You can be certain the Prime Minister is quite aware that tackling the Covid-19 pandemic will take more that one day of self imposed quarantine by the public. He still has to be lauded for his efforts because in all probabilities he has sensitised the public of India to be prepared for future lockdowns of longer duration as was practiced in the Hubei province in China, and is currently being practiced in all the big countries of Europe. California is on lockdown for the next 3 weeks, it would be well to remember that the GDP of the state of California is greater than that of the UK or India. As of now California has 1,497 confirmed cases ( as reported by the Los Angeles Times) with 27 deaths. California is home to about 40 million people. Confirmed coronavirus cases have climbed to more than 25,000 in the US. Spain already on lockdown for a week will seek congress approval for another fortnight of lockdown. France too is under lockdown with orders of arrest and fine for non compliance. Italy with the highest number of casualties in the world was the first to impose nationwide lockdown in early March. But Lockdowns do not have universal support. The WHO’s chief emergency expert is on record stating that efforts must be made to find those who are sick, those who have the virus and isolate them, find their contacts and isolate them. He said this in a BBC interview with Andrew Marr today. The reasoning is simple; if strong health measures are not put in place the virus will just jump back after restrictions are eased. “Once we’ve surpassed the transmission, we have to go after the virus. We have to take the fight to the virus.” To tackle the virus it becomes imperative to diagnose its presence, and that can be done only by testing. Hence testing will have to be done in more and more people. To suggest that testing should be restricted to only the symptomatic or only the severely symptomatic is laughable. The fire cannot fought blindfolded. The excuse should not and cannot be that there are not enough testing kits. The Americans ate on the brink of producing kits that can confirm the corona virus in a mere 45 minutes. We too have to straight for the bones or the RNA in this instance of the virus. Maybe we could forsake a couple of Mirage jets and invest in production of testing kits. We could easily become the leaders and a model to the world. Resources are always to be handled pragmatically, but to suggest that one restricts testing as we have only 150,000 kits so far is more bizarre than scientific. Right now our hospitals are not overwhelmed by a deluge of coronavirus patients. We still have the luxury of time. There is however always the possibility that the virus will become uncomfortable as temperatures rise across India. Delhi is nearing 30C while London, Madrid, Milan and Rome are much colder. That the virus could be vulnerable to rise in temperature is pure speculation of course., one can only hope but prepare for the worse. The vaccine should take a year to be used in the public, keeping in mind that the common flu vaccine is only 40 to 60% effective for prevention.
There are so many Whatsapp messages rocketing around about Covid-19 nowadays, each as sensational as the headlines in Washington Post or the New York Times. I do not watch TV so have no information on Indian or ny electronic media. There is this chloroquine message that is piping hot. Apparently there is no chloroquine available with chemists in Delhi. Astonishingly there was not a strip of chloroquine available in my hospital’s pharmacy. There are authentic video clips in which president Donald Trump announces that the FDA had fast tracked its approval of chloroquine for Covid-19. Importantly the FDA denied this a short time later. The denial was necessary because so far there is not a single adequately powered randomised study on chloroquine in patients infected by the coronavirus. There are trials underway but not one has been completed or published in any peer reviewed journal. But a small observational study that is still not published compelled SpaceX founder Elon Musk to tweet that chloroquine was “maybe worth considering” as a treatment for Covid-19. Chloroquine has been used for the treatment of malaria since the 1940’s. The modern drug coms from the Cinchona plant, which was used by indigenous Peruvians for treatment of fever centuries ago. The trial that triggered president Trump’s statement on coronavirus in a press conference is based on only 20 confirmed coronavirus cases by RT-CPRl. The median age is 45 years, and no child below 12 years was included. There were 26 patients to begin with but one patient died, 3 patients required intensive care transfer, and 2 patients refused medication. Six patients were asymptomatic (17%) in this group of treated patients, the majority (61%) had upper respiratory disease (rhinitis or pharyngitis or isolated low grade fever with myalgia )while only 22% patients had pneumonia (confirmed by CT scan) or bronchitis. Sixteen patients in outside hospitals who served as controls were not provided chloroquine. A nasopharyngeal swab was collected every day to examine presence of the coronavirus. The treated patients were administered 200 mg hydroxychloroquine sulphate tablets thrice a day for 10 days. The primary endpoint was viral clearance at 6 days. Viral clearance was seen in 70% of treated patients on hydroxychloroquine but only in 13% of controls. Six patients in the hydroxychloroquine group were also given azithromycin for superadded infection; all 6 patients were virus free at 6 days. The authors of this paper concede that the number of patients are quite small in this study; that it was observational, follow up was short and 6 of 26 patients dropped out from the trial. An observational study of only 20 patients should at best be considered a pilot research; the findings of this study have to be confirmed by larger randomised trials; the FDA most certainly must be looking into this aspect. The WHO has so far not put its might behind this trial. There is no information about the 3 patients who had to shifted to intensive care. The patient who died on day 3 was PCR negative on day 2, the cause or manner of death is not explained in the French document.
