DEFINING XENOTRANSPLANTATION

For practical reasons, the primary animal used is the pig, though some research uses primates or other species. In modern medicine, xenotransplants are being developed for kidneys (for end-stage renal disease), hearts (for severe heart failure), livers (for acute or chronic liver failure), Islet cells (for type 1 diabetes), and skin and corneal tissues (for burns and eye‑disease patients).

BUT WHY PIGS?

• Thanks to their high reproductive capacity, a large number of pigs can be procured in a shorter amount of time.
• This means, in theory, that thousands of “organ-ready” pigs could be bred on demand, unlike the limited supply of human donor organs.
1. Advanced genetic‑editing tools
• CRISPR and other gene‑editing technologies have made it possible to make tailor-made organs fitting an individual.
• In landmark cases, pig kidneys and hearts used in humans carried up to 69 different genetic edits.

Because of this combination—anatomy, scalability, and genetic programmability—pigs have become the workhorse species for modern xenotransplantation.

GENETICALLY ENGINEERED PIGS

In short, we can say there are 3 major goals for genetic engineering:

Prevention of Transplant Rejection

Human immune systems has the ability to detect “self” from “non-self” antigens. Pig antigens like α‑Gal (Galactose‑α‑1,3‑galactose) and other glycan antigens are flagged as “foreign”. This led to hyperacute graft rejections within minutes in early xenotransplant attempts.

The scientists now use CRISPR to overcome this problem. Recent successful pig‑kidney cases involved multiple antigen‑knockout edits plus human‑gene insertions to fine-tune compatibility.

But preventing rejection isn’t just about removing pig markers. The compatibility can also be increased by the addition of human genes.  

• CD46, CD55, CD59: Regulate the complement system
• Thrombomodulin, EPCR (endothelial protein C receptor): Reduce abnormal clotting within the graft [major cause of early failure]
• CD47: Prevents phagocytosis of pig cells
• HO‑1 (heme‑oxygenase‑1): Has anti-inflammatory and protective effects on blood vessels inside the organ

In one landmark pig‑kidney transplant (2024–2025), the donor pig carried 69 different genetic edits—a mix of knockouts, knock-ins, and knockdowns. This genetically engineered organ functioned in a human recipient for over 270 days (nearly nine months).

Tackling Thrombosis

Chances of Zoonotic Infections

Pigs are a host to several different viruses, including porcine endogenous retroviruses (PERVs). These viruses are integrated in the pig’s DNA and can, in theory, infect human cells, raising concerns about long-term safety.

Recent advances include:

• Gene‑editing PERVs out of the pig genome using CRISPR.
• Protocols to check for any viral activation or transmission.

So far, no PERV transmission has been definitively documented in human xenotransplant cases, but the risk remains a key focus of regulatory scrutiny.

REAL-WORLD XENOTRANSPLANT CASES

Now let’s look at the most recent cases of xenotransplants…

Pig Kidney

The first truly durable pig-kidney transplant in a human was a compassionate use case in 2024–2025. A patient with end-stage kidney disease and no hope of a human donor received a kidney from a 69‑gene-edited pig.

Key outcomes:

• Normal filtration function, reducing the need for dialysis.
• The patient reported improved energy, better appetite, and fewer complications tied to chronic dialysis.
• The graft survived for over 270 days, far longer than any previous pig‑kidney xenotransplant.

In 2026, the first FDA‑sanctioned clinical trial for pig‑to‑human kidney xenotransplantation began in the United States at major centers including NYU Langone, Massachusetts General Hospital, and Johns Hopkins.

These trials are small, closely monitored, and follow strict protocols for patient selection, immunosuppression, and follow‑up.

Organizations like the National Kidney Foundation have also highlighted that clinical trials for pig‑to‑human kidney transplantation are now officially underway.

Pig Heart

Pig Liver

In 2025, a world‑first pig‑to‑human liver xenotransplant in a living patient was reported in China. The recipient, a patient with severe liver failure, received a 6‑gene‑edited miniature‑pig liver.

This liver functioned for several weeks, providing metabolic support and buying time for the patient’s condition to stabilize. While the graft did not last years, it demonstrated that pig livers can replace a human’s liver, even for a short duration.

Reports from the European Association for the Study of the Liver (EASL) and other liver‑disease societies now frame pig‑liver xenotransplants as a potential bridge for acute‑liver‑failure patients who would otherwise die within days.

Other Pig Transplants

Researchers are also exploring pig‑derived islet‑cell transplants for type 1 diabetes.

Scientists are also looking at:

• Pig‑skin grafts for burn patients (providing temporary coverage until human‑skin grafts can be prepared).
• Pig‑corneal transplants for patients with corneal scarring or infection.

RESPONSE OF HUMAN IMMUNE SYSTEM

Xenotransplantation is a constant battle against the immune system. The body’s reaction to a pig organ typically follows a sequence:

Chronic Immune Reactions

Even with genetic modifications, the human immune system continues to interact with the pig graft in the long run.

A 2026 immunology paper analyzing the first long‑lasting pig‑kidney xenograft showed that:

• Certain immune‑cell subsets remained active even months after transplant.
• Gene‑expression patterns in the graft revealed subtle changes reflective of ongoing immune stress.

Thrombosis and Coagulation

Thrombotic microangiopathy remains one of the toughest issues. Pig‑human blood‑clotting systems are not perfectly aligned, so:

• Microclots form in small vessels inside the graft.
• Over time, these clots block blood flow and cause organ failure.

Solutions now include:

• Genetic insertion of human-like clot-regulating genes (thrombomodulin, EPCR, CD47).
• Careful use of anticoagulant drugs around the transplant window.

 These interventions have significantly reduced early clotting-related failures in recent xenotransplants.

SIGNIFICANCE IN HUMAN PATIENTS

The primary driver of xenotransplantation is the uneven demand and supply chain. Xenotransplantation offers a possible way to close this gap by:

• Providing on‑demand organs not dependent on sudden accidents or deaths.
• Reducing waiting times and mortality for patients on dialysis, in heart‑failure clinics, or on liver‑support systems.
• Offering time for more options: a pig organ can keep someone alive and stable until a human organ becomes available.

For patients, the benefits are profound, including and not limited to improved quality of life, greater predictability, and potential longevity.

CHALLENGES AND ETHICAL QUESTIONS

Despite the promise, xenotransplantation is still high‑risk, experimental surgery with major open questions.

Long‑Term Survival and Function

Even the best‑case pig‑kidney xenografts have so far lasted months, not decades. Long‑term outcomes—like 10‑ or 20‑year survival—are still unknown.

Immunosuppression and Side Effects

Xenotransplant recipients need strong immunosuppressive drugs to suppress their immune systems enough to accept the pig organ. These drugs:

• Increase susceptibility to infections.
• Raise the risk of cancer.
• Can cause kidney damage, diabetes, and other metabolic problems.

Ethical Considerations

Xenotransplantation raises serious ethical issues:

• Is it acceptable to breed and modify pigs solely for human organ harvesting?
• Patients in end‑stage disease may feel pressured to accept experimental procedures with uncertain outcomes.
• Will xenotransplants become another tool for the wealthy, while the poor remain on dialysis or in heart‑failure clinics?

Cost and Scalability

Right now, xenotransplantation is extremely expensive: gene editing, pathogen‑controlled breeding, surgery, and long‑term monitoring all carry high costs.

Scaling this technology to hundreds of thousands of patients worldwide will require dramatic cost reductions and technological simplification.

REFERENCES

Tao P and Zhou K (2025) Recent progress in pig-to-human kidney xenotransplantation. Front. Immunol. 16:1735113. doi: 10.3389/fimmu.2025.1735113

Shirini, Kasra et al. “Xenotransplantation Literature Update: January-June 2025.” Xenotransplantation vol. 32,4 (2025): e70072. doi:10.1111/xen.70072

Clinical Trials for Pig-to-Human Kidney Transplantation Are Here. National Kidney Foundation. August 05, 2025.

Guilherme T. Ribas et al, Immune profiling in a living human recipient of a gene-edited pig kidney, Nature Medicine (2026). DOI: 10.1038/s41591-025-04053-3

U.S. FDA page summarizing regulatory concerns, infection risks, and oversight of animal‑to‑human transplants. Link. 

International Society for Heart and Lung Transplantation document on rules for patient selection, immunosuppression, and monitoring in pig‑heart xenotransplants. 20 February 2026.

National Kidney Foundation‑style page explaining what xenotransplantation is, how it works, and where trials stand. Link.

WHAT IS TELEMEDICINE?

• Live‑interactive video visits
• Store‑and‑forward: Patients or local clinics send photos, scans, and lab reports to a specialist who reviews them later and issues a report or recommendation
• Remote patient monitoring (RPM): Patients use devices (blood‑pressure cuffs, glucose meters, smartwatches, ECG patches) that transmit data to clinicians, who then track trends and intervene when needed.

In India, telemedicine has been formally guided by the Telemedicine Practice Guidelines (2020), updated in 2026. It requires the doctors to be registered, patient identity to be verified, proper documentation, informed consent, and treatment with the same professional standards as in-person visits.

PATIENT'S BENEFITS

For patients, telemedicine is primarily about access, convenience, and continuity.

• Telemedicine removes geography as a barrier to expertise.
• No long queues, no crowded waiting rooms. Also, greater compliance would be observed in cases of multiple regular follow-ups.
• For Chronic‑disease management, like diabetes, hypertension, heart failure, chronic kidney disease, and autoimmune conditions.  It can schedule regular check-ins, track lab results, and watch trends from home devices, helping the patient prevent avoidable hospitalizations.
• Tele‑counselling and tele‑psychiatry let people seek help from the privacy of their homes, reducing stigma and shame
• Post‑treatment and rehabilitation. After surgery, or hospital discharge, patients can receive physiotherapy guidance and nutrition coaching easily.

DOCTORS AND TELEMEDICINE

With a skewed doctor-to-population ratio here in India, telemedicine can provide a structure, thus decreasing OPD crowd, waiting time, and delivery of urgent care.

