Corona Virus

Diseases caused by Coronaviruses

-Common cold -GI tract infection -Severe acute respiratory syndrome -COVID 19 SARS -incubation 4-6 days -incidence is rare -30% resolution -70% severe infection -10% fatal -fever >100F, muscle pain, lethargy, cough, sore throat, malaise, SOB, Malaise COVID19 -2-14 day incubation period -almost 30,000 cases -80% resolution -20% severe infection -3.9% fatalality -symptoms mild-severe symptoms high fever, SOB, cough, muscle pain, dehydration, sepsis, ARDs, multi-organ failure

Risk factors for severe disease

-Immunosuppression (from long-term steroid use, cancer, AIDS/HIV infection, congenital immunodeficiency, use of immunosuppressant, etc.) -Age (individuals over 60 years old are at a higher risk) -Chronic diseases -Pregnancy The expression of ACE2 is highly increased in patients with diabetes mellitus or hypertension being treated with ACE inhibitors, which produces an upregulation of ACE2. ***Contrary to initial reports, the American College of Cardiology has pointed out that there is no data to support the claim that ACE inhibitors increase the risk of COVID-19 infection. As such, it is recommended that patients who are already on ACE inhibitors should continue to do so while further studies are performed

Prioritizing COVID 19 testing

1) Hospitalized patients with compatible signs and symptoms 2) Individuals who are at high risk of developing a severe form of the disease or a complication (e.g., patients who are elderly, immunocompromised, or have chronic conditions) 3) Any individual, including healthcare professionals, who within 2 weeks of symptom onset had close contact with a suspect or laboratory-confirmed COVID-19 patient, or who has a history of travel from affected geographic areas in the 2 previous weeks. If a complication is suspected, blood tests are performed to evaluate for leukopenia, leukocytosis, lymphopenia, and elevated AST and ALT levels. In patients who develop pneumonia, a chest CT will show bilateral involvement, multiple areas of consolidation, and ground-glass opacities. In the case of ARDS, arterial blood gas analysis shows hypoxemic respiratory failure with respiratory alkalosis, and a chest CT can show diffuse bilateral infiltrates, air bronchograms, atelectasis, and even pleural effusion.

More management

2) The decision to monitor a patient in the inpatient setting should be made on a case-by-case basis. Once hospitalized, supportive care and acute measures should be applied as necessary for complications, such as: 1) Oxygen therapy for patients who develop respiratory distress, hypoxemia, or shock 2) Empiric antimicrobials in the case of sepsis or secondary pneumonia 3) Glucocorticoids have been associated with an increased risk for mortality or severe forms of illness in patients with influenza and MERS-CoV infection. Therefore, the WHO and CDC recommend glucocorticoids not be used in patients with COVID-19 pneumonia unless there are indications related to underlying chronic conditions. 4) Advanced oxygen therapy, ventilatory support, and conservative fluid management in the case of acute respiratory distress syndrome 5) Fluid bolus and vasopressors in the case of septic shock

Severe cases and complications

Approximately 1 in 6 people with COVID-19 experience clinical deterioration and develop a complication in the second week of illness. These patients develop dyspnea, high fever, chest pain, hemoptysis, respiratory crackles, and progressive respiratory insufficiency that could potentially lead to death. The most common complications of COVID-19 are interstitial pneumonia and acute respiratory distress syndrome (ARDS), which is the cause of most of the fatalities. Other reported complications include cardiac injury, arrhythmia, septic shock, liver dysfunction, acute kidney injury, and multi-organ failure.

what is corona virus

COVID-19, also known as Coronavirus disease, is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2). Transmission mainly occurs via direct contact or aerosol droplets. The infection may present asymptomatically or with fever and dry cough. Individuals who are over 60 years of age, immunosuppressed, or have preexisting conditions have a higher risk of developing severe symptoms and complications. Management is based on supportive care

Transmission of SARsSCOV-2

CoV are zoonotic, which means they are transmitted to humans through animals. The natural reservoir for SARS-CoV 2 is hypothesized to be horseshoe bats or Malayan pangolins due to close genetic similarity to CoV strains found in these animals (still under investigation) Once in humans, the virus is transmitted mainly via direct hand-to-face contact from infected surfaces or inhalation of aerosol droplets from the coughing or sneezing of symptomatic individuals. Larger droplets tend to spread about 1 meter (3 ft) and drop towards the ground, while smaller droplets can travel as an aerosol cloud more than 2 meters (6 ft) from the infected individual and remain viable in the air for up to 3 hours under the right conditions. Fecal-oral transmission is also hypothesized, as was observed in SARS infection, but is still under investigation

Corona viruses as a whole

CoV tend to cause mild upper respiratory diseases in humans, such as the common cold. Of the 7 known species of CoV, only 3 are known to cause severe infections in humans: -Severe acute respiratory disease coronavirus (SARS-CoV): emerged in 2003 in southern China from civet cats -Middle East respiratory syndrome coronavirus (MERS-CoV): emerged in 2012 in Saudi Arabia from dromedary camels -SARS-CoV 2: emerged in December 2019 in China possibly from bats or pangolins (still under investigation)

Corona Virus Genome

Coronaviruses (CoV) are a family of enveloped, positive-sense, single-stranded RNA (+ssRNA) viruses. The SARS-CoV 2 virion is approximately 1,250 nm in diameter, and its genome ranges from 26 to 32 kilobases, the largest for an RNA virus. Helical Capsid

When can isolation and quarantine be discontinued

For hospitalized patients: negative results of PCR testing from at least 2 consecutive sets of paired nasopharyngeal and throat swab specimens collected ≥ 24 hours apart (total of 4 specimens: 2 nasopharyngeal and 2 throat) For at-home patients: negative results of PCR testing from at least 2 consecutive nasopharyngeal swab specimens collected ≥ 24 hours apart Or At least 3 days have passed since the resolution of fever without the use of antipyretics and improvement in respiratory symptoms AND At least 7 days have passed since the onset of symptoms

Prevention

Home isolation and/or avoiding public/crowded areas whenever possible to minimize the chance for exposure Washing hands regularly for at least 20 seconds with soap and water or with an alcohol-based hand sanitizer that contains at least 60% alcohol Maintain 1-2 m (~3-6 ft) distance from other people, "social distancing" Wearing a facemask if one is a healthcare professional, begins to present with symptoms, or when caring for a sick individual. The use of facemasks is not recommended for the general population.

Asymptomatic cases:

Infected individuals may not develop any noticeable symptoms, but are still carriers and transmitters of the virus. This has particularly hindered efforts to contain the outbreak. It has not yet been clearly determined how long asymptomatic individuals remain contagious after the initial infection.

Management

No specific treatment for COVID-19 is currently available. Patients with mild symptoms and no risk factors do not require hospitalization and are recommended to begin supportive at-home care. In the case of antipyretics, the use of ibuprofen is now considered safe according to the latest WHO advice (March 17, 2020). In the outpatient setting, one must seek professional medical assistance if any of the following emergency warning signs develop: -Difficulty breathing or shortness of breath -Persistent pain or pressure in the chest -Confusion or inability to arouse -Cyanosis (bluish-tint to lips or face)

Mild Cases

Patients present with a dry cough (31%), fever (81%), and common flu-like symptoms, including fatigue (63%), malaise, runny nose, nasal congestion, and sore throat. Less frequently, patients may develop diarrhea, nausea, vomiting, diffuse abdominal pain, productive cough, headache, and muscle or joint pain. Most common symptoms: -cough, fever, Flu-like symptoms

Diagnostics

Polymerase chain reaction (PCR) is currently the only test being used to confirm cases of COVID-19 infection and should be performed as soon as possible once a person under investigation (PUI) is identified, regardless of the time of symptom onset. Options: 1) Nasopharyngeal (NP) and/or oropharyngeal (OR) swab (for mild or asymptomatic suspected cases) -NP is the first choice. OP swabs are acceptable only if other swabs are not available. 2) Sputum (for patients with productive cough, inducing sputum is not recommended) 3)Bronchial and tracheal secretions or bronchoalveolar lavage (for patients receiving invasive mechanical ventilation) ***SARS-CoV 2 has also been detected in blood and stool specimens. These methods are not currently the gold standard for confirmation as results take longer to obtain, and this hinders infection control in the case of an outbreak.

SARS COV 2 proteins

SARS-CoV 2 has 5 structural proteins: spike (S), envelope (E), membrane (M), nucleocapsid (N), and hemagglutinin-esterase (HE). The main functions of the N protein are the formation of a complex with RNA and viral assembly after its replication. he S, E, and M proteins create the viral envelope. The S protein, assisted by HE, is responsible for the entry of the virion into the human cell. It is a club-shaped surface projection, giving the virus its characteristic crown-like appearance on electron microscopy.

