Which is the deadliest pandemic

The Spanish flu or 1918 flu pandemic was an unusually deadly influenza pandemic.

How long did it last

January 1918 to December 1920

How many people did it infect

500 million people – this translates to about a quarter of the worlds population at that time.

How many people died

50 million (3-5% of global population)

What was the age group that got killed

Most influenza outbreaks inordinately take the lives of the very young and the very old, with a higher survival rate for those in between, but the Spanish flu pandemic led to a higher than expected mortality rate for young adults. Several possible explanations have been given for the high mortality rate of the 1918 influenza pandemic.

Did it cause cytokine storm

Yes. And malnourishment, overcrowding in medical camps and hospitals, and poor hygiene promoted bacterial superinfection. The superinfection led to the deaths of most of the victims, typically after a somewhat prolonged death bed.

Which virus was it

The Spanish flu was the first among the two pandemics caused by the H1N1 influenza virus; the second was the swine flu in 2009.

How many people died in India

Some 12-17 million people died in India, about 5% of the population.

Were pregnant women at risk

Historian John M. Barry has stated that the most vulnerable of all, i.e., those most likely, of the most likely, to die were pregnant women. In thirteen studies of hospitalized women during the pandemic, the death rate varied between 23% and 71%. Of the pregnant women who survived childbirth, over a quarter of them (26%) lost the child.

Was it as winter flu

The outbreak was widespread in the summer and autumn (in the Northern Hemisphere); however, influenza is usually worse in winter.

Was there a deadly second wave

The second wave of the 1918 pandemic was way more deadly than the first one. The first wave resembled typical flu epidemics, with the sick and elderly being the most at risk. Younger, healthier people recovered easily. By August, as the second wave began in France, Sierra Leone, and the United States, the virus had mutated to a much more deadly form. October 1918 saw the highest fatality rate of the whole pandemic.

 What was aspirin poisoning

A 2009 paper published in the journal Clinical Infectious Diseases by Karen Starko stated that aspirin poisoning contributed substantially to the fatalities.

How was the end of the pandemic

After the lethal second wave began in late 1918, new cases declined suddenly, almost to nothing following the peak in the second wave.

In Philadelphia, 4,597 people died in the week ending 16 October, but by 11 November, influenza had almost disappeared from the city.

There is another theory which states that the 1918 virus mutated very rapidly to a less lethal strain. This is common with influenza viruses: pathogenic viruses tend to become less lethal with time, as the hosts of more dangerous strains tend to die out.

Why it is called forgotten epidemic

 Despite the high morbidity and mortality rates associated with the epidemic, the Spanish flu began to fade from public awareness over the decades until the arrival of news about bird flu and other pandemics in the 1990s and 2000s. That’s why some historians labeled the Spanish flu a "forgotten pandemic".

What were the non pharmacological methods used

Control efforts across the globe included non-pharmaceutical interventions including isolation, quarantine, good personal hygiene, use of disinfectants, and limitations of public gatherings, which were applied unevenly.

Where did we fault

We forgot earlier recommendation of flu

A:  NPIs that are routinely recommended for prevention of respiratory virus transmission, such as seasonal influenza, include personal protective measures for daily use (voluntary home isolation of ill persons, respiratory etiquette, and hand hygiene) as well as environmental surface cleaning measures (routine cleaning of frequently touched surfaces and objects).

During an influenza pandemic, these NPIs are recommended irrespective of the pandemic severity level.

Additional personal and community NPIs are also recommended.

Personal protective measures for pandemics include voluntary home quarantine of exposed household members and use of face masks in community settings when ill.

Community NPIs might include temporary closures or adjournment of child care facilities and schools with students in kindergarten through 12 (K–12), besides other social distancing measures that increase physical space between people (e.g., workplace measures such as replacing in-person meetings with teleconferences or modifying, postponing, or cancelling mass gatherings)

What are personal protective measures for everyday use

These include voluntary home isolation of ill persons, respiratory etiquette, and hand hygiene.

What are personal protective measures reserved for pandemics

These include voluntary home quarantine of exposed household members and use of face masks in community settings when ill.

What are voluntary home isolation (staying home when ill or self-isolation) measures

Persons with influenza stay home for at least 24 hours after a fever or signs of a fever (chills, sweating, and feeling warm or flushed) are gone (https://www.cdc.gov/flu/protect/preventing.htm), except to get medical care or other necessities.

