coronavirus%20disease%202019%20(covid-19)
CORONAVIRUS DISEASE 2019 (COVID-19)
Treatment Guideline Chart

It is a viral infection of the respiratory tract caused by a newly emergent coronavirus, SARS-CoV-2, that was recognized in Wuhan, China in December 2019.

Mode of transmission is through contact and droplet via direct indirect, or close contact with infected individuals through secretions ie saliva and respiratory secretions.

Generally after exposure to the virus, the mean time to develop symptoms is 4-6 days, with a range of between 1 and 14 days.

Coronavirus%20disease%202019%20(covid-19) Management

Isolation

  • The separation of infected COVID-19 patients from those who are not infected
  • Isolate asymptomatic COVID-19-positive patients and individuals with COVID-19 symptoms who can recover at home 
  • During isolation the patient should: 
    • Monitor symptoms and if there are warning signs, seek emergency care
      • Warning signs include difficulty of breathing, persistent or new-onset fever, respiratory rate >25, persistent pressure or pain in the chest, new confusion, inability to wake or keep awake, bluish lips or face
    • If possible, stay in a separate room from other members of the household
    • If possible, use separate bathrooms
    • Avoid contact with other members of the household and pets
    • Not share personal household items eg cups, towels, utensils
    • Wear a mask if around other people

Criteria for Releasing COVID-19 Patients from Isolation

  • For symptomatic patients: 
    • 10 days after onset of symptom, plus 
    • At least 3 additional days without symptoms (eg without fever and respiratory symptoms)
  • For asymptomatic patients: 10 days after positive test for SARS-CoV-2

Prevention

Hand Hygiene

  • Most effective action to be taken to reduce the spread of pathogens and prevent infections 
  • It is recommended to wash hands with soap and water whenever possible especially:
    • After coughing or sneezing
    • When caring for sick
    • Before, during and after preparing food
    • Before eating
    • After toilet use
    • When hands are visibly dirty
    • After handling animals or animal waste
  • Hand sanitizers are used if handwashing is not possible
  • Hand sanitizers should contain at least 60% alcohol
  • Apply the hand sanitizer properly by rubbing the gel over all surfaces of the hands and fingers until the hands are dry
  • It has been shown in the evidence from both the SARS and COVID-19 epidemics that hand hygiene is very important to protect healthcare workers from getting infected
  • Plain soap is effective at inactivating enveloped viruses such as the COVID-19 virus due to the oily surface membrane that is dissolved by soap thus killing the virus
  • Duration of alcohol-based hand rubbing is for 20-30 seconds while handwashing with soap and water should be for 40-60 seconds

Face Masks 

  • It is recommended that a face mask be worn in public settings, like in public and mass transportation, at events and gatherings, and anywhere that the person will be around other people
  • It is used for either protection of healthy persons or to prevent onward transmission
  • Medical face mask is recommended for:
    • Healthcare workers in clinical settings
    • Any person who is feeling unwell that includes those with mild symptoms, ie muscle aches, slight cough, sore throat or fatigue
    • COVID-19 positive individuals or those awaiting result of COVID-19 test
    • Those caring for suspected or confirmed COVID-19 patients outside of health facilities
    • Those aged ≥60 years old
    • Those at any age who have underlying conditions including chronic respiratory disease, cardiovascular disease, cancer, obesity, immunocompromised status and diabetes mellitus
  • Non-medical fabric mask is recommended for the general public under the age of 60 and who do not have underlying health conditions
  • Fabric mask should: 
    • Have good filtration rate 
    • Cover the nose and mouth completely
    • Snugly fit against the side of the face and does not have gaps
    • Have ≥2 layers of washable, breathable fabric
      • Inner layer of absorbent material, such as cotton
      • Middle layer of non-woven non-absorbent material, such as polypropylene
      • Outer layer of non-absorbent material, such as polyester or polyester blend
  • Medical/surgical masks should possess the following properties: 
    • Consist of 3 layers of synthetic non-woven materials
    • Configured to have filtration layers sandwiched in the middle
    • Available in different thicknesses
    • Have various levels of fluid resistance and filtration
  • Respirators (also known as filtering facepiece respirators – FFP) are available at different performance levels ie FFP2, FFP3, N95, N99 
    • Used to protect healthcare workers who provide care to COVID-19 patients in settings and areas where aerosol-generating procedures are undertaken
    • Before using the respirator, healthcare workers should be fit tested to ensure that they wear the correct size
  • Medical masks and respirator masks have similar protection value
  • Hands should be washed before putting on a mask
  • Do not touch the mask while wearing it
  • In taking off the mask, handle only by the ear loops or ties then fold outside corners together and dispose properly
  • In washing mask, use regular laundry detergent and the warmest appropriate water setting for the cloth used to make the mask and then leave in the dryer until completely dry
  • Masks or respirators with exhalation valves are not recommended

