COVID-19

Infectious Diseases


Clinicals: History

Fact Explanation
{"ops":[{"insert":"Introduction\n"}]}
{"ops":[{"insert":"COVID-19 is an infectious disease caused by the coronavirus SARS-CoV-2. Coronaviruses are positive-sense single-strand RNA viruses with a crown-like envelope. Transmission occurs primarily via respiratory droplets. The mean incubation period is on average 5-6 days (with a 2-12 day range). The spectrum of illness can range from asymptomatic infection to severe pneumonia requiring ICU admission.\n"}]}
{"ops":[{"insert":"No symptoms\n"}]}
{"ops":[{"insert":"Asymptomatic patients have subclinical disease. This is defined as the absence of symptoms and signs of COVID-19.\n"}]}
{"ops":[{"insert":"Constitutional symptoms\n"}]}
{"ops":[{"insert":"Patients may complain of fatigue, myalgia, headache, weakness, and chills. These symptoms are thought to be due to the inflammatory response.\n"}]}
{"ops":[{"insert":"Fever\n"}]}
{"ops":[{"insert":"Fever is one of the most common symptoms of COVID-19. This is thought to be due to the release of pro-inflammatory cytokines that are triggered by the immune response to the virus.\n"}]}
{"ops":[{"insert":"Respiratory symptoms\n"}]}
{"ops":[{"insert":"These include cough (which is usually dry, but can be productive), dyspnea, rhinorrhea, sore throat and chest pain. These symptoms are thought to be due to the inflammatory response to viral infection of the bronchial epithelial cells and alveolar pneumocytes. \n"}]}
{"ops":[{"insert":"Gastrointestinal symptoms\n"}]}
{"ops":[{"insert":"Nausea, vomiting, diarrhea and abdominal pain are common complaints. It is hypothesized that "},{"insert":"SARS-CoV-2 infects intestinal epithelial cells, impacting host microbial flora and causing gut inflammation.","attributes":{"color":"#212121","background":"#ffffff"}},{"insert":"\n"}]}
{"ops":[{"insert":"Neurological symptoms\n"}]}
{"ops":[{"insert":"This includes confusion or impairment of consciousness. New-onset anosmia and ageusia may also occur. "},{"insert":"This is thought to be due to the binding of SARS-CoV-2 to ACE2 receptors ","attributes":{"color":"#212529","background":"#ffffff"}},{"insert":"found in neurons, astrocytes, oligodendrocytes, and olfactory support cells.\n"}]}
{"ops":[{"insert":"Risk factors\n"}]}
{"ops":[{"insert":"Comorbidities such as advanced age (\u003E65 years old), obesity, male gender, chronic comorbidities (severe cardiovascular disease, chronic obstructive pulmonary disease, chronic kidney disease, cerebrovascular disease, diabetes, liver disease) predispose to more severe symptoms and a "},{"insert":"greater mortality risk.","attributes":{"color":"#212529","background":"#ffffff"}},{"insert":"\n"}]}
{"ops":[{"insert":"Symptoms of complications\n"}]}
{"ops":[{"insert":"Severe disease may result in interstitial pneumonia, acute respiratory distress syndrome (ARDS), impaired cardiac function, myocarditis, stroke, thromboembolic events, acute kidney injury, or multi organ failure. "},{"insert":"This is thought to be due to the cytokine storm that accompanies COVID-19 infection.","attributes":{"color":"#212529","background":"#ffffff"}},{"insert":"\n"}]}