The following are some possible scenarios:

• Pre‑visit triage: A patient can fill out an online, listing his symptoms, medications, and allergies. This information is then forwarded to the physician before the call starts.
• During the visit: The platform can access the patient’s medical history, lab results.
• Post‑visit automation: After the call, the system can auto‑generate notes, send prescription orders as suggested, schedule follow-up reminders, and flag patients with notifiable diseases.

REGULATIONS, PRIVACY AND ETHICS

Because telemedicine deals with highly sensitive health data, it sits at the intersection of law, ethics, and technology.

• Strict scrutiny over AI-generated results should be kept. Confirming the result with a physician could be one step towards it.

TELEMEDICINE IMPLEMENTATION GUIDE BY WHO

CASE STUDY: eSANJEEVANI

Launched in 2018 by the Ministry of Health & Family Welfare, Government of India, eSanjeevani is a cloud-based national telemedicine platform developed by C-DAC, Mohali. It was integrated with Ayushman Bharat Health & Wellness Centres (HWCs).

Objectives

Its main objectives were to:

• Address shortage of doctors and specialists at primary level
• Reduce burden on district and tertiary hospitals
• Create electronic health records and ensure continuity of care

During COVID-19 lockdown (when OPDs were closed), it was expanded into eSanjeevaniOPD, a free patient-to-doctor teleconsultation service for all citizens.

Parts of eSanjeevani

It has two components :

• eSanjeevaniHWC (Hub-and-Spoke Model)
  • Health worker to doctor teleconsultation
  • Used at rural HWCs
  • EMR created → patient connected to doctor → ePrescription issued → medicines dispensed locally
• eSanjeevaniOPD
  • Direct patient-to-doctor consultation via web/mobile app
  • Patient registers → receives token → waits in virtual queue → doctor consults → prescription issued

Lessons & Future Plans

• Higher internet penetration increased usage, but demand was strong even in low-connectivity and remote areas.
• Strong local technical support ensured 99.5% uptime.
• Integrated with Ayushman Bharat Digital Mission for health records linkage.
• Expanding to eSanjeevani 2.0 with AI features, multilingual interface, and capacity for 1 million consultations/day.

CHALLENGES AND LIMITATIONS

Despite having positive effects on the current healthcare infrastructure, it comes along with some challenges.

• Digital divide: People may lack stable internet, smartphones, or the digital literacy to use apps.
• Physical‑exam limitations: Conditions like acute abdominal pain, complex injuries, and certain surgical cases would still require in-person exams, palpation, or imaging that cannot be fully replicated remotely.
• Privacy and commercialization risks: Breaches, misuse of data, or aggressive marketing practices can erode patient trust too.

THE FUTURE OF TELEMEDICINE

• Instead of “in‑person vs. telemedicine,” the future is hybrid care—mixing face‑to‑face visits, video consults, phone calls, and remote monitoring based on each patient’s needs and condition.
• As smartwatches, continuous glucose monitors, ECG patches, and implantable devices become more accurate and affordable, telemedicine dashboards will receive richer, real-time data streams, thus enabling earlier intervention.
• Telemedicine will be a key tool for delivering specialist care in low‑resource and remote regions, including tribal belts and underserved districts of India, where building enough hospitals and training enough specialists in‑person is physically and financially challenging.

REFERENCES

Consolidated telemedicine implementation guide. 9 November 2022 Publication. ISBN: 978 92 4 005918 4

eSanjeevani, National Telemedicine Service. Link.

BASIC TERMINOLOGIES

ORAL REHYDRATION SALT SOLUTION

Constituents

 Given below is the list of ingredients present in the New ORS solution as advised by WHO. 

Dissolution of an ORS sachet in drinking water yields the following concentrations :

Difference between the Old and the New

The 'Old' ORS formulation is known as the Standard WHO ORS whereas the 'New' one is called the Reduced Osmolarity ORS. Previously, the ORS  had a total osmolarity of 311 mOsm/l, but a consultative technical meeting held in New York (USA) in July 2001 reviewed various studies evaluating this approach. During the meeting, experts provided technical recommendations to WHO and UNICEF regarding the efficacy and safety of reduced osmolarity ORS for treating children with acute non-cholera diarrhea, as well as adults and children suffering from cholera.

These studies showed that the efficacy of ORS solution for treatment of children with acute non-cholera diarrhoea is improved by reducing its osmolarity.  In a combined analysis of this study and studies with other reduced osmolarity ORS solutions  stool output was also reduced by about 20% and the incidence of vomiting by about 30%. 

However, it remains uncertain whether this finding can be confidently applied to patients with severe cholera-induced diarrhea, in whom electrolyte losses are extensive. In such cases, the risk of developing hyponatremia may be heightened, potentially leading to adverse clinical outcomes and diminishing the benefits of using reduced osmolarity ORS.

Role of the Constituents

• Glucose : Facilitates the absorption of sodium (and hence water) on a 1:1 molar basis in the
  small intestine
• Sodium and Potassium : To replace the body losses of these essential ions during
  diarrhoea (and vomiting)
• Citrate : Corrects the acidosis that occurs as a result of diarrhoea and dehydration.

Uses

DEHYDRATION :

OTHERS :

In a study about ORS as alternative to IV fluids in adult burn patients with >15% TBSA burn injuries, it was observed that :

• there were no major significant differences between the study group and control group.
• Even where there was a significant difference, apart from blood pressure in the first hour of the first day, the study group never crossed safe limits for other parameters.
• WHO-ORS with 5gm salt tablets, given according to Sørenson’s formula, is a safe and efficient alternative for IV resuscitation.
• It could even be a substitute, particularly in low resource settings and fire disasters.

FSSAI 

Dr. Santosh’s eight-year campaign shed light on companies marketing sugar-heavy drinks as ORS, falsely suggesting health benefits. Her advocacy emphasized the risks these products pose, especially to children and people with diabetes. And finally, FSSAI has now given is new directive in favour of her campaign. 

References

INTRODUCTION

Antimicrobial resistance (AMR) is emerging as one of the most serious challenges to global health, weakening the power of critical medicines and increasing the danger posed by infections that were once easily treatable, as well as by routine medical procedures.

Through its Global Antimicrobial Resistance and Use Surveillance System (GLASS), the World Health Organization (WHO) helps nations establish robust surveillance systems and produce comparable data that can drive informed public health policies.

On 13 October 2025, WHO published Global antibiotic resistance surveillance report 2025, which offers a comprehensive global picture of antibiotic resistance patterns, drawing on evidence from more than 23 million confirmed cases of bloodstream, urinary, gastrointestinal, and urogenital infections (including gonorrhoea). The findings are based on data submitted by 104 countries in 2023 and 110 countries over the 2016–2023 period. 

If you'd like to understand what AMR [Antimicrobial Resistance] is, then please look at this article. The following is a synopsis of the detailed analysis provided by WHO.

AT A GLANCE

Geographically, the South-East Asia and Eastern Mediterranean regions reported the greatest burden, with nearly one in three infections showing resistance, followed by the African Region, where one in five infections were resistant—both surpassing the global median.

Conversely, resistance was less prevalent in the European Region (one in ten) and lowest in the Western Pacific Region (one in eleven), highlighting marked regional differences.

This trend is concerning because these drugs are critical for treating severe infections. The rise in AMR is narrowing empirical treatment options and prompting a shift from oral to intravenous therapies, with increased dependence on second-line and last-resort antibiotics.

GLOBAL TRENDS 

Infections with AST

Here are some representations of numbers of infection episodes with AST results per million population in 2023.

Bloodstream Infections

Here are some representations of the National percentage resistance in bloodstream infections, 2023.

Gastrointestinal Infections

Here are some representations of the National percentage resistance to ciprofloxacin in gastrointestinal infections, 2023.

Urinary Tract Infections

Here are some representations of the National percentage resistance to selected antibiotics in urinary tract
infections, 2023.

Urogenital Infections

Here are some representations of the Percentage antibiotic resistance to ceftriaxone in N. gonorrhoeae urogenital infections, 2023

Percentage AMR 

Global trends in percentage AMR by infection type: median annual change (2018–2023) and 2023 percentage resistance estimates :

INDIAN STATS

The numbers below were a part of Global antibiotic resistance surveillance report 2025 :

AMRSN, 2013

Goals :

1. Establish network of hospitals to monitor trends in the antimicrobial susceptibility profile of clinically important bacteria and fungi limited to human health.
2. Include comprehensive molecular studies for identifying the clonality of drug-resistant pathogens and their transmission dynamics to enable better understanding of AMR in the Indian context and develop suitable interventions.
3. Disseminate information on AMR in pathogenic organisms to stakeholders to promote interventions that reduce AMR.
4. Create data management system for data collection and analysis.

Focus : 

•  Enterobacteriaceae causing sepsis,
• Gram negative non-fermenters,
• Enteric fever pathogens,
• Diarrheagenic bacterial organisms,
• Gram positives: staphylococci and enterococci and
• Fungal pathogens (excluded in WHO priority pathogens)-yeasts (Candida and Cryptococcus spp.) and mycelial fungi (Aspergillus spp. and Zygomycetes spp.)

REFERENCES

SOURCES OF VITAMIN B12

Analyzing the table, it is apparent that most of the sources are of animal-origin; meat, egg, milk, yoghurt, cheese, fish. This acts as an evidence to the fact that vegetarians and vegans are more prone to deficiency of vitamin B12.

Some other sources that one can take are dietary supplements and prescription medications. The most common form of supplement is cyanocobalamin. It is also taken in the form of adenosylcobalamin, methylcobalamin, and hydroxycobalamin.

DEFICIENCY OF VITAMIN B12

Vitamin B12 deficiency, medically referred to as cobalamin deficiency, occurs when the levels of vitamin B12 in the
blood and tissues are below the normal range.

But relying solely on blood tests to gauge deficiency isn't the most accurate method, as certain individuals with a deficiency might exhibit regular vitamin B12 blood levels. More reliable  indicators of actual vitamin B12 activity are the blood concentrations of methylmalonic acid, a byproduct of protein breakdown, and homocysteine. These values rise in the presence of a vitamin B12 deficiency.

