Guillain Barre syndrome (GBS) refers to an acute onset polyradiculoneuropathy, which commonly manifests with rapidly progressive weakness of all 4 limbs, usually starting in lower limbs, then ascending to involve upper limbs. Muscle tone is reduced (hypotonia) and the deep tendon reflexes are either sluggish or absent. Minor sensory symptoms such as distal paresthesia and pain are common. Autonomic system involvement is uncommon. GBS usually occurs following a viral infection. Therefore, it is also referred to as post-infectious demyelinating polyradiculoneuropathy.
Recently, Chinese researchers reported a case of GBS (published in Lancet Neurology, April 1, 2020), with a history of travel from Wuhan. Patient presented with one day history of acute onset weakness, starting in lower limbs, which progressed to involve upper limbs within 3-4 days. DTRs were absent and muscle tone was reduced. She had no symptoms of fever, cough, chest pain or diarrhoea at onset. 3 days later, she worsened with decrease in muscle power and distal sensory loss. On day 4, CSF analysis showed normal cells, and high protein. On day 5, NCV studies confirmed a diagnosis of GBS, after which she was treated with intravenous immunoglobulins (IVIG).
On day 8, patient developed dry cough and fever. CT chest showed ground glass opacities in both lungs. Oro-pharyngeal swabs were positive for SARS CoV 2 on RT-PCR assay. She was shifted to isolation room and given supportive care along with antiviral drugs. Her condition gradually improved by 20, and she was near normal at discharge on day 30. Respiratory symptoms also improved.
GBS can occur early and can be a presenting feature of SARS CoV 2 infection.
The course of GBS in SARS CoV2 seems to be para-infectious (along with the infection), rather than the typical GBS, which is post-infectious (a few days after the infection)
Treatment with IVIG results in good clinical outcome.
COVID 19 TESTING: INDIA VERSUS THE REST- WHERE DO WE STAND?
Covid 19, a global pandemic, which began in China in late December 2019, has spread to more than 200 countries in the world. The total numbers of Covid 19 infected people have been rapidly increasing in some countries such as USA, UK, Italy, Spain, Iran, etc. Compared to that, the rise in the number of cases has not been that rapid in India.
Are the numbers in India really low?
There is no doubt that the number of confirmed cases of Covid 19 in India is lower than many countries, considering that it has more than 1.3 billion people. As on 9th April, 2020, India has about 6500 confirmed cases of Covid 19, which is a miniscule number as compared to USA (4,54,000), Spain (1,52,400), Italy (1,43,600), Germany (1,15,100), France (1,12,900), China (81,900), Iran (66,200), UK (60,700), Turkey (42,300) and Belgium (25,000), the top 10 most affected countries.
What are the possible reasons for low numbers in India?
Several reasons have been put forward, however there is no confirmed reason for the low numbers of Covid 19 in India so far. Some of the possible reasons could be:
Lesser number of testing for Covid 19 in India,
Greater immunity against Covid 19 in Indians,
Universal BCG vaccination in India,
Lower virulence of SARS CoV 2 virus in India,
Higher temperature and greater humidity in India.
We will leave points 2 to 5 for a later date, and the focus would be on point no 1 today.
How is India doing when it comes to Covid 19 testing?
In India, testing is done for high-risk groups, as suggested by Indian Council of Medical Research (ICMR). The latest guidelines published on 9th April 2020 have been enclosed.
11 million tests have been conducted across the globe so far. Most people look at tests conducted per capita and say India has done the least (0.04 per 10,000 population), so, has the least number of cases. However, there is no correlation between per capita tests and “flattening of curve”. Spain and Italy have done the highest number of tests per capita (18 and 16 per 10,000 population), however, they are still seeing huge number of cases. On the other hand, South Korea and Russia both have done fewer tests per capita (about 0.6 per 10,000 population), but they have flattened their curves.
A more useful indicator would be the positivity rate (number of confirmed cases out of the total tested), as this would give a true picture of disease prevalence.