Social/Physical Distancing

  • It is keeping a safe distance of at least 6 feet (about 2 arms length) between people who are not living in the same household
  • It should be practiced along with handwashing, wearing of masks and avoiding touching face with unwashed hands
  • It is important to have social distancing since the virus can be spread by people who are asymptomatic but already have the disease
  • It is also important for the protection of people who are at higher risk for severe illness from COVID-19
  • Helps limit chances of coming into contact with contaminated surfaces and infected people outside the home 

Other Preventive Measures

  • Avoid touching eyes, nose, and mouth with unwashed hands
  • Cover cough or sneeze with a tissue, then throw the tissue in the trash
  • Clean and disinfect frequently touched objects and surfaces

Ventilation

  • The intentional introduction of fresh air into a space while the stale air is removed to be able to maintain the quality of air in the space 
  • It is important in preventing the spread of SARS-CoV-2 virus indoors by reducing the airborne concentration of the virus that can come in contact with the occupants 
  • It is recommended to have an increased ventilation rate through natural or mechanical means, preferably without recirculation of the air 
    • Natural ventilation should be considered by opening windows or doors if possible and safe to do so 
    • For mechanical systems, use economizer modes of heating, ventilation and air conditioning (HVAC) operations and potentially as high as 100% in order to increase the percentage of outdoor air
    • Filters should be cleaned regularly in cases of air recirculation

Personal Protective Equipment (PPE)

  • Healthcare personnel caring for patients with suspected or confirmed COVID-19 should have PPE composed of the following:
    • N95 respirator (or equivalent or higher-level respirator) or facemask (if a respirator is not available) should be worn before entry into the patient’s room; should be removed and disposed properly upon exiting patient’s room and hand hygiene should be done
    • Eye protection using goggles or a face shield that covers the front and sides of the face should be worn before entering the patient’s room; it should be compatible with the respirator
    • Gloves that are clean and non-sterile should be worn before entry into patient’s room; should be removed and disposed properly upon exiting patient’s room and hand hygiene should be done; double gloving is not recommended 
    • Isolation gown that is clean should be worn before entry into patient’s room; should be removed and disposed properly upon exiting patient’s room and hand hygiene should be done; wearing >1 gown at a time is not recommended

Vaccines

  • As of 22 October 2021, based on WHO data, there are 128 vaccines undergoing clinical development
  • As of 20 October 2021, a total of 6,655,399,359 vaccine doses have been administered worldwide as per WHO data 
  • Vaccines can be given to the following:
    • Adults
      • Vaccines with recent emergency use authorization approval can only be administered to patients age ≥16-18 years old and above with some vaccines indicated only for patients up to 59 years of age
    • Adolescents 12-15 years old but only with one of the mRna vaccines that had recent emergency use authorization (EUA) approval
    • Patients who are planning to conceive
    • Currently pregnant or who are lactating
    • Immunocompromised or cancer patients would need clearance from their physicians
  • The following COVID-19 vaccines are currently undergoing large-scale clinical trials; please refer to local drug regulatory agency for further information

mRNA Vaccines

  • Eg mRNA-1273 given EUA approval in some countries, BNT162b1 was recently approved by US FDA for patients ≥16 years of age
  • Nucleoside-modified RNA (mRNA) that encodes the spike glycoprotein (S-protein) present on the surface of SARS-CoV-2 virus that generates sufficient immunogenic response and induces vigorous binding antibody responses to both full-length spike protein and receptor-binding domain
  • Both B cells and T cells are involved in the immune response
  • Contains no live components thus there is no risk of the vaccine triggering the disease
  • Immunogenicity is modifiable, efficacy is stable and there is no anti-vector immunity
  • Due to the high immunogenicity of these vaccines it may cause increased reactogenicity that may result to more reports of local and systemic adverse reactions 
  • Ultra-cold storage is required in some of the mRNa vaccines

