210 Countries affected, over 2.83 M Cases; Deaths to Cross 250,000 with Current Trend of > 6000 deaths per day if new cases continue for another 10 days with Minimum 206024, First reported Case: 10th January

Situation around the Globe

Likely minimum deaths (197245 + 58523 x 15 = 8779) = 206024    

Total cases: 2,830,051 (new Cases +105,616)

Deaths: 197,245 (New Deaths 6174)

Recovered: 798,772

ACTIVE CASES: 1,834,034

Currently Infected Patients

1,775,511 (97%) in Mild Condition

58,523 (3%) Serious or Critical

CLOSED CASES: 996,017

798,772 (80%): Recovered/Discharged

197,245 (20%): Deaths

363 cases per million population (India 18)

25.3 deaths per million population (India 0.6)

India

India Cases on 25^th 24,447; Cases on 15th 12370 cases

Doubling time: 10 days

Expected Number: To cross 50,000 in 15 days

India Death Rate: 3.19%

Death Rates: Other places

Europe: 9.57 % [cases 1,225,314, deaths 117324]

North America: 5.646 % [cases 997,428; 56339 deaths]

Asia: 3.70 % [448,241 cases and 16603 deaths]

South America: 4.60% [120,273 cases with 5539 deaths]

Africa: 4.644 % [29,825 cases with 1328 deaths]

Oceania 1.17% [8,249 cases and 97 deaths]

World 6.96 % [2,830,051 cases with 197245 deaths] 

Revised COVID-19 Sutras

It’s a COVID-19 pandemic due to SARS 2 Beta Coronaviruses (different from SARS 1 where spread was only in serious cases); with three virus sequences floating (one similar to Wuhan, second similar to Iran and the third strain similar to USA – UK); has affected up to 10% (5.7%  South Korea) of the population; Causes mild or asymptomatic illness in 82%, moderate to severe illness in 15%, critical illness in 3% and death in 2.3% cases (15% of admitted serious cases, 71% with comorbidity; Male > Females); affects all ages but predominantly males (56%, 87% aged 30-79, 10% Aged < 20, 3% aged > 80); with variable incubation period days (2-14; mean 5.2 days);  mean time to symptoms 5 days;  mean time to pneumonia 9 days; mean time to death 14 days; mean time to CT changes 4 Days; Reproductive number (R0) 1.5 to 3  (Flu 1.2 and SARS 2); Epidemic doubling time 7.5 days; Origin possibly from bats (Mammal); Spreads via human to human transmission via large and small droplets and surface to human transmission via viruses on surfaces for up to three days. Enters through MM of eyes, nose or mouth and the spike protein gets attached to the ACE2 receptors.  ACE2 receptors make a great target because they are found in organs throughout our bodies (heart muscle, CNS, kidneys, blood vessels, liver). Once the virus enters, it turns the cell into a factory, making millions and millions of copies of itself — which can then be breathed or coughed out to infect others.

New York: 13.9% prevalence rate state-wide; New York City has even higher rate at 21.2%. (Results may be high since only those people were tested who were out, not those who are isolating at home. The early figures would decrease the fatality to infection rate to 0.5%) (World population 2%, estimate 5%). In an Ohio prison that conducted widespread testing, 73% of inmates (over 1,800 people) were confirmed to have the virus, many without symptoms. A new analysis of widespread testing in the town of Vo, Italy, confirmed that 43% of those who tested positive showed no symptoms.

Among 5700 patients hospitalized with confirmed COVID-19 in New York, there was a 21% mortality rate among those who had been discharged or died, according to a study published April 22 in JAMA.

Autopsy and biopsy reports have revealed that viral particles can be present not only in the nasal passages and throat, but also in tears, stool, kidneys, liver, pancreas, and heart. One case report also found evidence of viral particles in the fluid around the brain in a patient with meningitis.

Severe damage to the lungs activates and overstimulates the immune system via an onslaught of signaling chemicals, known as cytokines. The flood of these chemicals can incite a "cytokine storm." This complex interplay of chemicals can cause blood pressure to fall, attract more killer immune and inflammatory cells, and result in even more injury within the lungs, heart, kidneys, and brain. Cytokine storms may result in sudden decompensation, leading to critical illness in COVID-19 patients.

Abnormal clotting, or thrombosis, may also play a vital role in lethal COVID-19. There are clots everywhere – large-vessel clots, including deep vein thrombosis (DVT) in the legs and pulmonary emboli (PE) in the lungs; clots in arteries, causing strokes; as well as small clots in tiny blood vessels in organs throughout the body. Early autopsy results have shown scattered clots in several organs. University of Pennsylvania specialists say that these clots are happening at high rates despite the fact that patients are on blood thinners for clot prevention. In a study from the Netherlands, 31% of patients hospitalized with COVID-19 got clots while on blood thinners.

Like pandemic influenza, the SARS-CoV-2 virus is likely to enter long-term circulation alongside the other human beta-coronaviruses (which has immunity lasting only for one year). Recurrent wintertime outbreaks will probably occur. In absence of other innovations and interventions, the key successes will be prolonged or intermittent social distancing (till 2022-24) along with building up critical care capacities and surveillance till 2024 or more. About 70% persons need to be immune for no outbreak to occur.

Longitudinal serological studies are needed to determine the extent and duration of immunity to the virus.  Consistent long-term immunity, if detected, will lead to effective elimination of the virus and lower overall incidence of infection BUT low levels of cross immunity from the other beta-coronaviruses against SARS-CoV-2 could make SARS-CoV-2 seem to die out, only to resurge after a few years. Therefore, even in the event of apparent elimination, SARS-CoV-2 surveillance should be maintained since a resurgence in contagion could be possible as late as 2024.

During the peak, most important is to trace and treat the patients and after the peak, most important is to trace and treat the close contacts (close physical contacts starting 2 days before the symptoms and contact time of more than 10 minutes).

Increased spread: close environment, crowded place with close physical contacts with no ventilation (singing choirs; sporting non ventilating complexes)    

Four phases are: No case; sporadic cases; cluster of cases and community cases. Aim is the shift to the left in any situation. Each one has a different containment strategy.

Containment: from community mitigation to individual containment; broader good over individual autonomy; perfect cannot be the enemy of the good; pandemics are fought on the grounds and not the hospitals.

If the new coronavirus ends up being an acute infection, like other coronaviruses, most people who recover should develop at least a short-term immunity. Its also possible that the virus may persist as a latent infection, like chickenpox, lying dormant in the body, only to re-emerge periodically as shingles does, or become a chronic infection, like hepatitis B, living within the body for a sustained period of time, causing long-term damage.

We must learn to live with coronavirus now.

COVID-19 clinically may present with

1. Classical symptoms (fever in all, cough 75% and breathlessness 50%)2. Atypical and unusual symptoms [Encephalitis; Guillain Barry Syndrome (6 cases); Diarrhea; Loss of smell and loss of taste (mild to moderate cases, may last for over a month); AKI (5%, tremendously catabolic with hyperkalemia, hyperphosphatemia, and profound metabolic acidosis to a degree not seen in typical kidney failure patients); Hepatopathy; Deranged liver enzymes); Conjunctivitis; Diabetes and hyperglycemia without prior diabetes; Thrombocytopenia (20.7%); Low total white count; Low lymphocyte count (< 800 serious, < 1000 common); High ESR, High CRP and high ferritin; Cardiac involvement in 10% (myocarditis, heart attack with high Pro BNP, LDH, Troponin test); Microvascular thrombosis (high D-Dimer); Severe hypoxemia with normal respiratory compliance (need oxygen not pressure). Rash can be general rash consistent with viral exanthema, or consistent with superficial clotting in blood vessels close to the skin called “COVID toes," or pernio (small clots in toes and fingers, especially in children.)

Elderly: They may sleep more than usual or stop eating; They may even seem unusually apathetic or confused, and lose orientation to their surroundings; They may become dizzy and fall. Sometimes, the elderly stop speaking or simply collapse.

3. Insignificant Symptoms: Confused with ALI and Allergy
4. Pre symptomatic(20% of asymptomatic developing symptoms in 2-3 days)
5. Asymptomatic (6-70%)

Treat the patient and not the test report

1. Tests are based on molecular test (NAAT) and RT PCR for detecting the RNA
2. Antigen test to detect the viral fragments (currently active)
3. Antibodies: IgM, IgG and IgA (positive only after 7 days) via ELISA or RDT.
4. Antibodies are only for sero-surveillance and only for research purposes. They have no role for active diagnosis.
5. For active diagnosis, the test is molecular tests (positive on day 1).
6. IgM, if positive, needs confirmation with RT PCR (RDT IgM can be false positive in pregnancy, immunological diseases)
7. Pooled tests (< five persons) if the seroprevalence is <5% (preferable < 2%). Reliability depends on no contamination, no mixing of samples, number of samples pooled. It is linked to success story of pooling in blood banks.
8. 2 PCR required (if low viral load situations)
9. PCR can remain positive for 8 weeks (active RNA or inactive detectable virus RNA as reported by South Korea)
10. Samples which can be tested are: Respiratory material (upper and lower), stool, blood
11. Point of care molecular test, if reliable, is the need.

No test is 100% sensitive or specific. In view of only 67% positivity of RT PCR test on nasal sample and unreliable rapid blood antibodies tests IgG and IgM and both with false negative and false positive known results, we cannot rely on the test report for the treatment.  

Like acute flaccid paralysis is treated as polio unless tested negative, all cases of SARI (serious acute respiratory illness) and ALI should be notified and treated as COVID-like illness even if detected negative or end up with complications.

Clinical diagnosis should be backed by early treatment to reduce the viral load and prevent cytokine storm using off label use of drugs like hydroxychloroquine with azithromycin; ivermectin, remdesivir; tocilizumab - interleukin (IL)-6 receptor inhibitor; convalescent plasma therapy (given early; bridge compassionate therapy, donor 14 days symptoms free, single donation can help 4 patients); Lopinavir-ritonavir and Favipiravir.

Hypoxic patients should be treated with low flow oxygen (< 6l/mt) up titrated to high flow oxygen using non breathing mask, Venti mask, HFNC and helmet CPAP, NAV in supine or prone position. Early intubation with prone ventilation, if progressive.

Future will be decided by vaccines like BCG (ICMR); Anti-Leprosy Vaccine called Mw Mycobacterium w or mycobacterium indicus pranii (CSIR and Cadila), Novavax (antigens derived from the Coronavirus spike (S) protein vaccine JV with Cadila), m RNA vaccines.

 Unanswered questions: How long plasma antibodies will last in the recipient? 

Updates

• Tablighi Jamaat has contributed a large number in India, Malaysia and Shincheonji Church in South Koreacases.
• Singapore’s coronavirus surge is in the crowded dormitories where migrant laborers live.
• In Delhi all the 186 novel coronavirus cases found positive in the capital on 18th April were asymptomatic.
• In New York City, in a universal testing of pregnancy trial, investigators found that 13.7% had COVID-19 infection (87.9% were asymptomatic and 12.1% were pre symptomatic)
• In India, it is also affecting younger people (< 50 years) with mild symptoms
• All healthcare workers and on HCQS prophylaxis should fill the form https://www.surveymonkey.com/r/6KPW8CR
• Do not ignore polio, measles, rotavirus, routine immunization and TB notification. Isolate all MDR and TB positive cases till sputum negative
•  Consider every surface and every asymptomatic person as virus carrier
•  Post @ https://mobile.twitter.com/ChestImaging?s=08: Post COVID positive X rays, CT images.
•   Collateral benefits: Reduction in air pollution, clear Ganges, reduction in overall deaths (low pollution, less stress, more hygiene, no traffic accident deaths).
•   ZIKA Brazil Model: Army used for the crisis. Keep Army at standby.
•   Convalescent plasma therapy: Start early to reduce viral load. One COVID-19 recovered patient (2 weeks after antigen negative) can give it to four patients at a time (500Ml) and ten patients over time.
•  Significant exposure to COVID-19: Face-to-face contact within 6 feet with a patient with symptomatic COVID-19 that is sustained for at least a few minutes (and some say more than 10 minutes or even 30 minutes). The chance of catching COVID-19 from a passing interaction in a public space is minimal.
• Mask Policy:All health workers in healthcare setting should wear tight sealed N 95/three ply (outer layer hydrophobic, middle filter and inner layer hydrophilic) surgical mask or double mask of surgical over N 95 and general public should wear two layer cotton cloth mask with or without additional middle carbon layer mask when on the roads.
• The cost of API used in hydroxychloroquine touched Rs 70,000 per kg, from Rs 6,500 per kg in February and of azithromycin has doubled to Rs 16,000 a kg. China is a major supplier of APIs.
•   A six-day delay by China: On January 14, top Chinese officials sensed a pandemic. The head of Chinas National Health Commission, Ma Xiaowei, in a confidential teleconference with provincial health officials, said: "The epidemic situation is still severe and complex, the most severe challenge since SARS in 2003, and is likely to develop into a major public health event." Yet in the six days that followed, Wuhan hosted a banquet attended by thousands and millions of Chinese migrated within the country for the Lunar New Year celebrations. On January 20, President Xi Jinping warned the public, saying the outbreak "must be taken seriously". The same day, a leading Chinese epidemiologist, Zhong Nanshan, announced for the first time that the virus was transmissible from person to person on national television. But by then, more than 3,000 people had been infected.
•   12 days of silence added to the fuel: From Jan. 5 to Jan. 17, Chinas CDC did not register any case of pneumonia-like disease from local officials. Yet during that time, hundreds of patients were appearing in hospitals not just in Wuhan but across the country. On January 2, local officials of the Chinese Communist Party punished eight doctors for "rumor mongering" for warning friends on social media about the emerging SARS-like threat. One of the doctors, Dr. Li Wenliang, later died on Feb. 7.
•   Two Chinese companies sold UK 2 M home test kits for $20 million on upfront payment on take it or leave it terms. The simple pregnancy test like option was a potential game changer but the tests did not work.
•   More doubt on coronaviruss Wuhan origin: In a paper published earlier this month, geneticists said it may have started spreading as early as mid-September, and from elsewhere in China. (PNAS, Newsweek)
• US Secretary of State Mike Pompeo pressed China to allow inspectors into sensitive laboratories. Pompeo has refused to rule out that the deadly virus leaked out of a laboratory in the Chinese metropolis of Wuhan, a scenario denied by Beijing.
• As per a Lancet study, more than 232,000 people may have been infected in the first wave of COVID-19 in mainland China, four times the official figures, according to a study by Hong Kong researchers.
•   The coronavirus crisis has killed more than 7,000 people at nursing homes across USA
•   To expedite the process, the US FDA made a criticized move and allowed a free-for-all for developers to begin marketing antibody teststhat had not gone through the agencys evaluation and validation process.  It result in a flood of over 90 unapproved tests that are of a dubious quality. The FDA quickly did damage control, conducting evaluations of the tests to distinguish the potentially useful from the useless. So far, they have issued emergency use authorizations (EUAs) to only four tests, those marketed by Cellex, Ortho Clinical Diagnostics, Chembio Diagnostic Systems, and the Mount Sinai Laboratory.

