SCOME-Ethiopia; Public Health Measures and Clinical Management of COVID-19

In this document you will find about the basics of COVID-19, presentation and lab tests, current management guideline, roles and responsibilities of medical students and links of different sites from the IFMSA COVID-19 library. .

Remember that facts about COVID-19 are being updated regularly, so update yourselves frequently.

2020 G.C /2012 E.C Addis Ababa, Ethiopia.

Contributors Heaven Y. Tatere (EMSA-Ethiopia)

Sabrina Zeleke (EMSA-Addis Ababa)

Issrafil Mussa (EMSA-St.Paul)

Tiyobista Yohannes (EMSA-Addis Ababa)

Jalene Gedefa (EMSA-Bahirdar)

Yadeni Gedefa (EMSA-Jimma)

Frenesh Sahilu (EMSA-Gondar)

Maryamawit Solomon (EMSA-Adigrat)

Editors Heaven Yeshaneh Tatere (MD) Abel Mekonnen Tesfaye (MD) Kaleab Ashebir Debebe (MD) Tigest Abebaw Zewdie (MD)

Special thanks Dr. Bilal Shikur Endris (MD, MPH)

Dr.Bersabeh Mekasha (MD)

Dr. Wubishet Assefa (MD, Pathologist)

Dr.Nehemiah Andargachew (MD)

Dr. Tigist Seleshi Mekonnen (MD,Internist)

Dr.Abraham Genetu (MD)

Dr. Yasmin Abdulsemed (MD)

Dr.Miraf Y. Tatere (EMSA)

Graphic Design Kaleb Sheleme +251 933 203167

TABLE OF CONTENTS Preface................................................................................................................. 03 Introduction ......................................................................................................... 05 Etiology............................................................................................................................... 05 Pathogenesis...................................................................................................................... 06 Transmission...................................................................................................................... 07 Disease Presentation............................................................................................ 08 Diagnosis.............................................................................................................. 12 Principle of management..................................................................................... 13 Approaches used to combat COVID-19............................................................... 14 Do Nothing........................................................................................................................ 14 Mitigation Strategy............................................................................................................ 15 Herd Immunity................................................................................................................... 15 Suppression Strategy........................................................................................................ 16 Roles and Responsibilities of Medical Students.................................................. 18 Here is some basic information for Health education.......................................... 19 Intervention and Evidence of effectiveness................................................................... 19 Face masks......................................................................................................................... 20 Hand Hygiene.................................................................................................................... 22 Physical and Social distancing......................................................................................... 24 Respiratory Hygiene.......................................................................................................... 24 Myth Busters...................................................................................................................... 26 Detailed management of COVID-19.................................................................... 29 IFMSA COVID-19 Library Guide........................................................................... 41 References............................................................................................................ 44

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PREFACE Our world keeps on struggling with the COVID-19 pandemic unable to have successfully synthesized neither a vaccine nor a cure so far. As of today, May16, 2020, the total number of cases has reached 4,673,809 and 312,646 individuals have died because of COVID 19. In our country Ethiopia, the total number of confirmed cases is 317 where 5 individuals have succumbed to death.

The initial cases of this outbreak were a cluster of patients with pneumonia of, at the time, unknown cause in late December 2019, Wuhan, China. Most of these cases were vendors and patrons at an animal food market in the city. In early January the cause of the outbreak was confirmed to be a novel Coronavirus, with genetic resemblance to the SARS virus and some bat Coronaviruses.

By January 13, 2020, the first confirmed case outside China was reported from Thailand. By late February confirmed cases were reported in all continents, many of which have established community transmissions. On March 11, WHO officially declared the COVID 19 outbreak a pandemic- (a sudden outbreak that becomes very widespread and affects a whole region, a continent, or the world due to a susceptible population or according to WHO, it is the worldwide spread of a new disease).

As COVID 19 keeps shaking the world and challenging the health care systems of so many nations, the front-line health care providers are at the greatest risk of exposure to the virus. So many health care providers have been infected with the disease where some have died. Regardless of the big risk posed to the health care professionals, these health care professionals can’t possibly remove themselves from this threat for there is no other body or group of population equipped to combat it. This puts health care professionals at an avoidable vicious cycle of risk exposure. There have been situations where the number of health care professionals had been scarce to combat the burden of COVID 19 hospitalizations where medical students have been called in to help. The baseline medical knowledge possessed by medical students places them as bench line individuals that could be readily disposed when hospitalization burden becomes unbearable to health care professionals. It is under this context that we found it necessary to compile this concise document for medical students.

The Ethiopian Medical Students Association National Standing committee of medical education (EMSA SCOME) presents this document to equip medical students in two aspects. The first aim of this document is to provide medical students with basic clinical background of the disease which contains details of COVID 19 clinical diagnosis and management. The second plan this document hopes to achieve is equip students with the necessary public health measures. This includes the roles and responsibilities of health care professionals and medical students in understanding the significance of the prevention methods such as social distancing and basics of health education. At the end of this document are links which are updated daily for further reference.

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This document has tried to address COVID 19 in a holistic manner specifically for medical students. It is to be shared among the different local chapters of the association and medical students all over Ethiopia. But it is to be noted that this document is neither to replace nor to be used as an alternative to guidelines released by the world Health Organization, Health ministries of countries or other health organizations.

Heaven Yeshaneh Tatere (MD) National Medical Officer, EMSA-Ethiopia

The recent update can be found on

https://www.arcgis.com/apps/opsdashboard/index.html?fbclid=IwAR1nUkJjv4YlQsuTdBtTdXlaP211YoiP9liOt1ekUn10VJj7G3V6sFFzP-c#/bda7594740fd40299423467b48e9ecf6

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INTRODUCTION Etiology • Coronaviruses belong to the Coronaviridae family in the Nidovirales order. Corona represents crown-like spikes on the outer surface of the virus; thus, it was named as a coronavirus.

• Coronaviruses are minute in size (65–125 nm in diameter) and contain a single-stranded RNA as a nucleic material, size ranging from 26 to 32kbs in length.

• The subgroups of coronaviruses family are alpha (a), beta (b), gamma (c) and delta (d) coronavirus.

• Coronaviruses are important human and animal pathogens. Commonly they cause common cold, but more severe species caused SARS, MERS and now COVID-19.

• The virus that causes COVID-19 is designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); previously, it was referred to as 2019-nCoV. • In February 2020, the disease caused by SARS-CoV-2 was named by the World Health Organization a COVID-19, which stands for coronavirus disease 2019.

• Full-genome sequencing and phylogenic analysis indicated that the coronavirus that causes COVID-19 is a betacoronavirusin the same subgenus as the severe acute respiratory syndrome (SARS) virus.

• The structure of the receptor-binding gene region is very similar to that of the SARS coronavirus, and the virus has been shown to use the same receptor, the angiotensin-converting enzyme 2 (ACE2), for cell entry.

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PATHOGENESIS Unique feature- it causes both upper and lower respiratory tract infection Steps 1. First the virus attaches to specific cellular receptors via the spike protein 2. Transformational change, leading to fusion between the virus and cell membrane 3. Release of nucleocapsid into the cell (transcription and translation) 4. Alteration of DNA and production of proteins and certain specific enzymes 5. Alteration of cell function and production 6. Release of excess cytokines and chemokines, increased acute phase reaction 7. Hyperinflammation 8. Cause of death will be due to complications caused by ‘cytokine storm syndrome’ ›› Severe acute respiratory syndrome

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Transmission • Person-to-person spread of severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) is thought to occur mainly via respiratory droplets, resembling the spread of influenza.

• With droplet transmission, virus released in the respiratory secretions when a person with infection coughs, sneezes, or talks can infect another person if it makes direct contact with the mucous membranes; infection can also occur if a person touches an infected surface and then touches his or her eyes, nose, or mouth.

• Droplets typically do not travel more than six feet (about two meters) and do not linger in the air. Given the current uncertainty regarding transmission mechanisms, airborne precautions are recommended in certain situations.

• Airborne transmission is still important especially in the medical setting in which procedures or support treatments that generate aerosols are performed; i.e., endotracheal intubation, bronchoscopy, open suctioning, administration of nebulized treatment, manual ventilation before intubation, turning the patient to the prone position, disconnecting the patient from the ventilator, non-invasive positive-pressure ventilation, tracheostomy, and cardiopulmonary resuscitation.

• Period of infectivity — The interval during which an individual with COVID-19 is infectious is uncertain. Most data informing this issue are from studies evaluating viral RNA detection from respiratory and other specimens. However, detection of viral RNA does not necessarily indicate the presence of infectious virus.

• Viral RNA levels appear to be higher soon after symptom onset compared with later in the illness; this raises the possibility that transmission might be more likely in the earlier stage of infection, but additional data are needed to confirm this hypothesis.

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DISEASE PRESENTATION Majority of patients have symptoms 4 or 5 days after exposure, although incubation period might be from 14-21 days

Spectrum of illness severity- most infections are not severe (14% will have severe illness and 5% will require ICU care). The case-fatality rate ranged from 7.2 percent to 0.7 percent.

