What we need to know about the Corona Virus

May 4, 2020

Introduction

Knowledge of the Corona virus in this situation is very important, because we know very little about how the virus affects the body, but we do know enough about how it spreads in the community and how rapidly it leads to critical illness and even death.

Staying away from this virus is the ideal and important thing to do for now, until we have figured out more details about the way it spreads, its pathophysiology and are prepared with safe treatment protocols and vaccines.

For this we need to study in depth the pathophysiology of the virus, disease progression and our body’s immune response. More emphasis is needed on its community spread and to reason why and what has led to this dreadful pandemic in spite of current advances in science and healthcare.

Where did it come from?

Coronavirus is a group of viruses that cause mild to moderate upper respiratory symptoms, including the common cold, while more severe types can cause pneumonia and death. The name for this kind of virus comes from the crown like spikes it has on its surface — “corona” is Latin for “crown.”

Coronaviruses originate in animals like camels, civets and bats and are usually not transmissible to humans. But occasionally a coronavirus mutates and can pass from animals to humans and then from human to human, as was the case with the SARS epidemic in the early 2000s. (SARS stands for “severe acute respiratory syndrome.”)

This Covid-19 outbreak began in Wuhan, China, in December 2019. Scientist Leo Poon, who first decoded the virus, thinks it likely started in an animal ( bats or pangolins ) and spread to humans. Since then, the virus has mostly spread through person-to-person contact.

However, it remains unclear exactly how the virus first spread to humans.

In December 2019, a cluster of pneumonia cases of unknown origins occurred in Wuhan, Hubei Province, China. On 30 December 2019, 3 patients with pneumonia of unknown etiology were tested with Real-time PCR (RT-PCR) assay, and were positive for pan-Betacoronavirus.

The disease has rapidly spread from Wuhan to other areas in China, as well as other countries across the globe. Thereafter, the World Health Organization (WHO) has recently declared the COVID-2019 a public health emergency of international concern.

Route of transmission

Routes of transmission COVID-19 is transmitted via droplets and fomites during close unprotected contact between a person already infected with the virus and someone who is not.

The virus has been found to be more stable on plastic and stainless steel (up to 72 hours) compared with copper (up to 4 hours) and cardboard (up to 24 hours).This study also found that the virus was viable in aerosol particles for up to 3 hours; however, aerosols were generated using high powered apparatus that do not reflect normal human cough conditions or a clinical setting where aerosol-generating procedures are performed. The World Health Organization has confirmed that there have been no reports of airborne transmission so far.

The contribution to transmission by the presence of the virus in other body fluids is unknown; however, the virus has been detected in blood, cerebrospinal fluid, saliva, tears, and conjunctival secretions. Facial-oral transmission may be possible (virus has been detected in the stool samples of almost half of the patients in one meta-analysis), although it has not been reported yet.

Nosocomial transmission in healthcare workers and patients has been reported in 41% of patients in one case series.

Widespread transmission has been reported in long-term care facilities and on cruise ships (19% of 3700 passengers and crew were infected aboard the Diamond Princess)

Signs, Symptoms & Disease progress 

Symptoms of COVID-19 are non-specific and the disease presentation can range from no symptoms (asymptomatic) to severe pneumonia and death.

However, typical signs and symptoms include: fever (87.9%), dry cough (67.7%), fatigue (38.1%), sputum production (33.4%), shortness of breath (18.6%), sore throat (13.9%), headache (13.6%), myalgia or arthralgia (14.8%), chills (11.4%), nausea or vomiting (5.0%), nasal congestion (4.8%), diarrhea (3.7%), and hemoptysis (0.9%) and conjunctival congestion (0.8%).1

The mean incubation period 5-6 days, range 1-14 days.

Most people infected with COVID-19 virus have mild disease and recover. Approximately 80% of laboratory confirmed patients have had mild to moderate disease, which includes

non-pneumonia and pneumonia cases, 13.8% have severe disease requiring hospitalization and 6.1% are critically ill needing ICU care. Asymptomatic infection has been reported, but the majority of the relatively rare cases who are asymptomatic on the date of identification/report went on to develop disease.