CAUSES OF DEFICIENCY:

Vitamin B12 deficiency primarily has 3 etiologies : Dietary Insufficiency, Malabsorption, and Autoimmune.

Therefore, individuals practicing a vegetarian or vegan dietary regimen should incorporate B12-fortified foods or take B12 supplements. This is of particular significance for pregnant women, as proper vitamin B12 is crucial for fetal neurological development, and deficiency can result in permanent neurological impairment.

surgery (weight loss surgery) may develop the deficiency. Also, a surgical resection of terminal ileum (due to Crohn's disease) may increase the risk of deficiency. To know more about Crohn's disease and its holistic treatment, you may visit Ayurvedic Herbalist. 

GASTROINTESTINAL DISORDERS : 

Certain diseases including Crohn’s and celiac disease that negatively impact the digestive tract also increase the risk of deficiency. Other than that, gastritis (inflammation of stomach lining) is a common cause of B12 deficiency. This occurs due to a lack of hydrochloric acid, which is a key component for absorption. You can understand more about the way B12 is absorbed in 'Introduction to Vitamin B12'.

These medications can slow down the release of stomach acid or reduce its production, which could potentially impede the conversion of vitamin B12 into a usable form in the stomach. Nevertheless, current research has not provided evidence for a significantly higher incidence of vitamin B12 deficiency in people using these medications.

HIGH RISK POPULATIONS:

• AGE OVER 75 : Individuals above the age of 75 are more susceptible to developing vitamin B12 deficiency due to potential difficulties in fully absorbing the vitamin by their bodies.
• GI DISORDER : Conditions like celiac disease and Crohn’s disease can complicate the absorption of vitamin B12 in the body.
• STRICT VEGAN OR VEGETARIAN DIET : Those who follow this diet are at an increased risk of vitamin B12 deficiency if their diet lacks sufficient fortified foods containing the vitamin.
• TAKING SPECIFIC MEDICATIONS : Certain medications can lead to decreased levels of vitamin B12 in the body. These include metformin (a medication used to manage diabetes), proton pump inhibitors (PPIs used to treat GERD and peptic ulcers), histamine H2 blockers (used to reduce stomach acid production), and oral birth control pills (oral contraceptives).

SYMPTOMS:

NEUROLOGICAL :

• Numbness or tingling in your hands and feet.
• Vision loss.
• Having a hard time remembering things or getting confused easily.
• Having a difficult time walking or speaking like you usually do.

PHYSIOLOGICAL :

• Feeling depressed, irritable and
• Experiencing a change in the way you feel and behave.

Neglecting to address vitamin B12 deficiency can lead to enduring and significant consequences that impact the nervous system and brain. Some of the more severe and lasting effects of untreated vitamin B12 deficiency are :

• Megaloblastic Anemia: It is characterized by red blood cells that are larger than normal. As the red blood cells are too large, they may not be able to exit the bone marrow to enter the bloodstream and deliver oxygen.
• Nerve damage with numbness, tingling in the hands and legs
• Depression
• Paranoia and delusions
• Memory loss

PREVENTION OF B12 DEFICIENCY

VITAMIN B12 SUPPLEMENTS : Numerous multivitamins contain vitamin B12, and standalone supplements focused solely on vitamin B12 are also available. This is one of the few options available to vegans and vegetarians, apart from fortified foods.

REFERENCES

Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B(6), Folate, Vitamin B(12), Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academies Press; 1998. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK114310/

Vitamin B12-Fact Sheet for Medical Professionals. National Institutes of Health (NHI). Retrieved from https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/#en1

Vitamin B12 Deficiency. Diseases and Conditions, Health Library, Cleveland Clinic. Retrieved from https://my.clevelandclinic.org/health/diseases/22831-vitamin-b12-deficiency

Vitamin B12. The Nutrition Source, Harvard T.H. Chan. Retrieved from https://www.hsph.harvard.edu/nutritionsource/vitamin-b12/

Vitamin B-12. By Mayo Clinic Staff. Retrieved from https://www.mayoclinic.org/drugs-supplements-vitamin-b12/art-20363663

Ankar A, Kumar A. Vitamin B12 Deficiency. [Updated 2022 Oct 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441923/

METHODS OF ABSORPTION

There are two ways for absorption of Vitamin B12. The first one is by passive absorption due to a difference in its concentration between the lumen and the cells of the intestine. 

The other way is via active transport with the help of protein carriers. Vitamin B12 is usually bound to a protein in the foods we eat. So, the first step is dissociating the food-bound B12 with the help of HCl (stomach acid) and pepsin (protease) in the stomach.  

The freed B12 now binds to a cobalamin-binding protein secreted by the salivary glands & the gastric mucosa (moist inner lining of stomach).  When the partially digested chyme enters the small intestine, the protein-bound B12 is attacked by pancreatic proteases. This results in the separation of B12 from the protein.  

Now, B12 forms a complex with intrinsic factor which was secreted by the parietal cells of stomach. The intrinsic factor has two functions; to assist the vitamin’s absorption & to protect it from catabolism by intestinal bacteria. This B12-IF complex can be absorbed by enterocytes (cells lining the intestine) of distal ileum via receptor-mediated endocytosis.  

FUNCTIONS

Given below are the diverse functions of Vitamin B12:  

• Being a part of Vitamin Bs, it is involved in the metabolism of proteins, fats, and carbohydrates.  
• It also has a role in erythropoiesis or red blood cell formation.
• It is required for DNA & RNA synthesis and is important for the development and maturation of red blood cells. 
• Also, for proper cell division, growth and repair, an adequate amount of vitamin B12 is essential. 
• It is involved in synthesis of myelin. Myelin is found in the long axonal region of a neuron. It facilitates fast impulse transmission and acts as a protective layer. 
• Adequate B12 levels are also associated with good cardiovascular and mental health.  

RECOMMENDED INTAKE

Vitamin B12 recommended intake values vary with age and gender. They are provided in the Dietary Reference Intakes (DRIs) developed by the Food and Nutrition Board (FNB) at the National Academies of Sciences, Engineering, and Medicine.  

According to the National Cancer Institute, any substance or process that is used primarily on non-living objects to kill germs, such as viruses, bacteria, and other microorganisms that can cause infection and disease is called as a disinfectant. [1]

Most disinfectants are harsh chemicals but sometimes heat or radiation may be used. (Fig 1-1)

Other subtances do exist which give the same result but at different locations. Antibiotics work inside our body and antiseptics work on living surfaces. 

Disinfectants too can be classified on the basis of their location of use :

• Medical grade
• Instrument grade
• Low, Intermediate and High level [due to their effect on different microorganisms]
• Sterilant
• Household grade
• Commercial grade

 and their chemical composition :

• Oxidising Agent
• Peroxides
• Chlorine and its derivatives
• Heavy metals
• Organic [Alcohol, Aldehyde, Phenol, Ammonium salt]

Although effective in completing their role, there are hazards of disinfectants that the user should be aware of.

DIRECT HARMFUL EFFECTS OF SYNTHETIC DISINFECTANTS

Chlorine (Cl2) has been commonly used throughout the world as a chemical disinfectant, with the purpose of being a principal barrier to microbial contaminants in drinking-water. The evident biocidal attributes of chlorine have been somewhat offset by the formation of disinfectant by-products (DBPs) of public health concern during the chlorination process. Consequently, alternative chemical disinfectants, such as ozone (O3), chlorine dioxide (ClO2) and chloramines (NH2Cl, monochloramine), are increasingly being used; however, each has been shown to form its own set of DBPs. [2]

Chlorine gas, chloramine and chlorine dioxide are powerful respiratory irritants. Bleach (chemically, sodium hypochlorite NaOCl) has been observed to be used in human poisoning. [3]

Improper cleaning of surfaces applied with disinfectants can contain residual disinfectants. They will react easily with organic compounds found in saliva and stomach content, resulting in the formation of by-products.[4] These foreign compounds can be absorbed by the body, which can affect the pHof the blood, disturb the inner linings of organs, or even necroses some tissues.

On 18th April 2020, the Union Health Ministry of India issued an advisory against spraying of disinfectant on people for COVID-19 management. They stated "Spraying of individuals or groups is not recommended under any circumstances. Spraying an individual or group with chemical disinfectants is physically and psychologically harmful”.[5] (Fig 2-2)

EFFECTS OF CHLORINE :

Chlorine has long been recognised as a lung irritant and its amount is negligible in drinking water, but it surely has some occupational hazards. Similarly, Sodium hypochlorite (NaOCl) or calcium hypochlorite (Ca(OCl)2) are also extensively used as disinfectants, for they are highly caustic. This too leads to a clear concern for occupational exposure.

Some major sources of toxicity in humans are by exposure to chlorine and hypochlorite solutions, chlorine gas, and intake of sodium hypochlorite, marketed as bleach.

Yarington (1970) demonstrated that instillation of bleach (NaOCl) into the oesophagus of dogs causes irritation. The minimal exposure of 5 mins with 10 ml commercial bleach produced irritation. (Fig 2.1-4) [6]

The irritating effects of chlorine have been well observed and recorded, thanks to the chemical warfare during World War I.(Fig 2.1-3) [7] In the follow-up of survivors of gas chambers in concentration camps, no permanent lung damage was observed, however breath sounds indicated bronchitis and limited chest and diaphragmatic movement, even emphysema.

EFFECTS OF CHLORAMINE :

Chloramine is primarily used as a residual disinfectant, and chloramines (as a group) are a potent respiratory irritant.

Eaton et al. (1973) concluded with his research that chloramine is capable of inducing methemoglobinemia at low concentrations when there is a large reservoir of chloramine. This is a different exposure pattern from that of normal mammals, as they consume small volumes of water in comparison to the volume of red blood cells exposed to the water. [8]

The primary harmful effects have been observed in human poisoned by chloramine formed when household bleach (NaOCl) was mixed with ammonia (NH3) for use as a cleaning solution.