Other researchers have begun trials with chloroquine. The University if Minnesota is one of them, it is studying the impact of chloroquine on people exposed to coronavirus. The results should be available in weeks. Till then chloroquine should not be bought over the counter, it should be administered in hospital settings by critical carte doctors. Quit the contrary has happened in Delhi, and probably the rest of the country. People have rushed to chemist shops to buy all the chloroquine available, without ascertain whether the drug works or not. It would be terrific if a randomised trial reported efficacy with chloroquine, its a generic drug costing a few Rupees. It can be manufactured by the millions by Indian drug companies. The University of Minnesota has also launched 2 trials with an angiotensin receptor blocker (Losartan) in patients with Covid-19.
DOI: 10.1056/NEJMoa2001282
Astonishingly little or no news has been reported by the mainstream media of a drug combination that actually significantly cut mortality in confirmed coronavirus patients. This was a randomised trials including 199 patients infected by Covid-19 in China. The fact that it reduced mortality from 25% to 17% has gone completely under the radar. The drugs are freely available in India. The NEJM published this trial on 18th March 2020. The researchers studied 199 patients with confirmed Covid-19 patients. The patients had to have severe infection; the oxygen sat on room air had to ne below 94% or they had to have a ratio of partial pressure of oxygen to fraction of inspired of oxygen less than 300 mm Hg. Patients were randomised to receive lopinavir-ritonavir (400 mg and 100 mg respectively) twice a day for 14 days, in addition to standard care or standard care alone. The primary endpoint was time to clinical improvement. The lopinavir-ritonavir cohort had 99 patients while the standard group had 100 patients. The researchers found that time to improvement did not differ between the 2 groups. Gastrointestinal side effects were common in the treated group but serious adverse effects were more common in the standard group. The authors concluded that hospitalised patients with severe Covid-19 did not benefit with the lopinavir-ritonavir combination. Future trials in severely infected patients may clarify efficacy with this combination. Lopinavir -ritonavir are p[rotease inhibitors used in HIV patients because they prevent virus multiplication. Now it is time to examine this randomised trial done in China carefully. This apart form being randomised is much larger; it includes 199 patients while the French trial had only 20 patients. The time to clinical improvement remained approximately 16 days in both groups, so no difference. The median age of patients was 58 years. The remarkable finding of this trial is the 28 days mortality, albeit a secondary outcome. There 28 day death rate was lower in the lopinavir-ritonavir group than in the standard care group for both intention to treat population (19% versus 25% ) and in the modified intention to treat population (16.7% versus 25%). A difference of absolute 8.3 % points lower mortality with lopanivir -ritonavir. Also patients in the untreated group and shorter ICU stay in the intensive group the standard care group ( 6 days versus 11 days). Also clinical improvement was at day 14 was higher in the lopanavir-ritonavir group (45% versus 30%). Respiratory failure, acute kidney injury, and secondary infection were more common in standard care patients. It must be borne in mind that the small French trial had almost 80% patients with mild or no symptoms, whereas the Chinese trial are far more serious with death rate of 25% in the standard care group. The trial was open label , meaning the researchers knew which patients were being treated with lopinavir-ritonavir, and hence susceptible to bias. Moreover 34% of patients also received corticosteroids and interferon (11%). An editorial tellingly asks why the drugs did not work, and provide 2 explanations. The population studied by the Chinese researchers were severely ill and hence challenging, as confirmed by the high death rate in the control group. Even advanced bacterial pneumonia is difficult to treat with the best antibiotics. Also the serum levels of lopinavir-ritonavir may have been lower than desired for optimal efficacy. However there was little difference in viral shedding with lopinavir-ritonavir despite reduction in mortality. But was the viral load detected adequate for further transmission is still unclear.
The mainstream keeps reiterating that more and more people are dying of Covid-19, sensational headlines appear every morning reporting of fresh deaths in different countries. As I write , the Economic Times reports that so far 7 people have died due to Covid-19, while there are 360 cases. The prevalence of coronavirus right now is 0.000269%, if the population of India is 1.34 billion.The mortality rate is 0.00000522%. Do the math yourself. 300,000 paeople have been infected in the world; 0.04% considering 7.7 billion people inhabit the planet.I personally am very sceptical of the mathematical models regarding the spread of the coronavirus disease; for instance 75% of Americans will be affected was the headline by yesterdays New York Times. India is still not under complete lockdown, despite many travel restrictions. A balance will have to be made between the transmit ability of coronavirus and the economic debility inflicted by long lockdowns. Also once a lockdown is imposed , the decision to relax or remove it altogether will depend entirely on a tight surveillance program involving identification, isolation, contact tracing isolation by testing and more testing. We must have some numbers to define the stage of the epidemic and we also need numbers for calling a lock down off. Too many lives are at stake to operate on whims and fancies. Spare a thought for the daily wager apart form the small businesses desperately trying to recover from the demonetisation strike. Also keep in mind the doctor in India unlike his western counterparts will soon have to distinguish Covid-19 from dengue from malaria from typhoid from chikungunya from common flu and from various common respiratory viruses. Not a small task by any means.