More on PCR

Steps: 1) Denature (high temp 95C) 2) annealing of primers (low temp) 3) synthesis (intermediate temp) via Taq DNA Polymerase

Epidemiology

The first case of COVID-19 was traced back to Wuhan, China, in late November 2019, with an outbreak developing in December. The virus quickly spread, with widespread ongoing transmission occurring globally. More than 290,000 people were infected and over 12,700 died within the first 4 months of global spread. COVID-19 was characterized as a pandemic on March 11, 2020. As of march 18th 2020: -392,331 total confirmed cases -17,156 deaths -169 countries/regions death rate hypothesized to be 10x that of the flu

Clinical Presentation

The incubation period for COVID-19 ranges from 2-14 days, with an average of 5 days. For COVID-19, data suggests that: -80% of infections are mild or asymptomatic -15% are severe infections (requiring oxygen therapy) -5% are critical infections (requiring ventilation) ***this proportion of severe and critical to mild cases is higher than what is observed for influenza infections

SARS CoV2 infectious period

The infectious period ranges from 2 days before the onset of symptoms up to 2-3 days after their resolution. SARS-CoV 2 is highly contagious due to the production of high viral loads and efficient shedding of virions from the upper respiratory tract. However, asymptomatic individuals are also contagious, albeit to a slightly lesser degree, which has posed a real challenge for contagion prevention. The reproductive number, or the number of secondary infections generated from 1 infected individual, is between 2 and 2.5, higher than for influenza. The mortality rate of COVID-19 ranges from ~0.1 to 9% across different nations, with a global average of 4.3%; with 292,142 cumulative cases and 12,784 deaths according to the WHO

Treatment of type 1 respiratory failure

Treatment: -supplementation of oxygen with increased FiO2 via venturi mask, non-rebreathing bag if very hypoxic -aim for saturations above 90% and a comfortable respiratory rate -next step would be CPAP (will lead to the recruitment of more alveolar units) -next step would be intubation and artificial ventilation

Persistance of viral particles outside the body

The virus will remain infectious on surfaces outside a host from a few hours up to a few days. Its life span will vary depending on the type of surface and temperature and/or humidity of the environment. Air= 3 hours copper=4hrs Cardboard= 24hrs plastic and stainless steel: 2-3 days

Vaccine

There is no FDA-approved vaccine yet available to prevent COVID-19. A Phase 1 clinical trial evaluating an investigational vaccine began on March 16, 2020, in the Kaiser Permanente Washington Health Research Institute (KPWHRI) in Seattle, WA, USA. The vaccine is called mRNA-1273, and is designed to encode for a prefusion-stabilized form of the S protein. The trial will enroll 45 healthy adult volunteers aged 18 to 55 years over approximately 6 weeks. 6 total vaccines in development

Respiratory failure

Type 1= hypoxia alone, PaO2 < 8 no matter the FiO2 -can be caused by ARDs, pneumonia, aspiration, Pulmonary edema, PE, emphysema, interstitial lung disease type 2=hypercapnia, PaCo2> 6.7 -can be caused by OSA, obesity hypoventilation, chest wall and muscle diseases

SARS 2-CoV binding

binds, via its S protein, to the host cell through angiotensin-converting enzyme 2 (ACE2) and basigin (BSG). ACE2 is expressed by epithelial cells of the intestine, kidney, blood vessels, and most abundantly in type II alveolar cells of the lungs. The viral spike protein induces a drop in the levels of ACE2 in human cells, possibly inducing lung damage

Refractory cases

it is suggested that male patients with anorexia and absence of fever may have a higher risk of refractory cases

Drugs that might treat covid 19

there is no available data as of March 23, 2020, to support the recommendation of any of the following investigational therapeutics for patients with confirmed/suspected COVID-19: 1) Remdesivir is reported to have in-vitro activity against SARS-CoV and MERS-CoV by incorporating into nascent viral RNA chains and producing pre-mature termination. 2) Chloroquine and hydroxychloroquine, widely-used antimalarial drugs, are reported to block viral entry by inhibiting virus/cell fusion. 3) Lopinavir-ritonavir, a combined protease inhibitor usually used for HIV infection, was reported as having in vitro inhibitory activity against SARS-CoV. However, no benefit was observed in hospitalized adult patients with severe Covid-19 in trials conducted in China. 4)Tocilizumab is an anti-IL-6 receptor agent used for rheumatoid arthritis. It is currently being investigated in patients with severe COVID-19 presenting with high IL-6 levels.