FORMATION OF DISINFECTANT BY-PRODUCTS 

Disinfectant By-Products (DBPs) are formed upon the reaction of chemical disinfectants with DBP precursors. Natural organic matter (NOM) acts as the organic precursor, whereas bromide ion (Br-) serves as the inorganic precursor. DBP formation is influenced by water quality (e.g., bromide, pH, temperature, etc.) and treatment conditions (e.g., disinfectant dose, contact time, removal of NOM before the point of disinfectant application, prior addition of disinfectant, etc.). [9]

CHLORINE BY-PRODUCTS : 

Chlorine is used in the form of gaseous chlorine or hypochlorite (OCl-). As an oxidizing agent, chlorine reacts with a wide variety of compounds, in particular those that are considered reducing agents (hydrogen sulfide [H2S], manganese(II), iron(II), sulfite [SO32-], Br-, iodide [I-], nitrite.

Chlorine gas hydrolyses in water almost completely to form hypochlorous acid (HOCl) (Eq 3.1-1). The hypochlorous acid dissociates into hydrogen ions (H+) and hypochlorite ions in the reversible reaction (Eq 3.1-2).

Chlorine in the form of hypochlorous acid/hypochlorite ion (HOCl/OCl-) reacts with bromide ion, oxidizing it to hypobromous acid/hypobromite ion (HOBr/OBr-).(Eq 3.1-3) Hypobromous acid is a weak acid (pKa = 8.7); like hypochlorite, hypobromite is metastable. In alkaline solution, it decomposes to give bromate and bromide.(Eq 3.1-4)

Another reaction that occurs with chlorine is the formation of chlorate (ClO3-) in concentrated hypochlorite solutions.(Eq 3.1-5 and Eq 3.1-6)

Hypochlorous acid (a more powerful oxidant) and hypobromous acid (a more effective halogenating agent) react collectively with NOM to form chlorine DBPs, including trihalomethanes (THMs), haloacetic acids (HAAs), haloacetonitriles (HANs), haloketones, chloral hydrate and chloropicrin. [10]

CHLORINE DIOXIDE BY-PRODUCTS :

Chlorine dioxide is generally produced by reacting aqueous (sodium) chlorite with chlorine.(Eq 3.2-7) An alternative approach to chlorine dioxide generation is with hydrochloric acid (HCl), a process that results in less chlorate during production.[11] (Eq 3.2-8)

Chlorine dioxide is one of the few compounds that exists almost entirely as monomeric free radicals. Concentrated chlorine dioxide vapour is potentially explosive because of which it must be manufactured at the point of use. Chlorine dioxide in water does not hydrolyse to any appreciable extent. Neutral or acidic dilute aqueous solutions are quite stable if kept cool, well-sealed and protected from sunlight.

Chlorine dioxide represents an oxidation state (+4) intermediate between those of chlorite (+3) and chlorate (+5). No acid or ion of the same degree of oxidation is known.

Chlorine dioxide is a powerful oxidizing agent that can decompose to chlorite; in the absence of oxidizable substances and in the presence of alkali, it dissolves in water, decomposing with the slow formation of chlorite and chlorate [12] (Eq 3.2-9) When chlorine dioxide reacts with aqueous contaminants, it is usually reduced to chlorite ion. The corresponding electron transfer reactions are comparable to those occurring when singlet oxygen acts as an oxidant (Tratnyek & Hoigne, 1994).[13]

Bromide (in the absence of sunlight) is not oxidized by chlorine dioxide. (Eq 3.2-10) Therefore, water treatment with chlorine dioxide will not transform bromide ion into hypobromite and will not give rise to the formation of bromoform (CHBr3) or bromate. This is an important difference between the use of chlorine dioxide as an oxidant and the use of chlorine or ozone as an oxidant. Unlike the other disinfectants, the major chlorine dioxide DBPs are derived from decomposition of the disinfectant as opposed to reaction with precursors.[12]

OZONE BY-PRODUCTS :

Ozone is a strong oxidizing agent. Oxidation reactions initiated by ozone in water are generally rather complex; in water, only part of the ozone reacts directly with dissolved solutes. Another part may decompose before reaction. Such decomposition is catalysed by hydroxide ions (OH-) and other solutes.

Highly reactive secondary oxidants, such as hydroxyl radicals (OH-), are thereby formed. (Eq 3.3-11) These radicals and their reaction products can additionally accelerate the decomposition of ozone. (Eq 3.3-12) Consequently, radical-type chain reactions may occur, which consume ozone concurrently with the direct reaction of ozone with dissolved organic material.

Many oxidative applications of ozone have been developed, including disinfection, control of algae, removal of tastes and odours, removal of colour, removal of iron and manganese, microflocculation, removal of turbidity, removal of organics by oxidation of phenols, detergents and some pesticides, and control of halogenated organic compounds.

For disinfection and for oxidation of many organic and inorganic contaminants (Eq 3.3-13, 14, 15) in drinking-water, the kinetics of ozone reactions are favourable; on the other hand, for many difficult-to-oxidize organic compounds, such as chloroform (CHCl3), the kinetics of ozone oxidation are very slow (Hoigne et al., 1985) [14]

CHLORAMINE BY-PRODUCTS : 

Monochloramine is a poor primary disinfectant. Additionally, it is a poor oxidant and is not effective for taste and odour control or for oxidation of iron and manganese. However, because of its persistence, it is an attractive secondary disinfectant for the maintenance of a stable distribution system residual. [15]

The use of disinfectants such as ozone or chlorine dioxide combined with chloramines as a secondary disinfectant appears to be attractive for minimizing DBP formation (Singer, 1994b).[16] Monochloramine is the only useful ammonia-chloramine disinfectant. Dichloramine (NHCl2) and nitrogen trichloride (NCl3) are too unstable to be useful and highly malodorous.

TOXICOLOGY OF DISINFECTANT BY-PRODUCTS

We have previously discussed the harmful effects of disinfectants and their reactions to form disinfectant by-products. Various studies have proved the dire biological effects of DPBs.

TRIHALOMETHANES : 

(Tab 4-1) Trihalomethanes (or THMs) are the most pervasive by-products of disinfection by chlorine. THMs are volatile liquids at room temperature, thus vaporise during water usage. So, inhalation becomes the primary source of exposure route, in addition to ingestion. Major THMs which have been extensively observed are: Chloroform, Bromodichloromethane (BDCM), Dibromochloromethane (DBCM), and Bromoform.

Fatal acute chloroform intoxication via inhalation was reported to be the root cause for cardiomyocyte fragmentation and waviness which indicated acute heart failure, possibly due to arrhythmias or cardiac depression (Harada et al., 1997). [17]

IARC (International Agency for Research on Cancer) concluded that there is sufficient evidence for carcinogenicity of BDCM in experimental animals but inadequate evidence for carcinogenicity of BDCM in humans. Thus, it was assigned to be possibly carcinogenic to humans. (IARC, 1991, 1999) [18] [19]

No strong evidence of acute, short-term, chronic, reproductive, and developmental toxicity; neurotoxicity; toxicity in humans; carcinogenicity and mutagenicity were reported for DBCM.

Bromoform was used in the late 19th and early 20th century as a sedative for children with whooping cough. Patients were given 1 drop 3-6 times a day. (Burton-Fanning, 1901). [20] A few rare instances of death or near-death were reported, cause being accidental overdose. (Dwelle, 1903) [21]

HALOACETICACIDS : 

(Tab 4-1) Haloacids like Dichloroacetate (DCA) and Trichloroacetate (TCA) are present at higher concentrations than its counterpart,

Monochloroacetate in drinking water treated with chlorine. Dichloroacetate, widely known as dichloroacetic acid, is a salt and is found ionised in water. DCA was first administered as an oral hypoglycaemic agent to patients suffering from diabetes mellitus (Stacpoole et al., 1978). [22] But soon DCA was not in use due to the study by Moore et al.(1979b) and Stacpoole(1989) as it induced reversive polyneuropathy in patients. [23] [24]

Like DCA, TCA also exists as in salt form in the pH of drinking water.[25]Being a strong acid, it is known that contact of TCA with skin can form acid burns, and the ingestion of the same can damage the GI tract. [26]

HALOALDEHYDES AND HALOKETONES :

The most important compound found in drinking water is trichloroacetaldehyde (or chloral hydrate). Trichloroacetaldehyde is hydrated in water and in the body to form a well-known sedative-hypnotic chloral hydrate.

Chloral hydrate is primarily known for its depressant effects on the central nervous system (Gilman et al., 1991) [27]. The most important acute toxic effect is the production of cardiac arrhythmias. Lower doses of chloral hydrate have been associated with some adverse side-effects. A study of new-borns administered chloral hydrate indicated a high incidence of direct hyperbilirubinaemia (Lambert et al., 1990) [28]. There have been occasional reports of liver damage induced by high doses of chloral hydrate by ingestion (van Heijst et al., 1977; Gilman et al., 1991) [27] [29].

In general, aldehydes are irritant chemicals, and substitution of chlorine generally increases this irritancy. Concentrations of chloroacetaldehyde as low as 0.02% produced intradermal irritation, 7.5% produced rather severe dermal irritation and 0.03% irritated the eyes of rabbits (Lawrence et al., 1972). [30]

There are considerable data on the mutagenic properties of various halogenated aldehydes and ketones. there is a potential carcinogenic hazard associated with the halogenated aldehydes. Only a single compound, chloroacetaldehyde, was evaluated as a carcinogen in a lifetime study, and only one dose level was studied. It appears to be more potent as a carcinogen than the corresponding THM and HAA by-products.

CHLORATE :

There have been sporadic reports of poisoning with sodium or potassium salts of chlorate (Temperman & Maes, 1966; Mengele et al., 1969; Yoshida et al., 1977; Bloxham et al., 1979; Helliwell & Nunn, 1979; Steffen & Seitz, 1981). [31] [32] [33] [34] [35] [36] Most of these cases involved ingestion of preparations of sodium chlorate used for pesticidal purposes. There was generally evidence of oxidative damage to erythrocytes, methaemoglobin formation and the renal complications of haemolytic anaemia.