Protein Subunit Vaccines

  • Include harmless pieces (proteins) of the virus that cause COVID-19 instead of the entire microbe
  • Once vaccinated, the immune system recognizes that the proteins do not belong in the body and begins making T-lymphocytes and antibodies
  • If the individual is re-infected in the future, memory cells will recognize and fight the virus
  • Both B cells and T cells are involved in the immune response
  • Suitable in patients who are immunocompromised
  • Contains no live components thus no risk of the vaccine triggering the disease
  • Relatively stable
  • May require adjuvant and booster shots

Viral Vector Vaccines

  • Eg non-replicating viral vector (ChAdOx1-S), human adenovirus (Ad26.COV2.S) that were recently given EUA approval in some countries
  • Use a modified version of a different virus (the vector) to induce both humoral and cellular immunity
  • Both B cells and T cells are involved in the immune response triggered by the antigen
  • Those who have been previously exposed to the human virus used as vector may have a weaker immune response to the vaccine due to previous immunity to the vector

Inactivated Vaccines

  • Eg CoronaVac that was given EUA approval in some countries
  • Completely inactivated or killed pathogen induces protective antibodies against epitopes of hemagglutinin glycoprotein on surface of the virus
  • Tend to produce a weaker immune response than live attenuated vaccines, thus adjuvants are required to provide an effective immune response
  • Both T cells and B cells are involved in the immune response
  • Not suitable to those who are immunocompromised
  • Relatively sensitive to temperature thus it is necessary to have a careful storage

Vaccine Booster

  • Refers to another dose of a vaccine that was given to a patient that gained enough protection after vaccination but with a waning immunity
  • Recently, US FDA has granted EUA for BNT162b2 & mRNA-1273 to be used as a single booster dose and to be given at least 6 months after completion of the primary series in the following population:
    • ≥65 years old
    • 18-64 years old at high risk of severe COVID-19
    • 18-64 years old who has high risk of serious complication of COVID-19 including severe COVID-19 due to frequent institutional or occupational exposure to SARS-CoV-2
  • US FDA has also granted EUA for JNJ-78436735 to be used as a single booster dose to be administered at least 2 months after completion of the single-dose primary regimen to patients ≥18 years old
  • The US FDA EUA also states that the available COVID-19 vaccines may be used as a heterologous (or "mix & match") booster dose to all eligible individuals following the completion of the primary regimen of a different COVID-19 vaccine 
  • WHO together with the Strategic Advisory Group of Experts (SAGE) on Immunization and its COVID-19 Vaccines Working Group are still reviewing the emerging evidence on the need for and timing of booster dose
  • Declining vaccine effectiveness, epidemiological setting, risk group, vaccine coverage rates and global vaccine supply and global and national equity should be considered before giving booster doses

Comorbidities

  • There is an increased risk for severe COVID-19 illness in adult patients of any age with certain underlying conditions
  • There are currently limited data and information on the effects of many comorbidities on the risk for severe COVID-19 illness
  • It is essential that those people at increased risk of severe illness of COVID-19 and those who live with them to protect themselves from getting COVID-19 

Asthma

  • Systematic reviews have shown that people with asthma are not at increased risk of acquiring COVID-19 
    • However, there is an increased risk of COVID-19 deaths in asthmatic patients who recently needed treatment with oral corticosteroids
  • It is recommended that patients with severe asthma continue to take biologic therapy or oral corticosteroids if prescribed 
  • When asthma worsens, it is recommended to increase controller and reliever medications
  • If appropriate, a short course of oral corticosteroids can be taken for patients with severe asthma exacerbations
  • Nebulizers should be avoided, where possible, in order to avoid spread of the virus
    • It is preferred to use pressurized metered-dose inhaler via a spacer except for life-threatening exacerbations
  • In patients with confirmed or suspected COVID-19, avoid spirometry

Cardiovascular Disease (CVD)

