Chapter 1

COVID Overview

SymptomsCopy Link!

Common SymptomsCopy Link!

Updated Date: May, 2020
Literature Review:
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Tool:
CDC Symptom Self-Checker

This section covers symptom prevalence, click here for Triage Based on Symptom Questionnaires.

Many patients are asymptomatic. Among patients with symptoms, most present with an influenza-like illness (fevers, myalgias, respiratory symptoms), but many do not present with this classic combination. Some may present with less-usual findings such as perniosis (COVID toes) or anosmia. These ranges are pulled from the following articles, and symptom prevalence varies greatly depending on testing and survey methodology (Arentz et al; Chen et al; Guan et al; Li et al; Wu et al; Zhou et al; WHO-China Joint Mission on COVID-19; Young et al; Yan et al; Jiang et al; Huang et al; Tostmann et al).

  1. Fever, 44-94%
  1. We recommend using >= 38°C to define fever, taking into account the patient’s age, immune status, medications (steroids, chemotherapy, etc.), and recent use of fever-reducing medications.
  2. Children are less likely to have fever or cough (Bialek et al).
  1. Cough, 68-83%
  2. Anosmia and/or ageusia (loss of sense of taste and/or smell) ~70%
  3. Upper respiratory symptoms (sore throat, dripping nose, nasal or sinus congestion), 5-61%
  4. Shortness of breath, 11- 40%
  5. Fatigue, 23-38%
  6. Muscle aches 11-63%
  7. Headache 8-14%
  8. Confusion 9%
  9. Gastrointestinal symptoms (nausea, vomiting, diarrhea), 3-17%

Clinical CourseCopy Link!

Literature Review: University of Washington Literature Report (Clinical Characteristics)

Incubation and Window PeriodCopy Link!

Updated Date: December 19, 2020

Incubation period is the time from exposure to symptom onset. Latency period is the time from exposure to infectiousness (or viral detection, depending on the definition). COVID-19 has a relatively long incubation period, and typically at least 2 days of infectivity before symptoms develop.

IncubationCopy Link!

Time from exposure to symptom onset: mean and median 5 days (common range 2-7 days). (Li et al; Guan et al; Velavan et al; Chan et al; Nie et al).

  • 97.5% of exposed cases will develop symptoms within 11 days and 99% within 14 days. Over 95% of cases develop symptoms within 13 days of infection (Nie et al).
  • Incubation periods of up to 24 days are shown in some reports (Nie et al).

Window PeriodCopy Link!

Samples taken before symptom onset have high false negative rates, as modeled by (Kurcirka et al). 68% false negatives one day before symptoms, compared to 38% false negatives on the first day of symptoms, based on serial testing. They estimated the window period between exposure and detectability of SARS-CoV-2 RNA on nasopharyngeal sampling at 3-5 days, with peak sensitivity 8 days after exposure or 3 days after symptom-onset in their model. As with incubation, individual cases may show longer delays. Asymptomatic patients should still be tested in certain circumstances, but a negative result does not rule out infection.

Duration and Time CourseCopy Link!

Updated Date: May, 2020
Literature Review (Clinical Course):
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Median duration of common symptoms (median in survivors only), drawn from (Zhou et al; Young et al):

  1. Fever: 12 days
  2. Shortness of breath: 13 days
  3. Cough: 19 days

Time course from symptom onset to complications (Zhou et al, Feldstein et al):

  1. Multi-System Inflammatory Syndrome in Children (MIS-C): 6 days (range 4-8 days).
  2. Sepsis: median onset 9 days (range 7-13 days)
  3. Acute Respiratory Distress Syndrome (ARDS): median onset 12 days (range 7-15 days)
  4. Need for mechanical ventilation: median onset 10 days (range 3-12.5 days)
  5. Acute cardiac injury: median onset 15 days (range 10-17 days)
  6. Acute kidney injury: median onset 15 days (range 13-19.5 days)
  7. Secondary infection: median onset 17 days (range 13-19 days)
  8. Death: Median 18.5 days, interquartile range 15-22 days (Zhou et al)
  1. Illness severity has been noted to have two peaks at ~14 days and ~22 days (Ruan et al)

SeverityCopy Link!

Updated Date: May, 2020
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The majority of patients have only mild symptoms, however the percentage of patients who develop severe or critical disease is far greater than for most other respiratory viruses, including influenza. See how mild, moderate, and severe cases are defined.

  • Asymptomatic infection is present in at least 20% of cases, maybe more (Bi et al; Mizumuto et al; Pollan et al).
  • Mild symptoms to mild pneumonia: 81-91% of symptomatic patients
  • Severe symptoms (need for supplemental oxygen, or >50% lung involvement): 9-14% of patients
  • Critical symptoms (respiratory failure, shock, multiorgan dysfunction): approximately 5% of patients (Wu et al).
  • Among critically-ill patients, many receive mechanical ventilation. Median time on ventilator ranges from 11-17 days (Chen et al; Ling et al).
  • Presentation with shock is rare, but vasopressors are eventually used in 67% of critically-ill patients.
  • Cardiomyopathy (heart tissue injury) is noted in 33% of critically-ill patients (Ruan et al).

Prognostic IndicatorsCopy Link!

Updated Date: May, 2020

Demographic and Health FactorsCopy Link!

Literature Review (Comorbidities): Gallery View, Grid View
Literature Review (Sex Differences):
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Multiple factors have been associated with worse prognosis in people infected with SARS COV-2.

  1. Age: increased age is associated with more severe disease and higher rates of death (Wu et al; Chen et al; Yang et al; Qin et al).
  1. Children are less likely to have severe disease, but pediatric deaths have been reported (Bialek et al).
  2. Children appear to be as likely to contract the infection as adults, although symptomatic cases of children are more rare (Bi et al).
  1. Comorbidities: The following conditions are associated with more severe COVID-19 disease and are often associated with worse outcomes (Fang et al; Guan et al; Yang et al; Zhang et al; Chen et al; Tang et al; Zhou et al; WHO-China Joint Mission on COVID-19; Yu et al).
  1. Hypertension
  2. Diabetes
  3. Coronary Artery Disease
  4. Chronic Lung Disease (Though Asthma may be an exception)
  5. Malignancy (cancer)
  1. Race: Please see Health Equity for a discussion on racial differences in COVID infection and severity.
  2. Sex: Men appear to be more severely affected by COVID-19 than women. Conclusive evidence related to sex differences is limited by methodology of existing studies. (Schiffer et al).
  3. Smoking: Smoking may offer a small risk reduction for COVID infection, though it is not clear why and this finding may be subject to confounding. It does appear to be associated with worse outcomes. See Smoking for more details.

Laboratory IndicatorsCopy Link!

The most significant laboratory abnormalities associated with severe COVID-19 disease and death include the following (Zhou et al; Huang et al; Chen et al; Wu et al; Ruan et al):

Lab test

Results

Normal ranges (For many US labs, units and values may vary)

White Blood Cell Count (WBC)

> 10 K/uL (K/uL=10^3/uL)

Male and Female- Adults: 3.4-9.6 x10^3/uL

Lymphopenia

< 1.00 K/uL (K/uL=10^3/uL)

Male and Female- Adults: 0.95-3.07 x10^3/uL

Platelets

< 150 K/uL (K/uL=10^3/uL)

Male Adults: 135-317 x 10^3/uL

Female Adults: 157-371 x10^3/uL

Creatinine

> 1.5 mg/dL

Male Adults: 0.74-1.35 mg/dL

Female Adults: 0.59-1.04 mg/dL

Albumin

< 3 g/dL

3.5-5.0 g/dL

Alanine transaminase (ALT)

> 40 U/L

Males: 7-55 U/L

Females: 7-45 U/L

Creatinine kinase (CK)

> 185 U/L

Males: 39-308 U/L

Females: 26-192 U/L

Troponin T, high-sensitivity (hs-TnT)

> ~20 ng/L

Male <23 ng/L

Female <15 ng/L

C-reactive protein (CRP)

> 125 mg/L

< or =8.0 mg/L

Lactate dehydrogenase (LDH)

> 245 U/L

Adults: 122-222 U/L

Ferritin

> 300 ug/L (severe disease); Ferritin > 1000 ug/L (death)

Males: 24-336 ug/L

Females: 11-307 ug/L

Interleukin 6 (IL-6)

> 10 pg/mL

< or =1.8 pg/mL

D-Dimer

> 1000 ng/mL

< 250 ng/mL

Procalcitonin

> 0.5 ng/mL

< or =0.15 ng/mL

MortalityCopy Link!

Updated Date: December 16, 2020
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Cause of DeathCopy Link!

Determining and reporting the cause of death for patients with COVID-related diseases is complex (as it is with any disease).

  • Cause of Death: This is usually the acute medical diagnosis that caused a patient to die, and often relates to a medium-term or long-term diagnosis as well. It will often include other diseases as co-morbid or contributing factors (e.g. pneumonia due to COVID-19 infection or Acute Myocardial Ischemia due to COVID-19 infection and Coronary Artery Disease).
  • Mechanism of Death: Defined as the immediate physiologic issue resulting in death (for example, hypoxemia).

A significant number of COVID-related deaths do not have clear delineation of cause of death (CEBM). The majority of people who die from COVID-19 die from respiratory failure. Because definitions of cause of death are reported differently it can be hard to determine exact numbers, but here are estimates (Ruan et al, 68 cases), (Zhang et al, 82 cases):

  • Respiratory failure alone: 53% - 69%
  • Circulatory failure alone: 7%-14.6%
  • Mixed respiratory and circulatory failure, sepsis, or multiorgan failure: 28-33%
  • Hemorrhage: 6.1%
  • Renal failure: 3.1%

Tool: Improving Cause of Death Reporting
Tool: Guidance for Reporting COVID-Related Deaths

Case Fatality RateCopy Link!

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  • Case fatality rate (CFR) is typically the proportion of deaths from a disease relative to the number of people diagnosed with the disease in a specific period of time. Some people define a “case” as showing symptoms.
  • Infection fatality rate (IFR) is the proportion of deaths from a disease but relative to all infected individuals including asymptomatic people and infections that were missed. It is harder to measure, and thus most places report CFR.
  • Case fatality rate is variable in different countries. Range around the world seems to be between 0-16%, with most countries in the 1-3% range.

Tool: Johns Hopkins Summary of Case Fatality Ratios
Tool: Forecast Hub (Compilations of forecasts by country or state)

PathophysiologyCopy Link!

PathophysiologyCopy Link!

Updated Date: December 16, 2020

Literature Review (ACE2): Gallery View, Grid View

Literature Review (Human Genetics) Gallery View, Grid View

Classification: SARS-CoV-2 is a positive-stranded RNA virus with a nucleocapsid and envelope, belonging to the coronavirus family, of which seven viruses (including the original SARS-CoV in 2003 and MERS in 2013) have crossed from zoonotic origins into humans.

Cell Entry and Replication: For cell entry, the SARS-CoV-2 spike protein binds to the ACE2 receptor, expressed in nasal and bronchial epithelium, pulmonary endothelium, alveolar Type 2 cells, proximal renal tubule cells, cardiac myocytes, gastrointestinal epithelial cells, and others. Cleavage/priming by serine protease TMPRSS2 facilitates SARS-CoV2 cell entry, followed by viral replication using host cell machinery and then exocytosis (Kumar et al).

Cellular Targets and Resulting Lung Injury: The cells that express ACE2 may be the cell populations most injured by infection or targeted by the immune response. Alveolar Type 2 cells secrete surfactant, so injury may result in alveolar collapse at low opening pressures and high PEEP sensitivity, while damage to pulmonary endothelial cells may cause capillary leak and trigger an influx of monocytes and neutrophils, with formation of hyaline membranes. The highly inflamed lung parenchyma can develop microthrombi that help explain some of the thrombotic complications of COVID (Wiersinga et al).

Literature Review (Acute Lung Injury): Gallery View, Grid View

Inflammatory Cascade: Infection with the SARS-Cov-2 virus can cause apoptotic cell death, which triggers an inflammatory cascade of cytokine release, as well as the recruitment of immune cells including macrophages and dendritic cells, and later, antigen-specific T lymphocytes (Bohn et al). If the immune response is not properly checked, a state of hyperinflammation occurs, with the development of Cytokine Storm Syndrome, and sometimes multi-organ failure.

Blood type: There is evidence that A blood type is a risk factor for COVID-19 respiratory failure, and O may be protective. This was based on a genome-wide association study (GWAS) of 835 patients and 1255 control participants from Italy and 775 patients and 950 control participants from Spain. Respiratory failure was defined as a patient requiring supplemental oxygen or mechanical ventilation (Ellinghaus et al).

Literature Review (ABO): Gallery View, Grid View

Histology and AutopsyCopy Link!

