A CONSICE BOOK OF COVID - 19 A CONSICE BOOK OF COVID 19 ASHIK TN B – pharm 2nd year student 7 /14/2020 Basics of COVID - 19 THE COVID - 19 ashik.tn THE COVID - 19 Disease are now not a new wonder for humans it was been there far earlier than human started to see the world starting from the phytoplankton to the complex homosapions everything has been changing so fast in their both genetic and physical structures the change in the genetic make up of the genetic material is known as genetic mutation which helps the corresponding species thrive in the rapidly changing environment and this has become a curse for the humans leading to the origination of new mutants of micr oorganisms ie. bacteria virus amoebas plasmodium fungi protozoa algae etc the main species that is studied for their causative disease are bacteria virus and fungi though other species cannot be omitted but they are found more prominent and can cause serious illness to humans and animal species not all the microbes are found harmful to us but can be used in various to help human mankind ie . in bacterial species - lact obacillus, bifidobacteria, finds uses in various fields such as food processing, fermentation, etc and virus are not found used food processing and biochemical processes but finds use in medicinal applications ie specific viruses can be used as an host to carry the required substance for treatment of cancers to inhibit the process of cell division and also finds use in genetic engineering etc and also these microbes can also cause serious illness and lethal disease to human mankind ie bacteria can cause the diseases like tuberculosis (M .kansassi) meningitis (mainly by streptococcus pneumoniae) to the most dangerous diseases such as MREA(staphylococcus aureus) and virus caused diseases like AIDS(HIV virus) hepatitis, herpes to the most dangerous diseases such as Ebola,smallpox(which is now completely eradicated), COVID - 19 (SARS CoV – 2) etc . Bacterial diseases can be treated with antibiotics ie penicillin, amoxicillin, chloramphenicol etc and viral disease can be treated upto an extend with antiviral drugs ie abcavir(for hiv),acyclovir (for herpes, chickenpox) etc The current prevailing pandemic COVID - 19 is worsening the condition. T he COVID - 19 is caused by a RNA virus called the SARS CoV - 2 ( the name “ corona ” due to crown like appearance in EMC (electron micorscopic studies) study's) it was estimated that the first case was reported in 31 December 2019 in which the virus originated from the wuhan sea food market in China jianghan district and reports found that 1 THE COVID - 19 ashik.tn there were also intense selling of wild animal meats and is estimated that the virus would have been originated from here the latest report finds that the virus has been spread over 140 countries as per WHO and a reported cases of 7.55M worldwide and is still not slowed and having an estimated death toll of 423 ,000 deaths across worldwide The virus is a type of ssRNA virus having spiked projections on the outer shell of its protein sheath and inside lays the genetic material RNA this virus resembles the SARS CoV - 2 which caused SARS (severe acute respiratory syndrome) in 2002 and this virus attaches to the receptors on the alveolar cells called type 2 pnumocytes called ACE2 (human angiotens in converting enzyme 2 ) and the genetic material is transferred into the cell and the multiplication leads to new infected cells. This disease mainly affects the respiratory system the by resulting in clogging goblet cell which produces mucus and the cilia cells and leading to imparted fluid build (pneumonia) in the air sacs of lungs and can eventually cause respiratory arrest and the patient's who have been effected by the virus have to be incubated in severe conditions the incubation period of the virus i s about 14 days the virus is most likely to effect old people and the chances are higher for the patients accompanied with other prevailing disease conditions such hypertension , diabetics , heart disease etc and report s show that the diseases is also likely to effect the children not regarding their age group as per the report. thi s disease spreads rapidly mainly by human to humans by droplet s pread the person who is in contact at a radius of 1 - 2 meter can have high chances of getting infected they can get into the human body by touching the hands which is contaminated by the virus in nose, mouth, eye etc. Corona Virus emerging from infected cells 2 THE COVID - 19 ashik.tn The structure of corona virus Structures of the virus and its