  • COVID-19 patients with cardiovascular comorbidities are common and they have higher risk of morbidity and mortality 
    • Thus, CVD prevention strategies are essential especially strategies that brings a wide spectrum of possible beneficial effects
  • SARS-CoV-2 counteracts the effects of angiotensin II in conditions with excessive activation of renin-angiotensin system
  • >25% of critical cases of COVID-19 exhibit myocardial injury and present as acute myocardial injury and dysfunction on presentation and myocardial injury that develops as illness severity intensifies
    • It can be caused by direct myocardial injury associated with upregulation of ACE2 in the heart and coronary vessels, or can be secondary to molecular mimicry following the activation of adaptive autoimmune-type mechanisms, or be exacerbated by hypoxia in the context of respiratory failure
  • It is recommended to continue clinically indicated ACE inhibitor and angiotensin receptor blocker (ARB) medications at this time
  • Case series data have shown that there is a massive inappropriate activation of the coagulation cascade that occur in COVID-19 patients
    • Low-molecular-weight Heparin or Fondaparinux has been recommended in hospitalized COVID-19 patients

Hypertension

  • Most frequent comorbidity in COVID-19 patients
  • It is believed that the use of ACE inhibitors contributes to the entry of SARS-CoV-2 in the cells but present data show no association between COVID-19 and hypertension
  • No clinical data showed beneficial or adverse outcomes in those who used ACE inhibitors, ARBs, or other renin-angiotensin aldosterone system antagonists in COVID-19
  • It is recommended to continue clinically indicated ACE inhibitor and ARB medications at this time, and until further information becomes available, it is recommended to treat hypertensive patients based on current clinical practice guidelines 

Diabetes Mellitus

  • Individuals with diabetes with poor glycemic control have a high risk of severe illness or poor prognosis from COVID-19 
  • Mechanisms that can increase the ability of COVID-19 to impact patients with diabetes include: 
    • Decreased viral clearance
    • Diminished function of T-cell
    • Increased susceptibility to hyperinflammation and cytokine storm
    • Presence of cardiovascular disease
  • Poorer prognosis of patients with diabetes might be caused by the syndromic nature of the disease and the following conditions that increase the risk: Hyperglycemia, older age, comorbidities in particular hypertension, obesity and cardiovascular disease
  • For patients with mild COVID-19, glucose-lowering therapies should be continued and blood glucose monitoring should be performed
  • In hospitalized patients with severe COVID-19, there might be a need to modify their diabetes therapy that includes withdrawing ongoing treatments and initiating insulin therapy depending on the severity of the COVID-19 disease
  • Insulin and dipeptidyl peptidase-4 (DPP-4) inhibitors therapy may be continued in patients with COVID-19
  • Antiviral drugs such as Lopinavir and Ritonavir may lead to hyperglycemia and may worsen glycemic control
  • Glucocorticoid use may cause worsening of insulin resistance or glycemic control, sustaining gluconeogenesis, and marked hyperglycemia

Dyslipidemia

  • Generally, all individuals in lipid-lowering therapy should continue medications even in pandemic or in patients with increased risk of COVID-19 infection 
  • In patients with confirmed COVID-19, lipid lowering therapy may still continue with care on the avoidance of drug interaction between lipid-lowering medications and drugs that is being used for treatment of COVID-19 especially in patients with abnormal liver function tests 
  • Statin therapy initiation may be considered in high-risk patients during severe manifestations of COVID-19 to prevent some of the life-threatening cardiovascular complications 
    • Some studies have shown that statin therapy helps in plaque stabilization, cholesterol reduction, CVD risk prevention and reduction of inflammation and have potential antiviral properties

Obesity

  • Has been associated with more severe illness of COVID-19 and death
  • Abdominal fat has detrimental ventilatory effect as there is a need for more mechanical ventilation for those with a BMI >35 kg/m2 than those with BMI <25 kg/m2
  • Intravascular disseminated coagulation may develop causing impaired lung perfusion in patients with severe COVID-19
  • Associated with immune dysregulation and chronic inflammation that could cause organ failure in patients with COVID-19

SARS-COV-2 Reinfection

  • Repeat testing for evaluation of reinfection should be considered only for those patients that have fully recovered from initial SARS-CoV-2 infection but present with symptoms compatible with COVID-19 with no obvious alternative etiology
  • Reinfection often occurs in those with weak immune response during the initial infection, as is usually reported in those with mild illness
    • May also occur as initial immune responses wane over time
  • Treatment of reinfection is the same as that for initial infection
 