The infection can present within a spectrum of disease severity. This ranges from asymptomatic to mild uncomplicated illness without pneumonia, to mild or severe pneumonia, ARDS and other potentially fatal complications.

The frequency of asymptomatic infections is unknown. In a report of an outbreak on a cruise ship in Japan, half of the patients who tested positive were asymptomatic at the time diagnosis, of which around 18% were still asymptomatic at the end of the assumed incubation period. Such cases might be of epidemiologic importance.

The most frequent symptom in those who develop symptoms is fever. However, fever is not universal, might be very low grade and might not be persistent. Other common symptoms are fatigue, cough (which is usually dry but might be productive in 27% from 1 report), anorexia, myalgia, dyspnea, anosmia and dysgeusia. Less commonly headache, sore throat, rhinorrhea and gastrointestinal symptoms are also reported.

Although there is differing information on what proportion of cases the different classes of severity account for, an often-quoted initial report from China states the following. Mild (with no pneumonia or mild pneumonia) 81%, severe disease (with dyspnea, hypoxia, or >50% lung involvement within 24-48 hours) 14% and critical disease (with ARDS, respiratory failure, shock) 5%.

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High risk Risk factors for severe illness- Severe illness can occur in otherwise healthy individuals of any age, but it predominantly occurs in adults with advanced age or underlying medical co morbidities.

Risks for developing severe disease, including mortality, are advanced age (80% of deaths occur in those >65 years in a report from USA), cardiovascular disease, diabetes mellitus, hypertension, chronic lung disease, cancer, chronic kidney disease, immune-compromising conditions, severe obesity and liver disease. Some patients with initially mild symptoms may progress over the course of a week and patients with no apparent risk can develop severe disease.

Pneumonia is the most common serious manifestation, and is characterized by fever, cough, dyspnea and bilateral infiltrates on chest imaging. ARDS is a major complication in cases with severe disease. Other complications include arrhythmias, acute cardiac injury and cardiomyopathy and shock.

Possible laboratory finding include WBC abnormalities (leukopenia, leukocytosis or lymphopenia), elevated aminotransferases, AKI, and elevated LDH and markers of inflammation (CRP, pro-calcitonin, ferretin, D-dimer (>1mcg/ml)). Elevated PT, elevated Troponin and elevated CPK. Derangements in certain laboratory values may predict severe disease and poor outcome.

Another testing modality that might become clinically important, are antibody based serologic tests. Although, most serology test are currently in the research stage they offer a range of theoretical advantages. These include detection of patients with both current

Page 10 and resolving infections and differentiating between the two (IgM vs. IgG), faster result time, less cost, point of care testing, residential screening and easier mass population testing. This might enable a better understanding of the burden of the infection. A possible disadvantage is that antibody response may be delayed, up to 14 days in some reports, and this might lead missed infection in patients who are actively shedding the virus.

There is a general enthusiasm in the medical community about this modality of diagnosis. Early reports that tested different assays in different countries report good sensitivity and specificity (95.6% and 93.8% in one such report from China). There are also reports from the US where after clinical, radiologic and/or epidemiologic suspicion and a negative PCR, diagnosis was made using serology.

When widely available serologic tests might serve an important role as an adjuvant or substitute to PCR. Other possible ways of definitive diagnosis include, INNA, Whole genome sequencing and viral culture. Currently the use of these tests is limited to research settings.

Imaging findings —Chest x-ray- bilateral infiltrates. Chest CT in patients with COVID-19 most commonly demonstrates ground-glass opacification with or without consolidative abnormalities, consistent with viral pneumonia. Case series have suggested that chest CT abnormalities are more likely to be bilateral, have a peripheral distribution, and involve the lower lobes. Less common findings include pleural thickening, pleural effusion, and lymphadenopathy. Chest CT may be helpful in making the diagnosis, but no finding can completely rule in or rule out the possibility of COVID-19.

Recovery time appears to be around two weeks for mild infections and three to six weeks for severe disease.

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DIAGNOSIS The WHO has recommended that the following case definitions be used for surveillance for disease.

Suspect case a. . A patient with acute respiratory illness (fever and at least one sign/symptom of respiratory disease, e.g., cough, shortness of breath), AND a history of travel to or residence in a location reporting community transmission of COVID-19 disease during the 14 days prior to symptom onset; OR b. A patient with any acute respiratory illness AND having been in contact with a confirmed or probable COVID-19 case (see definition of contact) in the last 14 days prior to symptom onset; OR c. A patient with severe acute respiratory illness (fever and at least one sign/symptom of respiratory disease, e.g., cough, shortness of breath; AND requiring hospitalization) AND in the absence of an alternative diagnosis that fully explains the clinical presentation.

Probable Case a. A suspect case for whom testing for the COVID-19 virus is inconclusive; OR b. A suspect case for whom testing could not be performed for any reason.

Confirmed case A person with laboratory confirmation of COVID-19 infection, irrespective of clinical signs and symptoms.

The definitive diagnosis can be made by microbial testing, done by PCR. SARSCoV-2 RNA is detected by reverse-transcription polymerase chain reaction (RT-PCR). This test is provided in Ethiopian in different regional institutions. All suspected cases should be transferred to designated facilities till results are available.

The preferred and routinely done sample collection method for testing is a nasopharyngeal swab. Oropharyngeal, nasal mid-turbinate and expectorated sputum (in patients with productive cough) are acceptable specimens. In intubated patient’s lower respiratory tract aspirates can be used. Samples should be collected with due infection prevention protocol.

A positive test generally confirms infection, although false positivity is possible.

There was one such case in Ethiopia. False negative results are also possible. Negative initial tests in patients with suggestive clinical and CT scan features in admitted patients, which later turned out to be positive have been reported. Lower respiratory tract specimen might be more sensitive.

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PRINCIPLE OF MANAGEMENT Currently there is no specific treatment or vaccine available for COVID 19. However numerous clinical trials are undergoing thus requiring up to date knowledge of clinicians.

Here we only highlight the general management principles of COVID 19. The details will be discussed in the Detailed management section at the end. ›› Early identification of cases and categorize patients with risk and severe disease. ›› Implement appropriate IPC measures starting from the triage. ›› Determine the treatment area based on the clinical condition of the patient and the resource availability. ›› Initiate supportive care as it is the main stay of treatment for covid-19 patients. ›› Give symptomatic treatment with antipyretics and analgesics. ›› Transfer patients with severe disease or those with risk factor to hospitals for inpatient care. ›› Early admission to ICU if intensive monitoring and treatment is required. ›› Give supplemental oxygen if hypoxic, in respiratory distress or shock. ›› Early recognition of sepsis and initiation of empiric antimicrobials within one hour and further modification can be made based on culture and sensitivity result. ›› Use IV antibiotic for severe case but oral antibiotics can suffice for uncomplicated case. ›› Prevention of complications like hospital acquired infections, venous thromboembolism, ARDS, organ failure and the like. ›› Patient care should be with respect and dignity which include but not limited to: medical support, food/water supply and accurate and timely information.

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APPROACHES USED TO COMBAT COVID-19 Do Nothing If we do nothing: Everybody gets infected, the healthcare system gets overwhelmed, the mortality explodes, and ~10 million people die.

So, what’s the catch? With all these numbers, it’s easy to get confused. But there’s only two numbers that matter: What share of people will catch the virus and fall sick, and what share of them will die.

How Should We Think about the Fatality Rate?

This is the same graph as before, but now looking at hospitalized people instead of infected and dead:

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The light blue area is the number of people who would need to go to the hospital, and the darker blue represents those who need to go to the intensive care unit (ICU). You can see that number would peak at above 3 million.

Mitigation Strategy This tries to delay the spread of the virus by closing schools and universities, and encouraging people to work from home, isolating people who are infected or most at risk and encouraging physical distancing practice. This approach attempts to slow the outbreak or “flattening the curve” to ease burdens to the health facilities till vaccinations get available or natural/ herd immunity kicks off!

Mitigation goes like this: “It’s impossible to prevent the coronavirus now, so let’s just have it run its course, while trying to reduce the peak of infections. Let’s just flatten the curve a little bit to make it more manageable for the healthcare system.”

Herd Immunity This is strict physical distancing and quarantining options reserved only to vulnerable individuals and all the remaining people move freely and schools keep functioning without getting the economy crippled.

The aim is those individuals at higher risk of developing severe illness are later shielded by immune individuals after waning of the outbreak.

Page 16 This approach is being used by Sweden and Belarus and was once considered as an option by the UK before it backed off.

The idea is that all the people who are infected and then recover are now immune to the virus. This is at the core of this strategy Except this assumes one thing: the virus doesn’t change too much. If it doesn’t change much, then lots of people do get immunity, and at some point, the epidemic dies down.

But this virus has mutated.