functions • S spikes : for binding to the ACE 2 receptor C ORONA VIRUS IN ELECTRON MICROSCOPE 8 THE COVID - 19 ashik.tn • Hemigutinin estera sedimer : helps in the entry of the virus to virus along with spike protein • M protein • E protein • Nucliocapsid protein • E nvelop • Viral RNA which Is +SSRNA(positive single stranded RNA) Types of corona virus 1. Human corona virus 229E or HcoV - 229E – alpha corona virus 2. Human corona virus OC43 – alpha corona virus 3. SARS coV – beta corona virus 4. Human corona virus NL63 ( Netherlands origin) – alpha corona virus 5. HKV - 1 (Honkong origin ) – beta corona virus 6. MERS CoV - beta corona virus 7. SARS CoV - 2 – beta corona virus which cause COVID 19 9 Attachment of SERS CoV - 2 on type 2 pnumocytes ( lungs cells ) THE COVID - 19 ashik.tn How the virus acts on the human bod y E x posure to the the virus It enters the respiratory tract It reaches the lungs through the trachea bronchi ,bronchioles and to finally alveoli. It attaches to the ACE - 2 receptors and transmembrane sere protease type 2 ( SMPRSS - 2) receptors of the cells of alveoli called the type 2 pnumocytes Transfer of the genetic material of the virus ( SS RNA ) to the type 2 cells present in the lungs along with multiplication of the genetic material or MRNA by the enzyme ssRNA or (RNA depend RNA polymerase ) generates multiple copy’s of the viral RNA The SS RNA of the virus is used by the lung cells to replication by the ribosomes present in the lung ce lls The ribosome convert the SS RNA to pol y proteins by tansilation The poly proteins are converted into the viral structures such as pappalomers or glycoprotein spikes outer protein coat from the golgi apparatus etc TRANSILATION BY ENZYME PROTEASE BOTH THE VIRAL RNA AND VIRAL STRUCTURS COMBINE TO FORM AN NEW VIRUS THIS AS THESE COPYS MULTPLY LEADING TO BURST OF CELLS OR APOPTISIS AND THE FORMED VIRUS GETS OUT OF THE CELLS BY A PROCESS CALLED EXOCYTOSIS In the cell Out of the cell 10 New virus EXOCYTOSIS ENDOCYTOSIS THE COVID - 19 ashik.tn Histology slide of lungs of COVID 19 infected patient Diagrammatic representation of viral multiplaction 13 THE COVID - 19 ashik.tn X ray findings of a COVID – 19 patient The patient required mechanical v entilation and was admitted to intensive care. During her stay in ICU, poor evolution to respiratory distress syndrome and to multi - organic failure. The patient died 24 hours later. Imaging findings: a) At admission : Ill - defined bilateral alveolar consolidation with peripheral distribution. b) 4 hours later : Radiological worsening, with affectation of lower lobes. Endotracheal tube and central venous line were required. c) 24 hours : Bilateral alveolar consolidation. d) 48 hours: Radiological worsening. Bilat eral alveolar consolidation with panlobar affectation. e) 72 hours : Bilateral alveolar consolidation with panlobar affectation, with typical radiological findings of ARDS. 24 hours later the patient passed away. chest films of a 72 - year patient admitted with acute respiratory failure, fever (38ºC) and dyspnoea. And was tachypneic (30bpm), with lymphopenia and low oxygen saturation (SpO2 85%). During first four phases of disease progression Pneumonia progressed to ARDS ( severe cond ition of ARDS ) 14 THE COVID - 19 ashik.tn when the type 2 pnumocyetes are damaged causes by apoptosis it causes the release of inflammatory mediators The inflammatory response activate the macrophages which when stimulated release cytokines su ch as IL - 1(interleukin - 1), IL - 6 ( interleukin - 6 And TNF - alpha (tumour neurotic factor ) ,IL - 8(interleukin - 8),along with gamma interferons (IFN - gamma) These cytoki nes IL - 1, IL - 6 and TNF – alpha acts on endothelial cells of the alveolar capillary causing vasco dilation and increase in the capillary pearmibilty which leads to which leads to leakage of the plasma fluid to the interstitial space surrounding alveoli resu lts in the accumulation of the interstitial fluid into the alveoli ( alveolar e dema ) The increased alveolar accumulation leads to the decreased surfactant concentration ( surfactant is produced by the type 1 pnumocytes to decrease the surface tension or to prevent collapsing of the of the alveoli ) .The decreased concentration of the surfa ctant leads to the collapse of the alveoli disrupting the alveolar gas exchange leading to decrease PO2 ( hypoxemia ) and increased PCO2(hypercarbia) which leads to increased WOB ( work of breathing , causes increases forceful inspiration ) The action of the cytokines trigger the migration of the nutrophills to the