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Coronavirus Disease 2019 (COVID-19)

Frank J. Domino, MD, Robert A. Baldor, MD, Kathleen A. Barry, MD, Jeremy Golding, MD and Mark B. Stephens, MD Reviewed 04/2020
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Subject: Coronavirus Disease 2019 (COVID-19)

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BASICS

DESCRIPTION

  • Coronavirus Disease 2019 (COVID-19) is a severe acute respiratory syndrome which was recently detected in Wuhan City, Hubei Province, China.

  • The disease results from a novel virus, newly named coronavirus 2 (SARS-CoV-2).

  • The syndrome may lead to respiratory failure and death, particularly in elderly and immune-compromised individuals.

EPIDEMIOLOGY

Incidence

ETIOLOGY AND PATHOPHYSIOLOGY

  • A novel (new) coronavirus (originally named "2019-nCoV," now officially coronavirus 2 [SARS-CoV-2]) caused the coronavirus disease COVID-19.

  • First detected in Wuhan City, Hubei Province, China

  • SARS-CoV-2 is related to bat coronaviruses and to other Severe Acute Respiratory Syndrome (SARS) coronaviruses.

  • Believed to evolve in animals; some strains of coronaviruses cause illness in people and others primarily infect animals, including camels, cats, and bats

  • Initial spreading for this novel coronavirus may have been from animal to man via exposure to a large seafood and animal market.

  • COVID-19 mean incubation time in a Chinese cohort was 5.5 days.

  • For over 95% of infected persons, symptoms appear within 11.5 days. Median incubation time to fever was 5.7 days.

  • In 108 patients diagnosed outside mainland China, median incubation time was 5.5 days (1).

  • Retrospective cohort study from Wuhan found the median duration of viral shedding to be 20 days, with the longest shedding at 37 days.

RISK FACTORS

  • Travel from countries of the world or specific regions that are experiencing outbreaks

  • The U.S. State Department issues travel bans and/or advisories as conditions change around the world, and advice can be found at https://travel.state.gov.

  • Can be spread through community contact

  • Spread via respiratory droplets produced when an infected person coughs or sneezes

GENERAL PREVENTION

  • Similar as for the influenza virus; hand washing, avoid others if ill

  • Social distancing: a public health intervention that keeps people and communities at a distance from others so those infected with an illness cannot pass it on to others. Includes keeping six feet apart from others, closing of schools, workplaces, meetings, social and religious gatherings, and sporting events. Its goal is to slow or stop the spread of an epidemic or pandemic, but is not as stringent as a quarantine.

  • Wearing surgical masks in public likely reduces risk of transmission to others.

  • Self-quarantine for all people with symptoms of fever or new cough until symptoms resolve

  • Hand washing for 20 seconds with soap lowers viral carriage and lowers risk of transmission.

  • Influenza vaccine: while not protective against the COVID-19 virus, this will help reduce the risk of severe illness or death from influenza

  • Vaccine is not available.

  • In lab evaluation, comparing SARS Corona Virus to COVID-19 found: COVID-19 virus was detectable 72 hours after application to plastic and after 48 hours on stainless steel; on cardboard was less than 24 hours (2).

  • Office-based triage protocol:

    • Reschedule all health maintenance visits and follow-up visits unless acute needs are present.

    • See non-COVID-19 symptom patients in office only if absolutely necessary.

    • Establish Telemedicine protocol and provide follow-up visits and patient questions by phone.

    • Instruct patients who arrive to wear a surgical mask.

    • Ask all patients, "Have you been exposed to someone who has tested positive for COVID-19?" and "Have you recently traveled to China, Hong Kong, Italy, Iran, Japan, or South Korea?" and "Have you been to any of these areas, including an airport or a flight connection?"

    • If the patient screens positive for travel to any of these areas in the last 14 days AND has a fever or new cough, ensure that they and any visitors are properly masked.

    • While staying six feet away from them, move all members of the party to an isolated room.

    • Remind parents who wish to have a child seen not to bring other family members into the office, and only bring in one child at a time.

  • Telemedicine is able to be billed for all types of visits (including new and established E/M, prenatal, behavioral health, pre-op visit, advanced care planning, occupational therapy and speech therapy) EXCEPT: Welcome to Medicare visits, well child visits, and "physicals" (3).

DIAGNOSIS

HISTORY

  • Initially:

    • Although afebrile in the initial pre-symptomatic phase, most symptomatic cases mount a fever > 38°C/100.4°F.

    • Cough and chest discomfort

    • Abdominal pain/diarrhea

  • 25% of patients may have no symptoms at all, but shed virus. In total, 80% of those with COVID-19 have mild illness or no symptoms at all.

ALERT

Any ill patient presenting to an office should don a surgical mask immediately and be placed in airborne isolation (ideally, negative air pressure with staff wearing an N-95 respirator) if the patient meets the following criteria:

  • Fever AND symptoms of lower respiratory illness (e.g. cough, shortness of breath, etc.) and in the last 14 days before symptom onset, has a:

    • History of travel to a country with a high prevalence of COVID-19, OR

    • Close contact with a COVID-19 patient or a person who is under investigation for the COVID-19 virus infection (PUI) while that person was ill, OR

    • Travel on a cruise ship in past 14 days

  • Risk factors for progression to acute respiratory distress syndrome (ARDS), based upon Wuhan data:

    • Age >65 years, neutrophilia, and organ or coagulation dysfunction (4)

    • Chronic lung disease, immunocompromise, obesity (5)

    • Hypertension and diabetes (6)

 

PHYSICAL EXAM

  • Mild-to-severe respiratory illness with fever, cough, dyspnea, and chest discomfort

  • Wheeze and rales are not typically found

  • Hypoxia

DIFFERENTIAL DIAGNOSIS

Influenza, other virally-mediated respiratory illness 

DIAGNOSTIC TESTS & INTERPRETATION

For any patient meeting criteria for evaluation for COVID-19, clinicians are encouraged to contact and collaborate with their state or local health department. 

Initial Tests (lab, imaging)

  • Work with local and state health departments to coordinate testing through public health laboratories, or use COVID-19 diagnostic testing, authorized by the Food and Drug Administration under an Emergency Use Authorization (EUA) through clinical laboratories.

  • Priority should be given to:

    • Hospitalized patients

    • Healthcare workers with symptoms

    • Patients in long-term care facilities with symptoms

    • Patients 65 years of age and older with symptoms

    • Patients with underlying conditions with symptoms

    • First responders with symptoms

    • Individuals with mild symptoms in communities experiencing high rates of COVID-19

  • Test: CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time Reverse Transcriptase (RT)-PCR Diagnostic Panel

    • Intended for use with upper and lower respiratory specimens collected only from persons who meet CDC criteria for COVID-19 testing

    • Sensitivity likely 60%-70% in routine use

    • Given the poor sensitivity of this test, consider the possibility of a false negative test in patients for whom you have a high degree of clinical suspicion, and recommend treatment and quarantine.

    • Specimens will need to be collected and refrigerated at 2-8ºC

      • Nasopharyngeal swab AND oropharyngeal swab (use only synthetic fiber swabs with plastic shafts with a viral transport media), or oral swabbing AND nasal swabbing on a single swab

      • Sputum

      • Serum (1 tube [5-10 mL]) of whole blood in a serum separator tube)

    • For worsening symptoms: chest X-ray, confirmatory CAT scan; showing bilateral or multifocal pneumonia

Follow-Up Tests & Special Considerations

For patients who are positive, consider obtained LDH, hsCRP and D-dimer as a baseline should they progress to significant dyspnea. 

TREATMENT

GENERAL MEASURES

MEDICATION

Oxygen and other supportive treatments 
ALERT

Use of chloroquine or hydroxychloroquine, either alone or with azithromycin, should NOT be prescribed for outpatients. Experimental protocols with sicker inpatients are underway. Use in outpatients may well cause harm and decrease availability of medication for patients with known need (e.g. rheumatoid arthritis, systemic lupus erythematosus).

 
ALERT

Patients who have worsening symptoms with declining function should be admitted to the hospital for observation for further deterioration.

 

First Line

  • Treat as if bacterial pneumonia until proven otherwise.

  • No other antimicrobial agent should be prescribed in the outpatient setting.

  • Medications under investigation:

    • Failed: Lopinavir-Ritonavir was studied in an open-label randomized study in Wuhan, China. Fourteen days of lopinavir-ritonavir therapy did not differ from standard case regarding clinical improvement or decrease in viral RNA load (7).

    • A very small open label study of 36 hospitalized patients with proven COVID-19 evaluated hydroxychloroquine lowered "viral carriage" at day 6. A subset of these patients were treated with both hydroxychloroquine and azithromycin, and at day 6 also showed a reduced viral load compared to hydroxychloroquine alone or no mediation. No further outcome data was included in the study, and this was published without peer review (8).

    • A French researcher issued a video suggesting hydroxychloroquine may be effective at reducing the infectivity of the virus within 6 days, but this has not been published and has not been replicated.

ALERT

Hydroxychloroquine, alone or with azithromycin, should NOT be used in the outpatient setting for the prevention of or treatment of COVID-19 infections.

 
  • Experimental therapies being discussed but not recommended for outpatient use include:

    • A Letter to the Editor (9) from virologists from China evaluated a variety of agents "in vitro" (in a lab vessel, not human) models and found:

      • Nafamostat, a potent inhibitor of MERS-CoV, which prevents membrane fusion, was inhibitive against the 2019-nCoV infection.

      • Nitazoxanide, a commercial antiprotozoal agent with an antiviral potential against a broad range of viruses including human and animal coronaviruses, inhibited the 2019-nCoV at a low-micromolar concentration and will likely be evaluated in vivo studies.

      • Remdesivir (a broad-spectrum antiviral agent): in-vitro studies of remdesivir found it can inhibit coronaviruses such as SARS-CoV and MERS-CoV replication; this is currently being studied in SARS-CoV2 (the coronavirus causing COVID-19) (10).

  • A small study from Wuhan found that in those with COVID-19-induced ARDS, methylprednisolone was associated with significantly better outcomes: 23 of 50 (46%) methylprednisolone recipients died compared with 21 of 34 (61.8%) nonrecipients (hazard ratio 0.38).

  • Convalescent serum from those recovered from COVID-19 (2 infusions of plasma [total volume, 400 mL] from donors) was used on 5 critically ill patients in China who were being mechanically ventilated. They also received intravenous corticosteroids and at least 2 of the following: lopinavir /ritonavir, interferon alfa-1b, favipiravir, arbidol, and darunavir. Outcomes reported include body temperature returned to normal in 4 of 5 patients within 3 days and ARDS resolved in 4 patients at 12 days after transfusion, with 3 of the patients weaned from mechanical ventilation within 2 weeks of treatment. Coronavirus viral loads became negative within 12 days after the transfusion (11).

  • To address obtaining convalescent serum, the Red Cross in the United States is seeking people who are fully recovered from COVID-19 and may be able to donate plasma to help current patients with serious or immediately life-threatening COVID-19 infections, or those judged by a healthcare provider to be at high risk of progression to severe or life-threatening disease.

  • If you have a patient who has recovered from COVID-19, and is interested in donating plasma, go to https://www.redcrossblood.org/donate-blood/dlp/plasma-donations-from-recovered-covid-19-patients.html and follow the links.

  • The U.S. Food and Drug Administration has approved the use of plasma from recovered patients to treat people who are critically ill with COVID-19. The decision is based upon past experience with other respiratory infections (2009-2010 H1N1 influenza virus pandemic, 2003 SARS-CoV-1 epidemic, and the 2012 MERS-CoV epidemic). Criteria for this treatment:

ISSUES FOR REFERRAL

For any patient meeting criteria for evaluation for COVID-19, clinicians are encouraged to contact and collaborate with their state or local health department. 

SURGERY/OTHER PROCEDURES

Inform patients that elective procedures and surgeries are postponed. 

ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS

  • Any patient who has had a potential exposure and is ill should NOT enter an ambulatory healthcare facility; remain at home to allow quarantine.

  • Patients at lower risk for infection may be seen and evaluated with disposable plastic gown, surgical mask, and eye protection.

  • When caring for those patients undergoing cough-inducing procedures (including nasopharyngeal swabbing, intubation, and bronchoscopy/endoscopy), an N-95 mask and higher-level PPE is required.

ONGOING CARE

  • Anxiety of patients with infection with coronavirus and their close contacts, along with the general population, remains high. Reassure those who test positive to monitor their breathing and shortness of breath and to contact you for any worsening.

  • For the general population, offer support and tele-counseling sessions. Limit anxiolytics as they can compromise symptom recognition in patients who may become ill from any severe illness or infection. Consider using a face mask when they go out to the store or have the potential to inadvertently come in close contact to others.

