key “self-disciplined”; practice social distancing, personal hygiene.
·        This is an opportunity to be self-sufficient, self-reliant and promote “Make in India”. The pandemic started with virtually no PPE but there are now over 600 manufacturers.
·        We have to devise ways to keep the economy running as the pandemic has greatly affected the jobs leading to a negative GDP.
·        This is an opportunity to decongest slums.
·        We need to have a White Paper on national health security.


Seven lungs from patients who died of confirmed COVID-19 and seven lungs obtained during autopsy from patients who died from H1n1 ARDS in 2009, showed three distinctive features of COVID-19:

·        Severe endothelial injury associated with intracellular SARS-CoV-2 virus and disrupted endothelial cell membranes
·        Widespread vascular thrombosis with microangiopathy and occlusion of alveolar capillaries
·        Significant new vessel growth through intussusceptive angiogenesis.

This is a respiratory virus that causes a vascular disease, and the damage to the blood vessels

May 21 in the New England Journal of Medicine.

Although lungs from influenza sufferers also showed diffuse alveolar damage, in the COVID-19 lungs, there were 9-fold as many segments occluded by microthrombi (P < .001).

Although tissue hypoxia was probably a common feature in the lungs from both these groups of patients, the greater degree of endothelialitis and thrombosis in the lungs from patients with COVID-19 may contribute to the relative frequency of sprouting and intussusceptive angiogenesis observed in these patients

The amount of angiogenesis seen was unexpected, and about 2.7-fold higher than that seen in lungs from patients with influenza (P < .001).

Wuhan Update
In two weeks, the Chinese health authorities managed to administer 6.5 million tests for the coronavirus in Wuhan, the city where the pandemic began and where six new infections detected two weeks ago raised fears of a second wave of contagion.  200 cases were found, mostly people who showed no symptoms.

Tuesday, May 26, 2020


Covid in CMAAO countries vs Europe vs USA (Part 2)


Dr K K Aggarwal
President Confederation of Medical Associations of Asia and Oceania, HCFI, Past National President IMA, Chief Editor Medtalks

927: Minutes of Virtual Meeting of CMAAO NMAs

23rd May, 2020, Saturday


Member NMAs

Dr KK Aggarwal, President CMAAO
Dr Yeh Woei Chong, Singapore Chair CMAAO
Dr Kar Chai Koh, Malaysia, Vice Chair of Council
Dr Ravi Naidu, Past President CMAAO, Malaysia
Dr Rajan Sharma, National President IMA
Dr RV Asokan, Secretary General IMA
Dr Thirunavukarasu Rajoo, Hon. General Secretary, Malaysian Medical Association
Dr Alvin Yee-Shing Chan, Hong Kong
Dr Marie Uzawa Urabe, Japan
Dr Sajjad Qaisar, Pakistan
Dr Ashraf Nizami, Pakistan
Dr Deborah Cavalcanti, Brazil
Dr Marthanda Pillai, Member World Medical Council
Dr Md Jamaluddin Chowdhary, Bangladesh
Dr N Gnanabaskaran, President Malaysian Medical Association


Dr Russell D’Souza, UNESCO Chair in Bioethics, Australia
Dr KK Kalra, Former CEO NABH
Dr Sanchita Sharma, Editor IJCP Group