alveoli acts upon the virus releasing reactive oxygen species and proteases to destroy the virus . the reactive oxygen species an d proteases acts on the walls of the the alveoli causing damage to the alveolar wall causin g damage in type 1 and type 2 cells in alveoli which leads to the accumulation of the damaged cells in the alveoli (consolidation) which effects the gas exchange lea ding t o the decrease PO2 ( hypoxemia ) and increased PCO2(hypercarbia) which causes the accumulation of carbonic acid which can lead to respiratory acidosis. Effect on CNS Physiological effect on respiratory system The IL - 1 , IL - 6 along with TNF alpha in high concentration effec ts the thermoregulatory centre ( hypothalamus ) to release the prostaglandins ie . PGE - 2 etc which causes pyrexia or fever The IL(interlukins),prostakinins with other cytokinines stimulate the the vagus nerve to introduce cough reflex commonly dry cough and also productive cough. 11 Due to the Interleukins - 1,6,8 etc there is an increase of adhesion proteins called adhesion protein molecule known as VCAMS( vascular capillary adhesion molecules ) in endothelium these molecules helps in the adhesion of RBC to transfer to the alveoli due to the increase in the VCAMS there is more adhesion of wbc , nutrophills, and macrophages which increases th e inflammatory response of the alveolar cells THE COVID - 19 ashik.tn Effect on circulatory system The inflammatory response causes SIRS ( systemic inflammatory response syndrome) starts to spread t o the systemic circulation leading to the increase in the capillary permeability of the systemic circulation which increase the accumulation of the plasma fluid to the interstitial space simultaneously also causes vaco dilation thus causing decrease total peripheral resist ance and decreased blood volume causing the decrease in blood pressure or hypotension causes the the decrease in the perfusion of blood to the organs which can lead to septic shock which may lead to organ failure pulmonary embolism in severe cases of the disease there is an increased production of the cytokines by the alveolar macrophages this is called cytokine storm due to the high activities of cytokines which can lead to decrease in procougalance (increase in coagulation ) and s imultaneously and decrease in anticou a galance property which can potentially lead to formation of a clot(emboli) in the pulmonary capillaries called pulmonary embolism Effect on body summary ▪ Effect of senses : decrease in olfactory functions , decrease in taste , and cause sore throat ▪ Effect on respiratory system : cause viral pneumonia , ARDS acute distress respiratory syndrome SIRS systemic inflammatory response syndrome which eventually lead to MSOF mul ti system organ falure, pulmonary edema ▪ Effect of heart : decrease the cardiac function which leads to cardio myopathy ▪ Effect On GI system : causes abdominal pain nausea vomiting and sometimes diaherroea can also occur ▪ Effect on renal system : decrease the renal function and can lead to oligourea ( less urine output) ▪ Effect on liver : decreased liver functions causing metabolic disturbances 12 THE COVID - 19 ashik.tn Common signs and symp toms Precautions and safety concerns ▪ always be aware of the location of spread of the disease ▪ Follow the directions of your local health authority. ▪ Stay home if you feel unwell. ▪ Include food with vitamin c for better immunity ▪ use only boiled water for drinking ▪ never do self treatment if showing signs of disease ▪ maintain a proper body hygiene( change the wearing after you visited places prone to the disease an wash with soap) ▪ always wash your hands for 20sec after reaching home and before touching your face ( the nano particles in the soap helps to break the lipid layer of virus coat) or use hand sanitizer of alcohol conc of ~60% ▪ al ways wash your hands for 20sec after reaching home and before touching your face ( the nano particles in the soap helps to break the lipid layer of virus coat) ▪ Seek immediate medical attention if you have serious symptoms. Always call before visiting your doctor or health facility Most common symptoms : 1. fever 2. dry cough 3. tiredness Less common symptoms : 1. aches and pains 2. sore throat 3. diarrhoea 4. conjunctivitis 5. headache 6. loss of taste or smell 7. a rash on skin, or discoloration of fingers or toes Serious symptoms : 1. difficulty breathing or shortness of breath 2. chest pain or pressure 3. loss of speech or movement On average it takes 5 – 6 days from when someone is infected with the virus for symptoms