COVID 19 ; MALARIA; HCQ; ICMR ; ANTIBODIES; FRENCH HEALTH MINISTRY BANS HCQ, WHO SUSPENDS HCQ.

 

Chloroquine has been around since 1984 and not 100 uyaers vas suggested by the ICMR. It has been used to treat malaria all these years but not Covid-19. The big Lancet observational study has documented increased death with hydroxychloroquine and chloroquine. The WHO has suspended HCQ in its SOLIDARITY trial. The French health ministry has outright banned use of HCQ. But the ICMR without any published data insist on touting the efficacy of HCQ in post exposure prophylaxis to prevent Covid-19.

 

Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis Mandeep R Mehra, Sapan S Desai, Frank Ruschitzka, Amit N Patel Published Online May 22, 2020 https://doi.org/10.1016/ S0140-6736(20)31180-6 ;The Lancet.

 

ARTICLE IN PRESS International Journal of Antimicrobial Agents xxx (xxxx) xxx Contents lists available at ScienceDirect International Journal of Antimicrobial Agents journal homepage: www.elsevier.com/locate/ijantimicag [m5G;April 25, 2020;22:47 ] Short Communication Can post-exposure prophylaxis for COVID-19 be considered as an outbreak response strategy in long-term care hospitals? Sun Hee Leea,1, Hyunjin Sonb,1, Kyong Ran Peckc.

 

medRxiv preprint doi: https://doi.org/10.1101/2020.05.19.20101832.this version posted May 22, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Serologic responses to SARS-CoV-2 infection among hospital staff with mild disease in eastern France Samira FAFI-KREMER1,2,*,, Timothée BRUEL3,*, Yoann MADEC4, Rebecca GRANT4, Laura TONDEUR4, Ludivine GRZELAK3,5, Isabelle STAROPOLI3, François ANNA6, Philippe SOUQUE7, Catherine SCHMIDT-MUTTER8, Nicolas COLLONGUES8,14, Alexandre BOLLE8, Aurélie VELAY1,2 , Nicolas LEFEBVRE9, Marie MIELCAREK10, Nicolas MEYER10,11, David REY 12, Pierre CHARNEAU6,7, Bruno HOEN13, Jérôme De SEZE8,14, Olivier SCHWARTZ3,** and Arnaud FONTANET4,15,**

 

medRxiv preprint doi: https://doi.org/10.1101/2020.04.30.20085613.this version posted May 5, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Humoral immune response and prolonged PCR positivity in a cohort of 1343 SARS-CoV 2 patients in the New York City region Authors: Ania Wajnberg MD, Mayce Mansour, MD, Emily Leven, MD, Nicole M. Bouvier, MD, Gopi Patel, MD, Adolfo Firpo, MD, Rao Mendu, PhD, Jeffrey Jhang, MD, Suzanne Arinsburg, DO, Melissa Gitman, MD MPH, Jane Houldsworth, PhD, Ian Baine, MD PhD, Viviana Simon, MD PhD, Judith Aberg, MD, Florian Krammer, PhD, David Reich, MD, Carlos Cordon-Cardo, MD, PhD Author affiliations: Icahn School of Medicine at Mount Sinai, New York NY

TREAT COVID-19 EARLY FOR BEST RESULTS

 

 

Data on mortality is coming in fast and furious. It is more our less clear that the mortality figure of 3.4% by the WHO was highly exaggerated. As was the 0.9 to 1% by the Imperial College, London. The infection fatality rate (IFR)is ranging from 0.2 to 0.4% across the globe. The Iranians have provided a figure off 0.12% , while the Germans have noted an IFR of 0.36%. Stanford University too reports 0.17% fatality while the University of Southern California suggests 0.2%. The mortality in India per million is one of the lowest in the world at 3 per million. The total number of cases so far are 139049 with 4024 deaths, giving a crude mortality of 2.89%. The number of infections should be at least 10 times more , hence the Indian infection fatality rate will be around 0.28 % to 0.028%; this is more or less akin to the mortality figures form other nations.

 

The deaths per million are strikingly less in Asian countries than Europe, China is 3, Bangladesh is 1, Pakistan is 5, Singapore is 4, Indonesia has 5, Japan is 5, South Korea is 5, and Malaysia is at 4 per million. The substantial difference in mortality can only be speculated upon, maybe younger population groups or higher local temperatures.

 

One should not worry too much on the increase in new number of cases in India. The prevalence is still reassuringly low, and even if there is a surge in new cases , we inch towards “herd Immunity.” I would prefer to term it “public” or “people” or even “community immunity” rather than herd immunity because the word “herd” is associated more with animals. A herd of elephants.deer, cows, horses, or sheep. We are people and not sheeple. A group of humans is better termed a clan of humans. I would not mind “clan immunity.”

 

The testing has been ramped up, so there is a bigger number of new cases each day. But a new case means an infection , not a death warrant. The majority of people will be asymptomatic or mildly symptomatic. Most of the patients landing up in hospital will be treated by oxygen alone. Till some time back 5-6% required intensive care management with high mobility and mortality. But with greater knowledge of the virus and treatment protocols this should be considerably lowered. We know that SARS-CoV-2 peaks very soon after symptom onset. Unlike SARS and MERS, in which the viral load peaks after a week, Covid -19 is characterised by the viral load at its highest within a week of symptom onset. The common flu is also accompanied by an early peak of viral load. The trick therefore will be to use an antiviral as soon as possible after onset of symptoms in patient with Covid-19.

 

This article was published on May 22, 2020, at NEJM.org.
DOI: 10.1056/NEJMoa2007764

 

A large double blind randomised trial including almost 1100 patients with CVovid-19 has reported significantly shortened recovery time with remdesivir as compared to placebo, from 15 to 11 days. There was also a rent towards lower mortality with remdesivir. Remedesivir acts against the enzyme polymerase that is essential for the replication of the Covid-19 virus. Interestingly remdesivir did not work in hepatitis nor was it very successful against ebola. Remdesivir, however, is currently considered the most promising therapeutic drug against Covid-19. There are other on going randomised trials with remdesivir and results are awaited. It is hoped that good sense prevails with the company manufacturing remdesivir; it keeps the price within reach of the common man. Bangladesh has already begun manufacturing the medicine by virtue of a special arrangement with Gilead, there should be similar understanding with Indian companies. Remdesivir was unable to reduce mortality below 5% (it did bring it down to 7%) in the trial, but this may have been because almost 25% patients were hooked to ventilators. Remdesivir was probably given too late in them. Patients reach the stage of ventilator support after the viral load has begun to diminish but the body has unleashed a wayward immunity response against itself, this is called the cytokine storm. The immune system attacks the lungs and other organs in the patients body with a vengeance. The antiviral now becomes incapable of treating the pathology.

Gilead Sciences has signed non-exclusive, licensing agreement with five generic manufacturers to expand access to its experimental antiviral drug remdesivir for Covid-19 patients.

The licensees include Mylan, Cipla, Hetero Labs and Jubilant Life Sciences in India, as well as Ferozsons Laboratories in Pakistan. The companies will be able to manufacture and distribute remdesivir in 127 countries.

However,  a senior scientist at the Indian Council of Medical Research (ICMR) has said that “it will consider using the drug if Indian firms are able to make it,” as per the BBC. The ICMR continues with its antics.

 

Published Online
May 8, 2020 https://doi.org/10.1016/ S0140-6736(20)31042-4

 

The other interesting randomised trial has emerged from Hong Kong. The researchers successfully cut down recovery time to 7 days alone with the use of a triple therapy combination. The troika consisted of lopinavir/ ritonavir (anti HIV), ribavarin (anti hepatitis C) and interferon versus lopinovir/ritonavir alone. The time to become negative for virus was only 7 days in the triple combination group as opposed to 12 days in the control group. Symptoms were alleviated in 4 days and there was suppression of interleukin levels. Raised interleukin levels indicate a grossly inflammatory state within the body. Treatment was given within 7 days from symptom onset. The researchers concluded that treatment with interferon should be initiated as soon a possible, definitely within a week of becoming ill. Interferon is considered the backbone of the triple combination treatment. The researchers have earlier shown reduction in mortality with the triple combination in patients with SARS. In the Covid-19 study, patients given triple therapy tested negative in 7 days as compared to 12 days in controls. Symptom duration was reduced from 8 to 4 days. The triple therapy worked when used early and probably will not give equally good results in patients on ventilators.

 

NATURE

 

Two studies, one from Germany and the other from Singapore have confirmed that infective viral shedding is upto 10 days only. A patient may shed virus or be positive for as long as 6 weeks but will not be infective. After 10 days the PCR test is picking up dead virus. Till 10 days subgenomic messenger RNA can be seen in the Covid-19 virus, indicating that the virus can be isolated, cultured and above all is infective. If the virus ceases to be infective after 10 days , the protocol of 2 consecutive negative PCR tests becomes redundant. The viral load may be high after 10 days but the virus is not infective. Despite virus detection by PCR, the virus is not viable after 10 days. The PCR may detect high viral loads but the person concerned is not infective after 10 days of symptom onset.

 

 

The PCR test is best described by the inventor himself. Kary Mullis writes in his autobiography “Dancing naked in the minefield” that he figured out the PCR test one night as he drove back to his home with his future wife. He gives a nice analogy. Picking up a number plate of a car from the moon would be next to impossible. But this could be made easier if somehow the number plate was multiplied millions or billions of times. The human DNA is like a very long number plate. The SARS-CoV-2 has a genome or telephone number of 30000 numbers. Mullis imagined that a fragment of the DNA could be split into 2 by an enzyme, “polymerase.” The two fragments could again be split into two and then again into two; the reaction could go on. After 10 cycles we would have a thousand fragments , after 20 cycles a million and after 30 cycles a billion. It would become easier to identify the target fragment after this magnitude of amplification. Mullis called it the “polymerase chain reaction” and soon the PCR test came into being. It could not only be helpful in solving crimes but could also be used to study the DNA of an animal that existed 40,000 years ago. The PCR test is used to detect the presence of the Covid-19 virus. The test is not infallible because errors in collection of sample and transportation can account for a negative test. But more about the fact that the PCR test can be quite fallible some time later.

The take home message is that combination antiviral treatment is a must in Covid-19, and this should be begun within a week of symptom onset. But selection of the patient who would most benefit from treatment  remains unclear.

HYDROXYCHLOROQUINE PROPHYLAXIX FOR COVID-19

 

 

 

India has one of the lowest death rate at 3 per million population; there is as of now no evidence that hydroxychloroquine is effective for prophylaxis; the ICMR provides no reference in its advisory ; vaccines are being tested at “warp speed”; lets hope one works.