  • Death rate is much lower in Asian countries compared to that in Europe and US. This low death rate is despite high population density.
  • In the US, death rate is higher in Black population. A reason for this can be that ACEIs do not work in this population. Could the level of ACE receptors be different in people from Asia vs Europe vs North US? We do not know.
  • Vaccine developed from a virus from US or Europe may not work in Asian population.
  • In an update, the CDC has said that person-to-person transmission is the primary and most important mode of transmission for COVID-19. Surface to human transmission is not the main way the virus spreads.
  • A latest study from Israel study says that 5% of population is responsible for the remaining 95% of cases.
  • Super-spreader is must to cause infection; in the absence of a super-spreader the infection will die out. If a super-spreader is present in closed space, the chances of transmission of infection are very high.
  • One reason for low mortality can be good ICU care. Good ICU care makes a difference in mortality by only 0.3-0.5%.
  • Another reason for low mortality is the availability of Airborne Infection Isolation (AII) rooms or negative pressure rooms.
  • Countries like Hong Kong, Singapore, South Korea have more number of AII rooms, which also serve as triage rooms and the patient is shifted to a Covid/non-Covid ward depending on the report, which is available within 3 hours in the triage room itself.
  • In countries like India who do not have AII rooms, the patient should be in a room which has an air purifier with at least 10 exchanges per hour.
  • The difference in clinical manifestations of the virus may influence mortality rates.  
o   It is a viral illness, so it is self-limiting disease in majority; antiviral drugs like remdesivir may work
o   It has bacterial activity as in some patients, high procalcitonin; antibiotics like doxycycline, azithromycin may be effective.
o   It has some HIV like properties, as there is lymphopenia (viruses usually cause lymphocytosis), decrease in CD4 cell count; such patients may respond to anti-HIV drugs.
o   It causes immuno-inflammation: Viral disorders do not cause immunoinflammation. But, increase in ESR, CRP, ferritin (acute phase reactants) is seen in Covid-19. Anti-inflammatory drugs (hydroxychloroquine) may be effective. Immunoinflammation is being seen much more in European countries than in Asian countries.
o   It causes thrombo-inflammation: Increase in d-dimer and fibrinogen; patient requires anticoagulation.
o   Silent hypoxia (walking dead phenomenon): Low oxygen but patient is conscious. Usually, people with hypoxia are drowsy, irritable. This was predominant in Italy. Their mortality improved when they stopped using ventilators.
o   Cytokine storm: ARDS
o   If we know the clinical pattern of patients in different countries, we can find out mortality and also identify a country-specific treatment. In the UK, multisystem immune inflammation is more with increased mortality. This is not seen in Asian countries.
  • Asian countries have lower mortality when compared to Europe and the US, but we do have a reasonable mortality rate and it may increase if we calculate accurately, register all cases and there is better investigation and reporting of cases. It may go up to 2.5-3% in Pakistan.
  • Other reasons can be: Asians already have high immunity; testing is not as aggressive as in Europe, US, the strain of the virus is not aggressive so mostly mild to moderate cases
  • Low mortality in Hong Kong may be attributed to: preventive measures (universal masking, people complying with the directives), local culture (no hugging/kissing), cases are in younger population and are imported, which are mild and lastly, well-prepared investment in ICU facilities and ventilators. Those who died had comorbidity like diabetes.
  • In Singapore, most cases are in migrants, who are young and therefore have mild infection.
  • The lower mortality in Malaysia is because of early interventions, the govt. has been preparing for the worst since March, and all persons who qualify for PUI (person under investigation) are screened and isolated based on the result.
  • Japan has 16,000 positive cases; 800 have died; mortality rate is 5%; Japan has limited PCR tests so this rate compared to the population is very low. Japan is carrying out genome analysis in 500 patients (from asymptomatic to patients with severe symptoms). HLA typing is on the way. High IgM level is related to the severity of disease. Some patients may have early detection of IgG. This may be related to previous infection with other coronavirus. Further research is needed.
  • India: Despite high numbers, the mortality rate is 3%. Experience of the European countries has helped us to lower mortality; also, there is genetic protection from the infection.

Contact time: 10-30 minutes
  • If contact time is less than 10 minutes with precautions, the chances of transmission is very low
  • If a doctor is wearing a N95 mask and the contact time is less than 30 minutes, this is usually not a problem

Protocol of non-Covid clinic in Singapore

A patient who came to the clinic in the morning and tests positive in the evening, answer the following question:

Was the patient wearing a mask? If yes, then ask,

Was the doctor wearing a mask? If yes, then ask,

Was the surface decontaminated in the morning? If yes, then ask,

What was the contact time?

  • If less than 30 min: Monitor
  • If more than 30min: Quarantine

Covid-19 infection in children

  • 13% of children all over the world have Covid-19; mortality is 0.5% in children below 15 years of age.
  • Child to child transmission is rare; but, children can infect the elderly.
  • For children <2 years: no masking
  • For children >2 years: Country-specific guidelines for masking
  • European countries do not recommend masking for children; we do not have a guideline for Asian countries.

Chances of infection are highest when sitting face to face; chances of infection are lower when sitting side to side or face to side.

In schools and colleges, students sit facing front. So chances of infection very low; distance between students should be at least 6 feet. Students should go home immediately after school/college.

Monday, May 25, 2020

CMAAO CORONA FACTS and MYTH BUSTER 104 Immuno hyper inflammation

Dr K K Aggarwal

President Confederation of Medical Associations of Asia and Oceania, HCFI, Past National President IMA, Chief Editor Medtalks

926: IMA-CMAAO Webinar on “Update on Covid-19 -Immuno-hyper inflammation”

23rd May, 2020


Dr KK Aggarwal, President CMAAO
Dr Rajan Sharma, National President IMA
Dr RV Asokan, Honorary Secretary General IMA
Dr Ramesh K Dutta
Dr Jayakrishnan Alapet
Dr Sanchita Sharma


Dr Rohini Handa
Senior Consultant Rheumatologist, Apollo Hospitals, New Delhi
Former Prof, Dept of Rheumatology, AIIMS, New Delhi


·        The Covid-19 virus is behaving differently in different people. Up to now, we have seen 7 different manifestations of the coronavirus.

