COVID-19 Task Force Updates

COVID-19 DIGEST

From the Infectious Diseases Divisions at UCSF, ZSFGH, and VAMC

Update: March 27, 2020
EPIDEMIOLOGY

Local

As of today, there are 4,205 confirmed COVID-19 cases and 85 deaths in California. In San Francisco, there are 279 confirmed COVID-19 cases and 3 deaths. Across the UCSF/ZSFG/VA system, 26 patients with COVID-19 are hospitalized (12 in ICU). Testing capability has ramped up at all three hospitals, with local capacity in the three associated clinical labs.

National

The US, which is the third most populous nation on the planet, now has the highest number of cases of COVID-19 in the world, exceeding those in China and Italy as of Thursday, March 26. Latest US estimates are over 100,000 cases and 1,500 deaths. The surge in cases in the US has been most dramatic in New York State, which accounts for just under half of the nation’s infections. New York State as of today had44,635 confirmed cases, 5,327 hospitalizations, and 519 deaths. The majority of the cases and deaths were in New York City, with 25,573 cases and 365 deaths. Over 100 deaths were reported in NY on March 26 and hospital systems were overwhelmed, including emergency rooms, inpatient wards, and intensive care units. Governor Andrew Cuomo of New York had ordered a lock-down of the state with all non-essential services to be closed and people sheltering in place on March 20. New York is not the only city or region facing case surges. Cook County (Chicago), Wayne County (Detroit), and Atlanta are others, to name a few.

Global

There are over 590,000 cases of COVID-19 and 26,943 deaths globally.* Europe was the epicenter of the pandemic until the US surpassed Italy in number of cases yesterday. Italy’s number of new cases of coronavirus has been slowing with lower numbers of new cases occurring daily for the 6th consecutive day as of today. However, the case fatality rate in Italy still remains the highest in the world with 8,215 deaths and 80,059 cases (10.1%)—see below for recent publication on Italy’s high mortality rate. (Global numbers via Johns Hopkins.)

Public Health Action:

Major public health actions continue worldwide, with Prime Minister Narendra Modi of India announcing a national lockdown on the country on Tuesday, March 24 for 21 days, impacting 1.3 billion people. Countries across Africa and many in Latin America are on lockdown although Brazil and Mexico were initial “hold outs” for such public health measures. The government of Mexico mandated stay at home orders on Tuesday March 24 and many cities across Brazil (despite President Jair Bolsonaro’s reluctance) has imposed shelter in place mandates. The global number of people under some form of lockdown is now around 2.6 billion – one-third of the human population, more humans than were even alive during World War II.


DAILY UPDATES
https://www.who.int/emergencies/diseases/novel-coronavirus-2019


UP TO THE MINUTE DISPATCHES

Can pregnant women transmit COVID-19 to their infants?

We previously reported there was no evidence to date for congenital COVID-19. In multiple small case series (n<20 in each), newborns to women with COVID-19 were either asymptomatic or had mild disease consistent with post-natal acquisition. However, two articles published in JAMA on March 27, 2020 suggest vertical transmission might occur [Dong et al, Zeng et al]. A total of three infants born to women with mild COVID-19 disease were found to have elevated SARS-CoV-2 IgM levels at birth. Because IgM molecules are generally too large to cross the placenta (in contrast to IgG and cytokines), these results provide serologic evidence of in utero transmission. These infants remained asymptomatic and had negative RT-PCR virologic testing. Limitations of these reports include their small number and the potential false positivity of IgM. So, as of today, we can say the answer to this question is “Maybe.” UCSF has launched a nationwide registry for pregnant women with suspected or confirmed COVID-19 and their infants called PRIORITY.

Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy
SARS-CoV-2 case fatality rate in Italy is 10.1%, substantially higher than that observed in China (2.3%) and South Korea (1.0%). Authors attributes this discrepancy to three possibilities: 1) Population age. The case fatality rate (CFR) within age strata from 0-69 years is similar between Italy and China. However, older people in Italy make up a greater proportion of those diagnosed. The overall older age distribution in Italy might in part explain the higher overall CFR. However, even when the sample is stratified by age, the mortality rate of older Italians is substantially higher (20.2% vs 14.8% for those over 80). 2) Case definition. Clear criteria for the definition of COVID-19-related deaths are not available. In Italy, death was attributed to COVID-19 in any patient with positive SARS-CoV-2 PCR, regardless of pre-existing diseases or indication for admission. 99% of COVID-19 deaths in Italy involved at least one medical comorbidity; 3) Testing strategies. The Italian government prioritized testing for patients with more severe clinical symptoms--nearly 20% of all tests were positive. This is in contrast to other countries like South Korea, which instituted widespread testing (larger denominator) and thus far has calculated a case fatality rate of around 1.0%. These are reasonable points, but we still have much to learn to explain these wide ranging mortality rates.


FAQ

1. What proportion of cases of COVID-19 in the US are among health care workers?
We do not yet know the answer for the US. We do have some data from other countries. Among 72, 314 cases in mainland China (through 2/11/20), 3.8% were in health care personnel [Guan et al]. 75% of these cases were diagnosed in Hubei Province. In a separate study of a selected group of 1099 patients from mainland China with laboratory-confirmed COVID-19 the percentage of healthcare workers among the cases was 3.5% [ICN]. In Italy, which continues to experience widespread community transmission, 9% of COVID-19 cases are in healthcare workers. Currently the California Department of Health is reporting 42/3006 (1.3%) in their latest stats that include HCW. It is likely that depending on local outbreaks this number will vary. We can say HCW transmission is lower than seed with SARS. In the SARS outbreak in Canada in 2002-2003, 43% of the cases were in healthcare workers.

2. Can SARS-CoV-2 cause cardiac injury?
Perhaps. This is an evolving story. We know patients with underlying cardiovascular disease are at higher risk for severe COVID-19. However, COVID-19 itself may be associated with cardiac injury. Studies of patients hospitalized with COVID-19 in China reported cardiac injury in 17-20% of cases. One study found that patients with cardiac injury were older, had more comorbidities, and a higher risk of death when compared to those without cardiac injury. Another study reported that 7% of 68 COVID-19 related deaths were due to myocardial damage/heart failure. Whether COVID-19 associated cardiac injury is due to direct viral injury or other mechanisms requires further research. Awareness of this potential complication, particularly when considering medications with potential cardiac toxicities is to be noted while researchers study potential mechanisms.

3. Should patients without symptoms undergoing transplantation or intensified immunosuppression be tested for COVID-19 in settings with widespread community circulation?
Yes, if the logistics allow for it. Physicians may decide to alter management for a patients with a positive PCR for COVID-19 undergoing these procedures. We have described in prior digests that patients can have high viral loads detected on PCR prior to symptoms. It is important to note that the current tests are is only 70% -80% sensitive—so using current assays, one is reducing but not eliminating the possibility the patient has COVID-19 underlying disease. In other words, a positive test confirms disease, but a negative test does not completely rule it out.

4. Are loss of smell and loss of taste symptoms of COVID-19 infection?
Yes, this is likely true. Physicians in several countries have reported anosmia/hyposmia (loss of/decreased smell) and ageusia/dysgeusia (loss of/dysfunction of taste) as symptoms associated with COVID-19 infection. A cross-sectional survey of 59 hospitalized COVID-19 patients in Italy demonstrated that 34% had at least 1 taste or olfactory disorder symptom; 19% had both. Onset of symptoms occurred prior to hospitalization in 20% (including 91% of taste disorders); the remaining 14% occurred during the hospital stay. Symptoms were more common in women (53%) vs. men (25%) and in younger individuals (affected median age 56 vs. non-affected median age 66). Anecdotal reports have described anosmia in 30% of a COVID-19 cohort in South Korea and in >66% of 100 non-hospitalized COVID-19 patients in Germany. The American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) proposed that anosmia and dysgeusia is included in clinical screening algorithms for when alternative explanations are absent (i.e. allergic rhinitis, rhinosinusitis).

Any questions, please feel free to reach out.
 