To ensure that fever is no more there, patients’ temperature should be measured in the absence of medication that lowers fever. Besides fever, common influenza symptoms include cough or chest discomfort, muscle or body aches, headache, and fatigue. People also might experience sneezing, a runny or stuffy nose, sore throat, vomiting, and diarrhea (https://www.cdc.gov/flu/consumer/symptoms.htm).

What is the rationale for use as a public health strategy

Most people infected with an influenza virus might become infectious 1 day before the onset of symptoms and remain infectious up to 5-7 days after becoming ill. However, studies suggest that infants and immunocompromised people might shed influenza viruses for prolonged periods (up to 21 days and a mean of 19 days, respectively).

What is triple prevention

Voluntary home isolation, a form of patient isolation, prevents an ill person from infecting others outside of their household.

Respiratory etiquette limits the dispersion of droplets contaminated with influenza virus being propelled through the air by coughing or sneezing.

Hand hygiene tends to reduce the transmission of influenza viruses that occurs when one person touches another (e.g., with a contaminated hand).

Contamination can also occur by means of self-inoculation via fomite transmission (indirect contact transmission) when persons touch a contaminated surface and then touch their nose with the contaminated hand.

Why clean fingers

Studies have shown that influenza viruses can remain viable on the human hand for about 3-5 minutes and that influenza viruses can remain on fingers for 30 minutes post-contamination.

What are CDC recommendations for flu

Voluntary home isolation: CDC recommends voluntary home isolation of ill persons, i.e., staying home when ill, year-round and especially during annual influenza seasons and influenza pandemics.

Respiratory etiquette and hand hygiene: CDC recommends respiratory etiquette and hand hygiene in all community settings, including homes, child care facilities, schools, workplaces, and other places where people gather, year-round and particularly during annual influenza seasons and influenza pandemics.

How will face mask help in healthy individuals

Face mask use by well persons might play a role in reducing self-inoculation (e.g., touching the nose with the hand after touching a contaminated surface).

Face mask use by well persons is not routinely required in most situations to prevent contracting the influenza virus. However, use of face masks by well persons might help in certain situations, such as when persons at high risk for influenza complications cannot avoid crowded settings or parents are caring for ill children at home. 

When are Environmental surface cleaning measures recommended

These are recommended for frequently touched surfaces and objects in homes, child care facilities, schools, workplaces, and other places where persons tend to gather. These measures can be used for prevention of seasonal influenza and in all pandemic severity scenarios.

These measures might have some secondary consequences (e.g., failing to read instruction labels before applying disinfectants to ensure that they are safe and appropriate to use or cleaning with poor ventilation during the application process).

CMAAO Coronavirua Facts and Myth Buster 43

tPA for COVID ARDS

Fact: Physician-scientists at Harvard Medical School and Beth Israel Deaconess Medical Center are enrolling patients in a clinical trial to assess a common anticlotting drug for the treatment of COVID-19 patients with ARDS. The trial comes after a special report published by the team in the Journal of Trauma and Acute Care Surgery suggesting that the use of tPA (tissue plasminogen activator) could decrease deaths among patients with ARDS as a complication of COVID-19.

A clinical observation made about a subset of patients with COVID-19 induced ARDS made the idea seem relevant.

It has been reported, anecdotally, that a subset of patients with COVID-19 induced ARDS are clotting abnormally around their catheters and IV lines, stated senior author, Michael Yaffe, HMS instructor in surgery at Beth Israel Deaconess. These patients with aggressive clotting are being suspected to show the most benefit from tPA treatment, and this new clinical trial will go on to reveal if that is true.

Free tests in India

Fact: The Supreme Court on Wednesday directed the central government to issue directions to approved private laboratories to conduct COVID-19 tests free of cost. The two-judge bench of Justices Ashok Bhushan and Ravindra S Bhat was hearing a PIL. The court also held that the tests must be carried out in NABL-accredited labs. [TOI]

Mask compulsory

Fact: In India, Delhi and Uttar Pradesh joined Madhya Pradesh, Odisha and Nagaland to make it essential to cover the face while in public, either with a mask or a cloth. The municipal corporation of Mumbai, union territory of Ladakh and Chandigarh have also issued similar orders.