The positivity rate is highest for Iran at 30% (30 samples out of 100 tested were positive). This rate was 28% for Belgium, 26% for France, 20% for US, 18% for UK and 17% for Italy. For India, it is 3.8% (about 4 people testing positive for every 100 tested). Germany that conducted a larger number of tests also has relatively lower positivity rate at 5.6%.
What does a lower positivity rate indicate?
Lower positivity rate means the infection is less prevalent. If we test more, the absolute number of cases would go up, however, the positivity rate is likely to reduce. This is because with more widespread testing, we would be testing more people without covid 19, including those with non-covid 19 respiratory infections. This trend in decline in positivity rates has been noted with an increase in the testing numbers in India over the past few days.
Should we test more?
The main reason for limiting the number of tests is the cost factor and limited availability of testing kits.
Other reason for not doing widespread testing is that testing would require people to come out of their houses, which could lead to greater spread of infection.
Moreover, in the absence of a specific treatment for Covid 19, a positive or negative test does not make any difference in terms of treatment. People with mild symptoms should stay at home even if they test positive.
If a person tests negative today, it does not add any value to the patient. He still needs to follow all the precautions to avoid getting infected with SARS CoV2 (similar to a person not tested). This is because a person who tested negative has an equal chance of getting infected in future, if he comes in contact with a Covid 19 positive patient.
ICMR strategy of risk-based testing seems appropriate for now. However, in future, it can be scaled up on need basis.
INDIA AS A SUPPLIER OF HCQ TO REST OF THE WORLD: JUSTIFIED OR NOT?
There has been a lot of criticism of PM Modi after a ban on export of HCQs were lifted and India agreed to supply HCQ to US and other countries. However, is this criticism justified? First, let us look at Indian pharmaceutical industry in general. India ranks third in the world in terms of volume of pharmaceutical production. Indian pharma companies supply drugs to over 200 countries in the world, including 50% of vaccine supplies to the world. Therefore, India is termed as “the pharmacy of the world”. In 2018-19, our pharma exports were worth 19 billion USD, and our Indian market was also worth the same value, so, we are doing a fine balancing act. The quality of Indian drugs is among the best in the world, therefore, US, Europe, Australia and Japan has no hesitation in importing drugs from India.
HCQ PRODUCTION IN INDIA
India produces 70% of the world’s HCQ and about 50% of HCQ used in USA comes from India. Ipca laboratories and Zydus Cadila are the leading manufacturers of HCQ in India. There are a few smaller players too. These companies are capable of producing about 20 crore tablets of HCQ (200 mg) per month. A patient suffering from Covid 19 disease requires about 15-30 tablets for treatment, depending on the severity of disease. So, a month supplies from India can take care of HCQ needs of about 10 million patients (currently, the entire world has only 1.5 million patients). This should give you an estimate of how much surplus of HCQ supplies is there in India.
We have surplus but why should we give it to other countries?
1. There is no way Indian patients will run out of HCQ supplies even if reach the numbers of USA or Italy (which seems unlikely today, as we have only about 6500 cases today, 9th April, 2020). Moreover, central as well as state governments have stocked crores of HCQ tablets to take care of patients with Covid 19 and other rheumatological conditions. So, does it make sense to hoard HCQ, when we know that we are not going to use all of them?
2. It is the basic humanity and moral obligation to help each other during a state of global pandemic, when we are fighting an unprecedented Covid 19. Today, we are helping the world with HCQ. However, we need PPEs and N95 masks from other countries. Tomorrow, we may need a vaccine for Covid 19 from other countries. Already, we have received appreciation from heads of countries that have received HCQs.
3. It makes economic sense to earn revenues from exporting drugs (especially during this period when economy is really hurting). India has received requests for HCQ from 30 countries, which include neighbouring countries, Brazil, USA, etc. It is the right time to get some money along with the goodwill!
It is no secret that males are the weaker gender in many aspects. On an average, men die younger than women and the prevalence of life threatening diseases such as heart attacks; stroke and cancer are more in men than in women. The same holds true with respect to Covid 19 infection too.