Updated date: December 18, 2020

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Literature Review (Histology): Gallery View, Grid View

  • Autopsy studies indicate universal damage to pulmonary tissue (Falasca et al; Elsoukkary et al). Pulmonary histology of COVID-19 shows bilateral diffuse alveolar damage, desquamation of pneumocytes, pulmonary edema, hyaline membrane formation, inflammatory cell infiltrates, and multinucleated giant cells, as well as some evidence of direct viral injury (Xu et al; Geng et al). Vascular involvement in the lung is also quite common, with microthrombi, endotheliitis, severe capillaritis, vascular complement deposition, and pulmonary thromboemboli, often in small and mid-sized vessels (Calabrese et al).
  • Cardiac injury and thrombotic complications are widely prevalent, including cardiac inflammatory infiltrates, epicardial edema, and pericardial effusion in some autopsies (Falasca et al; Elsoukkary et al; Geng et al).
  • Acute kidney injury, while common in hospitalized COVID patients, was found to be mild in post-mortem patients with theoretical potential for recovery (Santoriello et al).
  • Neurologic lesions in autopsy series of 43 patients (not necessarily with neurologic manifestations) showed fresh ischemic lesions in 14%, and neuroinflammatory changes with infiltration of cytotoxic T lymphocytes most pronounced in the brainstem (also cerebellum and meninges) (Matschke et al). In patients with significant neurologic decline, more severe findings have been noted including hemorrhagic lesions through the cerebral hemispheres, marked axonal injury, areas of necrosis, and pathology similar to acute disseminated encephalomyelitis (ADEM). (See e.g. Reichard et al).

EpidemiologyCopy Link!

Literature Review: University of Washington Literature Report (Geographic Spread)

Literature Review: University of Washington Literature Report (Modeling and Prediction)

Case Counts and PrevalenceCopy Link!

Updated Date: December 19, 2020
Tool: Worldwide case counts are published by teams at the World Health Organization, Johns Hopkins University, and others.

Prevalence estimates depend significantly on testing availability and percentage of the population that has asymptomatic infection as well as on the severity of the epidemic in a specific location. Seroprevalence studies, measuring antibodies across an entire population, can help give a better estimate of true prevalence. In one meta-analysis of 47 studies on seroprevalence covering 399,265 people from 23 countries, the SARS-CoV-2 seroprevalence in the general population varied from 0.37% to 22.1%, with a pooled estimate of 3.38% (Rostami et al).

OriginsCopy Link!

Updated date: June, 2020
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COVID-19 transmission is primarily human-to-human following a suspected animal-to-human initiating event (Li et al). It is thought that it may have emerged from racoon dogs or civets, but this is still being investigated (Mallapaty). The virus was initially recognized in December 2019 by Chinese authorities in the setting of cases of pneumonia that seemed to be clustered around a seafood market in Wuhan, Hubei Province (Wuhan Municipal Health Commission, 2019).

New VariantsCopy Link!

Literature Review (Viral Genetics) Gallery View, Grid View

This section is in process

Laboratory samples collected in December 2019 yielded evidence of a novel betacoronavirus, genetically-distinct from previously identified SARS-CoV and MERS-CoV but genetically-similar to previously-published coronavirus strains collected from bats from southwestern China (Zhu et al). Viral genomes have been published to GenBank from diverse geographies.

Tool: Reports on real-time phylogenetic tracking of the viral genome can be found at NextStrain (Hadfield et al).

Infectivity and TransmissionCopy Link!

InfectivityCopy Link!

Updated Date: December 19, 2020

Viral Load, PCR Clearance, and Infectiousness TimelineCopy Link!

Literature Review (Viral Shedding): Gallery View, Grid View

Patients who are infected with SARS COV-2 and who have higher levels of virus in their respiratory tracts and oropharynx are the most infectious (Bullard et al). Patients who have higher levels of virus in their respiratory tracts and oropharynx are most infectious, irrespective of symptom status. Symptom status does not seem to correlate predictably with viral load (Walsh et al; Lee S. et al; Zou L et al).

Upper airway viral load peaks within ~5 days of symptom onset, followed by decline (Wölfel et al; Young et al). Consequently, patients appear to be most infectious in the 2-3 days before symptom onset and the 2-3 days after (Ferretti et al). PCR detection continues for a median of 20 days from time of symptom onset, with an interquartile range 17-24 days (Zhou et al). There are rare cases that remain positive up to ~60 days after infection (McKie et al). However, the virus is very rarely culturable (our closest proxy to infectivity) after 9 days (Cevik et al). The culture data underlies the newer guidance (after November 2020) about quarantine time. See testing for a diagram of test positivity compared with infectivity and symptoms.

Asymptomatic PatientsCopy Link!

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Asymptomatic, minimally symptomatic (paucisymptomatic), and pre-symptomatic patients can all transmit the virus (Bai et al; Rothe et al; Furukawa et al), though presence of symptoms is probably associated with increased frequency of transmission. In one study in Beijing, face masks worn by family members of pre-symptomatic COVID-19 patients were shown to be 79% effective (OR = 0.21) at reducing transmission, suggesting that presymptomatic transmission is an important mode of transmission and that masks can be effective at preventing it (Wang et al).

Recovered PatientsCopy Link!

Patients who have recovered from COVID sometimes will have fragments of viral RNA that continue to test positive by PCR. Shedding of viral RNA is longer in more severe disease, or in patients who are immunocompromised. However, recent data shows that this viral RNA does not likely represent infectious virions, but rather parts of the virus that are unable to replicate. As such, the CDC has changed it’s recommendations on the duration of isolation and quarantine as well as releasing patients from isolation (Cevik et al).

Vaccinated PeopleCopy Link!

We do not yet know how all available and pending vaccines will perform with respect to asymptomatic infection. This is an evolving area of research, but the data suggests that being vaccinated does NOT preclude asymptomatic infection or transmission from one person to another, and therefore most global agencies recommend that people who have been vaccinated continue transmission reduction measures like masks and distancing (CDC).

TransmissionCopy Link!

Updated Date: December 18, 2020
Literature Review: University of Washington
Literature Report (Transmission)

Basic Reproduction Number (R0)

Tool: For global estimates of R0, see here. For the United States, state-by-state estimates of R0 are available here (data from The COVID Tracking Project). Please keep in mind these are merely estimates and all models are fallible.

R0 (R-naught) is a measure of transmissibility. It represents the theoretical number of secondary infections from an infectious individual. This is a property both of the infectiousness of the virus and the behaviors of humans to decrease spread.

  • An R0 > 1 is consistent with sustained outbreak.
  • An R0 < 1 means an epidemic is declining.

The R0 for COVID-19 is likely similar to, or slightly higher than, many other respiratory viruses, but because it is so highly influenced by human behavior, it can be changed. The initial R0 of COVID in Wuhan in the absence of containment measures was thought to be about 2.5 (Majumder et al). However, R0 declines with control measures (Zhao et al; Riou et al; Flaxman et al; Read et al; Shen et al).

The pre-control R0 of 2.5 is:

Aerosol, Droplet and Fomite TransmissionCopy Link!

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It is believed that COVID-19 transmission primarily occurs through liquid respiratory particles that travel through the air between people who are within a distance of about 2 meters of one another. Growing evidence indicates that transmission beyond a distance of 2 meters is also possible, especially in poorly-ventilated spaces and with periods of exposure exceeding 30 minutes (Lancet Editorial).

Modes of transmission have been a contested topic. The discussion has been complicated by lack of standardized definitions and usage of terms such as large droplets, small droplets, and aerosols. It is believed that most transmission occurs with droplets produced when a person coughs or sneezes, though other modes also occur.

Droplet transmission: liquid respiratory particles vary in size and are produced during breathing, talking, singing, coughing, and sneezing (CDC). Larger particles of 60-100 micrometers typically do not travel through the air farther than 2 meters (Lancet Editorial).

Airborne/Aerosol transmission: very small respiratory droplets, often called aerosols, may remain suspended in the air and travel a distance exceeding 2 meters (Lancet Editorial). The risk of producing aerosols is heightened during coughing, sneezing, and certain medical procedures (WHO-China Joint Mission on COVID-19). Aerosolized particles appear to remain in the air for at least 3 hours (Van Dorelmalen et al).

Fomite (objects and surfaces) transmission: transmission may occur through touching contaminated objects before touching the mouth, nose, or eyes, but this is an inefficient mode of transmission (Kampf et al). While SARS-CoV-2 can persist for days on some surfaces, attempts to culture from surfaces have been unsuccessful. Viral particles have been shown to survive < 24h on cardboard and < 72h on plastic or steel (Van Dorelmalen et al). In cases of suspected transmission through fomites and direct contact, full exclusion of respiratory transmission as the actual mode has not been possible. Transmission through the handling of contaminated objects is presumed to be unusual (Meyerowitz et al). Adherence to standard precautions and disinfection of equipment and surfaces is still indicated (Mondelli et al).

Water and sewage: Persistence of SARS-CoV-2 virus in drinking-water is possible; indeed, some organizations and public health departments are tracking COVID infection rates by measuring waste-water RNA (see CDC wastewater testing, and Larsen et al). There is no evidence to date about survival of the virus in water or sewage, but it is likely to become inactivated significantly faster than non-enveloped human enteric viruses with known waterborne transmission (such as adenoviruses, norovirus, rotavirus and hepatitis A).

Bodily FluidsCopy Link!

  1. Feces and whole blood have been shown to contain viral ribonucleic acid (RNA) on PCR studies (Wölfel et al; Young et al). Significance for transmission is unclear (Chen et al), though in one systematic review of smaller studies, replication-capable virus was found in 35% of samples (van Doorn et al), meaning that fecal transmission may be possible.
  2. Urine does not appear to contain viral ribonucleic acid (Wölfel et al).
  3. Semen and vaginal secretions: COVID-19 virus has not been detected in vaginal secretions (Qiu et al). It is detectable in semen, but transmissibility is unclear. Likelihood of transmission via respiratory secretions during sexual encounters, however, is likely (Sharun et al).
  4. Tears: a few studies have indicated presence of COVID-19 virus in tears, while others have not. Current evidence is limited, but risk of transmission through tears is thought to be low (Seah et al).
  5. Cerebrospinal Fluid: Rarely, CSF has been noted to be positive by PCR (in 2 of 578 samples in one study, but not at levels that are infectious) (Destras et al).

Household and Community TransmissionCopy Link!

Household contacts of an index case appear more likely to contract the virus than other contacts (Bi et al). Most transmission events occur within households (Luo et al). The household secondary attack rate (e.g. number of people who get infected from an index case) is very variable, thought to be about 17.2% in one meta analysis (Fung et al), though very few studies tested more than once, so many cases may not have been missed The results ranged from 10.3-32.4% when contacts were tested at least twice. One recent study that did daily testing estimated SAR at 35% excluding those who had positive tests at enrollment, 53% including cases positive on enrolment. 75% of secondary cases occurred within 5 days of the index patient’s symptom onset (Grijalva et al). However, when prevalence increases, more community (meaning with no known exposure) transmissions tend to occur, highlighting the necessity of non-pharmaceutical interventions (e.g. masks) coupled with public health strategies such as sentinel and syndromic surveillance.

Super-Spreading Events (SSEs)Copy Link!

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Super-Spreading Events are when an individual directly spreads an infection to an unusually large number of others. Several cases of superspreading have occurred at choirs (Hamner et al), weddings (including a Maine wedding that led to 177 linked cases, including seven deaths), churches Daegu, South Korea, where “Patient 31” infected at least 40 others (Ryall), and even within the White House. SSEs are believed to be disproportionately responsible for COVID-19 cases globally, with several studies suggesting that ≈80% of secondary transmissions have been caused by a small fraction (≈10%) of initially infected individuals. (Althouse et al; Endo et al). SSEs are heavily dependent on sociobiological mechanisms, including individual viral load, numbers of susceptible contacts per person, residence or employment in congregate settings, and ‘opportunistic’ scenarios including temporary clustering of individuals in mass gathering events. Environmental factors also are very important with closed places, crowded places, and poor ventilation playing a significant role in SSEs. Because SSEs play such an outsized role in fueling the pandemic, they amount to a significant concern, but also serve as an opportune area for public health interventions, particularly the prevention of transmission events where over 10 people are infected. (Althouse et al).

SchoolsCopy Link!

Schools are unique settings and are likely to contribute to COVID-19 transmission between households and within communities. However, sustained closure of in-person schooling is expected to have an adverse effect on life outcomes for children and to worsen existing inequalities.

The American Academy of Pediatrics advocates that children should be physically present in school where possible (AAP Guidance). However, large-scale studies of over 500,000 contacts of 85,000 infected cases in India have noted that children are a significant source of spread, even despite school closures (Laxminarayan et al). This thorough review of the literature on school transmission and safety summarizes some of the unique challenges and recommendations (Massachusetts General Hospital COVID-19 Resource Library). Decisions on whether or not to open schools depends significantly on local policy and local epidemiology.

Tool: Strategies to Minimize Risk have been developed at the TH Chan School of Public Health at Harvard University.
Tool: CDC has published guidance on risk reduction and reopening of schools.

Air TravelCopy Link!

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The risk of contracting COVID-19 on airplanes is low. 50% of the air circulated in the cabin is brought in from the outside, and the remaining 50% is filtered through HEPA filters. Air enters the cabin from overhead inlets and flows downwards toward floor-level outlets. There is relatively little airflow forward and backward between rows, making it less likely to spread respiratory particles between rows (Pombal et al). To avoid transmission, it is advised to avoid moving up and down the aisles as much as possible, and to wear a mask for the duration of the flight.

Pets and AnimalsCopy Link!

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While transmission risk from pets is low, the United States Centers for Disease Control now recommend that social distancing rules should apply to pets as well as to humans (CDC). Dogs showed low susceptibility. Pigs, chickens, and ducks were deemed not susceptible according to early data. Evidence of viral replication was noted in inoculated ferrets and cats, with viral transmission occurring between cats (Chen et al). There is no current evidence of transmission to humans from cats and ferrets, though minks can transmit to humans (Meyerowitz et al). Virologist cited in Nature News suggests cat owners should not yet be alarmed, noting deliberate high-dose inoculation of said cats - unrepresentative of day-to-day pet/owner interactions, and that none of the infected cats developed symptoms in the aforementioned study (Mallapaty et al).

SeasonalityCopy Link!

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This section is in process.

Immunity and VaccinesCopy Link!

Antibody ResponseCopy Link!

Updated Date: December 18, 2020

The majority of patients with RT-PCR-confirmed COVID-19 develop antibodies against the virus (Zhao et al; Wang et al). These two large series of serial samples found antibodies in 161/173 and 308/310 patients respectively. Time to seroconversion, correlation with protection, and durability of immunity, continue to be studied.

When assessing research studies, details may depend on exactly which antibodies are being assessed(e.g,. IgA/IgM/IgG or total antibody, antibodies to the nucleocapsid vs those to the spike protein, or whether the antibodies are “neutralizing” -- for example, antibodies directed against the receptor-binding domain (a component of the spike protein) may appear earlier than antibodies to other antigens (To et al; Okba et al).

Seroconversion (detection of circulating antibodies) typically occurs 7-14 days after symptom onset (Deeks et al; Huang et al). In one study of 173 patients, 100% were seropositive (total antibody) at 15 days (Zhao et al).

  • Although IgM seroconversion is often thought of as occurring before seroconversion for IgG, this has not been consistently observed for SARS-CoV-2 (e.g., Qu et al; Xiang et al; Wang et al; Zhao et al).
  • IgA antibodies are important in mucosal immunity and may play an important role in the response to SARS-CoV-2 (Sterlin et al; Wang et al), but data are currently limited (Deeks et al).
  • The sensitivity of serology (IgM or IgG) may be higher than that of PCR by the second week of illness (day 8 in Zhao et al, day 6 in Guo et al), based on studies with serial samples from individual patients.
  • Antibody detection may identify cases with negative upper airway PCR but high clinical suspicion when timed appropriately; Guo et al found positive IgM in 54 of 58 probable cases without detectable nucleic acid.

Neutralizing antibodies prevent viral replication, usually by binding the spike glycoprotein that SARS-CoV-2 uses to enter cells. Not all antibodies are neutralizing; some bind to the virus but do not stop its activity.

Cross-reactivity occurs when a pre-existing immune response to seasonal human coronaviruses recognizes SARS-CoV-2. It has been seen in both T-cell (e.g., Mateus et al) and humoral (e.g., Ng et al) arms of the immune system. This presence or absence of this response has been hypothesized to contribute to variable outcomes in COVID-19 (Beretta et al). A possible altered immune response due to pre-existing antibodies has also raised the possibility of antibody-dependent enhancement after SARS-CoV-2 vaccination or convalescent plasma therapy. Fortunately, such enhancement has not been reported to date (Wen et al).

Reinfection and Durable ImmunityCopy Link!

Updated Date: December 18, 2020
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Reinfection refers to individuals who have been infected and cleared the original virus, but again show viral replication after exposure to a new SARS-CoV-2 virus. This has been documented in a handful of cases, most often in patients with weakened immune systems.

  • RT-qPCR alone does not distinguish reinfection with a new SARS-CoV-2 virus from prolonged or recrudescent infection with the same virus (Falahi et al). Conclusive demonstration of reinfection requires genomic sequencing of the virus during initial and subsequent infections and analysis to show the two viruses are too different to have incubated in a single host.

Tool: Track Cases of Reinfection.

The duration of immunity after infection is not yet conclusively known (Iwasaki), since COVID-19 is a new infectious disease. Host factors likely play a significant role, including immune status, age, and severity of initial infection. Studies documenting decay of IgG antibodies may underestimate immunity, since T-cell responses likely also play a significant role (Karlsson et al).

  • Patients with mild infection lose detectable antibodies more quickly but appear to have an immune memory that may allow them to rapidly produce antibodies again on re-exposure (Stephens et al).
  • Longer term analysis of 2003 SARS-CoV-1 infection showed IgG and neutralizing antibody titers peaked at 4 months and diminished over a 3-year follow up period (Cao et al). In a cohort of 23 patients with a history of SARS-CoV-1 infection, specific IgG Ab to SARS-CoV-1 was undetectable in 91.3% of former patients after 6 years (Tang et al).

VaccinesCopy Link!

Updated: December 17, 2020.
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Literature Review: University of Washington
Literature Report (Vaccines and Immunity)

At the end of 2020, there were approximately 75 vaccines worldwide in phases I through III of clinical research, 5 in limited use, and ~2 holding approvals (depending on country) for full use after completion of phase III (not counting trials underway for repurposing of pre-existing vaccines). Most of these vaccines fall into one of 4 categories:

  1. Genetic vaccines (typically lipid envelopes carrying SARS-CoV-2 genetic material into cells)
  2. Viral vector vaccines (repurposed viruses such as adenovirus carrying SARS-CoV-2 genetic material into cells)
  3. Protein-based vaccines (delivering coronavirus proteins only)
  4. Traditional “inactivated/attenuated” coronavirus vaccines.

The best-studied vaccines are the mRNA vaccines produced by Pfizer/BioNTech and Moderna, and key “viral vector” vaccines include adenovirus-vector examples produced by Oxford/AstraZeneca, CanSino Biologics (China), the Russian Ministry of Health, and Johnson & Johnson/Beth Israel Deaconess Medical Center.

Mechanisms:

  • The mRNA vaccines: code for the coronavirus “spike” protein to induce an immune response mediated by antibodies and T cells. Both Moderna and Pfizer versions have a greater than 90% efficacy after 2 doses (94.1 and 95%, respectively), although longer-term study is needed to determine how immunity and infectivity change over time. Due to the temperature-sensitivity of genetic material (Simmons-Duffin), these vaccines require somewhat different but very cold storage and transportation environments as well as restrictions on how long they can be kept at room temperature.
  • Adenovirus-vector vaccines: use a variety of engineered adenoviruses (common viruses that cause colds and related symptoms) as vectors to expose human cells to the SARS-CoV-2 spike. These are generally cheaper than genetic vaccines (Knoll et al), both due to ease of transport as they only require refrigeration to protect the virus vector, as well as due to less costly supply chains than those required for mRNA vaccine technology.

Efficacy of vaccines. Efficacy data is currently available for three vaccines. The Pfizer/BioNTech vaccine in its EUA cited efficacy of 95% at preventing symptomatic infection. Asymptomatic infection was not studied in this trial (Pfizer EUA). The Moderna vaccine showed 94% efficacy, and asymptomatic infection rates are not yet known after two doses, but after a single dose it reduces asymptomatic infection by 63% (data after the second shot is forthcoming, Moderna EUA). The Oxford/AstraZeneca vaccine had an efficacy of 90% at one dosing schedule (the now intended schedule) though they had two different dosing schedules and the other one did not perform as well. In the intended dosing schedule, it demonstrates 59% efficacy in preventing asymptomatic infection (Ledford; Knoll et al).

Adverse events/Reactogenicity: Most observed adverse events in trials of these vaccines are injection-related or reflect the body’s expected immune response. Many people feel ill following vaccine administration for about 1-3 days, especially after the second dose of the vaccine, and this is expected and does not mean that you have been infected with coronavirus.

Ability to transmit to others: We do not yet have information about viral transmission, but based on asymptomatic infection rates it is likely still possible to transmit the virus to others even if vaccinated and asymptomatic. Please see Transmission.

Special populations:

This section is forthcoming

  • Obstetrics
  • Pediatrics
  • Immunosuppressed

Tool: Vaccine Allocation Planner (helps states and countries plan vaccine allocation)
Tool: COVID Vaccine Development Tracker
Tool:
FDA COVID Vaccine FAQs

Vaccine EquityCopy Link!

While approval of the first vaccine marked the culmination of a tremendous scientific effort, the fight against COVID-19 now faces a new challenge: a massive worldwide vaccination campaign. The same embedded structural forces driving inequities in the burden of COVID-19 must also be considered within the context of vaccine access and distribution.

Vaccine prioritization: It is essential that COVID-19 vaccines be distributed equitably. People who should be prioritized for vaccination include (adapted from the National Academies of Sciences, 2020).

  • High-risk of COVID-related morbidity and mortality
  • Medical comorbidities
  • Over the age of 65
  • High-risk of contracting COVID-19
  • Residents of long-term care facilities and group homes
  • Incarcerated
  • Undomiciled
  • First-responders
  • Healthcare workers
  • Front line workers (e.g. supermarkets, factories, schools, agriculture, and meat-processing plants)

Due to generations of structural racism and socioeconomic inequalities, people of color, people with disabilities, immigrants and migrants, indigenous peoples, and the poor are all disproportionately represented in many of these groups.

Global Distribution: The distribution of vaccines among nations should follow similar principles. No country should have enough vaccines to vaccinate their entire population before another country has enough to vaccinate their high-risk populations. As of December, 2020 there is significant imbalance: Canada has ordered enough vaccines to inoculate six-times its population, the United Kingdom and the United States four-times their populations, and the European Union twice its population (New York Times).

COVAX, a global coalition including the WHO to assure vaccination, has proposed that all countries receive an adequate supply to inoculate at least 20% of their population before any nation receives additional vaccines. This will ensure that high-risk groups are vaccinated regardless of where they live. Following this initial roll-out, vaccines should be distributed based on the vulnerability of the country’s health system and the impact of COVID-19 on the country, prioritizing countries most in need (COVAX, 2020).

Vaccine hesitancy: In countries like the US, vaccine hesitancy and distrust of the medical system may further exacerbate inequity (Warren et al). This is shaped by the legacy of exploitation and oppression of marginalized groups in the name of science (for example, the Tuskegee Experiment). Meaningful community engagement and promotion of informed decision-making requires an acknowledgment that these historical and contemporary forces contribute to a rational distrust of the health system among marginalized communities (Burgess et al).

Herd ImmunityCopy Link!

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This section is in process

Health EquityCopy Link!

What is Health Equity?Copy Link!

Updated Date: December 17, 2020

Equity focuses on the fair and just treatment of all people. By extension, addressing inequities involves eliminating avoidable, unfair or changeable differences among groups, whether these are defined socially, economically, demographically, or otherwise. Upholding equity in health allows prioritization of fair opportunities for everyone to attain their full health potential (WHO Health Systems: Equity).

The COVID-19 pandemic has disproportionately affected historically oppressed populations around the world. Due to long-standing structural inequities, people from these communities are: 1) more likely to be exposed to disease, working essential jobs and living in crowded conditions; 2) less likely have to have access to quality healthcare, including COVID-19 testing and treatment; and 3) more likely to suffer from preexisting health conditions, as a result of adverse social determinants of health, putting them at increased risk of complications and death (Warren et al).

Not all of these can be included here, but we will address several major concerns. Inclusive data collection, while important, needs to be followed by evidence-driven steps to create an inclusive pandemic response and to be the foundation for equitable public health emergency planning (Reed et al).

Providers should screen for and Address Social Determinants of Health (SDOH): SDOH are the conditions under which people are born, grow, live, work, and age (AAFP's The EveryONE Project) which act to shape the health and well-being of people in complex ways. In the context of COVID-19, living situations coupled with job insecurity increase the risk of infection and then make safe isolation and quarantine difficult. In some neighborhoods in the United States, as many as 70% of positive cases required social support to safely isolate and quarantine (Kerkhoff et al).

Global and National Wealth InequalityCopy Link!

This section is in process

Racial DisparitiesCopy Link!

Updated Date: December 17, 2020
Literature Review:
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In the United States and United Kingdom multiple sources have demonstrated that Black and Latinx populations are disproportionately likely to be infected and/or die from COVID-19 (Garg; NYSDOH Fatalities, NYC DOH). A systematic review and meta-analysis of over 18 million patients across 50 studies from these two countries found higher COVID infection rates within Black, Latinx, and Asian communities (Sze et al). As of late November, 2020 Black and Latinx Americans have had 1.57 and 1.69-fold, respectively, as many cases as white Americans. Black deaths have been at 2.05-fold the rate of white Americans, and Latinx at 1.38-fold the white case fatality rate. (Covidtracking) In the United States, rates of hospitalization among Black and Latinx COVID patients are approximately 4.7 times than among non-Hispanic white patients (Mayo Clinic; Pan et al). In terms of years of potential life lost before age 65, Black Americans are 6.7 times higher, Latinx people 5.4 times higher, Indigenous e populations 4.0 times higher, and Asians 2.6 times higher compared to whites (Bassett working paper).

Tool: Race Statistics

Systemic health inequities affecting minority racial groups cause increased risk in the following categories:

  1. Exposure risk at work: more likely to work in healthcare, education, retail and other jobs that can’t be done from home. In the United States, Latinxs make up 21% of the essential workforce (Economic Policy Institute), but only 18% of the total population (Pew Research). In the United States, 30% of licensed practical and vocational nurses are Black. Close to 25% of the Black workforce in the United States is employed by the service industry (Mayo Clinic).
  2. Exposure risk on public transit: more likely to rely on public transport to attend work (Pew Research).
  3. Exposure risk in shared living spaces: more likely to cohabitate with others (Census).
  4. Comorbid health conditions:.Black people in the United States have a significantly elevated risk of hypertension, which is well-documented, and hypertension control rates are significantly poorer in Black, Latinx, and Asian adults (with acknowledgment of heterogeneity between communities included in population groups) (Saeed et al).
  5. Access to healthcare and testing: income inequality, lower rates of health insurance, and being situated farther from health centers make it harder for many minority groups to access care.
  6. Racism in healthcare delivery: many minority patients experience consciously- and subconsciously-biased health systems and providers when they seek care.
  7. Chronic stress: stress and allostatic load can affect immune function.
  8. Environmental factors: risk for severe COVID has been associated with poorer air quality (Wu et al; Pozzer et al).

Indigenous CommunitiesCopy Link!

Indiginous communities are particularly affected by COVID-19. The cumulative incidence of COVID-19 among American Indian and Alaska Native persons is 3.5 times that among non-Hispanic white persons (CDC) Rates of infection often significantly exceed those in major metropolitan outbreaks (like New York City in April, 2020). As of July, 2020 in New Mexico, American Indians represented 53% of COVID deaths but only 11% of the population (Sequist et al).

Immigrants and MigrantsCopy Link!

Updated Date: December 17, 2020
Literature Review:
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Global migration patterns have shifted during the pandemic, decreasing in some areas but increasing in others. Job losses have resulted in a trend of workers attempting to return to countries of origin, and border closures have resulted in ~3 million people left stranded during their return journeys as of October 2020. The pandemic’s longer-term impacts on poverty and food security have yet to be revealed, but it is anticipated that migration of necessity may increase (WFP).

Noncitizens disproportionately experience the health and financial effects of pandemic, but this is often overlooked as national statistics do not always include non-citizens (for example, data is not currently collected for analysis by the USA CDC). Structural factors that shape daily life for noncitizens place these groups at greater risk of becoming infected with COVID (Langellier et al).

  • Compared with citizens, noncitizens are more likely to live in larger multi-family households where bedrooms may be shared.
  • Non-citizens are also more likely to perform work that cannot be done remotely and depend on public transit.
  • Non-citizens are not currently eligible for public financial and food assistance programs such as Social Security, TANF, and SNAP. Paradoxically, eligible documented immigrants who receive support from these public assistance programs are ineligible for citizenship based on the “public charge” test.
  • Immigration and Customs Enforcement (ICE) has detained over 50,000 undocumented immigrants in holding facilities in the United States. Detainees in such facilities are subject to all of the same infection risks as prison inmates (see People who are Incarcerated), but may be more prone to poor outcomes since ICE’s operational COVID-19 containment protocols do not consistently reflect evolving CDC recommendations (Openshaw et al; Meyer et al; Keller et al).
  • International Medical Graduates (IMGs) make up roughly 25% of the specialist workforce in America but many are serving on H-1B (temporary employment) visas that disqualify them from disability benefits if they were to get COVID at work. This also exposes family members to forcible relocation in the event of their deaths (Tiwari et al).

Suggested policy interventions to improve health among non-citizen populations during pandemic include:

  • Elimination of citizenship barriers to public assistance programs and elimination of public assistance participation as a barrier to establishing citizenship (Langellier).
  • Ensure access to essential resources, such as food, medicine, and legal services (WFP).

Language remains one of the major barriers to quality care. Patients who cannot speak English in the United States are more likely to receive inadequate care (Ross et al). Here are strategies for communication with people with limited proficiency in the language of care providers, shared by the MGH Disparities Solutions Center:

  • Create screening and educational materials based on the languages spoken in your population.
  • Use interpreting services and tools whenever available (in-person interpreters, bilingual phones, and/or mobile screens such as iPads).
  • Use staff hotlines with people who are multilingual.
  • Target communication updates in multiple languages and through multiple platforms (posters, email, website, text messaging, etc.)
  • Create a registry with clinical staff who are multilingual and deploy them to applicable patient care sites.

People who are IncarceratedCopy Link!

Updated Date: November, 2020
Literature Review:
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People who are imprisoned are particularly vulnerable to COVID-19 infection due to overcrowding, poor ventilation, poor sanitation, lack of medical care, violence, and increased rates of chronic medical conditions (U.S. Department of Justice Special Report). Early data from the COVID-19 pandemic demonstrated up to 5 times higher rates of death among incarcerated people, despite disproportionately younger age distributions relative to nearby communities (Saloner et al). Since the start of the pandemic across all states, incarcerated persons have >3 times the per-capita number of cases as the general population (The Marshall Project).

Decarceration (release from prison) remains the most evidence-based intervention to reduce infection among incarcerated people, and by extension, the local communities that prison workers belong to (Hawks et al; Barnert et al; Okano et al). In place of full decarceration, compassionate release of low-risk offenders and elimination of cash bails that contribute to growing prison populations can also prevent infections (Nowotny et al).

When isolation and containment strategies are used in prisons, additional interventions should be supported to address the mental health burden they create for incarcerated people, especially those living with chronic mental illness (Hewson et al).

  • If available, some safe ways to support incarcerated people include waiving in-state licensure requirements for telemedicine and expanding access to virtual family visits through videoconferencing (Robinson et al).

Other solutions include mass testing of incarcerated people and prison workers, providing personal protective equipment (PPE), and improving sanitation (Akiyama et al). It is particularly critical to focus efforts on occupational health interventions that can prevent transmission of infection to nearby communities (Sears et al).

People with DisabilitiesCopy Link!

Updated Date: November, 2020
Literature Review:
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People with disabilities may be disproportionately marginalized by COVID-19 response efforts due to inadequate recognition of their unique needs. People with disabilities may not have equitable access to safe living situations or healthcare resources.

Policies and institutional guidance should consider the needs of disabled patients.

  • Alternative support structures should be considered for patients with disabilities who are unable to participate in standard public health protocols, such as home-based COVID testing for people with autism spectrum disorder (Eshraghi et al).
  • Health policy leaders must be attentive to inequities in access to care and resources, disproportionate hardships imposed by pandemic mitigation strategies, and increased risk of harm from COVID infection in the context of pre-existing health disparities (Armitage et al).
  • Creation of equitable resource allocation protocols, especially when considering Crisis Standards of Care, should be guided by near-term survival calculations and objective measures to avoid bias against people with physical and intellectual disabilities in allocating resources (Solomon et al).

During the pandemic, some strategies for providers to help patients with disabilities include:

  • When available, masks with clear impermeable windows can improve communication for those who are deaf of hard of hearing.
  • Seeing photographs of clinical care team members without their masks can relieve anxiety.
  • Trauma-informed care can help build trust (CDC guide).
  • Consider exceptions to Visitor Policies for patients who need support from caregivers in order to participate in care.
  • People who cannot remove a mask independently, avoid touching masks frequently, avoid excessive licking or saliva on masks, or otherwise tolerate wearing a mask should be excused from wearing one under CDC recommendations.

People without Secure HousingCopy Link!

Updated Date: November, 2020
Literature Review:
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Undomiciled (homeless) people under 65 years of age have all-cause mortality rates 5-10 higher than the general population at baseline (Baggett et al). Living conditions, higher rates of comorbidities (including substance abuse and mental illness), limited medical services, and the difficulty for public health agencies in tracing undomiciled individuals are all likely challenges during the pandemic (Tsai et al).

People Living in Congregate HousingCopy Link!

Updated Date: November, 2020
Literature Review:
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Skilled nursing facilities, nursing homes, and other congregate living settings often struggle with social distancing and house populations with significant medical risk factors for poor outcomes (McMichael et al).

  • In the United States, as of April 23, “there have been over 10,000 reported deaths due to COVID-19 in long-term care facilities (including residents and staff), representing 27% of deaths due to COVID-19 in those states (Kaiser Family Foundation).
  • COVID has impacted long-term care facilities around the world, with data from many countries showing 40% of COVID deaths to be connected to long-term care facilities. Rates in some higher-income countries are 80% (WHO).

Tool: Rates in Long Term Care Facilities (USA only, third chart) (Kaiser Family Foundation )

People with Substance Use Disorders (SUDS)Copy Link!

Updated Date: November, 2020
Literature Review:
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People with SUD are disproportionately likely to become sick with COVID and are more likely to experience severe illness and death. A team of researchers in the United States analyzing electronic health records found that 15.6% of the COVID cases were people with SUD, but people with SUD represented only 10.3% of the study population. Effects were strongest for those with opioid use disorder.

Possible explanations include higher rates of comorbid pulmonary and cardiac pathologies in people with SUD, as well as disparities in access to healthcare associated with stigma and marginalization. Black Americans with a recent diagnosis of opioid use disorder were four times more likely to become sick with COVID-19 than white peers (Wang et al).

Please see Alcohol Use Disorders and Opiate Use Disorders.

Tool: Harm Reduction Strategies
For people who use substances during the COVID-19 pandemic (Harm Reduction Coalition, English/US focus)

Chapter 2

COVID Testing

Whom to TestCopy Link!

Tool: PRIoritize_Dx, intended to help policy-makers allocate tests

Testing Symptomatic PatientsCopy Link!

Updated Date: December 19, 2020

Prioritize testing people with symptoms suggesting acute infection (see Screening Questions and Common Symptoms).

  • The standard of care for diagnostic testing symptomatic patients is PCR-based testing, as it has the best sensitivity and specificity.
  • If testing is very limited, prioritize testing patients when it will specifically change management or isolation status/location.
  • When PCR-based testing capacity is restricted, use of the antigen test can increase testing capacity as well as offer advantages in terms of more low-cost testing with short turnaround time. The antigen test is discussed in more detail in Types of Test Section.
  • Exact testing algorithms will depend on each institution and the availability and type of testing. One potential algorithm is presented below based on whether same day testing is available or not. Same day testing has advantages.

Algorithm for Symptomatic Patients Based on Whether Same Day Testing is AvailableCopy Link!

Details for each path are discussed below

  1. If same-day testing is available:
  1. Fast turnaround (same-day) Nucleic Acid Amplification Test (PCR)
  1. If positive, the patient is “confirmed COVID.”
  2. If negative, categorize according to Case Definitions and clinical suspicion.
  1. If discharging home, isolate at home and initiate contact tracing.
  2. If admitting, repeat testing in 12-24 hours.
  1. If negative on the second test:
  1. Consider alternative etiologies (influenza, malaria, other infections), and discontinue the “suspected” or “probable” Case Definition if one is found.
  2. Consider alternative testing (e.g. serology) or repeat testing (typically 72 hours from first) if clinical suspicion remains high.
  3. Consider downgrading the case to “suspected” from “probable” depending on clinical suspicion.
  1. Rapid antigen testing (antigen rapid diagnostic test or Ag RDT for short).
  1. If positive, admit as a “confirmed” case or isolate at home, initiate contact tracing. If in a high prevalence setting or in a symptomatic patient with likely COVID-19, confirmatory PCR testing is not needed.
  2. If negative, treat as a “suspected” or “probable” case based on Case Definitions and clinical suspicion.
  1. If discharging, isolate at home and follow-up with a call or visit, homevisit or clinic visit. Consider retesting 2 to 4 days later. Consider contact tracing if suspicion is high for COVID-19.
  2. If admitting, request PCR testing and if not available, repeat rapid antigen testing in 2-4 days (see ECDC report).
  1. If no same-day testing is available (testing is located offsite and/or turnaround times are long):
  1. Send the specimen to the facility with the fastest reliable turnaround times.
  2. Follow-up and retesting strategy:
  1. If discharging to home, isolate at home and call or arrange a visit to share results. If the test returns negative, consider retesting, especially if symptoms persist or worsen.Also, consider retesting if it is deemed important to understand whether the case is COVID-19 and doing so would lead to important contact tracing activities.
  2. If admitting, triage as “suspected” or “probable” case based on Case Definitions and clinical suspicion for disease. If the test returns negative, retest with PCR testing.
  1. If no testing at all is available:
  1. If no testing is available, use clinical judgement and risk factors to determine likelihood of COVID infection and treatment plan. Case Definitions can help. Consider other lab testing to help stratify if available, including lymphocyte count, LFTs, and C-reactive protein. Err on the side of isolation.

Testing Asymptomatic PatientsCopy Link!

Updated Date: December 19, 2020

Asymptomatic Patients with an ExposureCopy Link!

If test capacity permits, testing asymptomatic people with known exposure to COVID-19 may be helpful (ideally as a part of a contact tracing initiative).