Plasma treatment in India

Fact: Kerala has received approval for its protocol on experimental treatment using convalescent plasma therapy from the Indian Council for Medical Research. The treatment involves transfusion of blood plasma of a recovered patient, replete with antibodies that helped her fight the virus, to another patient.

New York the epicentre

Fact: New York State is the epicenter of the U.S. COVID-19 outbreak. It has reported more than 149,000 confirmed cases. The number is higher than any country outside the United States, including Italy and Spain, the two other countries that have been the hardest hit by the pandemic. The death toll hit another daily high but the rate of hospitalizations appeared to be flattening.

Is X-ray indicated in asymptomatic cases

A multinational consensus statement on the role of chest imaging in the management of patients with COVID-19 has been jointly published in the journals Radiology and Chest. The statement is endorsed by the Radiological Society of North America and the American College of Chest Physicians.

It voices the collective opinions of experts in thoracic radiology, pulmonology, intensive care, emergency medicine, laboratory medicine and infection control from 10 countries, that have the highest burden of COVID-19 worldwide.

The consensus statement suggests that imaging is not routinely indicated in asymptomatic individuals or patients with suspected COVID-19 and mild clinical symptoms. Chest imaging is indicated in patients with COVID-19 with worsening respiratory status.

Imaging is also indicated for patients with moderate to severe features of COVID-19 irrespective of COVID-19 test results.

When to go for chest CT

The panel stated that CT is appropriate in patients with functional impairment and/or hypoxemia following recovery from COVID-19. In the presence of known community transmission, evidence of COVID-19 has been incidentally found on CT scans. In such cases, patients should undergo COVID-19 testing using reverse-transcription polymerase chain reaction.

[Reference: https://pubs.rsna.org/doi/10.1148/radiol.2020201365]

What is the new ICMR testing policy

The Indian Council of Medical Research (ICMR) has revised its strategy to fight the spread of coronavirus. All symptomatic ILI (fever, cough, sore throat, runny nose) patients will now be tested for COVID-19 infection.

All symptomatic ILI patients will now be tested for rRT-PCR within 7 days of illness and after 7 days of illness, antibody test will be done. [The Economic Times]

What is the percentage positive rate of COVID-19 in SARI in India

For five weeks spanning from February 15 to April 2, ICMR tested 5,911 SARI (Severe Acute Respiratory Illnesses) patients for COVID-19. Overall, 104 tested positive (1.8% of those tested). These cases belonged to 52 districts in 20 states and union territories.

Some 40 cases (39.2% of those tested positive) didnt have any foreign travel history or any contact with a foreign traveler. These cases were reported from 36 Indian districts in 15 states.

In 15 states, over 1% of SARI patients were found to be positive for COVID-19.

Gujarat testsed 792 SARI patients; 13 cases (1.6%) were found to be positive for COVID-19

Tamil Nadu tested 577 SARI patients; 5 (0.9%) came out positive

Maharashtra tested 553 SARI patients; 21 cases (3.8%) were found to be positive

Kerala testsed 502 SARI patients; only 1 case (0.2% ) was positive

ICMR concluded, "COVID-19 containment activities need to be targeted in districts reporting COVID-19 cases among SARI patients. Intensifying surveillance for COVID-19 among SARI patients may be an efficient tool to effectively use resources towards containment and mitigation efforts." [India Today]

 COVID and thrombosis - more evidences

Systemic clotting problems have been noted in severe and critically-ill COVID-19 patients. Disseminated intravascular coagulation has been noted by Chinese physicians. Autopsies showing clots not only in the lungs but also in the heart, liver, and kidney, were described on a webinar co-sponsored by the Chinese Cardiovascular Association and American College of Cardiology held in March. [Medpage Today]

What is the role of D-dimer and FDP

Elevated D-dimer, a fibrin degradation product that indicates thrombosis, at the time of admission, has been linked with substantially increased likelihood of death in hospital among COVID-19 patients in Wuhan, China. [Medpage Today]

In which parts thrombosis is seen

COVID-19 disease is associated with thrombosis: large vessel clots, deep vein thrombosis/pulmonary embolism, maybe arterial events, and potentially small vessel disease, microvascular thrombosis. [Medpage Today]

Can prophylactic anticoagulation prevent

Hospitalized patients often develop blood clots despite being on prophylactic anticoagulation.