This graph represents the different mutations of the virus. You can see that the initial strains started in purple in China and then spread. Each time you see a branching on the left graph, that is a mutation leading to a slightly different variant of the virus.

This should not be surprising: RNA-based viruses like the coronavirus or the flu tend to mutate around 100 times faster than DNA-based ones—although the coronavirus mutates more slowly than influenza viruses.

Not only that, but the best way for this virus to mutate is to have millions of opportunities to do so, which is exactly what a mitigation strategy would provide: hundreds of millions of people infected.

Suppression Strategy This aims to stop the virus from spreading using mandatory home lockdowns and selfisolation. This is the kind of approach mainly used by china and its neighbors. It seems to be giving them a momentary relief from the outbreak.

The Mitigation Strategy doesn’t try to contain the epidemic, just flatten the curve a bit.

Meanwhile, the Suppression Strategy tries to apply heavy measures to quickly get the epidemic under control.

Page 17 Specifically: • Go hard right now. Order heavy social distancing. Get this thing under control.

• Then, release the measures, so that people can gradually get back their freedoms and something approaching normal social and economic life can resume.

Suppression would get us: • Fewer total cases of Coronavirus • Immediate relief for the healthcare system and the humans who run it • Reduction in fatality rate • Reduction in collateral damage • Ability for infected, isolated and quarantined healthcare workers to get better and back to work

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ROLES AND RESPONSIBILITIES OF MEDICAL STUDENTS • Update yourselves with recent information • Read the basics of viruses including definitions, presentation, laboratory diagnosis, basics of management and complications • Create awareness in your community regarding the pandemic; give health education in a controlled manner • Take the course prepared by the WHO Medical students can use this time to take the course given by the WHO and get certified.

Here are some useful courses that the WHO prepared to keep us up to date and be well prepared!

Steps: 1. Click the link - https://openwho.org/channels/covid-19 2. Select one of the courses.

3. You will find the “Enroll Me Now” button on the bottom-right side of the selected course.

4. When you click the “Enroll Me Now” button, the login page will pop-up. Then click the “Create Account” button if you didn’t have an account before for openWHO.org.

If you had one insert the login details and continue with the course.

Course (A) Infection Prevention and Control (IPC) for Novel Coronavirus (COVID-19) https://openwho.org/courses/COVID-19-IPC-EN/resume Course(B)COVID-19: Operational Planning Guidelines and COVID-19 Partners https://openwho.org/courses/UNCT-COVID19-preparedness-and-response-EN/ resume You will get free certification for the courses at the end of course (B).

• Update yourselves on articles released by WHO and Ministry of Health on a regular basis • Starting and assisting with phone triage * Many practices have moved toward telemedicine, meaning not in a setting, but meaning where patients call in and say what their symptoms are and if they should come in or not,” “By doing that [with adequate supervision] and telling a caller whether or not it looks like a COVID-19 situation, students can help reduce incoming traffic for nurse practitioners and physicians.

•

Involve in research activities regarding COVID-19.

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HERE IS SOME BASIC INFORMATION FOR HEALTH EDUCATION Intervention and Evidence of effectiveness ▪ ▪ ▪ ▪ ▪ ▪ ▪ ▪

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Face Masks How and when to use a face mask?

We should wear face masks when we have flu like symptoms and are caring for or are near others who are sick. This is important not only to protect other patients but also ourselves. Since this disease is of respiratory origin and spreads mainly via droplets, it is important to cover our nose and mouth when we are sick or are near other sick people.

Before putting on a mask, we should clean our hands with alcohol-based hand rub or soap and water (this helps avoid depositing the virus onto the mask by our hands).

We should use the mask to cover our mouth and nose making sure there are no gaps between our face and the mask. We also should avoid touching the mask while using it; if we do, we should clean our hands with alcohol-based hand rub or soap and water. If the mask gets dirty, replace it. Do not reuse disposable masks.

When removing the mask, take it off from the back without touching the front of the mask. Used masks should be discarded immediately in a closed bin. After taking off the mask, we must disinfect our hands using an alcohol-based hand sanitizer or wash our hands with soap and water, rubbing vigorously for 20 seconds.

When you hear about face masks for COVID-19 prevention, it’s generally three types: 1. homemade cloth face mask 2. surgical mask 3. N95 respirator Let’s explore each of them in a little more detail below, 1. Homemade cloth face masks To prevent the spread of the virus from people without symptoms, the Centers for Disease Control and Prevention (CDC) is now recommending that everyone wears cloth face masks, such as homemade face masks, while in public places where it’s difficult to maintain a 6-foot distance from others. This recommendation is in addition to continued social distancing and proper hygiene practices.

Recommendations include • Wear cloth face masks in public settings, especially in areas of significant communitybased transmission, such as grocery stores and pharmacies.

• Don’t put cloth face masks on children under the age of 2, people who have trouble breathing, people who are unconscious, or people who are unable to remove the mask on their own.

• Use cloth face masks rather than surgical masks or N95 respirators, as these critical supplies must be reserved for healthcare workers and other medical first responders.

• Healthcare professionals should exercise extreme caution when using homemade face masks. These masks should preferably be used in combination with a face shield that covers the entire front and sides of the face and extends to the chin or below.

Page 21 NOTE Wash homemade cloth masks after every use. When removing, be careful not to touch your eyes, nose, and mouth. Wash hands immediately after removing.

Benefits of homemade face masks: • Cloth face masks can be made at home from common materials, so there’s an unlimited supply.

• They may lower the risk of people without symptoms transmitting the virus through speaking, coughing, or sneezing.

• They’re better than not using any mask and offer some protection, especially where social distancing is hard to maintain.

Risks of homemade face masks: They may provide a false sense of security. While homemade face masks offer some degree of protection, they offer a lot less protection than surgical masks or respirators.

One 2008 study indicated that homemade face masks may be half as effective as surgical masks and up to 50 times less effective than N95 respirators.

They don’t replace or reduce the need for other protective measures. Proper hygiene practices and social distancing are still the best methods of keeping yourself safe.

2. Surgical masks Surgical masks are disposable, loose-fitting face masks that cover your nose, mouth, and chin. They’re typically used to: • Protect the wearer from sprays, splashes, and large-particle droplets • Prevent the spread of potentially infectious respiratory secretions from the wearer to others.

• Surgical masks can vary in design, but the mask itself is often flat and rectangular in shape with pleats or folds. The top of the mask contains a metal strip that can be formed to your nose.

• Elastic bands or long, straight ties help hold a surgical mask in place while you’re wearing it. These can either be looped behind your ears or tied behind your head.

3. N95 respirators An N95 respirator is a more tight-fitting face mask. In addition to splashes, sprays, and large droplets, this respirator can also filter out 95 percent of very small particles. This includes viruses.

The respirator itself is generally circular or oval in shape and is designed to form a tight seal to your face. Elastic bands help hold it firmly to your face. Some types may have an attachment called an exhalation valve, which can help with breathing and the buildup of heat and humidity.

N95 respirators aren’t one-size-fits-all. They actually must be fit-tested before use to make sure that a proper seal is formed. If the mask doesn’t seal effectively to your face, you won’t receive the appropriate protection.

Page 22 After being fit-tested, users of N95 respirators must continue to perform a seal check each time they put one on. It’s also important to note that a tight seal can’t be achieved in some groups. These include children and people with facial hair.

Can wearing a face mask protect against the 2019 coronavirus?

SARS-CoV-2 spreads from person to person via small respiratory droplets. These are generated when a person with the virus exhales, coughs, or sneezes. You can contract the virus if you breathe in these droplets.

Additionally, respiratory droplets containing the virus can land on various objects or surfaces. Touching a contaminated object or surface and then touching your eyes, nose, or mouth can also lead to infection.

Homemade face masks Homemade face masks only offer a small degree of protection, but they may help prevent the spread of SARS-CoV-2 from asymptomatic people. The CDC recommends using them in public settings, as well as practicing social distancing and proper hygiene.

Surgical masks Indirect evidence from the SARS epidemic was used to inform the question about the effectiveness of masks. Based on an existing systematic review of five observational studies in health care personnel, wearing any mask (surgical mask or N95 respirator) demonstrated a large reduction in the risk of developing infection (surgical masks: OR 0.13; 95% CI: 0.03,0.62) or (N95 respirator OR 0.12; 95% CI: 0.06,0.26).

However, not only does the mask not filter out smaller aerosol particles, but air leakage also occurs through the sides of the mask as you inhale, thus offering lesser protection.

N95 respirators N95 respirators can protect against smaller respiratory droplets, such as those containing SARS-CoV-2. However, the CDC currently doesn’t recommend their use outside of healthcare settings. There are a variety of reasons for this, including: N95 respirators should be fit-tested in order to be used appropriately. A poor seal can lead to leakage, lowering the respirator’s effectiveness.

Due to their tight fit, N95 respirators can become uncomfortable and stuffy, making them difficult to wear for extended periods of time.

