On This Page
- What's New
- Overall Risk Assessment
- COVID-19 Weekly Key Points (through April 2, 2020)
- Current Disease Situation
- Entry/Exit Procedures
- Travel Advisories
- Exit Restrictions, Travel Restrictions, and Internal Disruptions
- Predictive Modeling
- Clinical Manifestations
- Criteria for Testing of Suspected Cases
- Key Unanswered Questions
Last updated April 3, 2020.
Cumulative case numbers for COVID-19, caused by SARS-CoV-2, are as follows:
- Transmission occurring locally: more than 1,079,200 cases in 171 countries
- Cases occurring in Europe: more than 550,800 cases
- Cases occurring in the United States: more than 265,500 cases
- Cases reported from China: more than 81,600 cases plus more than 1,000 cases in asymptomatic persons
- Imported cases only with no local transmission: more than 390 cases in 36 countries
- Deaths worldwide: more than 58,200 (China: more than 3,300; Europe: more than 41,900; U.S.: more than 6,700)
- Transmission aboard cruise ships: more than 1,500 cases aboard at least 28 ships
More than 1,082,400 cases have now been reported worldwide; approximately 50% of these cases were reported in the past 8 days. The first 100,000 cases were reported over 3 months. The cases reported in the U.S. now exceed the cases reported in any other country, including China.
All health authorities recommend that face masks be worn by symptomatic persons to prevent onward transmission (source control). Some health authorities recommend that face masks be worn by all persons to prevent onward transmission (source control) in order to encompass asymptomatic transmission. The U.S. CDC now recommends the optional use of non-medical grade cloth face coverings in public settings where other distancing measures are difficult. A new study in Nature Medicine examined seasonal human coronaviruses (related to SARS-CoV-2), influenza viruses and rhinoviruses in exhaled breath and coughs of children and adults with acute respiratory illness. Surgical face masks significantly reduced detection of coronavirus RNA in aerosols (masks 0/11 vs. no masks 4/10 subjects), with a trend toward reduced detection of coronavirus RNA in respiratory droplets (masks 1/27 vs. no masks 6/23 subjects). Of note, these findings also indicate that the majority of participants with coronavirus infection did not shed detectable virus RNA in respiratory droplets or aerosols at all. The study did not examine the infectivity of the coronavirus RNA detected in exhaled breath by PCR. In practice, very few persons are able to use surgical or other masks appropriately for significant periods of time when out in the community, and the threshold level of implementation in asymptomatic persons that would have any effect on transmission is not clear. Consideration must also be given to the likelihood that almost all symptomatic persons are already at home or in the hospital. No population-based controlled trial of masks vs. no-masks during a pandemic has ever demonstrated efficacy of face masks. See Literature Watch Review: Delaying the Spread of Influenza—A 3-Armed Policy Review of Nonpharmaceutical Measures for Pandemic Influenza in Nonhealthcare Settings.
Saudi Arabia is considering postponement of future mass gathering events (including Hajj 1441H) if the pandemic continues to escalate. Pilgrims are advised to defer conclusion of Hajj travel contracts until further guidance is provided. Entry into the country has already been suspended for the purpose of Umra and/or visiting the Prophet's Mosque in Medina and for travelers with a tourist visa from countries with a COVID-19 outbreak.
Singapore has closed all schools until May 5. All businesses, including restaurants, bars, amusement parks, museums, and casinos, are closed, except for essential services. People are encouraged to wear face masks in public, to stay home as much as possible, to avoid socializing in groups, and to only go out for essential items.
The qSARS-CoV-2 IgG/IgM Rapid Test (Cellex Inc.) is the first serological test to receive an EUA from the FDA; testing is limited to laboratories certified to perform moderate and high complexity tests. The test can produce results in 15 to 20 minutes and has a 94% positive percent agreement and a 96% negative percent agreement. However, a negative result does not preclude SARS-CoV-2 infection and should not be used as the sole basis for patient management decisions. The sensitivity of the test early after infection is unknown, and false positives for IgG and IgM antibodies may occur due to cross-reactivity. Shoreland cautions against the use of any serological test for definitive diagnosis or assessment of immunity against future infection especially prior to granting of EUA status by the FDA or similarly robust regulatory body. Earlier press reports of an FDA EUA status for another serological test (Bodysphere’s COVID-19 IgG/IgM Rapid Test) have been retracted.
A new randomized controlled trial from Wuhan, China (still in preprint format) compared 31 patients treated with hydroxychloroquine with standard of care. Improvement of COVID-19 pneumonia occurred in 81% of study patients compared to 54% of control patients. All 4 patients who progressed to severe illness were in the control group.
More than 81,000 additional cases in countries with local transmission have been reported since April 2, 2020 (through April 3 at 2:00 p.m. EDT) in the U.S. (> 30,300 cases; > 1,100 deaths), Spain (> 7,400 cases; > 910 deaths), Germany (> 6,000 cases; > 160 deaths), France (> 5,200 cases; > 2,000 deaths), Italy (> 4,500 cases; > 760 deaths), the U.K. (> 4,400 cases; > 680 deaths), Iran (> 2,700 cases; > 130 deaths), Turkey (> 2,700 cases; > 65 deaths), Belgium (> 1,400 cases; > 130 deaths), Brazil (> 1,100 cases; > 90 deaths), and in 137 other countries. In Italy, the trajectory of deaths has slowed from doubling every 3 days to doubling every 10 days. In Spain, the trajectory of deaths has slowed from doubling every 2.5 days to doubling every 6 days. In France, deaths are doubling every 5 days. In Iran, deaths are doubling every 2 weeks.
In the U.S., more than 23,800 cases have been reported since April 2 in the top 8 states: New York (> 10,400 cases; > 560 deaths), New Jersey (> 4,300 cases; > 100 deaths), Pennsylvania (> 2,500 cases; > 20 deaths), Florida (> 1,500 cases; > 30 deaths), Michigan (> 1,400 cases; > 80 deaths), Massachusetts ( > 1,200 cases; > 30 deaths) Louisiana (> 1,100 cases; > 60 deaths), and California (> 1,100 cases; > 30 deaths). The U.S. has the steepest trajectory at this stage in its outbreak compared to any other country, with cases doubling almost every 2.5 days and deaths doubling every 3 days; New York's death toll is rising faster than any other subnational region in the world at this stage of its outbreak. The nationwide outbreak is estimated to peak on April 15; the outbreaks in New Jersey, New York, Washington, and California are estimated to peak on April 8, 9, 11, and 26, respectively. Since January 21, more than 265,500 cases and 6,700 deaths have been reported in all 50 states and Washington, D.C., mainly in New York (> 102,800 cases; > 2,900 deaths), New Jersey (> 29,800 cases; > 640 deaths), California (> 11,200 cases; > 240 deaths), Michigan (> 10,700 cases; > 410 deaths), Louisiana (> 10,200 cases; > 370 deaths), Florida (> 9,500 cases; > 160 deaths), Massachusetts (> 8,900 cases; > 150 deaths), and Pennsylvania (> 8,500 cases; > 100 deaths). In addition, more than 50% of all U.S. cases have been reported from just 18 counties and cities in California (Los Angeles County), Florida (Miami-Dade County), Illinois (Cook County), Louisiana (Orleans and Jefferson parishes), Michigan (Detroit and Oakland and Wayne counties), New Jersey (Bergen, Essex, and Hudson counties), New York (NYC, Nassau, Orange, Rockland, Suffolk, and Westchester counties), and Washington (King County). More than 57,100 total cases have been reported in NYC and pervasive community spread is apparent; Shoreland recommends avoidance of nonessential travel to NYC at this time.
In the U.S., at least 297 million people in 38 states, Washington, D.C., 48 counties, 14 cities, and Puerto Rico have been ordered to stay at home except for essential outings, and all nonessential businesses have been closed until at least the end of April 2020.
Overall Risk Assessment
As of March 11, WHO considers the outbreak to be a global pandemic. Cases and deaths reported outside of China now vastly exceed those reported in China (the origin of the pandemic). Europe and the U.S. are now the epicenters of the pandemic, with the U.S. earlier on the upward trajectory of case numbers than Europe and with the likelihood of exceeding European case numbers within a short time. The U.S. is beyond the time of being able to implement the WHO recommended strategy used by several Asian countries of hospitalizing and isolating all cases and quarantining all contacts (with testing upon development of symptoms). In the U.S., implementation of active contact tracing is no longer feasible. China, Hong Kong, and Singapore are now importing cases in returning nationals from other highly affected countries. China has now closed its borders completely to arriving foreigners. All countries of the world and all states of the U.S. should now be considered to have widespread community transmission. In the past 24 hours, more than 81,000 additional cases have been reported from 147 countries, with more than 58,100 from France, Germany, Italy, Spain, the U.K., and the U.S. As of April 3, more than 58,200 deaths have been reported worldwide. A continuing lack of coordinated robust epidemiological analyses between affected countries as a group is hampering a coordinated or optimal response.
No patient has had a positive viral culture more than 8 days after symptom onset. Shedding of viral RNA from sputum outlasts the end of symptoms and may occur for up to 21 days. Seroconversion (IgM or IgG) occurs after 7 days in 50% of patients (14 days in all patients) but is not followed by an immediate decline in viral load. Shoreland cautions against the use of any serological test for definitive diagnosis or assessment of immunity against future infection especially prior to granting of EUA status by the FDA or similarly robust regulatory body.
The true spectrum of clinical disease—which involves ascertaining the proportions of infected persons who are asymptomatic; who are symptomatic but apparently (to others) asymptomatic; who have influenza-like illness, focal pneumonia, or severe respiratory compromise; and fatalities is increasingly clear. Across almost all countries, severity proportions have been roughly 80% mild to moderate, 15% severe, and 5% critical (needing ICU admission). Robust disease spectrum data have emerged from the self-contained natural experiment on board the Diamond Princess cruise ship, where more than 700 cases occurred among 3,700 passengers (mostly older) and crew members (mostly younger). Of these cases, more than 380 were symptomatic and more than 330 were asymptomatic; among the symptomatic cases, 37 required intensive care and 9 died (all of whom were aged > 70 years).
A rigorous U.S. CDC study of a U.S. nursing-home outbreak, in a highly infectious environment with a high attack rate (30%), demonstrated that only 3 of 23 COVID-19 cases remained completely asymptomatic throughout the course of their infection, further reinforcing that rates of true asymptomatic infection are low. WHO has reinforced this low level (less than 10%) of truly asymptomatic infections (remaining asymptomatic at all times throughout the infection) based on available data from China and other countries. Asymptomatic transmission in the community is occurring but does not appear to be a major driver of the epidemic in most countries. Asymptomatic transmission among household contacts is important, and quarantine of all household contacts is an important mitigation strategy. Many minimally symptomatic people may not appear symptomatic to others. SARS-CoV-2 is capable of highly efficient human-to-human transmission and certainly has an overall CFR of approximately 1% in large populations studied and of up to 10% in vulnerable populations. Airborne transmission has not been proven to occur in the community; this was restated by WHO on March 29. Fecal transmission does not appear to occur despite the shedding of SARS-CoV-2 RNA in stool specimens for prolonged periods after illness resolution.
Overall, due to uncertainty, justification is present for the most cautious approach of having arrivals from all countries stay at home or in visitors’ accommodations for 14 days after their last possible exposure in the exposure country. Detection of virus by PCR in the respiratory tract of an asymptomatic individual does not differentiate between 1) being able to infect others while asymptomatic; 2) remaining asymptomatic and never becoming capable of infecting others; and 3) becoming symptomatic and being capable of infecting others during clinical illness. Both viral detection and epidemiological evidence of transmission are required to prove cause and effect of human-to-human transmission by an asymptomatic person. Potential super-spreading events from asymptomatic or minimally symptomatic persons appear to have already occurred in many countries but are not pandemic drivers. Fortunately, sequential sequencing of over 2,400 viral isolates over time, to date, indicates high homology (small mutations at fewer than 10 locations) and no functionally significant new viral mutations, although the virus can now be divided into multiple clades (S,G,V, and Other); mutations often increase transmission or virulence. The originally implicated animal market, now closed indefinitely, bears no relevance to the ongoing situation; human-to-human transmission in Wuhan appears to have been ongoing since mid-December. A reproductive number, R0, is estimated at 2–3 both by Chinese authorities and by multiple outside estimates. R0 greater than 1 indicates that each case leads to more than 1 subsequent case, making control much more difficult.
CFRs vary widely depending on circumstances of transmission, care, resources, and national preparedness.
- Robust disease spectrum and CFR data have emerged from the self-contained natural experiment on board the Diamond Princess cruise ship, where more than 700 cases occurred among 3,700 passengers (mostly older) and crew members (mostly younger). Of these cases, more than 380 were symptomatic and more than 330 were asymptomatic; among the symptomatic cases, 37 required intensive care and 9 died (all of whom were aged > 70 years). CFR modeling based on this data with application of China COVID-19 age distribution data indicate an overall CFR of 1.3% and a CFR for those over age 70 years of 6.4%.
- Overall, South Korea has reported more than 9,900 confirmed cases with more than 160 deaths (CFR 1.6%) through April 2. Deaths in South Korea, broken down by age (CFR %): younger than 30 years (0%); 30-39 years (0.10%); 40-49 years (0.15%); 50-59 years (0.59%); 60-69 years (1.83%); 70-79 years (7.09%); > 80 years (18.76%).
- Preliminary data from the first 4,200 U.S. cases, including 110 deaths (CFR 1.8%–3.4%), show the following deaths broken down by age (CFR %): 0-19 years (0%); 20-44 years (0.1%–0.2%); 45-54 years (0.5%–0.8%); 55-64 years (1.4%–2.6%); 65-74 years (2.7%–4.9%); 75-84 years (4.3%–10.5%); and ≥ 85 years (10.4%–27.3%).
- In contrast, Italy has reported a total of more than 115,200 confirmed cases, including more than 13,900 deaths (CFR 12.0%) through April 2. Deaths, broken down by age (CFR %): younger than 20 years (0%); 20-29 years (0.1%), 30-39 years (0.4%); 40-49 years (0.8%); 50-59 years (2.3%); 60-69 years (8.0%); 70-79 years (21.8%); 80-89 years (30.9%); > 90 years (28.7%).
- In China, deaths broken down by age (CFR %) are: 10-19 years (0.2%); 20-29 years (0.2%); 30-39 years (0.2%); 40-49 years (0.4%); 50-59 years (1.3%); 60-69 years (3.6%); 70-79 years (8.0%); > 80 years (14.8%). The case definition has varied in China over time. These CFRs are for all patients, without adjustment for comorbidities.
Severity is clearly 10-fold higher than with seasonal influenza. Serological assays to detect SARS-CoV-2 seroconversion in humans have now been prepublished by 2 established laboratories, 1 in the U.S. and 1 in Europe. Such methodology is critical for an accurate estimate of population-based asymptomatic and case-fatality rates (which is still not possible and will require more data) to properly effect mitigation and suppression strategies. Scale-up scenarios are uncertain at present.
COVID-19 Weekly Key Points (through April 2, 2020)
The full context of each key point can be found in the appropriate section of this Outbreak Report.
Current Disease Situation
The U.S. CDC advises against nonessential travel to all countries.
Total Cases in Countries with Local Transmission
More than 1,079,200 confirmed cases of COVID-19 (predominantly locally acquired) have been reported since December 8 (through April 3 at 2:00 p.m. EDT) in 171 countries. The incubation periods in these cases may have been as short as 3 days.
Countries Reporting More than 1,000 Cases and Additional Countries of Interest
U.S. (> 265,500 cases; > 6,700 deaths): Last case reported on April 3. Underreporting is ongoing due to continued limitations in testing capacity. The U.S. has the steepest trajectory at this stage in its outbreak compared to any other country, with cases doubling almost every 2.5 days and deaths doubling every 3 days; New York’s death toll is rising faster than any other subnational region in the world at this stage of its outbreak. The nationwide outbreak is estimated to peak on April 15; the outbreaks in New Jersey, New York, Washington, and California are estimated to peak on April 8, 9, 11, and 26, respectively. Meanwhile, deaths in Washington have begun to plateau, doubling every 11 days. Cases have been reported in all 50 states and Washington D.C., mainly in the states of New York (> 102,800 cases; > 2,900 deaths), New Jersey (> 29,800 cases; > 640 deaths), California (> 11,200 cases; > 240 deaths), Michigan (> 10,700 cases; > 410 deaths), Louisiana (> 10,200 cases; > 370 deaths), Florida (> 9,500 cases; > 160 deaths), Massachusetts (> 8,900 cases; > 150 deaths), and Pennsylvania (> 8,500 cases; > 100 deaths). More than 57,100 cases have been reported in NYC, and deaths continue to accelerate, doubling every 3 days; Shoreland recommends avoidance of nonessential travel to NYC at this time. Through April 3, using very stringent screening criteria, more than 1,352,700 people have been tested; approximately 17.9% were confirmed as positive. More than 1,400 cases have been imported (including 46 repatriated from the Diamond Princess cruise ship and 3 repatriated from Wuhan). Also see Cases on an International Conveyance (Cruise Ships) below.
Italy (> 119,800 cases; > 14,600 deaths): Last case reported on April 3. The trajectory of cases has slowed from doubling every 3 days to doubling more than every 7 days, and the deaths have followed a similar trajectory to doubling every 10 days. Cases have been reported in all 20 regions, mainly in Lombardy (> 47,500 cases), Emilia-Romagna (> 15,900 cases), Piedmont (> 10,800 cases), and Veneto (> 10,400 cases). Total cases and deaths are likely underestimated. Cases have been exported to more than 80 countries. The outbreak peaked on March 21, and daily case numbers, which peaked at more than 6,500 cases, have decreased from approximately 5,500 per day during March 22-28 to approximately 4,500 per day over the past 6 days.
Spain, Canary Islands, and Mallorca Island (> 117,700 cases; > 11,000 deaths): Last case reported on April 3. Cases are doubling almost every 3 days, and the trajectory of deaths has slowed from doubling every 2.5 days to doubling every 6 days; Catalonia Autonomous Community and Madrid are among the worst affected subnational regions. Cases have been reported in all 17 autonomous communities and Ceuta and Melilla, mainly in the Community of Madrid (> 34,100 cases) and Catalonia (> 23,400 cases), as well as on the Canary Islands (> 1,400 cases) and Balearic Islands (1,200 cases; including Mallorca Island). HCWs account for approximately 14% of the total cases. More than 9,200 cases were reported on March 31, marking the highest number of daily cases reported since the start of the outbreak; daily case numbers decreased to approximately 7,700 cases per day over the past 3 days.
Germany (> 89,900 cases; > 1,200 deaths): Last case reported on April 3. Cases are doubling about every 3 days and deaths every 2.5 days. Cases have been reported in all 16 states, mainly in Bavaria (> 20,200 cases), North Rhine-Westphalia (> 16,600 cases, including Heinsberg District), and Baden-Württemberg (> 16,000 cases).
China (> 81,600 cases; > 3,300 deaths): Last cases reported on April 3, and all but 2 new cases were imported. Cases have been reported in the provinces of Hubei (> 67,800; mainly in Wuhan), Guangdong (> 1,400), Henan (> 1,200), Zhejiang (> 1,200), Hunan (> 1,000), Anhui (> 990), and Jiangxi (> 930); in the cities of Chongqing (> 570), Beijing (> 570), and Shanghai (> 430); and throughout the rest of the country. In addition, more than 1,000 cases have been reported in asymptomatic persons. More than 76,500 cases have been discharged.
France (> 64,300 cases; > 6,500 deaths): Last case reported on April 3. Deaths are doubling every 5 days. Cases have been reported in all 13 regions, mainly in Île-de-France (including Paris) and Grand Est.
Iran (> 53,100 cases; > 3,200 deaths): Last case reported on April 2. Deaths are doubling every 2 weeks. Cases have been reported in all 31 provinces, mainly in Isfahan, Mazandaran, and Tehran. Case totals are likely underestimated. Cases have been exported to more than 25 countries; spillover cases are also occurring in neighboring countries.
U.K. (> 38,100 cases; > 3,600 deaths): Last case reported on April 3. Cases and deaths are doubling every 3 days. Cases have been reported in England (> 31,700 cases; mainly in London), Northern Ireland, Scotland, and Wales. As of April 3, more than 173,700 people have been tested in the U.K.; 21.9% were confirmed as positive. Both the Prince of Wales and the Prime Minister have tested positive for SARS-CoV-2.
Turkey (> 20,900 cases; > 420 deaths): Last case reported on April 3.
Switzerland (> 19,600 cases; > 600 deaths): Last case reported on April 3. Cases have been reported in all 26 cantons, mainly in Basel-Stadt, Geneve, Ticino (bordering Italy), and Vaud. The outbreak appears to have peaked on March 23, and daily case numbers, which peaked at 1,400, have decreased from approximately 1,200 per day during March 24-27 to less than 690 per day over the past week.
Belgium (> 16,700 cases; > 1,100 deaths): Last case reported April 3.
Netherlands (> 15,700 cases; > 1,400 deaths): Last case reported on April 3. Cases have been reported in all 12 provinces, mainly in North Brabant (> 3,900 cases), South Holland (> 2,600 cases), and North Holland (> 2,300 cases).
Canada (> 11,700 cases; > 170 deaths): Last case reported on April 3. Cases have been reported in all 10 provinces and in Northwestern Territories and Yukon Territory, mainly in Quebec (> 5,500 cases), Ontario (> 3,200 cases), British Columbia (> 1,100 cases), and Alberta (> 960 cases). More than 30% of these cases were imported or close contacts of the imported cases.
Austria (> 11,400 cases; > 160 deaths): Last case reported on April 3.
South Korea (> 10,000 cases; > 170 deaths): Last case reported on April 3. More than 80% of these cases are epidemiologically linked; more than 50% of these cases are associated with a super-spreading event linked to the Shincheonji Church of Jesus cluster. Cases have been reported in all 17 first-tier administrative divisions, mainly in Daegu Metropolitan City (> 6,700 cases) and Gyeongbuk Province (> 1,300 cases), as well as in Seoul (> 500 cases). As of April 3, more than 443,200 people have been tested in South Korea; 2.2% were confirmed as positive. The outbreak peaked on February 29, and daily case numbers, which peaked at approximately 900, have decreased to approximately 100 per day over the past 3 weeks.
Portugal, Azores, and Madeira (> 9,800 cases; > 240 deaths): Last case reported on April 3. Cases have been reported throughout the country, mainly in northern districts, as well as on the islands of Azores (> 60 cases) and Madeira (50 cases).
Brazil (> 8,200 cases; > 340 deaths): Last case reported on April 3. Cases have been reported in all 27 states, mainly in São Paulo (> 3,500 cases) and Rio de Janeiro (> 990 cases).
Israel (> 7,000 cases; 40 deaths): Last case reported on April 3.
Sweden (> 6,100 cases; > 350 deaths): Last case reported on April 3.
Australia (> 5,300 cases; 28 deaths): Last case reported on April 3. Cases have been reported in all 6 states and in Australia Capital Territory and Northern Territory, mainly in New South Wales State (> 2,300 cases), Victoria (> 1,000 cases), and Queensland (> 870 cases). More than 3,700 cases have been imported (including 10 cases that were acquired aboard the Diamond Princess cruise ship). The outbreak peaked on March 22, and daily case numbers, which peaked at 395, have decreased from approximately 365 per day March 23-27 to less than 230 per day over the past week.
Norway (> 5,200 cases; > 55 deaths): Last case reported on April 3. Cases have been reported throughout the country, mainly in Oslo, Vestland, and Viken counties. More than 1,500 cases were imported.
Ireland (> 4,200 cases; 120 deaths): Last case reported on April 3.
Russia (> 4,100 cases; > 30 deaths): Last case reported on April 3.
Czech Republic (> 4,000 cases; > 50 deaths): Last case reported on April 3.
Denmark (> 3,700 cases; > 130 deaths): Last case reported on April 3.
Chile (> 3,700 cases; 22 deaths): Last case reported on April 3.
Ecuador (> 3,300 cases; > 140 deaths): Last case reported on April 3.
Malaysia (> 3,300 cases; > 50 deaths): Last case reported on April 3. More than 1,300 cases are linked to a religious gathering in Kuala Lumpur held February 28 through March 1; additional cases have been reported in 6 other countries.
Poland (> 3,200 cases; 65 deaths): Last case reported on April 3.
Romania (> 3,100 cases; > 130 deaths): Last case reported on April 3.
Philippines (> 3,000 cases; > 136 deaths): Last case reported on April 3.
Japan (> 2,700 cases; > 70 deaths): Last case reported on April 3. Cases have been reported in 44 of 47 prefectures, mainly in Tokyo (690 cases), Aichi, Chiba, Hokkaido, and Osaka. At least 9 of these cases were reported among HCWs who boarded the Diamond Princess cruise ship while it was docked in Japan. Also see Cases on an International Conveyance (Cruise Ships) below.
Pakistan (> 2,600 cases; 40 deaths): Last case reported on April 3.
Luxembourg (> 2,600 cases; > 30 deaths): Last case reported on April 3.
India (> 2,500 cases; > 70 deaths): Last case reported on April 3.
Saudi Arabia (> 2,000 cases; 25 deaths): Last case reported on April 3.
Indonesia (> 1,900 cases; > 180 deaths): Last case reported on April 3.
Thailand (> 1,900 cases; 19 deaths): Last case reported on April 3.
Greece (> 1,600 cases; > 55 deaths): Last case reported on April 3.
Finland (> 1,600 cases; 20 deaths): Last case reported on April 3.
Mexico (> 1,500 cases; 50 deaths): Last case reported on April 3.
South Africa (> 1,500 cases; 9 deaths): Last case reported on April 3. Cases have been reported in all 9 provinces, mainly in Gauteng (> 660 cases) and Western Cape (> 250 cases).
Dominican Republic (> 1,400 cases; > 65 deaths): Last case reported on April 2.