Generally we recommend testing patients who meet criteria for an exposure as soon as possible when they become aware of the exposure and again 5-7 days after the first test. This is because initial tests are often negative early in disease. Please note that even if an initial test is negative, the patient must still quarantine until they meet criteria for release from quarantine (in selected cases, testing may be used to reduce quarantine duration). Some healthcare systems recommend against testing in these instances either because of limited testing resources, or because the concerns about false reassurance from early false negatives.

Asymptomatic Screening and Public Health SurveillanceCopy Link!

Literature Review (not comprehensive): Gallery View, Grid View

To understand population-level prevalence and incidence, local institutions or departments of health may perform testing (PCR or antibody) on entire cohorts regardless of exposure or symptoms. Details on design of epidemiologic, surveillance, or infection control studies are beyond the scope of this site.

Asymptomatic people who have a high likelihood of transmission to others should they become infected may be regularly tested for COVID-19, even without a confirmed contact. This is especially important if they spend time with persons that are at risk of complications from COVID-19, the classic example is periodically testing both residents and staff of nursing homes. This is sometimes called “asymptomatic screening” or “expanded screening”.

  • Common high-risk groups that may be considered for screening:
  • Health care workers, particularly those caring for patients with COVID-19 or in high patient-flow areas
  • People living or working in congregate living settings (nursing homes, dormitories)
  • Travelers coming from high prevalence areas
  • Teachers and students
  • Other essential employees (grocery workers, sanitation workers etc).

Asymptomatic Screening Frequencies by Prevalence Indicators:

Community Spread Level

Low

Moderate

High

Highest

New cases per 100,000 persons in last 7 days

< 10

10 to 50

51-100

> 100

Percentage of tests that are positive in last 7 days

< 5%

5% to 7.9%

8% – 10%

> 10.1 %

Frequency of Asymptomatic Screening

Focus on high-exposure people weekly

Weekly

Weekly or twice a week

Twice a week or more

Testing Previously Infected PatientsCopy Link!

Updated Date: December 19, 2020

Patients >90 days from initial illness with new symptoms of COVID-19 can be retested on a case-by-case basis. Reinfection is exceedingly rare, but not impossible.

  • If the patient tests positive, keep in mind the possibility of residual viral RNA even 90 days after initial infection, and consider alternate causes of illness (pulmonary embolism, bacterial superinfection) and (where possible) viral sequencing.
  • Recurrence of symptoms along with reemergence of positive PCR testing (particularly in patients with weakened immune systems) can occur in the absence of true reinfection.

Types of TestsCopy Link!

As the global pandemic grows, suspect cases should be immediately isolated regardless of test status. Remember:

  • No currently available test fully rules out the diagnosis, especially if clinical suspicion is high. When possible, negative or positive results that are inconsistent with the clinical pictures should be discussed with someone who has expertise in diagnostic testing of COVID-19
  • None of the commercially available tests measures active, infectious virus. Whether a person who tests positive is infectious requires clinical judgment and knowledge of their disease course.
  • In all cases, please follow local public health authority guidelines in reporting all suspected, presumed, and confirmed cases of COVID-19.

Testing OverviewCopy Link!

Updated Date: December 19, 2020

In a pandemic, clinically suspected cases should initially be isolated regardless of test status. See Screening, Case Definitions, and Isolation. All tests have both false positives and false negatives. A high index of suspicion should be used to protect staff and other patients.

The three most clinically relevant categories of testing for COVID-19 are:

  1. Nucleic acid amplification test (NAAT). While not a perfect test, NAAT is considered the gold standard. The test uses enzymes to amplify and detect the genetic material of the virus. The most familiar is RT-qPCR (reverse transcriptase - quantitative polymerase chain reaction; related versions are often referred to as PCR or RT-PCR), but there are others. These are often collectively called “molecular tests.”
  2. Antigen rapid diagnostic test (RDT). Requires less time and infrastructure to perform than NAAT tests. Uses manufactured antibodies to detect SARS-CoV-2 proteins.
  3. Antibody (IgM/IgG) RDT. Has different uses and interpretation than the nucleic acid and antigen tests. Uses manufactured antigens to detect a patient’s antibodies to SARS-CoV-2. Since this depends on the body’s immune response, it takes longer to turn positive than tests that directly detect the virus, and a negative antibody test DOES NOT rule out acute infection. The antibody test is NOT used as the sole test to diagnose active or contagious disease; it is more common in epidemiology and research. The test can be used to support the diagnosis in COVID-19 in patients that present late with symptoms (at least 8 days after the onset of symptoms) or to help assess whether a symptom or sequelae is due to a post-COVID-19 infection.

In these lists and elsewhere, tests that measure nucleic acids are often referred to as molecular assays, while antigen and antibody tests are considered immunoassays or serological assays.

General test characteristics are summarized in the table below

RT-qPCR (or other NAAT)

Antigen (Ag) RDT

Antibody (IgM/IgG) RDT

Sample

Nasopharyngeal, oropharyngeal, saliva, lower respiratory

Nasopharyngeal, oropharyngeal, saliva, lower respiratory

Blood

False positives

Rare, except for cases of sample contamination. However, can remain positive after virus is no longer viable.

Very low

Low to moderate, most commonly due to cross-reactivity with other coronaviruses.

False negatives

Occasional, especially early in infection.

Moderate, not as sensitive as NAAT.

Variable. Performs poorly at the onset of the symptoms.

Turnaround time/ Laboratory requirements

Usually hours - requires a laboratory with high technical capacity.

Under 30 min – no laboratory required.

Under 30 min – no laboratory required.

Specific data on the availability and performance of commercial COVID-19 diagnostic testing options continues to change rapidly.

Tool: PATH COVID-19 Diagnostics Dashboard to support product selection and procurement decisions. Collects data from U.S. FDA, WHO, FIND, and other lists curated by private entities. Includes information on regional or national regulatory approval.

Tool: The Foundation for Innovative New Diagnostics (FIND), a global non-profit, conducted Independent Evaluations of test kits between April and August of 2020.
Tool: The Cochrane Library, a resource by the international charitable organization Cochrane, has published independent reviews of Molecular/Antigen tests (updated 2020-08-26) and Antibody Tests (updated 2020-06-25).

Timeframe of Test PositivityCopy Link!

Updated Date: December 19, 2020


The relative time frames of exposure, symptoms, viral markers, and antibodies are illustrated in the subsequent figure. This is an illustration of average time frames and it should be noted that information is still emerging on the timeframes of incubation and window period, infectivity, and durable immunity.

  • Infectious period: On average, the person is most infectious 2 days prior to the onset of symptoms to about 5 days after the onset. This is referred to as the pre-symptomatic and early symptomatic time frame. In general, people are no longer infectious 10 days after symptom onset (20 days in severely ill persons, see infectivity).
  • The antigen test is likely to be positive at the same period that a person is most infectious - 2 days prior to the onset of symptoms to about 2-3 days after the onset. This is because the viral load is highest in this time period.
  • The RT-PCR test (and other NAATs) is more sensitive than antigen testing, it can (but does not always) pick up cases earlier than even 3 or 4 days before the onset of symptoms or 10+ days after symptom onset. These are average time frames for when the test is most likely to yield a positive result.
  • The antibody test in some cases turns positive after the patient may no longer be infectious. For this reason, the antibody test is not typically used to diagnose active disease.

Nucleic Acid Amplification TestsCopy Link!

Updated Date: December 19, 2020

Literature Review (not comprehensive): Gallery View, Grid View

These tests work by amplifying minute amounts of viral RNA. PCR (technically, RT-qPCR) of a nasopharyngeal swab specimen is most widely used and should be considered the standard of care when available.

How it WorksCopy Link!

Reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) works by reverse transcribing the viral RNA genome to DNA, and then amplifying the DNA exponentially by repeatedly cycling the reaction. Samples with a small amount of virus require more cycles to reach a detection threshold than samples with a large amount of virus, allowing some RT-qPCR tests to quantify how much virus was present and approximate viral load.

Newer amplification technologies are being developed to make this process cheaper, faster, and less dependent on complex laboratory infrastructure. The term nucleic acid amplification test (NAAT) includes PCR, isothermal amplification, and CRISPR-based tests (Behera et al., Kilic et al). Xpert® Xpress SARS-CoV-2 is an example of an automated cartridge-based system on the same Xpert® machines used for diagnosis of tuberculosis that does not need a sophisticated laboratory setting. All have the common feature of detecting minute quantities of SARS-CoV-2 nucleic acids.

The main advantages to nucleic acid testing are:

  • The amplification steps allow detection of very small amounts of viral RNA, with higher specificity than serological assays.
  • Live virus is not required. Samples can be inactivated and made safe to handle.
  • Nucleic acid amplification is common in biology research. Government labs, universities, and highly-resourced clinical labs may be able to rapidly deploy new or modified tests before commercial kits are available. This may become relevant if a new strain or resistant mutation emerges.

The main disadvantages to nucleic acid testing are:

  • Most methods require significant infrastructure, usually including custom machines, reliable electricity, cold storage, a supply chain for reagents, and skilled personnel.
  • Test performance can depend heavily on how and when a sample is taken. For example, lower respiratory samples can be positive when upper respiratory samples are not.
  • Fragments of viral nucleic acids can persist in the body long after the virus has been killed. Persistently positive tests may not mean that a person is still infectious.

Test PerformanceCopy Link!

Sensitivity and Specificity:

On artificial samples, NAAT sensitivity and specificity approaches 100% (Giri). NAAT tests have analytical sensitivity (the lowest viral concentration where >95% tests are positive; also called limit of detection) down to 100-5000 copies of viral RNA/ml. But published real-world estimates of sensitivities for different NAATs to diagnose COVID-19 range from ~60-95%, depending in part on what reference method is used as a comparator or “gold standard.” Specificity is excellent, and false positives are rare in the absence of contamination, though there is increasing recognition that false positives due to contamination or cross-reaction with other genetic material do occur and may have significant consequences (Surkova et al)

Interpreting reported clinical sensitivities involves a range of factors:

  1. There is significant variability in how studies define a "true positive" or "gold standard":
  1. The reference standard can be "composite," including laboratory, radiographic, and clinical data. A single center study at University of Kong Kong-Shenzhen, China, compared initial RT-qPCR in 82 patients to a a retrospective diagnosis made by combining serial RT-qPCR and chest CT findings, with a resulting sensitivity of 79% and a specificity of 100% (He et al).
  2. The reference standard is often serial NAAT. since this is often the only data available for large numbers of patients. A retrospective analysis of over 20000 patients used repeat PCR within seven days (felt too short for interim infection to play a large role) and found that only 3.5% of patients initially negative by PCR subsequently tested positive. This suggested a low false negative rate, but they pointed out that this was not a true clinical sensitivity since they lacked a final confirmatory diagnosis (Long et al).
  3. The reference standard can be other previously validated NAAT’s. FindDx reports that the tests they validated agreed 92-100% when comparing to their a reference PCR assay, demonstrating small but real variability between tests.
  1. The site of sampling might not contain virus at the time of sampling. See Sample Collection.
  2. Laboratory factors (sample storage, frequency of contamination).

These same factors should be systematically considered when a clinician suspects a false negative:

  1. Exactly what other data makes me feel like the patient has COVID-19?,
  2. Do we need to repeat the sample or collect another sample type?, and
  3. Could there have been a lab error?

Typical clinical use:

If you do not know your test’s characteristics, sensitivity of ~80% may be a reasonable approximation for nasopharyngeal swabs collected at the time of patient presentation, assuming no laboratory errors.

  • If the RT-PCR is negative but suspicion for COVID-19 remains, then ongoing isolation and re-sampling several days later should be considered.
  • In practice, test results should be interpreted based on negative and positive predictive values (NPV, PPV) rather than sensitivity and specificity, since these incorporate pretest probability.

Sample CollectionCopy Link!

Literature Review (not comprehensive): Gallery View, Grid View

Upper respiratory tract specimens. Most commercial kits have been evaluated on specific upper respiratory sample types. Of these, the nasopharyngeal swab is the most common and best validated; In most situations this is the best option unless a specific manufacturer recommends otherwise or there is a clinical reason to choose an alternative site.

Sites include:

  • Nasopharyngeal swab
  • Nasopharyngeal wash/aspirate
  • Oropharyngeal swabs
  • Mid-turbinate and anterior nasal swabs
  • A few manufacturers allow these to be collected by the patient at-home (unsupervised) or supervised by a provider at a safe distance resulting in less risk to the HCW.
  • Saliva
  • Potential to significantly simplify sample collection cost and complexity
  • Many new platforms being developed, but still limited comparative performance data (Wyllie et al)

Tool: U.S. CDC collection protocol

Tool: Video demonstration

Lower respiratory tract specimens are also sometimes used, though they often require different processing and validation due to the presence of mucus. When obtaining lower respiratory tract specimens, many sampling techniques require airborne precautions for providers (see aerosol generating procedures). Sites include:

  • expectorated deep sputum (similar to sputum collected for TB testing in patients with productive cough).
  • bronchoalveolar lavage
  • endotracheal aspirates
  • preferred in intubated patients due to higher sensitivity, though this depends on sample quality Like any respiratory sample, high quality samples are characterized by Gram stains with many polymorphonuclear cells and few epithelial cells.