Analysis of COVID 19 data suggests that more men get infected with SARS CoV 2 than women. The difference is more striking when we look at Covid 19 related deaths. About 70% of those dying due to Covid 19 are men. There could be several factors leading to these differences:
Women mount better immune response: Women mount a stronger immune response to vaccines as well as infections. The prevalence of autoimmune diseases is significantly higher in women than in men. Many of the critical immune genes are located on X chromosomes, and women have two of them (compared to one X chromosome in men). The protein by which corona viruses are sensed is encoded on X chromosomes. That means this protein is expressed at twice the dose on many immune cells in women compared to men, which in turn could well be boosting females’ ability to ward off COVID-19. (Philip Goulder, Oxford University)
Prevalence of comorbid conditions is higher in men: Studies have shown that deaths due to Covid 19 are higher in people with heart diseases, diabetes, hypertension, cancer, lung diseases, etc. Men tend to have a higher prevalence of these diseases than women.
Higher incidence of alcoholism and smoking: Death rates due to Covid 19 are higher in smokers and alcoholics. In most countries, drinking and smoking are more prevalent in men than in women.
Better hygiene among women: Women practise hygiene-related precautions such as hand-washing more often than men. Women, by culture or habit, tend to cover their faces more often than men, thereby reducing the risk of transmitting as well as acquiring Covid 19 infection.
Alcohol use is a global health concern, ranking seventh among the leading causes of death and disability. Alcohol consumption is associated with many serious illnesses including liver cirrhosis, dementia, cerebellar ataxia, nutritional deficiency, etc and it is also a major risk factor for road traffic accidents. Despite these health hazards, alcohol consumption is common in India and rest of the world. Here, I discuss specific issues of alcohol consumption in relation to the corona virus disease 19 (Covid 19) caused by SARS-CoV 2 virus, which has been declared a pandemic by the WHO.
1. Drinking Alcohol does not Prevent Corona Virus disease
It is a myth that drinking alcohol would prevent corona virus disease.
2. Chronic Alcohol Consumption can increase the Risk of Getting Corona Virus Disease
Regular alcohol consumption over a long period of time can weaken one’s immune system, making them more prone to develop infections, including Covid 19.
3. Increased Risk of Developing Alcohol Withdrawal Seizures and Delirium during Lockdown
Some people become dependent on alcohol and they consume alcohol on a daily basis, often alone, mostly in early mornings or sometimes multiple times per day. This group is more prone to develop alcohol withdrawal symptoms, when alcohol consumption is suddenly stopped due to a situation such as complete lockdown.
Symptoms of alcohol withdrawal symptoms usually begin within 24-48 hours of the last alcoholic drink. Mild symptoms include tremors of hands, sweating; sleep disturbance, anxiety, palpitations, etc. In some severe cases, seizures or fits can also develop. Severe cases of alcohol withdrawal are severe agitation, disorientation, restlessness, hallucinations, sweating, increased heart rate, high BP, etc and is referred to as delirium tremens (DT). DT usually develops 48-96 hours after the last drink.
It is a medical emergency requiring hospitalization and treatment, as it can be fatal if left untreated. Treatment includes hydration with IV fluids, thiamine supplements, benzodiazepines and anti-epileptic drugs as needed.
4. Increased risk of suicides during lockdown
Certain people, who are habituated to regular drinking, get frustrated when they are unable to drink. There has been an increase in the number of suicides after the lockdown started in various parts of the world, including India.
Loss of Smell and Taste Could be Early Symptoms of Covid 19
The typical symptoms of Covid 19 are fever, cough and breathing difficulty. However, several cases have been reported, where patients presented with lack of smell and taste, who were later diagnosed to be having Covid 19. Many of these patients had no respiratory symptoms suggestive of Covid 19, when they developed loss of smell and taste.
The mechanism of lack of smell seems to be the involvement of olfactory nerves and their brain connections by the SARS-CoV 2 virus (which causes Covid 19). Lack of smell and taste are not permanent, and as patients recover from Covid 19, smell and taste sensations also return to normal.
So, it is recommended that persons who develop new onset lack of smell and taste (without any common cold) should self-isolate themselves and if they develop symptoms suggestive of Covid 19 later, should present themselves for covid 19 testing.
The guidelines in this regard were published by American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) on 22nd march, 2020 and can be accessed at the following link:
Chloroquine and Hydroxychloroquine: Should you take them for Covid 19 Prevention?
Chloroquine is routinely used in the treatment of malaria. Hydroxychloroquine (HCQ) is used for treating malaria and rheumatological disorders such as rheumatoid arthritis, systemic lupus erythematosus, etc. Recently they have been in news with regards to their proposed role in preventing Covid 19 infection caused by SARS Cov2 virus. Pharmacies have reported frenetic buying of these two drugs by general public as well as healthcare professionals and stocks have been depleting fast.
What is the current evidence regarding their effectiveness in prevention of Covid 19?
Chloroquine and hydroxychloroquine for Covid 19 prophylaxis
Indian Council of Medical Research (ICMR) has approved the use of hydroxychloroquine for prevention of Covid 19 in high-risk individuals. People who can use are:
Asymptomatic healthcare professionals (doctors, nurses, etc) involved in taking care of Covid 19 patients.
Asymptomatic household contacts of laboratory confirmed Covid 19 cases.
For healthcare professionals: 400 mg twice on day 1, then, 400 mg once weekly for next 7 weeks, to be taken with meals
For household contacts: 400 mg twice on day 1 followed by 400 mg once weekly for next 3 weeks, to be taken with meals
General public should avoid indiscriminately taking HCQ for preventing Covid 19, as there could be serious adverse effects with it. HCQ should be avoided in patients with heart disease with QT prolongation, myasthenia gravis, retinal diseases, epilepsy and porphyria.
There is no evidence with regards to efficacy of chloroquine in Covid 19 prevention. So, chloroquine should not be used for Covid 19 prophylaxis.
Useful Information on Covid 19 Infection Caused by SARS-CoV2
Covid 19 infection caused by the SARS-CoV 2 virus has become a global pandemic. It started in China in late December 2019 and has rapidly spread to many countries across the world. As of now, the overall trends show an increase in the total number of cases as well as deaths, especially in Europe and USA. There is a real possibility of Covid 19 escalating to alarming levels, if we do not take appropriate precautions now. Today, there is information overload, especially on social media sites, many of which are not authentic and are inaccurate. This leads to misinformation. In this write up, I wish to share the current information regarding Covid 19 in the form of questions and answers, with references of reliable sources as needed.
Q: Is there a specific country or region, which is immune to Covid 19 infection?
A: Covid 19 does not spare any particular country; region and it has already spread to all regions.
Q: Will countries with warmer climates be spared from Covid 19 outbreaks?
A: As of now, there is no evidence of that. Viruses multiply within human body and human-to-human transmission can continue in countries with warmer climates too. Moreover, at room temperature, the viruses can survive for several days.
Q: Would Covid 19 transmission stop in summer or in warmer climates?
A: No. Covid 19 transmission will not stop in summer or warmer climates. Transmission rates are lower in warmer and more humid climates, as compared to cooler and more dry climates. However, after a temporary dip, the case numbers of Covid 19 are likely to go up as winter approaches, if other precautions (social distancing, isolation, etc) are discontinued. (Ref: Center for Communicable disease dynamics, Harvard)
Q: Are there any age or gender-related differences?
A: Children below 10 have milder infections, with extremely low mortality. On the other hand, older people especially those aged 80 and above have more severe infections. They have a greater need for ICU care & mechanical ventilation and have a higher mortality. Women have less severe infections and lesser death rates, as compared to men.
Q: What are the common symptoms of Covid 19 infection?
A: Common symptoms are fever, cough and difficulty in breathing.
Q: What is known about Covid 19 infection in children?
A: It is reassuring to note that infections in children are milder and often asymptomatic. The mean age of affected children is 6-7 years. Severe infections occur in fewer children and less than 2% require mechanical ventilation. Death rate is <1%. (Ref: NEJM, Mar 18, 2020)
Q: How does the Covid 19 infection spread?
A: 1. It can spread by inhalation of droplets released from the sneeze of infected persons. Viruses can survive for at least a few hours in air in the form of aerosols.