Individuals at highest risk for severe disease and death include people aged over 60 years and those with underlying conditions such as hypertension, diabetes, cardiovascular disease, chronic respiratory disease and cancer. Disease in children appears to be relatively rare and mild with approximately 2.4% of the total reported cases reported amongst individuals aged under 19 years. Studies which compared symptoms and investigations of adults and children with COVID -19 suggest a much milder immunological response in children and less immune damage. 

Pathophysiology

Although the exact detailed pathophysiology is currently unknown, it has been confirmed that the virus targets the angiotensin-converting enzyme-2 (ACE2) receptor in humans, which suggests a similar pathogenesis to SARS.

A unique structural feature of the spike glycoprotein receptor binding domain of SARS-CoV-2 (which is responsible for the entry of the virus into host cells) confers potentially higher binding affinity for ACE2 on host cells compared with SARS-CoV. A fur in-like cleavage site has been identified in the spike protein of the virus; this does not exist in other SARS-like coronaviruses.

Based on an analysis of single-cell RNA sequencing datasets derived from major human physiological systems, the organs considered more vulnerable to SARS-CoV-2 infection due to their ACE2 expression levels include the lungs, heart, oesophagus, kidneys, bladder, and ileum. Mechanistic evidence from other coronaviruses suggests that SARS-CoV-2 may down regulate ACE2, leading to a toxic over accumulation of angiotensin-II, which may induce acute respiratory distress syndrome and fulminant myocarditis.

High viral loads have been detected in nasal and throat swabs soon after symptom onset, and it is thought that the viral shedding pattern may be similar to that of patients with influenza. An asymptomatic patient was found to have a similar viral load compared with symptomatic patients.

Pharyngeal viral shedding is high during the first week of symptoms when symptoms are mild or prodromal, peaking on day 4. This suggests active virus replication in upper respiratory tract tissues.  

Management – Diagnosis & Treatment

Diagnosis

Basic investigations done are arterial blood gas analysis (as indicated to detect hypercarbia or acidosis), complete blood count, comprehensive metabolic panel, coagulation screen, inflammatory markers (serum procalcitonin and C – reactive protein), serum troponin, serum lactate dehydrogenase, serum creatine kinase.

The most common laboratory abnormalities in patients hospitalized with pneumonia include leukopenia, lymphopenia, leukocytosis, elevated liver transaminases, elevated lactate dehydrogenase, and elevated C-reactive protein. Other abnormalities include neutrophilia, thrombocytopenia, decreased haemoglobin, decreased albumin, and renal impairment.

RT-PCR- A nucleic acid amplification test, such as real-time reverse-transcription polymerase chain reaction (RT-PCR), for SARS-CoV-2 in appropriate patients with suspected infection, with confirmation by nucleic acid sequencing is recommended when necessary. One or more negative results do not rule out the possibility of infection. If a negative result is obtained from a patient with a high index of suspicion for COVID-19, additional specimens should be collected and tested, especially if only upper respiratory tract specimens were collected initially.

 Guidelines recommend that two consecutive negative tests (at least one day apart) are required to exclude COVID-19; however, there is a case report of a patient who returned two consecutive negative results and didn’t test positive until 11 days after symptom onset and confirmation of typical chest computed tomography (CT) findings.

Imaging

Chest X ray – All imaging procedures should be performed according to local infection prevention and control procedures to prevent transmission. Chest x-ray in all patients with suspected pneumonia is recommended. Unilateral lung infiltrates are found in 25% of patients, and bilateral lung infiltrates are found in 75% of patients.

CT Chest – The American College of Radiology recommends reserving CT for hospitalized, symptomatic patients with specific clinical indications for CT, and emphasizes that a normal chest CT does not mean that a patient does not have COVID-19 and that an abnormal chest CT is not specific for COVID-19 diagnosis. Abnormal chest CT findings have been reported in up to 97% of COVID-19 patients in one meta-analysis of 50,466 hospitalized patients. Also to be noted is that the evidence of pneumonia on CT may precede a positive RT-PCR result for SARS-CoV-2 in some patients.