Our worldwide supply of N95 respirators is limited, making it critical that healthcare workers and first responders have ready access to them.

NOTE: You can get videos of proper appliance and disposal method of PPEs using the link https://www.cdc.gov/coronavirus/2019-ncov/hcp/using-ppe.html

Hand Hygiene Respiratory viruses like coronavirus disease (COVID-19) spread when mucus or droplets containing the virus get into your body through your eyes, nose or throat. Most often, this happens through your hands. Hands are also one of the most common ways that the virus spreads from one person to the next.

Page 23 During a global pandemic, one of the cheapest, easiest, and most important ways to prevent the spread of a virus is to wash your hands frequently with soap and water.

Here’s everything you need to know about how to wash your hands the right way: How do I wash my hands properly?

To eliminate all traces of the virus on your hands, a quick scrub and a rinse won’t cut it. Below is a step-by-step process for effective handwashing.

Step 1: Wet hands with running water Step 2: Apply enough soap to cover wet hands Step 3: Scrub all surfaces of the hands – including back of hands, between fingers and under nails – for at least 20 seconds.

Step 4: Rinse thoroughly with running water Step 5: Dry hands with a clean cloth or single-use towel How long should I wash my hands for?

You should wash your hands for at least 20-30 seconds. An easy way to time it is by singing the full happy birthday song, twice. The same goes for hand sanitizer: use a sanitizer that contains at least 60% alcohol and rub it into your hands for at least 20 seconds to ensure full coverage.

When should I wash my hands?

In the context of COVID-19 prevention, you should make sure to wash your hands at the following times. ∘∘After blowing your nose, coughing or sneezing ∘∘After visiting a public space, including public transportation, markets and places of worship ∘∘After touching surfaces outside of the home, including money ∘∘Before, during and after caring for a sick person ∘∘Before and after eating In general, you should always wash your hands at the following times: ∘∘ After using the toilet ∘∘ Before and after eating ∘∘ After handling garbage ∘∘ After touching animals and pets ∘∘ After changing babies’ diapers or helping children use the toilet ∘∘ When your hands are visibly dirty How can we help children wash their hands?

You can help children wash their hands by making handwashing easier for them, for instance, by setting up a stool so they can reach water and soap by themselves. You can make it fun for them by singing their favorite songs while you help them rub their hands.

Page 24 Do I need to use warm water to wash my hands?

No, you can use any temperature of water to wash your hands. Cold water and warm water are equally effective at killing germs and viruses – as long as you use soap!

Do I need to dry my hands with a towel?

Germs spread more easily from wet skin than from dry skin, so drying your hands completely is an important step. Paper towels or clean clothes are the most effective way to remove germs without spreading them to other surfaces.

Avoid touching eyes, nose and mouth Why? Hands touch many surfaces and can pick up viruses. Once contaminated, hands can transfer the virus to your eyes, nose or mouth. From there, the virus can enter your body and can make you sick.

Physical and Social distancing Why 6 feet?

When someone coughs or sneezes, small, sometimes unsee able, drops of liquid are sprayed out. If you’re standing too close, you can breathe them in. Those droplets could contain the coronavirus, if the person coughing is infected, according to the World Health Organization. Six feet is just far enough to be out of reach. Six feet is the average distance that respiratory droplets from a sneeze or cough travel before they settle and are no longer likely to be inhaled by other people.

What if you’re standing 5 feet away?

You’re not protecting yourself properly. The distance of 3 feet to 6 feet from each other is known as the breathing zone. That means people within that space are breathing and exhaling basically the same air. If someone has the virus, they’re essentially exhaling it into the air you’re breathing.

How does social distancing help?

Social distancing measures include limiting large groups of people coming together, closing buildings, and cancelling events. When this happens, it is because we are all trying to do our part in minimizing the spread of a virus and protect people who are at high risk for serious infection. By practicing social distancing, we can slow the spread of the virus and can help keep the number of people who are sick at one time manageable for healthcare workers. This is sometimes referred to as “flattening the curve.” By practicing social distancing, you are helping protect not only yourself, but others too.

This doesn’t mean you should distance yourself from others emotionally. Reach out to friends, family and community members through social media, phone calls, texting, and video chat to stay connected.

Respiratory Hygiene Respiratory hygiene and cough etiquette are terms used to describe infection prevention measures to decrease the transmission of respiratory illness (e.g., influenza and cold viruses). A respiratory infection is spread when a person who is infected with a virus coughs or sneezes. The droplets released from an ill person’s cough or sneeze can

Page 25 travel for several feet reaching the nose or mouth of others and causing illness. Viruses can spread easily from person to person through direct contact via touching or shaking hands.

Why should we cover our mouth and nose when we sneeze and cough?

It’s not just good manners to cover our nose and mouth when we cough and/or sneeze.

It also happens to be the most effective way of preventing and controlling respiratory infections worldwide. Respiratory viruses, like the corona virus, are passed from one person to the other through fluids from mouth and nose secretions. When we cough and sneeze, those droplets go into the air. An uncovered cough or sneeze can send infected droplets up to six feet away and remain airborne for several hours. The live virus can also live on surfaces for up to 48 hours. Therefore, it’s our responsibility to cover our mouth and nose so those droplets don’t go into the air and don’t spread to other people.

We should sneeze and/or cough into a tissue or paper towel then dispose them properly afterwards. If you don’t have those with you, you can sneeze and/or cough into your bent elbow. This is helps limit the spread of the infection because it traps the virus and prevent it from spreading. It is always a good idea to wash our hands with soap or use hand sanitizer for about 20 seconds just in case any germs were transmitted from the tissue onto our skin.

Because we use our hands to manipulate things in our day to day activities, there is a high risk of depositing the virus on those materials we use if we sneeze and/ or cough into our hands. Therefore, we should avoid coughing and sneezing into our hands so there’s no chance we will spread germs to another surfaces. Otherwise, our dirty hands will touch door knobs, elevator buttons, remote controls, and also things like food we serve, hands we shake, and even our own face. Consequently, when someone else touches these surfaces, he or she will be at risk of getting infected.

The following measures to contain respiratory secretions are recommended for all individuals with signs and symptoms of a respiratory infection.

1. Cover your mouth and nose with a tissue when coughing or sneezing; 2. Use in the nearest waste receptacle to dispose of the tissue after use; 3. Perform hand hygiene (e.g., hand washing with non-antimicrobial soap and water, alcohol-based hand rub, or antiseptic handwash) after having contact with respiratory secretions and contaminated objects/materials.

Remember: If you have fever, cough and difficulty breathing, seek medical care early.

Stay home if you feel unwell. If you have a fever, cough and difficulty breathing, seek medical attention and call in advance. Follow the directions of your local health authority.

Why? National and local authorities will have the most up to date information on the situation in your area. Calling in advance will allow your health care provider to quickly direct you to the right health facility. This will also protect you and help prevent spread of viruses and other infections.

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Myth Busters 1. Exposing yourself to the sun or to temperatures higher than 25C degrees DOES NOT prevent the coronavirus disease (COVID-19) You can catch COVID-19, no matter how sunny or hot the weather is. Countries with hot weather have reported cases of COVID-19. To protect yourself, make sure you clean your hands frequently and thoroughly and avoid touching your eyes, mouth, and nose.

2. You can recover from the coronavirus disease (COVID-19). Catching the new coronavirus DOES NOT mean you will have it for life.

Most of the people who catch COVID-19 can recover and eliminate the virus from their bodies. If you catch the disease, make sure you treat your symptoms. If you have cough, fever, and difficulty breathing, seek medical care early – but call your health facility by telephone first. Most patients recover thanks to supportive care.

3. Being able to hold your breath for 10 seconds or more without coughing or feeling discomfort DOES NOT mean you are free from the coronavirus disease (COVID-19) or any other lung disease.

The most common symptoms of COVID-19 are dry cough, tiredness and fever.

Some people may develop more severe forms of the disease, such as pneumonia.

The best way to confirm if you have the virus producing COVID-19 disease is with a laboratory test. You cannot confirm it with this breathing exercise, which can even be dangerous.

4. Drinking alcohol does not protect you against COVID-19 and can be dangerous Frequent or excessive alcohol consumption can increase your risk of health problems.

5. COVID-19 virus can be transmitted in areas with hot and humid climates.

From the evidence so far, the COVID-19 virus can be transmitted in ALL AREAS, including areas with hot and humid weather. Regardless of climate,adopt protective measures if you live in, or travel to an area reporting COVID-19. The best way to protect yourself against COVID-19 is by frequently cleaning your hands.

Page 27 By doing this you eliminate viruses that may be on your hands and avoid infection that could occur by then touching your eyes, mouth, and nose.

6. Cold weather and snow CANNOT kill the new coronavirus.

There is no reason to believe that cold weather can kill the new coronavirus or other diseases. The normal human body temperature remains around 36.5째C to 37째C, regardless of the external temperature or weather. The most effective way to protect yourself against the new coronavirus is by frequently cleaning your hands with alcohol-based hand rub or washing them with soap and water.