Peru (> 1,400 cases; 55 deaths): Last case reported on April 3.
Panama (> 1,400 cases; > 35 deaths): Last case reported on April 3.
Serbia (> 1,400 cases; > 35 deaths): Last case reported on April 3.
Iceland (> 1,300 cases; 4 deaths): Last case reported on April 3.
Argentina (> 1,200 cases; > 35 deaths): Last case reported on April 3.
Algeria (> 1,100 cases; > 100 deaths): Last case reported on April 3.
Colombia (> 1,100 cases; 19 deaths): Last case reported on April 3.
Singapore (> 1,100 cases; 5 deaths): Last case reported on April 3. Epidemiological investigations have identified 25 main (currently known) clusters. Investigation continues for more than 120 of the total cases reported in Singapore without a known epidemiological link (including contact with a previous case or travel history to COVID-19–affected countries). Approximately 74 cases (including 20 imported cases) were reported on April 1, marking the highest number of daily cases reported since the start of the outbreak; approximately 57 cases per day were reported over the past 2 days.
Croatia (> 1,000 cases; 8 deaths): Last case reported on April 3.
United Arab Emirates (> 1,000 cases; 8 deaths): Last case reported on April 3.
Qatar (> 1,000 cases, 3 deaths): Last case reported on April 3.
Hong Kong (> 840 cases; 4 deaths): Last case reported on April 3. Of these cases, more than 470 were imported (10 of which were acquired aboard the Diamond Princess cruise ship), more than 140 are close contacts of a local case, more than 95 are possible locally acquired cases, more than 60 are locally acquired, more than 45 are close contacts of a possible locally acquired case, and 21 are close contacts of an imported case. More than 120 cases were asymptomatic. No deaths have been reported since mid-February. The outbreak appears to have peaked on March 27, and daily case numbers, which peaked at approximately 65 cases, have decreased to approximately 47 cases (mainly imported cases) per day over the past week.
Taiwan (> 340 cases; 5 deaths): Last case reported on April 3. Of these cases, more than 290 are imported. As of April 3, more than 34,500 people have been tested in Taiwan; 1.0% were confirmed as positive, indicating no widespread infection in the population to date. The outbreak appears to have peaked on March 20, and daily case numbers, which peaked at approximately 27 cases, have decreased to approximately 11 cases (mainly imported cases) per day over the past week.
Countries Reporting Less than 1,000 Cases
According to international health authorities, less than 1,000 laboratory-confirmed cases of COVID-19 (predominantly locally acquired) have occurred in the following countries without evidence of widespread community transmission (case number; date of last reported case): Afghanistan (> 200, 7 deaths; April 3), Albania (> 300, > 10 deaths; April 3), Andorra (> 400, > 10 deaths; April 3), Anguilla (3; March 27), Armenia (> 700, 7 deaths; April 3), Aruba (> 60; April 3), Azerbaijan (> 400, 5 deaths; April 3), Bahamas (> 20, 1 death; April 3), Bahrain (> 600, 4 deaths; April 3), Bangladesh (> 60, 6 deaths; April 3), Barbados (> 40; April 3), Belarus (> 300, 4 deaths; April 3), Belize (4; April 3), Bermuda (> 30; April 3), Bhutan (5; April 2), Bolivia (> 100, 9 deaths; April 3), Bosnia and Herzegovina (> 500, > 10 deaths; April 3), Brunei (> 100, 2 deaths; April 3), Bulgaria (> 400, > 10 deaths; April 3), Burkina Faso (> 300, > 10 deaths; April 3), Burma (20, 1 death; April 2), Cambodia (> 100; April 3), Cameroon (> 300, 7 deaths; April 3), Cayman Islands (> 20, 1 death; April 2), Channel Islands (> 200, 4 deaths; April 3), Costa Rica (> 300, 2 deaths; April 3), Côte d'Ivoire (> 100, 1 death; April 3), Cuba (> 200, 6 deaths; April 3), Cyprus (> 300, > 10 deaths; April 3), Democratic Republic of the Congo (> 100, > 10 deaths; April 3), Djibouti (> 40; April 3), Dominica (> 10; April 3), Egypt (> 800 cases, > 50 deaths; April 3), El Salvador (> 40, 2 deaths; April 3), Equatorial Guinea (> 10; April 3), Estonia (> 900 cases, > 10 deaths; April 3), Ethiopia (> 30; April 3), Faroe Islands (> 100; April 3), Fiji (7; April 2), French Guiana (> 50; April 3), French Polynesia (> 30; April 1), Georgia (> 100; April 3), Ghana (> 200, 5 deaths; April 2), Gibraltar (> 90; April 3), Grenada (10; April 2), Guadeloupe (> 100, 6 deaths; April 2), Guam (> 80, 4 deaths; April 2), Guatemala (> 50, 1 death; April 3), Guinea (> 70, 1 death; April 3), Guyana (> 10, 4 deaths; April 2), Honduras (> 200, > 10 deaths; April 3), Hungary (> 600, > 20 deaths; April 3), Iraq (> 800 cases, > 50 deaths; April 3), Jamaica (> 40, 3 deaths, April 3), Jordan (> 200, 5 deaths; April 2), Kazakhstan (> 400, 6 deaths; April 3), Kenya (> 100, 4 deaths; April 3), Kosovo (> 100, 1 death; April 3), Kuwait (> 400; April 3), Kyrgyzstan (> 100, 1 death; April 3), Laos (10; April 1), Latvia (> 400, 1 death; April 3), Lebanon (> 500, > 10 deaths; April 3), Liberia (7; April 3), Libya (> 10, 1 death; April 3), Lithuania (> 600, 9 deaths; April 3), Macau (> 40; April 3), Madagascar (> 60; April 3), Malawi (3; April 2), Maldives (> 10; April 1), Mali (> 30, 3 deaths; April 3), Malta (> 200; April 3), Martinique (> 100, 3 deaths; April 3), Mauritius (> 100, 7 deaths; April 3), Mayotte (> 100, 1 death; April 2), Moldova (> 500, 8 deaths; April 3), Monaco (> 60, 1 death; April 3), Montenegro (> 100, 2 deaths; April 3), Morocco (> 700, > 40 deaths; April 3), Mozambique (10; April 1), Namibia (> 10; April 2), New Caledonia (> 10; April 2), New Zealand (> 800 cases, 1 death; April 3), Niger (> 90, 5 deaths; April 3), Nigeria (> 100, 2 deaths; April 3), North Macedonia (> 300, > 10 deaths; April 2), Northern Mariana Islands (8, 1 death; April 3), Oman (> 200, 1 death; April 3), Palestinian Territories (> 100, 1 death; April 3), Paraguay (> 90, 3 deaths; April 3), Puerto Rico (> 300, > 10 deaths; April 3), Republic of the Congo (> 40, 2 deaths; April 3), Réunion (> 300; April 3), Rwanda (> 80; April 3), Saint Lucia (> 10; April 1), San Marino (> 200, > 30 deaths; April 3), Senegal (> 200, 1 death; April 3), Slovakia (> 400, 1 death; April 3), Slovenia (> 900 cases, 20 deaths; April 3), Sri Lanka (> 100, 4 deaths; April 3), Sudan (10, 2 deaths; April 3), Tanzania (20, 1 death; April 2), Togo (40, 3 deaths; April 3), Trinidad and Tobago (> 90, 6 deaths; April 3), Tunisia (> 400, > 10 deaths, April 3), Turks and Caicos Islands (5; March 30), Uganda (> 40; April 3), Ukraine (> 900, > 20 deaths; April 3), Uruguay (> 300, 4 deaths; April 3), U.S. Virgin Islands (> 30; April 3), Uzbekistan (> 200, 2 deaths; April 3), Venezuela (> 100, 5 deaths; April 3), Vietnam (> 200; April 3), Zambia (> 30, 1 death; April 2), Zimbabwe (9, 1 death; April 3).
Total Cases in Countries Reporting Only Imported Cases
More than 390 imported cases of COVID-19 (confirmed after arrival) have been reported at international ports of entry since January 6 (through April 3 at 2:00 p.m. EDT) in 36 countries.
Imported only, laboratory-confirmed cases of COVID-19 have occurred in the following countries (case number; date of last reported case): Angola (8, 2 deaths; April 2), Antigua and Barbuda (9; April 3), Benin (> 10; April 2), Botswana (4, 1 death; April 4), British Virgin Islands (3; March 31), Burundi (3; April 2), Cabo Verde (5, 1 death; March 27), Central African Republic (8; April 3), Chad (8; April 3), Curaçao (> 10, 1 death; March 30), Eritrea (> 20; April 2), Eswatini (9; March 27), Gabon (> 20, 1 death; April 3), Gambia (4, 1 death; March 30), Greenland (10, under investigation; March 27), Guinea-Bissau (9; April 1), Haiti (> 10; April 3), Liechtenstein (> 70, under investigation; April 2), Mauritania (6, 1 death; March 31), Mongolia (> 10; April 1), Montserrat (5; March 27), Nepal (6; April 2), Nicaragua (5, 1 death; April 1), Papua New Guinea (1; March 20), Saint Barthelemy (6, under investigation; March 30), Saint Kitts and Nevis (9; April 3), Saint Martin (> 20, 1 death, under investigation; April 2), Saint Vincent and the Grenadines (3 ; April 3), Seychelles (10; March 31), Sierra Leone (2; April 2), Sint Maarten (> 20, 2 deaths; April 3), Somalia (5; March 31), Suriname (10, 1 death; April 1), Syria (10, 2 deaths; March 31), Timor-Leste (1, under investigation; March 21), Vatican City (7, under investigation; April 3).
Cases on an International Conveyance (Cruise Ships)
More than 1,500 cases of infection have been reported aboard at least 28 cruise ships, including the Diamond Princess discussed above. Most major cruise lines have suspended operations.
At least 8 cruise ships are still at sea in search of open ports or are docked and under quarantine (as of March 25). Cases have been reported on the Coral Princess (12 cases; set to dock in Fort Lauderdale, Florida), Costa Luminosa (36 cases, 1 death; docked in Savona, Italy), Ovation of the Seas (31 cases; docked in Sydney, Australia), MS Zaandam (9 cases, 2 deaths, and > 180 ill passengers; passengers who are not ill have been transferred to the MS Rotterdam, and both ships are docked in Fort Lauderdale, Florida), Silver Shadow (1 case; docked and disembarking at the Port of Recife, Brazil), Silver Explorer (1 case; docked at Castro, Chile), and Voyager of the Seas (26 cases, 1 death; docked in Sydney, Australia). The remaining cruise ships have not reported any confirmed cases but are in search of an open port that will allow them to dock, including MV Artania (at sea, off the coast of Western Australia), Norwegian Jewel (passengers have disembarked, but crew remain on board; docked in Honolulu, Hawaii), Pacific Princess (docked in Fremantle, Australia), and the Vasco da Gama (docked at Rottnest Island, Australia). Passengers disembarked the Golden Princess after it docked in Melbourne, Australia on March 19. The MS Braemar (5 cases) arrived in Mariel, Cuba on March 18, and passengers were flown back to the U.K.
The nuclear-powered aircraft carrier, USS Theodore Roosevelt, currently docked in Guam, has reported more than 100 COVID-19 cases. The ship captain requested that 90% of the crew be allowed to offboard for quarantine to prevent further spread of the virus and to disinfect the ship. On April 2, approximately 1,000 sailors were evacuated from the ship. The other U.S. aircraft carrier currently in the Pacific Ocean has reported 2 cases on board.
Entry screening using questionnaires, fever screening, thermal scanning, or visual inspection at international ports of entry has been implemented in almost all countries. In most cases, anyone with fever and respiratory symptoms and a history of any international travel in the past 14 days may be detained and isolated or placed in self-isolation; persons without symptoms but with a similar travel history may be placed in quarantine or self-quarantine depending on where the exposures may have taken place.
Many countries have implemented management procedures for asymptomatic travelers (including citizens) who have arrived within the past 14 days from COVID-19–affected countries. These management procedures include self-observation (remaining alert for symptoms), self-monitoring (taking a temperature reading 2 times per day), social distancing (remaining out of congregate settings [crowded places such as shopping centers, movie theaters, and stadiums], avoiding mass gatherings and public transportation, and maintaining a distance of 2 m [6 ft] from others), and quarantine (mandatory or self-separation from others not exposed) for 14 days (unless otherwise noted). Isolation (self-isolation or mandatory separation from others not exposed) is used only for persons known or reasonably believed to be infected. Arrivals who develop fever or respiratory symptoms within 14 days of travel to the aforementioned areas should self-isolate; observe respiratory hygiene (cough and sneeze etiquette), hand hygiene (frequent, thorough handwashing with soap and water for 20 seconds [or using a hand sanitizer containing 60% alcohol]), and social distancing; wear a face mask; and contact public health authorities (or telephone ahead before presenting to a hospital). See Table 2 for additional travel restrictions. Information is provided for the following countries or multinational organizations:
Australia: Arrivals from any country will be subject to a mandatory quarantine at designated facilities.
Canada: Arrivals from any country will be subject to mandatory home quarantine and must self-observe.
China: Chinese nationals arriving from any country will likely be placed in a hotel for 1 to 2 days to await negative test results before being allowed to quarantine at home. Families and couples are allowed to stay together. If test results are negative, home quarantine is strictly enforced, and they may only leave for medical care at designated facilities.
Germany: Arrivals from Austria, Egypt, France, Iran, Italy, South Korea (Daegu, Gyeongbuk), Spain, Switzerland (Geneva, Ticino, and Vaud), and the U.S. (California, New Jersey, New York, and Washington) should report to health officials to complete an individualized survey; those determined to be at high risk of infection should self-quarantine and self-monitor.
Hong Kong: Arrivals from Iran, Italy (Emilia-Romagna, Lombardy, and Veneto), and South Korea (Daegu and Gyeongbuk) in the past 14 days will be subject to mandatory quarantine in a government-designated quarantine center. Arrivals from any other country will be subject to mandatory quarantine (at home or other accommodation). Fourteen categories of persons are exempt from quarantine (including academic researchers, select government officials, flight and cruise-ship crew members, and cross-boundary drivers) but are required to self-monitor with public health supervision and wear face masks during their stay in Hong Kong.
India: Arrivals (including Indian nationals) from China, France, German, Hong Kong, Italy, Iran, Japan, Kuwait, Malaysia, Oman, Qatar, Saudi Arabia, Singapore, South Korea, Spain, Thailand, United Arab Emirates, and the U.S. must self-quarantine; those arriving from any other country will be subject to a health screening and should self-monitor.
Israel: Arrivals from any country will be subject to mandatory home quarantine.
Japan: Arrivals from anywhere in Africa, China, Europe, Southeast Asia, South Korea, and the Middle East will be subject to mandatory quarantine in a government-designated location.
New Zealand: Arrivals from any country must self-quarantine.
Singapore: Arrivals from Hubei Province will be subject to a Quarantine Order (legal order for mandatory home quarantine or quarantine in a government-designated location); those from elsewhere in China and all other countries will be subject to a Stay-Home Notice (mandatory home quarantine and should self-monitor).
South Africa: Arrivals from anywhere in China and COVID-19–affected countries should self-quarantine and self-monitor.
South Korea: Arrivals from China, Hong Kong, Iran, Japan, and Macao should self-quarantine. Arrivals from Europe and the U.S. will be subject to home quarantine. Beginning April 1, arrivals from any country must self-quarantine.
Taiwan: Arrivals from any country must self-quarantine.
Thailand: Arrivals from China, Hong Kong, Italy, Iran, Macau, and South Korea will be subject to mandatory home quarantine and self-monitoring with public health supervision.
U.S.: Arrivals from any country and all passengers returning from a cruise should stay at home, self-monitor, and observe social distancing.
WHO: National discretion, in accordance with local laws and the International Health Regulations, should be used to decide whether further health measures are necessary for asymptomatic arrivals.
Australia, Canada, France, Germany, New Zealand, the U.K., and the U.S. have stated that all of their nationals who need to or intend to come home at any time during the COVID-19 outbreak should do so immediately with the expectation that shutdowns of air travel and borders will soon make repatriation impossible. The U.S. Peace Corps has suspended all operations globally and is repatriating all volunteers.
The following countries and/or organizations, among others, have published travel recommendations for outbound travel:
|Country Issuing||Avoid Travel||Avoid Nonessential Travel|
X (all international travel, including cruise-ship travel)
X (China: Hubei Province)
(all cruise-ship travel)
X (all international travel)
|China||X (China: Hubei Province)|
|France||X (all international travel, including cruise-ship travel)|
|Germany||X (China: Hubei Province)||X (all international travel)|
|India||X (China, France, Germany, Iran, Italy, Japan, South Korea, Spain)||X (all international travel)|
X (Andorra, Armenia, Australia, Austria, Bahrain, Belgium, Bosnia and Herzegovina, Brazil, Brunei, Bulgaria, Canada, Chile, China, Cote d'Ivoire, Croatia, Cyprus, Czech Republic, Democratic Republic of the Congo, Denmark, Dominica, Ecuador, Egypt, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Indonesia, Iran, Ireland, Israel, Italy, Kosovo, Latvia, Liechtenstein, Lithuania, Luxembourg, Malaysia, Malta, Mauritius, Moldova, Monaco, Montenegro, Morocco, Netherlands, North Macedonia, Norway, Panama, Philippines, Poland, Portugal, Romania, San Marino, Serbia, Singapore, Slovakia, Slovenia, South Korea, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, Vietnam, U.K., U.S., Vatican City)
X (all international travel, except for the countries listed to the left)
|New Zealand||X (all international travel)||X (cruise-ship travel)|
|Singapore||X (all international travel)|
|Spain||X (all international travel)|
X (China: Hubei Province)
(South Korea: Cheongdo, Daegu, Gyeongsan)
X (international travel)
|U.S. Department of State|| |
X (all international travel2)
(all cruise-ship travel, particularly for those with underlying medical issues)
|U.S. CDC|| |
X (South Korea: Daegu)
X (all international travel and cruise-ship travel)
|All other Schengen countries not listed above||X (U.S.)|
WHO continues to advise against the application of travel or trade restrictions to countries experiencing COVID-19 outbreaks.
Exit Restrictions, Travel Restrictions, and Internal Disruptions
Angola, Argentina, Bolivia, Colombia, Democratic Republic of the Congo, Ecuador, Ethiopia, Guatemala, India, Kenya, Kuwait, Morocco, Pakistan, Panama, Peru, Tunisia, Saudi Arabia, and the United Arab Emirates have closed their borders and restricted all air travel in and out of the country, making it difficult for citizens of other nations to repatriate. Algeria, Bolivia, Burma (Myanmar), Chile, Curaçao, El Salvador, Guadeloupe, Honduras, Malaysia, Martinique, South Africa, Turkey, Ukraine, Uruguay, and Venezuela are in the process of implementing similar measures.
According to WHO, more than 100 countries have now implemented some form of travel restriction. Different types of travel restrictions are in effect. Very few airlines are flying long-haul routes. China has ordered that each domestic airline only operate a single passenger flight per week from each country it serves and that each foreign airline operate a single passenger flight on a single route into China each week. Potential urgent travelers should check with booking websites.
Saudi Arabia is considering postponement of future mass gathering events (including Hajj 1441H) if the pandemic continues to escalate. Pilgrims are advised to defer conclusion of Hajj travel contracts until further guidance is provided. Entry into the country has already been suspended for the purpose of Umra and/or visiting the Prophet's Mosque in Medina and for travelers with a tourist visa from countries with a COVID-19 outbreak.
Land Borders with China Closed: Burma (Myanmar), Kyrgyzstan, Mongolia, North Korea, Russia (entire land border with China, except for the portion between Altai Republic and Nei Mongol Autonomous Region [Mongolia]); high speed rails, bus services, and ferry services are suspended, and all but 2 border crossings are closed in Hong Kong.
|Country/Union||No Travelers from Listed Countries1||Medical Certificate Required|
|European Union2||X (travelers from countries outside EU's external borders)|
|Algeria, Argentina, Aruba, Australia, Bahamas, Belize, Bhutan, Bolivia, Brazil, Canada, Chile, China, Colombia, Costa Rica, Cuba, Curaçao, Czech Republic, Denmark, Dominican Republic, Ecuador, El Salvador, Egypt, Estonia, Guatemala, Haiti, Honduras, Hong Kong, Indonesia, Jamaica, Jordan, Latvia, Lithuania, Mongolia, Namibia, Panama, Paraguay, Peru, Poland, Qatar, Russia, Saint Lucia, Saudi Arabia, Singapore, Saint Kitts and Nevis, Seychelles, Senegal, Sint Maarten, Slovakia, Sudan, Taiwan, Thailand, Trinidad and Tobago, Turks and Caicos, Uganda, Ukraine, Uruguay, Uzbekistan, Vietnam, Zimbabwe||X (all travelers; for CN: including foreign residents)|
|Angola||X (travelers from CN, ES, FR, IR, IT, KR, PT)|
|Antigua and Barbuda||X (travelers from CN, IR, IT, JP, KR, SG in past 28 days)|
|Azerbaijan||X (travelers from AE, BH, CN, IN, IR, IL, JP, KR, KW, MY, OM, QA, SA, US; excluding those with predeparture visas; the issuance of e-visas and visa on arrival has been suspended)|
|Bahrain||X (travelers from all 26 Schengen countries, CN, GB, HK, IR, IQ, JP, KR, LB, MY, or US, excluding nationals of BH, KW, OM, QA, SA, AE)|
|Bangladesh||X (AT, BE, BG, CH, DE, DK, EE, ES, FI, FR, GR, HR, HU, IE, IR, IS, IT, LI, LT, LU, LV, MT, NL, NO, PL, PT, RO, SE, SK, SI)||X (all travelers from CN, HK, IR, IT, KR, MT, TW with prearranged visas must have a medical certificate certified by the embassy)|
|Bermuda||X (travelers from countries with sustained community spread of COVID-19)|
|Bonaire, North Korea||X (travelers from CN [Hubei Province])|
|Botswana||X (travelers from AT, BE, CH, CN, DE, DK, ES, FR, GB, IN, IR, IT, JP, KR, NL, NO, SE, US)|
|Brunei, Malaysia||X (travelers from CN, EU, IR, JP, KR)||X (travelers holding passports or arriving from KR)|
|Burma (Myanmar)||X (nationals of CN can no longer obtain a visa on arrival or transit without a visa; travelers from Hubei, CN or Daegu and Gyeongbuk, KR in past 14 days)||X (travelers from KR who have been in areas other than Daegu and Gyeongbuk are required to present a medical certificate that proves no symptoms of acute respiratory illness prior to boarding)|
|Cambodia||X (travelers from DE, ES, FR, IR, IT, US)||X (all travelers)|
|Cayman Islands||X (travelers from all 26 Schengen countries, CN, IR, JP, KR, MC, SM, VA in past 14 days)|
|Comoros, Madagascar, Suriname||X (travelers from CN, IR; excluding US nationals)|
|Cook Islands||X (travelers who have transited or been in any country except for NZ in past 14 days)|
|Cyprus||X (all travelers, excluding those mentioned under medical certificates)||X (nationals and residents of CY, EU citizens, third country nationals working in CY, diplomats, foreign nationals who are students)|
|Equatorial Guinea, Laos, Mozambique, Northern Mariana Islands, Somalia, Sri Lanka||X (travelers from CN)|
|Fiji||X (travelers from CN, ES, EU, IR, IT, KR, US in past 14 days)|
|French Polynesia||X (all travelers; excluding nationals of FR and PF)||X (all travelers; certificate from ≤ 5 days prior to arrival)|
|Gabon||X (travelers from all 26 Schengen countries, BG, CN, CY, GB, HR, IE, KR, MC, RO, SM, US, VA in past 14 days)|
|Grenada||X (travelers from CN, EU, IR, KR, US)|
|Guadeloupe, Guyana, Martinique, Montserrat||X (all international air travelers)|
|Guam||X (travelers who have been in a country with confirmed COVID-19 cases for > 7 days must have a document certified by Guam Department of Social Health and Services from ≤ 7 days before arrival)|
|India||X (travelers from all 26 Schengen countries, BG, CY, GB, HR, IE, TR)||X (IT, KR)|
|Iran||X (travelers from CN)||X (nationals of CN, HK, MO) visa issued by Indonesian Embassy|
|Iraq||X (travelers from BH, CN, ES, FR, HK, IR, IT, JP, KR, KW, MO, SG, TH)|
|Israel||X (all travelers, except those who will stay in Israel for > 14 days and are able to provide a phone number and address of a person in Israel who can provide them with home quarantine)|
X (travelers from CH (Canton of Ticino or Basel-Stadt), CN [Hubei and Zhejiang provinces], ES (Community of Madrid, Basque Autonomous Community, La Rioja or Chartered Community of Navarre), IR [Alborz, Golestan, Isfahan, Lorestan, Markazi, Mazandaran, Qazvin, Semnan, Qom, Tehran, or Gilan provinces], IS, IT [San Marino, Emilia-Romagna, Lombardy, Marche, Piedmont, Veneto], KR [Daegu, Cheongdo, Gyeongsan, Andong, Yeongcheon, Chilgok, Uiseong, Seongju, or Gunwi] in the past 14 days)
(visas issued on or before March 8, 2020, by the embassies, consulates-general, and consulate of CN, HK, JP, KR are invalidated)
|Kazakhstan||X (nationals of CN, HK, MO; travelers from CN)|
|Kiribati||X (travelers from AE, AU, CN, DE, EG, ES, FR, GB, IT, JP, KR, MY, SG, TH, US, VN)||X (travelers who have been in AE, AU, EG, DE, FR, GB, IT, JP, KR, MY, SG, SP, TH, UK, US, VN must 14-day self-quarantine in a country not affected by COVID-19 and provide a medical clearance)|
|Kosovo||X (CN nationals)|
|Lebanon||X (travelers from CN, HK, IR, IT, KR, MO, TW in past 14 days)|
|Macau||X (all travelers)||X (foreign nationals from Hubei Province in past 14 days)|
|Maldives||X (travelers from CN, IR, KR [Daegu, Gyeongbuk, Busan, Seoul, Gyeonggi, Gyeongnam] in past 14 days)||X|
|Marshall Islands, Palau, Papua New Guinea||X (travelers from CN, HK, MO in past 14 days)|