1.    It is a viral illness, so it is self-limiting disease; antiviral drugs are effective
2.    It has bacterial activity, procalcitonin is high in some persons; antibiotics like doxycycline, azithromycin may work.
3.    It has some HIV like properties, as there is lymphopenia (viruses usually cause lymphocytosis), decrease in CD4 cell count; anti-HIV drugs may be effective.
4.    It causes immuno-inflammation: rise in acute phase reactants (ESR, CRP, ferritin and platelet count). Hydroxychloroquine may work.
5.    It causes thrombo-inflammation: Increase in d-dimer and fibrinogen; anticoagulation may be important.
6.    Silent hypoxia (walking dead phenomenon): Hypoxia (oxygen 60-70%) without loss of consciousness.
7.    Cytokine storm and ARDS

·        The mortality in Europe is 10-12%, in US 6-7% and in India it is 3-4%. In Europe, we are seeing multisystem inflammatory disease in children with multiorgan involvement (Kawasaki like).
A progressive in d-dimer levels with fall in leukocytic count is a sign of high mortality.

Inflammation is the protective response of the body to noxious stimuli resulting in containment of that insult at the site of injury, which can be cuts, innocuous injuries, infection, toxins etc.
Inflammation, in itself is not bad; it is the unchecked chronic inflammation, which creates problems.

Many diseases now have been identified to have inflammatory components e.g. bronchial asthma, atherosclerosis, obesity, rheumatoid arthritis.

Immunoinflammation is a subset of inflammation where the trigger is a dysregulated immune response. Immune-mediated inflammatory diseases are RA, SLE, systemic sclerosis, Sjogren, ANCA-associated vasculitides. The major trigger in these diseases is the aberrant immune response.

The host inflammatory response phase, which comes into play in some patients, is the major contributor of mortality.

·        Strictly speaking, in Covid-19, it is a hyperimmune response and not immunoinflammation.
·        In a dysfunctional immune response, the virus elicits a hyperimmune response, which is out of proportion to the inciting event in some people. This triggers a systemic cytokine storm, which is responsible for multiorgan failure and mortality.

·        In a healthy immune response, the virus is inactivated by the neutralizing antibodies. There is minimum inflammation and lung damage. This is how most people with viral infection, including Covid-19, recover.

·        But in a subset of people, the dysfunctional immune response goes on unchecked, called “hyperinflammation”, excessive infiltration of macrophages, monocytes and T cells, which leads to an inflammatory cascade, which triggers the cytokine storm, where a number of cytokines come into play leading to pulmonary edema, pneumonia and resulting in widespread inflammation and multiorgan damage.

·        Thrombo-inflammation is another manifestation of Covid-19, where there is interplay of coagulation and inflammation. The procoagulant pathway is triggered which produces microthrombi formation, seen in autopsy samples of Covid-19 patients who have succumbed to the disease.

·        The multiplicity of pathways is the reason why a variety of drugs are being tried.

·        Covid toes, thromboembolism, right heart involvement, Kawasaki-like multisystem inflammation have been seen, but without lung involvement (no ARDS and cytokine storm). So, there must be a separate pathway for hyperinflmmation other than cytokine crisis.  This means that hyperinflammation is only one part of the story; we have a long way to go before we understand the pathobiology of the infection and the pathogenetic mechanisms and the host response.
·        The stage at which the sample is collected will give different findings. This is a challenge.
·        Immuno-mediated inflammatory diseases like Rheumatoid, Sjogren’s, lupus, are no different from that encountered in the West. E.g. many people with history of joint pains, low levels of rheumatoid factor, no deformity are labeled as Rheumaotid, but they are actually Sjogren’s – no questions about dry eyes, dry mouth, caries are asked in these patients. We need to connect the dots.

·        Giant cell arteritis is extremely uncommon in India, Takayasu’s is more common.
·        In children, juvenile idiopathic arthritis (JIA), earlier known as juvenile rheumatoid arthritis, is the commonest type of immuno-inflammatory disease in children. But, it gets labeled as rheumatic fever in India.

·        If there is deforming arthritis in a child, which is not getting better, and Echo is normal, rethink about rheumatic fever. Not all aches and pains in a child are rheumatic fever.

·        Could a virus be linked to autoimmune disorder? The trigger of autoimmunity is not known yet. But it has been believed for long that a virus could trigger an autoimmune disorder. The classical example is parvovirus, which was thought to cause arthritis and now there is Chikungunya. It is believed that Chikungunya may unmask latent autoimmune disorder.

·        Registry data has shown that rheumatoid arthritis patients, who are on a moderate immunosuppression, do not get Covid-19 more than their counterparts and behave similarly, unless they are taking high dose of steroids, or cyclophosphamide.

·        Joint manifestations are not a prominent feature of Covid-19 so far.

·        Pre-existing rheumatoid may flare up with viral infection. But, there is no specific data on Covid-19.

·        Monoclonal antibodies are derived from single cell line; these are biologics as they are derived from living cell systems. They target all three components of the inflammatory pathway: cytokines, receptor and the cell. MAbs target one process and not a large group of cytokines. We do not know yet which is the key cytokine.