7. Taking a hot bath does not prevent the new coronavirus disease Taking a hot bath will not prevent you from catching COVID-19. Your normal body temperature remains around 36.5째C to 37째C, regardless of the temperature of your bath or shower. Actually, taking a hot bath with extremely hot water can be harmful, as it can burn you. The best way to protect yourself against COVID-19 is by frequently cleaning your hands. By doing this you eliminate viruses that may be on your hands and avoid infection that could occur by then touching your eyes, mouth, and nose.

8. The new coronavirus CANNOT be transmitted through mosquito bites.

To date there has been no information nor evidence to suggest that the new coronavirus could be transmitted by mosquitoes. The new coronavirus is a respiratory virus which spreads primarily through droplets generated when an infected person coughs or sneezes, or through droplets of saliva or discharge from the nose. To protect yourself, clean your hands frequently with an alcoholbased hand rub or wash them with soap and water. Also, avoid close contact with anyone who is coughing and sneezing.

9. Are hand dryers effective in killing the new coronavirus?

No. Hand dryers are not effective in killing the 2019-nCoV. To protect yourself against the new coronavirus, you should frequently clean your hands with an alcohol-based hand.

10. Can an ultraviolet disinfection lamp kill the new coronavirus?

UV lamps should not be used to sterilize hands or other areas of skin as UV radiation can cause skin irritation.

11. How effective are thermal scanners in detecting people infected with the new coronavirus?

Thermal scanners are effective in detecting people who have developed a fever (i.e. have a higher than normal body temperature) because of infection with the new coronavirus. However, they cannot detect people who are infected but are not yet sick with fever. This is because it takes between 2 and 10 days before people who are infected become sick and develop a fever.

12. Can spraying alcohol or chlorine all over your body kill the new coronavirus?

No. Spraying alcohol or chlorine all over your body will not kill viruses that have already entered your body. Spraying such substances can be harmful to clothes

Page 28 or mucous membranes (i.e. eyes, mouth). Be aware that both alcohol and chlorine can be useful to disinfect surfaces, but they need to be used under appropriate recommendations.

13. Do vaccines against pneumonia protect you against the new coronavirus?

No. Vaccines against pneumonia, such as pneumococcal vaccine and Hemophilus influenza type B (Hib) vaccine, do not provide protection against the new coronavirus. The virus is so new and different that it needs its own vaccine.

Researchers are trying to develop a vaccine against 2019-nCoV, and WHO is supporting their efforts. Although these vaccines are not effective against 2019nCoV, vaccination against respiratory illnesses is highly recommended to protect your health.

14. Can regularly rinsing your nose with saline help prevent infection with the new coronavirus?

No. There is no evidence that regularly rinsing the nose with saline has protected people from infection with the new coronavirus. There is some limited evidence that regularly rinsing nose with saline can help people recover more quickly from the common cold. However, regularly rinsing the nose has not been shown to prevent respiratory infections.

15. Can eating garlic help prevent infection with the new coronavirus?

Garlic is a healthy food that may have some antimicrobial properties. However, there is no evidence from the current outbreak that eating garlic has protected people from the new coronavirus.

16. Does the new coronavirus affect older people, or are younger people also susceptible?

People of all ages can be infected by the new coronavirus (2019-nCoV). Older people, and people with pre-existing medical conditions (such as asthma, diabetes, heart disease) appear to be more vulnerable to becoming severely ill with the virus. WHO advises people of all ages to take steps to protect themselves from the virus, for example by following good hand hygiene and good respiratory hygiene.

17. Are antibiotics effective in preventing and treating the new coronavirus?

No, antibiotics do not work against viruses, only bacteria. The new coronavirus (2019-nCoV) is a virus and, therefore, antibiotics should not be used as a means of prevention or treatment. However, if you are hospitalized for the 2019-nCoV, you may receive antibiotics because bacterial co-infection is possible.

18. Are there any specific medicines to prevent or treat the new coronavirus?

No. Spraying alcohol or chlorine all over your body will not kill viruses that have already entered your body. Spraying such substances can be harmful to clothes or mucous membranes (i.e. eyes, mouth). Be aware that both alcohol and chlorine can be useful to disinfect surfaces, but they need to be used under appropriate recommendations.

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DETAILED MANAGEMENT OF COVID – 19 This management section uses the Interim Guidance on Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected (WHO) and Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19) as its main source but also includes the national guideline for specific recommendations.

General principles of management of COVID-19 ∘∘ Identify severe/critical cases at triage then supportive treatment should start without delay ∘∘ Apply strict IPC measures when managing patients starting from triage ∘∘ Specimens for detecting COVID-19 can be obtained from nasopharyngeal or oropharyngeal swabs, sputum (if produced) or lower airways in special conditions ∘∘ Closely monitor patients isolated for COVID-19 infection ∘∘ Underlying/chronic diseases should be identified as early as possible with detailed history from patients and close family members or friends ∘∘ Consider drug interactions, adverse reactions and allergies when managing patients with COVID-19 ∘∘ Patient care should be with respect and dignity which include but not limited to: medical support, food/water supply and accurate and timely information.

Infection prevention and control (IPC) measures • Initiate IPC at the point of entry of the patient to hospital and Screening should be done at first point of contact at the emergency department or outpatient department/clinics.

• Apply standard precaution, droplet precaution, contact precaution and airborne precaution.

Specific treatments Based on the severity the management is classified as follow: 1. Management of MILD COVID-19: symptomatic treatment and monitoring Patients with mild disease (absence of viral pneumonia and hypoxia) do not require hospital interventions; but isolation is necessary to contain virus transmission and will depend on national strategy and resources.

• Implement appropriate IPC to contain and mitigate transmission (can be done either in hospital or in repurposed, non-traditional settings; or at home)

Page 30 • Patients with risk factors for severe illness should be monitored closely.

• Provide symptomatic therapies with antipyretics or analgesics (the main choice of antipyretic is acetaminophen).

• Counseling them about signs and symptoms of complicated disease is important.

• Advise patients to keep hydrated • Adults: paracetamol :1 g paracetamol PO (using Nasogastric Tube (NGT)) every 6–8 hours. Maximum 4g/ 24hr • Children: 10–15mg/kg paracetamol every 6 hourly, maximum dose 60 mg/kg/ day • For patients who develop pneumonia but without severity sign management is as above but we may need to add empirical oral antibiotics.

•

Adults: Amoxicillin 500 mg PO TID or Amoxicillin- clavulanate 1 gm PO BID or 625mg po TID for 5-7 days.

• Children: 5mg/kg/day Amoxacillin for days 2-5; to reassess* in 48 h

2. Management of SEVERE COVID-19: oxygen therapy and monitoring Some patients with COVID-19 will have severe disease requiring hospitalization for management. Inpatient management of COVID-19 revolves around the supportive management of the most common complications of severe COVID-19: pneumonia, hypoxemic respiratory failure/ARDS, shock, multiorgan failure, and the complications associated with prolonged hospitalization including secondary nosocomial infection, thromboembolism, gastrointestinal bleeding, and critical illness polyneuropathy/ myopathy.

Admission to ward Every adult should be evaluated for severity of pneumonia in addition to other complications of COVID-19 with the CURB-65 (Confusion, Urea>7mmol/L or abnormal Creatinine value, Respiratory rate >30, Blood pressure <90/60, Age >65) Those patients with score of > 2 should be admitted to the ward.

In pediatrics the presence of danger sign like inability to breastfeed or drink, lethargy or unconsciousness, or convulsions should alert the clinician for admitting the patient.

General principles of Inpatient management of COVID-19 • Immediately provide supplemental oxygen therapy to patients with SARI and respiratory distress, hypoxemia or shock with a target of SpO2 ≥90 % for adults and SpO2 ≥ 92%for pregnant mother and children.

• Use conservative fluid management in patients with SARI when there is no evidence of shock.

• Administer appropriate empiric antimicrobials (broad spectrum) within 1 hour of identification of sepsis after taking specimen for culture and sensitivity.

Page 31 • If infiltrate on CXR for adult patient /fast breathing or signs of respiratory distress in child: ■■ Same supportive care as above + ■■ Ceftriaxone1 2 g IV q24h (Adults) or 75-100mg /kg q12h (Children): to reassess* in 48 h; max 5 days AND ■■ Azithromycin2 500 mg po on day 1 (Adults) or 10mg/kg/day (Children), then 250 mg po die (Adults) or 5mg/kg/day (Children) for days 2-5; to reassess* in 48 h; max 5 days.

• If infiltrate on CXR + severe disease/critically ill, if there is no response with the above alternative or if culture and sensitivity is suggestive.