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COVID-19 DIGEST

From the Infectious Diseases Divisions at UCSF, ZSFGH, and VAMC

Update: March 24, 2020

The COVID-19 global epidemic spread is continuing to accelerate. The United States is joining Europe as an epidemic epicenter. New York is at the center of the increases. Last week, the US was #8 globally in number of confirmed cases. This week the US is #3. It is important to note that interpretation of increases in confirmed COVID-19 cases is highly dependent on testing access; however deaths (less subject to bias in detection) are rapidly increasing – 140 deaths in the US on Monday alone. Although hundreds of clinical trials for COVID-19 are ongoing, there is no proven treatment for this disease to date.

EPIDEMIOLOGY

Local

As of today, there are 152 confirmed COVID-19 cases and 0 deaths in San Francisco.* In many medical centers, the hospital census of persons under investigation (PUI) is far higher than hospitalized cases, in part because of slow testing turnaround in some settings. Disposition of non-critically ill PUI with unstable housing/supportive services also continues to be a challenge, leading to hospitalizations for this group. At present, intensive care needs are being met; and plans across the city are underway to meet possible increased demand as we carefully monitor our local epidemic curve under shelter-in-place conditions. (SF numbers are tracked by SFDPH.)

National

There are 46,805 confirmed cases in the US; on Monday over 10,000 new cases were reported. New York State (25,000 cases, of these ~15,000 in New York city) is experiencing a rapid surge in confirmed cases and hospitalized patients and now accounts for 5% of all global cases. New York City’s health care system is experiencing challenges in every level of the response including staffing, hospital and ICU beds, and PPE. City leaders are breaking new ground in innovative approaches to increase capacity for care provision including repurposing operating rooms and underutilized buildings. (National numbers via CDC.)

Global

There are over 407,000 cases of COVID-19 and 18,200 deaths globally. The death toll in Italy (~ 6,800 to date) continues to exceed what has been seen in many other regions in terms of case fatality rates, and the health systems are overwhelmed by critically ill patients. For 2 days, new cases and deaths in Italy decreased, but deaths rose to 743 today (Tuesday) - the epidemic is still raging.

Public Health Action:

We are seeing an escalation in public health interventions in most settings and de-escalation in a few Asian countries where the cases have declined. In the US, where cases are rapidly escalating, many states have joined California in shelter-in-place policies. The US has put strict restrictions on border crossing from Canada and Mexico. Increasingly, countries in South America and Africa are ramping up public health strategies, including shelter-in-place, with a goal to mitigate spread in their regions by acting early since COVID-19 came later to these regions. It is estimated that 1.2 billion persons are being asked globally to stay in their homes.

Several Asian countries/regions had rapid responses to COVID-19 including Hong Kong, Singapore and Taiwan. It will be instructive to watch as these regions scale back their public health interventions. Each of these countries has plans or is already implementing loosening restrictions. Hong Kong had previously reported only 150 cases, and on March 2, allowed persons to return to work. They subsequently noted a new spike of 30 cases associated with return of citizens to the island. Maintaining epidemic control is going to require robust contact testing and tracing systems to succeed when movement restrictions are loosened. The last 2 weeks has seen massive global movement of persons returning to their native countries (including to the US) which can be the source of new epidemic outbreaks.


DAILY UPDATES
https://www.who.int/emergencies/diseases/novel-coronavirus-2019


COVID TESTING CAPACITY

Testing capacity for inpatient facilities continues to improve. The turnaround for UCSF Health is ~ 12 hours, for ZSFG is 12-24 hours and for the VA is 24-48 hours.


UP TO THE MINUTE DISPATCHES

What are the data behind the new interest in using hydroxycholroquine and azithromycin for COVID-19 treatment?

A very small, non-randomized French study (available as a pre-print) evaluated hydroxychloroquine (HCQ) 200 mg TID for 10 days for treatment of hospitalized COVID patients. The control arm was COVID patients who declined treatment or who were at another medical center. At day 6, the SARS-CoV-2 was undetectable in 70% of those taking HCQ vs 12.5% of those not on HCQ. There was a suggestion that the addition of azithromycin, given at provider’s discretion, might increase potency, as HCQ plus azithromycin was associated with 100% viral load undetectable vs 57% with HCQ alone at day 6. However, there are several significant limitations: (1) patients in control group had higher baseline viral loads than those in the HCQ group vs. those in the HCQ/Azithro group, (2) six patients were lost to follow-up in the HCQ arm, including 3 who were transferred to the ICU and one who died and (3) clinical outcomes were not reported. Based on this study, it is not clear if hydroxychloroquine or hydroxychloroquine plus azithromycin reduces viral loads in patients or results in improved clinical outcomes. Randomized controlled data with clinical outcomes are needed. We need to be cautious about the potential side of effects of hydroxychloroquine, including QTc prolongation.

In case you missed it, intense tracking of hospital contacts of early case of COVID-19 in the US—the patient’s husband but not hospital contacts were infected.
Overview of the 1st known person-person transmission in the USA from The Lancet

The index patient was 60 year-old traveler who visited a sick relative and other family members in Wuhan, developed symptoms in retrospect as early as 1 day after return, was hospitalized with pneumonia and tested positive for COVID-19 seven days after returning to Illinois. Her only close contact (husband with COPD, did not travel), developed symptoms as early as 4 days after her return, became COVID-19 positive 11 days after her return, and was hospitalized 14 days after her return. Extensive contact tracing that included use of video surveillance cameras in the hospital revealed 372 contacts of both patients; 347 underwent active symptom monitoring for 14 days (152 community contacts and 195 HCW contacts; 66% low risk, 34% medium risk or higher). 43 PUI’s (fever, cough, and/or SOB within 14 d of exposure; 41% low risk, 59% medium risk or higher) and 32 asymptomatic, exposed HCWs tested negative. COVID-19 transmission occurred only in husband (1/347 monitored contacts), who had prolonged, unprotected exposure. There was no transmission to other contacts. This is a single case, and severity of illness, extent of viral shedding, and timing of exposures may have contributed to the apparent limited transmission. We will continue to share information on risk for HCW as the epidemic unfolds.


FAQ

1. Do infected persons gain immunity to SARS-CoV-2?
It is not known if infection with SARS-CoV-2 results in long-lasting immunity. However, a recent study in rhesus monkeys suggests that at least short-term immunity is likely. Researchers infected rhesus monkeys with SARS-CoV-2 and documented clinical disease and viral shedding. Twenty-eight days after primary infection, monkeys were re-exposed to the virus. None of the re-exposed monkeys demonstrated clinical disease nor were found to have viral shedding. However, studies of common coronaviruses that cause upper respiratory tract infection in humans have been shown to result in only partial, short-term immunity. Whether natural infection with SARS-CoV-2 will result in short term or durable immunity in humans remains unknown and an area for further research.

2. Does temperature (climate) effect COVID-19 spread?
SARS-CoV-2 transmissions have occurred predominantly within a temperature range of 3-17 C and a humidity of 4-9 g/m3, suggesting SARS-CoV-2 transmission may be less efficient in warmer humid climate (Bukhari). Similarly, in temperate climates, infections by other coronaviruses has been shown to occur primarily in winter (Gaunt). While it may be reasonable to expect a decline in contagiousness of SARS-CoV-2 in warmer weather, the degree to which weather will impact transmission is not known and will need further monitoring.

3. Why are people talking about ACE/ARB blockers in relation to COVID?
SARS-CoV-2 utilizes the angiotensin-converting enzyme 2 (ACE2) receptor for viral cell entry, the expression of which is increased when taking renin-angiotensin-aldosterone system (RAAS) inhibitors (ACE/ARB blockers that block the ACE1 receptor). The clinical significance of ACE2 modulation in human SARS-CoV-2 infection is unknown. RAAS inhibition has been argued to pose a theoretical increased risk of a higher susceptibility to infection due to increased ACE2 expression (Kuster). On the other hand, animal models suggest increased ACE2 expression is protective from severe acute lung injury induced by aspiration, sepsis, and SARS-CoV infection (Imai, Kuba). Currently, there is no data proving a causal relationship between ACE2 activity and human SARS-CoV-2 associated mortality. We do not recommend stopping or starting a RAAS inhibitor because of SARS-CoV-2 infection. There are intervention and observational studies planned to address this association.

4. What is the survival rate after intubation (mechanical ventilation)?
In published studies to date, the survival rate after intubation is quite low (0-14%). Yang et al reported on 52 critically ill patients in Wuhan and found that of 22 intubated patients, only 3 (14%) survived. Zhou et al reported on the clinical course of 191 patients in Wuhan and found that among 32 intubated patients, only 1 (3%) survived. Similarly, Wu et al reported on risk factors for ARDS and death in 201 patients from Wuhan; only 6 patients were intubated and none survived. Lastly, a report on 21 critically ill patients from Evergreen hospital in Washington was published last week (Arentz et al, JAMA March 19). They reported that 15 patients required intubation (71%) and of the 21 patients, 67% have died, 24% remain critically ill, and 10% have discharged from the ICU; they do not specify in the report a specific mortality rate for the intubated group.

Any questions, please feel free to reach out.

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COVID-19 DIGEST

From the Infectious Diseases Divisions at UCSF, ZSFGH, and VAMC

Update: March 20, 2020
EPIDEMIOLOGY

Local

As of today, there are 1039 confirmed COVID-19 cases and 19 deaths in California. In San Francisco, there are 76 confirmed COVID-19 cases and 0 deaths. Hospitals are seeing more patients seeking evaluation for COVID. The UCSF/ZSFG/VA campuses have all been activated and things are running smoothly in terms of rule-out procedures and treatment algorithms. It is important to note that we are still in influenza “season” in San Francisco. (SF numbers are tracked by SFDPH.)

National

Latest US estimates are 14,250 cases and 205 deaths. Testing is expanding to include drive-through options in many cities, but overall, capacity remains inadequate. On March 18, the CDC released data in the MMWR on outcomes among the 4,226 cases reported in the US since March 16. The report found that 31% of cases, 45% of hospitalizations, 53% of ICU admissions, and 80% of deaths occurred among adults aged ≥65 years with the highest percentage of severe outcomes among persons aged ≥85 years (similar to what was seen in China). As of this morning, New York City had 5,151 cases with ~1,250 hospitalized. Health systems are preparing for a surge in cases and have been limiting hospital visits, non-essential surgeries and clinic visits. There is a massive transition to telemedicine in many health systems in an effort to maintain the healthcare workforce. (National numbers via CDC.)

Global

There are over 247,400 cases of COVID-19 and 10,067 deaths globally. Europe is now the epicenter of the epidemic—with the greatest number of cases in Italy at 41,035 cases (3,405 deaths). The United Kingdom, slow to implement aggressive public health measures, has experienced a rapid increase in cases and reports with 3,297 cases to date. (Global numbers via Johns Hopkins.)

Public Health Action:

Over the last week, there has been more, important public health actions taken by US states and countries around the world (e.g. shelters in place, border closings, city “lock downs”). San Francisco and surrounding counties extended their early measures (limitations on gathering size and school closure) to shelter in place” on March 16, which was ahead of the nation. Yesterday on March 19, Governor Gavin Newsom gave a shelter in place order for the entire state of California (nearly 40 million people). Mayor Bill de Blasio put a strong stay at home order in place in NYC yesterday, but not as restrictive as in SF, and there has been an alarming rise in cases in New York State (now at 7,845 cases) over this past week. The UK, after an initially slow response, is now putting restrictive social distancing orders into place after an increase in cases. In Africa, 33 African countries had reported more than 600 cases and 17 deaths due to COVID-19, but testing has been limited. Many African countries (Kenya, Senegal, Rwanda, South Africa, Ethiopia, Zambia, Tanzania, among others) are putting restrictive orders in place for social distancing in anticipation. Countries in Latin America and the Caribbean have been affected later than other regions from the pandemic and therefore have a chance to flatten the curve of contagion; Columbia, Peru, Chile, Costa Rica and Panama, for instance, have all put aggressive public health measures in effect.


DAILY UPDATES

https://www.who.int/emergencies/diseases/novel-coronavirus-2019


COVID TESTING CAPACITY

COVID-19 PCR testing at UCSF Medical Center is currently at 80 tests/day and is expected to increase to 200-500 tests/day within a week. Currently, NP/OP swab kits are a limiting reagent. At Zuckerberg San Francisco General Hospital, capacity for inpatient samples is being met; outpatient testing remains limited. The turnaround for test results is 6-12 hours at UCSF and 24hours (from DPH) at ZSFGH and 3-5 days when sent to private labs who are experiencing extreme backlogs.


RESEARCH DISPATCHES

Lopinavir–Ritonavir not effective in Randomized study in Adults Hospitalized with Severe Covid-19 (NEJM 03.18.20)

Lopinavir-ritonavir, a viral 3CL protease inhibitor that had been commonly used to treat patients with HIV infection, has been shown in vivo to have activity against coronaviruses. A randomized, controlled, open-label trial comparing lopinavir-ritonavir in adults hospitalized with severe COVID-19 was just published. The study was conducted in China and randomized patients with confirmed (PCR+) COVID-19 and hypoxia (O2 saturation < 95% on room air OR PaO2/FiO2 < 300 mm Hg) to receive lopinavir-ritonavir (400mg/100mg) twice daily for 14 days versus placebo. Primary end-point was improvement on a seven-category ordinal scale or discharge from hospital. 199 patients were enrolled. Patients had a mean of 13 days of illness prior to randomization. Treatment with lopinavir-ritonavir was not associated with clinical improvement. Mortality was not statistically different in the treatment and control groups. There was also no difference in detectable viral RNA during the course of disease in either group. Gastrointestinal side effects were more common in the treatment group and 13.8% of patients in the treatment arm had stopped treatment stopped. There were several limitations in the trial; most notably, it was an open-label study. Although in vivo studies have demonstrated activity of lopinavir-ritonavir against SARS-CoV-2, it does not offer clinical benefit. It is terrific to have this information, and given the results of this study, we are not recommending regular use in the care of our patients with COVID-19. Its role in patients at earlier stage of disease is unknown.

SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients

COVID-19 early high viral load (NEJM 03.19.20)
Researchers recently published a study where they monitored SARS-CoV-2 viral loads in upper respiratory specimens from 18 patients in Guangdong, China within two family clusters. They analyzed the viral load in relation to the day of onset of any symptoms. Higher viral loads were detected soon after symptom onset, with higher viral loads detected in the nose than in the throat. The pattern of nucleic acid shedding with SARS-CoV-2 appeared very different from that previously reported in patients infected with SARS-CoV, where viral shedding for SARS-CoV peaked much later in the course of illness. The researchers also report a possible case of asymptomatic transmission of SARS-CoV-2. It is hypothesized that this early, high-level viral shedding may be a key factor in the transmission dynamics of SARS-CoV-2 and may help explain the difference in extent of spread of SARS-CoV-2 when compared to SARS-CoV.


FAQ

1. Can SARS-CoV2 be spread via blood products?
To date, there have not been any reported cases of SARS-CoV-2 spread via blood products. In a recent study that examined PCR samples from many body compartments, only 1% of 307 blood samples were positive. Viremia is most likely to occur in patients with symptomatic infection. Patients are not recommended to donate blood when they have signs and symptoms of COVID-19. Testing of blood products for SARS-CoV-2 is not presently used in the United States. Additional information from the American Association of Blood Banks can be found here.

2. What are best practices to reduce transmission of SARS-CoV2 who require surgical procedures?
(1) Avoid surgical procedures on patients with COVID-19 unless medically urgent; (2) minimize the number of people in the operating room during aerosol generating procedures (e.g., intubation and extubation); (3) all individuals in the OR during the surgical procedure require PAPR or N95 with face shield/goggles plus gowns and gloves; (4) bring patients directly to the OR and recover the patients in the OR—avoid pre-op holding and PACU

3. If my patient has COVID-19, how many days into their illness might they develop hypoxia and respiratory failure? In a study of 191 patients in China with COVID-19, dyspnea developed at about day 7 of illness and respiratory failure requiring ICU admission on day 12 of illness.

4. Is chloroquine useful for prophylaxis against COVID-19?
Data for use of hydroxychloroquine and chloroquine are limited to in vitro studies thus far, with a number of RCTs currently underway. These trials are examining the role of chloroquine or hydroxychloroquine for active COVID-19 treatment as well as post exposure prophylaxis. Given the lack of data available, providing these medications widely off-label to patients for prevention outside of a study is not advisable.