 

The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin

JAMA | OriginalInvestigation
Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State

Eli S. Rosenberg, PhD; Elizabeth M. Dufort, MD; Tomoko Udo, PhD; Larissa A. Wilberschied, MS;
Jessica Kumar, DO; James Tesoriero, PhD; Patti Weinberg, PA; James Kirkwood, MPH; Alison Muse, MPH; Jack DeHovitz, MD; Debra S. Blog, MD; Brad Hutton, MPH; David R. Holtgrave, PhD; Howard A. Zucker, MD

JAMA. doi:10.1001/jama.2020.8630 Published online May 11, 2020.

 

Hydroxychloroquine Versus COVID-19:
A Rapid Systematic Review and Meta-Analysis

Amir Shamshirian1,2, Amirhossein Hessami3, Keyvan Heydari2,3, Reza Alizadeh-Navaei2, Mohammad Ali Ebrahimzadeh4, Roya Ghasemian5, Elham Aboufazeli6, Hananeh Baradaran7, Keyvan Karimifar8, Aida Eftekhari8, Danial Shamshirian9*

The new england journal of medicine Original Article

Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19

This article was published on May 7, 2020, at NEJM.org.

DOI: 10.1056/NEJMoa2012410

 

 

 

 

 

INEXPLICABLE HEALTH MINISTRY ADVISORY ON PROPHYLACTIC HYDROXYCHLOROQUINE FOR COVID-19

 

The health ministry of India for some inexplicable reasons expanded yesterday the indications of prophylactic hydroxychloroquine (HCQ) on flimsy data, despite a huge observational study of 96000 patients with Covid-19 published yesterday in The Lancet concluding that HCQ is ineffective and could be even hazardous in treating Covid-19.

Why wait for a vaccine if HCQ is so effective ???

 

JAMA Netw Open. 2020;3(4):e208857. doi:10.1001/jamanetworkopen.2020.8857 OriginalInvestigation |

InfectiousDiseases Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection A

 

Randomized Clinical Trial www.thelancet.com Published online May 22, 2020 https://doi.org/10.1016/S0140-6736(20)31180-6

Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis Mandeep R Mehra, Sapan S Desai, Frank Ruschitzka, Amit N Patel

 

 

 

IS SPORTS AS WE KNOW IT POSSIBLE IN A POST COVID-19 WORLD ?

 

How do you envisage sports being conducted after the lockdown is lifted ? The masks may remain mandatory; as also the social distancing. You will have to stay 6 feet away from colleagues and strangers. Even your own family if they live elsewhere. So how do you play cricket? What rules do you modify? How far behind does Dhoni have to stay behind to ensure a stumping does not go waste? Ashwin and Kuldeep Yadav may become a trifle ineffective. How far away do the slip fielders position themselves from one another. The questions become starker with contact sport. You could watch the beautiful game from your homes, but how does the soccer player stay 6 feet away from the defender? Do you change the architecture of stadiums for athletics? How do you get the 100 m race run and ensure the athletes are in their lanes 6 feet away form one another? These are complex issues that need to be anticipated right now. Maybe the think tanks want to vaporise sports away for good. As you can see running a 5000 m or a cross-country race will become a near impossibility. Runners do get to jostle as they compete in these races that are both fascinating and thrilling to watch. Boxing and wrestling will evaporate away. German Bundesliga has done a first, organised a football match in a stadium devoid of spectators. The Germans have done it by testing all players and officials. We had the eerie spectacle of a goal being scored and the players rejoicing as they stood adequately apart from one another. However Augsburg’s head coach Heiko Herrlich had been penalised for leaving his hotel to buy toothpaste from a local supermarket, he was denied permission to attend the first ever football game his team was playing (in the Bundesliga) in Covid-19 times. It was to be his first game as head coach. Herrlich will be permitted to rejoin his team affairs after he tests negative twice for the virus. Toothpaste can become radioactive in a post Covid-19 world.

Tennis could carry on. So could badminton, table tennis, gymnastics, the long jump and high jump. Even pole vaulting and the throws. So also archery and shooting. But sports entailing proximity are more or less out. The knowledgables will turn to the magical vaccine. The solution they will say is quite simple. Get vaccinated and do your sport, represent your school, club or country. The catch that most people do not seem to understand is that making an effective vaccine is easier said than done. HIV has been around for more then 30 years, it has killed more than 30 million people, but even today we do not have a vaccine against it. The situation is the same with hepatitis C, no vaccine yet after decades. There is no vaccine against malaria or TB. Both have been around for hundreds of years. As I write there are not more 2-3 development trials testing a vaccine against TB, which kills more than 3000 people in one day. Note that Covid-19 has not resulted in 3000 deaths in 5 months in India. TB kills more than a million or 10 lakhs in a year. We have however more than a 100 trials scrambling to develop a Covid-10 vaccine. The vaccine against common flu has never been fully effective. The efficacy ranges form 20 to 60% only. The flu virus keeps mutating. Also despite the flu vaccine being around, more than 60,000 people died from it 2017-18 in the US alone. So getting a vaccine will not be a panacea.

Right now the company that is leading the charge to make the Covid-19 vaccine is a US based company called Moderna. Interestingly Moderna has never manufactured a vaccine ever before. Also it is trying a method that has not been employed previously. It hopes to inject a person with a messenger RNA that will coax the cell in ones body to make components of the SARS-CoV-2 . The messenger RNA is supposed to nudge or order a human cell to either make the spike or the nuceleocaspid component of the corona virus, but not the entire virus. By making only bits of the virus the vaccine will never get lethal, but elicit the immune system to kick in antibodies against SARS-CoV-2. The idea is dazzling on the drawing board but we however have to wait for it to work. A vaccine not only must be effective but be without serious hazards. Usually it takes years to develop a vaccine, as mentioned earlier many dangerous diseases are yet to prevented by an effective vaccine. It is being bandied about that the vaccine will be present as early as September. This is impossible. A vaccine has to first tested in animals and then in human volunteers. One has to wait to see if major side effects like paralysis, epilepsy or cancer may present as side effects. The list of ill effects is long and need not be mentioned here. But they have to watched out for.

Conjuring a vaccine in 6 months makes for sexy reading, but would entail too many corners getting cut. Maybe for all you know a vaccine is already there. We are merely going through the motions of developing one. This is too far fetched. Suffice to reiterate that an effective vaccine takes time to make, and once it is rolling it still may not be effective in the entire population. A direct intervention against this virus makes greater sense.

 

JAMA Cardiology Published online May 13, 2020

 

What does the sportsperson do even with a vaccine in her? The American College of Cardiology has hurriedly made guidelines about how an athlete can get back to competitive sports after bout of Covid-19. The society seems oblivious of the fact most contact sports shall be impossible anyway in the future. The guidelines imagine a world that has gone back to what it was till the November of 2019. The guidelines rely entirely on the protocol subsequent to spell of myocarditis, published in 2015. But makes absolutely no mention of issues related to masks or social distancing. The advisory albeit essential seems to miss the point that sports will be the first casualty of the new world.

The guidelines emphasise that the physician will have to first decide who has and who has not been infected with SARS-CoV-02. The problem is that almost 50% of infected people do not have symptoms. This means to know whether an athlete has been infected in the past a serological test for presence of antibodies will have to be done. I do not need to remind you that of the symptomatic people almost 80% have mild symptoms. Around 15% get sick enough to need hospitalisation while 5-6% need ICU treatment. How do we go about with people known to be infected? They will have to wait for 3-6 months before resuming serious raining. The waiting period is not decided as yet. After 3 -6 months each athlete will need a thorough cardiac evaluation. Covid-19 affects the heart in almost 20-25% in a variety of ways. There can be myocarditis, pericarditis, ischemia, myocardial infarction type 1 and 2, arrhythmias and even heart failure. SARS-CoV-2 can directly attack heart muscle or indirectly by producing an inflammatory state. Blood vessels (endothelium) can be damage or blood become more coagulable. All this happens in the acute phase. When the athlete wishes to resume competitive or leisure activity it has to be ensured the heart has healed.

 

(Circulation. 2015;132:e273-e280. DOI: 10.1161/CIR.0000000000000239.)

 

The ECG is a must and this must ideally not show any residual ischemic changes. An echocardiogram will be needed to ensure the heart muscles have recovered, the left ventricle ejection fraction has a normal ejection fraction. All cardiac biomarkers and inflammatory markers should have returned to normal. Troponins should be normal and also the brain natriuretic peptides (NT-pro-BNP). CRP, ferritin and D-dimer shouts also have fallen to normal levels. Holter monitoring will need to be done to rule out high grade ventricular premature beats or ectopy.

Obviously in the presence of ongoing myocarditis sports cannot be recommended. These rules are applicable for all types of viral myocarditis, not necessarily for Covid-19 alone. Cardiac MRI or endocardial biopsy could be reserved for specific cases. Cardiac MRI in the acute phase picks up more water in heart muscle and later the presence of gadolinium suggestive of myocarditis, active or healed. I do not know of any data on cardiac MRI in Covid-19 as of now.

I used to love to run as a boy, in fact I still do. Most if not all young people cannot do without some sport or the other. I don’t know for how long you can deny them a good game of cricket or foot ball. Will millions of young people have to wait for a vaccine before they can play or watch a game? The current men’s world record is 9.58 seconds, set by Jamaica’s Usain Bolt in 2009, who gets to break this ? The Indian cricket team will have to be tested both for the virus and antibodies. The BCCI, I am sure, must be working on this. It could buy the best antibody tests available in the world to pick up previous infection. The BCCI has the muscle if not the vaccine. Welcome to the manifestly abnormal post Covid-19 world.

SPORTS IN A POST COVID-19 WORLD.

How do children get to play games in a post Covid-19 world? How far away do slip fielders in cricket position themselves from one another? How do you get to play soccer or run a 100 m race ? These questions demand answers now. How and when does a patient resume running after a Covid-19 attack?

 

A Game Plan for the Resumption of Sport and Exercise After Coronavirus Disease 2019 (COVID-19) Infection.JAMA Cardiology Published online May 13, 2020.

 

AHA/ACC Scientific Statement Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 3: Hypertrophic Cardiomyopathy, Arrhythmogenic Right Ventricular Cardiomyopathy and Other Cardiomyopathies, and Myocarditis A Scientific Statement From the American Heart Association and American College of Cardiology (Circulation. 2015;132:e273-e280. DOI: 10.1161/CIR.0000000000000239.)

 

 

 

DO NOT STOP YOUR BLOOD PRESSURE PILL, LOCKDOWN OR NO LOCKDOWN

 

This article was published on May 1, 2020, at NEJM.org.
DOI: 10.1056/NEJMoa2007621

Drugs used in treatment of hypertension, heart failure or diabetes do not increase risk of higher rate of infection, severity of dies or death in patients with Covid-19. Covid -19 disease is caused when SARS-CoV-2 ( a beta coronavirus) enters your body via receptors called ACE 2 (angiotensin converting enzyme 2). At the beginning of the pandemic it was theorised that popular and effective classes of medicines often used to treat hypertension ,heart failure or diabetes , would be detrimental because they increase the ACE-2 receptor. The logic was single , a lot of hypertensives and patients with heart failure were falling down dead with Covid-19, so the usage of these drugs may explain increased mortality. The drugs are named angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blocker (ARB).

 

Examples of the ACEI group of medicines are ramipril, lisinopril, trandalopril, captopril…….so they can also be called the “prils.”. The angiotensin recep[tor blockers are losartan, telimisartan, valsartan……..also termed the “sartans.”. Randomised rials done over decades have confirmed efficacy and safety of these medicines in treatment of hypertension and heart failure. SARS-CoV-2 , the coronavirus, penetrates human cell by using the spikes attached to its surface on to the ACE2 receptors present in abundance in the lungs, heart, intestines , and kidney. It was no surprise that Whatsapp messages were spreading like wildfire regarding these medicines.

 

“Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?” This was the title of this scientific letter written to The Lancet on March 11, 2020 (Published OnlineMarch 11, 2020 https://doi.org/10.1016/ S2213-2600(20)30116-8). The authors of the letter went on “ suggest that patients with cardiac diseases, hypertension, or diabetes, who are treated with ACE2- increasing drugs, are at higher risk for severe COVID-19 infection and, therefore, should be monitored for ACE2-modulating medications, such as ACE inhibitors or ARBs’. A conundrum was treated for clinicians , because millions of patents were at stake. Do we continue with an ACEI or ARB or not was the burning question clinicians were asking amongst themselves ?

 

 

The picture is clearer now with 3 good, albeit, observational papers recently published. A large study included 8910 patients in 11 countries across 3 continents. All patients had been hospitalised. By applying statistics (multivariate logistic-regression analysis) they found out that age >65 years, coronary artery disease, heart failure, history of arrhythmia, chronic obstructive lung disease and current smoking were associated with raised risk of death. Females had a lesser risk. Importantly, both ACEI and ARB were not associated with increased risk.

 

An Italian study from the region of Lombardy similarly showed no increased risk with ACEI or ARB’s in confirmed cases of 6272 Covid-19 patients when compared with more than 30,000 controls having similar sex, age and place of residence. Once again logistic-regression multivariate analysis failed to show increased incidence of Coivid-19. Also there was no increased risk associated with these drugs in severely affected patients or in patients who died.

 

This article was published on May 1, 2020, atNEJM.org.
DOI: 10.1056/NEJMoa2008975

 

The third study analysed data from health records of 12, 594 patients; of these almost 6000 patients were founds to be infected. More than 1000 had severe infection, defined as admission to intensive care, ventilation or death. The researchers did not find association for any of the analysed drugs for a positive test to severe illness.

 

All 3 studies negate the theory that ACEI or ARB is associated with risk of SARS-CoV-2 infection , severity of illness or risk of death. There was a hint in one studies that there was in fact a lower risk of in hospital death with use if ACEI or statins, but this cannot be taken for granted as this was an observational trial. Every professional scientific society has advised ACEI or ARB should not be stopped due to concern of increased susceptibility or severity of Covid-19 infection.There is also no increased risk with other classes of medicines such as beta-blockers, thiazide diuretics and calcium channel blockers. Hence despite the theory that ACEI’s or ARBS’s could increase levels of the ACE2 proteins that happen to be the entry point for SARS-CoV-2 into human cell, there is no increased risk of Covid-19 infection or death by it.

 

SARS-CoV-2 receptor ACE2 gene expression and RAAS inhibitors.
Lancet Respir Med 2020
Published Online
May 13, 2020 https://doi.org/10.1016/ S2213-2600(20)30224-1

 

A recent letter in the Lancet describes experimental evidence that ACEI actually down regulates the ACE2 receptors in lung tissue. “It is possible that long-term ACEI use downregulates lung ACE2 expression by reducing substrate (ie, angiotensin II) availability, which might also explain why no effect of ARBs was seen. In theory, ACE2 down regulation might reduce the risk of SARS-CoV-2 infection because of reduced virus receptor availability.” But animal studies that reduced ACE2 can increase acute lung injury. The clinical significance of effect of ACEI on the ACE 2 receptor however remains unclear.

The message is simple , do NOT stop your blood pressure pill, lock down or no lock down.

COVID-19 PCR TEST MAY NOT BE THE GOLD STANDARD

The RT-PCR test is considered the gold standard for detection of SARS-CoV-2. But this was not based on an actual virus specimen or virus isolate ; the test was developed from the genome put up on the internet. The authors of the published paper concede this in their own paper.

 

 

 

Euro Surveill. 2020 Jan 23; 25(3): 2000045. doi: 10.2807/1560-7917.ES.2020.25.3.2000045

N Engl J Med 2020; 382:970-971 DOI: 10.1056/NEJMc2001468

FIVE MONTHS OF COVID-19 BUT STILL NO ANTIBODY TEST FOR HEALTH WORKERS !

 

Lancet Infect Dis 2020; 20: 565–74
Published Online
March 23, 2020

 

Every now and then a statement is thrown at us on television or the print media that warns us of the unknowns around Covid-19 disease. The WHO had gone to a great extent in highlighting the immunity conundrum regarding Covid-19, only to retract a few days later. This was a clear example of attempts being made to obfuscate at the highest levels. As per the WHO there was no clarity on the extent of antibody production post Covid-19 infection, they did not know the extent of nobodies produced, the ability of the antibodies to prevent further infection or how long these antibodies would persist in the body. They probably initially wondered whether antibodies were produced at all. This was an odd opinion, because just about every viral infection triggers an antibody response. We know that SARS (that burnt out in 2 years) produced antibodies for almost 3 years. MERS ( still present sporadically ) also manufactures antibodies for almost 3 years. Both are coronaviruses, in fact the Covid-19 virus resembles SARS-CoV-1 so much it is named SARS-CoV-2 after it.

 

medRxiv preprint doi: https://doi.org/10.1101/2020.04.30.20085613.t

 

There is already considerable data that both monkeys and humans make antibodies when infected with SARS-CoV-2. Measles and mumps provide antibodies for a life time, while tetanus kicks in antibodies for 11 years. Antibodies after typhoid can also last a lifetime. Now one more study posted online, echoes the fact that patients with Covid-19 do make antibodies, and do so vigorously. The paper,yet to be peer reviewed, includes more than 1300 patients of Covid-19. The strength of his paper is that the kit to detect antibodies was extremely efficient with a specificity of 99%. This means there is less 1% chance of a false positive result. The study provides very reassuring results. Even though the patients had mild symptoms , 99% developed antibodies. All patients were confirmed to be infected by SARS-CoV-2 by PCR testing. It had been assumed that people with moderate or severe infection are the one capable of manufacturing antibodies. This study from New York however reports that even mildly infected patients are capable of a robust immune response. Levels were highest 3 weeks after onset of illness. There was even a difference in antibody levels from day 20 versus day 24. Antibodies were produced regardless of sex, age or duration of illness.

 

Another interesting finding of the study is that PCR test for SARS-CoV-2 can be positive upto 28 days after onset of infection. Crucially however this does to mean that the virus is infected. Other studies have documented that this virus can only be cultured upto 8 days, indicating that after 8-10 days the PCR test is detecting non infectious genetic material. Genetic fragments of Ebola and Zika viruses are known to persist for more than 6 months.

 

It is clear that everyone who makes antibodies to SARS-CoV-2 has some level of immunity to it. Even if the levels decline a previously person will retain some protection from the virus. The Germans were well aware of the robustness of antibody response in Covid-19. They did not permit themselves to be confused by the WHO advisory at any point of time. They raced ahead with making as many antibody kits as possible, much before the rest of the Western world. They already have data that as many as 14% of Germans have antibodies to Covid-19 in some districts.

 

Munich has launched an ambitious project to check antibodies around the year in 3000 citizens. The aim is to figure how many people, even those without any symptoms, have already been infected by the virus. German leaders realise that understanding the prevalence of infection will help them make policy decisions regarding loosening restrictions. Germany was testing 120000 people a day for the virus one month ago, it is probably testing more now. Germany announced last week that a deal has been stuck with a supplier for 50 lakh antibody tests every month. Please note the number…..50 lakh or 5 million serological tests a month. More than one lakh antibody test a day ! The presence of antibody would enable a person to go about her or his work more freely.

 

I have been repeating ad nauseam that extensive anti body testing must be done in India. This should have begun months ago because Covid-19 has been around since December 2019. Five months have elapsed and despite China being a neighbouring country we are still to even pretend to begin antibody testing. Very worrisome to say the least. The people advising the government have either blanked out completely or the government is does not seek advise, the latter is unlikely.

 

medRxiv preprint doi: https://doi.org/10.1101/2020.04.16.20067835.

 

It is imperative that as many health workers as possible are tested for antibodies so that may work with confidence. I have done a primary PTCA just yesterday in a 75 year old gentleman presenting with an acute heart attack. We still await his virus report. Waiting for a PCR test could have imperilled the patients life, so we went ahead with a successful procedure. But throughout the procedure I worried for the technician and nurse woking alongside me during the life saving procedure. And of course there was a tinge of concern for my own self. I am quite fit but would hate to be infected by this virus. Remarkably, after 5 months of Covid-19 originating from neighbouring China we are still not in a position to health workers. If I have antibodies, I know I have been infected in the past. I also become aware that I have some level of immunity. I become incapable of infecting others or getting infected myself. I could even shake hands without fear.

 

It could also be quite probable that no one has told the leaders that one of the best ways to loosen the lockdown is to have an idea of how many have been infected by the virus in the past. Antibody testing is the best method to understand the penetration of this virus in the community. Most nations are striving to check for antibodies to making policy decisions.

 

ICMR TESTING PROTOCOL 9/4/2020

 

The ICMR however remains quite baffled. What else can explain its advice that antibodies be checked after one week in a person connected with a cluster (9/4/20)Even a third year medical student knows that antibodies take a fortnight to kick in. The New York study that I have cited recommends that antibodies be checked 3 weeks after symptom onset. The ambiguity among our health advisers is both perplexing and even unnerving. In the event the government lays down policy of serological testing in health workers, I am sure it will be magnanimous enough to do them free

Astonishingly the ICMR (27/4/20) still “advocates that RT-PCR throat/nasal swab is the best use for diagnosis of Covid-19”. Bewildering because there is considerable data that saliva is a better source for virus detection and much safer for the health worker

SEAL LOCKDOWN SHUTDOWN BREAKDOWN

If you can’t solve the problem, you are not employing evidence.

 

 

A lockdown CANNOT be imposed on a whim or a gut feeling. Crucially it should NEVER be imposed to garner approval ratings. There has to be a science behind it; the decision must be evidence based, not a reflection of a house constructed from sand. The lock down in India is laughable. It was imposed around the 25th of March. As per the WHO, there were a total of 434 cases that day, with a total of 9 deaths. Italy had 63927 cases with 6077 deaths, and the USA had 42,164 cases and 571 deaths. We now have more than 33000 cases with 1074 deaths, around 67 died yesterday. The lock down has obviously not worked one bit. The timing of the lockdown was too premature, draconian measures were imposed much before cases had begun to mount. No attempt was made by the government or the media to assure the public that all data on Covid-19 pointed to more than 80% people developing mild or no symptoms. The majority of people would simply shrug off the virus with absolutely no harm to themselves, especially if they were young (as most Indians are) or had no underlying disease.The number of cases keep rising every day for the simile reason that more people are being tested now than before. Mercifully the number of deaths are still in double figures. In previous years more than 20,000 Indians died in one day, because of a variety of reasons. This is not the time to discuss them but stay focussed on what is happening right under our noses. Millions of people have been displaced, lakhs of businesses are shuttered, all schools closed , restaurants and hotels shut, and manifestly millions without jobs or any means of sustenance. The poor have been hit like never before and before they realise it , the middle class will begin to crumble. Crores of children are corralled with unimaginable psychological adverse effects, domestic and child abuse that largely go unreported must be substantially elevated. These matters are well known to you. But the timing of a lock down is hardly known to the lay public or even most doctors. It is the job of public health doctors or epidemiologists. Most public health doctors worth their salt will endorse the fact that a lock down if needed must coincide with the peak incidence of cases; it should NEVER be too early or too late. It must be put in place at peak infection. The graphic provided clearly shows that despite the lock down cases in India have shown no decline. There has been a steady increase in number of cases since mid March; what could be the reason for this? The treason is simple, faulty timing of the lockdown.

 

 

SARS-Cov-2 is basically a respiratory virus, evolved from nature. Even if man made as some conspiracy theorists may imply it is near identical to SARS-Cov-1 and other corona viruses. It is also similar tom other viruses that affect the respiratory system , including the flu virus. Every respiratory virus, particularly the flu virus, has a pattern, it emerges in winter and after infection people for 6-8 weeks makes a retreat. In the process the flu virus manages to kill 30000 to 60000 people in the USA alone, and millions worldwide, without much hue and cry.

 

 

Covid -19 has played havoc in Spain and Italy but as expected the number of new cases are declining (seen in the graphs), the graph will be the same for almost all countries. A rapid increase in new cases and then fall in numbers over 4-6 weeks. This has been the natural history of flu as can be seen in the graph from Germany. But the moment a lock down is imposed you interfere with the natural history of the disease. The curve is simply flattened at most, meaning that cases/.deaths will take place but will be spaced out or delayed. The logic behind flattening the curve was to buy time to improve logistics in hospitals , get more beds and ventilators and PPE’s. And also to ramp up the ability to test for the virus and check for past infection (antibody tests).

 

 

The lockdown has done little to the number of new cases detected in Switzerland.. The situation is more or less the same in India. Switzerland is on the brink of unshackling , while India keeps extending it despite no advantage. The proportion of new cases  detected in India is considerably less than other countries; where it ranges from 5 to 25%.In  India it hovers around 4% only.

 

 

The situation however was completely different in India, the cases have been remarkably few and deaths fewer. The main reasons are 2; a younger population cohort and much higher temperatures than Wuhan, Europe and the US. Let the so called experts say whatever they want, a 35 C plus temperature will paralyse this virus. The small number of cases is ample evidence. Some may argue that the lockdown has been our great saviour. Not true. Because the new cases keep coming each day despite the most draconian lockdown on the planet, yet they are few. Most hospitals are lying empty with health workers twiddling their thumbs. The corporates have already announced significant reduction in salaries of doctors.

 

The ministry of health predictably has been found wanting on every front. The mandarins and their advisors seem to come from another planet or are just confused. A neighbouring country announces the arrival of a new respiratory virus on January 10th, and we do not still have a validated antibody test with us on May 1st ! So much for our preparedness or reflexes. This is a cruel joke that a nation that attempts at an unmanned landing on the moon , does not have the scientific intellect to set up an antibody test over 4 long months. Worse no one seems to care, just about no one. Even the medical fraternity, which should have been screaming for serological testing for themselves have drowned itself in deafening silence.

 

It is imperative that we know the incidence of infection. For example they did in 3300 people in Santa Calra, to find that 2.5-4% people had past infection or antibodies. The study was done by Stanford University if you like credentials. The simple math is that around 50000 to 85000 people in Santa Clara county have been infected, but only 1000 people had tested positive by PCR. The conclusion, and a correct conclusion, is that the true prevalence of Covid 19 is 50 to 85 times more than the PCR estimate. Use the math in India, around 3600 cases and 1200 deaths, a crude mortality rate of 3.3%, but if we extrapolate from the Santa Clara data mortality is less than 0.04% by Covid-19. Instead of telling the true death ratio, the media keeps banging non stop on the dangers of this virus. The propaganda has been terrific because I am sure if people were asked for loosening a significant number would clamour that it be kept on for 6-8 weeks more. People have become paralysed by fear, they are scared out of their minds. It will take a miracle to mitigate their apprehension or rather terror. Most doctors are so scared witless that they prefer staying not 6 but 12 feet away from a patient. These are remarkable times. The politician and his Babu in the blink of an eye are prepared to seal a hospital if a couple of cases are discovered in a hospital. Sealing a hospital on finding a Cover -19 case, which kills less than 0.05% affected people is more than absurd, it is scary. Albert Camus wrote of bad and good people in his fabulous book “The Plague”, but he too could never have imagined that the nation of the Mahatma would go around sealing hospitals if a case was spotted within them. Where else would you expect to find this virus if not in hospitals ? People go to hospitals for treatment but now you scare the hell out of them by sealing hospitals. No wonder thousands of patients are petrified of visiting a hospital even as they suffer chest pains or paralysis. Mark my words, there will be far more deaths die to heart attacks, cancers and strokes in the next 2-4 years, than Covid-19. A bizarre and impossible situation has been created in this country. How many know that Gandhiji actually treated patients of pneumonic plague in Johannesburg. Pneumonic plague has always been a killer, but Gandhiji had the guts in 1904 to actually try to treat the patients. The leadership today is limited to delivering messages on TV and Twitter. This is a fact, I do not know which leader has mingled with the people (albeit from the prescribed distance) or visited a single hospital. Instead it has been the usual vacuous soundbites with minuscule substance, and even lesser (if possible) reassurance. This virus has no respect for caste, creed, religion or political affiliation. It demands that we shed our intellectual laziness and get to know the truth in order to tackle it. But if we do not it certainly will not mind.

 

New York too tested 3000 people for antibodies to find that 14% had been infected, in fact 21% of New York City inhabitants were infected. The implication again was that almost 27 lakh people had got infected , the good news was that armed with this knowledge the Governor Andrew Cuomo could publicly declare an infection fatality rate of 0.5%. The numbers should be tempered with the knowledge that numerous patients got treated by ventilators that proved detrimental. Why then in Gods name are people so scared of this virus? So terrified that they have gone to the extent of sealing Delhi from both NOIDA and Haryana. Apparently Haryana police has dug up roads at the border as if they anticipate a tank brigade to attack them. It is a ludicrous situation. Laughable. I was compelled to to do 2 PTCA procedures yesterday. Both patients we’re hanging by a thread. The procedure by any standards was life saving in both of them. We knew the first patient was Covid-19 negative because he had been tested. The second patient was a post CABG man who entered the emergency room with sustained ventricular tachycardia and BP of 70 mm Hg systolic. He needed a 20 joule DC stock for reversion before he was hastily wheeled to the Cath lab. He had had severe chest pain preceding the VT, and so the procedure was absolutely essential. Both patients had successful procedures and wished to be discharges as soon as possible, that is today. A patient expects the doctor who has done a major procedure on him to examine him before discharge. So it was with these 2. But alas it could not be done. To my utter horror I was stopped at the border this morning on my way to hospital. The hospital falls in Dwarka, Delhi whilst I currently reside technically in Haryana. So thats it folks; I did not bother bro treason with the rotund pot bellied policeman, I knew it was a waste of time. The man had orders from “above.” The situation is just hilarious. A pandemic has gripped the planet. All agree an epidemic unfolds in this country, but the high command is not prepared to permit doctors from treating patients. George Orwell would have never thought of this one. In fact this is not a “new normal,” this is a “unique normal.”

 

Sweden is not under lockdown. It never went under lockdown. Schools and restaurants are open. People have been advised to maintain distance amongst themselves and apply common sense. They anticipate herd immunity by the next fortnight. Moreover their death rate is substantially lower than other European countries. It is more than their neighbours who are under lockdown but expect the figures to level off by the time the season is over. There is grudging admiration for the Sweden model; despite orchestrated critiques thrown in influential media sources. Mercifully the Swedes did not buy the “Ferguson from Imperial College “ fame that 2 million would die in the US and 50000 in Britain if a lockdown was not imposed. Remarkably Ferguson did not publish a peer reviewed paper any where. Moreover Imperial college does not even have a pre reviewed paper anywhere. They just have a document that forced the Brits to make a U turn. The same Ferguson then gave testimony before parliament that deaths would be around 20000 and two thirds of these would be deaths in the normal course off events. It must be kept in mind that almost 50% of deaths in Europe including Sweden have been in old age homes. Ironically the people for whose protection the lockdown was imposed in the first place turned out sadly to be the ones that got most neglected. Sweden has conceded to this sad state of affairs and is making amends.

 

We have faltered at every stage of this epidemic. We never got PCR testing done on time, we even today do not have a validated serology test, we have absolutely no randomised data on any intervention attempted during this pandemic, an ill timed lockdown is inflicted without any scientific evidence, we have no idea when was the peak of new cases, even today we do not know the virus genome, and crucially we have absolutely no clue of the infection rate. We all wait with bated breath for a vaccine to materialise in the next 6 to 18 months, in the meantime we are the classic deer in the headlights. It is imperative that we read up on this virus, attain some clarity while shedding off the trepidation. It is not enough to watch TV all day, especially not the health ministry sermons, it is time to realise that sealing hospitals, sealing borders and extending this lockdown indiscriminately will not prevent infection in the slightest way. A man of 42 years was turned back from a hospital in Delhi yesterday for a Ciovid-19 test. He had gone to hospital for chest pain, he died in his way back. Maybe he has gone to a better place, most probably he has.  Sealing borders and hospitals is the trend  today.  Patients should expect to be treated by chaps who  present glitzy pandemic models or mandarins of the health ministry. You declare a pandemic, create coloured zones, constantly go on that the virus lurks in front , behind and around you, continuously remind the average man that he is a sitting duck if he gets infected, and then merrily prevent a doctor from going to the hospital. Incredible India. Enforcing a lockdown without a shred of evidence is easy, but what parameters will you apply to lift it?

 

As of now there has been no impact on the curve, as was expected. Each new day brings more cases. If the lockdown is lifted the virus will come roaring back because most people would not have developed immunity against it, while confined in their homes. The elderly will continue to be vulnerable. The misery that has been inflicted on crores of people is compounded by the fact that a staggering amount of time, money and lives have been wasted. amid an officially declared  national medical emergency preventing a doctor from crossing the Delhi Gurugram/NOIDA border is not only bizarre but plain idiocy. The obsequious babu in his zest for lockdowns is totally oblivious of the fact that there are hundreds of other serious ailments apart from Covid-19  demanding both attention and treatment.

DEATHS DUE TO COVID -19 – ALONG WITH IT – AND EVEN WITHOUT IT.

 

For me the greatest revelation in the current pandemic has been the realisation by the New York critical care specialists that the lung pathology of Covid 19 is quite different form the much studied acute respiratory disease syndrome (ARDS). The chest X Ray and CT scans do look like that of ARDS but prompt intubation on spotting low oxygens in blood has led to mortality ranging from 70-100% in most centres. Doctors have frequently observed that patients suffering form Covid-19 present with dangerously and unheard levels of oxygen saturation, as low as 20% ! But the patient appears untroubled by the low oxygen sat, and even continues talking over the phone. This has never been seen before. A patient with such low oxygen level has always been accompanied with a fast heart rate and loss of consciousness. It is therefore being recognised that Covid-19 lung changes is a separate disease needing a different approach. The lungs in Covid 19 have high compliance to begin with, this is like a thin walled balloon that requires little pressure for inflation. Most patients with Covid-19 are being successfully managed with mere oxygen administration by a tube or CPAP, at most. The few who develop reduced compliance are the ones that need to be intubated and connected to a mechanical ventilator. Reduced compliance can be imagined as a balloon with thick walls that needs greater pressure for expansion. Most probably the high mortality with ventilators has been because of indiscriminate employment of ventilators. No one can be faulted for this because this disease is brand new and a midway change in protocol during a pandemic can be very difficult. Maybe a change in paradigm is required a fresh approach to ventilation needs to be sorted out by leading pulmonologists and critical care specialists coming together.I raise the point on the use of ventilators in the current pandemic because it may be possible to reduce mortality by as much 50 % in the sickest cohort of patients. But only a randomised study and time will reveal the truth. A recent study of 5700 patients admitted in New York City revealed that almost all patients had at least one co morbidity, and 88% had at least two. Only 6% had no previous health issue.50% suffered from hypertension, 40% had obesity and 30% were diabetics. About 20% of patients died. Of the 320 patients (intubated and connected to a ventilator) , 282 died (88%). Almost a third of patients did not have fever when they came to hospital, 17% had a respiratory rate greater than 24 per minute and 28% got supplemental oxygen. The take away is that a lot of sick patients may not have fever at admission. But crucially one must address the high mortality associated with ventilators, as has been done by a Dr Cameron Kyle-Sidell working in a Brooklyn hospital. He was one of the first to notice that the conventional protocol of treating Covid-19 patients as ARDS did not seem to work in a substantial number of patients.ARDS could be present in patients with Covid-19 but is not uncommonly associated with pneumonia, sepsis, and lung injury. Ventilators for every Covid-19 patient was red flagged in a letter to the editor published in late March by the American Journal of Respiratory and Critical Care Medicine that underscored: “an overwhelming number of patients” in northern Italy showed characteristics “in sharp contrast to expectations for severe ARDS.” The author of the letter is anaesthesiologist Dr. Luciano Gattinoni. One of the top American pulmonologist Prof. Martin Tobin too advised that lung pathology in Covid-19 patients differed from classic ARDS. As for now Dr. Kyle-Sidell has stepped down form his ICU position because his approach is against the grain of the conventional protocol. “These didn’t fit the protocol, and the protocol is what the hospital runs on,” he told Medscape “We ran into an impasse where I could not morally, in a patient-doctor relationship, continue the current protocols which, again, are the protocols of the top hospitals in the country. I could not continue those. You can’t have one doctor just doing their own protocol. So I had to step down.” Oddly the WHO advises prompt intubation and mechanical ventilation as the preferred approach, rather than use of CPAP.

 

 

In the mean time we must turn our attention to mortality associated with Covid 19; what better than to quote a leading German virologist and expert who has explained that a man can die because of SARS-CoV-2 , that causes the Covid-19 disease or could die along with the virus inside him. He gives the example of a man in his seventies dying from heart failure (not uncommon) without SARS-Cov-2 in his lungs, but being positive for the virus. The Italian Institute of Health (ISS) reported that only 12% of Covid -19 deaths were registered as being caused by the virus. Also 99% of the patients who died had at least one co morbidity. More than 75% had 2 chronic diseases. Italy’s death registration process does not distinguish those who are killed by the virus from those who have the virus in their body. Strangely almost all other countries are following the same methodology to registrar deaths by Covid-19. Germany also considers any Covid-19 infected person who dies as a Covid-19 death, whether or not it actually caused death. The CDC’s National Vital Statistics Service states “It is important to emphasise that Coronavirus Disease 19, or Covid-19, should be reported for all decedents where the disease caused or is presumed to have caused or contributed to death.” “In cases where a definite diagnosis of Covid-19 cannot be made, but is suspected or likely (e.g the circumstances are compelling within a reasonable degree of certainty), it is acceptable to report Covid-19 on a death certificate as “probable” or ‘presumed.”m In these instances, certifiers should use their best clinical judgement in determining if a Covid-19 infection was likely.” Northern Ireland’s HSC Public Health Agency defines a “Covid-19”death as “Individuals who have died within 28 days of first positive result, whether or not COVID-19 was the cause of death.” England is no better. The Office of National Statistics (ONS) was initially reporting only figures provided by the Department of Health and Social Care (DHSC), which records only those dying in hospital and have tested positive as Covid -19 deaths. But from now on the ONS will include patients who have died in the community, including those not tested for Covid-19 and in whom “suspected Covid-19” is presumed to be a ‘contributing factor.” The official NHS advisory for filling death certificates is “ If before death the patients had symptoms typical of COVID19 infection, but the test result has not been receive, it would be satisfactory to give “VOVID-19” as the cause of death, and then share the result when it becomes available. In the circumstances of there being no swab, it is satisfactory to apply clinical judgement.” The government is instructing doctors to declare deaths as being caused by Covid-19 without any evidence of infection. The office of the Chief Coroner does not require “Covid-19” to be referred to a coroner, doctors can sign off a cause of death for a body they have never seen. “Any registered medical practitioner can sign an MCCD ( Medical Certificate for Cause of Death), even if the deceased was not attended during their last illness and not seen after death, provided that they are able to state the cause of death to the best of their knowledge and belief.” Deaths in the community can now be considered as Covid -19 deaths without testing for the disease or even seen by a doctor. These deaths will not necessarily be referred to a coroner, and certainly not herd by a jury. One can clearly note that the merging picture is of inflated death rates due to to SARS-Cov-2. After publicly declaring that unchecked Covid-19 would kill more than 500000 people in Britain, Prof. Neil Ferguson in his testimony before parliament , said that he expects fewer than 20000 Covid-19 deaths in the UK, and two thirds of these people would have died anyway. Put in another way the crude figure for “Covid -19 deaths” is three times higher than there number who have actually been killed by Covid-19. The BBC reported : “An 18 year old in Coventry tested positive for coronavirus the day before he died and was reported as its youngest victim at the time. But the hospital subsequently released a statement saying his his death had been due to a separate “significant” health condition and not connected to the virus. The also clarified that it ‘had tested for Covid-19 on the day before he died, but this was not linked to his treason for dying.” But despite the hospital statement the fact remains that as per current rules in Britain the death of this boy remains a “Covid -19 death.” Also about 250000 to 65000 people die of flu or “flu like illness”, every year, anyway, so how do we separate these deaths from “Covid-19 deaths.” Instead of providing the correct numbers, most if not all governments are presenting inflated numbers that are driving the public witless with fear.

 

 

 

 

People have become so scared that they prefer suffering in silence rather than visiting a hospital. An Austrian study brings out the dark side elegantly. The number of patients usually treated for heart attacks (acute coronary syndrome or ACS) in a year hovers around 17,600 per year in 8.8 million people. In comparison to previous years the number of cases this March declined form 725 to only 275. A relative reduction of almost 40% in admissions for heart disease. Based on the data that cardiovascular mortality of untreated patients may be as high as 40% (as it was in the 1950’s) it can be presumed that 110 heart patients perished in March of this year. The official number of deaths in this time frame form Covid-19 in Austria was 86 . Hence more people could have died because of not going to hospital to get treated for heart disease than by Covid-19.There is always the possibility People have become so scared that they prefer suffering in silence rather than visiting a hospital. An Austrian study brings out the dark side elegantly. The number of patients usually treated for heart attacks (acute coronary syndrome or ACS) in a year hovers around 17,600 per year in 8.8 million people. In comparison to previous years the number of cases this March declined form 725 to only 275. A relative reduction of almost 40% in admissions for heart disease. Based on the data that cardiovascular mortality of untreated patients may be as high as 40% (as it was in the 1950’s) it can be presumed that 110 heart patients perished in March of this year. The official number of deaths in this time frame form Covid-19 in Austria was 86 . Hence more people could have died because of not going to hospital to get treated for heart disease than by Covid-19. There is always the possibility that one could die with Covid-19, because of Covid-19 or even without it; albeit not necessarily in this order.

 

A PATIENT CAN DIE WITH COVID-19 AND NOT NECESSARILY ALWAYS FROM IT

NEW YORK TIMES 14th APRIL; DECLINE IN INTUBATIONS IN NEW YORK STATE.

 

 

AJRCCM Articles in Press. Published March 30, 2020 as 10.1164/rccm.202003-0817LE Copyright © 2020 by the American Thoracic Society

 

Each day brings more information of the SARS-CoV-2, of its infectivity, its lethality, pathogenies and treatment. One of the most striking revelations has been that patients put on ventilators do extremely badly. Just about every centre reports very high rates of death once a tube is put in a patient. Some critical care doctors have stuck out their necks to explain that lung pathology in Covid-19 patients seems different from that of acute respiratory distress syndrome (ARDS). Professor Gattinoni, a leading expert from Italy, has suggested that the lungs of most Cover -19 patients retain their mechanical capacity to function despite severe hypoxia. Clinicians in New York have begun to notice that patients with Covid-19 having low oxygen saturations continue to lucid and clear. It is not uncommon to find a patient with an oxygen saturation as low as 50% speaking on the phone. The term “happy hypoxia” has been given to the condition, only for these patients to suddenly collapse. The initial paradigm of incubating patients as soon as oxygen saturation begins to drop is drawing sceptics. It is slowly being realised that patients with Covid-19 have a unique lung disease, not the classical ARDS. Treating doctor shave realised that somehow intubated patients fare badly, with mortality ranging from 30 to almost 100%. One explanation discussed among critical doctors is that air pushed in at high pressure by ventilators may be causing more harm to lungs than providing relief to them. It has been noticed by some doctors , serendipitously, that a patient with severe hypoxia but conscious did better with oxygen provided by a tube in the nostril. One trick employed is to turn the patient to her left or right or even prone (on the tummy). There is dramatic improved in oxygen saturation within minutes of applying this simple technique. Most probably the prime minister of England was treated with simple oxygen delivery. At the most he may have been given oxygen by continuous positive airway pressure or CPAP. The Covid-19 lugs seem to be more like those of high altitude sickness. As a New York doctor explains it is like dropping some on on the peak of the Mount Everest without any time to acclimatise. The SARS-Covid-19 virus, unlike conventional pneumonia, attacks both lungs. The patients come to hospital with low oxygen levels but not in distress. The usual patient is in acute distress once oxygen drops below 80%, but not the Covid -19 patient. The Covid-19 patient has a strange slime in his airsick that prevents oxygen exchange in the lungs. Increasing the force with which the ventilator can pump in air is of little or no help. Maybe ventilators may work at lower pressures in selected patients, but this will need a randomised trial. For now many critical care specialists are batting for simple oxygen administration to the patient, while she is kept in a prone position. No wonder there has been a substantial reduction in use of ventilators in Covid-19 patients in New York city. The current mantra is to use ventilators in selected cases but used to push in oxygen less aggressively.

 

 

FROM NEW YORK TIMES, 14 th APRIL

 

The simple oxygen administration technique is buttressed by the first autopsy report form one of the top US hospitals. The report consists of only 2 patients , but is revealing all the same. The first patient who died from the virus was an obese 77 years old hypertensive man, whose autopsy showed that the lung sacs were smeared with a substance that resembled thick paint. The man was confirmed to be positive by RT-PCR. The man had been symptomatic for 6 days, he had fever and chills. He died before he could be put on a ventilator. The lung sacs were inflamed and damaged, and full of lymphocytes ( proof of damage due to virus).

 

 

The second case albeit infected by SARS-CoV-2 did not die from it. The 42 years old man did not have the slime in his air sacs, he died of bacterial pneumonia. This man was admitted in a critical condition to hospital for fever, cough and shortness of breath. A CT scan done before he died showed bilateral ground glass opacities as well as bilateral pneumonia. Nasopharyngeal swabs were positive for SARS-CoV-2 by RT-PCR, but both lung swabs were negative. A standard respiratory pathogen was also negative. Bacterial cultures grew Escherichia coli and Proteus mirabilus. Under the microscope it was seen that the lungs had bronchopneumonia and aspirated food particles. The man had suffered from a muscular weakness disease. The final autopsy listed Covid-19 as a condition but not the cause., the manner of death was listed as natural. The patient had most probably died of bacterial pneumonia likely caused by aspiration. The authors of the paper emphasise “Therefore, this patient likely died with COVID-19, not from COVID- 19. These cases illustrate the challenges that pathologists and the medical community at large will face in deter- mining the cause of death in decedents who test positive for SARS-CoV-2. Some findings will represent true virus- related pathology, while others will reflect superimposed processes or unrelated illnesses.” Greater experience as the pandemic unfolds will help forensic pathologists tease out cases that die from SARS-CoV-2 rather than perishing with it.

 

It has been difficult explaining the difference between a patient dying from SARS-CoV-2 as compared to some one dying from some other disease but simultaneously infected by this virus. A postmortem is the only method for confirmation albeit even this could be demanding; but clinical confirmation of cause of death will certainly prove to be perplexing in a lot of cases. It is for this reason that I am unsure of the numbers of Coivid-19 deaths being provided by most countries. The Italians too have conceded that they are not sure of the exact number of deaths caused by SARS-CoV-2. Moreover the CDC is quite flexible regarding mention of cause of death; even confirmation of the presence of SARS-CoV-2 is not mandatory while filling death certificates.

 

The Times (London) has reported yesterday what I consider the only bright news in the previous 3 months regarding the Covid-19 pandemic. This information is considered a “leak.” Apparently a video is floating around that reveals a University of Chicago reviewing results for her colleagues, on a broad spectrum anti viral medicine called remdesivir. The university had recruited 125 patients with Covid-19 into 2 trials, one trial included 113 severe patients. There was no control or placebo arm, all patients were treated with intravenous remdesivir. Fever got reduced in many patients, some were taken off ventilators within a day and most patients did not need the full 10 days course with remdesivir. Importantly only 2 patients have died.Most patients were leaving hospital as early as 6 days. This is remarkable news if true. One hopes the leak was not deliberately engineered by the manufacturing company. In a statement, the University of Chicago said “drawing any conclusions at this point is premature and scientifically unsound.”The news item fails to inform us of the seriousness of the illness in the recruited patients, at what point of time the drug was administered, or how many were on ventilators . Moreover the trial is yet to be published, the company however has recruited 2400 severe Covid-19 patients from 152 clinical trial sites all over the world. More than 1600 patients with mild symptoms have also been included in clinical trials from across the world.

 

his article was published on April 10, 2020, at NEJM.org.
DOI: 10.1056/NEJMoa2007016

 

A small trial with remdesivir was published recently that included 53 patients with severe Covid-19 patients. All patients had oxygen saturation less than 94%, with almost half needing ventilators and 4 patients were on ECMO machine. All patients received remdesivir for 10 days on compassionate use basis. Improvement was seen in more then two thirds of patients , with 17 of 30 patients on mechanical ventilation getting off the machine. Almost half of patients studied became fit enough to be discharged. Mortality was 5% (1m of 9) in those not needing ventilation and 18% (6 of 34) in those attached to a ventilator. This was not a randomised trial, and did not have a placebo group. The trial should be considered preliminary with a hint that remdisivir may be effective in severe patients with Covid-19. Data form the larger trials will provide much needed clarity on treating the SARS-Cov-2 induced pandemic. Till then all reports should be considered anecdotal, even if there are some case reports showing marked improvement.

 

How does the drug work ? Remdesivir does not attack the virus directly. It instead goes after the copying machine of SARS-CoV-2.These viruses have a genome that consists of a strand of RNA. To make copies of themselves, they rely on a molecule called a polymerase to string together the individual building blocks of the viral genome. Remdesivir  mimics the appearance of one of the RNA letters, adenosine. It looks so similar that the polymerase can unknowingly pick it up instead of the real adenosine and insert it into the strand of viral genome that’s being constructed. Once in place, the analog acts as a cap, preventing any additional pieces from being strung on. This leaves the strand short of the full genome. The virus can’t go on to replicate or infect other cells.As a researcher put it “The polymerase grabs it almost accidentally and uses it in place of adenosine.”The usual caveats apply, the trials done so far have not included controls, so a bias can never be ruled out. A randomised trial is scheduled by the NIH (US), and we will have to wait for the results before drawing any conclusions.

 

The good news is that inspite of increased  testing the  number of new cases are in the decline, and number of deaths too follow the same trend. The WHO has reported a total of 437 deaths yesterday with 23 new deaths . Coronavirus cases in India rose to 14,792 on Saturday evening, according to the health ministry website. The death toll in the country stood at 488. 75.3% of those who died were over 60 years old. In 83% of the deaths, the patients had co-morbidities like diabetes, hypertension and heart disease. One should expect further reduction both in number of fresh cases and deaths with increase in temperature.

THE MYSTERY OF THE DIFFERENT COVID-19 INDIAN TRAJECTORY FROM THE WEST

 

 

 

On the advice of a very wise friend I am adding the above graph that reveals number of deaths in the most affected countries over time. Starting point is 100 deaths; both Iran and China do not have more than 5000 deaths even after 40 days. The European countries however suffered greater casualties; Italy, Spain and France had 5000 deaths within 20 days. The American worm has a trajectory of almost 90 degrees, 5000 people died by about 15 days but another 15000 have died in the next 15 days. India, as we approach mid April ,has 7987 active cases with only 308 deaths (13th April 2020). This virus should have penetrated India almost at the same time as it has the rest of the world, certainly along with Europe if not weeks before. There was regular traffic between India and China in the months of January and February, so the virus should have arrived in India by then if not before especially as Delhi airport is one of the busiest airports in the world. Already the number of new cases picked up each day are plateauing despite significant ramping up of testing.

 

 

The number of deaths increased from ( between 19th and 23 rd March) from 2978 to 5476 in Italy, and from 598 to 1720 in Spain; deaths on a single day (23 March) were 649 in Italy and 394 in Spain. Another way of looking at it is to see how the pandemic has unfolded since February 2020 to today, which is a period of almost 2 months.  On Feb 2020 India had 3 cases, the US had 15 cases, Italy had 3 cases and Spain had 2 cases. A fair start for each country. India has reported 34 new deaths in the last 24 hour while the numbers are 2000 for the US, 619 for Italy and 510 for Spain, respectively. The difference of rate in mortality due to Covid 19 is quite obvious, but the explanations are not very clear. The same virus has been plaguing these nations…… but the geography, season, and demographics are quite different. Till a month back, overall, older patients in the USA were the most likely to be hospitalised, to be admitted to ICU, and to die of COVID-19. A total of 31% of the cases, 45% of hospitalisations, 53% of ICU admissions, and 80% of deaths occurred in patients aged 65 years and older. The US has 562,742 cases, Spain 169,496, Italy 156,363, France 132,591, but India has 9240 cases. India has a population of 1.35 billion people.

 

JAMA. doi:10.1001/jama.2020.5394 Published online April 6, 2020.

 

Recent data on 1591 laboratory confirmed patients admitted in intensive care [median age 63 years (56 to 70)] from Lombardy, Italy, records that the majority were older men, with ICU mortality of 26%. 68% of patients had at least one comorbidity. Mechanical ventilation was needed in 88% patients in this series. Patients older than 64 years had 36% mortality while those below 64 years had 15% mortality. Less than 1% of admitted patients were less than 20 years, 4% patients were between 21-40 years, and 9% patients were between 41-50 years. More than 86% patients were more than 51 years.

 

One must keep in mind that data published today on Covid-19 is becomes almost obsolete the next day. But the trend of elderly people and patients with co-morbidities being more vulnerable to the virus continues. Information from China on the effect of age and comorbidity initially came form China. Preliminary data from the US too follows this trend. Analysis of 7162 of 122,653 positive American reported as of 28th March that 37% patients had on or more underlying conditions or risk factor. Co morbidities were commoner in those requiring hospitalisation (71%) and intensive care (78%). The most commonly reported diseases were diabetes, heart disease, and chronic lung disease. The majority of deaths (94%) occurred in patients with underlying conditions. People older than 65 years with or without underlying conditions are at greatest risk for severe disease and death.

 

This article was published on March 27, 2020, at NEJM.org.
DOI: 10.1056/NEJMoa2005412

Today’s Guardian reports that almost 50% of deaths in Europe are occurring in care homes that house elderly people. The report quotes figures from an American care home in which the residents had mortality greater than 34%. The median age of the residents was 83 years. Interestingly no health care personnel albeit positive for the virus died; their median age 43 years. Younger age does seem to be an advantage. Care homes are vulnerable primarily because the residents are elderly, social distancing is not ideal, and the staff are not medically savvy.

 

 

On combing the continuously evolving data from across the world one can clearly see the Indian trajectory of Covid-19 is quite dissimilar to that of other countries. Although strictly speaking it is still a matter of conjecture but one cannot help but sense that younger age and warmer temperatures may have mitigated the impact of Covid-19 in India. Time alone will confirm the truth behind the stark difference in the behaviour of SARS-CoV-2 in India as compared to the West.

 

Data from 5 European countries suggest that care home residents have so far accounted for between 42% and 57% of all deaths related to COVID-19.

 

INDIA HAS A FLATTER COVID-19 CURVE THAN THAT OF THE WEST

 


The entire world is reeling under the Covid-19 pandemic, thousands of people have died and the global economy is in shock even by conservative estimates. It will take many years for the post Covid world to recover. The virus is named severe acute respiratory syndrome corona virus 2 or SARS Cov 2; and the pandemic that it has caused is named Covid 19. The prevalence in India unlike the Western world has been observed to be substantially less. As per the health minister it is 3.8 per million. Testing, however, has been low with only one lac samples collected to date, the government has urged all states to ramp up testing to at least 2.5 lakhs by 14th April. In contrast, Americans are testing one lac people in a single day and more than 20 lac tests have been performed so far. In India as of today the number of total cases is 7447, with 239 deaths, giving a crude case fatality rate of 3.2% only. Deaths in India are considerably less than those in the US (`18,763), Italy (18849), Spain (16081) or France (13197). China has reported 3339 deaths while 4110 people have perished in Iran. Germany has had 2707 deaths.

 

http://www.ijmr.org.in on Saturday, April 11, 2020, IP: 49.36.142.188]

 

The ICMR has finally published data on prevalence of Covid-19 in 5911 patients admitted in hospital for severe acute respiratory illness. This is a cohort of sick people with respiratory disease, and not people walking about on the streets. Data was collected form more than 50 districts in 20 states. The researchers report of the 5911 patients only 104 tested positive for the SARS-CoV-2 virus (1.8%), from mid February to mid March. The median age of positive patients was 54 years and 83% were males. Majority of patients tested were from Gujarat that contributed 792 patients, Tamil Nadu 557, Maharashtra 553 and Kerala 502. Importantly more than one third of positive patients (39%) did not report international travel or any history of contact. Only 3 patients had history of foreign travel or contact with confirmed Covid-19 case.Data on exposure was not available for 58% positive patients. The authors concede that their sample may not reflect national trends, but a prevalence of just 2% in patients hospitalised for respiratory problems in current times is small by any standards. The researchers are to be congratulated for their efforts but information on mortality is also needed. Mortality in the positive cases as compared to the patients who were not found to be harbouring the virus. It should be kept in mind that this data extended to mid March. There was no positive case in those aged between 10-19 years, while 65% of positive cases were more than 50 years and 16% between 40 and 50 years.

 

POPULATION BREAK UP IN INDIA (APPROXIMATION)

 

The probable reasons for the remarkably fewer deaths in India cannot just be under-ascertainment. Demography must be playing a role. Analysis of Italian deaths in the current pandemic has revealed that 99% of people dying had at least one comorbidity, and more than two thirds had 2 or more co morbidities. The median age of those dying was 83 years, and 70% of deaths were in those more than 70 years. Covid 19 killed less than1% people who were without co-morbidities. As opposed to Italy, less than 5% of population is above 65 years in India, while almost 48% are less than 21 years. India is a country of young people, who it has been seen in, other countries, to be less susceptible to being infected by SARS-Cov-2.

 

Hindawi Publishing Corporation Advances in Virology
Volume 2011, Article ID 734690, 7 pages doi:10.1155/2011/734690

 

Research during the SARS epidemic of 2002 -2003 revealed that transmission of the SARS CoV significantly declined with rising temperatures. Activity of SARS virus almost became absent above 29 C. This paper was cited by a recent publication from MIT, that made the interesting observation that 94% of cases suffering from Covid-19 have been in areas with temperature below 17 C, only 6% of cases were seen in geographical areas above 17C. The current mean afternoon temperature in Delhi exceeds 30 C. Right now, Delhi has a temperature of 33 C, London 11C, Wuhan 17 C, Milan 14 C, Madrid 11 C, while both New York city and Washington DC will remain below 11 C all day. The mitigation in infectivity of SARS-Cov-2 by higher temperatures cannot be rule out. The combination of younger people and higher temperature may explain the lower prevalence in India. Importantly Australia has reported only 54 deaths , Perth has a temperature of 34 C and Sydney is at 21 C.

 

Scientists at University College, London recently found high rates of other coronavirus infections in February, but very low prevalence in summer. The researchers point out that a similar pattern may be possible with SARS-CoV-2 virus 2, but the effect of season may not have the same impact as social distancing. Arrival of summer also herald boosting of the immune system. Interestingly the original SARS CoV lost activity with mounting temperature and higher levels of humidity. Researchers from Hong Kong showed that SARS CoV viability on smooth surfaces was rapidly lost at higher temperatures and humidity ( 38 C). They suggested that this was the reason that countries such as Malaysia, Indonesia and Thailand with high temperature and humidity did not have major community outbreaks of SARS. It is well to understand that no SARS CoV likes sunlight, temperature and humidity. Sunlight reduces half life off the virus from 15 minutes to 2 and a half minutes, thats one of the reasons that Australia has seen less than 60 deaths so far; because they still have summer there. The virus gets uncomfortable at 30 C.

 

John Nicholls, a pathology professor at the University of Hong Kong, believes that SARS-CoV-2 is more like the coronaviruses that produce the common cold than SARS-CoV or MERS, that have much higher fatality rates. Nicholls reportedly has stated for the benefit of investment analysts that the natural environment shall be unfavourable to DSARS-CoV-2 in May. AccuWeather Founder and CEO Joel Myers hopes the picture regarding lowering of infectivity of SARS-CoV-2 due to temperature gets clearer by mid April. “Where spring comes early with above normal temps and more sunshine, the virus spread will faster than where clouds diminish the sunshine and temperature and humidities are slow to rise.” But this is a new coronavirus with no previous data correlating temperature with infectivity. An MIT paper buttressed by previous research on SARS-CoV reports that more than 90% of SARS-CoV-2 are localised in countries with temperature below 17 C. Chinese researchers postulate that one degree Celsius rise in temperature will reduce the reproduction (R) number by 0.02, reproduction number being the number of people one person infects, hence an R of 2 would imply one person is infection 2 persons. They have also shown that low temperature is favourable for SARS-CoV-2 transmission ( preprint server med Rxiv).

 

Clinical Infectious Diseases® 2017;65(7):1183–90

 

Apart from difference in age and variation in local temperature another tempting explanation for lower prevalence and less mortality in India may be the policy of universal BCG vaccination. Researchers have suggested that countries with a national program of universal BCG vaccination report lower incidence and fewer deaths. Countries that do not have compulsory BCG vaccination ( Italy and the US) have suffered much greater loss than those with. China did have a mandatory BCG program but this was disrupted severely in the 1950’s that saw considerable political churning.The Bacillus Calmette-Guerin vaccine was developed more than a hundred years ago to fight tuberculosis. It is named after the inventors, Dr Albert Calmette and Dr Camille Guerin , who developed it from tuberculosis bacteria infecting cows (bovine TB). The vaccine was first used for the first time in 1921Over the years it was found to be an effective immune system booster against virus, bacteria and parasites. Mortality has been shown to be reduced in underweight children with respiratory infections by BCG vaccine. A large randomised trial in underweight infants in Denmark demonstrated significant reduction in infectious disease mortality with the BCG vaccine. But there is no completed randomised trial on effect of BCG vaccination against Covid-19 as yet. A clinical trial including 1000 health care workers has ben initiated in Holland, and a larger trial is going on in Melbourne with 4000 healthy workers; half will be assigned to BCG vaccine plus the flu shot while the other half of participants will get only the flu jab. Results should be out in a few months to confirm whether the BCG vaccine provides protection against SARS-CoV-2.

 

The mystery of substantially lower prevalence and fewer deaths by SARS-CoV-2 may not be easily solved in the coming weeks. The fact however remains that incidence is low in India, which frankly has not done anything spectacular to contain Covid-19. Despite little effort the Indian “curve” is flatter than the ones seen in the West.Three possibilities have been discussed that could be keys to the puzzle. It would however be irresponsible and in fact foolish to lower ones guard against this new coronavirus. Meticulous hygiene and physical distancing is the new normal now and could stay with us for decades to come.But “social distancing” has to be appropriately timed for optimal effect, too early or too late implementation will simply flatten and broaden the curve to delay development of herd immunity. Handshakes or hugging may vanish in a post Covid-19 world. Maybe this virus will decide to suddenly vanish like its predecessor, the SARS virus in just a couple of years.I happen not only to be in the vulnerable age group but continue to manage heart patients every day; so I for one am longing for the temperature to climb to more than 40 C at the earliest. And yes to the best of my knowledge I did get a BCG jab as a child. The Chinese to their credit have published a staggering amount of data on Covid-19 but researchers are now facing a serious vetting program by their education ministry that wants to check all research investigating the cause of the pandemic. It therefore becomes imperative that research in India on SARS-Cov-2 is given the highest priority by the ministry of health, and the various medical publishing houses. This is of the utmost importance because 10 doctors have perished in the UK so far, all belong to BAME ( Black,Asian,and Minority Ethnic) background. We still are not at the end of the tunnel. And sealing hospitals right in the middle of an epidemic is plain ridiculous, because it is well known that a hospital is one place where one is bound to confront this new virus. Health workers are in close proximity to symptomatic patients / asymptomatic carriers and are therefore susceptible to infection, and sadly a few may succumb, but never before has their need been greater than now. Ostracising or abusing a health worker  should be considered a heinous offence. Moreover, risk of chronic diseases such as diabetes, hypertension, and atherosclerotic heart disease is bound to mount with lacs and lacs of people sequestered in their homes for weeks together. Covid -19 is not the only disease that a health worker or a hospital is to face for months and years to come. More than 2100 people have died in America in connection with this virus in the last 24 hours, but here in India only 22 people have perished. The incidence of Civid-19 is less in India and so is it its lethality. Hospitals are established  to heal sick people, not to be sealed on a whim. This is not the time for ham fisted knee jerk responses.