Treatment

No specific treatments are known at present to be fully effective for COVID-19 yet; therefore, the mainstay of management is early recognition and optimized supportive care to relieve symptoms and to support organ function in more severe illness. Patients should be managed in a hospital setting where possible; however, home care may be suitable for selected patients with mild illness unless there is concern about rapid deterioration or an inability to promptly return to hospital if necessary. Children are less likely to require hospitalization.

Drugs used currently

No treatments have been approved yet or shown to be safe and effective for the treatment of COVID-19. However, there are several treatments being used off-label. It is important to note that there may be serious adverse effects associated with these drugs, and that these adverse effects may overlap with the clinical manifestations of COVID-19. The World Health Organization and its partners have launched the Solidarity trial, a large international study to compare different treatments and ensure clear evidence of which treatments are most effective. The study will have five arms: standard of care; remdesivir; lopinavir/ritonavir; lopinavir/ritonavir plus interferon beta; and chloroquine.

How do these drugs work?

Chloroquine and hydroxychloroquine

Chloroquine and hydroxychloroquine are oral drugs that have been used for the prophylaxis and treatment of malaria, and the treatment of certain autoimmune conditions such as rheumatoid arthritis and systemic lupus erythematous. Both drugs have in vitro activity against SARS-CoV-2, with hydroxychloroquine having relatively higher potency.

Chloroquine acts by disrupting the virus’s ability to enter a cell. It can raise the pH of endosomes, vesicles inside cells that are hijacked as points of entry by viruses. Endosomes have a slightly acidic pH, which helps facilitate this process. Chloroquine can raise endosomic pH slightly, which prevents fusion and stops the virus from entering the cell. Chloroquine may also block enzymes involved in the fusion between the virus and lung cells or stymie the viral replication process.

The drug is potentially dangerous when used at high doses or for prolonged periods particularly in people having cardiac conduction anomalies. Hence, benefits and risks have to be considered and explained before use.

Remdesivir

A novel, investigational, intravenous nucleoside analogue with broad antiviral activity that shows in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical trials with remdesivir have started and currently being used for patients with severe illness, and pregnant women and children with confirmed infection. It appears to be safe to use in pregnancy. The EMA has published recommendations on compassionate use of remdesivir for COVID-19.

According to a new study done at the University of Alberta, US, the drug Remdesivir was found to be very potent inhibitor for coronavirus polymerases. According to Matthias Götte, chair of medical microbiology and immunology at Alberta, the RNA-dependent RNA polymerase (RdRp) is like the engine of the virus, responsible for synthesizing the virus’ genome.

“If you target the polymerase, the virus cannot spread, so it’s a very logical target for treatment,” Götte said.

The lab’s work shows how remdesivir tricks the virus by mimicking its building blocks. When the coronavirus RdRp is duped, the inhibitor is incorporated many times and the virus can no longer replicate.

Lopinavir/ritonavir

An oral antiretroviral protease inhibitor currently approved for the treatment of HIV Infection. Although there is currently no strong evidence of efficacy of Lopinavir/ritonavir in the treatment of COVID-19, it has been used in clinical trials for the treatment of COVID-19.

The SARS-CoV-2 virus is a single-stranded RNA beta-coronavirus, similar to SARS-CoV and MERS-CoV. These viruses enter host cells and replicate, producing strands that contain multiple copies of the viral genetic material (RNA – ribonucleic acid). The strands of genetic material accumulate at the periphery of the cell, ready to be cleaved, packaged and prepared for release from the host cell4. The enzyme 3-chymotrypsin-like protease (3CLpro) plays a crucial role in processing the viral RNA5 6. As LPVr is a protease inhibitor, it may inhibit the action of 3CLpro, thereby disrupting the process of viral replication and release from host cells. However, coronavirus proteases, including 3CLpro, do not contain a C2-symmetric pocket, which is the target of HIV protease inhibitors, leading some to question the potential potency of HIV protease inhibitors in treating these viruses. Further trials are needed to confirm the efficacy of this drug in the treatment of Covid 19.