|Mauritius||X (travelers from AT, BE, BG, CH, CN, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HK, HR, HU, IE, IR, IT, KR, LV, LT, LU, MO, MT, NL, PL, PT, RE, RO, SE, SI, SK, TW in past 14 days)|
|Micronesia||X (travelers from COVID-19–affected countries in past 14 days)||X (travelers from a country not affected by COVID-19 for ≥ 14 days who were previously in a COVID-19–affected country)|
|Nauru||X (travelers from CN, HK, IR, IT, KR, MO)|
|Nepal||X (travelers from CN, DE, ES, FR, HK, IR, IT, JP, KR, MO, TW)||X (nationals from CN, HK, IR, IT, JP, KR, MO)|
|New Zealand||X (travelers from CN, IR in past 14 days)|
|Niue||X (nationals of CN)||X (foreign nationals from a country not affected by COVID-19 for ≥ 14 days who were previously in CN; certificate from ≤ 3 days prior to arrival)|
|Nigeria||X (travelers from CH, CN, DE, ES, FR, GB, IR, IT, JP, KR, NL, NO, US)|
X (nationals of CN, IR, IT [excluding those with resident visas issued by OM])
(nationals of AE, BH, KW, QA, SA are no longer allowed to enter with a national ID card and must have a passport)
|Pakistan||X (all travelers)|
|Philippines||X (travelers from CN, HK, KR [Gyeongbuk], MO in past 14 days, excluding nationals of Philippines)|
|Samoa||X (all travelers; certificate from ≤ 3 days prior to arrival; travelers from BH, CN, DE, ES, FR, HK, IR, IT, JP, KR, KW, MO, SG, TH, TW 14-day self-quarantine in a country not affected by COVID-19)|
|Sint Maarten||X (travelers [including airline crew] from CN, HK, IR, IT, JP, SK, SG in the past 14 days are not allowed to transit or enter)|
|Solomon Islands||X (travelers from CN, HK, IR, IT, JP, KR, MO, SG, TH, TW in past 14 days)|
|South Africa||X (travelers from CN, DE, ES, FR, GB, IR, IT, KR, US)|
|South Korea||X (travelers from CN in past 14 days)||X (travelers from AT, BE, BG, CH, CN, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HK, HR, HU, IE, IR, IS,IT, JP, LI, LT, LU, LV, MO, MT, NL, NO, PL, PT, RO, SE, SK, SI)|
|Tajikistan||X (CN nationals and travelers from CN [who are nationals of AF, IR, IT, KR])|
|Timor-Leste||X (travelers from CN [Hubei Province])||X (all foreign nations in CN in past 4 weeks)|
|Tonga||X (travelers from CN)||X (all foreign nationals in CN > 14 days prior to arrival; certificate from ≤ 3 days prior to arrival)|
|Turkey||X (travelers from AE, AT, AZ, BE, CH, CN, DE, DK, EG, ES, FR, GB, IE, IQ, IR, IT, KR, MN, NL, NO, SA, UA, XK)|
|Tuvalu||X (travelers from CN in past 30 days)||X (travelers from HK, JP, SG, TH; certificate from ≤ 3 days prior to arrival)|
|United Arab Emirates||X (all travelers; except nationals of AE, BH, KW, OM, SA)|
|United States||X (travelers from all 26 Schengen countries, CN, GB, IE, IR, MC, SM, VA in past 14 days)|
|Vanuatu||X (travelers from any country with > 100 COVID-19 cases)||X (all travelers)|
Abbreviations: AE = United Arab Emirates, AF = Afghanistan, AM = Armenia, AO = Angola, AR = Argentina, AT = Austria, AU = Australia, BD = Bangladesh, BE = Belgium, BG = Bulgaria, BH = Bahrain, BN = Brunei, BO = Bolivia, BT = Bhutan, BY = Belarus, CA = Canada, CH = Switzerland, CN = China, CO = Colombia, CY= Cyprus, CZ = Czech Republic, DE = Germany, DK = Denmark, DZ = Algeria, EE= Estonia, EG = Egypt, ES = Spain, ET = Ethiopia, FI= Finland, FJ = Fiji, FR = France, GB = United Kingdom, GE = Georgia, GF = French Guiana, GR = Greece, GY = Guyana, HK = Hong Kong, HR= Croatia, HU= Hungary, IE = Ireland, IL = Israel, IN = India, IQ = Iraq, IR = Iran, IS= Iceland, IT = Italy, JP = Japan, KH = Cambodia, KG = Kyrgyzstan, KI = Kiribati, KN = Saint Kitts and Nevis, KR = South Korea, KW = Kuwait, KZ = Kazakhstan, LB = Lebanon, LI = Liechtenstein, LK = Sri Lanka, LT= Lithuania, LU= Luxembourg, LV= Latvia, MC = Monaco, MO = Macau, MT= Malta, MV = Maldives, MY = Malaysia, NG = Nigeria, NL= Netherlands, NO= Norway, NP = Nepal, NR = Nauru, OM = Oman, PE = Peru, PG = Papua New Guinea, PH = Philippines, PK = Pakistan, PL = Poland, PT = Portugal, PY = Paraguay, QA = Qatar, RE = Reunion, RO= Romania, RU = Russia, SA = Saudi Arabia, SC = Seychelles, SE= Sweden, SG = Singapore, SI = Slovenia, SK = Slovakia, SM = San Marino, SR = Suriname, SU = Sudan, SY = Syria, TH = Thailand, TR = Turkey, TW = Taiwan, US = United States, UY = Uruguay, UZ = Uzbekistan, VA = Vatican City, VE = Venezuela, VN = Vietnam, VU = Vanuatu, XK = Kosovo
China: Restrictions on movement throughout the country are lessening. Bars, restaurants, shops, businesses, schools, museums, and many major tourist attractions are slowly reopening across the country, with some restrictions in place; workplaces are capped at 50% of usual staffing levels, and all workers must remain at least 1 m (3 ft) apart. Face masks are required to be worn while in public in Beijing and Guangzhou, and temperature screenings occur at entrances of public places (including hospitals). China has stopped all inbound and outbound tour groups but not individual travel. Travel restrictions in and out of Hubei Province have been removed, except for Wuhan, which will reopen on April 8.
Europe: The European Union has closed its external borders until at least mid-April. Several European countries have banned public gatherings, including those as small as 3 people in Germany; have closed schools, cultural and religious institutions, and public spaces (including bars and restaurants); and have closed or restricted public transportation. Many governments have reduced the number of public services being offered and the number of public-sector employees in the work environment. Several large European businesses have banned or restricted international business travel and have canceled business meetings and conferences. France, Italy, Spain, Germany, the U.K., and other countries have ordered their residents to stay at home (except for travel to work, medical visits, and essential shopping), have banned public gatherings, and have closed all nonessential businesses. Italy's and Spain's health care systems are overwhelmed, with ICUs at capacity and shortages of hospital staff and supplies.
Hong Kong: Bars are closed until mid-April, and schools will remain suspended until at least April 20. Companies have been urged to allow telecommuting and flexible hours for workers. Public gatherings of more than 4 people have been banned. Persons are encouraged to maintain a suitable social distance (2 m [6 ft] from others), limit public outings, avoid crowded places, wear face masks, and observe hand and respiratory hygiene.
Japan: All major indoor events have been canceled or postponed in Tokyo and large-scale indoor and outdoor events in other areas of the country have also been canceled or postponed. Companies have been urged to allow telecommuting for workers. All schools have been temporarily closed through March. Tokyo has asked residents to avoid nonessential outings until April 12.
Singapore: Gatherings of 10 or more people are prohibited. All schools are closed until May 5. All businesses, including restaurants, bars, amusement parks, museums, and casinos, are closed, except for essential services. People are encouraged to wear face masks in public, to stay home as much as possible, to avoid socializing in groups, and to only go out for essential items.
South Korea: The southern cities of Cheongdo, Daegu, and Gyeongsan have been declared "special care zones," with schools, markets, and restaurants closing in some neighborhoods and a ban on all large public gatherings. Travel has not been restricted to and from Daegu and Cheongdo, although residents have been asked to stay home and wear face masks (even indoors) if possible. In Seoul, large public gatherings and protests have been banned. All individuals who have come within 2 m (6 ft) of a symptomatic COVID-19 case have been asked to self-quarantine for 14 days.
U.S.: At least 297 million people in 38 states, Washington, D.C., 48 counties, 14 cities, and Puerto Rico have been ordered to stay at home except for critical outings and have closed all nonessential businesses until at least the end of April 2020. Other states have closed schools, museums, bars, restaurants, houses of worship, and large gathering places. Many universities have moved to online classes. The U.S. CDC is recommending that all events and mass gatherings with 50 or more people should be canceled; local and state guidelines may differ. Professional and college sporting events have been canceled or postponed indefinitely. People with underlying medical conditions and older persons should avoid large gatherings, air travel, and cruise travel. Shortages of medical supplies and protective gear are already hampering care in heavily affected states. The U.S. Department of Defense has halted all domestic travel for service members, Department of Defense civilians, and their families until May 11. Domestic travel to NYC is discouraged, and people who have recently left the city have been asked to self-quarantine for 14 days. The U.S. CDC now recommends that residents of the states of New York, New Jersey, and Connecticut refrain from nonessential domestic travel for 14 days effective immediately because of the extensive community transmission in the area. This advisory does not apply to critical infrastructure employees (e.g., HCWs or financial, food supply, or trucking services).
The U.S.-Canada border is temporarily closed to nonessential traffic; trade and commuters will continue to cross the border but travel for recreation and tourism is banned.
The detailed epidemiology of possible causative animal exposures and zoonotic transmission at the outset of the outbreak remains unclear. Many (67%) of the cases in December 2019 and approximately 50% of cases in January 2020 were directly linked to the South China Seafood City market in Jianghan District, which sold seafood and other wildlife (including birds). Thirty-three environmental samples from the market tested positive for SARS-CoV-2, indicating that the market was an–or the–origin or amplification point of the large-scale outbreak. No samples taken directly from live animals have been reported as positive. The symptom-onset date of the first case identified in the outbreak was December 1, 2019; the case reported no exposure to the market. No epidemiological link has been detected between this case and later cases. An initial single jump of SARS-CoV-2 directly from bat to human, or from an intermediate animal host to a human, with subsequent initial human-to-human propagation within the seafood market, is likely. Infected intermediate animal hosts, if they exist, may still be present, but the sale of live animals in markets in China has officially ceased. Existing incomplete but published data indicate pangolins as the leading candidate.
All evidence to date suggests that the main route of transmission is via respiratory droplets or close contact with an infected person. Aerosolized transmission occurs during medical procedures and perhaps more broadly in hospital settings. A new study in Nature Medicine examined seasonal human coronaviruses (related to SARS-CoV-2), influenza viruses and rhinoviruses in exhaled breath and coughs of children and adults with acute respiratory illness. Surgical face masks significantly reduced detection of coronavirus RNA in aerosols (masks 0/11 vs. no masks 4/10 subjects), with a trend toward reduced detection of coronavirus RNA in respiratory droplets (masks 1/27 vs. no masks 6/23 subjects). Of note, these findings also indicate that the majority of participants with coronavirus infection did not shed detectable virus RNA in respiratory droplets or aerosols at all. The study did not examine the infectivity of the coronavirus RNA detected in exhaled breath by PCR.
A reproductive number, R0, is estimated at 2–3 both by Chinese authorities and by multiple other international estimates. R0 greater than 1 indicates that each case leads to more than 1 subsequent case, making control much more difficult. R0 is not a constant number and changes with the ongoing circumstances and evolution of an outbreak. Viral loads peak in the first 5 days after symptom onset and coronavirus RNA may be detected for up to 21 days. No culturable virus has been detected for longer than 8 days after symptom onset. Additionally, the viral load in asymptomatic persons is similar to that in the symptomatic persons.
SARS-CoV-2 was grown in culture from nasopharyngeal swabs from 9 pre- or minimally symptomatic infected contacts of a minimally symptomatic index case from Wuhan at a Munich business meeting. Such minimally symptomatic persons have some importance in transmission. A rigorous U.S. CDC study of a U.S. nursing-home outbreak, in a highly infectious environment with a high attack rate (30%), demonstrated that only 3 of 23 COVID-19 cases remained completely asymptomatic throughout the course of their infection, further reinforcing that rates of true asymptomatic infection are low. WHO has reinforced this low level of truly asymptomatic infection based on available data from China and other countries. Rates of presymptomatic individuals who may be infectious to others still require further study and are certainly much higher.