BROMATE : 

(Tab 4.5-1) Human poisonings have been associated with the ingestion of sodium bromate and potassium bromate. Many of these poisonings result from accidental or deliberate ingestion of preparations used as neutralizers in permanent wave kits (Warshaw et al., 1985; Lue et al., 1988).[37] [38] Clinical signs of bromate poisoning include anaemia and haemolysis, renal failure and hearing loss. Loss of hearing appears to be more common in adults than in children (Lichtenberg et al., 1989) [39]. The hearing loss and renal failure can have a prolonged course in some, but not all, people poisoned by bromate (Kuwahara et al., 1984) [40].

REASON FOR CHANGE

By now, we have accumulated an astronomical amount of data and evidence that suggests that the chemical disinfectants we use in day-to-day life is a double-edged sword. Although it is efficient in killing microbes, but we still have to pay the price for prolonged exposure to it. Hence, it is imperative that we take immediate action to lessen its impact. 

Even with strict laws regarding the manufacture and distribution of disinfectants, there are many factories where appropriate measures for protection of employees are absent. This can be explained by negligent implementation of laws by the government, lack of awareness between workers and almost no accountability taken by the employers. Even if this issue is solved, a major problem still remains. The manufacturing process and acquisition of raw materials for disinfectants have an undesirable effect on the environment. 

To overcome this, we need to adopt a more eco-friendly process which aligns with the Sustainability Development Goals. 

(Fig 5) The Sustainable Development Goals (SDGs) were born at the United Nations Conference on Sustainable Development in Rio de Janeiro in 2012. The objective was to produce a set of universal goals that meet the urgent environmental, political, and economic challenges facing our world.

Sustainable development has been defined in many ways, but the most frequently quoted definition is from Our Common Future, also known as the Brundtland Report :

"Sustainable development is development that meets the need of the present without compromising the ability of future generations to meet their own need"

With the help of this post, I'd like to assist this process of changing and conserving our environment.

The primary goals that will be focussed upon are :

Goal 3 : Good Health and Well Being [of the workers and users]

Goal 6 : Clean Water and Sanitation 

Goal 8 : Decent Work and Economic Growth [for companies trying to be more sustainable]

Goal 11 : Sustainable Cities and Communities [by lessening the negative impact of synthetic disinfectants and DBPs]

Goal 12 : Responsible Consumption and Production [for the betterment of ourselves anf the next generations]

Goal 13 : Climate Action [by decreasing the carbon footprint of the industries]

SUSTAINABLE ALTERNATIVES 

Although there does not exist an alternative of disinfectant for all possible uses, there are some that we can use at our households.

Internet is filled with recipes to remove stain and grease, brighten pots and clean tiles. Some of the ingredients commonly used are vinegar, baking soda, lemon, borax, washing soda, rubbing alcohol and hydrogen peroxide. The combinations of these substances have been proven to be effective, and can be readily tested at your home. 

One of the most important place for disinfectant use is in the medical field. From surgery to hospital beds, everything needs to be clean to prevent any further infection. Thus an excessive amount is used to ensure that. This has now led to the problem of superbugs, or strains of microorganisms that have evolved to be resistant to the synthetic disinfectants used. As the use of disinfectant is futile, it may lead to a serious problem in the far future. Thus, I believe that rather than continuing on this path, we should shift our attention to plant or other biological based solutions. 

This change is a long one and won't be done in a single night. So, we should further scrutinize the laws, fine tune them and make sure they are implemented correctly. Also, we should not irresponsibly use the disinfectants for our and the environment's wellbeing. 

One such sustainable alternative to disinfectants is Aloe vera. The second part of my project discusses as to why Aloe can be used and how does it disinfect. You can read more about it on the post 'Aloe Vera : A Sustainable Disinfectant'.

Hazards of Disinfectants Hazards of Disinfectants Hazards of Disinfectants Hazards of Disinfectants Hazards of Disinfectants  Hazards of Disinfectants Hazards of Disinfectants Hazards of Disinfectants Hazards of Disinfectants Hazards of Disinfectants Hazards of Disinfectants Hazards of Disinfectants Hazards of Disinfectants Hazards of Disinfectants Hazards of Disinfectants Hazards of Disinfectants Hazards of Disinfectants Hazards of Disinfectants Hazards of Disinfectants 

Hazards of Disinfectants  

Hazards of Disinfectants  

REFERENCES

CLASSIFICATION AND NOMENCLATURE

A virus is a an ultramicroscopic, metabolically inert, obligate parasites that replicates only within the cells of living hosts, composed of an RNA or DNA core, a protein coat, and, in more complex types, a surrounding envelope.

The International Committee on Taxonomy of Viruses (ICTV) is concerned with the designation and naming of virus taxa (i.e. species, genus, family, etc.) rather than the designation of virus common names or disease names. The virus' are classified according to the following features :

1. Virion morphology, including size, shape, type of symmetry, presence or absence of peplomers, and presence or absence of membranes.
2. Virus genome properties, including type of nucleic acid (DNA or RNA), size of genome, strandedness (single or double), whether linear or circular, sense (positive, negative, ambisense), nucleotide sequence, and presence of special features (repetitive elements, isomerization, 5′-terminal cap).
3. Genome organization and replication, including gene order, number and position of open reading frames, a strategy of replication (patterns of transcription, translation), and cellular sites (accumulation of proteins, virion assembly, virion release).
4. Virus protein properties, including number, size, and functional activities of structural and nonstructural proteins, amino acid sequence, modifications (glycosylation, phosphorylation, myristylation), and special functional activities (transcriptase, reverse transcriptase, neuraminidase, fusion activities).
5. Antigenic properties.
6. Physicochemical properties of the virion, including molecular mass, buoyant density, pH stability, thermal stability, and susceptibility to physical and chemical agents, especially ether and detergents.

But, the most commonly used system of virus classification was developed by Nobel Prize-winning biologist David Baltimore in the early 1970s.

BALTIMORE CLASSIFICATION :

Virologist & Nobel laureate David Baltimore developed a classification which mainly focusses on the central line below - [3] (Fig : 4.1-1, 4.1-2)

'All viruses must synthesize positive-strand mRNAs from their genomes, in order to produce proteins and replicate themselves'

The classification divides viruses into seven groups, depending upon type of nucleic acid (ss or ds, RNA or DNA), sense and method of replication. They are: [4][5] 

CLASSIFICATION AND NOMENCLATURE OF CORONAVIRUS :

During the initial outbreak in Wuhan, China, various names were used for the virus; some names used by different sources included the "coronavirus" or "Wuhan coronavirus".

In January 2020, the World Health Organisation recommended "2019 novel coronavirus" (2019-nCov) as the provisional name for the virus. This was in accordance with WHO's 2015 guideline against using geographical locations, animal species, or groups of people in disease and virus names.

On 11 February 2020, the International Committee on Taxonomy of Viruses adopted the official name "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2). To avoid confusion with the disease SARS, the WHO sometimes refers to SARS-CoV-2 as "the COVID-19 virus" in public health communications and the name HCoV-19 was included in some research articles.

So, of the realm Riboviria and order Nidovirales, the family Coronaviridae is classified as Group IV – helical enveloped ssRNA type virus. This family is further divided into two sub-families Letovirinae and Orthocoronavirinae. Orthocoronavirinae is classified into four genera – Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus (based on host).

The corona virus, of genus Betacoronavirus, is named as "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2). And the species to which the virus SARS-CoV-2 belongs is Severe acute respiratory syndrome-related coronavirus. The disease name has been designated as COVID-19 by the WHO. The '19' in COVID-19 stands for the year, 2019, that the virus was first seen. The number '19' has nothing whatsoever to do with virus strains, genotypes, or anything else related to the virus' genetics.[6]

STRUCTURAL BIOLOGY

Since January, structural biologists have been busy modeling the virus' vital proteins, which could lead to therapeutic breakthroughs. As soon as the genomic sequence of SARS-CoV-2, the virus that causes the COVID-19 disease, was mapped, researchers were off to the races in synthesizing its proteins and determining their structures.

Unlike the highly complex genome sequence encoded in human DNA, the new coronavirus has a much shorter sequence and stores its genetic information in a single strand of RNA.

The first structural models were uploaded to the Protein Data Bank, an international database for 3D structural data of large biomolecules, within five weeks of the earliest reported cases of COVID-19.

Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) are both similar to the novel coronavirus, which scientists used as a basis for identifying protein sequences and shapes.

X-ray crystallography had been used rapid and accurate data gathering., and was a key tool in structural biology. However, X-ray crystallography doesn't work for every protein, and thus a new technology was used for the study. The relatively new cryo-electron microscopy emerged as a standout method for capturing the proteins in SARS-CoV-2, reconstructing an array of 2D images into a clear 3D model which facilitated the study.

SARS-CoV-2 is an enveloped, non-segmented, positive sense RNA virus with a diameter of about 65–125 nm, containing single strands of RNA and provided with crown-like spikes on the outer surface. The proteins of SARS-CoV-2 consist of two large polyproteins: ORF1a and ORF1ab (that proteolytically cleave to form 16 nonstructural proteins), four structural proteins: spike (S), envelope (E), membrane (M), and nucleocapsid (N), and six accessory proteins: ORF3a, ORF6, ORF7a, ORF7b, ORF8, and ORF10. The non structural proteins are NSP1. NSP2, NSP3, NSP4, NSP5, NSP6, NSP7, NSP8, NSP9, NSP10, NSP11, NSP12, NSP13, NSP14, NSP15, and NSP16.