Convalescent plasma

Convalescent plasma from patients who have recovered from viral infections has been used as a treatment in previous virus outbreaks including SARS, avian influenza, and Ebola virus infection. The approach involves giving patients an infusion of antibody-rich plasma from people who have recovered from an infection with SARS-CoV-2. Clinical trials to determine the safety and efficacy of convalescent plasma that contains antibodies to SARS-CoV-2 in patients with COVID-19 have started.

A few studies have shown a positive result with the use of convalescent plasma with significant improvement in critically ill patients and in reducing the viral load. No serious adverse reactions were noted. In the US, the FDA is facilitating access to COVID-19 convalescent plasma for use in patients with serious or immediately life-threatening COVID-19 infections through the process of single patient emergency investigational new drug applications.

Treatments for cytokine release syndrome

Interleukin-6 receptor antagonist monoclonal antibodies (e.g., tocilizumab, sarilumab, siltuximab) are being trialed in COVID-19 patients for the treatment of virus-induced cytokine release syndrome. However, the decision to suppress the immune system of a critically unwell patient with COVID-19 is a difficult one; the beneficial anti-inflammatory effects of anti-inflammatory drugs must be weighed against the possibly detrimental effects of impairment of immunity. Other drugs currently in clinical trials for the treatment of COVID-19-associated cytokine release syndrome include the Janus kinase inhibitor fedratinib and the C-C chemokine receptor type 5 (CCR5) antagonist leronlimab.

Angiotensin-II receptor antagonists

Angiotensin-II receptor antagonists such as losartan are being investigated as a potential treatment because it is thought that the angiotensin-converting enzyme-2 (ACE2) receptor is the main binding site for the virus. However, some experts believe that these drugs may worsen COVID-19 due to overexpression of ACE2 in people taking these drugs.

Prevention – General prevention measures

  • The only way to prevent infection is to avoid exposure to the virus and people should follow these simple yet important practices.
  • Wash hands often with soap and water for at least 20 seconds or an alcohol-based hand sanitizer (that contains at least 60% alcohol), especially after being in a public place, blowing their nose, or coughing/sneezing. Avoid touching the eyes, nose, and mouth with unwashed hands
  • Avoid close contact with people (i.e., maintain a distance of at least 1 metre [3 feet]) including shaking hands, particularly those who are sick, have a fever, or are coughing or sneezing.
  • Practice respiratory hygiene (i.e., cover mouth and nose when coughing or sneezing, discard tissue immediately in a closed bin, and wash hands)
  • Seek medical care early if you have a fever, cough, and difficulty breathing, and share your previous travel and contact history (travelers or suspected/confirmed cases) with their healthcare provider
  • Stay at home if you are sick, even with mild symptoms, until you recover (except to get medical care)
  • Clean and disinfect frequently touched surfaces daily (e.g., light switches, door knobs, countertops, handles, phones).

Recommendations on the use of face masks

  • The World Health Organization recommends that medical masks should be reserved for healthcare workers.
  • People with symptoms should also wear a medical mask, those caring for a sick person at home when in the same room.
  • There is currently no evidence that wearing a mask (medical or other types) in the community setting can prevent infection with respiratory viruses, including COVID-19, in a healthy person.
  • The Centers for Disease Control and Prevention recommends that homemade cloth face coverings can be worn in public settings where social distancing measures are difficult to maintain (e.g., pharmacies, supermarkets), especially in areas where there is significant community transmission
  • Use of a mask alone is insufficient to provide adequate protection, and they should be used in conjunction with other infection prevention and control measures such as frequent hand hygiene and social distancing.
  • It is important to wash your hands with soap and water (or an alcohol-based sanitizer) prior to putting on a face mask, and to remove it correctly. Used masks should be disposed of properly

Screening and quarantine

  • People travelling from areas with a high risk of infection may be screened using questionnaires about their travel, contact with ill persons, symptoms of infection, and/or measurement of their temperature and irrespective of their symptoms are advised to self-isolate for 14 days.