to show, however it can take up to 14 days. 3 THE COVID - 19 ashik.tn How soap helps in eliminating corona virus The SARS coV 2 virus contains an outer most coat which is made up of bilayer lipid membrane the nano particles present in the soap is hydrophobic in nature there for it is has more tendency to attach to the lipid membrane of the the viral coat there for disrupting the arrangem ent of the lipid membrane which leads to the rupture of the viral coat leading to elimination of the virus 4 THE COVID - 19 ashik.tn How a sanitizer helps in eliminating the corona virus The important ingredients of a hand sanitizer is alcohol of concentration of approx 70% ,hydrogen peroxide 10%, glycerine 15% and essential oil such as aromatic oils or perfuming agents etc and colour if nessery. there are chances that the virus can get entrapped in our hands in which we may get infected from t he common reason for this is the formation of the oily layer in the palm which is ambien t for its survival. the function of the alcohol is to eliminate the oily layer of the skin surface which does not allow the entrapment of the virus. And the H2O2 (hydr ogen peroxide) helps in the elimination of the bacterial and fungal spores. The contac t of alcohol on the skin can lead to dry hands due to its volatile in which the glycerine comes into play by acting as a humificant and moisturises the hand. 5 THE COVID - 19 ashik.tn How wearing masks helps to eliminate corona virus The main mode of the spread which is estimated is dro plet spread and the droplet can travel a distance of 1to2 meters and thus in a conversation it is likely to get infected and masks also serves a barrier from touching our nose or mouth and face shields helps in breaking often contact with our eyes Types of masks ✓ Cloth masks its for daily use and and does not provide full protection and also does not effective in preventing the entry of the virus in a full extent but can be used to prevent spread to others and for a profalatic 6 THE COVID - 19 ashik.tn measure always use a bilayer cloth ma sks as possible for better protection ✓ Surgical masks it can be used for people who is actively involved in medical fields such as in people working in sampling sections , nurses, pharmacy and people who are working in sales in markets (which sale important stuffs only) and these should be u sed for only 6 hrs only and should be disposed properly ✓ N95 respirator masks these masks are ment to be used in for health workers who are in charge of treating the covid 19 patients and tiese provide a good proctection from viruses and also 95% of the particles are captured by the masks 7 THE COVID - 19 ashik.tn D iagonisis Taking swa b from nasopharyngeal swab RT - PCR test procedure mechanism 15 THE COVID - 19 ashik.tn Treatments Isothermal amplification assays A - Bilateral ground ‐ glass opacities in the upper lobes with a rounded morphology B - Bilateral ground ‐ glass opacities in the upper lobes with a rounded morphology. shows bilateral ground ‐ glass and consolidative opacities with a striking peripheral distribution C and D - this CT shows bilateral consolidative opacities, with a striking peripheral distribution in the right lower lobe and with a rounded morphology in the left lower l obe E and F - shows an area of faint ground ‐ glass opacification in the left upper lobe with a ring of denser consolidation “reverse halo” Imaging of chest shows the progressiveness of the disease 16 THE COVID - 19 ashik.tn ▪ Treatments include treating with antiviral drugs such as randasmvier, retenovier etc ▪ Hcq is widely used for its treatment hydroxy chloroqunine which is anti malarial drug ▪ Fluid therapy ▪ Oxygen therapy ▪ Extracorporenal oxygenation therapy ▪ R espiratory support with ventilator Ramde siver is nucleotide pro drug that inhibits viral RNA polymerase has shown invitro activity against SARS CoV - 2 Hcq or hydroxyl chloroqunine acts by increasing the ph within the intracellular vacuoles and alter processes such as protein degradation by acedic hydrolaces in the lysosome assembly of macromolecules in the endosomes and prosttranslation modification of protein in golgi apparatus 17 THE COVID - 19 ashik.tn Some myths abought COVID – 19 Myth 1 : C OVID – 19 can be cured with antibiotics ? Fact : covid - 19 cannot be cured with antibiotics and it is given to treat any bacterial infection prevailing or developed with it Myth 2 : prolonged use of masks cause CO2 intoxication and lead to O2 deffecency ? Fact : th e masks which properly worn cannot cause any kind of respiratory problems