Coronavirus Disease 2019 (COVID-19)

Please note that COVID-19–related information is evolving, including epidemiology and modes of prevention and treatments. Different variants and subvariants of SARS-CoV-2 become dominant within weeks, with data on treatment and prevention obtained earlier being applicable only indirectly. While jurisdictions are coming up with new instructions, various professional and international organizations differ in their assessment of the same body of evidence. This may be reflected in the divergent levels of confidence in the data as well as different values and preferences associated with certain outcomes, including the availability of resources and interventions. As of this update (September 2024), different recommendations and patterns of practice surrounding the use of several therapies and prevention strategies illustrate these not unexpected phenomena.

We started developing this chapter in the spring of 2020, when high-quality data essentially did not exist. With frequent updates, we proceeded through the publication of the first antiviral and anti-inflammatory treatment studies, platform trials, meta-analyses, and network meta-analyses concerning different interventions, as well as numerous practice guidelines. As of the current update our goal is to limit the review of original evidence and to provide readers with access to actionable recommendations.

EpidemiologyTop

The first cases of coronavirus disease 2019 (COVID-19) occurred in China and quickly developed into an epidemic centered in Hubei province. Subsequently, the pandemic has spread globally, with the United States, India, and Brazil reporting the highest number of cases. Current epidemiologic data are available at who.int, cdc.gov, and ecdc.europa.eu. As of September 2024, there were >775 million cases reported by the World Health Organization (WHO) and >7 million deaths worldwide. This significantly underestimates the actual number of cases, given that many jurisdictions have reduced testing and reporting efforts and some have ceased reporting altogether as the clinical severity of the disease decreased.

Etiology and PathogenesisTop

1. Etiologic agent: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an RNA virus that belongs to the Betacoronavirus (BetaCoV) genus. The genus also includes SARS-CoV, which was responsible for the epidemic in 2002 and 2003.

Throughout the COVID-19 pandemic, SARS-CoV-2 has mutated, leading to the emergence of viral variants. Initially 3 main variants of concern (VOCs)—more transmissible than the wild-type variant—were increasingly circulating in numerous countries, including the United Kingdom (B.1.1.7, Alpha), South African (B.1.135, Beta), and Brazilian (P.1, Gamma) lineages. In the summer of 2021, a variant first identified in India (B.1.617, Delta) became rapidly dominant in numerous geographic locations, including Canada. In November 2021, a report from South Africa announced the arrival of the already widespread B.1.1.529 variant (Omicron), likely more readily transmitted because of the mechanism of immune escape but possibly causing less severe disease. By the end of 2021, that variant had become dominant across North America and Europe. In the summer of 2022, subvariants of Omicron (BA.4 and BA.5) were dominant in many parts of the world. As of December 2022, the most prevalent forms of the virus according to global WHO data included Omicron descendants BQ.1, BA.5, BA.2.75, and XBB. Early 2023 data from the United States and Canada suggested the XBB.1.5 variant to be the dominant one, which led to the development of targeted vaccines. As of the second half of 2024, the predominant Omicron lineages include JN.1 with its sublineages: KP.3.1.1, KP.3, KP.2.3, and LB.1.

Vaccination campaigns are attempting to focus on updated vaccines targeting prevalent strains as much as feasible.

2. Pathogenesis: To enter the cell, the virus uses angiotensin-converting enzyme 2 (ACE2) as a receptor, binding to ACE2 using the spike glycoprotein on the viral envelope. In response to viral antigens, immune cells release proinflammatory cytokines and chemokines, which can result in an uncontrolled systemic inflammatory response (cytokine storm). This is one of the key mechanisms leading to the development of acute respiratory distress syndrome (ARDS).

3. Reservoir and transmission: An animal reservoir has not been clearly identified to date, but the virus most likely originated in bats. In the current epidemic the reservoir for SARS-CoV-2 is infected humans. However, transmission from animal to human species has been described.

SARS-CoV-2 transmits between people mainly when an infected person is in close contact with another person. The virus can be spread in small liquid particles of different sizes, ranging from very small (historically termed “aerosols”) to larger particles and splashes. The evidence to support transmission through fomites (contaminated objects) is limited, although it is considered a possible mode of transmission.Evidence 1Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness and risk of bias. Derqui N, Koycheva A, Jie Z, et al. Risk factors and vectors for SARS-CoV-2 household transmission: a prospective, longitudinal cohort study. Lancet Microbe. 2023 Jun;4(6):e397-e408. doi: 10.1016/S2666-5247(23)00069-1. Epub 2023 Apr 6. PMID: 37031689; PMCID: PMC10132910. Inhalation likely occurs more frequently during aerosol-generating medical procedures or in certain settings such as indoor, crowded, and poorly ventilated spaces. It has become clear that the Omicron variant transmits more easily than the previously dominant variants, likely due to the ability to escape preexisting antibodies. The virus may be found in blood at the early stages of the disease and in stool, but transmission through blood or the fecal-oral route has not been confirmed. The infection is spread predominantly by symptomatic and presymptomatic individuals with COVID-19 but also by those with asymptomatic infection with SARS-CoV-2.Evidence 2Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. 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 Apr 16;382(16):1564-1567. doi: 10.1056/NEJMc2004973. PMID: 32182409; PMCID: PMC7121658. Johansson MA, Quandelacy TM, Kada S, al. SARS-CoV-2 Transmission From People Without COVID-19 Symptoms. JAMA Netw Open. 2021 Jan 4;4(1):e2035057. doi: 10.1001/jamanetworkopen.2020.35057. Erratum in: JAMA Netw Open. 2021 Feb 1;4(2):e211383. PMID: 33410879; PMCID: PMC7791354.

4. Risk factors for infection: Epidemiologic risk factors include any setting with a higher likelihood of exposure to an infected individual, in particular through direct contact in an indoor environment (eg, classroom, meeting room, waiting room in a hospital). Prolonged contact increases the risk of infection. Transmission by contact with objects or materials (fomites) seems less important than originally assumed.