 Quarantine models

India: Early lockdown for forty days

Wuhan: Selective sealing of epicenter, isolate, contact monitor, elderly lockdown, bye time for infra structure

Vietnam: Sealing of a village with most cases

Bhilwara CLUSTER: Seal 2 km all around, fumigate each house, house to house survey for ALI and SARI, isolate infected cases, test all close contacts

Bird flu model: April 20, 2016, the Lebanese Ministry of Agriculture found H5N1 in 2 poultry farms on the border of Lebanon with Syria. Some 20,000 domestic birds died. The ministry culled all (60K) domestic birds within a 3-km radius. All farms were disinfected, and organic remains were disposed safely.

Germany, Sweden and Japan model: Selective isolation of elderly and high-risk comorbid patients

South Korea: Intensify testing amongst all or high-risk group

Italy: Deploy younger healthcare workers and women as front-line fighters (2 hospitals posted young doctors  40 years, 60% women on duties with no mortality in healthcare workers)

Singapore: Make available surgical masks at reception to be worn by all patients entering the hospital. Give N 95 masks to all healthcare providers and use AII rooms for all procedures on infected cases

Germany:  Random testing for antibodies is key in Germanys strategy. (New York Times)

AII rooms: Aerosol-generating procedures should take place in an airborne infection isolation room (AII) only. These are single-patient rooms at negative pressure relative to the surrounding areas, and with a minimum of six air changes per hour (12 air changes per hour recommended for new construction or renovation). When an AII room is not available, a portable high-efficiency particulate air (HEPA) unit can be placed in the room, although it does not compensate for the absence of negative air flow. If avoiding aerosol-generating procedures or use of a nebulizer is not possible, appropriate PPE for healthcare workers includes use of N95, eye protection, gloves, and a gown.

Aerosol-generating procedures/treatments - Bronchoscopy (including mini bronchoalveolar lavage); CPR; Colonoscopy; Filter changes on the ventilator; High-flow oxygen; Manual ventilation before intubation; Nasal endoscopy; Noninvasive ventilation; Open suctioning of airways; Tracheal intubation and extubation; Tracheotomy; Upper endoscopy (including transoesophageal echocardiogram); Swallowing evaluation, Nebulization

Total and new cases across the world

 COVID-19 Statewise status in India

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA