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Coronavirus Questions

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Abundance News
Sun, 01 Mar 2020 07:29:04 +0000
Description: Here is an analysis of the current Coronavirus epidemic (Covid-19) written by Dr. Megan Murray MD, MPH, ScD (tribute, bio, twitter) who is the Harvard Medical School Global Health Research Core Director and the Ronda Stryker and William Johnston Professor … Continue reading

Here is an analysis of the current Coronavirus epidemic (Covid-19) written by Dr. Megan Murray MD, MPH, ScD (tribute, bio, twitter) who is the Harvard Medical School Global Health Research Core Director and the Ronda Stryker and William Johnston Professor of Global Health at the Department of  Global Health and Social Medicine.

The Abundance Foundation has worked with Dr. Murray for nearly a decade to prevent the spread of epidemic disease as part of the Abundance Project for Global Health (in partnership with Harvard Medical School and Partners In Health). This work included Lancet-published research proving the efficacy of the Cholera vaccine during the Haiti epidemic and proving the accuracy of diagnostic tools during the Ebola epidemic in Sierra Leone.

When I spoke with Dr. Murray about Covid-19, I understood that many other people would likely appreciate hearing her insights into the current worldwide epidemic. I asked her to write up a Coronavirus FAQ’s that I could forward on to colleagues and friends. This does not represent an official statement or assessment of Harvard Medical School.

–Stephen Kahn, M.D.
President, Abundance Foundation
abundance.org

===========================

Frequently asked questions on the novel Coronavirus, Covid-19.

Megan Murray, MD, MPH, ScD

This was last updated on March 2
If we update this document, the most current version will be found on this webpage/URL.
This is not intended to be a substitute for current news or recommendation.
Here is the UpToDate page on Covid-19.
Abundance partners with Better Evidence at Ariadne Labs (Harvard) to distribute free UpToDate licenses to clinicians in resource-poor countries.
Through this donated access, an estimated 6900 clinicians and their colleagues use UpToDate in 120 countries, providing care for over 8 million patients yearly.

 

Where did it originate?

 

Analysis and comparison of the Covid-19 genome suggest that it originated in bats and was transmitted to humans through an intermediary host, possibly a pangolin or other non-domestic animal. Bats appear to have an altered innate immune system that allows them to tolerate some viral infections without developing disease and consequently, they are the reservoir for a wide range of infections, some of which infect humans.  Multiple different types of coronaviruses (>500) have been identified in bats and the coronavirus that caused SARS in 2002 almost certainly originated in bats and was transferred to humans via an intermediary civet cat. This probably came about because there is a substantial trade in China of “exotic” animals obtained from the wild; these are sold for food and traditional medicines. There is some speculation that the endangered pangolin (or scaly ant-eater) may have been the intermediary host in the current outbreak. Despite this, the actual origin of Covid-19 has not yet been identified. The closest bat coronavirus that has been identified shares about 96% of its genome with Covid-19 while the most recent report suggests that the closest coronavirus found in pangolins only shares 85 to 92% of the genetic material. (https://www.nature.com/articles/d41586-020-00548-w)

 

How is it transmitted?

Covid-19 is a respiratory virus (like the common cold) which is spread through respiratory droplets, meaning drops of fluid from the nose or mouth that are emitted during coughs, sneezes or even talking. It is possible that some of the viral particles emitted this way end up on surfaces (door handles, subway poles, coins) where they might remain viable. These objects then become “fomites,” inanimate objects that can transfer infection between people. It is also possible that Covid-19 can be transmitted as an aerosol – in other words, through the airborne route, so through direct inhalation of virus suspended in the air – but so far, there is no conclusive evidence of that (although that is challenging to prove one way or the other). The virus has also been identified in stool and less often, in other body fluids (blood, urine) raising the possibility that other routes of transmission – such as fecal-oral – are possible although it is not clear if that has contributed to the outbreak.

 

What is the clinical course of the disease?

Covid-19 disease usually begins with mild fever, dry cough, sore throat and malaise. Unlike the coronavirus infections that cause the common cold, it is not usually associated with a runny nose. In the early phase of the disease, illness is usually mild and most often, meaning in about 80% of cases, it remains mild and may not require direct medical intervention. About 14% of people develop severe pneumonia accompanied by hypoxia (poor oxygenation) and 5% are considered critical, meaning they experience respiratory failure requiring mechanical ventilation. Although we know that older people and those with cardiovascular disease or Diabetes mellitus are at especially high risk for severe disease, it is not yet clear why these people experience these outcomes. One theory is that these people have an altered immune response that is not self-regulating. Whereas normal inflammatory responses to pathogens are eventually dampened by other immune responses, this down-regulation may not occur in some people.  This could lead to the overproduction of certain immune cells and the massive release of inflammatory cytokines (cytokine storm) that is typical of acute respiratory distress syndrome (ARDS).

 

What is the mortality rate and who is most vulnerable?

A study in the Journal of the American Medical Association from China’s CDC reported that the case fatality rate (CFR) in approximately 45000 patients with confirmed Covid-19 in mainland China was 2.3%. The CFR varies by age and underlying health status, and ranges from 0 in patients 9 years of age and under to 14.8% in those 80 and older. The CFR is high in people with underlying cardiovascular disease (10.5%), diabetes (7.3%), chronic respiratory disease (6.3%) and hypertension (6%). This makes Covid-19 less lethal than the two other coronaviruses that have caused recent outbreaks; in 2002, SARS had a CFR of 9.6% and MERS of 34.4% – but it is nonetheless an order of magnitude more lethal than influenza (between .05-.1% depending on the year).  For unclear reasons, the CFR for Covid-19 is lower in other parts of China than Hubei with an estimated mortality rate less than 1%. The mortality rate appears to be higher in men than in women. There has been some speculation that this may reflect the gender difference in smoking in China.

 

How long are the incubation and infectious periods? 

The term incubation period refers to the time from an exposure that results in infection until the occurrence of symptomatic disease in an affected person. It can be measured in people who have a known discrete exposure and who go on to develop disease. Current data suggests that the mean incubation period is 4-5 days but that there is significant variability among people in this parameter – with some developing disease as early as 2 days after exposure and others as long as 14 days later. Recent case reports have raised the possibility that some outliers could have incubation periods of 24 days or even longer. It is not yet clear how the incubation period relates to the infectious period (defined as the number of days in which a person can transmit an infection).  Some transmission events have occurred from asymptomatic people prior to the development of clinical disease, suggesting that people can transmit before they are aware that they are ill, but it is not known how often asymptomatic transmission occurs or how long people remain infectious after they have been diagnosed.

 

How transmissible is it?

The transmissibility of any infectious agent depends on several things: the probability of an infection event given a contact between a susceptible person and an infectious person; the duration of infectiousness – or number of days that a person can transmit – and the number of contacts that an infectious person has per unit time. This means that the transmissibility can vary in different settings and will depend on things like crowding which increases the number of contacts. Based on a summary of multiple studies, it seems that each infectious person with Covid-19 is expected to infect between 2 and 3 people on average. But this term – on average – obscures the substantial variability observed in different people. Some people are much more infectious than others and other people don’t transmit at all. Epidemiologists refer to this as dispersion around a basic reproductive number (defined below). High levels of dispersion or variance affect the likelihood that an introduced case will cause an outbreak – so if 80% of people do not transmit and 20% infect 10 people each, the average will be 2 but the probability that a single introduction will lead to an outbreak is only 20% whereas if everyone infects exactly two people, there would be 100% probability of an outbreak. It appears that the infectiousness of Covid-19 is quite widely dispersed but more data is needed.

Another way to estimate the transmissibility of an infectious agent is to measure the secondary attack rate (SAR), or the proportion of people who develop disease after a discrete exposure. A Lancet study that used data on secondary transmission associated with specific discrete social events reported 48 secondary infections that occurred among 137 attendees of these events, for an SAR among close contacts of 35%. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30462-1/fulltext

 

What is the basic reproductive number?

The term “basic reproductive number” or R0 refers to the number of people who would be infected by a single infectious case if it were (hypothetically) introduced into an entirely susceptible population. If the parameters listed above (per contact infectivity, duration of infectiousness and number of contacts per unit time) are known, one can estimate the basic reproductive number simply by multiplying them. But we usually do not know these parameters, and some are very hard to measure, in particular the number of contacts over time. More often the R0 is estimated during the early phase of an epidemic by estimating the growth rate (as represented by the slope of the epidemic curve). Mathematically, the R0 = 1 + growth rate X the serial interval where the serial interval is defined as the time between one infection and the next in a transmission chain. Some possible issues with estimating R0 is that not all cases are reported and so they are not included in the epidemic curve. There are now more than 20 different publications/preprints estimating R0 using slightly different data sets and methods and the results range from 1.5 to 6 but most fall within the 2.3-3.2 range.

A basic rule of thumb is that the proportion of people who will not be infected by an epidemic pathogen (once the infectious disease has come to an equilibrium) is approximately the reciprocal of the R0. This is where the estimate that 40-70% of the world’s population could be infected by Covid-19 comes from. Of course, this depends on the efficacy of interventions, the mobility of infectious people and as noted above, the dispersion of the reproductive number.

 

What is the difference between quarantine, isolation and social distancing?

There are several different approaches to restricting movements in order to control epidemic disease. One can isolate people with the disease to try to prevent them from infecting others but this will only be completely effective if they are diagnosed with the disease at or before the time that they become infectious. If people are infectious before they have symptoms or if some infectious people never develop symptoms at all, transmission can take place before a person is diagnosed. For diseases with significant asymptomatic spread, quarantine is used to separate and restrict the movements of people without signs of illness who may have been exposed to an infectious case so that they do not infect others during that period. A less extreme measure is social distancing – asking people to avoid congregate settings such as schools, work-places, or large gatherings. For example, the Wuhan “lockdown” is an example of fairly rigorous social distancing.

All of these methods can have specific downsides. Patients that are isolated within health care facilities may receive suboptimal care if isolation measures make it more difficult for health care workers to attend to them. Quarantine can result in the housing of uninfected people with asymptomatic infectious people and can lead to much higher rates of spread within the quarantine facilities. If social distancing measures involve loss of employment, education or routine medical care, they too can have serious negative effects both on individuals’ physical and mental health as well as on the economy.  In the case of Covid-19, it is unclear whether school closures would be of benefit since few children develop the disease, although we do not yet know if they are asymptomatic carriers of the infection.

 

Do non-pharmacological interventions work to reduce spread?

The question of the efficacy of quarantine, isolation and social distancing depends on when in the course of the infection most transmission is taking place. If most transmission occurs during the asymptomatic period – as it does, say, for HIV – isolation of patients with disease will have little impact. If, on the other hand, most transmission takes place when people have identified themselves as ill (as it did for SARS in 2002), isolation can be a very effective way to reduce spread. The benefits of quarantine – restricting the movements of people who are known to be in contact with an infectious case – depend on how effectively one can identify all contacts and prevent them from mixing with the general public. For obvious reasons, this can be very challenging and can have unintended consequences if quarantined people are housed together and become infected in that setting. Social distancing cannot prevent all transmission but could have a substantial impact on delaying transmission since contact rates are often much higher in congregate settings such as schools, prisons and other residential facilities. None of these measures is likely to lead to complete control of an epidemic since transmission is expected to resume once these are discontinued. But they may delay spread and give health systems time to develop better responses to the disease, whether those are new drugs, vaccines or simply improved efficiency of supportive care.

 

Are masks effective in preventing transmission?

There are several different types of masks available to prevent infection. Surgical masks are used to prevent surgeons from contaminating a surgical site with respiratory droplets and are designed to protect others, but not necessarily the wearer. N95 masks are much more heavy-duty and fit tightly around the nose and mouth, blocking most transmission of even small airborne particles. These are worn either by patients themselves or by health care workers who come into close contact with known cases. They are quite uncomfortable and very expensive but they probably do reduce transmission of infections transmitted through the respiratory route.  WHO and the CDC are urging the general public not to buy N95 masks as they are needed by health-care workers and patients and are in short supply.

 

How is Covid-19 diagnosed?

Covid-19 is currently diagnosed by RT-PCR (real time polymerase chain reaction) or sequencing of respiratory and/or blood samples using “primers” based on the Covid-19 RNA sequence. This detects ongoing infection with live virus. The recent experience in China and elsewhere suggests that only 30-60% of cases are correctly diagnosed by RT-PCR during the initial presentation although it is still unclear if this low sensitivity is due to issues with sample collection, transportation or faulty kits. In the US, testing by RT-PCR has been slow to take off in part because kits initially provided by the CDC were found to give a higher than expected number of indeterminate test results. Current reports indicate that the problem with the tests was due to a faulty reagent and that this issue has now been resolved. The use of “home brew” or “laboratory developed tests” developed by hospital laboratories was not endorsed by the FDA in the case of this coronavirus although hospital labs are usually allowed to develop and use their own tests. (Apparently, this rule has been relaxed as of February 28.) Some reports recommend Chest CT scans as a more sensitive diagnostic tool than the PCR tests with one study suggesting that CT was 98% sensitive compared to 70% sensitivity of PCR.

While PCR tests indicate whether are not a person is currently infected, they do not indicate recent infection that has been resolved. For this, antibody tests are necessary. A team at Duke-NUS Medical School in Singapore reports having developed such a test which it used to trace a cluster of cases that have already cleared infection. Several other companies and teams have also reported developing this type of test. The antibody test will likely be more useful for surveillance and for retrospective studies of transmission clusters than for routine diagnostic testing of patients.

 

How is it treated?

There are no FDA approved treatments yet available for Covid-19, although multiple clinical trials of antiviral drugs have been initiated. Remdesivir is an investigational “broad-spectrum” antiviral which is currently being studied in China as well as in the US – for the latter, specifically among people from the Diamond Princess now quarantined in Nebraska. Other agents that target the virus include favipravir, ribavirin, and galidesivir, nucleoside analogues that target RNA-dependent RNA polymerase. Protease inhibitors that might be effective include disulfiram, lopinavir and ritonavir; these agents were reported to be active against SARS and MERS. Another approach to treatment is to target host responses; pegylated interferon has been proposed as has the immune modulator, chloroquine. In the absence of specific therapy, most treatment of critically ill patients has included mechanical ventilation, treatment of sepsis and other types of supportive ICU care.  I have been told that as many as 400 clinical trials are now underway in China.

 

Will Covid-19 go away with warmer weather?

Some respiratory viruses (influenza, RSV, the coronaviruses that cause the common cold) are seasonal, meaning that they tend to peak during winter months and decline in summer. This seasonal pattern is due to multiple factors. In temperate climates, schools tend to be in session in winter and people tend to congregate in warm buildings in cold weather; these behavioral factors mean that the contact rate is often higher in winter than in summer. Humidity is known to play a role in the transmission of influenza with higher rates of transmission during periods when the air is drier – which tends to be the case in winter in many areas. Some evidence exists that there are seasonal differences in host immune response. This is often attributed to vitamin D levels – which are higher in summer because they reflect exposure to UV light – and this theory is supported by the results of a recent meta-analysis which showed that vitamin D supplementation modestly reduced the occurrence of acute respiratory infections. One study of two other novel coronaviruses (SARS and MERS) found that these persisted on inanimate surfaces for longer periods of time in colder and drier conditions. (https://www.journalofhospitalinfection.com/article/S0195-6701(20)30046-3/fulltext)

In contrast, multiple observers note that Covid-19 has already circulated widely in Singapore where temperatures are in the 80s F. Several studies have compared the epidemic growth rates in different areas in China with differing levels of absolute humidity and found that changes in weather alone would be unlikely to reduce COVID-19 incidence without the implementation of public health interventions.

(https://www.medrxiv.org/content/10.1101/2020.02.12.20022467v1)

Even if Covid-19 transmission declines with increasing temperatures in the Northern hemisphere, the virus has already been detected in the Southern hemisphere and transmission in those regions could intensify as the weather there cools down.

 

Where are we with vaccine development?

Vaccine development has proceeded at an unprecedented pace. A number of companies and research teams already have candidate vaccines that are either ready or close to ready to trial in humans. ModernaTx has submitted its mRNA-1273 vaccine to the NIH – a Phase 1 clinical trial to measure safety and immunogenicity is scheduled to begin in April in Seattle. Other companies that report having vaccines include Innovio, Janssen, Sanofi, Curevac and Clover Biopharmaceuticals. The speed with which these are being developed is partly due to the fact that a great deal of work was done on a SARS vaccine after the 2002 epidemic and some of that can be applied to this organism. Much of this research was funded through the Norway-based organization CEPI (Coalition for Epidemic Preparedness Innovations) which is funded by the Wellcome Trust, The Gates Foundation, and the World Economic Forum as well as some governments.

 

How long till a vaccine is available for widespread use?

New vaccines require a complex set of trials to establish safety, immunogenicity, optimal dosing, etc. Phase 1 trials are usually conducted in small groups of healthy volunteers and are designed to establish whether serious adverse effects occur with escalating doses of the agent and whether the vaccine produces the expected immune response. Phase 2 trials are designed to replicate Phase 1 results in a more diverse populations of volunteers and to test different vaccine schedules. Once safety, immunogenicity and optimal dosing are established, Phase 3 studies are conducted to determine vaccine efficacy. Phase 3 studies are usually much larger than Phase 1 or 2 studies and are conducted in people at risk for the infection in question. During the 2014 Ebola outbreak, novel vaccine trial designs were proposed and carried out that allowed reduced sample sizes and sped up the trial process.

The completion of all three steps is required for a vaccine to be approved by the FDA. The director of NIAID (National Institute for Allergy and Infectious Disease) estimated that this process would take between 12-18 months to complete and that a commercially vaccine would not be available until after that. The first Phase 1 clinical trial (of the ModernaTX vaccine) is scheduled to begin in the next two months.

 

What proportion of cases have been detected?

Although it is impossible to know exactly what proportion of cases of Covid-19 have been detected, it is highly likely that most cases have remained undetected. Several research groups have tried to estimate the proportion of cases that go undetected by looking at data on new cases occurring in countries that received air travelers from high burden areas.  The basic idea is that if we know that  – say –  2% of people in Wuhan were infected at some period, and we know how many air travelers arrived from Wuhan in other countries, and we know the R0 or the SAR, we should be able to estimate how many cases should have occurred as a result of those introductions. The difference between the actual number of reported cases and the estimated number is meant to be a proxy for undetected cases. Although there are some flaws to this reasoning – for example, the prevalence in Wuhan might have been much higher than reported, these biases would tend to underestimate the proportion of undetected cases(https://www.medrxiv.org/content/10.1101/2020.02.04.20020495v2).  Using these methods, research teams have estimated that between 60-75% of cases are undetected (https://www.imperial.ac.uk/media/imperial-college/medicine/sph/ide/gida-fellowships/Imperial-College—COVID-19—Relative-Sensitivity-International-Cases.pdf). Other groups have used a sort of reverse method to estimate the number of undetected cases in Iran –  that is, going back from the number of exported cases that have been detected in people traveling from Iran. In one study, the group estimated that 18,300 Covid-19 infections had occurred in Iran although to date, only 388 (2% of the estimated number) have been reported.  (https://www.medrxiv.org/content/10.1101/2020.02.24.20027375v1)

 

Could there be undetected cases in the US?

On February 23, the first case of locally transmitted Covid-19 was reported in the US in a woman with no known travel history and no ill contact. She came from Solano in Northern California and was transferred to the UC Davis Medical Center on February  19. At the time of her transfer, she had already been diagnosed with a severe pneumonia and was intubated and on mechanical ventilation. With her medical team suspecting that she might have Covid-19, she was kept in isolation at UC Davis but it is unclear from news reports how long she had been ill prior to her transfer, for how many days she had been hospitalized, and whether she had been in isolation prior to arriving at UCD. The UC Davis team was unable to obtain CDC permission to get Covid-19 testing until February 23 when the test came back positive. Notably, Solano is also in close proximity to the Travis Air Force Base where American evacuees from China were quarantined. A whistle-blower has complained that federal workers at the AFB were in contact with quarantined evacuees without having received proper training and without protective gear. These events strongly suggest that community transmission of Covid-19 has occurred in this region and given the estimated proportion of cases that go undetected and the lack of easy access to testing in the US, that other infectious cases may currently be present in the community.

Over the past couple of days, a number of new US cases have been reported that had no known travel or exposure history. One of these was a person in Snohomish county in Washington State whose Covid-19 genome was sequenced and found to be very closely related to a travel-related case reported in the same county on January 20. This suggests that the earlier case is likely to have transmitted to others in this region and that the second detected case was likely to have been infected by an undetected person who was part of a transmission chain that stems back to the first imported case. By examining the differences in the two Covid-19 genomes and knowing how much time has elapsed between the two infections, the investigator (Dr. Trevor Bedford) is able to estimate of the number of people who could have been infected through this transmission chain. His best estimate is several hundred although given the limited number of genomes analyzed, the number is quite uncertain and could range from less than 100 to over 1000. This is an unpublished report available on Twitter but multiple experts have concurred with these conclusions. The most important point here is that there has almost certainly been undetected transmission of Covid-19 in the US for at least 5-6 weeks and the true scope of this problem will not be fully realized until testing is much more widespread.

 

Is it likely that the US will experience an epidemic?

Most experts believe that it is inevitable that Covid-19 will spread in the US. It may be possible to slow transmission through the adoption of the kinds of interventions listed above but it is unlikely that a vaccine will be available in the near future. There are several factors that may make control of an epidemic especially difficult in the US. We are in the midst of a particularly bad influenza season and it will be difficult to know if one has seasonal flu or Covid-19. This may increase the number of people who need to be tested markedly, making this both more expensive and more logistically challenging. Many patients may be reluctant to present for diagnosis of what they consider a mild illness because the uninsured and under-insured may need to pay out of pocket for testing or for a doctor’s visit. Sick individuals may also be reluctant to stay home from work if they do not have accumulated sick leave or receive any paid time off from their employer.

 

What are other consequences of the Covid-19 epidemic?

One of the consequences of the Wuhan epidemic is that people who needed medical care for other conditions have not been able to obtain that care because hospitals and medical staff are at full capacity dealing with the virus.  News reports describe people in the region who have been unable to get dialysis or chemotherapy for the past month. So far, we have been unable to obtain data on whether general mortality has increased in Wuhan as a result of this lack of access to care. It is worth noting that during the Ebola epidemic, rates of maternal mortality increased because of the effect of Ebola on the availability, uptake and outcomes of maternal and newborn health services in Sierra Leone.

 

What should you do?

There are lots of very practical suggestions available from the CDC or WHO on measures one can take to protect oneself from infection and to prepare for the possibility of an epidemic. Some of these are obvious:

  • Wash your hands frequently.
  • Try not to touch your face.
  • Avoid people who are coughing or obviously ill.
  • Avoid large crowds if possible.
  • Don’t go to work if you are sick. Send your sick workers home.
  • If you need to seek medical care for a flu-like illness, call in advance and ask for instructions on where to go.
  • If you are sick, don’t go and visit your elderly or immuno-compromised friends and neighbors.

Less obvious:

  • Consider having a plan for what you might do if social distancing measures are put into effect or if you were quarantined.
  • Consider forgoing unnecessary travel (and possibly even necessary travel if it is to high risk places).
  • Think through how you and your teams can work from home – what are the best options for conference calls, etc.
  • Get whatever books you might need out of the library now.
  • Make sure you have a reasonable supply of any prescription drugs you need.
  • Have some emergency provisions but don’t go crazy buying up the grocery stores’ entire supply of canned goods.
  • Consider using a humidifier.

 

What are the highest priority research questions?

Beyond the efficacy of new and repurposed drugs and vaccine candidates and the development and validation of rapid, reliable diagnostics, some of the most urgent questions that need to be resolved include the following:

  1. What role do children play in the transmission of Covid-19? Are they getting infected but just not getting disease and if so, are they infectious in this asymptomatic state? Or are they somehow protected from being infected as well? This is important since one social distancing approach is school closures, which of course would be fruitless if children are not involved in transmission. In principle, this question could be easily resolved though wider testing.
  2. Are people who have had Covid-19 infection immune from re-infection and if so, for how long? One of the things that slows down disease spread is when enough people in a population are immune so that “herd immunity” kicks in – either through people having acquired immunity through previous infection or through vaccination. If natural or vaccine-induced immunity is not robust or long-lasting, this means that the “brakes” that usually end epidemics may not work. Evidence from other coronaviruses suggests that some immunity to this class of organisms is acquired but it is not clear how long it lasts.  Several reports from Asia indicate that some people who have had Covid-19 have cleared the virus, only to have it re-appear later. It is not clear if this is due to re-infection or to a stuttering or relapsing course in which virus levels were undetected but not fully cleared.
wtopstaff
Asia News
Thu, 05 Mar 2020 16:29:34 +0000
Description: NEW YORK (AP) — And back down goes the U.S. stock market. The S&P 500 sank 1.7% in late morning…

NEW YORK (AP) — And back down goes the U.S. stock market.

The S&P 500 sank 1.7% in late morning trading Thursday, and Treasury yields fell toward more record lows as the market swung back to fear about the effects of a fast-spreading virus in its latest yo-yo move. Just a day earlier, stocks had soared, in part on hopes that more aggressive moves by governments and central banks around the world could help contain the economic fallout.

Get used to such vicious swings, which will likely keep going as long as the number of new infections continues to accelerate, many analysts and professional investors say. If the S&P 500 ends the day down at least 2%, it would be the fourth straight day the index has lurched that much in either direction, something that hasn’t happened since 2011.

The growing understanding that the spread of infections may not slow anytime soon is pulling sharply on markets. That pull has taken turns this week with the increasingly worldwide push that governments and central banks are trying to give markets through spending and interest-rate cuts. It’s a sharp turnaround from earlier this year, when the stock market pushed to new highs on the hopes that the virus may remain contained in China and be just a short-term challenge.

In China, where the number of new infections has been slowing drastically, Shanghai-traded stocks have rallied nearly 12% since hitting a bottom on Feb. 3. They’re just 1.6% away from wiping out the last of the losses they’ve sustained since the new virus began to spread late last year.

Factories in China are gradually reopening, and a return to a sense of normal life may even be on the horizon following swift and severe actions by the government to corral the virus.

But elsewhere in the world, the mood is much darker. There are about 17 times as many new infections outside China as in it, according to the World Health Organization. Widening outbreaks in South Korea, Italy and Iran are responsible for the majority of new infections.

In the U.S., the death toll climbed to 11 due to the virus. California declared a statewide emergency late Wednesday, joining Washington, Florida and Hawaii. Southwest Airlines warned its investors that it’s seen a sharp drop-off in ticket sales in recent days and an increase in customers cancelling trips.

The S&P 500 was down 1.7%, as of 11:07 a.m. Eastern time. It had been down as much as 2.9% earlier in the day. The Dow Jones Industrial Average fell 510 points, or 1.9%, to 26,580, and the Nasdaq was down 1.2%.

Losses were widespread, and all 11 sectors that make up the S&P 500 index were down at least 0.8%. Financial stocks had the sharpest losses, at 3.4%. .

“The Western world is now following some of China’s playbook, closing schools and declaring a state of emergency for example, but there is a sense that this is too little, too late,” said Chris Beauchamp, chief market analyst at IG.

Travel-related companies continued to fall sharply on worries that frightened customers won’t want to confine themselves in planes or boats with others. Royal Caribbean Cruises sank 13.1%, Carnival fell 10.5% and American Airlines Group lost 8.1%.

Asian stock markets started Thursday off higher, riding the wave of optimism and hope that sent the S&P 500 spurting up 4.2% on Wednesday. U.S. congressional leaders reached a deal on a bipartisan $8.3 billion spending bill to battle the coronavirus outbreak, and the Bank of Canada followed up on the Federal Reserve’s surprise cut to interest rates the day before with its own.

Some economists expect the European Central Bank to make some kind of move before its meeting on March 12, and speculation is rising that the Swiss National Bank could follow shortly afterward. The Bank of England meets on March 26 on rates.

Health care stocks got a particularly big boost Wednesday after victories by Joe Biden in state primaries launched him into contender status for the Democratic presidential nomination with Bernie Sanders. Many investors see Sanders’ health care plan as damaging to the industry’s profits.

Japan’s Nikkei 225 rose 1.1%, South Korea’s Kospi gained 1.3% and stocks in Shanghai jumped 2%.

But markets turned lower as trading moved west to Europe. The French CAC 40 fell 2%, Germany’s DAX lost 1.6% and the FTSE 100 in London dropped 1.8%.

Several measures of fear in the market clenched tighter.

The yield on the 10-year Treasury sank to 0.93% from 0.99% late Wednesday. Earlier this week was the first time ever that the 10-year yield dropped below 1%. Shorter-term Treasury yields fell as traders increase bets for more rate cuts by the Federal Reserve to try to limit the economic damage. The two-year Treasury yield fell to 0.57% from 0.62%.

Gold climbed as investors piled into investments seen as safe. It rose $18.10 to $1,661.10 per ounce.

Crude oil held relatively steady after OPEC members proposed a deep cut of production to shore up prices. Oil has been sliding on worries that a global economy weakened by the virus will burn less fuel.

Benchmark U.S. crude was flat at $46.78 per barrel. Brent crude, the international standard, slipped 14 cents to $50.99 per barrel.

___

AP Business Writer Yuri Kageyama contributed.

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wtopstaff
Election News
Thu, 05 Mar 2020 16:21:15 +0000
Description: Elizabeth Warren, who electrified progressives with her “plan for everything” and strong message of economic populism, dropped out of the Democratic presidential race on Thursday.

WASHINGTON (AP) — Elizabeth Warren, who electrified progressives with her “plan for everything” and strong message of economic populism, dropped out of the Democratic presidential race on Thursday, according to a person familiar with her plans. The exit came days after the onetime front-runner couldn’t win a single Super Tuesday state, not even her own.

The Massachusetts senator has spoken with Bernie Sanders and Joe Biden, the leading candidates in the race, according to their campaigns. She is assessing who would best uphold her agenda, according to another person who requested anonymity to discuss private conversations.

Warren’s exit all but extinguished hopes that Democrats would get another try at putting a female nominee up against President Donald Trump.

For much of the past year, her campaign had all the markers of success, robust poll numbers, impressive fundraising and a sprawling political infrastructure that featured staffers on the ground across the country. She was squeezed out, though, by Sanders, who had an immovable base of voters she needed to advance.

Warren never finished higher than third in the first four states and was routed on Super Tuesday, failing to win any of the 14 states voting and placing an embarrassing third in Massachusetts, behind Biden and Sanders.

Her exit from the race following Sen. Amy Klobuchar’s departure leaves the Democratic field with just one female candidate: Hawaii Rep. Tulsi Gabbard, who has collected only one delegate toward the nomination. It was an unexpected twist for a party that had used the votes and energy of women to retake control of the House, primarily with female candidates, just two years ago.

Warren’s campaign began with enormous promise that she could carry that momentum into the presidential race. Last summer, she drew tens of thousands of supporters to Manhattan’s Washington Square Park, a scene that was repeated in places like Washington state and Minnesota.

She had a compelling message, calling for “structural change” to the American political system to reorder the nation’s economy in the name of fairness. She had a signature populist proposal for a 2% wealth tax she wanted to impose on households worth more than $50 million that prompted chants of “Two cents! Two cents!” at rallies across the country.

Warren, 70, began her White House bid polling near the back of an impossibly crowded field, used wonky policy prowess to rocket to front-runner status by the fall, then saw her support evaporate almost as quickly.

Her candidacy appeared seriously damaged almost before it started after she released a DNA test in response to goading by Trump to prove she had Native American ancestry. Instead of quieting critics who had questioned her claims, however, the test offended many tribal leaders who rejected undergoing the genetic test as culturally insensitive, and it didn’t stop Trump and other Republicans from gleefully deriding her as “Pocahontas.”

Warren also lost her finance director over her refusal to attend large fundraisers, long considered the financial life blood of national campaigns. Still, she distinguished herself by releasing dozens of detailed proposals on all sorts of policies from cancelling college debt to protecting oceans to containing the coronavirus. Warren also was able to build an impressive campaign war chest relying on mostly small donations that poured in from across the country — erasing the deficit created by refusing to court big, traditional donors.

As her polling began improving through the summer. Warren appeared to further hit her stride as she hammered the idea that more moderate Democratic candidates, including Biden, weren’t ambitious enough to roll back Trump’s policies and were too reliant on political consultants and fickle polling. And she drew strength in the #MeToo era, especially after a wave of female candidates helped Democrats take control of the U.S. House in 2018.

But Warren couldn’t consolidate the support of the Democratic Party’s most liberal wing against the race’s other top progressive, Sanders. Both supported universal, government-sponsored health care under a “Medicare for All” program, tuition-free public college and aggressive climate change fighting measures as part of the “Green New Deal” while forgoing big fundraisers in favor of small donations fueled by the internet.

Warren’s poll numbers began to slip after a series of debates when she repeatedly refused to answer direct questions about if she’d have to raise taxes on the middle class to pay for Medicare for All. Her top advisers were slow to catch on that not providing more details looked to voters like a major oversight for a candidate who proudly had so many other policy plans.

When Warren finally moved to correct the problem, her support eroded further. She moved away from a full endorsement of Medicare for All, announcing that she’d work with Congress to transition the country to the program over three years. In the meantime, she said, many Americans could “choose” to remain with their current, private health insurance plans, which most people have through their employers. Biden and other rivals pounced, calling Warren a flip-flopper, and her standing with progressives sagged.

Sanders, meanwhile, wasted little time capitalizing on the contrast by boasting that he would ship a full Medicare for All program for congressional approval during his first week in the White House. After long avoiding direct conflict, Warren and Sanders clashed in January after she said Sanders had suggested during a private meeting in 2018 that a woman couldn’t win the White House. Sanders denied that, and Warren refused to shake his outstretched hand after a debate in Iowa.

Leaning hard into the gender issue only saw Warren’s support sink further heading into Iowa’s leadoff caucus, however. But even as her momentum was slipping away, Warren still boasted impressive campaign infrastructure in that state and well beyond. Her army of volunteers and staffers looked so formidable that even other presidential candidates were envious.

Just before Iowa, her campaign released a memo detailing its 1,000-plus staffers nationwide and pledging a long-haul strategy that would lead to victories in the primary and the general election. Bracing for a poor finish in New Hampshire, her campaign issued another memo again urging supporters to stay focus on the long game — but also expressly spelling out the weaknesses of Sanders, Biden and Pete Buttigieg, the former mayor of South Bend, Indiana, in ways the senator herself rarely did.

Warren got a foil for all of her opposition to powerful billionaires when former New York Mayor Mike Bloomberg entered the race. During a debate in Las Vegas just before Nevada’s caucus, Warren hammered Bloomberg and the mayor’s lackluster response touched off events that ended with him leaving the race on Wednesday.

For Warren, That led to a sharp rise in fundraising, but didn’t translate to electoral success. She tried to stress her ability to unite the fractured Democratic party, but that message fell flat.

By South Carolina, an outside political group began pouring more than $11 million into TV advertising on Warren’s behalf, forcing her to say that, although she rejected super PACs, she’d accept their help as long as other candidates did. Her campaign shifted strategy again, saying it was betting on a contested convention.

Still the longer Warren stayed in the race, the more questions she faced about why she was doing so with little hope of winning — and she started to sound like a candidate who was slowly coming to terms with that.

“I’m not somebody who has been looking at myself in the mirror since I was 12 years old saying, ‘You should run for president,’” Warren said aboard her campaign bus on the eve of the New Hampshire primary, previewing a ceasing of campaigning that wasn’t yet official. “I started running for office later than anyone who is in this, so it was never about the office — it was about what we could do to repair our economy, what we could do to mend a democracy that’s being pulled apart. That’s what I want to see happen, and I just want to see it happen.”

She vowed to fight on saying, “I cannot say, for all those little girls, this got hard and I quit. My job is to persist.”

But even that seemed impossible after a Super Tuesday drubbing that included her home state.

___

Catch up on the 2020 election campaign with AP experts on our weekly politics podcast, “Ground Game.”

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Jack Moore
Health & Fitness News
Thu, 05 Mar 2020 15:59:36 +0000
Description: See coronavirus test results from D.C., Maryland and Virginia as they are updated.

The novel coronavirus has infected more than 94,000 people worldwide and killed more than 3,200 since emerging in Wuhan, China, late last year.

There have been no confirmed cases in D.C., Maryland and Virginia as of March 4, but officials say they are prepared.

Recently, public health labs in all three jurisdictions were all cleared to perform their own COVID-19 testing, which is expected to speed up the testing.

See the test results provided by each jurisdiction’s public health department below. Figures will be updated at least once a day.

Updated March 5, 10:59 a.m.

D.C.

Number of patients tested for COVID-19: 8
Number of negative results: 6
Number of pending results: 2
Number of laboratory-confirmed cases: 0

Maryland

Number of patients tested for COVID-19: 31
Number of negative results: 17
Number of pending results: 14
Number of laboratory-confirmed cases: 0

Virginia

Number of patients tested for COVID-19: 21
Number of negative results: 18
Number of pending results: 3
Number of laboratory-confirmed cases: 0


More coronavirus coverage


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wtopstaff
Asia News
Thu, 05 Mar 2020 15:57:27 +0000
Description: BETHLEHEM, West Bank (AP) — Palestinian officials on Thursday indefinitely closed the storied Church of the Nativity in the biblical…

BETHLEHEM, West Bank (AP) — Palestinian officials on Thursday indefinitely closed the storied Church of the Nativity in the biblical city of Bethlehem over fears of the new coronavirus, weeks ahead of the busy Easter holiday season.

The announcement by the Palestinian tourism ministry threatened to derail the vital tourist season in the spot revered as Jesus’ birthplace and highlighted the spread of the virus across the Middle East, where worship at major holy sites has been greatly disrupted by the health scare. Iran, the epicenter of the virus in the region, said it would set up checkpoints to limit travel between major cities and urged citizens to reduce their use of paper money to fight the spreading outbreak, which has killed at least 107 people across the Islamic Republic.

The Church of the Nativity was closed after suspicions that four Palestinians had caught the virus, prompting a flurry of measures that included banning all tourists from the West Bank for an unspecified amount of time and shutting down other places of worship in Bethlehem for two weeks. If confirmed, the four suspected cases would be the first in the Palestinian areas.

Built on the grotto where Christians believe Jesus was born, the church joins a list of prominent tourist and holy sites to shutter their doors in the wake of rising fears over the spread of the virus, which has infected tens of thousands and killed more than 3,000 globally.

Just before 4 p.m., a bearded clergyman walked outside and locked the church’s wooden door with a large key. Just a few foreign tourists milled about outside.

Artur Joba, a Polish tourist visiting with his girlfriend, said he had decided to cut his stay in Bethlehem short and would head to nearby Jerusalem on Friday.

“I heard they found the coronavirus infection here and we decided to leave,” he said. “I’m going back to my hotel now to look for a hotel elsewhere.”

Later, a team of workers dressed in white overalls arrived with jugs of cleaning materials and walked through a side entrance to disinfect the building. Tariq al-Ali, one of the workers, said it was the second time his team disinfected the church. “We have disinfected many institutions in the past week. We are under pressure,” he said.

Saif Saboh, a Palestinian tour guide, said a number of groups had canceled visits in recent days. He said he has stopped shaking hands or getting too close to tourists and washes himself off each evening. “I’m terrified,” he said. “It is serious and any tourist could be infected.”

The virus has disrupted Muslim worship across the Middle East. Saudi Arabia banned pilgrimages to the holy city of Mecca, while Iran has canceled Friday’s Islamic prayers in major cities.

The Church of the Nativity receives some 10,000 tourists a day, according to Palestinian officials, and is expected to welcome tens of thousands of visitors during the busy Easter season.

Elias al-Arja, the head of the Bethlehem hotel owners union, angrily accused the government of caving in to panic. “This will cause huge damage to the economy. We have 3,000 workers in the tourist sector and they will all go home. Who is going to feed their families?” he said.

Anton Suleiman, the mayor of Bethlehem, acknowledged the difficult situation. “Even if this causes huge damage to the economy, public safety is the most important thing to us,” he said.

In Iran, Health Minister Saeed Namaki announced his country’s new restrictions at a televised press conference. He added that schools and universities will remain closed through Nowruz, the Persian New Year, on March 20.

“We will strictly control comings and goings,” he said.

Ali Darvishpour, deputy governor of Alborz province, said that except for medical centers, all governmental offices, banks and institutions will be closed Saturday, the first day of Iran’s work week, according to the semi-official ISNA news agency. He also urged people to stay at home.

U..S. special representative for Iran, Brian Hook, said Thursday the U.S. offered humanitarian assistance to Iran to help them deal with the virus outbreak, but “the regime rejected the offer.” Hook, speaking at a news conference in Paris, also said the U.S. has asked Iran to release Americans detained in prisons there “on medical furlough” over fears the coronavirus may be infesting the country’s prisons. He said that Washington was working through Switzerland and could not provide details.

The Mideast has seen over 3,740 confirmed cases in the region. Iran and Italy have the world’s highest death tolls outside of China.

Israeli officials said they were working closely with their Palestinian counterparts to contain the virus. COGAT, the Israeli defense body responsible for Palestinian civilian matters, said it had delivered 250 test kits to the Palestinians and was coordinating joint training sessions for Israeli and Palestinian medical workers.

For the time being, other major places of worship in the Holy Land remained open. Israeli officials said there were no special precautions at the Western Wall, the holiest site where Jews can pray, though hand sanitizing stations were placed at the site.

Western Wall Rabbi Shmuel Rabinowitz encouraged more visits. “In this time of distress, there is nothing more appropriate than coming to pray at the Western Wall,” he said.

The nearby Al Aqsa mosque compound was expected to welcome 50,000 worshipers for Friday prayers. The Islamic Waqf, which administers the site, encouraged the faithful to ensure good personal hygiene.

Israel, which has 16 confirmed virus cases, has taken strict measures in a bid to stave off an outbreak, including banning the entry of visitors from some 10 countries.

On Thursday, German airline Lufthansa said it and its Austrian and Swiss subsidiaries were canceling flights to and from Israel for three weeks starting Sunday because of Israeli restrictions on incoming tourists. With many tourists to the West Bank flying in through Israel’s international airport, the Palestinians are likely also being affected.

The virus has started to shake Israel’s tourism industry as well. Israeli airline El Al, which has canceled dozens of flights to countries with outbreaks, announced Wednesday that it was laying off 1,000 employees.

Earlier Thursday, the United Arab Emirates warned its citizens and its foreign residents not to travel abroad amid the ongoing outbreak, a stark warning for a country home to two major long-haul airlines. Both airlines, Emirates and Etihad, have encouraged staff to take time off as international travel has dropped due to the virus.

Worship continued to be disrupted elsewhere, as Iraq canceled Friday prayers in the Shiite holy city of Karbala, according to a statement Thursday. Millions of Iraqis look to the weekly sermon delivered by a representative of Grand Ayatollah Ali al-Sistani for guidance every Friday.

___

Associated Press writers Jon Gambrell in Dubai, United Arab Emirates; Amir Vahdat in Tehran, Iran; Qassim Abdul-Zahra in Baghdad, Josef Federman in Jerusalem and Elaine Ganley in Paris contributed.

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