2. These droplets can remain on surface (fomites) and viruses can survive for several days on them. When a person touches those surfaces with hands, the hands get infected. Infection can spread if the person touches eyes, nose or mouth with those hands. They survive longer on stainless steel and plastic, as compared to cardboard and copper. (Ref: NEJM, Mar 17, 2020)
Q: What precautions can one take to avoid the spread of infection?
A: 1. Those with a travel history to covid 19 infections should be quarantined for 14 days, so that they do not expose others to the infection.
2. Those with respiratory symptoms (such as cough, fever, sore throat, etc) should also self-isolate themselves at home.
3. Those who are asymptomatic or have no travel history should follow the following: washing hands frequently with soap & water or alcohol-based sanitizer, avoid touching eyes, nose & mouth with hands, avoid crowded areas, avoid going out as much as possible. Social distancing (maintaining 3 feet or one meter distance from each other) is also important.
Q: Are some people more prone to acquire Covid 19 infection?
A: Yes, the following groups of people are more people to acquire Covid 19 infection. These groups also have a more severe form of infection and higher death rates than others. These include: Older people, people with heart disease, diabetes, hypertension and cancer, people on immunosuppressive drugs (after transplant, for rheumatological or immunological disorders, etc)
Q: Are masks mandatory for everyone?
A: No, everyone need not wear masks. Healthcare professionals who are taking care of patients suffering from Covid 19 or other respiratory infections require masks. Persons who are suffering from a respiratory infection should also wear masks in order to prevent spread of infections.
Q: Can a person without any symptoms (asymptomatic people) spread Covid 19 infection?
A: Yes. Virus shedding begins even before symptoms show up. So, a person can transmit the infection to others 2-4 days prior to the day, when symptoms first show up. (NEJM, Mar 5, 2020)
Q: Is there a vaccine or tablet one can take to prevent Covid 19 infection?
A: No. There are multiple vaccines undergoing clinical trials. Hydroxychloroquine (HCQ) is also being tested to see whether it can prevent Covid 19 infection in a person not previously infected. So, at present no vaccine or tablet can be recommended to prevent the infection.
Q: Are there any treatments available for Covid 19 infection?
A: There are several treatments being tried and initial reports have been encouraging. However, these are small studies and data available is not very strong.
Chloroquine (500 mg twice daily for 10 days) was compared with hydroxychloroquine (400 mg twice daily on day 1 followed by 200 mg twice daily from days 2 to 5). HCQ was found to be more potent and less toxic. HCQ has anti-inflammatory properties and stops the cytokine storm that occurs in advanced stages of covid 19 infection. (Clin Infect Dis, Mar 9, 2020). Both chloroquine and HCQ can cause prolongation of QT interval (on ECG), especially in people with hepatic or renal disease. HCQ is safe in pregnancy.
HCQ along with azithromycin: Combination of HCQ and azithromycin is more effective than HCQ alone. HCQ dose: 200 mg thrice daily for 10 days. Azithromycin dose: 500 mg on day 1, 250 mg from days 2 to 5. Limitation was that this was tested on a small number of patients: 14 on HCQ alone, 6 both HCQ and azithromycin, 16 controls (no medicines). Treatment resulted in clearing the nasopharyngeal region from virus as early as on day 3 of treatment (normally viral shedding may continue for 20 days). (Ref: International Journal of Antimicrobial Agents, 17 Mar, 2020)
Remdesivir: It is a broad spectrum antiviral drug that inhibits viral replication through premature termination of RNA transcription. For patients in US, they can get this as part of clinical trials. Patients with pneumonia, who are not a part of clinical trials, can request remdesivir for compassionate use from manufacturers (firstname.lastname@example.org(Ref: CDC website)
Lopinavir-Ritonavir along with standard care was NOT BETTER than standard care alone in 199 adults on whom they were tested. (Ref: NEJM, Mar 18, 2020)
In conclusion, these treatments are still not fully proven. These should be taken only after prescription from a doctor and should not be self-prescribed.