During 14 days of active symptom monitoring of 445 close contacts (of the initial 12 imported confirmed U.S. COVID-19 cases), 54 (12%) developed symptoms and subsequently were tested for SARS-CoV-2. Two persons who were household contacts tested positive for SARS-CoV-2, for an overall symptomatic secondary attack rate of 0.45% and a symptomatic secondary attack rate of 10.5% among close contacts who were household members. Close contact was defined as either having spent at least 10 minutes within 2 m (6 ft) of the patient or having spent time in the same air space (e.g., the same examination room) for 0 to 2 hours after the confirmed COVID-19 patient.
Chinese researchers followed 391 people (who were diagnosed with COVID-19 based on their symptoms) and 1,286 of their close contacts to see whether the contacts would test positive for the virus even if they had not shown symptoms. Overall, the team found that children younger than 10 years who were potentially exposed to the virus were just as likely to become infected as other age groups, with about 7% to 8% of contacts of known cases later testing positive. Whether children are important in transmitting the virus, as they are with influenza, is not addressed by this study.
A careful analysis from Singapore shows that, up until March 16, in 7 clusters of cases totaling 157 locally acquired cases, 10 of the cases (6.4%) included likely presymptomatic transmission of COVID-19.
Limited experience indicates that no vertical transmission (from mother to fetus or newborn before, during, or immediately after delivery) of SARS-CoV-2 has been reported; SARS-CoV-2 was not detected in samples of amniotic fluid, and all infants tested negative. Limited data are available for vertical transmission for other coronaviruses (MERS-CoV and SARS-CoV).
Based on the limited data to date, SARS-CoV-2 has not been detected in the breast milk of infected women. Symptomatic mothers well enough to breastfeed should do so and wear a face mask and observe hand hygiene; symptomatic mothers not well enough to breastfeed should wear a face mask and observe hand hygiene while expressing milk for bottle feeding. Reports of breastfeeding women infected with SARS-CoV in 2002-03 were limited. The virus was not detected in breast milk, but SARS-CoV antibodies were detected in at least 1 sample.
A study from the U.S. National Institutes of Health showed that inocula of SARS-CoV-2 at 21-23°C (69.8-73.4°F) and 40% RH remained culturable for up to 72 hours on plastic and stainless steel, for 24 hours on cardboard (simulates packaged products), and for 4 hours on copper. SARS-CoV-1 remained culturable for up to 72 hours on plastic, for 48 hours on stainless steel, and for 8 hours on either cardboard or copper. Artificially generated aerosols (nebulizer; 21-23°C [69.8-73.4°F] and 65% RH) were collected at intervals over a 3-hour period, and both viruses remained viable and detectable throughout the 3-hour duration of the experiment. Variations of heat and humidity and viability in different matrices (such as nasal secretions, sputum and fecal matter) were not examined. A study from Hong Kong using virus suspended in growth media indicated viability on the outside of surgical masks for 7 days in comparison to less than 1 day on tissue paper or cloth.
Historically, studies have demonstrated survivability of zoonotic coronaviruses on different surfaces ranging from a few hours up to 9 days (longest on plastic) depending on ambient conditions, including temperature, humidity, and the specific infected bodily fluid contaminating the surface. The risk of spread is very low from items shipped at ambient temperatures over several days. No evidence exists of SARS-CoV-2 transmission associated with imported goods; no associated cases have been reported to date.
See Survival on Surfaces.
Disinfection processes that are effective for other zoonotic coronaviruses should be followed for now. Clean daily all "high-touch" surfaces, such as counters, tabletops, hard-backed chairs, doorknobs, light switches, handles, desks, bathroom fixtures, toilets, phones, remote controls, keyboards, tables, and bedside tables. Also, clean any surfaces that may have blood, bodily fluids, and/or secretions or excretions on them. After cleaning solid materials using a detergent, use a diluted bleach solution or a household disinfectant with a label that says "EPA-approved." To make a bleach solution, add 20 mL (4 teaspoons) of bleach to 1 L (1 quart) of water; for a larger supply, add 75 mL (5 tablespoons) of bleach to 4 L (1 gallon) of water. For surfaces sensitive to bleach, at least 70% ethanol should be used. Alcohol-based hand disinfectants and common hospital personal disinfectants are all effective against SARS-CoV-2 but provide no ongoing protection between uses.
Modeling data from a leading group in the U.K. suggest that, even with optimal suppression strategies in the U.S. and the U.K., the epidemic might last as long as it takes for a vaccine to be available, possibly 18 months or more. The model shows that relaxation of suppression could lead to an immediate rebound to peak epidemic levels. Suppression, as defined, includes social distancing in all community settings (remaining out of congregate settings [crowded places such as shopping centers, movie theaters, and stadiums], avoiding mass gatherings and public transportation, and maintaining a distance of 2 m [6 ft] from others) for the entire population, home isolation of all cases, isolation of all household members, and rigorous and rapid testing capability. Models are useful tools but are only as good as each of their many (up to dozens) assumptions; 1 or more weak assumptions based on the lack of significant knowledge of a parameter at the time the model is run can dramatically change the findings. Several assumptions in all the current models are based on data made available from the Chinese outbreak; the data suffer from weak initial testing capability and case ascertainment, and some data components may be partially fictionalized. Assumptions on asymptomatic infection rates are not based on population-based antibody studies, and assumptions on asymptomatic transmission are based largely on household transmission and not random community transmission. Robust data from Singapore that included meticulous, state-of-the-art electronic contact tracing and rapid testing indicated almost all transmission to be via close contacts. Many of the models assume much higher asymptomatic transmission rates in the community.
Interventions across 11 European countries modeled will have averted 59,000 deaths (through March 31; [95% credible interval 21,000-120,000]) and that more deaths will be averted by ensuring that interventions remain in place until transmission drops to low levels. The estimate is that, across these 11 countries, between 7 and 43 million individuals have been infected with SARS-CoV-2 (through March 28), representing between 1.88% and 11.43% of the population. The ultimate long-term effect of interventions to date is still uncertain, and a continuation of efforts should be pursued.
A new model of the U.S. situation, based on assumptions derived from Chinese and other international experiences to date, indicates that if current lockdowns are sustained through April/May, the death toll in the U.S. will be approximately 80,000 (confidence range up to > 100,000). The epidemic will peak at different times; New York will be hit hardest and first, peaking over the next 10 days. Peaks in other states will range through April into May. Peak demand for ventilators nationwide will peak the second week of April at 20,000 ventilators, and peak demand for excess hospital beds above current availability and for ICU beds will be 65,000 and 17,000 respectively at that time. Evidence (including this model) is behind the indications for ongoing national mitigation measures at least through April 30.
Marked declines in transmission have occurred in a few areas of the world. Community household population serosurveys answering 2 important outstanding questions are imperative to inform the many predictive models and planning: How many infections are going undetected? What level of population-wide immunity is being attained?
As with all previous models discussed in Travax, models can be regarded as bases for worst-case scenarios for planning, given knowledge of current situations and current understanding of proposed or ongoing interventions; models need to be frequently rerun as knowledge evolves. Variables and intangibles (for which no current data exist) are only possible to include in future runs of the particular model. Other nonpharmaceutical and pharmaceutical preventions and treatments may come into play at uncertain times in the future, testing capacity will become more robust, and the rate of rise of immune individuals within a community is impossible to predict with a new organism. All models are wrong; some, however, are useful at the time they are run.
An incubation period of 2 to 7 days appears most common (5 days typical across many studies), with an upper range of 14 days. As with any infection, very small numbers of outliers with longer incubation periods have been reported. Most cases exhibit symptoms of fever, dry cough, progressing to breathlessness in the second week, and pneumonia in those who progress further; sputum production has been reported in one-third of cases; rhinitis is uncommon; 25% to 43% of patients are afebrile at the time of presentation. Loss of the senses of smell and taste as the first symptom of infection has been consistently reported in up to 100% of patients; no data have been published to date. CT scan findings include ground-glass opacification, consolidation, bilateral involvement in most, and peripheral and diffuse distribution. The sequence and evolution of these radiologic findings is not yet clear. Asymptomatic patients with CT scan abnormalities have been reported. CT scans may not offer information beyond what is in the chest x-ray of a patient in an intensive care unit. Up to 5% of patients with COVID-19 have developed acute respiratory distress syndrome. Mild illness may occur for up to 14 days, with late and often very acute onset of severe respiratory compromise; influenza has a much more sudden onset at the outset. White blood cell counts are typically normal, and a lymphocyte count of less than 1.5 x 109/L is frequently seen in patients. Abnormal liver function tests, especially LDH, appear to be common and may be a poor prognostic sign. Diarrhea may occur, but incidence has been highly variable in several cohorts. Based on both China CDC data and current U.S. experience in California and Washington, more than 80% of hospitalized cases have mild presentations, 14% are severe, and 5% are critical. Recovery time is about 2 weeks for persons with mild disease and 3 to 6 weeks for persons with severe or critical disease, many of whom require intensive care.
Among 7,000 U.S. COVID-19 patients with available data on underlying disease, the percentage with at least 1 underlying health condition was higher among those requiring ICU admission (78%) and those requiring hospitalization without ICU admission (71%) than that among those who were not hospitalized (27%). Among patients aged ≥ 65 years, the percentage of non-ICU hospitalizations was higher among those with underlying health conditions (43.2%) than among those without underlying health conditions (17.5%); the percentage of cases that resulted in an ICU admission was also higher for those with underlying health conditions (21.5%) than those without these conditions (6.2%). Among all patients aged ≥ 19 years, the percentage of non-ICU hospitalizations was higher among those with underlying health conditions (28.5%) than among those without underlying health conditions (7.5%); the percentage of cases that resulted in an ICU admission was also higher for those with underlying health conditions (13.9%) than those without these conditions (2.3%). Underlying health conditions or risk factors included chronic lung disease (including asthma, chronic obstructive pulmonary disease, and emphysema); diabetes mellitus; cardiovascular disease; chronic renal disease; chronic liver disease; immunocompromising condition; pregnancy; current smoker; former smoker; or other chronic disease.
A new randomized controlled trial from Wuhan, China (still in pre-print format) compared 31 patients treated with hydroxychloroquine with standard of care. Improvement of COVID-10 pneumonia occurred in 81% of study patients compared to 54% of control patients. All 4 patients who progressed to severe illness were in the control group. Two previous uncontrolled trials in a small number of patients, 1 in China and 1 in France, indicated dramatic effects of hydroxychloroquine or chloroquine on viral replication in humans. In contrast, a small randomized pilot trial published in the Chinese literature indicated no difference in outcomes between placebo and hydroxychloroquine arms. Data on eventual outcomes in large well-designed trials are unclear, but no other drug data have been published to indicate viral suppression by any other drug in humans. Hydroxychloroquine is more potent in vitro than chloroquine against SARS-CoV-2 and is safer due to lesser effects on cardiac QT intervals.
An FDA EUA (not an FDA approval) has been issued for the use of chloroquine phosphate and hydroxychloroquine sulfate (by prescription only) for the treatment of hospitalized COVID-19 adolescent and adult cases weighing ≥ 50 kg (110 lb) for whom a clinical trial is not available, or participation is not feasible. The EUA only applies to medication donated to and supplied by the SNS to state PHA; to date, 30 million doses of hydroxychloroquine sulfate (Sandoz) and 1 million doses of chloroquine phosphate (Bayer Pharmaceuticals) have been donated. These medications are in short supply in outpatient settings in the U.S. but the SNS supply is unaffected. Some manufacturers have hydroxychloroquine available and others have it on allocation, with priority for existing customers; larger shipments of chloroquine are scheduled for the next 8 months. The safety profiles of these medications have only been studied for FDA-approved indications (e.g., lupus, malaria, rheumatoid arthritis). The optimal dosing and duration of treatment for both medications are unknown; the following suggested dosing may be updated as data from clinical trials become available.
- Hydroxychloroquine sulfate: 800 mg on day 1, followed by 400 mg daily for 4 to 7 days based on clinical evaluation
- Chloroquine phosphate: 1000 mg on day 1, followed by 500 mg daily for 4 to 7 days based on clinical evaluation
No other oral drug options for noncritical patients are offered by U.S. CDC. Due to unmanageable demand, intravenous remdesivir, the most promising drug candidate, is no longer available in the U.S. for compassionate use, except for in severely ill pregnant women and children younger than 18 years. Patients with pneumonia alone or pneumonia and hypoxia may be enrolled as part of a placebo-controlled trial in a small but increasing number of academic centers. An alternative expanded-access scheme for patients who are ineligible for remdesivir clinical trials will be implemented in the next few days. WHO has prioritized 4 drugs for a randomized (but unblinded) comparative multinational trial with simplified data and outcomes entered on a central server at WHO; the drugs are remdesivir, hydroxychloroquine/chloroquine, lopinivir/ritonavir, and lopinivir/ritonivir plus interferon-beta. Through a patient emergency Investigational New Drug Applications program, the FDA has approved convalescent plasma for the treatment of serious or immediately life-threatening COVID-19 infections.
Lopinavir/ritonavir (readily available as Kaletra in most countries) was used empirically in China and elsewhere but appears to have little effect. No preliminary studies to date have shown a beneficial effect of tocilizumab on critical patients with cytokine storm syndrome. Studies of over 70 other drugs are ongoing worldwide, and only the most promising agents endorsed by U.S. CDC, WHO, FDA, EMA or data on randomized controlled trials will appear in Travax. Usual antiviral drugs (including oseltamivir [Tamiflu] and acyclovir) are ineffective. Steroids should not be used.