Risk factors for severe versus mild infection include advanced age (in patients ≥80 years mortality rates with earlier variants were reported to be up to 15%, although some mildly symptomatic patients might not be counted, thus increasing the observed risk), male sex, chronic respiratory disease, cardiovascular disease including hypertension, malignancy, diabetes mellitus, active smoking, obesity, immunosuppression, and lack of vaccination. Residents of long-term care facilities are particularly vulnerable. The role of pregnancy as a risk factor for severe disease is under debate; a systematic review suggested a slightly higher risk for intensive care unit (ICU) admission and ventilation, with the main risk factors being preexisting diabetes, hypertension, elevated body mass index (BMI), and advanced maternal age. The risk of preterm labor and maternal death was reported to be elevated about 3-fold.Evidence 3Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the risk of bias. Pettirosso E, Giles M, Cole S, Rees M. COVID-19 and pregnancy: A review of clinical characteristics, obstetric outcomes and vertical transmission. Aust N Z J Obstet Gynaecol. 2020 Oct;60(5):640-659. doi: 10.1111/ajo.13204. Epub 2020 Aug 10. PMID: 32779193; PMCID: PMC7436616.

5. Incubation and contagious period: The incubation period for the wild-type variant and initial VOCs is typically 2 to 14 days (5 days on average, with >95% of cases developing by day 11). The incubation period for the Omicron variant is likely shorter and estimated to be 3.5 days. Symptomatic individuals may transmit the virus to others; the extent of transmission from those who are presymptomatic is likely substantial.Evidence 4Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Arons MM, Hatfield KM, Reddy SC, et al. Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility. N Engl J Med. 2020 May 28;382(22):2081-2090. doi: 10.1056/NEJMoa2008457. Epub 2020 Apr 24. PMID: 32329971; PMCID: PMC7200056. Gandhi M, Yokoe DS, Havlir DV. Asymptomatic Transmission, the Achilles' Heel of Current Strategies to Control Covid-19. N Engl J Med. 2020 May 28;382(22):2158-2160. doi: 10.1056/NEJMe2009758. Epub 2020 Apr 24. PMID: 32329972; PMCID: PMC7200054. Li R, Pei S, Chen B, et al. Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV2). Science. 2020 May 1;368(6490):489-493. doi: 10.1126/science.abb3221. Epub 2020 Mar 16. PMID: 32179701; PMCID: PMC7164387. Wei WE, Li Z, Chiew CJ, Yong SE, Toh MP, Lee VJ. Presymptomatic Transmission of SARS-CoV-2 – Singapore, January 23–March 16, 2020. MMWR Morb Mortal Wkly Rep. 2020 Apr 10;69(14):411-415. doi: 10.15585/mmwr.mm6914e1. PMID: 32271722; PMCID: PMC7147908. Viral load/shedding is probably the highest at the time of symptom onset and shortly afterwards; however, it may last longer in patients who develop severe infection. The duration of the contagious period is estimated as a maximum of 10 days from the onset of symptoms for most cases and is likely shorter for the Omicron variant. A small number of patients with severe COVID-19 may shed replication-competent viruses for several weeks, particularly in the context of critical illness or significant immunocompromised state.Evidence 5Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Centers for Disease Control and Prevention. Duration of Isolation and Precautions for Adults with COVID-19. Updated October 19, 2020. Accessed November 29, 2020. https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html

Clinical Features and Natural HistoryTop

The clinical course may be varied and ranges from asymptomatic/subclinical infection to severe pneumonia with ARDS:

1) Symptomatic uncomplicated infection: Patients have nonspecific manifestations, such as fever, cough, shortness of breath, malaise, myalgias, sore throat, headache, diarrhea, runny nose or nasal congestion, conjunctivitis, and anosmia. Patients with mild or uncomplicated infections do not have dehydration, dyspnea, or features of sepsis. Elderly individuals and immunocompromised patients may have atypical symptoms.

2) Mild pneumonia: Confirmed clinically and radiologically but without features of severe pneumonia listed below.

3) Severe pneumonia: Fever or other symptoms of respiratory tract infection with ≥1 of severe respiratory distress, tachypnea >30/min, or hemoglobin oxygen saturation in arterial blood (measured with pulse oximetry) (SpO2) on room air <90%.

4) ARDS occurs in up to 15% of hospitalized patients with COVID-19.

5) Sepsis and septic shock: The incidence of sepsis in patients with COVID-19 is not well described. The incidence of shock in published reports was highly variable, ranging between 2% and 20%, and has been certainly lower in 2024.

6) Postinfectious phenomena, such as multisystem inflammatory syndrome (MIS)—a disorder similar to Kawasaki disease—has been described in children (MIS-C) and adults aged ≥21 years (MIS-A).

7) The severity of COVID-19 can be described in different ways. One of them is the 4C Mortality Score, which can differentiate between <2% and >50% mortality (available at mdcalc.com; for more detailed information, also see tables 1 and 4 in a paper on external score validation by Gordon AJ et al [doi:10.1136/bmjopen-2021-054700]).

DiagnosisTop

Diagnostic Tests

1. Identification of the etiologic agent: The key diagnostic method is detection of viral genetic material using reverse transcriptase–polymerase chain reaction (RT-PCR), with RT-PCR from nasopharyngeal swabs (NPSs) considered the reference standard. Other specimen types include lower respiratory tract samples (intubated patients only; endotracheal aspirates [ETAs] or bronchoalveolar lavage [BAL]), mid-turbinate swabs, throat swabs, uninduced sputum, and even spit. As sensitivity remains imperfect (although it may be as high as 95%), a high index of clinical suspicion has to be considered even in patients with negative test results. In hospitalized patients with suspected COVID-19, it is therefore recommended to obtain an NPS first and if the initial test result is negative, it can be followed with a lower respiratory tract sample as needed. Of note, the sensitivity of specimens varies with the course of the illness, and the sensitivity of upper airway samples may be lower than of those obtained from lower airways later in the course of symptomatic disease. In general, sensitivity is likely highest at the beginning of symptoms and then declines.

By the end of 2022, COVID-19 antigen tests, predominantly offered as point-of-care rapid tests, were widely available for the diagnosis of active infection. Compared with PCR, they have high specificity, lower sensitivity, and the benefit of fast turnaround times as well as lower likelihood of picking up residual RNA in patients who are no longer infectious. They also require less operator training and can be done in fairly remote settings or used at home.Evidence 6Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Mina MJ, Parker R, Larremore DB. Rethinking Covid-19 Test Sensitivity - A Strategy for Containment. N Engl J Med. 2020 Nov 26;383(22):e120. doi: 10.1056/NEJMp2025631. Epub 2020 Sep 30. PMID: 32997903.

2. Serologic tests: Serologic tests are not generally recommended as clinical tests to diagnose active COVID-19, as they usually yield negative results in early infection. They have greater utility for epidemiologic purposes. One application of serologic tests may be in the presence of postinfectious complications, such as MIS in children (MIS-C) where NPS testing yields negative results. Additionally, the target of serologic testing may depend on vaccination status. Anti-spike (S) antibodies are produced with both vaccination and infection, whereas anti-nucleocapsid (N) antibodies are generated by infection alone. However, the conversion of N antibodies in individuals with infection after vaccination may be diminished and needs to be interpreted with caution.Evidence 7Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Follmann D, Janes HE, Buhule OD, et al. Antinucleocapsid Antibodies After SARS-CoV-2 Infection in the Blinded Phase of the Randomized, Placebo-Controlled mRNA-1273 COVID-19 Vaccine Efficacy Clinical Trial. Ann Intern Med. 2022 Sep;175(9):1258-1265. doi: 10.7326/M22-1300. Epub 2022 Jul 5. PMID: 35785530; PMCID: PMC9258784.

3. Other tests:

1) Laboratory tests: Patients commonly have leukopenia and lymphopenia, but leukocytosis may also occur. Procalcitonin levels are usually normal but may be elevated in patients requiring admission to the ICU. Serum aminotransferase levels may be increased. Thrombocytopenia, ferritin, C-reactive protein (CRP), and D-dimer levels correlate with disease severity.

2) Radiography:

a) Chest radiography: Most frequently shows features of bilateral pneumonia.

b) Chest computed tomography (CT): Radiographic abnormalities can be seen early, even before symptom onset. They are usually bilateral, show peripheral distribution, and are more often located in the inferior lobes. Extensive ground-glass opacification can be seen especially in the second week of the disease, which progresses to a mixed pattern by week 3 or 4. Patients may also have pleural thickening, pleural effusion, and lymphadenopathy. More detailed discussion of CT findings: see COVID-19: Computed Tomography.

3) Chest ultrasonography, including point-of-care ultrasonography, may provide information and limit the number of required CT scans. More detailed discussion of ultrasound findings: see COVID-19: Point-of-Care Ultrasonography.

4) Clinical monitoring involves following of vital signs (respiratory rate and effort, blood pressure, heart rate, SpO2) and the quick sequential organ failure assessment (qSOFA) (see Sepsis and Septic Shock).

Diagnostic Criteria

Case definitions are used mostly for surveillance purposes and change with the evolving epidemiologic situation. Current Ontario documents (revised September 2023) include confirmed case (see below) and probable case definitions.

A confirmed case is defined as:

1) A person with laboratory detection of ≥1 specific gene target by a validated laboratory-based nucleic acid amplification test (NAAT) (eg, real-time PCR or nucleic acid sequencing) or by a validated point-of-care NAAT that has been deemed acceptable by the Ontario Ministry of Health to provide a final result.

2) A person with seroconversion in viral-specific antibody in serum or plasma within a 4-week interval demonstrated using a validated laboratory-based serologic assay for SARS-CoV-2.

Individual countries may need to adapt the case definitions based on their local epidemiologic situation. Many jurisdictions consider a positive rapid antigen test result in a symptomatic patient to serve as evidence of a confirmed case.

Differential Diagnosis

1. Influenza.

2. Other viral respiratory infections.

3. Atypical pneumonia.

4. Pneumocystosis.

5. Other causes of ARDS (see Acute Respiratory Distress Syndrome).

6. Middle East respiratory syndrome (MERS).

TreatmentTop

State of Research

Several major research projects investigating numerous potential therapies were developed and yielded a wealth of data within a short time frame. Among them are the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial coordinated out of the United Kingdom, SOLIDARITY trial coordinated by the WHO, ACTT (Adaptive COVID-19 Treatment Trial) coordinated by the National Institutes of Health (NIH), and REMAP-CAP trial (Randomised, Embedded, Multi-factorial, Adaptive Platform Trial for Community-Acquired Pneumonia). Findings from those trials and their timeline provide a fascinating history of a worldwide effort to combat major global health threats.

Results from the RECOVERY trial (acetylsalicylic acid [ASA], baricitinib, tocilizumab, convalescent plasma, monoclonal antibodies, colchicine, azithromycin, dexamethasone, lopinavir/ritonavir, hydroxychloroquine, empagliflozin, molnupiravir or nirmatrelvir/ritonavir [brand name Paxlovid] in hospitalized patients) can be found at recoverytrial.net.

SOLIDARITY trial results (remdesivir, hydroxychloroquine, lopinavir, interferon) can be found at who.int.

The ACTT trial has reported on the effects of remdesivir (ACTT-1; doi:10.1056/NEJMoa2007764) and baricitinib (in combination with remdesivir; doi:10.1056/NEJMoa2031994).

The REMAP-CAP trial has reported at least partial data on tocilizumab/sarilumab, convalescent plasma, therapeutic anticoagulation, dexamethasone, and hydroxychloroquine or chloroquine with or without a macrolide. The published results can be accessed online at remapcap.org.

Note: The speed of evidence generation (although slowing considerably as of 2024) and emergence of new variants have resulted in a large number of clinical practice guidelines, some already outdated by the time of publication and others presenting indirect recommendations with applicability unclear due to rapidly changing variants. We attempt to summarize the main elements of the current pattern of practice in our area (Hamilton, Canada, September 2024) while acknowledging that alternative recommendations or suggestions are being followed in other regions, depending on the assessment of evidence and availability of different therapies.

Examples of such guidelines include those prepared by the Infectious Diseases Society of America (idsociety.org), WHO (app.magicapp.org), and Ontario Government (ontario.ca).

Examples of graphs summarizing suggested management could be found on WHO site (app.magicapp.org). Of note, ongoing NIH guideline updates were stopped in March 2024.

Our Pattern of Practice

Treatment generally depends on the severity of the disease (evaluated mostly by the degree of hypoxia and need for supportive measures), presence of risk factors, vaccination status, and disease stage (which roughly corresponds to a viral phase during the first week of illness and a predominantly inflammatory phase thereafter). In most situations the severe phase of the disease, associated with profound hypoxia, is related to the inflammatory phase. The pattern of management continues to evolve and is guided by ongoing studies, including those indicated above.

1. In the ambulatory outpatient setting asymptomatic patients with a positive test result would typically not receive any treatment. Symptomatic patients not requiring oxygen or hospitalization for COVID-19 symptoms who are at low risk of deterioration based on age and risk factors usually receive no specific treatment. However, early oral and IV therapies may reduce the hospitalization risk and alleviate symptoms in individuals at higher risk for severe disease.

Treatment should be considered in those with risk factors, such as older age (in Ontario recommended for patients >60 years), immunocompromised state, lack of COVID-19 immunity (those who are unvaccinated, incompletely vaccinated, or had the primary series and last vaccination dose or infection >6 months ago); or those with comorbidities (obesity [BMI ≥30 kg/m2]), undergoing dialysis or with stage 5 kidney disease (estimated glomerular filtration rate [eGFR] <15 mL/min/1.73 m2), with diabetes, cerebral palsy, intellectual disability of any severity, sickle cell disease, chronic lung disease, cardiac conditions, chronic liver disease, receiving active cancer treatment, or post solid organ or stem cell transplant).

A more discriminating approach is proposed by the WHO guideline panel, where patients are categorized as being at high risk (6%) of hospitalization (those with immunodeficiency syndromes, after solid organ transplant and receiving immunosuppressants, or with an autoimmune illness and receiving immunosuppressants); at moderate risk (3%) of hospitalization (those aged >65 years, with obesity, diabetes, and/or chronic cardiopulmonary disease, chronic kidney disease, chronic liver disease, active cancer, disabilities, and comorbidities of chronic disease); and at low risk (0.5%) of hospitalization (other individuals, being a vast majority).

Largely, these therapies include antiviral therapies, such as Paxlovid or remdesivir, and they should be initiated within 5 to 7 days of symptom onset, respectively. Our current practice rarely entails the use of monoclonal antibodies. Disease response modifiers, which reduce inflammation, such as fluvoxamine and inhaled glucocorticoids, are occasionally used.

Due to the ease of oral administration, Paxlovid for 5 days is considered the first choice where available and in the absence of contraindications or drug interactions. Alternatively, patients could be offered remdesivir for 3 days (200 mg IV on day 1, then 100 mg IV on days 2 and 3), particularly those at high risk with contraindications to Paxlovid. Other oral antiviral treatments such as molnupiravir may also be used as an oral alternative when Paxlovid (or remdesivir) cannot be used (not recommended in the Ontario guidelines). While these therapies are not appropriate for all patients, those at the highest risk of hospitalization should be considered for early antiviral therapy as soon after symptom onset as possible. Of note, eligibility criteria to receive those therapies differ depending on jurisdictions.

In patients at low risk, fluvoxamine and inhaled budesonide are considered by some, although as of October 2023 the NIH guidelines declared lack of sufficient evidence to support their use. The same panel also did not support the use of colchicine. Commencing statins as part of COVID-19 treatment, as of September 2024, is not part of our usual practice.

2. In hospitalized mildly affected patients (not requiring physiologic support with oxygen and IV hydration) treatment is mostly supportive, but the above considerations of Paxlovid, remdesivir, and molnupiravir apply, especially in the case of patients hospitalized for other reasons or those with nosocomial infection.

3. In hospitalized moderately affected patients admitted because of COVID-19 (broadly defined as those requiring supplemental oxygen), we routinely use a 10-day course of dexamethasone (6 mg/d) and interleukin 6 (IL-6) inhibitor tocilizumab (within 14 days of hospital admission, especially in those with evidence of systemic inflammation, CRP ≥75 mg/L, rapid disease progression, or a combination of those) and a 5-day course of remdesivir. In settings where tocilizumab is unavailable, the IL-6 inhibitor sarilumab or JAK-2 inhibitors, such as baricitinib (4 mg/d orally for 14 days or until hospital discharge), may be alternatives.Evidence 8Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Marconi VC, Ramanan AV, de Bono S, et al; COV-BARRIER Study Group. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Lancet Respir Med. 2021 Dec;9(12):1407-1418. doi: 10.1016/S2213-2600(21)00331-3. Epub 2021 Sep 1. Erratum in: Lancet Respir Med. 2021 Oct;9(10):e102. PMID: 34480861; PMCID: PMC8409066. A combination of baricitinib and IL-6 inhibitors is allowed in some guidelines. In moderately affected patients without contraindications, we suggest full-dose anticoagulation with low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH), but this may be well modified by a perceived increased risk of bleeding and limited to prophylactic dosing.

4. In severely and critically ill patients (those requiring invasive ventilatory or circulatory support), we use dexamethasone and tocilizumab, but not remdesivir (especially late in disease course). Sarilumab can also be used if tocilizumab supplies are limited. We use prophylactic rather than full-dose or intermediate anticoagulation, as routine full-dose anticoagulation may be harmful unless indicated for a separate condition. Baricitinib is suggested in patients receiving dexamethasone, but in Ontario not in combination with IL-6 inhibitors (tocilizumab). Of note, WHO guidelines allow for the combination of those 3 classes of drugs, although American guidelines recommend using one of either IL-6 or JAK-2 inhibitors.

We individualize the use of remdesivir and anticoagulation in patients requiring oxygen delivery through a high-flow nasal cannula or noninvasive ventilation (of note, these interventions were considered ICU care in anticoagulation trials).

We recommend against the use of chloroquine and hydroxychloroquine, azithromycin, lopinavir/ritonavir, and ivermectin. We do not use monoclonal antibodies.

A number of other therapies were considered but have not been used in our setting (except in the context of clinical trials). These include convalescent plasma, ribavirin, favipiravir, vitamin C, zinc, and antibacterial treatment (unless justified for other reasons or secondary bacterial infection).

Symptomatic and Supportive Treatment

In addition to the treatments above, supportive care is key. In patients with features of respiratory failure and shock, oxygen therapy should be administered (see Oxygen Therapy), with a target of SpO2 ≥90% (≥92%-95% in pregnant women). Start from an oxygen flow rate of 5 L/min and titrate as needed. Antibiotic treatment should be used if bacterial superinfection is suspected. Although empiric antibiotics are frequently used in patients with COVID-19 and pneumonia as part of supportive care, a meta-analysis has shown the incidence of bacterial coinfections to be low (6.9%), with slightly higher rates in ventilated patients, and thus empiric antibiotics should be avoided.

Nonspecific treatments with a potential of benefit include prone positioning of nonventilated and ventilated patients and common use of high-flow oxygen therapy through a nasal cannula (see Nasal High-Flow Therapy [NHFT]).Evidence 9Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness, heterogeneity, and imprecision. Frat J-P, Quenot J-P, Julio Badie J, et al; SOHO-COVID Study Group and the REVA Network. Effect of High-Flow Nasal Cannula Oxygen vs Standard Oxygen Therapy on Mortality in Patients With Respiratory Failure Due to COVID-19: The SOHO-COVID Randomized Clinical Trial. JAMA. 2022 Sep 27;328(12):1212-1222. doi: 10.1001/jama.2022.15613. PMID: 36166027; PMCID: PMC9516287. Perkins GD, Ji C, Connolly BA, et al; RECOVERY-RS Collaborators. Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Patients With Acute Hypoxemic Respiratory Failure and COVID-19: The RECOVERY-RS Randomized Clinical Trial. JAMA. 2022 Feb 8;327(6):546-558. doi: 10.1001/jama.2022.0028. PMID: 35072713; PMCID: PMC8787685. Ospina-Tascón GA, Calderón-Tapia LE, García AF, et al; HiFLo-Covid Investigators. Effect of High-Flow Oxygen Therapy vs Conventional Oxygen Therapy on Invasive Mechanical Ventilation and Clinical Recovery in Patients With Severe COVID-19: A Randomized Clinical Trial. JAMA. 2021 Dec 7;326(21):2161-2171. doi:10.1001/jama.2021.20714. PMID: 34874419; PMCID: PMC8652598. Oczkowski S, Ergan B, Bos L, et al. ERS Clinical Practice Guidelines: high-flow nasal cannula in acute respiratory failure. Eur Respir J. 2021 Oct 28;2101574. doi: 10.1183/13993003.01574-2021. Attention is also directed towards the high prevalence of thrombotic complications with implication of a low threshold for full-dose anticoagulation. As the frequency of thrombotic presentations or thrombotic complications is high, numerous studies evaluated relative merits of prophylactic versus full-dose anticoagulation with heparin. As of the end of 2023, data suggested the advantage of full-dose anticoagulation in hospitalized patients who did not require ICU-level organ support, but only prophylactic doses were suggested in patients requiring such ICU-level support (particularly invasive ventilation, inotropes, or vasopressors; the course of action is less clear in patients receiving oxygen through a high-flow nasal cannula or noninvasive ventilation and may depend on the perceived risk of bleeding).Evidence 10Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision, indirectness, and heterogeneity. National Institutes of Health. Full-dose blood thinners decreased need for life support and improved outcome in hospitalized COVID-19 patients. Published January 22, 2021. https://www.nih.gov/news-events/news-releases/full-dose-blood-thinners-decreased-need-life-support-improved-outcome-hospitalized-covid-19-patients ATTACC Investigators; ACTIV-4a Investigators; REMAP-CAP Investigators; Lawler PR, Goligher EC, Berger JS, et al. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19. N Engl J Med. 2021 Aug 26;385(9):790-802. doi: 10.1056/NEJMoa2105911. Epub 2021 Aug 4. PMID: 34351721; PMCID: PMC8362594. REMAP-CAP Investigators; ACTIV-4a Investigators; ATTACC Investigators; Goligher EC, Bradbury CA, McVerry BJ, et al. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19. N Engl J Med. 2021 Aug 26;385(9):777-789. doi: 10.1056/NEJMoa2103417. Epub 2021 Aug 4. PMID: 34351722; PMCID: PMC8362592.

Management in sepsis and septic shock: see Sepsis and Septic Shock.

Some additional specific practice trends, based on collective experience and observational data, include moving away from early intubation and paying particular attention to lung compliance, which frequently may be normal and thus require lower positive end-expiratory pressure (PEEP) and plateau pressures.

Special ConsiderationsTop

Occupational Exposure of Health Care Personnel

The management of occupational and nonoccupational high-risk exposures differs depending on the region, epidemiologic situation, and resources.

An exposure leading to infection refers to mucosal contamination with biological materials that may contain the virus. According to the US Centers for Disease Control and Prevention (CDC), materials that warrant postexposure management include respiratory secretions but not after exposure to body fluids on intact skin. To assess the risk of transmission of SARS-CoV-2, consider:

1) Duration of exposure (longer exposure increases the risk of transmission).

2) The patient’s clinical symptoms.

3) Whether a well-fitted facemask was used by the health care provider (HCP).

4) Whether the HCP used other personal protective equipment (PPE), including eye protection.

5) Whether aerosol-generating procedures were performed.

6) Whether a face covering was used by the patient.

High-risk exposures are defined as situations where an HCP is not wearing PPE that protects their mouth, nose, and eyes in the setting of large infectious respiratory particles (IRPs) (historically termed droplets; eg, coughing) or during an aerosol-generating procedure, or situations where an HCP has direct unprotected contact with secretions from a patient with COVID-19 (cardiopulmonary resuscitation, intubation, extubation, bronchoscopy, nebulization, sputum induction). An example of a nonoccupational high-risk exposure is a household member with an active infection.

Medium-risk and low-risk exposures are typically no longer considered as relevant from a contact-tracing perspective at this point of the pandemic.

Individuals who were vaccinated and exposed to SARS-CoV-2 in the health care environment were considered to be at reduced risk of acquiring COVID-19 in the pre-Omicron era; however, vaccination status is less protective in the context of the Omicron variant and as such, the management of vaccinated and unvaccinated HCPs with high-risk exposure should be identical. This may change with vaccines developed to target subvariants of Omicron, including BA.4 and BA.5.

The management of high-risk exposures in HCPs differs based on organizational or jurisdictional rules as well as staffing shortages. Some jurisdictions may still require isolation of HCPs from work for 5 to 10 days following exposure, with or without testing during this period. Currently most jurisdictions require the HCP only to actively monitor for the presence of symptoms and potentially to perform PCR (often around day 5 post exposure) or rapid antigen testing.

PrognosisTop

Prognosis: Acute Disease

The overall mortality rate varies by country, pattern of testing, and demographic characteristics in a given report. During the first months of the pandemic, ~5% of diagnosed symptomatic patients became critically ill with acute respiratory failure, shock, and multiorgan dysfunction. Among such critically ill patients, the mortality rate initially approached 50%. In the first 2 years of the pandemic, the overall mortality in hospitalized patients declined from >16% to ~9%.Evidence 11Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Grasselli G, Pesenti A, Cecconi M. Critical Care Utilization for the COVID-19 Outbreak in Lombardy, Italy: Early Experience and Forecast During an Emergency Response. JAMA. 2020 Apr 28;323(16):1545-1546. doi: 10.1001/jama.2020.4031. PMID: 32167538. Bennett TD, Moffitt RA, Hajagos JG, et al; National COVID Cohort Collaborative (N3C) Consortium. Clinical Characterization and Prediction of Clinical Severity of SARS-CoV-2 Infection Among US Adults Using Data From the US National COVID Cohort Collaborative. JAMA Netw Open. 2021 Jul 1;4(7):e2116901. doi: 10.1001/jamanetworkopen.2021.16901. PMID: 34255046; PMCID: PMC8278272. In general, the severity of the disease caused by the Omicron variant was lower, presumably also due to natural and vaccine-induced immunity and availability of early treatment options for the most vulnerable populations.

The reported proportion of severely and critically ill patients among all currently infected patients (with active infection) fluctuates depending on the rate of new infections, testing criteria, and changes in the dominant variant; in 2024 it is likely <1%. However, even these declining rates have a wide margin of error and are probably inflated as, due to selective testing, there may be an overrepresentation of hospitalized and severely ill patients with confirmed infection. Many patients with mild infection do not undergo testing and are therefore missing from the denominator. The future may depend on the virulence of the new variants and vaccination status of affected individuals (eg, in the past the probability of a new SARS-CoV-2 infection among those vaccinated with ≥2 doses vs those not vaccinated was ~2.5-fold lower; of requiring hospitalization, ~4-fold lower; and of the need for ICU admission, ~4-fold lower).Evidence 12Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Ontario Dashboard. https://covid19-sciencetable.ca/ontario-dashboard COVID-19 Indicator Roadmap. https://covid19-sciencetable.ca/covid-19-indicator-roadmap

An 8-factor risk score to predict mortality among patients hospitalized with COVID-19 was published in the British Medical Journal (BMJ) (doi: 10.1136/bmj.m3339). It is based on age, sex, number of comorbidities, Glasgow Coma Scale, respiratory rate, oxygen saturation, urea level, and (in the older version) CRP (see mdcalc.com; the site offers also numerous other online calculators). Of note, these tools were developed for use with initial variants and in the unvaccinated population.

Prognosis: Post–COVID-19 Condition

Clinically, patients with mild infection typically recover within 1 to 2 weeks. Some experience long-term nonspecific postviral symptoms lasting 12 weeks or occasionally longer.Evidence 13Moderate Quality of Evidence (moderate confidence that we know true effects). Quality of Evidence lowered due to changing epidemiology and severity of disease (indirectness). Global Burden of Disease Long COVID Collaborators; Wulf Hanson S, Abbafati C, Aerts JG, et al. Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021. JAMA. 2022 Oct 25;328(16):1604-1615. doi: 10.1001/jama.2022.18931. PMID: 36215063; PMCID: PMC9552043. Nasserie T, Hittle M, Goodman SN. Assessment of the Frequency and Variety of Persistent Symptoms Among Patients With COVID-19: A Systematic Review. JAMA Netw Open. 2021 May 3;4(5):e2111417. doi: 10.1001/jamanetworkopen.2021.11417. PMID: 34037731; PMCID: PMC8155823. Walter K. An Inside Look at a Post-COVID-19 Clinic. JAMA. 2021 May 25;325(20):2036-2037. doi: 10.1001/jama.2021.2426. PMID: 33950195. Ayoubkhani D, Khunti K, Nafilyan V, et al. Post-covid syndrome in individuals admitted to hospital with covid-19: retrospective cohort study. BMJ. 2021 Mar 31;372:n693. doi: 10.1136/bmj.n693. PMID: 33789877; PMCID: PMC8010267. Sivan M, Taylor S. NICE guideline on long covid. BMJ. 2020 Dec 23;371:m4938. doi: 10.1136/bmj.m4938. PMID: 33361141. Del Rio C, Collins LF, Malani P. Long-term Health Consequences of COVID-19. JAMA. 2020 Nov 3;324(17):1723-1724. doi: 10.1001/jama.2020.19719. PMID: 33031513; PMCID: PMC8019677. When covid-19 becomes a chronic illness. The Economist. August 22, 2020. https://www.economist.com/science-and-technology/2020/08/22/when-covid-19-becomes-a-chronic-illness Williams FMK, Muirhead N, Pariante C. Covid-19 and chronic fatigue. BMJ. 2020 Jul 30;370:m2922. doi: 10.1136/bmj.m2922. PMID: 32732337. These long-term sequelae of the disease are referred to as post–COVID-19 condition (PCC), post-COVID syndrome, or long COVID and occur in >6% of patients, >3% of whom have persistent fatigue with bodily pain or mood swings resembling chronic fatigue syndrome, >2% have cognitive problems, and ~4% have ongoing respiratory problems with dyspnea and cough. In those aged ≥20 years, long COVID symptoms are more common in women than in men (10.6% vs 5.4%). In both sexes aged <20 years, ~3% of patients are affected. At present, no clear specific interventions have been recommended. The mean duration of long COVID symptoms was reported to last 9 months in hospitalized patients and 4 months in the nonhospitalized group. Among those with long COVID symptoms at 3 months after infection, a minority (~15%) continued to have symptoms at 12 months.

PreventionTop

Specific Prevention

1. Vaccination: see Vaccines: COVID-19.

In 2022, mass vaccination projects were conducted around the world. Several vaccines were approved by various national and international agencies, including mRNA, viral vector, and inactivated virus vaccines. With the Omicron VOC, reports suggested an efficacy rate of ~50% in preventing symptomatic disease with a significant waning of the effect in the months following vaccination. A higher and longer-lasting efficacy is observed in preventing hospitalization, critical illness, and death.Evidence 14Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Polack FP, Thomas SJ, Kitchin N, et al; C4591001 Clinical Trial Group. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020 Dec 31;383(27):2603-2615. doi: 10.1056/NEJMoa2034577. Epub 2020 Dec 10. PMID: 33301246; PMCID: PMC7745181. Vaccines and Related Biological Products Advisory Committee Meeting: December 17, 2020. FDA Briefing Document: Moderna COVID-19 Vaccine. Published December 17, 2020. Accessed December 24, 2020. https://www.fda.gov/advisory-committees/advisory-committee-calendar/vaccines-and-related-biological-products-advisory-committee-december-17-2020-meeting-announcement Altarawneh HN, Chemaitelly H, Ayoub HH, et al. Effects of Previous Infection and Vaccination on Symptomatic Omicron Infections. N Engl J Med. 2022 Jul 7;387(1):21-34. doi: 10.1056/NEJMoa2203965. Epub 2022 Jun 15. PMID: 35704396; PMCID: PMC9258753. Chalkias S, Harper C, Vrbicky K, et al. A Bivalent Omicron-Containing Booster Vaccine against Covid-19. N Engl J Med. 2022 Oct 6;387(14):1279-1291. doi: 10.1056/NEJMoa2208343. Epub 2022 Sep 16. PMID: 36112399; PMCID: PMC9511634. Barouch DH. Covid-19 Vaccines - Immunity, Variants, Boosters. N Engl J Med. 2022 Sep 15;387(11):1011-1020. doi: 10.1056/NEJMra2206573. Epub 2022 Aug 31. PMID: 36044620; PMCID: PMC9454645.

2. Pharmacologic prevention: Numerous potential strategies are being investigated.

Prophylaxis with tixagevimab/cilgavimab (brand name Evusheld) against COVID-19 is used in heavily immunocompromised patients unable to mount immunity from vaccines.Evidence 15Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Levin MJ, Ustianowski A, De Wit S, et al; PROVENT Study Group. Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of Covid-19. N Engl J Med. 2022 Jun 9;386(23):2188-2200. doi: 10.1056/NEJMoa2116620. Epub 2022 Apr 20. PMID: 35443106; PMCID: PMC9069994. However, concerns over resistance to newer variants in late 2022 has led to a recommendation against its routine use.

Nonspecific Prevention

See Nonspecific Methods of Infection Prevention Among Medical Staff.

1. General recommendations:

1) Frequently perform hand hygiene with soap and water or alcohol-based hand sanitizers.

2) Avoid touching the face.

3) Avoid crowds and large gatherings.

4) Maintain at least 1- to 2-meter distance from others (odds decreased ~5-fold with the absolute difference in risk ~10% in high-risk situations), with 2 meters providing further protection (~2-fold additional risk decrease).Evidence 16Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the observational nature of studies and increased due to the large effect size and dose-response gradient. Chu DK, Akl EA, Duda S, Solo K, Yaacoub S, Schünemann HJ; COVID-19 Systematic Urgent Review Group Effort (SURGE) study authors. Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis. Lancet. 2020 Jun 27;395(10242):1973-1987. doi: 10.1016/S0140-6736(20)31142-9. Epub 2020 Jun 1. PMID: 32497510; PMCID: PMC7263814.

5) Reduce exposure and infections by wearing facemasks (odds decreased 6- to 7-fold with the absolute difference in risk ~14% in high-risk situations; this represents combined data from the evaluation of surgical masks and N95 masks, with surgical masks alone likely providing a 3-fold decrease in the odds of infection).Evidence 17Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the observational nature of data. Chu DK, Akl EA, Duda S, Solo K, Yaacoub S, Schünemann HJ; COVID-19 Systematic Urgent Review Group Effort (SURGE) study authors. Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis. Lancet. Jun 27;395(10242):1973-1987. doi: 10.1016/S0140-6736(20)31142-9. Epub 2020 Jun 1. PMID: 32497510; PMCID: PMC7263814. As of the end of 2023/2024 the debate on the utility of masks continued.Evidence 18Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to heterogeneity and indirectness. Jefferson T, Dooley L, Ferroni E, et al. Physical interventions to interrupt or reduce the spread of respiratory viruses. Cochrane Database Syst Rev. 2023 Jan 30;1(1):CD006207. doi: 10.1002/14651858.CD006207.pub6. PMID: 36715243; PMCID: PMC9885521. Gurbaxani BM, Hill AN, Patel P. Unpacking Cochrane’s Update on Masks and COVID-19. Am J Public Health. 2023 Oct;113(10):1074-1078. doi: 10.2105/AJPH.2023.307377. PMID: 37672741; PMCID: PMC10484132.