Q: Who should be tested for Covid 19 infection?
A: All cannot and need not be tested for two reasons. 1. Testing is expensive and not widely available, 2. Treatment is mild in a majority and patients recover on own (testing would not change the outcome). The following groups of people should be tested for Covid 19 infection:
Current testing strategy (as per ICMR, 20th March, 2020)
All asymptomatic individuals who have undertaken international travel in the last 14 days:
They should stay in home quarantine for 14 days.
They should be tested only if they become symptomatic (fever, cough, difficulty in breathing)
All family members living with a confirmed case should be home quarantined
2. All symptomatic contacts of laboratory confirmed cases.
3. All symptomatic health care workers.
4. All hospitalised patients with Severe Acute Respiratory Illness (fever AND cough and/or shortness of breath).
5. Asymptomatic direct and high-risk contacts of a confirmed case should be tested once between day 5 and day 14 of coming in his/her contact.
Cardio-embolic strokes refer to infarcts in brain due to embolism from heart. Typically, infarcts in cardio-embolic strokes involve multiple arterial territories. In the MRI shown above, we can see multiple acute infarcts in bilateral anterior as well as posterior circulation territories. This patient was a 60 year old lady, with patent foramen ovale (PFO) and left atrial clot (LA clot). She was started on anticoagulation with low molecular weight heparin.
Corona virus infection, better known as Covid 19 infection, which started in China about three months ago, has rapidly spread to about 150 countries. So far, about 1,50,000 people have been infected with Covid 19, out of whom about 5,500 people have died.
Various forms of media (including TV, newspaper) and social media (facebook, whatsapp, etc) are full of news and information about Covid 19 infection. Various government agencies too have started awareness campaigns about Covid 19 infections and methods to limit its spread. Countries across the world have initiated partial to total shutdown. WHO has declared Covid 19 infection as a pandemic.
A problem of this magnitude, affecting the entire world is rare and many people have not faced a similar situation in their lifetime. This has resulted in anxiety and fear of varying magnitude. Recently, pulmonologist Dr Chandrakant Tarke encountered two patients with extreme anxiety.
Both patients were women, aged 23 and 30 years respectively, from Hyderabad, India. They presented with mild cold and no other significant symptoms. They had no risk factors to develop Covid 19 infection (no history of travel to Covid 19 affected countries or exposure to a Covid 19 infected patient). They had extreme fear that they were suffering from corona virus infection. They had developed obsessive trait of washing their hands multiple times with sanitizers despite staying at home and no exposure to outside. Clinical examination was normal except for hyperventilation. The fear had started after the news about Covid 19 infection in India started flashing on Indian TV channels. The fear became extreme on listening to Covid 19 awareness caller tune initiated by Government of India (which started with coughing sounds, followed by steps to prevent Covid 19 spread). A diagnosis of anxiety disorder induced by fear of having contracted Covid 19 infection was made. Women were counselled and referred to psychiatrist for further management.
With increase in the number of Covid 19 cases across the world and the disruption resulting due to it, we are likely to come across many more people suffering from Covid 19 related anxiety disorder. As a health care professional we need to be aware of it, promptly diagnose it (clinical diagnosis suffices) and advise appropriate treatment (counselling, referral to psychiatrist/psychologist).
Steps to prevent Covid 19 related anxiety
1 .Avoid seeking constant updates about Covid 19 from TV channels or social media (updating twice a day- morning and evening- should be sufficient),
2. Do not constantly discuss about Covid 19 with your family, friends and colleagues,
3. Focus on the positive aspects of Covid 19- more than 80% have mild infections and more than 90% survive this infection,
4. Take steps to prevent Covid 19 (as already outlined across various media platforms)
5. Go for walks, exercise and engage in leisure activities (music, gardening, etc)
6. Consult a healthcare professional if you develop anxiety or fear related to Covid 19
Dr Sudhir Kumar MD DM (Neurologist), Apollo Hospitals, Jubilee Hills, Hyderabad Dr Chandrakant Tarke MD DM (Pulmonologist), Apollo Hospitals, Jubilee Hills, Hyderabad