{"ops":[{"insert":"Introduction\n"}]}
{"ops":[{"insert":"COVID-19 is an infectious disease caused by the coronavirus SARS-CoV-2. Coronaviruses are positive-sense single-strand RNA viruses with a crown-like envelope. Transmission occurs primarily via respiratory droplets. The mean incubation period is on average 5-6 days (with a 2-12 day range). The spectrum of illness can range from asymptomatic infection to severe pneumonia requiring ICU admission.\n"}]}
{"ops":[{"insert":"No symptoms\n"}]}
{"ops":[{"insert":"Asymptomatic patients have subclinical disease. This is defined as the absence of symptoms and signs of COVID-19.\n"}]}
{"ops":[{"insert":"Constitutional symptoms\n"}]}
{"ops":[{"insert":"Patients may complain of fatigue, myalgia, headache, weakness, and chills. These symptoms are thought to be due to the inflammatory response.\n"}]}
{"ops":[{"insert":"Fever\n"}]}
{"ops":[{"insert":"Fever is one of the most common symptoms of COVID-19. This is thought to be due to the release of pro-inflammatory cytokines that are triggered by the immune response to the virus.\n"}]}
{"ops":[{"insert":"Respiratory symptoms\n"}]}
{"ops":[{"insert":"These include cough (which is usually dry, but can be productive), dyspnea, rhinorrhea, sore throat and chest pain. These symptoms are thought to be due to the inflammatory response to viral infection of the bronchial epithelial cells and alveolar pneumocytes. \n"}]}
{"ops":[{"insert":"Gastrointestinal symptoms\n"}]}
{"ops":[{"insert":"Nausea, vomiting, diarrhea and abdominal pain are common complaints. It is hypothesized that "},{"insert":"SARS-CoV-2 infects intestinal epithelial cells, impacting host microbial flora and causing gut inflammation.","attributes":{"color":"#212121","background":"#ffffff"}},{"insert":"\n"}]}
{"ops":[{"insert":"Neurological symptoms\n"}]}
{"ops":[{"insert":"This includes confusion or impairment of consciousness. New-onset anosmia and ageusia may also occur. "},{"insert":"This is thought to be due to the binding of SARS-CoV-2 to ACE2 receptors ","attributes":{"color":"#212529","background":"#ffffff"}},{"insert":"found in neurons, astrocytes, oligodendrocytes, and olfactory support cells.\n"}]}
{"ops":[{"insert":"Risk factors\n"}]}
{"ops":[{"insert":"Comorbidities such as advanced age (\u003E65 years old), obesity, male gender, chronic comorbidities (severe cardiovascular disease, chronic obstructive pulmonary disease, chronic kidney disease, cerebrovascular disease, diabetes, liver disease) predispose to more severe symptoms and a "},{"insert":"greater mortality risk.","attributes":{"color":"#212529","background":"#ffffff"}},{"insert":"\n"}]}
{"ops":[{"insert":"Symptoms of complications\n"}]}
{"ops":[{"insert":"Severe disease may result in interstitial pneumonia, acute respiratory distress syndrome (ARDS), impaired cardiac function, myocarditis, stroke, thromboembolic events, acute kidney injury, or multi organ failure. "},{"insert":"This is thought to be due to the cytokine storm that accompanies COVID-19 infection.","attributes":{"color":"#212529","background":"#ffffff"}},{"insert":"\n"}]}