Whether everybody with COVID-19 in the hospital should be on blood thinners

Fact: The answer is probably yes.

Should they be on higher than usual prophylactic doses

The answer is possibly yes.

Is there a microvascular thrombosis

Full-dose anticoagulation is being considered even if patients dont have documented blood clots, as it may be microvascular thrombosis in the lung, in the kidneys that results in pulmonary failure and renal failure and eventually death. [Medpage Today]

What are the guidelines

Recommendation from the International Society on Thrombosis and Haemostasis states that all hospitalized COVID-19 patients, including those not in the ICU, should be given prophylactic-dose low molecular weight heparin (LMWH), unless contraindicated (active bleeding and platelet count <25×109/L).

What are British recommendations

Recommendations from Britain also call for VTE prophylaxis for high-risk patients as well as considering PE for patients with sudden onset oxygenation deterioration, respiratory distress, and reduced blood pressure. LMWH is suggested rather than oral anticoagulants, including switching patients normally taking a direct oral anticoagulant (DOAC) or vitamin K antagonist.

What are threshold values upon which to start systemic anticoagulation

Fact: Around a D-dimer >1,500 ng/mL and fibrinogen >800 mg/mL.

What about heparin

Long chain (unfractionated) heparin would theoretically be preferable on account of anti-inflammatory effects. While LMWH has less of an anti-inflammatory effect, DOACs have little. Inflammation plays a key role in COVID-19. IV unfractionated heparin has an advantage - that it can be stopped quickly if bleeding occurs.

Is it practical to give twice LMWH

Practical matters may dominate. In New York City, several hospitals have opted for DOACs.

They dont want the nurses to go into the patients room to give unfractionated heparin two or three times a day or to adjust IV unfractionated heparin. Its much easier to give an oral anticoagulant with a large number of patients. [Medpage Today]

What about antiphospholipid autoimmune responses

Three ICU patients with COVID-19 in China demonstrated antiphospholipid autoimmune responses, reported researchers from Peking Union Medical College Hospital in Beijing, in a letter to the New England Journal of Medicine. All three tested positive for anticardiolipin IgA and anti-β2-glycoprotein I IgA and IgG.

The presence of these antibodies may rarely lead to thrombotic events that are difficult to differentiate from other causes of multifocal thrombosis in critically patients, such as disseminated intravascular coagulation, heparin-induced thrombocytopenia, and thrombotic microangiopathy.

D-dimer was more than 21 mg/L in the first patient, who had evidence of ischemia in the lower limbs bilaterally and in digits two and three of left hand. CT imaging of the brain exhibited bilateral cerebral infarcts in multiple vascular territories. Lab results revealed leukocytosis, thrombocytopenia, elevated prothrombin time and partial thromboplastin time, and elevated levels of fibrinogen.

D-dimer was around 3 mg/L in the other two patients. Both had multiple cerebral infarctions in the right frontal lobe and other locations in the brain, and other findings were similar as well.

Lupus anticoagulant was not identified in any of them. [Medpage Today]

How sensitive is antiphospholipid autoimmune responses

Investigators have cautioned against drawing any causal conclusions. Antiphospholipid antibodies are known to be transiently positive at the time of acute infectious illness. Also, antiphospholipid antibody titers and lab assay used were not reported. [Medpage Today]

What is the mechanism of microvascular thrombosis

The SARS-CoV-2 virus enters cells through the angiotensin converting enzyme 2 (ACE2) receptors. As the virus binds to these cells, it may cause damage to the blood vessel, particularly the microcirculation of the small blood vessels, thus inciting platelet aggregation. [Medpage Today]

Is their any autopsy confirmation

Autopsies have shown inflammatory changes in the heart with fine interstitial mononuclear inflammatory infiltrates, but no viral inclusions in the heart. Other potential mechanisms for cardiac damage include hypoxia-induced myocardial injury, cardiac microvascular damage, and systemic inflammatory response syndrome. [Medpage Today]

Is thrombosis the major reason for multiorgan failure

If thrombosis is the major reason for multiorgan failure, then anticoagulation is really important.

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA