COVID-19
Updates on theCOVID-19 pandemic from the Johns Hopkins Center for Health Security.

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EPI UPDATE The WHO COVID-19 Dashboard reports 30.95 million cases and 959,116 deaths as of 10:30am EDT on September 21. Last week, the WHO reported more than 2 million new cases, a new weekly record and an increase of 6.5% from the previous week.

Total Daily Incidence (change in average incidence; change in rank, if applicable)
1. India: 91,593 new cases per day (-94)
2. USA: 40,691 (+5,897)
3. Brazil: 30,596 (+3,034)
4. Argentina: 10,922 (+254)
5. Spain: 10,531* (+790)
6. France: 10,381 (+2,336)
7. Colombia: 6,965 (-149)
8. Russia: 5,798 (+469; ↑ 1) 
9. Peru: 5,611 (-52; ↓ 1)
10. Israel: 4,547 (+840; new)

Per Capita Daily Incidence (change in average incidence; change in rank, if applicable)
1. Israel: 676 daily cases per million population (+97)
2. Montenegro: 432 (+169; ↑ 1) 
3. Bahrain: 412 (+8; ↓ 1)
4. Andorra: 407 (+168; ↑ 1)
5. Argentina: 242 (+6; ↑ 1)
6. Costa Rica: 232 (-8; ↓ 2)
7. Spain: 225* (+17)
8. Czech Republic: 174 (+67 ; new)
9. Peru: 170 (-2)
10. Bahamas: 161 (+22 ; new)
*Spain’s average daily incidence is not reported for today; these values correspond to the previous day’s averages.

India appears to have passed a peak in terms of daily incidence, reporting more than 93,000 new cases each on September 17 and 18 before decreasing for 3 consecutive days. Mexico fell out of the top 10 in terms of total daily incidence, and it was replaced by Israel. Kuwait and Panama fell out of the top 10 in terms of per capita daily incidence, and they were replaced by the Czech Republic and the Bahamas. Additionally, the Occupied Palestinian Territory is reporting 166 daily cases per million population, which would be #10 in terms of per capita daily incidence if it were a WHO Member State.

UNITED STATES
The US CDC reported 6.75 million total cases and 198,754 deaths. The US is averaging 40,207 new cases and 794 deaths per day. In total, 22 states (increase of 1) are reporting more than 100,000 cases, including California with more than 700,000 cases; Florida and Texas with more than 600,000; New York with more than 400,000; Georgia with more than 300,000; and Arizona and Illinois with more than 200,000.

The Johns Hopkins CSSE dashboard reported 6.82 million US cases and 199,636 deaths as of 12:30pm EDT on September 21.

US CDC TESTING GUIDANCE Several weeks ago, the US CDC published controversial SARS-CoV-2 testing guidance indicating that individuals with known exposure to COVID-19 cases “do not necessarily need” to be tested. Since then, information has emerged in various media reports that the guidance was drafted by officials at the Department of Health and Human Services (HHS) and the White House Coronavirus Task Force and did not undergo the traditional CDC review process before being posted to the CDC website. On Friday, the CDC published another update that now recommends testing for all individuals with known exposure to COVID-19 cases. The update is very clear regarding individuals who have been within 6 feet of someone with known SARS-CoV-2 infection for at least 15 minutes: “You need a test.” Additionally, the update recommends that individuals with known exposure self-quarantine/isolate for 14 days, regardless of whether their test result is positive or negative.

In the weeks since the previous update, a number of experts have called for this kind change to the testing guidance, particularly in light of the current understanding of the role of asymptomatic and presymptomatic transmission in the pandemic. Notably, we are not aware of any new studies or information since the previous change that significantly affects our understanding of asymptomatic or presymptomatic transmission, so it appears that the most recent update is a correction to the previous guidance.

VACCINE SAFETY Vaccine safety continues to be an object of concern among the public. A poll conducted by the Pew Research Center found that only 51% of US adults would definitely or probably get a SARS-CoV-2 vaccine if it were available, a substantial decrease from 72% in late April and early May. Additionally, 77% of respondents indicated that they expect a vaccine to be approved before its safety and efficacy is fully studied, and 78% indicated that a rushed approval process is their greatest concern regarding the vaccine. More than 90 health organizations issued an open letter to the US FDA to address these fears, encouraging the FDA to complete Phase 3 clinical trials and utilize existing regulatory processes to fully evaluate and authorize a vaccine for public use.

A group of Black physicians from the National Medical Association created an independent expert panel to review data on candidate vaccines and therapeutics with the aim of increasing confidence and uptake of effective medical countermeasures among Black communities who have been disproportionately affected by COVID-19. The National Medical Association was founded in 1895, at a time when Black doctors were excluded from other medical associations, and it aims to eliminate health disparities affecting Black patients. In addition to safety and efficacy data from clinical trials, the panel will also review study design to evaluate the extent to which racial and ethnic minorities are included. The panel hopes its review and recommendation will ensure the appropriate evaluation of candidate vaccines and help improve uptake of safe and efficacious vaccines among Black and other racial and ethnic minorities.

After pressure from health experts to increase transparency regarding their vaccine clinical trials, AstraZeneca, Moderna Therapeutics, and Pfizer disclosed their Phase 3 clinical trial protocols. Study protocols for clinical trials have historically not been made public until after the trial is completed. The study protocols describe how the 3 companies intend to analyze the trial data, including outcomes of interest and conditions that would result in early termination. The studies also describe the points at which preliminary data will be analyzed and the conditions for applying for an Emergency Use Authorization prior to the completion of the trial. AstraZeneca’s protocol is of particular interest after the Phase 3 trials were suspended as a result of a serious adverse event in one of the participants. The trials were resumed in the UK following an independent safety review, but the company has released only minimal information about the event and related data.

AIRBORNE/AEROSOL TRANSMISSION On Friday, the US CDC updated its guidance regarding SARS-CoV-2 transmission, in particular with respect to droplet and airborne/aerosol transmission routes. The update emphasized the role of airborne/aerosol transmission, noting that aerosols are believed to “be the main way the virus spreads” and that “airborne particles” can remain suspended in the air for prolonged periods of time and travel distances beyond 6 feet. This represented a major shift in how the CDC communicated regarding respiratory transmission of SARS-CoV-2, which previously focused on “droplet” transmission (ie, via larger respiratory particles). This morning, the CDC issued a statement that the information updated on Friday was a draft version of guidance that was published prematurely. The website was updated again today to revert to the previous iteration of the guidance (ie, that emphasizes droplet transmission as the primary route).* The current website on SARS-CoV-2 transmission notes that the CDC is in the process of updating its guidance and that new language will be published “once [the] review process has been completed.” If the CDC shifts its focus to airborne/aerosol transmission as the primary concern for SARS-CoV-2, it is unclear if associated recommendations regarding mask use (which are less or minimally effective at reducing aerosols compared to larger droplets), physical distancing, face shields or other solid barriers, or other mitigation measures will change as well.
*We have been unable to identify an archived version of the changes from Friday, so we are unable to confirm the content of the changes beyond what is reported in the media.

BRADYKININ STORM Bradykinin is a peptide commonly found in the human body that is involved in a myriad of biological functions—including lowering blood pressure, contracting smooth muscle in the lungs and gut, assisting kidney diuresis, creating pain sensation, and triggering inflammation—and new analysis suggests that it could potentially account for certain unexplained facets of COVID-19 disease. Researchers at the Oak Ridge National Laboratory and several US universities found that an enzyme known as DABK accumulates as a result of SARS-CoV-2 binding to ACE2 receptors, which then triggers an increase in bradykinin in the body. This increased level of the peptide could explain clotting issues in COVID-19 patients that can cause serious effects such as heart attacks or strokes as well “COVID toes.” Increased bradykinin could also cause lungs to become more watery or release blood and immune cells to their interior, which could cause respiratory distress and breathing issues in patients. The myriad of functions of bradykinin could also potentially be linked to thyroid and neurological symptoms in COVID-19 patients. The bradykinin hypothesis could also potentially explain increased disease severity in male COVID-19 patients compared to females, as females typically produce twice as much of a specific protein that protects against certain effects of bradykinin over-accumulation. Bradykinin could also factor into the effects of vitamin D deficiency and corticosteroids in COVID-19 disease progression and severity. Scientists are currently pursuing treatment options that may address the role of bradykinin in COVID-19 patients, such as repurposing the drug icatibant and beginning clinical trials for new treatments. Further research is required to better characterize any direct or indirect effects of bradykinin in COVID-19 patients.

HUMAN/PET TRANSMISSION A study published in the US CDC’s Emerging Infectious Diseases journal provides further evidence that SARS-CoV-2 can be transmitted between animals and humans, potentially including pets. The study tested 50 cats for COVID-19 in Hong Kong and identified 6 SARS-CoV-2 infections. Based on findings during the 2003 SARS epidemic, Hong Kong initiated a policy of quarantining mammalian pets belonging to humans with confirmed SARS-CoV-2 infection. While the researchers identified 6 feline infections, they were not able to definitively identify specific instances of human-to-animal or animal-to-human transmission.

LONG-TERM CARE FACILITIES Nursing homes and other long-term care facilities provide ideal conditions for the spread of SARS-CoV-2, including prolonged indoor contact and residents at elevated risk for infection and severe disease, and nursing homes account for a disproportionately high fraction of US COVID-19 cases and deaths. Last week, the Centers for Medicare and Medicaid Services (CMS) unveiled the report by an expert panel convened to provide additional recommendations for improving safety at long-term care facilities in the midst of the US epidemic. The expert panel cited increased testing, PPE availability, and increased training and pay for nursing staff as key factors in mitigating the risk. Some patient care advocates have criticized the report for not holding the facilities themselves more accountable for patient safety. In fact, one of the panel members reportedly refused to endorse the report over these concerns.

Researchers at the CDC and the West Virginia Bureau for Public Health published a study in the US CDC’s MMWR that analyzed the odds of a COVID-19 outbreak based on CMS ratings at long-term care facilities in West Virginia. The ratings are based on health inspections, staffing ratios, and 15 “physical and clinical measures,” and each facility is assigned a rating of 1 (lowest) to 5 (highest) stars. In West Virginia COVID-19 outbreaks were reported in 14 of 123 total facilities. The researchers found that the odds of a COVID-19 outbreak in West Virginia facilities rated as 4 or 5 stars were 94% lower than in 1-star facilities, and the odds in 2- and 3-star facilities were 87% lower than in 1-star facilities. Of the 14 outbreaks in long-term care facilities in West Virginia, 7 were 1-star facilities, compared to 5 outbreaks in 3-star facilities and 1 in a 4-star facility*. Statewide, 12% of long-term care facilities were rated as 1 star, but 1-star facilities accounted for 50% of the outbreaks in long-term care facilities.
*One (1) facility had no star rating due to “a history of serious quality issues;” there were no outbreaks documented in 2- or 5-star facilities.

EYEGLASSES Researchers from China published findings from study investigating whether the use of eyeglasses provides protection against SARS-CoV-2 transmission. The study, published in JAMA: Ophthalmology, included a cohort of 276 hospitalized COVID-19 patients in Hubei Province in January-March. Among these patients, 5.8% routinely wore eyeglasses—defined as more than 8 hours per day—compared to an estimated 31.5% among the general public. The researchers hypothesize that wearing glasses could reduce the amount that people touch their eyes, which could reduce SARS-CoV-2 transmission. While protective eyewear is recommended for healthcare professionals, peer-reviewed evidence is limited regarding any potential protective effect for the general public. Further research is necessary to better characterize any effect of eyeglasses on mitigating SARS-CoV-2 transmission risk outside the context of the healthcare setting.

SPORTS As countries attempt to relax social distancing measures and resume some measure of normal social activity, sporting events seem to remain among the top priorities in many parts of the world. Sports and leagues have taken a variety of approaches to resuming play, and some have faced additional challenges as a result of surging COVID-19 incidence. The French Open (tennis) is scheduled to start later this week, but several players have been forced to withdraw due to positive SARS-CoV-2 tests, including several who had close contact with a coach who tested positive. The tournament will permit 5,000 spectators per day, despite increasing COVID-19 incidence in France, including the Paris area, although this is still much fewer than the 20-30,000 anticipated previously. All spectators will be required to wear a mask. Players will participate in a “bubble,” with dedicated housing and periodic testing throughout the tournament. Following the report of positive tests among players and coaches, some players have expressed concern about how tournament officials are managing the player’s bubble.

College football has resumed in many parts of the US, and more conferences are planning to resume play in the near future. The start of the season has not been without setbacks, however, with multiple games being postponed or possibly cancelled due to COVID-19. The opening game between the University of Virginia and Virginia Tech was postponed after positive SARS-CoV-2 tests at Virginia Tech did not leave enough players to play the game. Similarly, the game between the University of Houston and Baylor University was postponed due to Baylor not having enough players. The head coach for Louisiana State University (LSU) recently reported that “most of [the] players have caught it [COVID-19].” It is unclear exactly how many players have tested positive, at LSU or any other school, but these cases do not appear to be affecting conference plans to continue the season. As we have covered previously, the risk of longer-term health effects remains uncertain; however, evidence continues to emerge of COVID-19 patients experiencing long-term issues, younger and healthier adults that exhibit mild symptoms during the acute phase of their disease.

Despite these events, the Big Ten Conference announced last week that it intends to resume play on October 23-24. Notably, a number of states in the Midwest (where most Big Ten schools are located) are reporting concerning COVID-19 trends, including on college campuses. In fact, several days before the announcement, health officials in Ingham County, Michigan (home to Michigan State University), asked all students to “self-quarantine” for 2 weeks due to a recent increase in local COVID-19 incidence. Interestingly, the guidance recommends that students remain at home except for in-person classes, sports practices, their jobs, medical care, or shopping, which does not sound much like quarantine.

Ten (10) people have been ordered to quarantine following the NFL game between the Houston Texans and the Kansas City Chiefs. The Kansas City Chiefs permitted a limited number of spectators into the stadium for the game, and one subsequently test positive for SARS-CoV-2. The team coordinated with local health officials to conduct contact tracing efforts in order to identify those who may have been exposed.