A year on, COVID-19 is still an unsolved mystery

several severe side-effects of COVID-19 continue to emerge while research scientists struggle to develop an effective, safe vaccine

The first case of novel Coronavirus -- SARS-CoV2 -- was reported on November 17, 2019, in China's Wuhan city, and in March, the WHO declared the respiratory disease a pandemic that has left many across the world with poor mental health, disturbed sexual health and impending poverty. All this has become a matter of concern for health experts. mid-day recaps the impact of the coronavirus disease [COVID-19], a year later.

"One year later, the pandemic has impacted every walk of life globally. And, COVID-19 has posed the biggest challenge to the medical fraternity, as no specific treatment to target the virus has evolved yet," Dr Ketan Vagholkar, professor of surgery at D Y Patil Medical College, said. "Gradually, unknown after-effects of COVID-19 are coming to light, posing yet another, bigger challenge to medical professionals. Research scientists are still struggling to develop a fully effective and safe vaccine."

Impact on mental health

Pointing to the pandemic's impact on the economies and jobs worldwide, Dr Vagholkar said, "Many self-employed businesses have shut down. There have been pay cuts in many firms, and the world is witnessing a staggering increase in unemployment. This has added to the mental stress of the global population, which is already living in fear of contracting the deadly virus. The incidents of depression has increased, especially among the younger working population and social relationships within families have also crumbled."

Also Read: COVID-19: Mumbai's cases count rises but casualties see a fall

He added that the adverse mental health has led to an increase in the incidence of suicide.

Dr Subhash Hira, professor of Global Health at the University of Washington, said, "First year's score of pandemic performance given by scientists: 2-3/10. Long way to go! The COVID-19 pandemic is the most disorganised one because all stakeholders were caught unawares despite having prior inkling of what was coming. Multiplicity of untested, diverse interventions have reduced trust of the general public and healthcare system's credibility to such an extent that not many seems to be sure of what to do next. This burnout, fatigue and reduced earnings exhibit themselves in several ways such as emotional exhaustion, reduced sense of personal accomplishment or meaning in life, mental exhaustion, decreased interactions with others (isolation), depersonalization (symptoms disconnected from real causes) and physical exhaustion."

Dr Hira continued, "Left unchecked, pandemic fatigue can lead to two consequences: poor performance and poor health. People show poor judgement, make errors, and less than desirable interactions with family and friends. Personally, they may suffer physical ailments such as headaches and gastrointestinal problems and exhibit psychosocial traits such as apathy, detachment, depression and irritability. They may also be impacted by a lack of willingness to observe the COVID-19 prevention guidelines, disturbed sleep, loss of self-worth, loss of hope, and changes in their worldview and spirituality."

Dr Ketan Vagholkar, professor, D Y Patil Medical college

A challenge to all

Dr Wiqar Shaikh, senior allergy and asthma specialist said, "The pandemic has thrown an open challenge to the preamble of the countries around the world, including the richest and the most advance nations which have now realised that they were ill prepared for such a disease, both on the medical front and economy front."

He added, "With no medication or vaccine in sight, it appears that we are going to face difficult and uncertain times, especially with wave after wave of the virus returning to various countries, including India."

Also Read: COVID-19: Wary of second wave in Mumbai, BMC steps up testing

Dr Shaikh listed several areas of concern that has evolved during the outbreak:

How information evolved

Initially, the disease was not taken seriously, but as the number of deaths increased, governments worldwide sprang into action and lockdowns were imposed in an attempt to control and curb the spread of the virus.

What is interesting is that COVID-19, which was first thought to be only affecting the lungs, is a year later acknowledged to cause adverse impact on multiple organs such as the heart, brain, liver, kidneys, blood vessels, hearing and muscles, and is also known to have psychiatric manifestations.

Drugs

Another major problem with COVID-19 today is the absence of effective medicines. Initially, drugs such as HCQ, remdesivir, tocilizumab, favipiravir and plasma therapy were extensively being used in the treatment of the disease. However, the WHO in October declared both HCQ and remdesivir as ineffective. Similarly, studies to date have failed to convincingly prove that the other drugs have any effective role in curing patients.

Vaccines

A large number of pharmaceutical companies across the world, including in India, are involved in a race to develop a vaccine, and several candidates are in various phases of clinical trials. Any vaccine needs to be both efficacious in preventing the disease and safe, without any side effects. In the history of medicine, no vaccine has been developed and marketed before five to 10 years of research. So, a question mark hangs on the launch of a safe and effective vaccine for COVID-19.

The public needs to be cautioned not to delay appropriate treatment, which is related to a significant increase in complications and mortality in patients. The same caution and warning have been also echoed by the US Centres for Disease Control and Prevention.

Herd immunity

Finally, in the absence of a cure, the only solution is herd immunity. This is a 100-year-old immunology concept proved in various epidemics and pandemics. Despite scepticism regarding herd immunity, the world does not seem to have alternative answers to COVID-19 as of today.

Flashback of Nov 17, 2019

The SARS CoV2 surfaced on November 17, 2019, when the virus was first reported in a 55-year-old individual from Wuhan in the Hubei province of China. It was not clear then how or from where this virus originated. One theory was that the virus was transmitted from fish to human beings in the sea food market of Wuhan. Another theory stated that it transmitted to humans through bats, and then there was one about a leakage from an experimental laboratory in Wuhan. However, till date, the origin of the virus remain unsolved.

In early December 2019, Dr Li Wenliang, an ophthalmologist at the Wuhan Central Hospital, warned his fellow doctors about the outbreak of an illness causing severe acute respiratory syndrome (SARS) with pneumonia, now known as COVID-19. Dr Li died of COVID-19 on February 7, 2020. Dr Zhang Jixian, a pulmonologist at the Hubei Provincial Hospital, had also reported Dr Li's findings at the end of December 2019. The warnings of both doctors went unheeded by the Chinese authorities, the WHO and indeed the rest of the world. The first confirmed case in India was reported in Kerala on January 30, 2020, in an individual who had returned from Wuhan. By then, China had reported 7,736 cases and the disease had begun to spread to other countries. Although deaths were reported from China earlier, the first death outside China was reported from the Philippines on February 2, 2020. What is shocking is that despite all this information, the WHO declared COVID-19 a pandemic as late as March 11, 2020.

A look at timeline of events since the outbreak

Dr Hira lists the sequence of important happenings since the outbreak in China

November 17, 2019: According to an unpublished report from the Chinese government, the first case of COVID-19 was traced back to 17 November 2019: 55-year old person had developed pneumonia. He used to deliver bats and wild animals to Huanan Seafood Wholesale Market, which was believed to be the epicentre of the outbreak as the cases of the virus started to appear from this same area at that time. Four men and five women were reported to be infected with pneumonia in November, but none of them were labelled as "patient zero" by Wuhan Health Commissioner.

December 2019: No information was officially shared by the Chinese government with the health agencies around the world. China continued to sequence the coronavirus in Wuhan Virus Research Laboratory and released it to the world around January 19, 2020. However, several of its neighbouring countries that had confidential access to information about this epidemic, namely, Taiwan, Cambodia, Thailand, South Korea, Japan, etc, shut down their flights to and from China. Those countries escaped the wrath of pandemic early on.

January 2020: The World Health Organisation in Geneva was ascertaining information of the epidemic for a full month, and declared the "novel coronavirus outbreak a Public Health Emergency of International Concern" January 30, 2020. On the same day, the first case of COVID-19 was reported in India from Kerala's Thrissur district after a student of Wuhan University in China tested positive on coming home on a vacation. A classic example of public health disaster was seen when an ICMR scientist blindly followed WHO advice against use of face masks. It took ICMR three to four months to correct the basic principle of respiratory infectious disease to block droplet transmission. By February 4, Kerala declared coronavirus a state calamity after a third case emerged.

February 2020: On February 11, the WHO coined an official name for the disease -- COVID-19, an acronym that stands for coronavirus disease-2019. Iran emerged as a second focus point and explosive growth in cases started in Italy from initial five cases to more than 150 within a few days. By end of February, 800 people were infected in Italy, and neighbouring countries, like France, Germany, England and Switzerland also started reporting cases.

March 2020: The WHO declared COVID-19 a pandemic on March 11. As the world struggled to contain the spread of SARS-CoV-2, several governments started to shut down their country entirely, some locked down selective cities and districts, or milder restrictions were placed on the movement of people and their congregation with schools, colleges, offices, malls and most other business establishments were shut. In India, Kerala was the first state to ban all public gatherings and suspend classes in all schools and colleges, and exams. Prime Minister Narendra Modi announced a one-day "Janata Curfew" on March 22 and urged millions of people to stay home and practice physical distancing so that the chain of the virus is broken. The curfew turned out to be the pre-cursor for moderately stringent and largest lockdown in the world for over 80 days.

April 2020: By march 29, 2020, India had recorded 1,000 COVID-19 cases and the numbers quickly grew to 10,000 by mid-April, due to rapid increase in testing facilities. Death toll reached 100 by mid-April. Dr Hira, who has been working actively since the pandemic began, shared his experience. "The early clinical picture of COVID-19 during Phase 1 [imported cases from abroad] in January-March 2020 comprised of fever, cough, headache, fatigue and muscle pains, difficulty in breathing with hypoxia, loose motions, etc. A low percent [2-3 per cent] of patients progressed to vascular clots and auto-inflammatory syndrome mediated through interleukins such as IL-6, IL23 etc."

May 2020: The US became the country with top-most number of COVID-19 cases. Cases iin India doubled from 50,000 to 1 lakh within 11 days. "Towards the beginning of the 21st century that saw huge pandemics of HIV/AIDS, tuberculosis. Malaria, dengue, NIPAH, ebola, swine flu, SARS, MERS, zika, among others, the world leaders started to pay attention to the health sector. The 21st century was hailed as the "Century of Pandemics" for several biologic reasons. Then lightening struck the world with COVID-19 that rapidly became a pandemic."

June 2020: Cases doubled in India from 2 lakh to 4 lakh within 18 days and the country ranked fourth among those with highest number of cases, followed by the US, Brazil, and Russia. The entire world started to report cases to WHO. Soon thereafter, the pandemic in India moved to Phase II [local human transmission] during April-June 2020 since local contacts were identifiable as source cases and additional clinical features such as loss of taste and smell as an early feature was document, as also 'ground glass opacities in lungs' on CT scan, cardiomyopathies, kidney shut downs, and vessel and brain clots causing multiple paralyses were documented.

July 2020: India became the third country with most cases and cases rose to 16 lakh. The intensely debated Phase III [community transmission] occurred in high containment zones starting June-July 2020. The clinical features attributed to COVID-19 have added the following symptoms to those described above, namely, dermatologic swellings on tips of fingers/toes, neural deafness, transient blindness with retinal clots, etc, mostly attributed to hyper coagulation of blood in circulation due to auto-inflammatory syndrome attributed to 'cytokine storm' released from COVID-19-infected human cells on-or-after 12 to 15 days of onset of early symptoms described above.

August 2020: India recorded 35 lakh cases and ranked second. Likely sexual transmission of SARS-CoV-2 was suggested by two European studies after novel coronavirus was detected in semen. Treatment of hyper coagulation and cytokine storm gradually emerged "when CRP tends to gallop up, that is the time to start dexamethsone and blood thinners (Clopidogrel, heparin, or aspirin) to prevent the occurrence of blood clots in vessels or brain, cardiomyopathies, acute heart failure, acute kidney shutdown, etc. Alternative drugs like tocilizumab, monoclonal antibody cocktail and remdesivir, emerged for experimental use," said Dr Hira.

September 2020: India's cases doubled to 64 lakh and maintained second highest spot after the US. COVID-19 death rate reached 53/million population, and health workforce death rate was reported at 122/million. WHO convened meetings, discussed unknown areas of natural immunity after COVID-19 infection, it's quality, it's durability, etc, as also the unknown correlation between the natural immunity and the vaccine-induced immunity! However, Dr Hira said that "among so many unknowns about COVID-19 so far, there were some precedence in science whereby once vaccine efficacy is established, the world does not wait for findings about immunity and neutralising antibodies. A classical case was cited of Hepatitis B vaccine that was introduced for human use in 1986 after twenty years of vaccine research wherein immunity markers remained unresolved till then. It took another 20 years after use of Hepatitis B vaccine that it's neutralising antibodies and immunity questions became evident to the scientific world."

October 2020: India started recording fewer cases, which reached 83 lakh. "With the onset of winters round the corner, common cold and influenzas are likely to add on to the disease burden in India, in addition to the ongoing COVID-19 cases. The following are differences seen in patients with different diseases: COVID-19 starts with low-grade fever and gradually adds on more illnesses; common cold begins with sore throat and gradually adds on watery eyes, sneezing and running nose. Influenza starts with cough, and abruptly add high-fever, headache, sore throat and running nose, body pains etc. General practitioners should be able to use this paradigm to try and separate out the cases of COVID-19 from oncoming cases of common flu and influenzas. With passing time, physician-scientists will be able to compile full progression and management of COVID-19 in newer medical textbooks and as monographs", said Dr Hira. " The Solidarity clinical trial of four medicines, namely Remdesivir, HCQ, Lopinavir/ritonavir, and Interferon coordinated by WHO-Geneva and implemented between April-July 2020 at 405 hospitals with varied characterisation in 30 countries and involved 11,262 patients did not endorse benefits of these "repurposed meds" on two counts.

November 17, 2020: India has witnessed a fresh wave of infections taking the count to 89 lakh due to winter and high air pollution that has increased the transmission of SARS-CoV-2 in northern India and major cities. "As the COVID-19 pandemic moves in to the end of first year of its tirade, several analogies have been used by medical scientists to compare it with the past pandemics. Most commonly referred to is the Spanish flu of 1918-1920 that killed over 50 million people, and that included a disproportionate large number of Indians who had died. However, the better analogy of past pandemic that is comparable to COVID-19 is influenza pandemic of 1956-1958, also known as the Asian flu, that was a global pandemic of influenza A," said Dr. Hira. Three vaccines, mainly containing synthetic mRNA have shown unspecified immunity in 90-94% of volunteers in interim analysis of Phase-3 trials. Durability of this immunity remains undisclosed by the sponsors!

Nov 17
Day, in 2019, the first COVID-19 case emerged, in China

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