COVID-19-Associated Pulmonary Aspergillosis (CAPA)

 
  • SARS-CoV-2 infection may cause severe damage to the airway epithelium that will enable aspergillus invasion
  • There have been reports that this is caused by azole-resistant aspergillus
  • Presence of any of the following clinical findings warrant diagnostic investigation for CAPA in patients with refractory respiratory failure for >5-14 days despite receiving all therapy for severe COVID-19 patients: 
    • Refractory fever for >3 days or new fever after a period of defervescence of >48 hours during appropriate antibiotic therapy in the absence of any other obvious cause
    • Worsening respiratory status (eg tachypnea or increasing oxygen requirements)
    • Hemoptysis
    • Pleural friction rub or chest pain
  • IV Voriconazole or Isavuconazole is a recommended treatment while for azole-resistant aspergillus, liposomal Amphotericin B is recommended
    • It is suggested to have 6- to 12-week treatment course 
  • Weekly therapeutic drug monitoring of patients with CAPA is recommended especially in cases of fully susceptible Aspergillus sp

COVID-19 and Mental Health

  • In early May 2020, the United Nations has recommended that actions should be done in order to minimize mental health consequences of the COVID-19 pandemic
  • Studies made in Spain and China show an association of the job situation, the expected negative economic consequences, the perceived worsening of health and habits and the worries about COVID-19 infection with depressive symptomatology during the confinement
  • Depression and difficulty with thinking and concentration (sometimes referred to as "brain fog") are among the common long-term symptoms in patients who have recovered from COVID-19 infection

Multisystem Inflammatory Syndrome in Children (MIS-C)

  • Also called pediatric multisystem inflammatory syndrome (PMIS), pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), pediatric hyperinflammatory syndrome or pediatric hyperinflammatory shock
  • A confirmed <21 year-old COVID-19 patient or had COVID-19 exposure in the past 4 weeks with no alternative diagnosis presenting with the following: 
    • Fever
    • Laboratory evidence of inflammation
    • Clinically severe illness requiring hospitalization
    • Multisystem (≥2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic, or neurological)

Signs and Symptoms

  • Persistent fever
  • Evidence of organ dysfunction or shock
  • Kawasaki disease-like symptoms eg conjunctivitis, red eyes, red or swollen hands or feet, rash, red cracked lips, swollen glands
  • Toxic shock syndrome-like features with hemodynamic instability
  • Cytokine storm/macrophage activation or hyperinflammatory features
  • Thrombosis, poor heart function, diarrhea and gastrointestinal symptoms, acute kidney injury
  • Shortness of breath suggestive of congestive heart failure
  • Respiratory symptoms typically reported in adults with COVID-19 may not be present in pediatric patients with MIS-C

Laboratory Findings

  • Abnormal levels of inflammatory markers in the blood eg elevated ESR/CRP and ferritin, LDH
  • Lymphopenia <1000, thrombocytopenia <150,000, neutrophilia
  • Elevated B-type natriuretic peptide (BNP) or NT-proBNP (pro-BNP), hyponatremia, elevated D-dimers

Treatment

  • IVIG 1 to 2 g/kg with timing of administration influenced by patient’s cardiac function and fluid status
  • Steroid therapy (ranging from 2 to 30 mg/kg/day of Methylprednisolone depending on severity of illness) and biologics (eg Anakinra 2 to 10 mg/kg/day, subcutaneously or intravenously, divided every 6 to 12 hours) 
    • Patients often go home with a 3-week taper of steroids and/or biologics
  • Concurrent antibiotic therapy has been given due to need of early intervention and need to initiate treatment for multiple possible etiologies
  • For patients with Kawasaki-like syndrome, low-dose Aspirin at a minimum is given 
  • For patients with thrombosis, Enoxaparin is given 

Prevention

  • Patients with suspected MIS-C that have been hospitalized should be considered as patients under investigation for COVID-19
    • RT-PCR and antibody testing for COVID-19 should be done

Follow-up

  • Starting 2-3 weeks after discharge, patients diagnosed with MIS-C should have close outpatient pediatric cardiology follow-up
  • For patients diagnosed with myocarditis, cardiology-directed restriction and/or release from vigorous activities is recommended
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