The Department of Homeland Security (DHS) Science and Technology Directorate (S&T) developed the following “master question list” that quickly summarizes what is known, what additional information is needed, and who may be working to address such fundamental questions as, “What is the infectious dose?” and “How long does the virus persist in the environment?” The Master Question List (MQL) is intended to quickly present the current state of available information to government decision makers in the operational response to COVID-19 and allow structured and scientifically guided discussions across the federal government without burdening them with the need to review scientific reports, and to prevent duplication of efforts by highlighting and coordinating research.
Updated 7/7/2020
Table of Contents
Infectious Dose – How much agent will make a healthy individual ill? ..................................................................................... 3
The human infectious dose of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown by all exposure routes. SARS-CoV-2 is the cause of coronavirus disease 19 (COVID-19). Studies from other animal models are used as surrogates for humans.
Identifying the infectious dose for humans by the various routes through which we become infected is critical to the effective development of computational models to predict risk, develop diagnostics and countermeasures, and effective decontamination strategies. Animal studies are a plausible surrogate.
Transmissibility – How does it spread from one host to another? How easily is it spread? ...................................................... 4
SARS-CoV-2 is passed easily between humans, likely through close contact with relatively large droplets and possibly through smaller aerosolized particles.
Individuals can transmit SARS-CoV-2 to others before they have symptoms.
Undetected cases play a major role in transmission, and most cases are not reported.543
Individuals who have recovered clinically, but test positive, appear unable to transmit COVID-19.
The relative contribution of different routes of transmission, such as close contact and droplet transmission versus aerosol transmission and contaminated objects and surfaces (fomites), is unknown and requires additional research.
Host Range – How many species does it infect? Can it transfer from species to species? ......................................................... 5
SARS-CoV-2 is closely related to other coronaviruses circulating in bats in Southeast Asia. Previous coronaviruses have passed through an intermediate mammal host before infecting humans, but the identity of the SARS-CoV-2 intermediate host is unknown.
SARS-CoV-2 uses the same receptor for cell entry as the SARS-CoV-1 coronavirus that circulated in 2002/2003.
To date, ferrets, mink, hamsters, cats, and primates have been shown to be susceptible to SARS-CoV-2 infection. It is unknown whether these animals can transmit infection to humans.
Several animal models have been developed to recreate human-like illness, though to date they have been infected with high dose exposures. Lower dose studies may better replicate human disease acquisition.
Incubation Period – How long after infection do symptoms appear? Are people infectious during this time?.......................... 6
The majority of individuals develop symptoms within 14 days of exposure. For most people, it takes at least 2 days to develop symptoms, and on average symptoms develop 5 days after exposure. Incubating individuals can transmit disease for several days before symptom onset. Some individuals never develop symptoms but can still transmit disease.
The incubation period is well-characterized. Patients may be infectious, however, for days before symptoms develop.
Clinical Presentation – What are the signs and symptoms of an infected person? ................................................................... 7
Many COVID-19 cases are asymptomatic. Most symptomatic cases are mild, but severe disease can be found in any age group.3 Older individuals and those with underlying medical conditions are at higher risk of serious illness and death. The case fatality rate varies substantially by patient age and underlying comorbidities.
Additional studies on vulnerable subpopulations are required.
Children are susceptible to COVID-19,132 though generally show milder85, 303 or no symptoms.
The true case fatality rate is unknown, as the exact number of cases is uncertain. Testing priorities and case definitions vary by location. The proportion of asymptomatic infections is not known.
Protective Immunity – How long does the immune response provide protection from reinfection? ........................................ 8
Infected patients show productive immune responses, but the duration of any protection is unknown. Currently, there is no evidence that recovered patients can be reinfected with SARS-CoV-2.
As the pandemic continues, long-term monitoring of immune activity and reinfection status is needed.
Clinical Diagnosis – Are there tools to diagnose infected individuals? When during infection are they effective? .................... 9
Diagnosis relies on identifying the genetic signature of the virus in patient nose, throat, or sputum samples, or by identifying SARS-CoV-2 antibodies in individuals exposed to the virus. Confirmed cases are still underreported.
Validated serological (antibody) assays are being developed to help determine who has been exposed to SARS-CoV-2. Serological evidence of exposure does not indicate immunity.