Clinicals: Examination

Fact Explanation
{"ops":[{"insert":"Fever\n"}]}
{"ops":[{"insert":"Fever is a common examination finding.\n"}]}
{"ops":[{"insert":"Signs of shock\n"}]}
{"ops":[{"insert":"In severe illness, shock may occur, resulting in signs such as tachycardia, hypotension, cyanosis, cool or dry skin, and delayed capillary refill. This is thought to be due to an overwhelming inflammatory response to the virus. \n"}]}
{"ops":[{"insert":"Respiratory signs\n"}]}
{"ops":[{"insert":"Crepitations may be heard on auscultation. This is thought to be due to the inflammation of the small bronchi, bronchioles and fluid in the alveoli. The respiratory exam can also be normal.\n"}]}
{"ops":[{"insert":"Signs of thromboembolism\n"}]}
{"ops":[{"insert":"COVID-19 appears to give rise to a prothrombotic coagulopathy, resulting in venous and arterial thromboembolic events (e.g., deep venous thrombosis, pulmonary embolism, etc.). Typical abnormal coagulation parameters include prolonged prothrombin time, thrombocytopenia, elevated D-dimers, and low fibrinogen.\n"}]}
{"ops":[{"insert":"Fever\n"}]}
{"ops":[{"insert":"Fever is a common examination finding.\n"}]}
{"ops":[{"insert":"Signs of shock\n"}]}
{"ops":[{"insert":"In severe illness, shock may occur, resulting in signs such as tachycardia, hypotension, cyanosis, cool or dry skin, and delayed capillary refill. This is thought to be due to an overwhelming inflammatory response to the virus. \n"}]}
{"ops":[{"insert":"Respiratory signs\n"}]}
{"ops":[{"insert":"Crepitations may be heard on auscultation. This is thought to be due to the inflammation of the small bronchi, bronchioles and fluid in the alveoli. The respiratory exam can also be normal.\n"}]}
{"ops":[{"insert":"Signs of thromboembolism\n"}]}
{"ops":[{"insert":"COVID-19 appears to give rise to a prothrombotic coagulopathy, resulting in venous and arterial thromboembolic events (e.g., deep venous thrombosis, pulmonary embolism, etc.). Typical abnormal coagulation parameters include prolonged prothrombin time, thrombocytopenia, elevated D-dimers, and low fibrinogen.\n"}]}

Differential diagnosis

Fact Explanation
{"ops":[{"insert":"Other respiratory illnesses\n"}]}
{"ops":[{"insert":"COVID 19 may mimic other viral, bacterial, and fungal respiratory illnesses that present with rhinorrhea, sore throat, fever and cough (e.g., influenza, respiratory syncytial virus, other respiratory viruses, community-acquired pneumonia, Pneumocystis jiroveci pneumonia, etc.). Differentiation may be impossible based on"},{"insert":" clinical symptoms alone; and viral swabs and chest imaging may be required to identify the causative organism.","attributes":{"color":"#212529","background":"#ffffff"}},{"insert":"\n"}]}
{"ops":[{"insert":"Pulmonary embolism\n"}]}
{"ops":[{"insert":"COVID 19 may present similarly to pulmonary embolism with acute dyspnea, tachypnea, and tachycardia. However, fever is also often present in such patients, while being comparatively rare in pulmonary embolism. I"},{"insert":"maging studies (e.g., CT pulmonary angiography) may be required for differentiation.","attributes":{"color":"#212529","background":"#ffffff"}},{"insert":"\n"}]}
{"ops":[{"insert":"Other respiratory illnesses\n"}]}
{"ops":[{"insert":"COVID 19 may mimic other viral, bacterial, and fungal respiratory illnesses that present with rhinorrhea, sore throat, fever and cough (e.g., influenza, respiratory syncytial virus, other respiratory viruses, community-acquired pneumonia, Pneumocystis jiroveci pneumonia, etc.). Differentiation may be impossible based on"},{"insert":" clinical symptoms alone; and viral swabs and chest imaging may be required to identify the causative organism.","attributes":{"color":"#212529","background":"#ffffff"}},{"insert":"\n"}]}
{"ops":[{"insert":"Pulmonary embolism\n"}]}
{"ops":[{"insert":"COVID 19 may present similarly to pulmonary embolism with acute dyspnea, tachypnea, and tachycardia. However, fever is also often present in such patients, while being comparatively rare in pulmonary embolism. I"},{"insert":"maging studies (e.g., CT pulmonary angiography) may be required for differentiation.","attributes":{"color":"#212529","background":"#ffffff"}},{"insert":"\n"}]}

