COVID-19 Update 3/11/20
see the email below from jon pincus (published with his consent). it is a really useful compilation of data and emerging trends in coronavirus. i added a really interesting new study that came out yesterday, which is small but adds some very useful information about when and how this virus attacks....
there was an interesting study just published on a more detailed assessment of coronavirus in a small cohort exposed to a single case (see https://www.medrxiv.org/content/10.1101/2020.03.05.20030502v1.full.pdf). in brief:
--9 patients who acquired their infection from close contact to a known index case in Munich, Germany [this has the advantage of tracking the virus from a single source and seen over a short period of time, and less affected by larger samples of symptom-based contacts from multiple sources at different stages of disease and with potentially different genetic variants]
--all patients were tested for the other usual culprits (all negative): RSV, influenza A and B, rhinovirus, enterovirus, human parainfluenza virus 1-4, human metapneumovirus, adenovirus, human bocavirus, and an array of other coronaviruses (HCoV-HKU1, -OC43, -NL66, -229E). ie, no coinfections in this group
--all were diagnosed by oro- or nasopharyngeal swabs. and there was no difference in viral loads or detection rates comparing naso- and oro-pharyngeal specimens (needs to be tested in larger group, but as you suggest below, the oral sampling is less likely to spread the virus. would be great to have larger studies/more data to confirm). and in 2 people they showed that swab samples had higher sensitivity than sputum
--earliest swabs were taken on day 1 of symptoms (almost all patients had very mild or prodromal URI-type symptoms): all swabs taken between day 1-5 were positive. all had large viral RNA loads, average 6.76x105, then decreased to 5.13x103 (maximum virus detected was on day 4 of symptoms). detection rate after day 5 was down to 46%. of note, the viral detection at the peak was 1000 times higher than with SARS. all of this explains the much higher infectivity rate of the current virus, since it has high concentrations when people are only a little sick (ie, the majority of people are likely shedding virus even before they are first tested)
--live virus isolation (which is really what is associated with infectivity): in the first week, virus was isolated from 17% of swabs and 83% of sputum samples, and no virus was isolated after day 8 (though there continued to be high viral loads). we really need large scale data on this to be sure
--stool samples had high viral RNA loads, but no viral isolation. the presence of high viral loads in the stool may signify high active replication in the GI tract, though this small study did not find active virus and only one patient had intermittent diarrhea. need more data here (though in China diarrhea was found in only 2 of 99 cases)
--one thought here is that if this virus is really spread by respiratory shedding, the primary focus should be on controlling droplet spread (cough, etc) with reinforced keeping distance from coughers, using masks, etc. fomite-spread (eg being on surfaces, such as tables, etc) is still a potential source: a recent study did find that the SARS-CoV-1 can last up to 4 hours on copper, 24 hours on cardboard, and 2-3 days on plastic an stainless steel (see https://www.medrxiv.org/content/10.1101/2020.03.09.20033217v1.full.pdf ).
--no virus detected in blood or urine samples
--they sequenced full virus genomes and found: in some patients with virus isolated from the throat vs sputum (ie, lung), there were different/independent mutations. this may be really important. initial studies suggested a large viral tropism for ACE2 binding in the lung, hence the significant pulmonary infections detected early-on in China. and there are not so many ACE2 receptors in the upper airways. these genetically independent variants suggest that the virus is proliferating both in the upper and lower respiratory tracts independently (and explaining that 7 of these 9 patients just had upper tract symptoms, and it seems that the presentation and statistics you note below reflect more of the upper tract findings with not so much cough/fever/etc as initially reported)
--of some concern, as symptoms waned in the first week, viral RNA remained positive longer even after full resolution of symptoms after mild courses of illness. but in this small study, whole virus isolation (and presumed infectivity) was not found
--seroconversion by IgG and IgM in serum was not found between days 3-6. those patients followed 2 weeks did have neutralizing antibodies (they suggest seroconversion happened between 6-12 days), though the titer did not correlate with clinical course. and there was no abrupt virus elimination at time of seroconversion
by the way, another difference from the flu: it seems that the pulmonary infections are (so far) from the virus itself and not from a secondary bacterial infection, as sometimes happens with the flu
From: Jonathan Pincus
Cases worldwide 119,132
Deaths worldwide 4,284
Massachusetts - 51 new cases, total = 91
Health Care workers infected in China ~ 1700
Summary Basics
Virus: COVID-19
Clinical infection: SARS-Cov2
Age distribution: median age 56,
Symptoms:
Lab/imaging:
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Treatment - Remdesivir in RCT, Kaletra (in vitro activity), corticosteroids NOT effective ? harmful
IDSA handout for patients
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Testing
According to Quest’s Website as of 5pm March 10, 2020 “This test is now available nationally.”
The test is run in California with a 3-4 day turn around. Testing should now be available from MDPH, Quest and LabCorp.
Per CDC: and MDPH : For initial diagnostic testing for COVID-19, CDC recommends collecting and testing upper respiratory (nasopharyngeal AND oropharyngeal swabs), and lower respiratory (sputum, if possible) for those patients with productive coughs.
Both Labcorp and Quest indicate that nasopharyngeal OR oropharyngeal swabs are acceptable.
I cannot find data on the relative test characteristics of NP vs OP vs NP/OP sampling. OP specimens seem like they would involve less risk for health care personnel so in the absence of a proven benefit for NP swabs, I would suggest we use OP swabs.
BEFORE TESTING, please review personal protection equipment recommendations for specimen collection. The best I could find are from Nebraska and may use a different collection system than we do. Video Infographic
Specimens - Upper respiratory samples should be collected using 1 nasopharyngeal swab in M4, VCM, or UTM media or 1 oropharyngeal swab in another M4, VCM or UTM media. Only sterile Dacron® or Rayon swabs should be used. Do not use calcium alginate as they may contain substances that inhibit PCR testing. Wooden shaft swabs should also not be used.
Recommended Videos/Teleconferences
CROI Special COVID-19 Session (1st presentation is a must watch)
CDC guidelines on doffing and donning personal protective equipment. (or the MGH trainings: donning and doffing)
Ways to view the numbers
Information is Beautiful (thank you Dr Huntington)
Please also consider reviewing and signing the open letter to Vice President Pence
Some potential useful sites are:
Reference list: Clinical Characteristics of Coronavirus Disease 2019 in China initial analysis from the outbreak in China Corticosteroids may be harmful in COVID-19
New Information from 3/10/20
China Response (Please view CROI session above for and excellent report from China CDC)There is some discussion about missed opportunities in the first few weeks of the first cases in China including the suppression of the ophthalmologist who tried to publicize the outbreak on social media and was infected and later died. However from the time of the identification of a cluster of patients with pneumonia in late December to tracking it to the Hunan Seafood market was 4 days and the market was closed the next day. The virus was identified within 7 days and a test was developed 4 days after that. In under 1 month the city of Wuhan (population ~11,000,000) was shut down and subsequently ~1.4 Billion people underwent 10 days of home isolation. >50,000 hospital beds were added including 3 new hospitals and 16 temporary modular hospitals and >40,000 health care workers were sent to Hubei. People in China are now being tracked via cell phone QR codes with required check ins a various locations to track those with possible exposures based on where cases are identified. With the aggressive actions taken, China CDC estimates that they averted 1,000,000 cases and the number of new cases in China has plummeted.
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Concerning issues
The Seattle Flu Study Dr. Helen Chu in Seattle coincidentally was running a flu study collecting nasal swabs in Puget Sound. She requested permission from CDC and FDA to test specimens for COVID-19 but was told no because they were not a clinical lab and because they did not have informed consent for COVID-19 testing. After repeated attempts she went ahead and started testing. On the first round they identified a teenager with COVID-19. They were told that since it was a research study and not a clinical lab they could no notify subjects of results - they did and notified the student shortly after he had returned to school following an illness. The school was closed. Dr. Chu was then told by CDC and FDA to stop testing. On March 2 the IRB determined that it would be unethical not to test the samples and testing restarted but was later shut down by state regulators.
Cruise Ship Cases - The Diamond Princess Cruise ship off the coast of Japan initially had 10 passengers that tested positive on February 3. The ship was quarantined and not evacuated until February 20. 619 of the 3700 passengers and crew have tested positive and 7 have died. Mathematical modeling suggested that:
- the delay resulted in an 8 fold increase in the number of infections (from 76 to 619)
- the R0 (R naught or reproductive number) the number of new infections from each infected person was estimated to be 14.8 which is about 4 times that seen in Wuhan.
- they calculated the population density in Wuhan and on the cruise ship and estimated that the population density on the ship was about 4 times that of Wuhan suggesting that the R0 was related to the population density
The Grand Princess Cruise ship has 3500 passengers and crew and 21 people with known COVID-19 infection. The US held the ship off the coast for 6 days before it allowed the start of an evacuation on Tuesday 3/10. Even now it is estimated that it will take 2-3 days to evacuate the ship AND the 1,100 crew members, 19 of whom have tested positive will be kept on the ship and sent back to sea to be treated and quarantined on the ship. Given the data from the Diamond Princess analysis and the ongoing risk to the uninfected crew not allowed to evacuate this is unconscionable. (opinion, not fact)
Worrisome at risk populations/areas in the US will include nursing homes, homeless shelters, ICE detention centers, rural America where hospitals have closed, immigrant populations afraid to seek medical care, those with no insurance and those with no sick time benefits afraid to/unable to not go to work when they are ill. Assuming the transmissibility or R0 is related to population density and that access to treatment including ICU care is important for keeping the mortality rate down what will happen if/when this infection hits refugee camps in Greece, cities with high population densities (Manilla 119,600/sqmile vs Wuhan 3,200/sqmile) or cities with high population densities and extremely limited medical and public health resources e.g. Port-au-Prince with ~65,000 people/sqmile.
“The emerging situation in Italy seems quite different from China. The situation is most acute in Lombardy, the northern region that is the worst-affected part of the country, with 5,469 cases, including 440 in intensive care.
Antonio Pesenti, coordinator of the region’s intensive care crisis unit, told Italy’s Corriere Della Serra newspaper that the already dire situation would become “catastrophic” if people did not observe orders to stay home.
“By now, we’re forced to provide intensive care treatment in the corridor, in the operating rooms, in the recovery rooms,” he said. “We gutted entire hospital wards to make room for the seriously ill. One of the best healthcare systems in the world, the Lombard one, is one step away from collapse.”
Lombardy’s top health official, Giulio Gallera, told Bloomberg that the region had dedicated 80% of its 1,123 acute-care beds to coronavirus. But Pesenti said that according to some forecasts, Lombardy could have 18,000 hospitalized coronavirus patients by March 26, between 2,700 and 3,200 of whom would require acute care.”
reportedly, 70 infections have been linked to a conference of 175 people in Boston on February 26 which included at least one person from Italy. In addition there may be related cases from infected individuals who traveled after the conference to Tennessee, North Carolina, Indiana, New Jersey, Washington DC, Norway and pssibly Germany, Australia and Argentina. One person from the conference became ill and presented to MGH for testing but was told that testing was not indicated. After several more employees became and were turned away for testing, Biogen notified DPH to report a cluster of 50 attendees with flu-like symptoms. The following day the company notified DPH that at least two people from Europe who were at the conference had tested positive. The next day the company followed up with attendees from the conference and learned that three had tested positive outside of Massachusetts.
A 50 year old attorney with no travel risks reportedly presented to the doctor numerous times and eventually went to the hospital. He was diagnosed with pneumonia and placed in a regular room with no precautions. 4 days after admission he was diagnosed with COVID-19 infection. His condition deteriorated , he was intubated and transferred to another with no special precautions. Reportedly ~90 cases have been linked to this infection including 1 hospital worker, the person who drove him to the hospital, his Rabbi and multiple family members of infected individuals. A containment zone of 1 mile has been established in the area.
One of the new New York City cases confirmed over the weekend is a 33-year-old Uber driver in Queens. He went to St. John’s Episcopal Hospital in Far Rockaway on February 22 with flu symptoms, then was sent home only to return when his symptoms worsened. 40 doctors and nurses from the hospital have self-quarantined themselves as a result of their exposure to the patient. According to Mayor de Blasio, the man did not have a TLC license and drove passengers in Long Island.
Workflow issues/Administration
we might want to consider
Travel history period – in order to be most inclusive, I think we should use a travel history of 1 month when assessing patients. While the incubation period for COVID-19 is not known, it may be as long as 2 weeks and thus if we see someone who has had a cough for a week and ask about travel in the past two weeks we might miss cases.
Staff Interaction – at this point I think it is prudent to limit staff exposure to any potential COVID-19 cases. We should look at our workflows and try to minimize the number of people entering the room for potential cases e.g. excluding medical students, ?residents, having provider take vitals instead of MA, not allowing staff to remain in the room during nebulizer treatments.
We should review policies for sick leave to encourage staff who are ill NOT to come to work including those that may not yet have sick time.
We should consider if some staff can work from home.
We should consider if, over the next few weeks as we learn more, some non urgent visits can be postponed especially for our elderly patients.
We should explore if some visits can be conducted via telehealth or car visits.
As with similar epidemics in the past we should avoid stigmatizing patient based on the ethnicity, country of origin or travel
Table in progress -
COVID-19
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Influenza A
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SARS
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Case Fatality Rate
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0.3-1.0%
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0.1%
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10%
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Total Cases
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US 2019/20 season
~40,000,000
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~8000
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Total Deaths
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US 2019/20 season
18,000 - 46,000
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~800
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Presymptomatic infectious Period
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5-6 days
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1-2 days
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0 days
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R0
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2-3
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1.1-1.5
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3
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Annual Air travel during outbreak
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4 billion
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1 billion
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