■■ Same supportive care as above + ■■ Meropenem 1g IV q8h: to reassess* in 48h; Children 20mg/kg/24 IV q8h,max 5 days; ± Vancomycin 1 gm IV BID ■■ Azithromycin2 500 mg po on day 1 (Adults) or 10mg/kg/day (Children), then 250 mg po die (Adults) or 5mg/kg/day (Children) for days 2-5; to reassess* in 48 h; max 5 days • Patients who are critical, previously hospitalized or previous structural lung disorder: ceftazidime/Cefepime 2 gm IV TID ± Vancomycin 1 gm IV BID. • If aspiration pneumonia is suspected add Metronidazole 500 mg IV TID for 7 days.

• When patient improves and able to take PO, change antibiotic to PO Augmentin 2 gm PO BID for 7-10 days.

• Recognize severe hypoxemic respiratory failure when a patient with respiratory distress is failing standard oxygen therapy and prepare to provide advanced oxygen/ventilatory support.

• Do not routinely give systemic corticosteroids for treatment of viral pneumonia outside of clinical trials unless there are other clinical indications.

Oxygen Therapy Give supplemental oxygen therapy immediately to patients with SARI and respiratory distress, hypoxemia or shock and target > 94%.

• For adults: Adults with emergency signs (obstructed or absent breathing, severe respiratory distress, central cyanosis, shock, coma or convulsions) should receive airway management and oxygen therapy during resuscitation to target SpO2≥ 94%.

Initiate oxygen therapy at 5 L/min and titrate flow rates to reach target SpO2 ≥ 93% during resuscitation; or use face mask with reservoir bag (at 10–15 L/min) if patient in critical condition. Once patient is stable, the target is > 90% SpO2 in non-pregnant adults and ≥ 92–95% in pregnant patients.

• For children: target of SpO2 ≥ 94% in acute resuscitation is recommended; otherwise, the target SpO2 is ≥ 90%. Use of nasal prongs or nasal cannula is preferred in young children, as it may be better tolerated.

Page 32 °° In pediatrics patients Nebulization should be avoided to prevent the risk of aerosolization of the virus.

• The recommendation of the WHO and SSC on the targets of oxygen therapy are nearly similar other than the additional SSC recommendation in acute hypoxemic respiratory failure where SPO2 be maintained no higher than 96%.

Close Monitoring • Patients with COVID-19 should be monitored for signs of clinical deterioration, such as rapidly progressive respiratory failure and sepsis and respond immediately with supportive care interventions.

• Hematology and biochemistry laboratory testing, and ECG should be performed at admission and as clinically indicated to monitor for complications, such as acute liver injury, acute kidney injury, acute cardiac injury or shock.

• Understand the patient’s co-morbid condition(s) to tailor the management of critical illness. Determine which chronic therapies should be continued and which therapies should be stopped temporarily.

• Monitor for drug-drug interactions.

• Use conservative fluid management in patients with SARI when there is no evidence of shock. Patients with SARI should be treated cautiously with intravenous fluids, because aggressive fluid resuscitation may worsen oxygenation, especially in settings where there is limited availability of mechanical ventilation.

3. Management of Critical COVID-19 A)

Acute Respiratory Distress Syndrome (ARDS) Management

Acute respiratory distress syndrome (ARDS) is a clinical syndrome of severe dyspnea of rapid onset, hypoxemia, and diffuse pulmonary infiltrates leading to respiratory failure.

Diagnosis is made with the fulfillment of the following criteria.

• Onset within 1 week of a known clinical insult or new or worsening respiratory symptoms.

• Bilateral opacities on Chest imaging (radiograph, CT scan, or lung ultrasound) consistent with pulmonary edema but not fully explained by volume overload, lobar or lung collapse, or nodules.

• Respiratory failure should not fully explained by cardiac failure or fluid overload.

• Therefore objective assessment (e.g. echocardiography) need to be done to exclude hydrostatic cause of infiltrates/oedema.

• Oxygenation impairment in adults quantified as • Mild ARDS: 200 mmHg < PaO2/FiO2a≤ 300 mmHg (with PEEP or CPAP ≥ 5 cmH2O, or non-ventilated) •

Moderate ARDS: 100 mmHg < PaO2/FiO2 ≤ 200 mmHg (with PEEP ≥ 5 n-ventilated)

Page 33 • Severe ARDS: PaO2/FiO2 ≤ 100 mmHg (with PEEP ≥ 5 cmH2O, or nonventilated) • When PaO2 is not available, SpO2/FiO2 ≤ 315 suggests ARDS (including in non-ventilated patients).

• Oxygenation impairment in children: • Bi-level (NIV or CPAP) ≥ 5 cmH2O via full face mask: PaO2/FiO2 ≤ 300 mmHg or SpO2/FiO2 ≤ 264 • Mild ARDS (invasively ventilated): 4 ≤ OI < 8 or 5 ≤ OSI < 7.5 • Moderate ARDS (invasively ventilated): 8 ≤ OI < 16 or 7.5 ≤ OSI < 12.3 Severe ARDS (invasively ventilated): OI ≥ 16 or OSI ≥ 12.3.

(OI = Oxygenation Index and OSI = Oxygenation Index using SpO2.)

Use PaO2-based metric when available. If PaO2 not available, wean FiO2 to maintain SpO2 ≤ 97% to calculate OSI or SpO2/FiO2 ratio.

Hypoxemic respiratory failure in ARDS commonly results from intrapulmonary ventilation-perfusion mismatch or shunt and usually requires mechanical ventilation.

Among all patients, a range of 3% to 17% developed ARDS compared to a range of 20% to 42% for hospitalized patients and 67% to 85% for patients admitted to the ICU. Oxygen therapy whether standard or advanced follows a step-up approach .in the following we will try to highlight the major principles and recommendation in regards to HFNO, NIPPV, mechanical ventilation and ECMO. HFNO and NIPPV • High-flow nasal oxygen (HFNO) and Non-invasive ventilation (NIV) should only be used in selected patients with hypoxemic respiratory failure.

• Compared with standard oxygen therapy, HFNO reduces the need for intubation, has similar contamination risk to that of conventional oxygen and is more comfortable than NIPPV. • Patients with hypercapnia (exacerbation of obstructive lung disease, cardiogenic pulmonary edema), hemodynamic instability, multiorgan failure, or abnormal mental status should generally not receive HFNO. • In adults with COVID-19 and acute hypoxemic respiratory failure, SSC suggest using HFNC over NIPPV. • Adult HFNO systems can deliver 60 L/min of gas flow and FiO2 up to 1.0.

Pediatric circuits generally only handle up to 25 L/min, and many children will require an adult circuit to deliver adequate flow.

• The SSC were not able to make a recommendation regarding the use of helmet NIPPV compared with mask NIPPV. It is an option, but they are not certain about its safety or efficacy in COVID-19. This helmet NIPPV isn’t in common usage in our country but you could see it being use in many European countries like ITALY.

Page 34 • Patients receiving HFNO should be in a monitored setting and cared for by experienced personnel capable of endotracheal intubation in case the patient acutely deteriorates or does not improve after a short trial (about 1 hour).

• If HFNC is not available and there no urgent indication for endotracheal intubation, SSC suggest a trial of NIPPV with close monitoring.

Mechanical ventilation and ECMO ARDS commonly results from intrapulmonary ventilation-perfusion mismatch or shunt and usually requires mechanical ventilation. The recommendations here mostly revolve around standard ARDS care like decreasing barotrauma by having low tidal volume, avoiding decruitment by having higher PEEP and practicing prone ventilation to increase homogeneity of the ventilation.

The principal benefits of mechanical ventilation during respiratory failure are improved gas exchange and decreased work of breathing. Mechanical ventilation improves gas exchange by improving ventilation-perfusion (V/Q) matching.

• Endotracheal intubation should be performed by a trained and experienced provider using airborne precautions. Patients with ARDS, especially young children or those who are obese or pregnant, may desaturate quickly during intubation. Pre-oxygenate with 100% FiO2 for 5 minutes, via a face mask with reservoir bag, bag-valve mask, HFNO or NIV. •

Implement mechanical ventilation using lower tidal volumes (4–8 mL/ kg predicted body weight, PBW) and lower inspiratory pressures (plateau pressure < 30 cmH2O). In children, a lower level of plateau pressure (< 28 cmH2O) is targeted, and lower target of pH is permitted (7.15–7.30). Tidal volumes should be adapted to disease severity: 3–6 mL/kg PBW.

• In adult patients with severe ARDS, prone ventilation for 12–16 hours per day is recommended. Prone positioning should be recommended even in non ICU patients since it has shown to greatly improve V/Q mismatch in Covid-19 patients.

• In patients with moderate or severe ARDS, higher PEEP instead of lower PEEP is suggested.

• SSC suggest using, as needed, intermittent boluses of neuromuscular blocking agents (NMBA), over continuous NMBA infusion, to facilitate protective lung ventilation. In the event of persistent ventilator dyssynchrony, the need for ongoing deep sedation, prone ventilation, or persistently high plateau pressures, they suggest using a continuous NMBA infusion for up to 48 hours.

•

If recruitment maneuvers are used, SSC recommend against using staircase (incremental PEEP) recruitment maneuvers.