CLEARED FOR PUBLIC RELEASE 1
REQUIRED INFORMATION FOR EFFECTIVE INFECTIOUS DISEASE OUTBREAK RESPONSE SARS-CoV-2 (COVID-19)
In general, PCR tests appear to be sensitive and specific, though confirmation of symptoms via chest CT is recommended. The sensitivity and specificity of serological testing methods is variable, and additional work needs to be done to determine factors that affect test accuracy.
Medical Treatments – Are there effective treatments?...........................................................................................................10
Treatment for COVID-19 is primarily supportive care,185, 320 and no single standard of care exists. Drug trials are ongoing. Remdesivir shows promise for reducing symptom duration in humans.33Hydroxychloroquine is associated with risk of cardiac arrhythmias and provides limited to no clinical benefit at this time. Dexamethasone may significantly reduce mortality in severely ill and ventilated patients.
Other pharmaceutical interventions are being investigated.
Additional information on treatment efficacy is required, particularly from large randomized clinical trials.
Vaccines – Are there effective vaccines?.................................................................................................................................11
Work is ongoing to develop a SARS-CoV-2 vaccine in human trials (e.g., Operation Warp Speed). Early results are being released, but evidence should be considered preliminary until larger trials are completed.
Published results from randomized clinical trials (Phase I – III) are needed.
Non-pharmaceutical Interventions – Are public health control measures effective at reducing spread?.................................12
Broad-scale control measures such as stay-at-home orders are effective at reducing movement and contact rates, and modeling shows evidence that they reduce transmission.
Research is needed to help plan for easing of restrictions.
As different US states have implemented differing control measures at various times, a comprehensive analysis of social distancing efficacy has not yet been conducted.
Environmental Stability – How long does the agent live in the environment?.........................................................................13
SARS-CoV-2 can persist on surfaces for at least 3 days and on the surface of a surgical mask for up to 7 days depending on conditions. If aerosolized intentionally, SARS-CoV-2 is stable for at least several hours. The seasonality of COVID-19 transmission is unknown. SARS-CoV-2 on surfaces is inactivated rapidly with sunlight.
Additional testing on SARS-CoV-2, as opposed to surrogate viruses, is needed to support initial estimates of stability. Tests quantifying infectivity, rather than the presence of viral RNA, are needed.
Decontamination – What are effective methods to kill the agent in the environment? ..........................................................14
Soap and water, as well as common alcohol and chlorine-based cleaners, hand sanitizers, and disinfectants are effective at inactivating SARS-CoV-2 on hands and surfaces.
Additional decontamination studies, particularly with regard to PPE and other items in short supply, are needed.
PPE – What PPE is effective, and who should be using it? .......................................................................................................15
The effectiveness of PPE for SARS-CoV-2 is currently unknown, and data from other related coronaviruses are used for guidance. Healthcare workers are at high risk of acquiring COVID-19, even with recommended PPE.
Most PPE recommendations have not been made on SARS-CoV-2 data, and comparative efficacy of different PPE for different tasks (e.g., intubation) is unknown. Identification of efficacious PPE for healthcare workers is critical due to their high rates of infection.
Forensics – Natural vs intentional use? Tests to be used for attribution. ................................................................................16
All current evidence supports the natural emergence of SARS-CoV-2 via a bat and possible intermediate mammal species. Identifying the intermediate species between bats and humans would aid in reducing potential spillover from a natural source. Wide sampling of bats, other wild animals, and humans is needed to address the origin of SARS-CoV-2.
Genomics – How does the disease agent compare to previous strains? ..................................................................................17
Current evidence suggests that SARS-CoV-2 accumulates substitutions and mutations at a similar rate as other coronaviruses. Mutations and deletions in specific portions of the SARS-CoV-2 genome have not been linked to any changes in transmission or disease severity, though modeling work is attempting to identify possible changes.
Research linking genetic changes to differences in phenotype (e.g., transmissibility, virulence, progression in patients) is needed.
Forecasting – What forecasting models and methods exist?...................................................................................................18
Forecasts differ in how they handle public health interventions such as shelter-in-place orders and tracking how methods change in the near future will be important for understanding limitations going forward.