STRUCTURAL PROTEINS : 

Spike or S Glycoprotein 

The spike or S glycoprotein is a transmembrane protein, with a molecular weight of about 150 kDa, is found in the outer portion of the virus. S protein forms homotrimers protruding on the viral surface and facilitates binding of envelope viruses to host cells via angiotensin-converting enzyme 2 (ACE2). This glycoprotein is cleaved by the host cell furin-like protease into 2 sub units namely S1 and S2. [7]

Nucleocapsid or N Protein

The nucleocapsid, known as N protein, is the structural component of CoV localizing in the endoplasmic reticulum-Golgi region that structurally is bound to the nucleic acid material of the virus. Because the protein is bound to RNA, the protein is involved in processes related to the viral genome, the viral replication cycle, and the cellular response of host cells to viral infections [8]. N protein is also heavily phosphorylated and suggested to lead to structural changes enhancing the affinity for viral RNA [9]

Envelope or E Protein

E protein which is the smallest protein in the SARS-CoV structure that plays a role in several aspects of the virus’ life cycle, such as assembly, budding, envelope formation, and pathogenesis.[8]

Membrane or M Glycoprotein

The membrane or M protein, which is the most structurally structured protein and plays a role in determining the shape of the virus envelope. This protein can bind to all other structural proteins. Binding with M protein helps to stabilize nucleocapsids or N proteins and promotes completion of viral assembly by stabilizing N protein-RNA complex, inside the internal virion.

NON STRUCTURAL PROTEINS OR NSPs :

ACCESSORY PROTEINS :

GENETIC MATERIAL

The SARS-CoV-2 virus belongs to the B lineage of the β-coronaviruses (β-CoVs); this family comprises an enveloped, non-segmented, positive-sense single-stranded RNA virus genome, with a 5′ cap structure and 3′ poly-A tail, allowing to perform as an mRNA for translation of the replicase poly proteins.

Among the known RNA viruses, coronaviruses, which are single-stranded and positive-sense RNA viruses have the largest genome between other RNA viruses, with the GC content ranging from 32% to 43%. [29] [30] The genomic organization includes 5′- leader sequence - ORF1/ab - S - ORF3a - E - M - ORF6a - ORF7a - ORF7b - ORF8 - N - ORF10 -3′ from left to right and lacks the hemagglutinin-esterase gene which is detected in some β-CoVs. [31]

About two-thirds of SARS-CoV-2's RNA comprises ORF1a/b region, which with 16 non-structural proteins (nsp1-16) is considered as the largest ORF. The remaining one-third of the genome near the 3′-terminus contains ORFs encode structural and accessory proteins. [32]

ZOONOTIC ORIGIN 

As defined by the WHO, a zoonoses is any disease or infection that is naturally transmissible from vertebrate animals to humans. Some examples are MERS, and SARS-CoV-1.

The word 'zoonoses' is derived from Greek words 'Zoon' meaning animl and 'Noses' meaning disease. The term was first used and coined by Rudolf Virchow, who used it for communicable diseases. 

CLASSIFICATION BY RESERVOIR HOST : 

Anthropozoonoses

• Infections transmitted to humans from lower vertebrates. 
• Eg - Rabies, Plague, Leptospirosis, etc. 

Zooanthroponoses

• Infections transmitted from humans to lower vertebrates. 
• Eg - Streptococci, Staphylococci, Diphtheria, Human Tuberculosis in parrots and cattles, etc. 

Amphixenoses

• Infections maintained in both humans and lower vertebrates and transmitted in either direction. 
• Eg - Salmonellosis, etc.

CLASSIFICATION BY MODE OF TRANSMISSION :

Direct Zoonoses

• From an infected vertebrate host to a susceptible host [human] by direct contact, or fomite transmission.
• Eg - Rabies, Anthrax, Leptospirosis, etc.

Cyclozoonoses

• Requires more than one vertebrate host species, but no invertebrate needed for completion of life cycle.
• Eg - Taeniasis

Metazoonoses

• Transmitted biologically by invertebrate vectors, in which the agent multiplies and(or) develops.
• Always an extrinsic incubation period before transmission to another vertebrate host.
• Eg - Plague, Leishmaniasis, etc.

Saprozoonoses

• Requires a vertebrate host and a non-animal developmental site [like soil, plant material, pigeon dropping etc] for the development of the infectious agent.
• Eg - Histoplasmosis, Zygomycosis, etc.

TRANSMISSION OF ZOONOSES :

People tend to get infected with zoonotic diseases by five major ways - (Fig : 7.3-17)

Direct Contact

• First is by coming in direct contact with saliva, blood, urine, mucous, feces, or other body fluids of an infected animal. 
• Examples include petting or touching animals, and bites or scratches. 

Indirect/Fomite

• Encountering areas where animals live and roam, or objects or surfaces that have been contaminated with germs. 
• Examples include aquarium tank water, pet habitats, chicken coops, barns, plants, and soil, as well as pet food and water dishes. 

Vector or Water or Food Borne

• Other way could be the transmission by vectors like a tick, mosquito or a flea. 
• The most common way is via faeco-oral route, i.e. the disease could be waterborne or foodborne. [33]
• Eg - 
• Being bitten by a tick, or an insect like a mosquito or a flea. 
• Eating or drinking something unsafe, such as unpasteurized (raw) milk, undercooked meat or eggs, or raw fruits and vegetables that are contaminated with feces from an infected animal.
•  Contaminated food can cause illness in people and animals, including pets. 
• Drinking or coming in contact with water that has been contaminated with feces from an infected animal.

ZOONOTIC ORIGIN OF SARS-CoV-2 : 

Jumping the Species Barrier

The first patients of SARS-CoV-2 worked in the wet animal markets in Wuhan, China. It is believed that SARS-CoV-2 was introduced from the animal kingdom to human populations during November or December 2019. The spillover of SARS-CoV-2 from animals to humans took place at the beginning of December 2019 and clinical cases appeared at the end of December 2019.

Now, several evidences based on genome sequences, the homology of the ACE2 receptor, and the presence of single intact ORF on gene 8 indicate bats as a natural reservoir of these viruses.

However, an unknown animal is yet to be unravelled as an intermediate host. [36][37]Initial investigations on animal source origin of SARS-CoV-2 have inconclusively revealed snakes, pangolins, and turtles. [34] [35]

Recently, a Pomeranian dog as a probable intermediate host was identified; however, such reports are yet to be validated, and research is underway to explore the emergence of this infectious disease at the animal-human interface. [38][39]

A study reported that the SARS-CoV-2 might infect the cats and further transmitted by the infected cat to other cats. [40] Furthermore, along with dogs and cats, the zoo animals like tigers and lions were also reported to get the SARS-CoV-2 infection and exhibit clinical signs such as vomiting, diarrhoea, dry cough, breathing difficulty and wheezing. [41][42]

Spillover of SARS-CoV-2 was also reported in mink farms of Netherlands, further increasing the concern of transmission to humans.

Zoonotic Spillover

Since the beginning of 2002 till the end of 2019, three coronaviruses viz. SARS-CoV, MERS-CoV, and SARS-CoV-2 have caused havoc in the human population globally and will continue to do so.

Earlier identified betacoronaviruses (SARS-CoV and MERS-CoV) were reported in Guangdong province of China in November 2002 and Saudi Arabia in 2012, respectively SARS-CoV-2 is the third zoonotic betacoronaviruses recognized in this century. Both SARS-CoV and SARS-CoV-2 showed prominent similarities in their pathogenesis and epidemics. In both cases, bats were considered as the natural host, and the cold temperature and low humidity in cold, dry winter provided conducive environmental conditions that promoted the survival of the virus in the environment. [43]

Zoonotic spillover is the transmission of pathogens to humans from vertebrate animals. At present, these spillovers are of significant concern as in the past, many spillovers in the form of Nipah, Hendra, Ebola, SARS, MERS, and ongoing COVID-19 involving many animal species like pigs, horses, monkeys, camels, civets, among others, were documented.

Spillover is governed by the interaction of viral-specific proteins like S protein and host ACE2 receptor. [44] Mutations in amino acid sequences of RBDs [Receptor Binding Domains] results in a change in specificity of a receptor, interaction and binding, hence alteration in transmissibility, pathogenicity and cross-species jumping with a predisposition to novel and more severe diseases. [45]

In the case of SARS-CoV-2, RBD of S protein has 10–15 times affinity ACE2 receptor. [45] The enhancement of pathogenicity has been recorded previously too, which was bestowed upon by intermediate hosts, and thus helped in a spillover event.

Transmission to Humans

(Fig : 7.4.3-18) The involvement of intermediate hosts in maintaining and transmitting the virus to susceptible host predisposes humans to novel CoVs leading to the emergence of new diseases in humans.Usually, one or more types of animal hosts are involved in the transmission cycle of CoVs to humans. [44]

Bats have been the natural hosts for most human CoVs of Alphacoronavirus and Betacoronavirus genera. Genome sequence analysis has revealed bats as a natural host for SARS-CoV-2 [44]

In natural or reservoir hosts, CoVs adapts well, however, being unstable RNA viruses, they keep multiplying continuously without producing disease thereby enabling persistence or survivability and accumulation of mutations over the time resulting in the emergence of newer and novel strains of viruses. These unique strains or viruses occasionally spill over to other species including animals or humans, adapting to their body systems and hence broaden the biological host range for evolutionary sustainability; however, results in epidemiological widening of disease sphere as well.

In the context of SARS-CoV-2, snakes, pangolins and bats have been suspected as intermediate hosts since the first cases of COVID-19 had links to Huanan Sea Food Market where different animals, birds, and wild animals were being sold along with seafood items. [46] [47]

Bats are the natural reservoir host of many CoVs.The bat coronavirus, BatCoV RaTG13, has shown higher relatedness to SARS-CoV-2 at the whole genome level and spike gene in particular. [48] Based on Resampling Similarity Codon Usage (RSCU), snakes (Bungarus multicinctus and Naja atra) were suggested as wildlife reservoirs of SARS-CoV-2 and reported to be associated with the cross-species transmission and later it was disapproved by other researchers.

Unfortunately, to date, the intermediate host of the SARS-CoV-2 is abstruse what results in its escalation in the human population around the globe.