Myth 3 : people with mild and moderate symptoms cannot recover from it ? Fact : people with mild and moderate symptoms can recover from it Myth 4 : Does COVID - 19 only affect old people, meaning young people don’t have to worry ? Fact : While COVID - 19 can be more dangerous in older people, anyone can get it including young people, some of whom become seriously ill. While we don’t yet fully understand why some people get more serious symptoms, we do know that young people are more likely to develop serious symptoms if they have certain underlying health conditions, for example asthma, heart conditions or untreated HIV Myth 5 : Can COVID - 19 spread in warm sunny weather ? Fact : COVID - 19 can survive temperatures higher than 25C. You can catch it no matter how sunny and warm it is. So, whatever the weather you should follow the official advice to protect yourself from the virus Myth 6 : Will drinking lots of hot drinks stop COVID - 19 ? Fact : There is no drink hot or cold that will protect you from COVID - 19 or cure the illness. So far, there’s no proven cure for COVID - 19 but most people recover by themselves. Taking paracetamol, drinking lots of liquids, and getting enough rest can help you man age your symptoms Myth : Will most people who g et COVID - 19 get very sick or die? Fact : This statement is untrue. As we mentioned above, COVID - 19 is only fatal for a small percentage of people Myth 8 : Can Black and African people get COVID - 19 ? Fact : Anyone can get COVID - 19, regardless of race or skin colour. Older people and people with other health conditions, such as asthma, heart diseases and diabetes, are more at risk of getting seriously ill. 18 THE COVID - 19 ashik.tn Summary The outbreak of corona virus disease 2019 (COVID - 19) has created a global health crisis that has had a deep impact on the way we perceive our world and our everyday lives. Not only the rate of contagion and patterns of transmission threatens our sense of agency, but the safety measur es put in place to contain the spread of the virus also require social distancing by refraining from doing what is inherently human, which is to find solace in the company of others the virus whic h cause their disease is called SARS CoV2 which causes respi ratory illness conditions such as pneumonia which ultimately leads to ARDS which further progresses to become fatal the. All people can get infected by the virus but researches find that the old p eople with pre - existing comorbidities are more vulnerable to get infected. Covid 19 directly impacts the lungs and damages the alveoli (tiny air sacs). The function of the alveolus is to transfer oxygen to the blood vessels. These blood vessels or capillaries carry the oxygen to the RBCs (Red blood cells). It is th e RBCs that finally deliver the oxygen to all the internal organs in the body. The virus works by damaging the wall and the lining of the alveolus and capillaries. The debris from the damage, which is plasma protein accumulates on the alveolus wall and thi ckens the lining. As the walls’ thicken, the transfer of oxygen to the red blood cells is impaired. The thicker the wall gets, the more difficult it gets to transfer oxygen to the red blood cells, which causes difficulty in breathing as the body is running short of oxygen. And the lack of oxygen to the internal organs results in a deficit in the body and impairs the functioning of the organs. At this juncture, the body fights to increase oxygen. intake Signs and symptoms of coronavirus disease 2019 (COVID - 1 9) may appear two to 14 days after exposure. This time after exposure and before having symptoms is called the incubation period. Common signs and symptoms can include fever, cough, tiredness, Shortness o f breath or difficulty breathing, Muscle aches, Chills, Sore throat, Loss of taste or smell, the diagnosis include antibody test , RT - PCR , imaging etc. treatments Currently, no medication is recommended to treat COVID - 19 , and no cure is available. Antibio tics aren't effective against viral infections such as COVID - 19 . Researchers are testing a variety of possible treatments. Some of the treatments include treating with antiviral drugs , fluid therapy , rest , pain relievers etc While a vaccine for Covid 1 9 is still under work and might take a while before it is tested and certified for usage, our best bet right now is to stay safe, stay indoors and avoid crowds. A few simple precautions like maintaining hygiene and sanitizing your environment will go a lon g way in countering the spread of Covid 19 infection 19