The relative performance of testing different sample types, optimal timing for sample collection relative to exposure or symptoms, and the interpretation of discordant results (for example, if the nasopharynx is negative but sputum is positive), all continue to be studied.

U.S. CDC guidelines for processing of sputum specimens for SARS-CoV-2 RT-PCR recommend the use of dithiothreitol (DTT) for liquefaction of viscous mucoid/mucopurulent material prior to nucleic acid extraction

Tool: CDC Specimen Processing

Other specimens. Viral RNA has been documented in other body sites including stool and rarely blood, but it is not known whether this represents transmissible virus (Wang et al). Testing samples from these sites requires extra laboratory expertise for sample handling and clinical expertise for interpretation. These sites should not be tested routinely.

Antigen Rapid Diagnostic TestsCopy Link!

Updated Date: December 19, 2020
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How it WorksCopy Link!

Rapid diagnostic tests (RDT’s) for viral antigens use premade, labeled antibodies to the virus to capture viral particles. The most common approach is the lateral flow test, where sample diffuses along a manufactured strip in a way that can be visually detected at the “test line” only if viral antigens are present. Note that a few manufacturers do make “rapid” NAAT assays. This discussion does not address those tests.

The main advantages to antigen RDT’s are:

  • Running a test involves adding the sample (and sometimes a single liquid reagent) and waiting for diffusion.
  • They generally do not require special trainings or machinery to run, and many are licensed to be run outside of a laboratory setting (e.g. CLIA waiver)
  • They are typically fast, cheap, and have a simple visual yes/no readout that does not require interpretation.

The main disadvantages to antigen testing are:

  • They are less sensitive than NAATs, since there is no amplification step. Negative tests may need confirmation with NAAT if clinical suspicion is high.
  • As with NAATs, performance can depend heavily on how and when a sample is taken.
  • Fragments of viral proteins can persist after the virus has been killed, though likely not as long as nucleic acids.
  • If future viral mutations change the antigen region targeted by a particular test, it will take longer to create new antigen RDT’s (which involves new manufacturing) than it would to modify most NAAT’s (which involves new reagents only).
  • Consult the manufacturer’s insert for specimen collection requirements; many are designed for nasopharyngeal swab only.

Test PerformanceCopy Link!

Clinical sensitivity for antigen RDT’s is highly variable. The average of sensitivity was 56% for four antigen RDT’s reviewed in an August 2020 Cochrane review, with 95% confidence interval of ~30-80%. The same review found much higher average specificities of 99.5% (95% confidence interval 98.1-99.9%). (Dinnes et al.) The sensitivity may vary based on symptomatology, with some performing as poorly as 32% sensitive (Quidel EUA), and others as high as 79% (Alemany et al.) in asymptomatic people. However, many of the cases that these tests miss may not be infectious, but this is still an area of active research.

Finding the real-world sensitivity of antigen RDT’s suffers from many of the same difficulties discussed in the NAAT section above, though these are usually compared with NAAT as a gold-standard. The minimum performance requirements for Ag-RDT set by the WHO are >80% sensitivity and >97% specificity compared to a NAAT reference assay (WHO)

Use of RDTs for ScreeningCopy Link!

Rapid Antigen RDTs are an alternative to NAAT as screening tests where testing capacity is limited and the proportion of test positivity is high (≥10%) (ECDC recommendation). Positive and negative predictive values (PPV and NPV) of all in vitro diagnostic tests depend on disease prevalence in the target population and the test performance.

In a high prevalence setting CDC considers high prevalence to be when NAAT positivity over the last 14 days is greater than 5% or when there are greater than 20 new cases of COVID-19 per 100,000 persons within the last 14 days., rapid antigen tests will have a high PPV, meaning a positive result from a rapid antigen test is likely to indicate a true infection and may not require confirmation by RT-PCR. In contrast, any negative test result should be confirmed by RT-PCR immediately or with another rapid antigen test a few days later (where RT-PCR is very limited).

In a low prevalence setting CDC considers low prevalence to be when NAAT positivity over the last 14 days is less than 5% or when there are fewer than 20 new cases of COVID-19 per 100,000 persons within the last 14 days., rapid antigen tests will have a high NPV but a low PPV. Therefore, a negative antigen test most likely represents a true negative and may not require confirmation by NAAT, however false negatives are still possible and people being tested should be reminded that they should still take all precautions to prevent spread (e.g. masking, distancing, etc). In this situation, a negative test result may not require confirmation by NAAT, whereas a positive test will need confirmation by NAAT.

Scenarios where Antigen RDT Can be Used for Screening of asymptomatic individuals: (modified from WHO and ECDC). (For use of Antigen RDT for symptomatic individuals, including contacts, see testing symptomatic patients).

Scenarios for use of SARS-CoV-2 Ag-RDT

Populations Where RDT Can Be Used For Screening where NAAT testing is limited

Negative testing should NEVER exempt people from standard transmission prevention practices (masks, distancing, hand washing). See IPC.

Outbreak response

To respond to suspected outbreaks of COVID-19 in remote settings, institutions and semi-closed communities

Outbreak investigation

To support outbreak investigations (e.g. in closed or semi-closed groups including schools, care-homes, cruise ships, prisons, workplaces and dormitories, etc.)

Monitor trends in disease incidence

To monitor trends in disease incidence in communities, and particularly among essential workers and health workers in regions of widespread community transmission

Community Transmission Screening for Congregate settings

Where there is widespread community transmission, RDTs may be used for early detection and isolation of positive cases in health facilities, COVID-19 testing centers/sites, care homes, prisons, schools, front-line and health-care workers.

Testing of Asymptomatic contacts/ Contact tracing

Testing of asymptomatic contacts of cases (either as part of outbreak investigations or household contacts) may be considered even if the Ag-RDT is not specifically authorized for this use. However, given the high pre-test probability in this population, a negative test often does not rule out infection (has a low negative predictive value) and where possible should be confirmed by NAAT or repeat RDT as described above. Even in the setting of a negative test, contacts should continue to remain in quarantine until they meet criteria to discontinue quarantine.

Antibody TestingCopy Link!

Updated Date: December 19, 2020
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How it WorksCopy Link!

Antibody tests measure the host adaptive immune response, rather than the presence of the virus. This test is most often performed on circulating blood (from fingerstick or blood draw).

Adaptive immune response requires several days to make antibodies that bind to the pathogen. See antibody response and durable immunity for a more in-depth discussion of antibody patterns over time. It is not yet known what impact antibodies have on the risk of transmission to others or risk of re-infection.

The main advantages to antibody testing are:

  • Respiratory samples are not required. Antibody testing can be done on blood drawn for other reasons in clinical care. There are versions to test dried blood spots.
  • IgG may last for months to years, so it is useful in epidemiology to know who has been previously infected (even if they were asymptomatic).
  • A strategy that uses both NAAT and serology may improve sensitivity for COVID-19 over using NAAT alone (Guo et al).

The main disadvantages (and why antibody testing alone is not recommended to guide clinical decision making) are:

  • Antibodies take several days for the human body to develop, so antibody testing is often negative in early infection; this is known as the “window period.” In fact, a positive IgG argues against acute early infection.
  • False positives can occur due in patients who have been exposed to coronaviruses other than SARS-CoV-2, including some types of the common cold.
  • IgM is often less specific than IgG, so false positives may be more common for IgM results, making the test less accurate for acute infection.
  • Although antibody RDT’s using principles of lateral flow are available, the most sensitive versions require laboratory infrastructure for techniques such as ELISA.
  • The immune system simultaneously makes many different antibodies, but test manufacturers choose a single antibody to detect. This can result in increased variability between test performance from different manufacturers.
  • For these reasons, antibody testing alone is not recommended to guide clinical decision making.

Test performanceCopy Link!

Combined IgM/IgG testing has low sensitivity early in infection (30%) but reaches 91% by 15-21 days after onset of symptoms, in a June 2020 Cochrane Review summarizing 54 cohorts with a total of nearly 16000 patients. The same review found a high average specificity of ~98% (Deeks et al).

InterpretationCopy Link!

IgM

IgG

Interpretation

Negative

Negative

  • No serological evidence of infection with COVID-19.
  • Potentially in the “window period” before antibodies have developed
  • Also might be a weak, late or absent antibody response, particularly in older patients, those with poor nutritional status or immunodeficiency, and rarely in severe COVID-19 disease.

Positive

Negative

  • Potentially early infection, before IgG is detectable.
  • Also might be a false-positive IgM (cross-reaction to other coronaviruses).
  • IgM is often less specific than IgG, so false positives from other viruses may be more common in this case.

Negative

Positive

  • Likely either late or resolved infection.
  • Also might be a false-positive IgG (cross-reaction to other coronaviruses)..

Positive

Positive

  • Potentially active infection.
  • Also might be late or recovery phase of the disease, before IgM has declined.
  • Also possibly a false-positive resulting from cross-reaction with other coronaviruses.

Viral CultureCopy Link!

Updated Date: December 19, 2020

Viral culture is not generally used in clinical settings. Availability is very limited, since safe viral culture requires laboratories with advanced biosafety capabilities (typically BSL 3 in the USA). It is the most definitive test for the presence of viable virus, since both antigens and RNA can persist even after the virus is “killed.”

  • It is often used in research settings to tell which types of samples are potentially infectious.
  • It can be used to confirm that patient or pharmaceutical antibodies neutralize viral replication, since some antibodies might bind to the virus without inhibiting replication.

Viral SequencingCopy Link!

Updated Date: December 19, 2020
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Full-genome viral sequencing is not generally useful in the acute clinical setting. When available, viral genomic sequencing from patient samples can be used for local outbreak tracing, assessing re-infection, and large-scale epidemiology. Sequencing may also be used in the future to look for mutations and decreased responsiveness to vaccines or therapeutics, though this will require significantly improved understanding of SARS-CoV-2 biology.

Several groups are developing technologies to reduce the hardware and infrastructure investment needed and finding innovative applications that may eventually impact front-line workers (Khatib et al).

Technical GuidanceCopy Link!

This section is forthcoming

Chapter 3

Infection Prevention and Control

Transmission PreventionCopy Link!

This section addresses transmission prevention. Please see COVID overview for the causes of Infectivity and Transmission.

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Wearing Face Masks and ShieldsCopy Link!

Updated Date: December 19, 2020
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This section covers general public use of face masks and shields, for health care usage, see Personal Protective Equipment

Universal masking has been shown to reduce transmission. More data exist for medical settings, but the United States CDC and the WHO both recommend mask use in non-medical settings as well (CDC, WHO).

How do Face Masks Work?Copy Link!

  1. Face Masks provide a barrier against a high percentage of the viral particles released from a wearer’s mouth and nose (Ma et al).
  1. Wearing a medical mask has been demonstrated to result in a six-fold decrease in particle emission during breathing (Asadi et al). Systematic review of research literature on face masks shows that they reduce risk of infection by 85%, with greater effect noted in healthcare settings (MacIntyre et al).
  1. Available evidence also indicates that face masks can protect the wearer from inhaling viral particles. Face masks with multiple layers of cloth containing higher thread counts are more effective (CDC).
  2. Populations can more easily adhere to universal masking advice than stay-at-home orders in some settings. Face masks allow people to leave their homes for essential reasons with less risk to others.

Can Face Masks Harm People?Copy Link!

Face masks do not interfere with the exchange of oxygen or carbon dioxide, even in patients with severe lung impairment (Samannan et al). Depending on the face mask, it may change the rate of flow of air, which can make people feel uncomfortable, especially if they have obstructive lung disease that also impedes air flow, such as COPD or asthma. Wearing a medical mask can be uncomfortable, but will not cause oxygen deficiency or carbon dioxide intoxication. Make sure that face masks remain dry (WHO). CDC recommends face masks above age 2; WHO recommends against requiring face masks for children under the age of 5 (WHO).

Types of Face MaskCopy Link!

There are several major categories of face masks. In many places manufactured medical-grade face masks (surgical, KN95, and 95) are in short supply. If there is a shortage of medical-grade face masks, they should be reserved for healthcare workers, confirmed COVID-19 patients, patients with symptoms of COVID-19, or patients at high risk of complications (WHO). More details on different types of medical-grade masks are available in PPE Types and Uses.

Tool: Instructions on How to Make Your Own Face Mask.

Face Shields and GogglesCopy Link!

Face shields and goggles are meant to prevent droplets and sprays from entering the eyes (for example, when caring for a hospital patient or a sick family member at home).Regulatory guidance and standards on forms of eye protection are highly variable. For best protection, wear a face shield that fits snugly against the forehead and extends the full length of the face and to the point of each ear (Roberge).. There is lack of evidence to demonstrate that face shields alone are sufficient as a form of source control for protecting others (CDC). They are also not sufficient to protect the wearer when worn alone, and should generally be worn with a face mask (Roberge). When a face mask cannot be worn, a face shield can be worn instead but does not offer the same level of infection control(CDC)

When to Wear a Face MaskCopy Link!

  1. When leaving the house
  2. In quarantine/self-quarantine/isolation when contact with others is necessary
  3. In workplaces and on public transportation
  4. When entering someone else’s home to provide an essential service
  5. When indoors with people who do not belong to your household, including relatives
  6. When cleaning streets or disposing of domestic rubbish
  7. A face mask is suggested, but not absolutely necessary in some outdoor areas if a 2-meter distance can be kept from other people at all times. Consult local rules and regulations.

How to Use a Face MaskCopy Link!

  1. Wash your hands with soap and water or an alcohol-based hand sanitizer before putting on, touching, or removing a face mask (WHO). This prevents you from accidentally contaminating your face if you have coronavirus on your hands. Avoid touching the front of a face mask by touching the strings or ties instead.
  2. The face mask must be worn over both the mouth and the nose, it is not effective if used over the mouth alone. Tie securely to minimize gaps between face and mask.
  3. Avoid touching the face mask while wearing it. If you do, perform hand hygiene.
  4. When removing a face mask, undo the ties and carefully fold the face mask inside-out. Place directly in a designated area for disposal or washing, or in a plastic bag.
  5. Wash cloth face mask in soap or detergent, preferably with hot water. If hot water cannot be used, boil the mask for 1 minute after washing with detergent (WHO). Only use a cloth face mask that has been properly cleaned.
  6. If a face mask becomes damp or noticeably soiled, replace it immediately with a clean one.

Tool: WHO Infographics on How to Wear a Face Mask

Policy Interventions Around Face Mask UseCopy Link!

Adapted in large part from the South African recommendations:

  1. Public health leaders should create media campaigns to educate the public on the use of face masks, including how to safely use them.
  2. In COVID-19 hotspots it is reasonable for policy makers to make face masks mandatory, especially in spaces where physical distancing is challenging. Educational campaigns should be prioritized over punitive measures to promote adherence.
  3. Face masks are not a substitute for other preventive measures like regular handwashing, cleaning surfaces, physical distancing and contact tracing. All must be done together whenever possible.

Physical DistancingCopy Link!

Updated Date: December 19, 2020
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Physical DistancingCopy Link!

The World Health Organization recommends people maintain a physical distance of 1 meter between them. This is based on research on bacterial meningitis and rhinovirus spread (WHO)

In contrast the United States Centers for Disease Control (CDC) recommend a distance of 2 meters. This recommendation is based on measurements of influenza transmission, sometimes from studies in the 1930-40s (Wells).

There is no known distance cutoff that absolutely protects a person from being exposed to any droplets or aerosolized particles (see Aerosols, Droplets, and Fomites). Sneezing and coughing can create turbulent gas clouds that can spread droplets well past a distance of 2 meters (Bourouiba). However, the density of droplets seems to decline the farther away from another person you stand.

Outdoor TransmissionCopy Link!

Transmission is less likely outdoors and in other well-ventilated spaces. Systematic review of evidence indicates that COVID transmission is significantly reduced outdoors: outdoor transmission is responsible for <10 % of reported transmissions globally (Bulfone et al). In indoor spaces, low ventilation and lack of ventilation are both associated with higher transmission rates of airborne diseases (WHO). In one study of transmission in China, only one case among 7300 was associated with outdoor transmission (Qian).

Surface DecontaminationCopy Link!

Updated Date: December 19, 2020
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Surface decontamination can help prevent the spread of COVID-19, though transmission through transmission from surfaces and fomites is not common (see Aerosols, Droplets, and Fomites). Particular attention should be paid to cleaning high touch surfaces frequently. Instructions for making cleaning products and example cleaning schedules are found in Disinfection and Cleaning.

Hand HygieneCopy Link!

Updated Date: December 19, 2020

Effective hand washing is a proven way to remove bacteria and viruses from hands and prevent illness. The exact contribution hand washing has made to population health during the COVID pandemic is currently unknown (CDC), but it is presumed to reduce COVID transmission. Hand washing should be performed with soap and water for at least 20 seconds. Alcohol solutions with at least 70% alcohol can also be used.

When around someone with known COVID-19 infection, hand washing is always a critical protection for staff, patients, and families. Gloves should be used for all blood and body fluids.

The WHO recommends handwashing at five times:

  1. Before touching a patient
  2. Before clean/aseptic procedures
  3. After touching a patient
  4. After body fluid exposure
  5. After touching a patient’s surroundings

Exposures, Isolation and QuarantineCopy Link!

Exposure to COVIDCopy Link!

Updated Date: December 19, 2020
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If a patient believes they have been exposed to COVID-19 it is important to assess risk in order minimize anxiety of lower-risk exposures and identify higher-risk exposures and prevent further transmission.

Definition of COVID ExposureCopy Link!

An exposure is defined differently by different groups. Some general guidance is being within 1 meter (WHO) or 2 meters (CDC) feet of an infectious COVID positive person for greater than 15 minutes or direct physical contact without PPE. It should be noted that there is no evidence for a minimum amount of time that it takes when exposed to become infected.

  • A person is considered infectious:
  • If symptomatic: from 2 days before symptom onset until 14 days after (WHO) or until meeting criteria for discontinuing isolation (CDC) (see Releasing Patients from Isolation)
  • If asymptomatic: from 2 days before the date of positive test until meeting criteria for discontinuing isolation.

Risk of Developing Disease After ExposedCopy Link!

Risk depends considerably on the duration and proximity of the exposure and how symptomatic the original patient was. Using a similar exposure definition to the CDC definition, investigators found 13% of exposed individuals subsequently developed COVID-19 (Boulware et al). This is higher amongst household contacts (see Household Transmission).

Prophylaxis: At this time, there are no known effective pre- or post-exposure prophylaxis for COVID-19. A large trial of hydroxychloroquine as post-exposure prophylaxis demonstrated no benefit and increased risk of self-reported adverse events in the treatment arm (Boulware et al).

Quarantine and IsolationCopy Link!

Updated Date: December 19, 2020

IsolationCopy Link!

Isolation is the separation of a sick person with a contagious disease from people who are not sick. We recommend isolation for all suspected, presumptive and confirmed cases of COVID-19. Duration of isolation depends on many different factors, and this is covered in Releasing Patients from Isolation. (CDC guidelines). Facility based isolation of COVID-19 cases is discussed in Transmission Prevention in Facilities.

QuarantineCopy Link!

Quarantine is the separation of people who were exposed to a contagious disease to see if they become sick. We recommend quarantine of all persons that have been exposed to COVID-19 cases.

  • Duration of quarantine is typically 14 days from last exposure.
  • December 2, 2020 CDC guidance states quarantine can be reduced in certain circumstances. Keep in mind this may not apply everywhere, and local authorities may have longer or shorter guidelines as they consider changing evidence and resources. As the CDC states:
  • Quarantine can end after Day 10 without testing and if no symptoms have been reported during daily monitoring. With this strategy, residual post-quarantine transmission risk is estimated to be about 1% with an upper limit of about 10%.
  • Quarantine can end after Day 7 if a diagnostic specimen (collected within 48h of Day 7) tests negative and if no symptoms were reported during daily monitoring. With this strategy, the residual post-quarantine transmission risk is estimated to be about 5% with an upper limit of about 12%.

IPC for Home Quarantine or IsolationCopy Link!

Requirements for Isolation and Quarantine

Physical distance

  • Accept no visitors from outside the home
  • Maintain a distance of >1 meter from other household members, with only one person assigned to be the caregiver to the patient (this should not be anyone at high risk of severe COVID disease.)
  • Keep patient in a well-ventilated single room, ideally on a separate floor If a fan is available, point it out of one window and keep another window open to facilitate increased air exchange.
  • Have the patient use a separate bathroom if possible; if not clean the bathroom after use
  • No visitors should come to the home during the 14 days.
  • If patient is a primary caregiver to another household member, assign someone else to take over those responsibilities
  • Know When to Seek Care

Hygiene

  • Patients and caregivers should wear masks when not physically separated. Ideally, surgical masks would be used, but cloth masks are an alternative if surgical masks are not available.
  • Caregivers should wash hands after any type of contact with the patient, before and after preparing food, and before eating.
  • All should cover their mouths when coughing or sneezing.
  • Use dedicated eating utensils for the patient. Utensils should be cleaned with soap and water
  • Use dedicated linens for the patient. Linens should be cleaned with hot water and detergent
  • Surfaces should be cleaned with soap, and high-touch” surfaces (e.g. doorknobs) with a household disinfectant daily. Can use a bleach solution (1 part 5% pure bleach diluted with 9 parts water to make a 0.5% solution.)

Releasing Patients from IsolationCopy Link!

Updated Date: December 19, 2020
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Knowing when a patient has recovered from COVID infection and is no longer infectious is important to allowing them to return to contact with other individuals, including work, school, and living environments.

Time based vs testing based criteria: Most situations call for time-based criteria, because the interpretation of positive tests after infection is complicated (PCR often remains positive even in people who are no longer infectious, see Infectivity.) A test-based strategy can be used for selected recovered persons for whom there is low tolerance for virus shedding and infectious risk (for example, working in healthcare facilities, residing in congregate living facilities, immunocompromised, etc). Some institutions require more stringent clearance criteria than those outlined here.

Tool: CDC When Can You Be Around Others When You’ve Had COVID-19

Tool: WHO Criteria for Releasing from Isolation

  1. Symptomatic patients:
  1. Time-based criteria: 10 days after illness onset and 3 days after symptom resolution defined as resolution of fever without the use of fever-reducing medications; and improvement in respiratory symptoms

(whichever is longer) (CDC, WHO).

  1. Asymptomatic patients
  1. Time-based criteria: 10 days after positive test (CDC, WHO)
  1. Patients with severe illness or patients with prolonged symptoms:
  1. Time-based criteria: The CDC recommends up to 20 days from symptom onset. WHO makes no distinction based on severity when determining duration of isolation for symptomatic patients.
  1. Currently hospitalized patients:
  1. Time based criteria: This is not universally defined. BWH uses 30 days since first positive test + 1 day after symptom resolution
  2. Test based criteria: This is not universally defined. BWH uses 10 days since first positive test + 1 day after symptom resolution + at least 2 negative PCR swabs
  1. Severely immunocompromised patients: Defined by the CDC as patients on chemotherapy for cancer, untreated HIV infection with CD4 T lymphocyte count < 200, combined primary immunodeficiency disorder, and receipt of prednisone >20mg/day for more than 14 days
  1. Time based criteria: 20 days after symptom onset (+ 1 days after symptom resolution). Exact determination of isolation duration in immunocompromised patients should be made in consultation with an Infectious Disease specialist (CDC)

Transmission Prevention in FacilitiesCopy Link!

Updated Date: December 20, 2020

In health care facilities, IPC is critical to reducing the spread of COVID-19.

Screening and movement: Screen all people (staff, patients, and visitors) entering clinical spaces using Screening Questions. Make modifications to patient flow to ensure patients with symptoms of or at risk for COVID-19 are appropriately classified by likelihood of disease, transported safely, and isolated in designated locations.

Physical distancing: Modify waiting and treatment areas to allow physical distancing

  • Distances between people should be at least 1 meter (WHO recommendation), and ideally 2 meters (CDC recommendation) in all contexts.
  • Avoid gatherings of staff in confined spaces. For example, consider outdoor staff meetings or use technology to hold remote meetings. Rotate meal times to avoid crowds in dining areas and rearrange break areas to allow physical distancing so staff can eat and drink safely. Add additional work spaces to avoid congregating at nursing stations.
  • In spaces where COVID-related care is provided, the number of people (staff, patients, and visitors) should be kept to the minimum needed. Whenever possible, avoid large groupings of people.

PPE: Use appropriate Personal Protective Equipment and train staff on its use

  • Universal masking in healthcare spaces is always necessary. Medical-grade masks should be used whenever available.
  • Wards and rooms should be clearly marked with appropriate and standardized signage indicating the category of precaution and PPE that is required to enter.

Isolation: Use appropriate facilities and protocols to isolate patients (see isolation). Positive COVID patients, PUIs, and patients without COVID symptoms should not be cohorted together. Ideally, patients should be separated as quickly as possible into separate spaces based on at least three categories (screening negative for possible COVID infection, screening low-likelihood for COVID infection, and screening high-likelihood for COVID infection). Some settings may use as many as five cohorting categories. See Likelihood Categories (Case Definitions), and Isolation.

Ventilation: Using outdoor spaces and spaces with good filtration or air turnover can decrease risk. All indoor spaces should be sufficiently ventilated and COVID care areas should be negative pressure whenever possible (see Ventilation and Filtration).

Decontamination: Clean all contact surfaces between patients for areas with frequent patient turnover (e.g. clinic rooms and triage areas) and equipment that is rotated between patients (e.g. vital sign monitors). Facilities should develop cleaning protocols for all patient and non-patient care areas.

IsolationCopy Link!

Updated Date: December 19, 2020

Isolation in Hospital Rooms and WardsCopy Link!

Never co-house a patient who screens negative in the same room or ward as confirmed positive COVID patients or PUIs. Confirmed positive patients should only ever be housed with other confirmed positives.

There is no universal set of strategic recommendations for inpatient housing arrangements. Healthcare settings vary greatly in terms of floor plan, layout, equipment, and other resources.These are some principles that can be adapted to local context.

Isolation in RoomsCopy Link!

Which patients need single rooms?: In settings where most patients are kept in single or double rooms, confirmed positive COVID cases can be cohorted together in shared rooms. However, PUIs should never be roomed together, as this may result in COVID transmission from one roommate to another if one PUI is actually COVID-negative.