Investigations: Diagnosis

Fact Explanation
{"ops":[{"insert":"Polymerase chain reaction (PCR)\n"}]}
{"ops":[{"insert":"PCR testing of nasopharyngeal swabs detects the genetic material of SARS CoV-2 and is the current gold standard for diagnosis. The sensitivity varies with timing of testing relative to exposure, peaking at day 3 after symptom onset. Bronchoalveolar lavage is the most sensitive specimen source and is recommended where an initial upper respiratory sample result is negative in the setting of high clinical suspicion.\n"}]}
{"ops":[{"insert":"Serological studies\n"}]}
{"ops":[{"insert":"Serology is not recommended for diagnosis due to a high rate of false positive results. Furthermore, antibodies appear at least three to four weeks after symptom onset and at least two weeks after symptoms resolution. Serology may support the clinical diagnosis if infection is suspected in a patient with negative viral RNA testing. It is still unclear whether the presence of antibodies reduces susceptibility re-infection or how long immunity lasts.\n\n"}]}
{"ops":[{"insert":"Basic laboratory studies\n"}]}
{"ops":[{"insert":"Full blood counts typically reveal leukopenia and mild thrombocytopenia. Elevated C-reactive protein (CRP), lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminostransferase (AST) levels are also are common. Note that lymphopenia and increased D-dimer levels are negative prognostic markers. Increased levels of inflammatory markers (e.g., elevated interleukin-6, ferritin, and CRP) have been associated with cytokine storms and may herald ARDS.\n"}]}
{"ops":[{"insert":"Imaging studies\n"}]}
{"ops":[{"insert":"Chest x-rays may show interstitial opacities. Chest CT findings are more specific and include diffuse or peripheral ground glass opacities that may evolve into consolidation and ARDS. Air bronchograms, smooth or irregular interlobular or septal thickening, and thickening of the adjacent pleura may also be seen.\n"}]}
{"ops":[{"insert":"Blood gas analysis\n"}]}
{"ops":[{"insert":"Blood gas analysis "},{"insert":"typically reveals impaired gas exchange with type 1 respiratory failure (i.e., hypoxemia and normo- or ipocapnia) due to the involvement of lung interstitium.","attributes":{"color":"#4a4a4a","background":"#ffffff"}},{"insert":"\n"}]}
{"ops":[{"insert":"Polymerase chain reaction (PCR)\n"}]}
{"ops":[{"insert":"PCR testing of nasopharyngeal swabs detects the genetic material of SARS CoV-2 and is the current gold standard for diagnosis. The sensitivity varies with timing of testing relative to exposure, peaking at day 3 after symptom onset. Bronchoalveolar lavage is the most sensitive specimen source and is recommended where an initial upper respiratory sample result is negative in the setting of high clinical suspicion.\n"}]}
{"ops":[{"insert":"Serological studies\n"}]}
{"ops":[{"insert":"Serology is not recommended for diagnosis due to a high rate of false positive results. Furthermore, antibodies appear at least three to four weeks after symptom onset and at least two weeks after symptoms resolution. Serology may support the clinical diagnosis if infection is suspected in a patient with negative viral RNA testing. It is still unclear whether the presence of antibodies reduces susceptibility re-infection or how long immunity lasts.\n\n"}]}
{"ops":[{"insert":"Basic laboratory studies\n"}]}
{"ops":[{"insert":"Full blood counts typically reveal leukopenia and mild thrombocytopenia. Elevated C-reactive protein (CRP), lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminostransferase (AST) levels are also are common. Note that lymphopenia and increased D-dimer levels are negative prognostic markers. Increased levels of inflammatory markers (e.g., elevated interleukin-6, ferritin, and CRP) have been associated with cytokine storms and may herald ARDS.\n"}]}
{"ops":[{"insert":"Imaging studies\n"}]}
{"ops":[{"insert":"Chest x-rays may show interstitial opacities. Chest CT findings are more specific and include diffuse or peripheral ground glass opacities that may evolve into consolidation and ARDS. Air bronchograms, smooth or irregular interlobular or septal thickening, and thickening of the adjacent pleura may also be seen.\n"}]}
{"ops":[{"insert":"Blood gas analysis\n"}]}
{"ops":[{"insert":"Blood gas analysis "},{"insert":"typically reveals impaired gas exchange with type 1 respiratory failure (i.e., hypoxemia and normo- or ipocapnia) due to the involvement of lung interstitium.","attributes":{"color":"#4a4a4a","background":"#ffffff"}},{"insert":"\n"}]}