INFECTION AND TRANSMISSION 

ROUTES OF TRANSMISSION : 

Respiratory Droplets and Aerosols 

(Fig : 8.1.1-19)The SARS-CoV-2 mainly spread from person to another through small respiratory droplets from the nose or mouth when a person confirmed COVID-19 coughs or exhales. These droplets land on objects and surfaces around the person. Other people may catch the virus by breathing in droplets or touching these objects or surfaces, then touching their eyes, nose, or mouth. [49]

These respiratory emissions can range in size, with large droplets typically referring to those above 5-10 µm in diameter, and small droplets or aerosols referring to those below 5-10 µm diameter. Forceful respiratory actions such as coughing and sneezing can produce a burst of droplets that range in size and could include both large droplets and aerosols that present an exposure risk in close proximity to an infected person.

Under experimental conditions, SARS-CoV-2 has been found to remain viable when airborne over short distances for several hours and in field studies, viable virus has been isolated from air samples at distances greater than two metres from a COVID-19 patient. [50]

Fomite Transmission

(Fig : 8.1.2-20) Contact with contaminated surfaces (fomites) followed by touching of the eyes, mouth or nose is another possible mode of SARS-CoV-2 transmission, although it is not considered to be the main route. Fomites can become contaminated by deposition of droplets, aerosols, sputum or feces, either directly or by cross-contamination by touching an object with contaminated hands. Surfaces that are frequently touched by many people, such as door handles, or faucets may be more important in fomite transmission compared to objects or surfaces that are only touched incidentally and less frequently.

The virus appears to remain viable for longer periods (one to seven days or more) on smooth hard surfaces such as stainless steel, hard plastic, glass, and ceramics and for shorter periods (several hours to two days) on porous materials such as paper, cardboard, and textiles, although viability may be dependent on other factors such as temperature. [51] [52]

Faeco-Oral Route

Generally, many respiratory pathogens, such as influenza, SARS-CoV and MERS-CoV, cause enteric symptoms, so is SARS-CoV-2. In early reports from Wuhan, 2–10% of patients with COVID-19 had gastrointestinal symptoms such as diarrhea or vomiting. [53]

The study found that the detection of SARS-CoV-2 nucleic acid positive in a few feces of patients with confirmed COVID-19 cases indicated the presence of a live virus. Considering the evidence of fecal excretion for SARS-CoV-2, the virus can also be transmitted via the fecal-oral transmission route or re-transmitted through the formation of aerosols in virus-containing feces. 

Blood-Borne Spread

Cytokines (CK) are key factors regulating the immune response caused by many infectious pathogens that can significantly damage host organs and tissues. In the early stages of SARS-CoV infection, cytokine levels in the blood are rapidly elevated, the elevation of which is associated with the progression of lung invasion and injury [54]

The concentrations of various cytokines in the blood of severe patients with SARS-CoV-2 infection were significantly higher than those of non-serious patients. The concentration of cytokines can indicate the severity of the disease.

In severe cases of infection, immune system was overstimulated, resulting in a cytokine storm that leads to severe immune damage to the lungs and other organs. More and more cases reported that the brain, kidney, and heart impairment induced by the virus infection, may contribute to multi-organ failure and death eventually. [55]

Massive accumulation of SARS-CoV-2 leads to a surge of immune cells and more and more pro-inflammatory cytokines, resulting in a rapid increase in CK levels in the blood, or releasing more virus particles into the blood circulation. The virus and cytokines positively induce high expression of ACE2 in the intestinal epithelium and other organs which accelerated over-expression of ACE2 and viral binding, causing systemic infections with the virus.

PROCESS OF INFECTION : 

Introduction

(FIG : 8.2.1-22) Viruses enter cells and initiate infection by binding to their cognate cell surface receptors. The expression and distribution of viral entry receptors therefore regulates their tropism, determining the tissues that are infected and thus disease pathogenesis. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third human coronavirus known to co-opt the peptidase angiotensin-converting enzyme 2 (ACE2) for cell entry. The interaction between SARS-CoV-2 and ACE2 is critical to determining both tissue tropism and progression from early SARS-CoV-2 infection to severe coronavirus disease 2019 (COVID-19).

Angiotensin-converting enzyme 2 is a zinc membrane-bound metalloproteinase that acts as a carboxypeptidase able to hydrolyze Ang I to Ang-(1-9) and Ang II to Ang-(1-7). ACE converts angiotensin I to angiotensin II, a highly active octapeptide that exhibits both vasopressor (vascular contraction to increase blood pressure) and proinflammatory activities. The carboxypeptidase activity of ACE2 converts angiotensin II to the heptapeptide angiotensin-(1-7), a functional antagonist of angiotensin II.

The Renin Angiotensin System (RAS) seems to be involved in COVID-19 natural course, since studies suggest the membrane-bound Angiotensin-converting enzyme 2 (ACE2) works as SARS-CoV-2 cellular receptor. The renin–angiotensin–aldosterone system (RAAS) is a critical regulator of blood volume and systemic vascular resistance. While the baroreceptor reflex responds in a short-term manner to decreased arterial pressure, the RAAS is responsible for more chronic alterations. It is composed of three major compounds: renin, angiotensin II, and aldosterone. These three act to elevate arterial pressure in response to decreased renal blood pressure, decreased salt delivery to the distal convoluted tubule, and/or beta-agonism. Through these mechanisms, the body can elevate the blood pressure in a prolonged manner.

The ACE2 receptor is present in most organs: it is attached to the cell membrane of mainly lung type II alveolar cells, enterocytes of the small intestine, arterial and venous endothelial cells, and arterial smooth muscle cells in most organs. Since the introduction of virus is mostly through the respiratory pathway, most cases of infection are isolated in those areas.

Entry into the Cell via ACE2

(Fig : 8.2.2-23) Like all coronaviruses, SARS-CoV-2 utilizes the S glycoprotein to promote entry into the host cell. This protein contains two functional domains: an S1 receptor-binding domain (RBD), and a second S2 domain that mediates the fusion of the viral and host cell membranes.

SARS-CoV-2 S protein binds to the ACE2 receptor on the host cell, initially through the S1 receptor binding domain. The S1 domain is then shed from the viral surface, allowing the S2 domain to fuse to the host cell membrane. This process is dependent upon activation of the S protein, by cleavage at two sites (S1/S2 and S2’) via the a cellular serine protease, TMPRSS2, and, in a smaller rate, an endosomal cysteine protease, cathepsin B, and L (CatB/L) (Hoffmann et al., 2020)[70].

Furin cleavage at the S1/S2 site may lead to conformational changes in the viral S protein that exposes the RBD and/or the S2 domain. TMPRSS2 cleavage of the SARS-CoV-2 S protein is believed to enable the fusion of the viral capsid with the host cell to permit viral entry[71][72]

Exposure of the RBD in the S1 protein subunit creates an unstable subunit conformation. Consequently, during binding, this subunit undergoes conformational rearrangement between two states, known as the up and down conformations. The down state transiently hides the RBD, while the up state exposes the RBD, but temporarily destabilizes the protein subunit[73][74][75]. Within the trimeric S protein, only one of the three RBD is present in the accessible conformation to bind the human Angiotensin 2 (hACE2) host cell receptor[76].

The critical functions of the SARS-CoV-2 S protein, ACE2, and the Furin and TMPRSS2 enzymes in binding and mediating viral entry to the host cell make these proteins key targets for drug development and viral inhibition in the efforts against COVID-19.

Analysis of COVID-19 and SARS-CoV-2

Viral Gene Expression

(Fig : 8.2.3-24) The release of the coronavirus genome into the host cell cytoplasm upon entry marks the onset of a complex programme of viral gene expression, which is highly regulated in space and time.

The translation of ORF1a and ORF1b from the genomic RNA produces two polyproteins, pp1a and pp1ab, respectively. Sixteen non-structural proteins are co-translationally and post-translationally released from pp1a (nsp1–11) and pp1ab (nsp1–10, nsp12–16) upon proteolytic cleavage by two cysteine proteases that are located within nsp3 (papain-like protease; PLpro) and nsp5 (chymotrypsin-like protease).

Proteolytic release of nsp1 is known to occur rapidly[77], which enables nsp1 to target the host cell translation machinery[78],[79],[80]. Nsp2–16 compose the viral RTC and are targeted to defined sub cellular locations where interactions with host cell factors determine the course of the replication cycle[81],[82],[83]. Nsp2–11 are believed to provide the necessary supporting functions to accommodate the viral RTC (Replication/Transcription Complex), such as modulating intracellular membranes, host immune evasion and providing cofactors for replication, whereas nsp12–16 contain the core enzymatic functions involved in RNA synthesis, RNA proofreading and RNA modification [84],[82].

RNA synthesis is performed by the nsp12 RNA-dependent RNA polymerase (RdRP) and its two cofactors nsp7 and nsp8, the latter with proposed primase or 3′-terminal adenylyltransferase activity[84],[82],[85],[86]. Notably, nsp14 provides a 3′–5′exonuclease activity that assists RNA synthesis with a unique RNA proofreading function[87] .

The establishment of the viral RTC is crucial for virus replication and thus a promising target for antivirals against SARS-CoV-2. One such target is Mpro, which resides in nsp5. Mpro releases the majority of nsps from the polyproteins and is essential for the viral life cycle. Furthermore, as Mpro is very sequence specific, compounds that structurally mimic those cleavage sites can specifically target the viral protease with little or no impact on host cellular proteases[88],[89],[90].

RNA Synthesis

(Fig : 8.2.4-25) Viral genomic replication is initiated by the synthesis of full-length negative-sense genomic copies, which function as templates for the generation of new positive-sense genomic RNA. These newly synthesized genomes are used for translation to generate more nsps and RTCs or are packaged into new virions.

A hallmark of coronaviruses and most members of the order Nidovirales is the discontinuous viral transcription process, first proposed by Sawicki and Sawicki[91], that produces a set of nested 3′ and 5′ co-terminal subgenomic RNAs (sgRNAs)[91],[92].

During negative-strand RNA synthesis, the RTC interrupts transcription following the encounter of transcription regulatory sequences (TRSs) that are located upstream to most ORFs in the 3′ one-third of the viral genome. At these TRS elements, also called TRS ‘body’, the synthesis of the negative-strand RNA stops and is re-initiated at the TRS adjacent to a leader sequence (TRS-L) located at about 70 nucleotides from the 5′ end of the genome [91],[92],[93],[94],[95].