• In mechanically ventilated adults with COVID-19 and ARDS, SSC suggest using systemic corticosteroids, over not using corticosteroids • Avoid disconnecting the patient from the ventilator, which results in loss of PEEP and atelectasis.

Page 35 • Use in-line catheters for airway suctioning and clamp endotracheal tube when disconnection is required (for example, transfer to a transport ventilator).

•

B)

In settings with access to expertise in extracorporeal membrane oxygenation (ECMO), consider referral of patients with refractory hypoxemia despite lung protective ventilation.

Septic Shock Management:

Standard care includes early recognition and applying the six-sepsis management bundle with in 1 hour: appropriate fluid management, oxygen delivery, send specimen for culture and sensitivity, monitor lactate and urine output hourly, antimicrobial therapy, and initiation of fluid bolus and vasopressors for hypotension. ♦♦ Recognize septic shock in adults when infection is suspected or confirmed and vasopressors are needed to maintain mean arterial pressure (MAP) ≥ 65 mmHg AND lactate is ≥ 2 mmol/L, in absence of hypovolemia. ♦♦ Recognize septic shock in children with any hypotension (systolic blood pressure [SBP] < 5th centile or > 2 SD below normal for age) or two or more of the following: altered mental state; tachycardia or bradycardia (HR < 90 bpm or > 160 bpm in infants and HR < 70 bpm or > 150 bpm in children); prolonged capillary refill (> 2 sec) or feeble pulses; tachypnea; mottled or cold skin or petechial or purpuric rash; increased lactate; oliguria; hyperthermia or hypothermia.

• For the acute resuscitation of adults with COVID-19 and shock, SSC recommend using balanced crystalloids over colloids. SSC recommend against the use of hydroxyethyl starches,gelatins, dextran’s, albumin.

• Immediate aggressive volume expansion with isotonic solution, preferably R/L or alternative with normal saline, is the main stay of treatment. ›› Adults: start with at least 30 ml/kg in the first hours, then additional fluid boluses. ›› Children: 20 ml/kg as rapid bolus and up to 40-60ml/kg in the first hour.

■■ Reassess and decide the need for further fluid administration.

■■ If any sign of congestion decreases or discontinue fluid administration.

• In adults, administer vasopressors when shock persists during or after fluid resuscitation. In children administer vasopressors if there are signs of shock, ageappropriate blood pressure targets are not achieved; or signs of fluid overload are apparent.

• In adults with COVID-19 and shock, SSC suggest using dynamic parameters skin temperature, capillary refilling time, and/or serum lactate measurement over static parameters in order to assess fluid responsiveness .The initial blood pressure target is MAP ≥ 65 mmHg and serum lactate level should be >2mmol/L in adults and improvement of markers of perfusion.

Page 36 • For adults with COVID-19 and shock, SSC suggests using norepinephrine as the firstline vasoactive agent. If norepinephrine is not available, they suggest using either vasopressin or epinephrine as the first-line vasoactive agent adding vasopressin as a second-line agent, over titrating norepinephrine dose, if target mean arterial pressure (MAP) cannot be achieved by norepinephrine alone. °° For adults with COVID-19 and shock, SSC suggests using norepinephrine (230 µg/min or 0.1-1 µg/kg/min) as the first-line vasoactive agent. °° Epinephrine (2-30 µg/min or 0.1-1 µg/kg/min) OR dopamine (2-20 µg/kg/min) can be used respectively and titrate dose based on response. °° For children, epinephrine (0.1-0.3 µg/kg/min) is the first line vasopressor.

• For adults with COVID-19 and refractory shock, SSC suggest using low-dose corticosteroid therapy (“shock-reversal”), over no corticosteroid therapy. A typical corticosteroid regimen in septic shock is intravenous hydrocortisone 200 mg per day administered either as an infusion or intermittent doses.

• Broad spectrum antibiotics.

Special considerations for pregnant patients • Pregnant women with suspected or confirmed cases of COVID-19 should be treated with supportive therapies as described above, taking in to account the physiologic adaptations of pregnancy.

• Emergency delivery and pregnancy termination decisions are based on gestational age, maternal condition and fetal stability.

• Depending on the maternal and fetal condition consult with obstetrician, neonatologist and intensive care specialists.

• Up on delivery temporarily separate the newborn from the mother to reduce the risk of transmission pf the virus.

• Family members who give care to the newborn must wear PPEs. • If no family member to care for the newborn the mother must wear a medical mask and practice hand hygiene before each feeding or other close contact with her newborn.

• Mothers who intend to breastfeed must be encouraged to express their breast milk to establish and maintain milk supply.

C) Prevention of Complications: Implement interventions based on Surviving Sepsis or other guidelines, and are generally limited to feasible recommendations based on high-quality evidence.

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Page 38 Adjunctive therapies for COVID-19: corticosteroids Corticosteroids are not generally recommended for treatment of COVID-19 or any viral pneumonia. The benefit of corticosteroids in septic shock results from tempering the host immune response to bacterial toxin release. The incidence of shock in patients with COVID-19 is relatively low (5% of cases). It is more likely to produce cardiogenic shock from increased work of the heart need to distribute oxygenated blood supply and thoracic pressure from ventilation. guidelines for management of critically ill adults with COVID-19 specify when to use low-dose corticosteroids and when to refrain from using corticosteroids. The recommendations depend on the precise clinical situation (e.g., refractory shock, mechanically ventilated patients with ARDS); however, these particular recommendations are based on evidence listed as weak. An open-label prospective trial is planned to study clinical improvement in patients treated with methylprednisolone IV. Investigational Drugs and Biologics No drugs or biologics have been proven to be effective for the prevention or treatment of COVID-19. Numerous antiviral agents, immunotherapies, and vaccines are being investigated and developed as potential therapies. Searching for effective therapies for COVID-19 infection is a complex process.

Few examples of prospective treatments are discussed below.

Antiviral Agents Remdesivir The broad-spectrum antiviral agent remdesivir is a nucleotide analog prodrug. It was studied in clinical trials for Ebola virus infections but showed limited benefit. It has activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and related coronaviruses (including SARS and MERS CoV) both in vitro and in animal studies. Several phase 3 clinical trials are testing remdesivir for treatment of COVID-19.

One of those studies , known as the Adaptive COVID-19 Treatment Trial (ACTT) which is a randomized, placebo-controlled international trial sponsored by NIAID, which is part of the National Institutes of Health, USA , enrolled 1063 patients and began on February 21 . It is being conducted at 68 sites â&#x20AC;&#x2022; 47 in United States and 21 in countries in Europe and Asia. https://clinicaltrials.gov/ct2/show/NCT04280705

The interim results, which have not been published but were discussed in the press conference and in a NIAID press release, show that time to recovery (i.e., being well enough for hospital discharge or to return to normal activity level) was 31% faster for patients who received remdesivir than for those who received placebo (P < .001).The median time to recovery was 11 days for patients treated with remdesivir, compared with 15 days for those who received placebo. Results also suggested a survival benefit, with a mortality rate of 8.0% for the group receiving remdesivir and 11.6% for the patients who received placebo (P = .059).

The US Food and Drug Administration (FDA) on May 1 issued an emergency use authorization (EUA) for remdesivir for the treatment of suspected or laboratoryconfirmed COVID-19 in adults and children hospitalized with severe disease.

Page 39 Severe COVID-19 disease defined as • patients with an oxygen saturation (SpO2) ≤94% on room air or • requiring supplemental oxygen • requiring mechanical ventilation • requiring extracorporeal membrane oxygenation (ECMO) Optimal treatment duration is unknown but two phase 3 randomized open-label trials of remdesivir are comparing 5-day, 10-day, and standard-of-care treatments. https://clinicaltrials.gov/ct2/show/NCT04292899 https://clinicaltrials.gov/ct2/show/NCT04292730 Lopinavir/ritonavir A combination of lopinavir/ritonavir plus IFNb treatment improved clinical parameters in marmosets and mice infected with MERS-CoV.An in vitro study showed that the antiviral activity of remdesivir plus interferon beta (IFNb) was superior to that of lopinavir/ ritonavir. The use of this agent for treatment of COVID-19 has been described in case reports, but its efficacy is unclear, and it is being evaluated in larger randomized trials.

Hydroxychloroquine and chloroquine Hydroxychloroquine and chloroquine are widely used antimalarial drugs that were brought to the spot light after they were claimed to be the magic bullet for COVID -19 which lead to stock outs in pharmacy here and abroad. As inhibitors of heme polymerase, they are also believed to have antiviral activity via alkalinisation of the phagolysosome, which inhibits the pH-dependent steps of viral replication. It is reported that chloroquine effectively inhibits SARS-CoV-2 in vitro. Based on physiologically based pharmacokinetic (PBPK) models, recommend a loading dose of hydroxychloroquine 400 mg PO BID, followed by 200 mg BID for 4 days.