 

 

 

 

COVID-19 AND THE GUT

 

 

Lancet Gastroenterol Hepatol
2020
Published Online
March 19, 2020 https://doi.org/10.1016/ S2468-1253(20)30083-2

First the unvarnished fact, without the slightest intention of grabbing brownie points. A scientific letter was published last week in the “Lancet Gastroenterol Hepatol Journal” that reported results of the presence of coronavirus in respiratory and faecal samples confirmed by real time reverse transcription polymerase chain reaction (RT-PCR). Respiratory and faecal samples could be collected from 74 of 98 patients infected with Covid-19 (76% of patient group). Respiratory swabs remained positive for 15.4 days from symptom onset. Faecal samples were positive in 41 (55%) of 74 patients and remained positive for 27.9 days, while the respiratory swabs remained positive for only 16.7 days after first symptom onset. Simply put patients infected with Covid -19 had virus in their stools by an average 11 days more than in their respiratory swabs . However,45% of patients had negative faecal samples, that is almost half of the patients did not have their guts infected with Covid-19. Some crucial observations pointed out by the researchers need to be emphasised; presence gastrointestinal symptoms was not associated with faecal viral positivity; severity of disease was not associated with extended duration of virus in faeces; but importantly there was an association of faecal virus with anti-viral treatment.

 

The authors of the letter suggest that routine stool sample testing should be done by RT-PCR even after respiratory samples become negative. But they concede that do not know whether the virus in stool is viable based upon RT-PCR testing; and that no case of transmission has been reported by the faecal-oral route with Covid-19 : “which might suggest that infection via this route is unlikely in quarantine facilities, in hospital, or while under self -isolation.” Further studies are obviously needed to to determine viability and infectivity of Covid-19 in faeces. Based upon this scientific letter the plausible conclusions we can draw are the Covid-19 virus is present for more days in faeces, but little is known of the viability and infectivity of this virus. Crucially the letter does NOT mention transmission of Covid-19 by flies anywhere.

 

The news report by Hindustan Times today quoting a famous Bollywood celebrity therefore comes a surprise. The Hindustan Times elaborates “If the house fly sits on this excreta and then on some food particles and spread the disease.” It is possible this is a hacked tweet. It certainly is not based on any scientific peer reviewed publication. Hindustan Times provides a reference but this is a comment on recommendations for stool transplant from prospective donors, who should be screened for typical Covid-19 symptoms within the previous month, travel to areas infected by Covid -19 or close contact with an infected person. If any of the above are present such a donor must have confirmation by RT-CRP testing. The recommendations would be applicable to all types of donors. Incidentally faecal microbiota transplantation is now successfully being used in the management of recurrent Clostridoides difficile infection.

 

The study cited by Hindustan Times is not on faecal-oral transmission of Covid-19 but does provide a reference of a study (yet to be proof read) on 73 patients infected with Covid-19 virus. Of the 73n patients about half were stool postive for a duration ranging from 1 day to 12 days. About 23% patients persisted with positive stool samples after respiratory samples had become negative. The authors note that their study provides evidence of gut infection and its “possible” faecal-oral route transmission. Entry into the gastrointestinal tract is by ACE 2 receptors present in the stomach, duodenum and rectum. The CDC recommendation that once a patient has 2 consecutive negative respiratory samples can be considered disease free may not hold because of extended presence of the virus in the gut. But again this paper too does not dare to make specific extrapolations on infectivity by this route.

 

The global pandemic has brought the planet to standstill. Economies across the world are getting brutally battered. Scientists are scrambling to provide answers. There have been mixed signals regarding the new disease in almost every country. Understandably people are under extremes stress; but it is exactly in such times that we have hold our nerves. It is imperative that we keep our wits about us and gather information from peer reviewed publications in scientific journals. Newspaper headlines albeit interesting could be quite misleading or worse add to the confusion. Never before has the lay public needed to pay more attention (only) to qualified scientists; this hold good for any country, but especially for us in India. Celebrities for all their laudable efforts in disseminating information may inadvertently add to the chaos. We cannot afford a Mr. Idris Elba staring into the camera in all seriousness to announce that he is infected with Covid -19 with his wife (Covid-19 negative) next to him. Obviously Mr. Elba, good enough to be in the James Bond loop for years, is completely unaware that he is sending the wrong message, or he is quite sure he will not transmit the virus to his wife. Silence was never more golden.

 

The Indian ministry of health has a website up with daily bulletins on the do’s and dont’s regarding the Covid-19 virus.

LOSS OF SMELL; NEW SYMPTOM OF THE COVID-19 DISEASE

 

 

Lancet 2020; 395: 507–13

 

The coronavirus juggernaut is exactly that, merciless and destructive. The pandemic just refuses to be tamed or slowed down. The social, economic and clinical complexities keep evolving by the day. Each new day brings incremental information on the new virus. Launched from Wuhan, it put the fear of God in northern Italy, and today the United States has become epicentre of the pandemic. Johns Hopkins University suggests that the United States has the world’s largest numbers (more than 82,000 of Covid-19 cases) with about 1200 deaths, giving a case fatality ratio of 1.5%. Globally there are more than 500,000 cases now. India has announced more than $ 23 billion economic stimulus plan for the millions of people affected by the largest lockdown in the world. Mercifully number of deaths so far are relatively less than other nations. Even as I write the UK prime minister Boris Johnson has tested positive for Covid-19. He has fever accompanied by persistent cough, and shall self isolate in Downing Street. In his own words: “I have developed mild symptoms of the coronavirus that is to say a temperature and a persistent cough…stay at home , protect the NHS and save lives.” Luckily for him he manages the short 2 minute video recorded message without a sniffle, sneeze, or a cough.

 

We know from Chinese data of 1099 confirmed patients the most common symptoms are fever ( 44% on admission and 89% during hospitalisation) and cough (68%). The median incubation period was 4 days. Another Chinese of 99 confirmed cases reported fever in 83% , cough in 82%, and shortness of breath in 31%. A few patients presented with muscle ache (11%), confusion (9%) sore throat (5%) and even chest pain (2%). Yet another retrospective analysis of 191 severely ill patients found that 94% patients had fever, almost 80% had cough, while 15% had muscle pain. An observational study of 36 children published 2 days ago reports that almost half of the children (mean age 8 years) were either asymptomatic or had mild symptoms. Common symptoms at admission were fever (36%) and dry cough (19%). I have presented these observational studies to underscore the commonest symptoms of patients with coronavirus are fever and cough. All studies have one thing in common where symptoms are concerned; a combination of fever and cough.

 

This article was published on February 28, 2020, and last updated on March 6, 2020, at NEJM.org.
DOI: 10.1056/NEJMoa2002032

Crucially, no peer reviewed study to date has reported a patient losing the ability to smell or taste. But the world of otolaryngology is today abuzz with the terms “anosmia” and “ageusia,” An otolaryngologist is also known as an ear nose and throat doctor, or an ENT surgeon for short. And just about all of us have visited an ENT doctor at least once in out life time for symptoms ranging from a sore throat to to an ear ache, especially when we were children. Anosmia is the loss of smell, and hyposmia is reduced sense of smell. Smelling things that are not around is phantosmia. Ageusia is the complete absence of taste while dysgeusia is decreased ability to taste. It is important to get the definitions clear because of reports swirling around of a new symptom in coronavirus patients , who complain of loss of smell and even of taste. Anecdotal reports from many patients across the globe infected with coronavirus suffering from anosmia and ageusia have prompted the American Academy of Otolaryngology- Head and Neck Surgery and ENT UK to issue alerts about patients infected with the new coronavirus presenting with only the symptom of altered smell or taste. A detailed joint statement by the presidents of the Rhinological Society and ENT UK has underscored that there rapidly growing number of reports of proven patients infected with coronavirus losing the ability to smell, without any other symptom ascribed to the new virus. A significant number of Covid-19 proven patients have developed anosmia/hyposmia in China, South Korea and also Italy. Germany reports that 2 in 3 confirmed cases have anosmia. South Korea with wide spread testing has almost 30% confirmed positive cases having loss of smell as the major p[resenting symptom. In fact the UK statement documents the occurrence of 4 patients (all under 40 years) with only anosmia as the presenting symptom. But because these 4 patients had no other symptoms they did not merit testing or self isolation. Mention of these 4 patients in this statement becomes problematic because they are not coronavirus confirmed cases. The authors , very senior ENT professionals, are suggesting that anosmia be strongly considered , even if the only symptom, as a marker for Covid-19 infection. A person without fever, without any cough, or muscle pain, but developing sudden loss of smell should be considered a Covid-19 patient. She should be tested and also isolate at least for 7 days. The contacts of such a person should also quarantine themselves for a fortnight. Importantly the association of anosmia with Covid-19 underscores the importance of personal protection (PPE) of ENT surgeons, because they along with intensive care doctors and dentists are very much in the front line.

 

However it is imperative to appreciate that loss of smell is not an uncommon symptom in the community. A review of more than 5000 patients attending a taste and smell clinic for 4 decades , reported loss of smell in 87% and loss of taste in 62% of these patients. Remember these numbers are not of a community but 5000 people complaining of altered sense of smell or taste, evaluated over 40 years. Moreover these people were suffering from chronic smell and taste dysfunction, and were associated with post influenza type hyposmia and hypogeusia (27%), idiopathic or unknown causes (16%), allergic rhinitis (15%) and subsequent to head injury (14%). The researchers highlight the fact that the senses of smell and taste are vital for a fulfilling life albeit not in the same league as loss of sight or loss of hearing.

 

 

 

The UK ENT statement also clarifies right at the beginning that 40% of anosmia cases are due to viral infection. There are over 200 different viruses that can cause upper respiratory infection like the common cold or a running nose. Therefore it should not come as a surprise that the new coronavirus can affect smell or taste. The UK ENT experts however, based upon global anecdotal reports, warn that people developing sudden anosmia in the absence of other well known symptoms could be carriers of Covid-19, and should be isolated. The WHO so far has so far not added loss of smell or taste in their list of symptoms but are mulling over it. The British experts have been endorsed by the American Academy of Otolaryngology, who urge that anosmia or loss of taste, in the absence of allergies, sinusitis or rhinitis should warrant self isolation and testing. The American Academy recognising that loss of taste has been observed in patients ultimately testing positive for the coronavirus with no other symptom, has proposed “that these symptoms be added to the list of screening tools for possible Covid-19 infection.”

 

There are a lot of people with altered smell or taste because of reasons already mentioned, and not because of Covid-19. We already have a list of established symptoms in patients with Covid-19 that primarily include over and cough. Anosmia may become a marker in asymptomatic carriers but this will need confirmation in positive cases with Covid-19. To do that we have to start testing as many patients ,with sudden onset of anosmia or ageusia, for the new coronavirus; patients with only have anosmia or ageusia should be compared with a group of people who have absolutely no symptoms. Someone must have designed such a study Loss of smell or taste in a Covid -19 patient is not permanent; it usually resolves in 2 weeks. The mechanism for loss is still unclear; the virus affects the cells in the nostrils to the the olfactory nerve ( nerve of smell). However the insult is quickly rectified by regeneration of new cells.There is little or no taste without smelling. Eating delicious food is actually a combination of smell and taste.

 

Obviously Mr. Johnson has not noticed so far any alteration in his smell or taste . One should, in his position, retain the the ability to sniff out the best measures to tackle this pandemic, even as scientists across the planet strive to tackle the Covid-19 pandemic.