Requirements for rooms: The ideal room is a single private negative pressure room with transparent windows, doors that close, and continuous wireless pulse oximetry monitoring. This arrangement is often unavailable outside of critical care settings, even in the world’s best-resourced practice settings. If a room does not have adequate space and monitoring (direct patient visualization, pulse oximetry, and/or telemetry), rooming and location must balance patient safety risks and infection control needs.

Isolation in Wards and Common AreasCopy Link!

COVID-care wards should be as separated as possible (ideally in a different building) from care areas for patients who screen negative for possible COVID infection.

Separating wards by likelihood level: If single isolated rooms are not available or feasible we recommend using multiple wards or areas to separate patients by likelihood of disease,. Wards for suspected or confirmed COVID patients should always be separate from wards for patients who screen negative for COVID symptoms. Providers should always move from low-risk patients to high-risk patients.

Whenever possible, at least three separate COVID-care wards should be established to safely cohort the following categories. For additional details, see Likelihood Categories (Case Definitions).

  1. Lower-risk PUIs, including minimally symptomatic and asymptomatic patients with known exposure.*
  2. Higher-risk PUIs, including symptomatic suspected cases and probable cases). Ideally these groups would be further subdivided into separate wards or areas based on their likelihood of having COVID (for example, separating suspected lower-likelihood cases from suspected and probable cases with a higher likelihood of disease).*
  3. Confirmed positive COVID cases.

*These first two categories require the highest level of IPC to reduce transmission, as patients in these spaces are a mix of positive and negative.

When it is not possible to separate wards by likelihood level: If separate wards for each level are impossible, PUIs patients may be cohorted within the same ward and grouped according to risk level with physical distance or barriers between each group of patients. Since not all PUIs will have COVID, it is important to adequately distance (1-2m) PUIs from each other, arrange the ward from the least likely to the most likely patients. Strict IPC and PPE practices are imperative, and providers should try to move from low to high risk patients if possible.

PrecautionsCopy Link!

Updated Date: December 19, 2020
Literature Review (Airborne v Droplet):
Gallery View, Grid View
Literature Review (Aerosolization):
Gallery View, Grid View

Precaution Type for COVID-19Copy Link!

WHO guidance recommends standard, contact and droplet precautions when caring for suspected or confirmed COVID-19 patients. If an Aerosol Generating Procedure is being performed airborne precautions are needed (WHO).

  • Some hospitals may create their own definitions and specific policies with slightly more stringent requirements, such as Enhanced Droplet Precautions. Given concerns that coughing and sneezing may themselves cause aerosols, some hospitals may choose to put all patients on airborne precautions

Tool: CDC Guidance on Contact, Droplet and Airborne Precautions (including sample signs)

Tool: Detailed CDC Guidance Defining Different Levels of Precaution

Standard, Contact and Droplet PrecautionsCopy Link!

Standard, Contact, and Droplet precautions (drawing from CDC guidance) in the setting of COVID include the following (adapted from CDC and WHO) guidance:

  1. Use high-quality hand washing
  2. Use adequate PPE to protect against contact with the patient’s environment and droplets suspended in air (PPE is covered extensively here)
  3. Use Respiratory hygiene/ cough etiquette (cover mouths when coughing and sneezing, tissues, no-touch receptacles)
  1. Patients should wear medical masks whenever possible
  1. Use appropriate patient rooming and distancing (see “isolation” above)
  2. Use safe injection practices
  3. Use safe waste management and linen management
  4. Use designated equipment for COVID patients (or wards) and adequately sterilize equipment (stethoscope, blood pressure cuff, pulse oximeter) between each patient (e.g. with ethyl alcohol 70%).
  5. Minimize patient movement and transportation and use appropriate precautions when transport is needed (see transport below) (see “transport”)
  6. Maintain good ventilation
  1. open doors and windows when possible, though be careful not to ventilate from COVID areas to non-COVID areas.
  1. Whenever possible, healthcare workers should move lower-risk to higher risk patients (from asymptomatic to symptomatic and then to confirmed positive patients).
  2. Some additional guidance on specific procedures, lab transport, etc is available in BWH’s ICU Strict Isolation Manual

Airborne PrecautionsCopy Link!

Use airborne precautions when there is a risk of aerosolized particles. In the hospital setting, this generally means during Aerosol Generating Procedures (AGPs). (The role of aerosols in COVID-19 transmission is discussed in Aerosols, Droplets, and Fomites). Airborne precautions should be used for all patients (not only confirmed CoVID-19 patients and PUI) for AGPs in places with high prevalence, or where testing to rule out infection prior to the procedure is not possible. In addition to gown, gloves, and eye protection, aerosol-resistant respirators (N95 masks) are needed during aerosol-generating procedures and until adequate air turnover has occurred afterward (air turnover depends on your facility, in most BWH rooms this is 47 minutes). Please see Personal Protective Equipment for guidance.

  1. Use negative pressure rooms wherever possible, or in a well - ventilated space if not (see Ventilation and Filtration).
  2. Limit the number of people in the room to the fewest necessary.
  3. There should be no other patients and no visitors present.

Aerosol Generating ProceduresCopy Link!

Updated Date: December 19, 2020
Literature Review (Airborne v Droplet):
Gallery View, Grid View
Literature Review (Aerosolization):
Gallery View, Grid View

Aerosol Generating Procedures (AGPs) must be performed with airborne precautions for COVID patients, and most non-COVID patients (see airborne precautions). Not all institutions use the same definition of an aerosol generating procedure. Some potential examples include:

  1. Intubation
  2. Extubation
  3. Bronchoscopy
  4. Sputum induction
  5. Cardiopulmonary resuscitation (CPR) with chest compressions
  6. Open suctioning of tracheostomy or endotracheal tube
  7. Manual ventilation (e.g. manual bag- mask ventilation before intubation)
  8. Nebulization
  9. High flow oxygen therapy and non-invasive positive pressure ventilation (e.g., CPAP, BIPAP) (though this is not universal in different institutions, and it is not clear if this increases aerosols beyond coughing, see HFNC)
  10. Oscillatory ventilation
  11. Disconnecting patient from ventilator
  12. Upper airway procedures / surgeries
  13. Upper endoscopy (including transesophageal echocardiogram) and lower endoscopy
  14. Chest physical therapy
  15. Autopsy
  16. Thoracentesis/small-bore (pigtail) chest tube placement (due to the increased risk of cough)
  17. Airway surgeries
  18. Tracheostomy changes
  19. Disconnecting patients from ventilators and ventilator circuit manipulation
  20. Upper endoscopy (including TEE)
  21. Lower endoscopy
  22. Mechanical In-Exsufflator
  23. Dental procedures
  24. Venturi mask with cool aerosol humidification (this is highly institution-dependent)

The following are NOT usually considered aerosol generating procedures:

  1. Venturi mask without humidification
  2. Nonrebreather, face mask, or face tent to 15 liters
  3. Humidified trach mask to 20L (with inline suctioning
  4. Routine trach care
  5. In-line suctioning of endotracheal tube when ventilator circuit has a viral filter in place
  6. Labor and Cesarean section
  7. Nasopharyngeal swab
  8. Proning (unless ET tube becomes dislodged)

Patient TransportCopy Link!

Literature Review: Gallery View, Grid View

Within FacilitiesCopy Link!

Updated Date: December 19, 2020

Limit transport and movement of patients. When transport is necessary, follow guidelines outlined below.

  1. If a patient must be moved, all staff who come into contact with the patient should don clean PPE.
  2. Patients must wear face masks during transport. Generally this is a medical mask. If this is not possible, a cloth mask should be used. Surgical masks should be used over oxygen delivery devices if possible and if not, well-sealing oxygen delivery devices should be used. Some hospitals permit transport on CPAP/BIPAP or High Flow Nasal Cannula, others do not.
  3. Once a patient is in an isolation area they should not leave it unless to go to a dedicated bathroom, a specific testing or healthcare delivery location (accompanied by a healthcare worker), or upon discharge.

InterfacilityCopy Link!

Updated Date: January 11, 2021

Reasons to transferCopy Link!

There are many potential reasons to transfer a COVID19 patient to another facility including:

Stabilization Prior to TransferCopy Link!

A full discussion on stabilization for transfer is beyond the scope of this site. For the transfer of COVID19 pneumonia patients the top concern is generally is the amount of oxygen required by the patient safe for transport and whether to intubate prior to transfer. This is especially true as patients considered for transfer often have a rapidly worsening trajectory and are at high risk for deterioration.

Whether to intubated prior to transfer:

Intubation should not be done if it is not indicated (see candidacy for intubation). Intubation carries risks, especially in certain patients (e.g. patients with right heart failure or a difficult airway). The decision about whether to intubate prior to transfer should balance risks and benefits and take into consideration the following questions:

  1. Is the patient likely to require intubation en route?
  1. Altered or depressed mental status. Patients may be at risk for aspiration, airway obstruction, hypoventilation or agitation, prompting rapid deterioration.
  2. Hemodynamic instability. Unstable patients are difficult to intubate under controlled circumstances and even more challenging to manage during an emergent intubation during transport.
  3. Known or suspected difficult airway. Challenging airways are also even more difficult to manage during an emergent intubation during transport.
  4. Severely elevated work of breathing. Patients may be at risk for developing fatigue and rapidly deteriorating respiratory failure during transport.
  5. Rapidly escalating oxygen requirement.
  1. Is safe intubation feasible at the transferring facility? If not, but the patient may need intubation en route, sometimes the transporting team may have more familiarity and may be able to safely intubate the patient before departure.
  2. Is emergent intubation possible during the transfer? Intubation during transfer may not be possible or may be higher-risk depending on skill and available equipment during transport.
  3. Is the patient nearing the limits of oxygen delivery capability of the transport system? See below for specifics on air transport. Generally, mechanical ventilation for intubated patients consumes less oxygen supply than non-intubated patients on oxygen delivery devices with high oxygen flows.

Calculating Transport Oxygen NeedsCopy Link!

Non-intubated patients on oxygen delivery devices with high oxygen flows (e.g. high flow nasal cannula, non-rebreather facemask, CPAP/BIPAP/NIPPV) may rapidly exhaust or exceed the available oxygen supply during transport. This can be life threatening.

  1. Calculate total oxygen demand in advance. For example, for an 8-hour transport time, a patient on a non-rebreather facemask at 15 liters per minute will require either 2 portable oxygen concentrators (may vary depending on device output) and a reliable portable power generator, or two full J cylinders (See Oxygen Cylinder Duration Calculator).
  2. Factor in a buffer in case oxygen demand increases, or the trip is longer than expected.
  3. Make sure there is at least one power backup for electrically-powered delivery devices.

Additional air transport needs: During air transport barometric pressure drops, while FiO2 stays constant. The result is less partial pressure of oxygen delivered to the alveoli and the volume expansion of any trapped gas. This can precipitate the deterioration of a patient in two ways:

  1. Worsening hypoxia at altitude. Pressurized aircraft are generally maintained at the equivalent of 5000ft (~1500m) to 8000ft (~2500m) above sea level. This is roughly the equivalent of three quarters of the oxygen delivered at sea level that is delivered in each breath. The effective altitude during transport should be accounted for when estimating oxygen needs during transport.
  2. Expansion of gas in body cavities and pneumothorax, including a tension pneumothorax. Providers should have the ability to assess pneumothorax through auscultation (difficult with the sound of an aircraft) and chest rise, and be trained to perform a needle decompression if needed.

Contraindications to TransferCopy Link!

Relative

Absolute

  • High levels of support from noninvasive ventilation with depressed level of consciousness, marginal oxygenation, tachycardia or hypotension (consider intubation before transfer).
  • Severe, uncorrected, electrolyte disorders
  • Severe obesity that cannot be accommodated in transport bed and vehicle
  • Unable to tolerate supine position for duration of transport
  • Use of accessory muscles for spontaneously breathing patients, (consider intubation before transfer).
  • Receiving facility unable to provide higher level of care
  • Receiving facility does not have available PPE or cohorting capacity for droplet and airborne transmission.
  • Transport team does not have adequate PPE
  • Pneumothorax without a chest tube
  • Severe hemodynamic instability
  • Patient or family opposed to transfer
  • Futility with extremely poor short-term prognosis
  • Impending need for emergency procedures (surgery, catheterization, intubation), unless transferring for that purpose and within the allotted time-window
  • Pregnancy without adequate obstetrics and pediatrics care available at the receiving facility, unless no such facility is available.
  • Lack of access to a transport team capable of safe transport
  • Inadequate portable oxygen supply for patient’s needs
  • Inadequate power supply for equipment

Adapted and modified from Mazzoli et al.

Tool: Tools for Interfacility Transfer and Documentation (OCC)

Tool: Interfacility Transfer Checklist

Tool: Guidelines for Interfacility Transport Without Ambulance Systems (PIH)

Tool: Algorithm for COVID-19 Triage and Referral by WHO

Tool: Medical Transport Accreditation Standards, 11th edition by Commision on Accreditation of Medical Transport Systems

Chapter 4

Personal Protective Equipment