Updates on the emerging novel coronavirus pandemic from the Johns Hopkins Center for Health Security.

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EPI UPDATE The WHO COVID-19 Situation Report for August 6 reports 18.61 million cases (259,344 new) and 702,642 deaths (6,488 new). The WHO data indicates that the global daily incidence could potentially be approaching a peak or plateau. This afternoon’s update will be the 200th daily COVID-19 Situation Report published by the WHO, dating back to January 21.

The continent of Africa is expected to surpass 1 million cases in this afternoon’s Situation Report. Notably, Africa includes countries from both the WHO African Region and Eastern Mediteranean Region. The African Region has reported 848,053 cases, but when adding the incidence for Djibouti, Egypt, Libya, Morocco, Somalia, Sudan, and Tunisia, the total across the continent totals 997,841 cases. South Africa represents more than half of all cases reported in Africa. While South Africa’s incidence is beginning to taper off, however, the continental total continues to increase steadily, indicating that the incidence reported in other countries continues to increase.

Brazil reported 53,139 new cases, and it appears as though it is on pace to report decreased incidence compared to the previous 2 weeks. Brazil remains #3 globally in terms of daily incidence. Colombia reported 11,996 new cases, its highest daily incidence to date. Columbia’s average daily incidence has doubled since July 15, and it remains #4 globally in terms of daily incidence. Mexico’s average daily incidence has decreased slightly over the past several days, and it may be approaching a peak or plateau. Mexico fell to #7 globally in terms of daily incidence. Including Brazil, Colombia, and Mexico, the Central and South American region represents 5 of the top 10 countries globally in terms of daily incidence, along with Peru (#7) and Argentina (#8), and multiple other countries in the region are reporting more than 1,000 new cases per day. Additionally, the region includes 5 of the top 10 countries in terms of per capita daily incidence—Panama (#2), Peru (#3), Brazil (#4), Colombia (#5), and Bolivia (#9)—and several other countries are reporting more than 100 new daily cases per million population.

Following several days of decreasing daily incidence, India reported 2 consecutive sharp increases, up to a new high of 62,538. India technically remains #2 globally in terms of daily incidence, but it is reporting essentially the same incidence as the US and still increasing. We expect India to surpass the US as #1 globally in terms of daily incidence in its next update. The Philippines continues to average more than 4,000 new cases per day, but it may be starting to level off. The Philippines remains #10 in terms of daily incidence.

South Africa reported 8,307 new cases and remains among the top countries globally in terms of both per capita (#10) and total daily incidence (#5).

Bahrain (#6) is the only country in the Eastern Mediterranean region remaining in the global top 10 in terms of per capita daily incidence, and Kuwait is the only other country in the region reporting more than 100 new daily cases per million population. Nearby Israel (#8), in the WHO’s European region, remains among the top countries globally as well.

The Maldives is the only country reporting more than 250 new daily cases per million population, and it remains #1 globally in terms of per capita daily incidence.

The US CDC reported 4.80 million total cases (53,685 new) and 157,631 deaths (1,320 new). This is the second consecutive day that the CDC reported more than 1,000 deaths. The US will likely reach 5 million cases by the end of this weekend or Monday. In total, 13 states are reporting more than 100,000 cases, including California with more than 500,000; Florida with nearly 500,000; and Texas with more than 450,000. The US remains #7 in terms of per capita daily incidence, and it is still #1 in terms of total daily incidence, but India is reporting essentially the same daily average. We expect the US to fall to #2 in the next update.

The US may be approaching a peak in terms of daily mortality, and reporting over the next several days will provide insight on the longer-term trend. The peak daily incidence was on July 25, so the timing is appropriate to begin observing an associated peak in mortality.

The Johns Hopkins CSSE dashboard reported 4.90 million US cases and 160,255 deaths as of 1:30pm on August 7.

VACCINE TRIALS & EVALUATION As we look ahead to future SARS-CoV-2 vaccines, it is critical to establish public trust and support in order to ensure the vaccine is widely accepted. Growing vaccine hesitancy and the rapid development and evaluation of SARS-CoV-2 vaccine candidates, along with widespread misinformation efforts and mistrust of government officials and agencies, is giving rise to concerns about the public’s willingness to receive a SARS-CoV-2 vaccination if or when one becomes available. With this challenge in mind, a coalition of more than 400 medical and public health experts issued an open letter to US FDA Commissioner Dr. Stephen Hahn calling for increased transparency around the US government’s evaluation of SARS-CoV-2 candidate vaccines. In the letter, the authors emphasize the importance of providing insight into the evaluation and associated deliberations regarding potential vaccines, including on expected benefits and risks, in order to establish trust in the public regarding the evaluation process. Concerns regarding the authorization and recommendations regarding hydroxychloroquine have raised concerns that the vaccine evaluation process could be impacted by political considerations, which could erode public confidence and adversely affect willingness to be vaccinated. Even if a vaccine is efficacious against the virus, it will not be an effective tool unless the public is willing to receive it.

PANDEMIC INSURANCE Businesses around the world pay insurance premiums for business interruption policies, which are designed to offset financial losses if businesses cannot operate as the result of an emergency. Many of these businesses, however, are finding that their policies may not cover pandemics, driving some to file lawsuits against their insurance companies. Following the emergence of the original SARS virus in 2003—which caused major economic disruptions, particularly in Asia—insurance companies realized that they could simply not afford to make insurance payouts as a result of disease-related emergencies. In contrast to many other types of emergencies—such as natural disasters, fires, and floods—disease events can have a much larger geographic spread and can affect many aspects of social and economic activity without having to cause any physical damage. Some of these businesses are arguing that the inability to open constitutes a “loss” of their building, which could be viewed as a form of physical damage, but these lawsuits will likely take months or years to resolve. From a financial perspective, the principles on which insurance is built—essentially, pooling risk across many individuals or businesses so that those not affected by an event can pay for those that are—break down for a pandemic scenario, in which all businesses or individuals are affected.

INTERNATIONAL RESURGENCE Numerous countries around the world that previously had success against COVID-19 are experiencing an increase in incidence. Countries in East and Southeast Asia as well as the Western Pacific were among the first to experience the COVID-19 pandemic, and several—including Japan and South Korea—were able to gain relative control of their epidemics through strict “lockdowns,” expansive testing and contact tracing programs, and public cooperation with various social distancing and other risk mitigation measures, including mask use.

Several countries in the region are now taking renewed action against COVID-19 due to recent increases in transmission. In central Japan, the Aichi prefecture is implementing a local state of emergency, including advisories against travel and a nighttime curfew. Businesses are also being asked to limit their hours or close altogether. In Danang, Viet Nam, the Tien Son Sports Palace, a 10,000 square meter arena, has been converted into a field hospital to provide 1,000 additional beds to supplement local hospitals. Viet Nam previously went 3 months without reporting community transmission, but Danang has reported more than 200 cases since July 25. Following the initial outbreak report, thousands of tourists were evacuated from Danang in an effort to limit local transmission. Government officials in Viet Nam’s capital of Hanoi are retesting 72,000 people who recently returned from Danang using more sensitive nasopharyngeal swab tests rather than the blood-based rapid tests that Viet Nam uses for screening purposes.

In Melbourne, Australia, the government has imposed more restrictive“lockdown” measures to combat its surging outbreak, including a curfew between 8pm and 5am. The state of Victoria, where Melbourne is located, reported 725 new cases on Wednesday, compared to only 14 new cases for the rest of Australia. Approximately 250,000 people are out of work due to new prohibitions on non-essential activities. Melbourne was placed under lockdown earlier in the pandemic, but it was forced to re-institute similar restrictions 4 weeks ago. Now, the restrictions have been enhanced to Stage 4, and the new lockdown is scheduled to last for another 6 weeks.

ESTIMATING COVID-19 MORTALITY The WHO published a Scientific Brief to outline challenges and recommendations for estimating COVID-19 mortality in real time. Challenges in testing, diagnosis, and reporting introduce numerous barriers into calculations of case fatality ratio (CFR) and infection fatality ratio (IFR; which accounts for asymptomatic infections). Reported incidence typically underestimates the true scale of an epidemic, in particular for mild cases and populations that have poorer access to testing and healthcare services. Additionally, cases take time to progress through disease to death, so estimating mortality at any given point in time does not account for the current cases that will eventually die, leading to an underestimate of mortality. The guidance provides information for estimating both CFR and IFR and discusses challenges and limitations of these calculations in the context of an ongoing epidemic.

In addition to the traditional CFR and IFR calculations, the document provides an alternative calculation that aims to mitigate the effect of current cases that will ultimately die. Rather than including all known cases/infections in the CFR/IFR calculation, estimates can be generated based on only those with known outcomes (ie, the sum of deaths and recoveries) as the denominator. This requires access to patient-level data to identify recovered patients, but it could reduce the degree to which the standard approach underestimates CFR and IFR. The guidance also recommends estimating CFR and IFR for different risk groups (eg, age, sex, underlying health conditions) in order to better characterize variations in mortality across populations. Finally, the document highlights common biases in CFR/IFR estimates, including the effects stemming from delays in reporting cases and deaths, focusing on severe cases early in an epidemic, and challenges determining the correct cause of death.

US SCHOOLS REOPENING Schools in numerous US states have started reopening for in-person classes. As classes resume, health officials and other experts are monitoring them closely for signs of increased transmission within schools and in the community. Tennessee has reported at least 14 COVID-19 cases in 2 school districts that are connected to schools that recently reopened, driving both to close or alter their schedules. Mississippi, Indiana, and North Carolina have also reported cases among students following schools reopening. Families that are uncomfortable sending their children back for in-person classes have faced tough choices, with some schools allegedly threatening suspension or expulsion for students who do not return. Teachers have faced similar threats, with some reportedly being told to resign if they had concerns of being infected at schools.

Despite guidance from the US CDC and other experts regarding appropriate risk mitigation strategies for COVID-19, there is evidence that some schools are not implementing some of these recommended measures. In Georgia, for example, photos of a high school show students packed closely together in a hallway, with few wearing masks and nobody maintaining appropriate physical distancing. The school district superintendent commented that the schools are learning from their experiences and updating policies to promote a safe learning environment, although mask use will not be mandated. The specific risk mitigation protocols used will inevitably vary between schools and communities, but experts generally agree that physical and social distancing practices, including mask use and proper ventilation, and enhanced hygiene and sanitization standards can mitigate transmission risk to some degree. The current CDC guidance notes that the level of community transmission should be a principal consideration when making decisions regarding when and how to reopen schools. 

REMDESIVIR PRODUCTION & PRICING On August 4, a bipartisan group of 31 state Attorneys General (AGs) issued an open letter to senior US health agencies urging the federal government to permit other companies to manufacture remdesivir in order to increase availability, arguing that the drug’s developer and manufacturer, Gilead Sciences, has not yet provided sufficient supply. Remdesivir is the only drug that has demonstrated efficacy as a COVID-19 treatment in randomized clinical trials. The letter was sent to HHS, NIH, and the FDA urging them to remove Gilead’s exclusive rights over the product, in light of the company’s inability to produce the drug at reasonable prices and volume. The AGs also argue that Gilead’s projection of 2 million treatment courses by the end of the year is too low to manage the US epidemic, and they highlight that Gilead received substantial funding from the US government to facilitate development, testing, and production of the drug.

Gilead responded with a statement arguing that the AGs misrepresented the situation. Gilead stated that it is largely meeting existing demand and that it is investing in production capacity and should exceed global demand by October. Gilead has also worked with manufacturers in India and Pakistan to improve access to remdesivir in other countries. It should be noted that remdesivir produced by Gilead costs approximately US$340 per vial, while the generic product manufactured in India costs only US$60 per vial. The AGs argued that allowing other manufacturers to produce generic forms of remdesivir in the US will alleviate domestic supply and pricing barriers.

HAND SANITIZER POISONING The US CDC published findings from an investigation of multiple instances of individuals ingesting hand sanitizer. The study, published in the CDC’s Morbidity and Mortality Weekly Report (MMWR), addresses a series of 15 individuals from Arizona and New Mexico who were hospitalized for methanol poisoning in May and June after ingesting hand sanitizer. Among these patients, 7 were discharged from the hospital, 4 remained hospitalized at the time the report was written, and 4 died. Of those who were discharged, 3 reported new visual impairment. Methanol poisoning can cause headache, blurred vision, and nausea or vomiting, and severe or untreated cases can lead to seizures, blindness, or death.

Hand sanitizer should contain at least 60% ethanol or 70% isopropyl alcohol to be effective, but it should not contain methanol, which can be toxic to humans. The US FDA is closely monitoring hand sanitizers, and it has generated a list of unsafe products and issued numerous orders to stop production and recall unsafe products. The current list includes 115 products, added between July 2 and August 3, including more than 100 that contain methanol or were produced at facilities that made other products contaminated with methanol. Methanol can be absorbed through the skin, but methanol poisoning via this route of exposure is relatively rare.

It is not clear exactly why these individuals ingested the hand sanitizer products, but there are reports of some individuals ingesting them as a substitute for traditional alcoholic beverages and children swallowing them unintentionally. The CDC and FDA recommend checking hand sanitizer products and disposing of any that contain methanol—in hazardous waste containers and not flushed or poured down a drain. As more hand sanitizer products have become available during the pandemic, particularly from companies that do not have a well-established history of manufacturing them, it is important to ensure that you are using safe and authorized products and doing so in an appropriate manner.

US TRAVEL ADVISORIES The US Department of State updated its travel advisories yesterday to remove the global Level 4 (Do Not Travel) advisory. Rather, the State Department replaced the global advisory with individual countries, based on country-specific risk assessments. The list now includes more than a full page of entries for Level 4 advisories, nearly 3 pages of Level 3, four Level 2 advisories, and two Level 1 advisories (Macau and Taiwan). Notably, not all of the advisories updated yesterday pertain directly to COVID-19 (eg, Level 2 advisory for Antarctica for weather-related hazards). The global Level 4 advisory had been in place since March 19. Despite these changes, travel restrictions still exist in many countries for travelers arriving from the US.

The US CDC also updated its travel alerts to transition from a global alert to individual countries. The vast majority of countries remain at Level 3 (COVID-19 Risk is High; Avoid Nonessential Travel), and the CDC notes that non-US citizens/residents who have been in Brazil, China, Iran, Ireland, the UK, and most of Europe in the past 14 days are prohibited from entering the US. The CDC also published a new COVID-19 travel guidance webpage, which provides a number of recommendations, considerations, and other information for before, during, and after travel.

US COVID-19 STIMULUS BILL Efforts to finalize a Phase 5 COVID-19 stimulus package continue between the US Senate, House of Representatives, and White House. After more than a week of negotiations, it appears that there are still major barriers to reaching an agreement, and it is unclear what timeline might be necessary to reach a compromise on the outstanding issues. Notably, at least a handful of Republican Senators have indicated that they are opposed to any stimulus package, which could make it even more difficult to pass a bill through the Congress. Like last week, when expanded unemployment payments and eviction protections expired, several provisions of the CARES Act will end this week if a new agreement is not reached today, including the Paycheck Protection Program, which helps small businesses continue to pay employees. US President Donald Trump indicated that his staff is preparing executive orders to continue certain portions of the emergency COVID-19 funding and that he could sign them as early as this weekend, if Congressional leaders are not able to reach an agreement.

US COVID-19 MORTALITY Following comments made by President Trump in a recent interview with Axios, there has been considerable attention on COVID-19 mortality in the US, particularly with respect to how it compares to other countries. There are many ways to evaluate disease mortality, and regardless of the method used, analysis is limited by the quality of available data. With that in mind, the data and metrics used can have a major effect on how we understand disease mortality. In light of this recent attention, here is a look at how the US is faring in terms of COVID-19 mortality, including some challenges associated with various mortality metrics.

Perhaps the most obvious number to start with is cumulative deaths. From this perspective the US is #1 globally with 157,631 total COVID-19 deaths since the onset of the pandemic. While this allows us to compare the full magnitude and severity of national COVID-19 epidemics, it poses challenges in comparing countries with different size populations. To account for population size, we can look at per capita mortality. This is often displayed in terms of “per 100,000 population” or “per million population,” but as long as you are using the same scale for both countries, the comparison is the same. In terms of per capita deaths, the US has reported approximately 484 COVID-19 deaths per million population, which places it #10 globally. Notably, the top 10 also includes San Marino and Andorra, both of which have very few total deaths (42 and 52, respectively) but very small populations.

It is also important to evaluate the number of deaths compared to the number of cases, which can provide insight into how countries’ health systems are able to handle the epidemic. For this, we look at case fatality—the number of deaths divided by the number of cases, or infection fatality—based on the number of total infections, including asymptomatic infections. As discussed above, challenges and delays associated with detecting and reporting cases and deaths make case fatality and infection fatality notoriously difficult to determine in real time. In terms of case fatality, the US is somewhere in the middle of the pack compared to other countries. At an estimated 3.28%, the US is faring better than approximately one-third of countries, but many countries are doing better. The US case fatality has decreased over the past several weeks, due in part to increased testing and surging transmission; however, it appears to be leveling off.

We can also use daily mortality to evaluate current trends, as opposed to the cumulative totals. Daily reports can vary widely, particularly over weekends and holidays, so using weekly averages helps to smooth out these variations. Looking at the total daily mortality, the US recently surpassed Brazil as #1 globally, reporting approximately 1,148 new deaths per day. On a per capita basis, the US is reporting approximately 3.47 new deaths per day per million population, putting it at #10 globally. Additionally, reported COVID-19 mortality depends heavily on the quality of COVID-19 surveillance and testing systems. Alternative methods, such as excess mortality, can help estimate the disease burden that may not be captured by COVID-19 specific reporting systems. These analyses can involve various reporting databases, however, which can make them difficult to compile and compare across many countries, and they can include deaths not directly due to COVID-19.

While there are many other metrics, and variations on those metrics (eg, different windows over which to average daily reports), these are among the most common ways to evaluate disease mortality. Whether you look at total deaths or mortality with respect to population or reported cases, the US remains either relatively high or near the top of all of the metrics described here. This illustrates that the US continues to struggle with its COVID-19 epidemic. National daily incidence may be continuing to decline, but we have not yet observed a similar decrease in deaths. Mortality trends typically lag several weeks behind incidence, so we could potentially expect daily mortality in the US to reach a peak in the near future.