This discontinuous step of coronavirus RNA synthesis involves the interaction between complementary TRSs of the nascent negative strand RNA (negative-sense TRS body) and the positive strand genomic RNA (positive-sense TRS-L). Upon re-initiation of RNA synthesis at the TRS-L region, a negative strand copy of the leader sequence is added to the nascent RNA to complete the synthesis of negative-strand sgRNAs.

The discontinuous step of negative strand RNA synthesis results in the production of a set of negative-strand sgRNAs that are then used as templates to synthesize a characteristic nested set of positive-sense sg mRNAs that are translated into structural and accessory proteins. Although the coronavirus sg mRNAs are structurally polycistronic, it is assumed that they are functionally monocistronic.

Expression of Structural and Accessory Proteins 

The ORFs encoding the structural proteins (that is, S protein, envelope (E) protein, membrane (M) protein and nucleocapsid (N) protein) are located in the 3′ one-third of coronavirus genomes. Interspersed between these ORFs are the ORFs encoding for so-called accessory proteins.

In general, coronavirus structural proteins assemble and assist in the budding of new virions at the endoplasmic reticulum (ER)-to-Golgi compartment that are suggested to exit the infected cell by exocytosis [96],[97],[98]. These proteins are translated from positive sense sg mRNA.

At least five ORFs encoding accessory genes have been reported for SARS-CoV-2: ORF3a, ORF6, ORF7a, ORF7b and ORF8 (GenBank entry NC_045512.2). In addition, ORF10 has been postulated to be located downstream of the N gene. However, not all of these ORFs have been experimentally verified yet and the exact number of accessory genes of SARS-CoV-2 is still debated [93],[99].

Replication Compartment 

After translation, the structural proteins, along with accessory proteins and its genome, form new viruses (virion) capable of infecting other cells. The mechanism of the formation of virions is still being researched and is out of scope of this project.

SYMPTOMS of COVID-19

Infection of SARS-CoV-2 can lead to symptoms, both common and fatal. The most common symptoms are : [56]

Apart from the above symptoms, a part of the population affected shows the following symptoms :

DIAGNOSIS

There are many different types of tests available for the fast diagnosis of COVID-19, but bellow are the four main tests available in India :

RT-PCR is the test widely used in India and around the world. The test detects the virus’ RNA, which will be present in the body before antibodies form or symptoms of the disease are present, and tells whether or not someone has the infection very early on. It proceeds by converting the RNA to DNA through a process called ‘reverse transcription’, before detecting the virus. (Fig 10-27)

Rapid Antibody tests are fast, inexpensive, and can be used to gauge the extent of infection within a community. Unlike RT-PCR, antibody tests require a blood sample to determine whether the human body has antibodies for coronavirus. Since the results are not 100 per cent reliable (they can give false positives), the ICMR has advised that if a person tests positive through a rapid test, they have to undergo a confirmatory RT-PCR test before treatment. (Fig : 10-28)

Like RT-PCR, the Rapid Antigen test too, seeks to detect the virus rather than the antibodies produced by the body. It has been approved by ICMR for use in containment zones and healthcare settings. The test is reliant on the amount of virus, or the viral load, in a nasal swab. An antigen refers to any toxin in the body that triggers an immune response. (Fig : 10-29)

TruNat test, commonly used for detecting tuberculosis and HIV, works on the same principle as RT-PCR, but with a smaller kit, and produces faster results. ICMR recently approved TrueNat, manufactured by a Goa-based company, for screening and confirmation for COVID-19. (Fig : 10-30)

Other than the above tests, there are some other confirmatory tests which could be used to ensure an accurate diagnosis like:

VULNERABLE POPULATION

Severe illness means that a person with COVID-19 may require :

• hospitalization, 
• intensive care, or a 
• ventilator to help them breathe, or 
• they may even die. 

Risk for severe illness with COVID-19 increases with age, with older adults at highest risk. Certain medical conditions can also increase risk for severe illness. People at increased risk, and those who live or visit with them, need to take precautions to protect themselves from getting COVID-19.

Analysis of COVID-19 and SARS-CoV-2

AGE : 

Older adults are at greater risk of requiring hospitalization or dying if they are diagnosed with COVID-19. As you get older, your risk of being hospitalized for COVID-19 increases. (Fig 11-32)

PRE-EXISTING CONDITIONS : 

Adults of any age with the following conditions are at increased risk of severe illness from the virus that causes COVID-19 like,

• Cancer
• Chronic kidney disease
• COPD (chronic obstructive pulmonary disease) 
• Down Syndrome 
• Heart conditions (heart failure, coronary artery disease, or cardiomyopathies) 
• Immunocompromised state from solid organ transplant 
• Obesity (body mass index [BMI] of 30 kg/m2 or higher but < 40 kg/m2) 
• Severe Obesity (BMI ≥ 40 kg/m2) 
• Pregnancy 
• Sickle cell disease 
• Smoking 
• Type 2 diabetes mellitus

Moreover, adults of any age with the following conditions might be at an increased risk for severe illness from the virus that causes COVID-19 :

• Asthma (moderate-to-severe) 
• Cerebrovascular disease (affects blood vessels and blood supply to the brain) 
• Cystic fibrosis 
• Hypertension or high blood pressure 
• Immunocompromised state from blood or bone marrow transplant; immune deficiencies; HIV; use of corticosteroids, etc 
• Neurologic conditions, such as dementia 
• Liver disease 
• Overweight (BMI > 25 kg/m2, but < 30 kg/m2) 
• Pulmonary fibrosis (having damaged or scarred lung tissues) 
• Thalassemia (a type of blood disorder) 
• Type 1 diabetes mellitus 

People who also need extra precaution fall under these categories :

• People Living in Rural Communities 
• People with Disabilities 
• People with Developmental & Behavioral Disorders 
• People Experiencing Homelessness 
• Pregnant People & Breastfeeding 
• Racial & Ethnic Minority Groups (Fig 11-33)

PREVENTATIVE MEASURES

Actions to Protect Ourselves in Public : 

(Fig 12.1-34)

• Avoid touching your face , especially your eyes, nose and mouth. 
• Wash your hand frequently with soap and water or use alcohol-based rub. 
• Seek immediate medical advice if you have fever, cough or are experiencing breathing difficulties. 
• When coughing or sneezing, discard the used tissue immediately into a closed bin. 
• Maintain distance of at least 1 metre from someone who is coughing or sneezing 
• When coughing or sneezing, cover your mouth and nose with flexed elbow or tissue. 
• If you have cough, fever, and difficulty in breathing, wear a mask correctly and seek medical advice. 

Actions to Protect Ourselves at Home : 

• Clean your home regularly, particularly frequently touched surfaces like door knobs, refrigerator handles, etc. 
• Stay home stay safe. Stay physically fit. Exercise regulary. Eat a nutritious diet. Don’t smoke. 
• Follow the Golden Rule. Wash your hands frequently with soap and water or use alcohol based hand-rub. 
• Stay positive. Avoid alarmist news. Be connected to friends and family. Have a hobby. 
• If any member of the household shows symptoms of Covid-19, seek medical advice and follow your local health authority's guidance.

Message for the Elderly and those having Other Diseases : 

(Fig 12.3-35)

• Take care if you are elderly 
• Avoid Exposure: Stay at home. Wash hands or use alchohol-based rub. 
• Avoid touching your face. 
• Eat nutritious food, exercise regularly. Stay connected with friends and family. 
• Be prepared: Keep a supply of essential medicines. Keep all helpline numbers handy. 
• Keep at least 1 meter apart from others. 

Precautions for Pregnant and New Mothers : 

(Fig 12.4-36)

• Stay at home and avoid meeting outsiders. Wash your hands with soap and water or use alcohol-based hand rub. Prepare for delivery and make arrangements to reach hospital. Its safer to deliver in a hospital, even during the COVID-19 pandemic.
• Always be alert on pregnancy related warning signs. Continue visiting your doctor or midwife for regular check ups. Immediately contact the doctor in case of symptoms like pain in abdomen, bleeding, watery discharge and severe headache. In case of an emergency visit nearest hospital. 
• Wash hands before and after touching and feeding your baby. Wash clothes and sterilize all utensils & articles that come in contact with you or your baby. 
• Breastfeed within 1 hour of birth and continue. It protects your baby from infections. Keep your baby close to you. Practice skin-to-skin contact (Kangaroo care) for small or preterm babies. 
• If the mother is COVID positive, wear a medical mask while breastfeeding the baby. Wash your hands with soap and water or use alcohol-based hand rub before feeding. Routine clean and disinfect surfaces around you. Keep at least 1 meter distance from others.

Precautions at Work Places : 

(Fig 12.5-37)

• Keep physical distance of at least one metre.
• Wear a mask when close to others.
• Minimise the need for physical meetings by teleconferencing.
• Defer or suspend work place events and social gatherings.
• Take special care if you have pre-existing medical conditions, are pregnant or above 60 yrs in age.
• Wash your hands frequently with soap and water or use alcohol-based hand rub.
• Ensure respiratory hygiene by covering mouth and nose with flexed elbow/tissue during cough or sneeze.
• Avoid physical contact like hugging, touching, shaking hands, etc.
• If you show symptoms of COVID-19; such as sore throat, fever, difficulty in breathing, then isolate yourself, take medical advice and do not come to work.

Taking these extensive measures to prevent the spread of a pandemic is of utmost importance. Social distancing, wearing masks, and using disinfectants are a must nowadays. Although many are lathering themselves with sanitizers, people are not aware of the risks and hazards of the long term exposure to these chemical disinfectants. You can read about this in the post 'Hazards of Disinfectants' where we discuss about the disinfectants and their by-products, their toxicity and effects. While there is no need to panic, we should start moving towards a more sustainable and holistic alternative. You can read about one such alternative on 'Aloe Vera : A Sustainable Alternative'.

Analysis of COVID-19 and SARS-CoV-2

REFERENCES

Analysis of COVID-19 and SARS-CoV-2