According to the American Heart Association, the American College of Cardiology, and the Heart Failure Society of America, COVID-19 patients who have underlying hypertension, heart failure, or ischemic heart disease should not stop taking their angiotensin-converting–enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs). WHO, the FDA, and the EMA have now stated that no scientific evidence establishing a link between ibuprofen and worsening of COVID-19 exists. Data from unrelated French studies should not be overinterpreted at this time, and ibuprofen may be used in COVID-19–infected persons as needed.
Reports of reinfection or relapse in recovered and discharged cases in China and Japan should be regarded with caution. These recovered cases later tested positive again for SARS-CoV-2 by RT-PCR; however, RNA detection in human bodily fluids is not proof of infectivity or even of viral viability. Late presence of RNA more likely represents excretion rather than current presence of live virus in the sample fluid. A similar situation occurs with Zika virus, where RNA can be detected in semen for up to 1 year, but viral cultures could only detect viable Zika virus for approximately 30 days in a large study cohort.
Pregnant women are generally more susceptible to viral respiratory infections, including COVID-19. Adverse pregnancy outcomes (pregnancy loss, low birth weight, preterm birth) have occurred with influenza viruses and other related coronaviruses (MERS-CoV and SARS-CoV). No data are available regarding pregnancy loss in women with COVID-19, but preterm birth has been reported based on limited case reports. High fevers (from any cause) during the first trimester increase the risk of certain birth defects. No information is available on long-term health effects of SARS-CoV-2 infection in utero.
SARS-CoV-2 was initially isolated and the genome was published internationally by Chinese scientists on January 10. Electron microscopy demonstrates classic coronavirus particles. SARS-CoV-2 is the seventh member of the family of coronaviruses that infect humans. Novel coronaviruses from Wuhan, together with 2 bat-derived SARS-like strains, form a distinct clade in lineage B of the subgenus sarbecovirus. SARS-CoV-2 is a group 2b coronavirus (as are MERS-CoV and SARS-CoV), with a whole genome similarity of up to 80% to SARS-CoV but with a similarity between different gene segments ranging from 60% to 90%. SARS-CoV-2 exhibits a 96.5% similarity to the known bat coronavirus precursors in the same viral clade. The cellular infectivity of isolated viruses can be completely neutralized by the sera collected from convalescent patients. Transgenic human ACE2 mice and Rhesus monkeys intranasally challenged by this virus isolate induced multifocal pneumonia with interstitial hyperplasia; SARS-CoV-2 was detected and isolated in the lung and intestinal tissues of the challenged animals.
In the most sophisticated and authoritative analysis of the available data to date, 2 notable features of the SARS-CoV-2 genome have been identified: 1) the presence of a uniquely configured receptor binding domain (RBD) on the virus, which appears to be optimized for binding to the human ACE2 receptor and 2) a polybasic (furin) cleavage site on the protein spike extending from the virus surface. Several important observations have been made, although proof awaits. Pangolin CoV is identical to SARS-CoV-2 at all 6 key RBD residues, but no pangolin CoV (which does not carry the polybasic cleavage site insertion) has yet been identified that is sufficiently similar to SARS-CoV-2 across its entire genome to support direct human infection. A possibility exists that a progenitor to SARS-CoV-2 jumped from animals to humans, with the genomic features described above acquired through adaptation during subsequent human-to-human transmission. Once these adaptations were acquired (either together or in series), it would have enabled the outbreak to accelerate. If SARS-CoV-2 preadapted in an animal species (pangolin or other), then risk exists for future reemergence events in the continued presence of the intermediate animal host, even if the current epidemic is controlled. In contrast, if the described adaptive process occurred in humans, then even with repeated zoonotic transfers in the future, human transmission is unlikely to accelerate unless the same series of mutations occurs; this seems less likely.
The analysis above also provides evidence that SARS-CoV-2 is neither a laboratory construct nor a purposefully manipulated virus. SARS-CoV-2 is not derived from any previously used or known virus backbone. Although SARS-CoV-2 is well suited to human infection, the unique RBD is not structured in such a way that someone with intent to manipulate would have predicted using current computational models and previously known coronavirus constructs. In terms of mutations introduced by repeated artificial laboratory passage of existing viruses, new polybasic cleavage sites have only been observed after prolonged passaging of low pathogenicity avian influenza virus (not coronaviruses) in cell culture or animals. Thus, although genomic evidence does not in any way support the idea that SARS-CoV-2 is a laboratory construct, proving or disproving any other theories of its origin is not completely possible at this time.
Evidence from subsequent whole genome sequences acquired over the past several weeks show little genetic variation, indicating that the virus jumped from an animal reservoir to humans within the past few months.
In the U.S., an FDA EUA has been granted for more than 20 RT-PCR tests (https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#2019-ncov), with more than 1,000,000 of the Roche cobas SARS-CoV-2 testing kits in place in many large commercial and health-system laboratories already equipped with cobas high-throughput analyzers. The ID NOW COVID-19 (Abbott Diagnostics) test has received an EUA from the FDA for the detection of SARS-CoV-2 RNA. The tabletop ID NOW analyzer has a wide installed base in clinics, acute care centers, and individual medical practices. Although results are available in a maximum of 15 minutes, only 1 sample can be run at a time in the machine, limiting daily throughput.
All states are able to authorize tests developed and used by laboratories in their states without federal oversight, but U.S. CDC testing guidelines must still be met; an EUA will not be pursued for these tests. Cities in at least half the states across the U.S. have opened drive-through stations to test symptomatic persons; plans are being made to expand these testing services across the country. Testing capacity across the U.S. is more than 110,000 patients per day but may be adversely affected by a decreasing availability of reagents, nasal swabs, and viral transport media; capacity varies by individual laboratory. Possible alternatives to the preferred viral transport media/universal transport media include liquid Amies-based transport media or a dry swab in saline. Using these alternatives, storage can be up to 72 hours at 4°C (39°F) or frozen for longer storage without meaningful degradation of the RNA. Calcium alginate swabs or swabs with wooden shafts may inactivate the virus and inhibit PCR testing and should not be used.
The 2 largest commercial reference laboratories in the U.S., Quest Diagnostics and LabCorp, are able to receive and test specimens (collected in hospitals or provider offices and that meet U.S. CDC clinical and/or epidemiological criteria for testing) for SARS-CoV-2; neither company's service centers collect respiratory specimens from suspected COVID-19 cases. Quest Diagnostics' testing turn-around time is 4 to 5 days (2-3 days for hospitalized patients and symptomatic HCWs) and they can process more than 25,000 tests per day; ordering of the Roche cobas SARS-CoV-2 test is encouraged. LabCorp's turn-around time is 4 to 5 days, and they can process more than 20,000 tests per day; options are being explored to prioritize testing of hospitalized patients. More than 50 brands of commercially available diagnostic test kits (FDA notified or EUA planned or submitted) are available.
Testing criteria in the U.S. allow clinicians to use their clinical judgement if an ill patient has signs and symptoms compatible with COVID-19, but an adequate supply of test kits is still lacking. Testing kits for routine respiratory pathogen testing, needed to rule out other respiratory agents and stimulate testing for SARS-CoV-2, are now in short supply as well. See Criteria for Testing of Suspected Cases.
HKU1, NL63, 229E, and OC43 are human coronaviruses that are detected by some routine multiplex PCR panels used in routine clinical practice. These coronaviruses are associated with minor upper respiratory infections and viral pneumonia, but unlike SARS-CoV, MERS-CoV, and SARS-CoV-2, these agents are not associated with major outbreaks or severe respiratory distress syndrome.
SARS-CoV-2–specific blood antibody detection tests that would be especially useful for population-based studies to detect asymptomatic individuals are unavailable, even in research laboratories. Two laboratories, 1 in the U.S. and 1 in Europe, have published robust protocols. These standard antibody ELISA format tests will also be commercialized soon. Although detection of IgG will be presumed to indicate immunity, the overall sensitivity and specificity of these tests will require rigorous validation.
Point-of-care rapid antibody tests do not generally perform well in asymptomatic individuals with low pretest probability of infection (such as travelers); even with a specificity of ≥ 98% in a low-risk population, more than 90% of positive tests will be false positives. Such tests work better on ill people in epidemic areas, where the pretest probability is high. Nevertheless, development and proper validation of such tests is technically much more difficult than with RT-PCR tests that detect replicating virus directly and can be assumed highly accurate no matter the source. A large number of such point-of-care antibody tests, mainly from small diagnostics companies, have appeared and are being heavily marketed worldwide. Under recently relaxed FDA guidelines, manufacturers can develop, ship, and sell the tests once validated in-house, and they can be used by the purchaser while an EUA submission/approval is being developed and is pending. Only minimal performance data need to be posted on the manufacturer’s website and peer-reviewed publication is not necessary. Many manufacturers with letters of permission to ship tests and then submit an EUA application indicate that this is somehow consistent with an FDA approval. To date, only 1 antibody-based ELISA or point-of-care rapid antibody test has had an EUA approved by the FDA. The qSARS-CoV-2 IgG/IgM Rapid Test (Cellex Inc.) is limited to use by laboratories certified to perform moderate and high complexity tests. The test can produce results in 15 to 20 minutes and has a 94% positive percent agreement and a 96% negative percent agreement. However, a negative result does not preclude SARS-CoV-2 infection and should not be used as the sole basis for patient management decisions. The sensitivity of the test early after infection is unknown, and false positives for IgG and IgM antibodies may occur due to cross-reactivity. Shoreland cautions against the use of any serological test for definitive diagnosis or assessment of immunity against future infection prior to granting of EUA status by the FDA or similarly robust regulatory body. Only the most promising antibody tests endorsed in some way by U.S. CDC, WHO, FDA, EMA or data from peer-reviewed trials will appear in Travax.
Criteria for Testing of Suspected Cases
Diagnostic testing availability is increasing and the criteria for evaluation of a PUI has widened to allow clinicians to use their clinical judgement for symptomatic persons with fever or signs/symptoms of lower respiratory illness (e.g., cough, shortness of breath). Testing priorities are designed to ensure optimal care, decrease community spread, and ensure the health of essential workers.
Priority 1: Ensure optimal care for hospitalized cases, lessen the risk of nosocomial infections, and maintain the integrity of the health care system
- Symptomatic hospitalized patients
- Symptomatic HCWs
Priority 2: Ensure that those at highest risk of poor outcome are rapidly identified and appropriately triaged
- Symptomatic residents of nursing homes or long-term care facilities
- Symptomatic persons aged ≥ 65 years
- Symptomatic persons with underlying medical conditions [diabetes, heart disease, chronic lung or kidney disease, moderate to severe asthma], immunocompromising conditions [including cancer treatment or use of immunosuppressive medications], or severe obesity [BMI > 40])
- Symptomatic first responders
Priority 3: As resources allow, test individuals in a community with rapidly increasing hospital cases to decrease community spread and to ensure the health of essential workers
- Symptomatic critical infrastructure workers
- Symptomatic persons not in one of the above categories
- Asymptomatic HCWs and first responders
- Mildly symptomatic persons in communities experiencing a high number of COVID-19–related hospitalizations
Nonpriority: Asymptomatic persons
Local epidemiology of COVID-19 as well as the clinical course of the illness should be considered in the decision making, and appropriate testing for other causes of respiratory infections (including influenza) should be performed.
WHO now recommends, as part of its case definition, that a contact includes a person who was exposed during the 2 days before and the 14 days after the onset of symptoms of a probable or confirmed case. Contact includes any amount of direct physical contact or face-to-face contact at less than 1 m (3 ft) for more than 15 minutes. Close contacts should be rapidly identified, quarantined early, and tested only if they are symptomatic; however, testing of asymptomatic contacts may be considered based on clinical judgement (e.g., high-intensity contact in a family, workplace, social, or health care setting).
Fever may be subjective or confirmed (≥ 37.8° C [100.4° F]). Close contact is defined as 1) being within 2 m (6 ft) of a confirmed COVID-19 case for a prolonged period and can occur while caring for, living with, or sharing a health care waiting area or room or 2) having direct contact with infectious secretions of a COVID-19 case (e.g., being coughed on). The precise definition of a prolonged period to be a close contact is left to a case-by-case assessment by public health authorities by U.S. CDC; however, in the case of the contact being in the health care setting, the definition (out of caution) has been set to more than 1 to 2 minutes. In Hong Kong and according to ECDC, the time limit for a close contact in the community setting has been set at more than 15 minutes of face-to-face exposure.