Investigations: Management

Fact Explanation
{"ops":[{"insert":"Repeat PCR\n"}]}
{"ops":[{"insert":"Retesting is required to discontinue precautions in healthcare settings. Note that prolonged viral RNA detection is possible even after resolution of clinical symptoms.\n"}]}
{"ops":[{"insert":"Repeat PCR\n"}]}
{"ops":[{"insert":"Retesting is required to discontinue precautions in healthcare settings. Note that prolonged viral RNA detection is possible even after resolution of clinical symptoms.\n"}]}

Management: Supportive

Fact Explanation
{"ops":[{"insert":"Close monitoring\n"}]}
{"ops":[{"insert":"Close monitoring of vital parameters (e.g., pulse rate, blood pressure, respiratory rate, and oxygen saturation) is required in patients with significant symptoms. Transfer to a high-dependency or critical care setting is warranted if respiratory failure develops.\n"}]}
{"ops":[{"insert":"Oxygen\n"}]}
{"ops":[{"insert":"Some patients will require supplemental oxygen therapy. A high-flow nasal cannula is an option for persons who are still hypoxemic despite oxygen via nasal prongs. Individuals with severe illness require invasive mechanical ventilation. Prone positioning may be helpful if hypoxemia worsens despite intubation and ventilation.\n"}]}
{"ops":[{"insert":"Prevention of infection\n"}]}
{"ops":[{"insert":"In the community setting, social distancing and wearing a mask in public are measure recommended to prevent spread of infection; the exact measures recommended will vary depending on local protocols.\n\nIn the hospital setting, early recognition of patients with suspected COVID-19 followed by rapid implementation of source control measures (i.e., isolation and cohorting of patients with confirmed infection) and the use of standard precautions (e.g., hand hygiene, use of personal protective equipment - PPE, and environmental cleaning) is necessary. \n\nHealth workers providing direct care to COVID-19 patients should wear a medical mask along with other PPE that are part of droplet and contact precautions. A respirator (N95, FFP2, FFP3) is recommended in care settings where aeresol -generating procedures are performed. \n"}]}
{"ops":[{"insert":"Triaging of patients\n"}]}
{"ops":[{"insert":"Patients with cough\/cold symptoms, normal chest imaging, and no dyspnea or hypoxia may be managed as outpatients. Individuals with pneumonia on chest imaging or hypoxia requiring oxygen supplementation should be hospitalized. Persons with hemodynamic decompensation, hypoxia requiring mechanical ventilation, or ARDS should be managed in a critical care setting.\n"}]}
{"ops":[{"insert":"Outpatient management\n"}]}
{"ops":[{"insert":"Patients who qualify for outpatient management should remain at home, with their temperature, respiratory rate, and oxygen saturation (SpO2) being monitored on a daily basis. Self isolation\/quarantine is warranted until the patient has two sequential negative COVID-19 PCR tests. If SpO2 is \u003C93%, the patient should be transported to a setting capable of a higher level of care (e.g., a COVID-19 dedicated clinic or a hospital).\n"}]}
{"ops":[{"insert":"Close monitoring\n"}]}
{"ops":[{"insert":"Close monitoring of vital parameters (e.g., pulse rate, blood pressure, respiratory rate, and oxygen saturation) is required in patients with significant symptoms. Transfer to a high-dependency or critical care setting is warranted if respiratory failure develops.\n"}]}
{"ops":[{"insert":"Oxygen\n"}]}
{"ops":[{"insert":"Some patients will require supplemental oxygen therapy. A high-flow nasal cannula is an option for persons who are still hypoxemic despite oxygen via nasal prongs. Individuals with severe illness require invasive mechanical ventilation. Prone positioning may be helpful if hypoxemia worsens despite intubation and ventilation.\n"}]}
{"ops":[{"insert":"Prevention of infection\n"}]}
{"ops":[{"insert":"In the community setting, social distancing and wearing a mask in public are measure recommended to prevent spread of infection; the exact measures recommended will vary depending on local protocols.\n\nIn the hospital setting, early recognition of patients with suspected COVID-19 followed by rapid implementation of source control measures (i.e., isolation and cohorting of patients with confirmed infection) and the use of standard precautions (e.g., hand hygiene, use of personal protective equipment - PPE, and environmental cleaning) is necessary. \n\nHealth workers providing direct care to COVID-19 patients should wear a medical mask along with other PPE that are part of droplet and contact precautions. A respirator (N95, FFP2, FFP3) is recommended in care settings where aeresol -generating procedures are performed. \n"}]}
{"ops":[{"insert":"Triaging of patients\n"}]}
{"ops":[{"insert":"Patients with cough\/cold symptoms, normal chest imaging, and no dyspnea or hypoxia may be managed as outpatients. Individuals with pneumonia on chest imaging or hypoxia requiring oxygen supplementation should be hospitalized. Persons with hemodynamic decompensation, hypoxia requiring mechanical ventilation, or ARDS should be managed in a critical care setting.\n"}]}
{"ops":[{"insert":"Outpatient management\n"}]}
{"ops":[{"insert":"Patients who qualify for outpatient management should remain at home, with their temperature, respiratory rate, and oxygen saturation (SpO2) being monitored on a daily basis. Self isolation\/quarantine is warranted until the patient has two sequential negative COVID-19 PCR tests. If SpO2 is \u003C93%, the patient should be transported to a setting capable of a higher level of care (e.g., a COVID-19 dedicated clinic or a hospital).\n"}]}