According to a consensus statement from a multicentre collaboration group in China, chloroquine phosphate 500 mg (300 mg base) twice daily in tablet form for 10 days may be considered in patients with COVID-19 pneumonia ( which is 14 times the typical dose of chloroquine used per week for malaria prophylaxis and 4 times that used for treatment).

Positive results regarding the effectiveness of hydroxychloroquine was generated from small scale and uncontrolled studies. Following this some countries have adopted it in their guideline while others recommend against it outside clinical trials. The other issue has been the safety profile especially concerning the arrhythmogenicity since high dose of hydroxychloroquine was being used for COVID patients. Thus emphasizing the cautious use of such recommendations until sufficient data is available through RCT studies.

Page 40 Hydroxychloroquine plus azithromycin This combination gained fame in the media and after one study in France reported improved nasopharyngeal clearance of the virus on day 6 which was an unusual approach. In addition, there were other irregularities with the study that weakened any evidence that could be driven from this.

Another small open-label study of hydroxychloroquine in France included azithromycin in 6 patients for potential bacterial superinfection (500 mg once, then 250 mg PO daily for 4 days). These patients were reported to have 100% clearance of SARS-CoV-2. While intriguing, these results warrant further analysis. The patients receiving combination therapy had initially lower viral loads, and, when compared with patients receiving hydroxychloroquine alone with similar viral burden, the results are fairly similar (6/6 vs 7/9).

All in all, further RCT studies are needed to clearly delineate the benefit and the risk of using this combination drugs.

Since this medications are being used in our country it’s good to be aware of their adverse effects like QT prolongation when the two drugs are co-administered.

Overall IDSA recommends hydroxychloroquine/chloroquine ± azithromycin, lopinavir/ ritonavir, tocilizumab, convalescent plasma only in the context of clinical trial due to knowledge gap.

Other investigational antivirals Other investigational antivirals being tested for efficacy against COVID-19 include tocilizumab (IL-6 inhibitor), rintatolimod (toll-like receptor 3 [TLR-3] agonist), azvudine (nucleoside reverse transcriptase inhibitor), danoprevir (NS3/4A HCV protease inhibitor), plitidepsin (targets EF1A), and favipiravir (viral RNA polymerase inhibitor).

Discharge criteria for COVID-19 cases admitted to treatment centers 1. Patient diagnosed with COVID-19 pneumonia can be discharged when the symptoms have subsided, body temperature remains normal for at least 3 days, two consecutive lab tests are negative and radiological improvement.

2. Any person who has contact with confirmed COVID-19 case has to be followed for 14 days: • If no symptoms develop within 14 days follow up, discharge from follow up.

• If symptoms develop during the 14 days quarantine, admit the patient, treat and follow the same protocol for discharge.

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IFMSA COVID-19 LIBRARY GUIDE Situation Reports + Interactive Maps: Updated on a daily basis 1. WHO Situation Dashboard: https://covid19.who.int/ 2. CSSE COVID-19 Global Map: https://www.arcgis.com/apps/opsdashboard/index. html?fbclid=IwAR1nUkJjv4YlQsuTdBtTdXlaP211YoiP9liOt1ekUn10VJj7G3V6sFFzP-c#/ bda7594740fd40299423467b48e9ecf6 3. WHO Situation reports: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports 4. COVID-19 Response Fund: https://covid19responsefund.org/ Guidelines: 1. WHO-CDC Guidelines for Clinical Management of COVID-19: https://www.who.int/docs/default-source/coronaviruse/clinical-management-of-novelcov.pdf?sfvrsn=bc7da517_2 2. WHO Guidelines for Health Workers: https://www.who.int/docs/default-source/coronaviruse/who-rights-roles-respon-hwcovid-19.pdf?sfvrsn=bcabd401_0 3. WHO Guidelines for Workplace Safety: https://www.who.int/docs/default-source/coronaviruse/getting-workplace-ready-forcovid-19.pdf 4. WHO-UNICEF COVID-19 Prevention in Schools: https://www.who.int/docs/default-source/coronaviruse/key-messages-and-actions-forcovid-19-prevention-and-control-in-schools-march-2020.pdf?sfvrsn=baf81d52_4 5. WHO Mental Health Considerations during COVID-19 Outbreak: https://www.who.int/docs/default-source/coronaviruse/mental-health-considerations. pdf?sfvrsn=6d3578af_2

Page 42 Online Trainings: 1. WHO Operational Planning Guidelines and COVID-19 Partners Platform to support country preparedness and response: https://openwho.org/courses/UNCT-COVID19-preparedness-and-response-EN 2. WHO Infection Prevention and Control for COVID-19: https://openwho.org/courses/COVID-19-IPC-EN 3. WHO COVID-19 Simulation Exercise: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/training/simulationexercise 4. FutureLearn: disease outbreak prevention courses: https://www.futurelearn.com/subjects/healthcare-medicine-courses/outbreakprevention Videos: A. Videos (longer videos): i. What can people do to protect themselves and others from getting the new coronavirus? https://youtu.be/bPITHEiFWLc ii. How to wash hands (WHO): https://www.youtube.com/watch?v=3PmVJQUCm4E iii. How to wash hands (CDC): https://www.youtube.com/watch?v=d914EnpU4Fo iv. Why is it recommended to avoid close contact with anyone who has fever and cough? https://youtu.be/bPITHEiFWLc v. How is the new coronavirus affecting people who get it? https://youtu.be/bPITHEiFWLc vi. Q and A: On Mental Health https://www.facebook.com/WHO/videos/819204905251053/ UzpfSTE3MTIyMzUzNjI1NTI0NjozMDE0MzY3Mjk1Mjc0MTc1/ vii. Q and A: Travelling with Coronavirus outbreak https://youtu.be/bPITHEiFWLc viii. WHO: Q and A: on mental health: https://www.pscp.tv/w/1OwxWQboPqDGQ

Page 43 B. Videos (shorter videos):

7 simple steps to protect yourself and others from:

https://www.instagram.com/p/B9mAMvwJKyx/?igshid=lt69pbk9arba

WHO: How is COVID Spread and how do you protect against it (IGTV)

https://www.instagram.com/tv/B9WxI3IpR6k/?igshid=1j0jhbm0vd6nq

WHO: What can people do to protect themselves and others:

https://www.instagram.com/tv/B9FyJVXJzRL/?igshid=zzl55hbggtf3 C. Other Instagram posts:

WHO: How to Hand Wash:

https://www.instagram.com/p/B9gPu23pB0W/?igshid=1gc8giedq4lcg

WHO: How to Handrub:

https://www.instagram.com/p/B9fSP4MpkuL/?igshid=t73rcidmnmkh

WHO: The #SafeHands Challenge

https://www.instagram.com/tv/B9q7cXxpkZ6/?igshid=1df71ld9rryt1

United Nations:

https://www.instagram.com/tv/B9sk4rlJ9LB/?igshid=x9dhpm5eq48l Region-Specific Maps: 1. WHO European Region Dashboard: https://who.maps.arcgis.com/apps/opsdashboard/index.html?fbclid=IwAR1dDD94QOVcy9ozO1vhBMW2eTba570sMayf91GotXfmFVOMDalZafKHwfM#/ ead3c6475654481ca51c248d52ab9c61 2. European Centre for Disease Prevention and Control: https://www.ecdc.europa.eu/en/cases-2019-ncov-eueea

Q and A:

WHO: https://www.who.int/news-room/q-a-detail/q-a-coronaviruses?fbclid =IwAR0N3eBzJB4YEbLw44nxijhajzXOATPtK0RG7qhbCHgE4_zcHvrFTANYT0A Apps: ECDC App: https://www.ecdc.europa.eu/en/publications-data/ecdc-news-palm-your-hand-download-our-app?fbclid=IwAR3F0roj0C9Qs15EDgzLuFmoJ4dTve5qAInsNJLWgaEs6wZbmNDBpb9KcYc Local Data (Ethiopian) http://www.moh.gov.et http://www.moh.gov.et/covid19-courses/

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REFERENCES CDC Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19) revised, April 3, 2020 Medscape Coronavirus Disease 2019 (COVID-19) Treatment &Management, Updated: Apr 06, 2020 NICE COVID-19 rapid guideline: critical care in adults Published date: 20 March 2020 Last updated: 31 March 20 Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19) UpToDate Coronavirus disease 2019 (COVID-19), updated: Mar 05, 2020 WHO Interim Guidance on Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected ,13 March 2020 Imperial College COVID-19 Response Team -Report 9 Imperial College COVID-19 Response Team - The Global Impact of COVID-19 and Strategies for Mitigation and Suppression National COVID-19 Response Advisory Council- Effectivenes of Non-Pharmacological Interventions for COVID-19 Prevention and Control: Evidence and Recommended Interventions for Ethiopia FMOH, National Comprehensive COVID19 Management Handbook, First edition - April 2020 ht tps://medium.com/@ tomaspueyo/coronavirus-the-hammer-and-the-dancebe9337092b56?source=---------10------------------