Social distancing

  • Many countries including India have implemented mandatory social distancing measures in order to reduce and delay transmission (e.g., city lockdowns, stay-at-home orders, curfews, non-essential business closures, bans on gatherings, school and university closures, travel restrictions and bans, remote working, quarantine of exposed people/travellers).
  • Shielding is a measure used to protect vulnerable people (including children) who are at very high risk of severe illness from COVID-19 because they have an underlying health condition. Shielding involves minimizing all interactions between those who are extremely vulnerable and other people to protect them from coming into contact with the virus.

Who are the vulnerable people at high risk?

  • Solid organ transplant recipients
  • People with specific cancers
  • People with severe respiratory conditions (e.g., cystic fibrosis, severe asthma, or COPD)
  • People with rare diseases or inborn errors of metabolism that increase the risk of infections
  • (e.g., sickle cell anaemia, severe combined immunodeficiency)
  • People on immunosuppression therapies sufficient to significantly increase the risk of infection
    Women who are pregnant with significant heart disease (congenital or acquired).

These groups are advised to stay at home at all times, and avoid any face-to-face contact for a period of at least 12 weeks (this time period is subject to change).

Tips to remember & Follow!!

  • The virus is not a living organism, but a protein molecule (DNA) covered by a protective layer of lipid (fat), which, when absorbed by the cells of the ocular, nasal or buccal mucosa, changes their genetic code (mutation) and convert them into aggressor and multiplier cells. It decays on its own and the disintegration time depends on the temperature, humidity and type of material where it lies.
  • The virus is very fragile; the only thing that protects it is a thin outer layer of fat. That is why any soap or detergent is the best remedy, because the foam disintegrates the fat By dissolving the fat layer, the protein molecule disperses and breaks down on its own.
  • Heat melts fat; this is why it is so good to use water above 25 degrees Celsius for washing hands, clothes and everything. In addition, hot water makes more foam and that makes it even more useful.
  • Alcohol or any mixture with alcohol over 65% dissolves any fat, especially the external lipid layer of the virus.
  • Never shake used or unused clothing, sheets or cloth. While it is glued to a porous surface, it is very inert and disintegrates only between 3 hours (fabric) , 4 hours (copper) and wood, because it removes all the moisture and does not let it peel off and disintegrates) , 24 hours (cardboard), 42 hours(metal) and 72 hours (plastic). But if you shake it or use a feather duster, the virus molecules float in the air for up to 3 hours, and can lodge in your nose.
  • The virus molecules remain very stable in external cold, or artificial as air conditioners in houses and cars. They also need moisture to stay stable, and especially darkness. Therefore, dehumidified, dry, warm and bright environments will degrade it faster.
  • The virus cannot go through healthy skin.
  • Vinegar is not useful because it does not break down the protective layer of fat.
  • No spirits nor vodka will serve the purpose as the strongest alcohol to drink is 40% alcohol, and you need 65% or more to disintegrate the virus effectively
  • The more confined the space, the more concentration of the virus there can be. The more open or naturally ventilated, the less.
  • You have to wash your hands before and after touching mucosa, food, locks, knobs, switches, remote control, cell phone, watches, computers, desks, TV, etc.
  • You have to humidify hands dry from so much washing them, because the molecules can hide in the micro cracks.
  • Also keep your nails short so that the virus does not hide there.
  • As the pH of the virus is between 5.5 to 8.5, it is advised to take more alkaline foods ( high pH ) like lemons, avocadoes, garlic, mangoes, pineapples and oranges.

This needs to be taken seriously, and if we all follow the simple steps, insist our family and friends to do the same and maintain social distancing, we can together end this pandemic soon.

Stay safe and healthy.

Dr Nanda Rajaneesh

MBBS, MS, MRCS

Consultant – GI/Laparoscopy/Breast Surgeon

Apollo Spectra Hospitals, Koramangala