6) Avoid contact with individuals with respiratory symptoms.

7) Reduce exposure and infections by wearing eye protection (goggles, safety glasses; odds of infection decreased ~4- to 5-fold with the absolute difference in risk ~10% in high-risk situations). This prevention measure is recommended first and foremost for HCPs.Evidence 19Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the observational nature of data. Chu DK, Akl EA, Duda S, Solo K, Yaacoub S, Schünemann HJ; COVID-19 Systematic Urgent Review Group Effort (SURGE) study authors. Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis. Lancet. 2020 Jun 27;395(10242):1973-1987. doi: 10.1016/S0140-6736(20)31142-9. Epub 2020 Jun 1. PMID: 32497510; PMCID: PMC7263814.

2. Quarantine or self-isolation: Healthy individuals who had contact with an infected person may want to reduce social contacts for 5 to 10 days or may require self-isolation as per public health rules in a given jurisdiction.

3. Isolation advice for individuals with COVID-19: The rules differ across jurisdictions and over time. The current advice in Ontario (ontario.ca) includes staying at home until symptoms have been improving for ≥24 hours (or 48 hours if nausea, vomiting, and/or diarrhea are present), there is no fever, and no additional symptoms developed. When no longer isolating at home, an individual is advised for the total of 10 days from symptom onset to wear a well-fitted mask in all public settings, avoid nonessential activities where one needs to take off the mask (eg, dining out), avoid nonessential visits to anyone who is immunocompromised or may be at higher risk of illness (eg, seniors), and avoid nonessential visits to the highest-risk settings in the community, such as hospitals and long-term care homes.

4. Isolation of infected individuals in high-risk settings: Isolation precautions can be used (1) to prevent transmission through large IRPs (historically droplet transmission) or direct contact transmission or (2) during aerosol-generating procedures, to prevent transmission through inhalation. Before entering the patient’s room, don a set of PPE. After leaving the room, PPE should be removed in a designated area with a waste container for single-use PPE and hand decontamination equipment. Extended use and reuse protocols as well as reprocessing are still often considered, depending on the availability of supplies.

Precautions for what was historically termed droplet transmission and direct contact transmission: Patients should be placed in well-ventilated rooms with access to a washroom (in rooms with natural ventilation an average ventilation rate of 60 L/s per patient should be provided). If available, single-patient rooms are preferred. Patients with confirmed SARS-CoV-2 infection can be cohorted, or they can be cohorted with recently recovered patients. The number of visitors should be limited. Medical equipment should be single-use or dedicated for a single patient only (in the case of reusable equipment, eg, stethoscope, thermometer, blood pressure monitor, pulse oximeter). If reusable equipment is shared by different patients, it should be disinfected between uses. Room surfaces and equipment in the patient’s environment should be regularly cleaned and disinfected. Patient transportation within the hospital should be limited to a minimum. When feasible, portable diagnostic equipment should be used (eg, bedside radiography). If the patient must be transported (eg, for diagnostic evaluation), use the shortest route and notify the HCPs in the receiving area in advance. The patient should be wearing a well-fitting facemask. Transport personnel and receiving personnel having contact with the patient must use PPE. Minimize exposure for staff, other patients, and visitors during transport.

Precautions for transmission through inhalation (airborne infection isolation rooms [AIIRs]): If available, aerosol-generating medical procedures should be performed in well-ventilated rooms maintaining constant negative pressure, providing ≥12 air exchanges per hour, and with controlled direction of airflow (preferably) or in a naturally ventilated room with an average ventilation rate ≥160 L/s per patient.

5. PPE: A minimum set of PPE should include (recommendations in different jurisdictions differ and evolve):

1) PPE for respiratory protection: Well-fitting surgical or procedural masks should be used, with the level of fluid resistance depending on the potential risk of splashes. Through much of the pandemic the WHO and the Public Health Agency of Canada (PHAC) have recommended surgical masks as sufficient while providing routine care and reserved N95 respirator masks for aerosol-generating procedures. It should be noted that surgical masks may not provide sufficient protection against inhalation of microbes. In the context of infections with the Omicron variant and the associated uncertain concerns of higher transmissibility, the PHAC recommended the use of an N95 respirator (or equivalent) for care of all individuals with suspected or confirmed COVID-19 in the health care setting. However, recent randomized controlled trial data suggest that medical masks are noninferior to N95 respirators for routine care (non–aerosol generating medical procedures).Evidence 20Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to heterogeneity and indirectness. Loeb M, Bartholomew A, Hashmi M, et al. Medical Masks Versus N95 Respirators for Preventing COVID-19 Among Health Care Workers: A Randomized Trial. Ann Intern Med. 2022 Dec;175(12):1629-1638. doi: 10.7326/M22-1966. Epub 2022 Nov 29. PMID: 36442064; PMCID: PMC9707441. The utility of different types of masks and even masks in general remains a topic of debate and opinions, certainly associated with a relatively low confidence in the available evidence. Local guidelines need to be consulted.

2) PPE for eye protection: Goggles or a face shield.

3) PPE for body protection: A long-sleeved gown or protective suit.

4) PPE for hand protection: Gloves.

Health care facilities should have PPE available in different sizes.

Video instructions on wearing and removing PPE:

1) Precautions: Inhalation (aerosol-generating procedures), see a video from Sunnybrook Health Sciences Centre, Toronto, Canada: youtube.com/watch?v=syh5UnC6G2k.

2) Precautions: Large IRPs (historically droplets), see a video from St Joseph’s Healthcare Hamilton, Canada: youtube.com/watch?v=i_J2qtM1Aus.

6. Individuals caring for infants: Infants cannot use respirator masks or facemasks and require special precautions to prevent viral transmission. Adults should use a respirator mask, perform hand hygiene before touching the infant, and regularly disinfect toys and other objects in the infant’s environment.

7. Reporting: Individuals traveling from countries where COVID-19 is present or who had contact with a patient infected with SARS-CoV-2 should notify public health authorities and discuss further management.