HCWs entering the room with a PUI should use standard precautions, contact precautions, airborne precautions, and eye protection (e.g., goggles or a face shield). PUIs for COVID-19 should be asked to wear a face mask as soon as they are identified and be evaluated in a private room with the door closed, ideally in an airborne-infection isolation room if available. Increased experience in the U.S. is indicating that contact and droplet isolation in a regular room is likely to be just as effective as placement in an airborne-infection isolation room, and care in practice is moving in this direction. The ideal outpatient scenario is a dedicated triage desk where any person with fever and/or upper respiratory infection symptoms would initially present (whether the patient comes as a walk-in or by ambulance). When patients come via EMS, the ambulance staff should be wearing N95 masks. The person working the triage desk should wear an N95 mask. Any PUI should be provided with a face mask at the earliest opportunity and should wear it at all times in the clinical spaces and upon leaving the clinic. PUIs should be escorted from the triage desk to a negative pressure examination and treatment area by personnel who are wearing N95 masks.
Selected clinic staff should provide services to the population of patients under investigation and should wear N95 masks. Staff that are not involved in this care do not need to take N95 mask precautions.
Avoidance of Health Care Settings
In the U.S., limited availability of PPE has meant that many HCWs have been exposed but are not being quarantined because all possible HCWs are needed to facilitate patient care. With limited available testing, many large hospitals have relaxed their guidelines regarding any exposure to a confirmed case, up to and including unprotected exposure (e.g., not wearing PPE) during an aerosolizing procedure. Exposed HCWs are immediately being sent back to work, with closely observed temperature monitoring for 7 days. Such persons will only be tested and sent home if symptoms develop. Persons in the U.S. should avoid presenting to hospitals with other than immediately life-threatening illness. Telemedicine visits should be utilized for all but essential care; routine vaccination of infants and young children aged ≤ 24 months is a top priority in the context of well-child care and should be prioritized when possible. Well visits and vaccination of older children may still be conducted or may be postponed to a later date depending on community circumstances and resources. Consider scheduling well visits in the morning and sick visits in the afternoon to reduce the risk of contagious-disease exposure.
The U.S. Drug Enforcement Agency, under the declaration of a public health emergency, has temporarily relaxed the controlled substance prescribing rules to allow providers to prescribe these medications using telemedicine, without the usual in-person medical examination.
Travel to Countries with Community Transmission
Travelers (especially those at higher risk of poor outcome, such as older adults and persons with underlying medical conditions) going to countries with community transmission should observe hand hygiene and social distancing and avoid contact with ill-appearing persons and animals (alive or dead), animal markets, and products that come from animals (such as uncooked meat). Those at higher risk of poor outcome should consider postponing travel, especially if by airplane or cruise ship. Current influenza vaccination is recommended to decrease the risk of simple influenza being mistaken for COVID-19 upon return.
An mRNA vaccine (mRNA-1273) encoding for a prefusion stabilized form of the spike (S) protein began a Phase 1 study of 45 volunteers in Seattle, Washington on March 16. Dozens of other vaccines are earlier in development. Most vaccines in development involve novel mechanisms of action or novel constructs; an effective vaccine for distribution is unlikely in less than 12 to 18 months. Preliminary data from primate experiments indicate acquired immunity to reinfection in animals recovered from a primary infection and development of diagnostic and protective antibodies in 10 to14 days. The negligible to slow mutation rate of SARS-CoV-2 to date indicates a single vaccine construct would be protective for subsequent years should SARS-CoV-2 become endemic.
Three comprehensive review papers by a highly established group in Hong Kong did not find evidence to support a protective effect of nonpharmaceutical interventions in preventing or substantially reducing influenza transmission during a pandemic. This conclusion reflects the poverty of the database, gaps in the understanding of the biology of influenza virus transmission, low adherence to preventive measures, and the inherent speed of pandemic transmission and spread of influenza. Evidence indicates that SARS-CoV-2 may transmit more like influenza than other zoonotic coronaviruses affecting humans; lessons here may be applicable to the current COVID-19 outbreak. See Literature Watch Review: Delaying the Spread of Influenza—A 3-Armed Policy Review of Nonpharmaceutical Measures for Pandemic Influenza in Nonhealthcare Settings.
All health authorities recommend that face masks be worn by symptomatic persons to prevent onward transmission (source control). Some health authorities recommend that face masks be worn by all persons to prevent onward transmission (source control) in order to encompass asymptomatic transmission. The U.S. CDC now recommends the optional use of non-medical grade cloth face coverings in public settings where other distancing measures are difficult. In practice, very few persons are able to use surgical or other masks appropriately for significant periods of time when out in the community, and the threshold level of implementation in asymptomatic persons that would have any effect on transmission is not clear. Consideration must also be given to the likelihood that almost all symptomatic persons are already at home or in the hospital. No population-based controlled trial of masks vs. no-masks during a pandemic has ever demonstrated efficacy of face masks. See Literature Watch Review: Delaying the Spread of Influenza—A 3-Armed Policy Review of Nonpharmaceutical Measures for Pandemic Influenza in Nonhealthcare Settings.
In the Workplace and Schools
To help prevent workplace exposure to acute respiratory illnesses, including COVID-19, U.S. CDC recommends that, beginning immediately, employers actively encourage (through generous leave policies) employees with fever (≥ 37.8° C [100.4° F]) using an oral thermometer), signs of fever, or symptoms of respiratory illness to remain at home, to observe hand hygiene (frequent, thorough handwashing with soap and water for 20 seconds [or using a hand sanitizer containing 60% alcohol]), to observe respiratory hygiene (cough and sneeze etiquette) and social distancing if possible, to avoid sharing of household items, and to avoid contact with pets or other animals. Employees who become ill at work should be immediately isolated from other employees and sent home. Employee education on the aforementioned measures should be aggressive. Worksite hygiene measures and worksite disinfection should be active and continuous.
Generous leave policies should also be applied to employees that must stay home to care for a sick household member. Contingency planning guidance is provided by U.S. CDC at https://www.cdc.gov/coronavirus/2019-ncov/guidance-business-response.html.
Shoreland guidance below requires that employees be asymptomatic for the specified period in order to return to work. The U.S. CDC symptom guidance stating an improvement in cough or shortness of breath only refers to discontinuation of home isolation and return to work for HCWs (who are desperately needed); no guidance is provided for non-HCWs returning to work. Employees, including HCWs, with confirmed or suspected COVID-19 should not return to work until they test negative for SARS-CoV-2 (at least 2 negative consecutive nasopharyngeal specimens collected ≥ 24 hours apart), are free of fever and other symptoms for ≥ 72 hours without the use of fever-reducing or other symptom-altering medications (e.g., cough suppressants), and ≥ 7 days have passed since symptom onset. HCWs returning to work early should wear a face mask until all symptoms are completely resolved or until 14 days have passed since symptom onset, whichever is longer; they should also avoid contact with severely immunocompromised patients until 14 days have passed since symptom onset.
Symptomatic persons who meet testing criteria (including older persons and those with underlying or immunocompromising medical conditions) but who have a negative test may return to work once asymptomatic (as noted previously) for ≥ 72 hours. Symptomatic persons who do not meet local COVID-19 testing criteria may return to work once asymptomatic for at least 24 hours, similar to the guidelines for influenza. In cases where employers nevertheless consider an employee to be a high risk of being positive for some reason, Shoreland recommends that the employer may choose to require either a negative COVID-19 test result or, if testing is not available or test status is not known, that ≥ 7 days have passed since symptom onset and the employee has remained asymptomatic for ≥ 72 hours before allowing a return to work. Asymptomatic persons with a positive test may return to work if ≥ 7 days have passed from the date of the positive test and they have remained asymptomatic.
Persons in critical infrastructure roles (e.g., emergency first responders and HCWs) may continue to work (at the discretion of state and local health authorities) following potential exposure to SARS-CoV-2 as long as they remain asymptomatic. These persons should self-observe (remaining alert for symptoms) and self-monitor (taking a temperature reading 2 times per day) under the supervision of their employer’s occupational health program; symptom assessment and a temperature reading should be taken prior to starting work.
The U.S. CDC guidance for K-12 schools and childcare programs is based on the level of community transmission (none, minimal to moderate, or substantial) and includes coordination with local health officials to determine the best course of action (e.g., social distancing for gatherings, classrooms, and movement through the building or extended dismissal). In general, if schools are closed then childcare programs should also close, with the exception of programs serving essential and emergency personnel. If a confirmed COVID-19 case enters a school building (regardless of community transmission), coordinate with local health officials, assess risk, and implement a short-term dismissal (2-5 days) of students and most staff; this allows time for disinfection, contact tracing, and further assessment of risk and appropriate mitigation efforts. K-12 school and childcare program closures will increase the risk to some older adults with underlying medical conditions because almost 40% of U.S. grandparents routinely provide childcare for their grandchildren.
Management of Asymptomatic Persons with Community of Direct Exposure to COVID-19
Specific contact tracing is not part of current mitigation measures in the U.S. and most European countries but is widely implemented in many Asian countries.
Arrivals who develop fever or respiratory symptoms within 14 days of travel to countries with community transmission should self-isolate; observe respiratory hygiene (cough and sneeze etiquette), hand hygiene, and social distancing; wear a face mask; and contact public health authorities (or telephone ahead before presenting to a hospital).
Management strategies for asymptomatic persons are based on the person's exposure category, as shown in Table 3.
|Exposure Category||Movement Restrictions and Public Activities||Monitoring|
Exposure in any country (all are considered to have widespread, sustained transmission)
Travel on a cruise ship or river boat
Remain at home or in a comparable setting until 14 days after arrival or last exposure.
Observe social distancing.
Avoid contact with persons at risk of poor outcome (unless they live in the same home and had the same exposure)
|Possible unrecognized community exposure2||Observe social distancing.||Self-observation|
Self-observation: remaining alert for symptoms (fever, cough, or difficulty breathing)
Self-monitoring: taking a temperature reading 2 times per day
Social distancing: remaining out of congregate settings (crowded places such as shopping centers, movie theaters, and stadiums), avoiding mass gatherings and public transportation, and maintaining a distance of 2 m (6 ft) from others
Discontinuation of home isolation: Confirmed or suspected COVID-19 cases may discontinue home isolation 1) once they test negative for SARS-CoV-2 (at least 2 negative consecutive nasopharyngeal specimens collected ≥ 24 hours apart) and fever has resolved without the use of fever-reducing medications and respiratory symptoms have improved or 2) ≥ 72 hours have passed since recovery (fever resolution without the use of fever-reducing medications and improvement of respiratory symptoms) and ≥ 7 days have passed since symptom onset.
Based on advanced information and employee or visitor medical screening, additional preventive measures may be required (e.g., increased ventilation, larger meeting rooms with more personal space per participant, disinfection of work areas and lavatories, and provision of alcohol wipes). Some health authorities recommend that face masks be worn by all persons to prevent onward transmission (source control) in order to encompass asymptomatic transmission.The public use of face masks by all persons may prevent onward transmission (source control) from asymptomatic persons. Household members of a PUI should observe hand hygiene and social distancing if possible and should avoid sharing household items. Such persons should self-monitor, and employers should consider the various options above, including exclusion from the workplace until 14 days after the last possible day of infectiousness for a PUI.
The U.S. CDC, Singapore's Ministry of Health, and Hong Kong's Centre for Health Protection essentially state that household members of asymptomatic individuals in self-quarantine after arrival from COVID-19–affected countries are not considered case contacts and may continue their daily activities (e.g., work or school) while continually monitoring their health and seeking medical attention if symptoms develop. However, businesses may conservatively opt to implement restrictions on a case-by-case basis.
Caregivers of a confirmed case or a PUI should take additional precautions to include the use of disposable gloves, gowns, and face masks and the proper disposal of these items.
Key Unanswered Questions
- Spectrum of clinical disease: proportions of asymptomatic persons; persons who are symptomatic but apparently (to others) asymptomatic; those with influenza-like illness, focal pneumonia, or severe respiratory compromise; and fatalities
- Hospital admission criteria to efficiently use a scarce resource
- Role of children as possible silent reservoirs
- Numerical risk for travelers going to areas with sustained transmission (i.e., destinations with cases occurring without known exposure to other cases)
- Implications of virus detection in the respiratory tracts of asymptomatic individuals
- Onset and duration of infectivity with respect to symptoms
- Existence and frequency of super-spreading events
- Role of surfaces and inanimate objects in transmission
- Reproductive number: on average, how infectious is the typical case
- Differences in clinical manifestation in Chinese (smoking, pollution) versus other populations
- Likelihood of mutations within the genome with serial passage through humans
- Mechanism of species jump from bats to humans and whether animals still pose a threat
- Speed of vaccine development
- Utility of very traditional Chinese methods of social distancing and quarantine in the twenty-first century
BMI = body mass index
CFR = case fatality rate
COVID-19 = coronavirus disease 2019
ELISA = enzyme-linked immunosorbent assay
EMA = European Medicines Agency
EPA = Environmental Protection Agency
EUA = Emergency Use Authorization
HCW = health care worker
ICU = intensive care unit
IV = intravenous
MERS-CoV = Middle East respiratory syndrome coronavirus
NYC = New York City
PCR = polymerase chain reaction
PHA = public health authorities
PPE = personal protective equipment
PUI = person under investigation
RH = relative humidity
RT-PCR = reverse transcription polymerase chain reaction
SARS-CoV = severe acute respiratory syndrome coronavirus
SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2
SNS = Strategic National Stockpile