Management: Specific

Fact Explanation
{"ops":[{"insert":"Remdesivir\n"}]}
{"ops":[{"insert":"Remdesivir is an RNA polymerase inhibitor with demonstrated antiviral activity in vitro against SARS-CoV2. Recent evidence shows that it is superior to placebo in shortening time to recovery for hospitalized adults. The benefit is greater if the drug is initiated early.\n\nThe adult dosage is a 200mg IV loading dose on day 1 followed by a 100mg IV daily maintenance dose. Course durations range from 5 to 10 days. There seems to be no difference in efficacy between a 5 day course or 10 day course in patients with severe COVID-19 not requiring mechanical ventilation.\n"}]}
{"ops":[{"insert":"Dexamethasone\n"}]}
{"ops":[{"insert":"Recent evidence supports the use of dexamethasone 6 mg orally or IV once daily up to 10 days. This appears to reduce the duration of hospitalization and lower mortality rates in both patients receiving mechanical ventilation and patients receiving supplemental oxygen without mechanical ventilation. Dexamethasone did not appear to confer a statistically significant reduction in mortality rates in patients not on supplemental oxygen or mechanical ventilation.\n"}]}
{"ops":[{"insert":"Remdesivir\n"}]}
{"ops":[{"insert":"Remdesivir is an RNA polymerase inhibitor with demonstrated antiviral activity in vitro against SARS-CoV2. Recent evidence shows that it is superior to placebo in shortening time to recovery for hospitalized adults. The benefit is greater if the drug is initiated early.\n\nThe adult dosage is a 200mg IV loading dose on day 1 followed by a 100mg IV daily maintenance dose. Course durations range from 5 to 10 days. There seems to be no difference in efficacy between a 5 day course or 10 day course in patients with severe COVID-19 not requiring mechanical ventilation.\n"}]}
{"ops":[{"insert":"Dexamethasone\n"}]}
{"ops":[{"insert":"Recent evidence supports the use of dexamethasone 6 mg orally or IV once daily up to 10 days. This appears to reduce the duration of hospitalization and lower mortality rates in both patients receiving mechanical ventilation and patients receiving supplemental oxygen without mechanical ventilation. Dexamethasone did not appear to confer a statistically significant reduction in mortality rates in patients not on supplemental oxygen or mechanical ventilation.\n"}]}

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