FOLLOW-UP RECOMMENDATIONS

  • The CDC makes the following recommendations for "Return to Work" for the general public:

    • The CDC recommends the decision to discontinue home isolation based upon local infection rates. Options now include 1) a time-since-illness-onset and time-since-recovery (non-test-based) strategy, and 2) a test-based strategy.

      • Time-since-illness-onset and time-since-recovery strategy (non-test-based strategy)

        • Persons with COVID-19 who have symptoms and were told to care for themselves at home may discontinue home isolation under the following circumstances:

          • At least 3 days (72 hours) have passed since recovery, defined as resolution of fever without the use of fever-reducing medications and improvement in respiratory symptoms (e.g. cough, shortness of breath); and

          • At least 7 days have passed since symptomsfirst appeared.

      • Test-based strategy

        • Persons who have COVID-19 who have symptoms and were told to care for themselves at home may discontinue home isolation under the following conditions:

        • Individuals with laboratory-confirmed COVID-19 who have not had any symptoms may discontinue home isolation when at least 7 days have passed since the date of their first positive COVID-19 test and have had no subsequent illness (12).

  • The U.S. CDC makes the following recommendation for "Return to Work" for Healthcare Personnel with confirmed or suspected COVID-19:

    • Use one of the below strategies to determine when HCP may return to work in healthcare settings:

      • Test-based strategy. Exclude from work until

      • Non-test-based strategy. Exclude from work until

        • At least 3 days (72 hours) have passed since recovery defined as resolution of fever without the use of fever-reducing medications and improvement in respiratory symptoms (e.g. cough, shortness of breath); and,

        • At least 7 days have passed since symptoms first appeared.

      • If healthcare personnel were never tested for COVID-19 but have an alternate diagnosis (e.g. tested positive for influenza), criteria for return to work should be based on that diagnosis.

    • Return to work practices and work restrictions

      • After returning to work, HCP should:

        • Wear a facemask at all times while in the healthcare facility

        • Be restricted from contact with severely immunocompromised patients (e.g. transplant, hematology-oncology) until 14 days after illness onset

        • Adhere to hand hygiene, respiratory hygiene, and cough etiquette in CDC's interim infection control guidance (e.g. cover nose and mouth when coughing or sneezing, dispose of tissues in waste receptacles)

        • Self-monitor for symptoms and seek re-evaluation from occupational health if respiratory symptoms recur or worsen.

      • Crisis strategies to mitigate staffing shortages

        • A "surge" of patients looks to bring large numbers of patients into healthcare settings at the same time healthcare providers may become ill from COVID-19, resulting in staffing shortages. Healthcare systems, healthcare facilities, and the appropriate state, local, territorial, and/or tribal health authorities might determine that the recommended approaches cannot be followed due to the need to mitigate HCP staffing shortages. In such scenarios:

          • HCP should be evaluated by occupational health to determine appropriateness of earlier return to work than recommended above.

          • If HCP return to work earlier than recommended above, they should still adhere to the Return to Work Practices and Work Restrictions recommendations above (13).

Patient Monitoring

Encourage those who test positive to monitor their breathing, and if they develop dyspnea with activity or at rest, to contact their PCP or be seen in an emergency department. 

PATIENT EDUCATION

  • Frequently clean hands by using alcohol-based hand rub or soap and water.

  • When coughing and sneezing, cover mouth and nose with flexed elbow or tissue. Throw tissue away immediately and wash hands.

  • Avoid close contact with anyone who has fever and cough.

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

  • Patients with COVID-19 should not stop taking their angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs), based upon a Statement from the American Heart Association, the Heart Failure Society of America, and the American College of Cardiology (14).

  • The U.S. FDA has stated: "FDA is not aware of scientific evidence connecting the use of NSAIDs like ibuprofen with worsening COVID-19 symptoms. The agency is investigating this issue further."

  • Patients with mild illness should self-isolate/quarantine until symptoms have completely resolved for 48 hours minimum.

  • Excellent patient resource on how to care for yourself at home: https://www.cdc.gov/coronavirus/2019-ncov/downloads/10Things.pdf

PROGNOSIS

  • 80% of patients have mild, self-resolving illness requiring no intervention.

  • Duration of immunity from infection is unknown. In other coronavirus infections, immunity may only last 1-2 years. In SARS and MERS, survivors of these infections have longer-lasting immunity.

  • Data on those severely ill from COVID-19 from Wuhan data (4):

    • Median hospital stay was 12 days, 33% required mechanical ventilation, and median time from admission to ARDS was 2 days.

    • Abnormal laboratory findings include elevated lactate dehydrogenase in 194 (98%), elevated high-sensitivity C-reactive protein in 166 (85.6%), elevated interleukin-6 in 60 (48.8%), and elevated D-dimer in 44 (23.3%).

    • Age >65 years, neutrophilia, and organ or coagulation dysfunction were associated with ARDS and death.

  • Characteristics of severely ill patients that correlate with death include: age 68 vs. 51, being male, having a history of hypertension and cardiovascular disease.

  • Laboratory findings that correlate with an increased mortality include: leukocytosis with lymphopenia, and highly-elevated LFTs, creatinine, lactate dehydrogenase, troponin, N-terminal-pro-brain natriuretic peptide, and d-dimer compared to those who recovered.

  • Morbidities that correlate with death include acute respiratory distress syndrome, sepsis, acute cardiac injury, heart failure, acute kidney injury, and encephalopathy (15).

REFERENCES

1
Lauer SA, Grantz KH, Bi Q, et al. The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application. Ann Intern Med. 2020 Mar 10. [Epub ahead of print]
2
van Doremalen N, Bushmaker T, Morris DH, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. N Engl J Med. 2020 Mar 17. [Epub ahead of print]
3
Centers for Medicare & Medicaid Services. Medicare Telemedicine Health Care Provider Fact Sheet. https://www.cms.gov/newsroom/fact-sheets/medicare-telemedicine-health-care-provider-fact-sheet. Updated March 17, 2020. Accessed April 1, 2020.
4
Wu C, Chen X, Cai Y, et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients with Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Mar 14. [Epub ahead of print]
5
Centers for Disease Control and Prevention. Coronavirus Disease 2019 (COVID-19): People Who Are At Higher Risk. https://www.cdc.gov/coronavirus/2019-ncov/specific-groups/people-at-higher-risk.html. Access March 28, 2020.
6
World Health Organization. (2020). Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected: interim guidance, 13 March 2020. World Health Organization. https://apps.who.int/iris/handle/10665/331446. License: CC BY-NC-SA 3.0 IGO
7
Cao B, Wang Y, Wen D, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe COVID-19. N Engl J Med. 2020 Mar 18. [Epub ahead of print]
8
Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Mar 20: 105949. [Epub ahead of print]
9
Wang M, Cao R, Zhang L, et al. Remedesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271.
10
Al-Tawfiq JA, Al-Homoud AH, Memish ZA. Remdesivir as a possible therapeutic option for the COVID-19. Travel Med Infect Dis. 2020 Mar 5:101615. [Epub ahead of print]
11
Shen C, Wang Z, Zhao F, et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. 2020 Mar 27. [Epub ahead of print]
12
Centers for Disease Control and Prevention. Coronavirus Disease 2019 (COVID-19): Disposition of Non-Hospitalized Patients with COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-in-home-patients.html#st1. Accessed March 28, 2020.
13
Centers for Disease Control and Prevention. Coronavirus Disease 2019 (COVID-19): Return-to-Work Criteria for Healthcare Workers. https://www.cdc.gov/coronavirus/2019-ncov/healthcare-facilities/hcp-return-work.html. Accessed March 28, 2020.
14
Heart Failure Society of America. Patients taking ACE-i and ARBs who contract COVID-19 should continue treatment, unless otherwise advised by their physician. Statement from the American Heart Association, the Heart Failure Society of America and the American College of Cardiology. https://www.hfsa.org/patients-taking-ace-i-and-arbs-who-contract-covid-19-should-continue-treatment-unless-otherwise-advised-by-their-physician/. Accessed March 28, 2020.
15
Chen T, Wu D, Chen H, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020 Mar 26;368:m1091.

ADDITIONAL READING

SEE ALSO

CODES

CLINICAL PEARLS

  • Coronavirus Disease 2019 (COVID-19) is a severe acute respiratory syndrome which originated in China and has spread world-wide, causing a pandemic.

  • The disease results from a novel virus, newly named coronavirus 2 (SARS-CoV-2).

  • The syndrome may lead to death, particularly in elderly and immune-compromised individuals.

  • PCR test sensitivity is low, so consider pre-test probability, especially in evaluating negative results, and recommend self-quarantine for those with a high-risk exposure and/or symptoms.

  • For any meeting criteria for evaluation of COVID-19, clinicians are encouraged to contact and collaborate with their state or local health department.

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