Any questions, please feel free to reach out.

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COVID-19 DIGEST

From the Infectious Diseases Divisions at UCSF, ZSFGH, and VAMC

Update: March 17, 2020
EPIDEMIOLOGY

Local

As of today, there are 43 confirmed COVID-19 cases and 0 deaths* in San Francisco. Hospitals are seeing more patients seeking evaluation for COVID. It is important to note that we are still in influenza “season” in San Francisco. As of last week, 10-20% of samples sent to labs are positive for influenza. *from SF DPH

National

Latest US estimates are 4,226 cases and 75 deaths. * Testing is expanding to include drive through options in many cities, but overall, capacity still remains inadequate. Health systems are preparing for a surge in cases and have been limiting hospital visits, non-essential surgeries and clinic visits. There is a massive transition to telemedicine in many health systems in an effort to maintain the healthcare workforce. *from CDC

Global

There are over 196,00 cases of COVID-19 and 7,800 deaths globally. Europe is now the epicenter of the epidemic; with the greatest number of cases in Italy. The United Kingdom, slow to implement aggressive public health measures has experienced a rapid increase in cases and reports around 1,950 cases to date. *from Johns Hopkins CSSE

Public Health Action:

Over the last 72 hours, there has been unprecedented actions taken by countries around the world (e.g. border closings, mandatory 14 day quarantines of all persons entering a country, regional quarantines). After a period of inaction, the US Federal government has put in place multiple aggressive measures (e.g, closing border to Europeans) to contain the spread of COVID-19. San Francisco and surrounding counties extended their early measures (limitations on gathering size and school closure) to “shelter in place”—a new term for most persons. The three week “shelter in place” public order requires citizens to stay at home unless they are providing (e.g. health care) or executing (e.g. food purchase) essential services.

Some optimistic news from Italy: A region (Lodi) that implemented strict adherence to measures consistent with “shelter in place” in mid -February has contained cases vs a region (Bergamo) that did not. See Figure 1.


DAILY UPDATES
https://www.who.int/emergencies/diseases/novel-coronavirus-2019


COVID TESTING CAPACITY

COVID-19 PCR testing at UCSF Medical Center is currently at 80 tests/day and is expected to increase to 200-500 tests/day within a week. Currently, NP/OP swab kits are a limiting reagent. At Zuckerberg San Francisco General Hospital, capacity for inpatient samples is being met; outpatient testing remains limited. The turnaround for test results is 6-12 hours at UCSF and 24hours (from DPH) at ZSFGH and 3-5 days when sent to private labs who are experiencing extreme backlogs.


PATIENT EVALUATION

UCSF Health updated its adult inpatient/ED algorithm, developed workflow for the ambulatory setting, and is working to provide clarification of points around PPE use.

  • Updates in testing: In an effort to maximize sensitivity of testing while conserving testing materials, they now recommend either a single nasopharyngeal (NP) swab when using a single flocked swab kit or when using a dual flocked swab kit, place the NP swab and oropharyngeal swab into a single vial. Also, all respiratory viral testing (COVID-19, RVP, rapid flu/RSV) should be done on the same swab. Order should be either for RVP or rapid flu/RSV but not both.
  • Workflow for patients with respiratory symptoms in the ambulatory setting: Depending on patients symptoms and risk factors, they may be triaged to either home self-monitoring, a UCSF Health respiratory screening clinic, or the emergency department. Details can be found on UCSF Health link below
  • PPE for patients being evaluated for COVID-19 or diagnosed with COVID-19:
    • Routine care for patients who are not receiving aerosol-generating interventions: Don surgical mask/eye protection plus gloves/gown
    • Obtaining an NP+/-OP swab: Don (N95 mask/eye protection or PAPR) plus gloves/gown
    • Patient receiving nebulized medication or other discrete aerosol-generating procedures: Don (N95 mask/eye protection or PAPR) plus gloves/gown (1-hour after procedure is complete can return to routine care recommendations)
    • Patient intubated, high-flow nasal canula, non-invasive ventilation, or tracheostomy in place: Don (N95 mask/eye protection or PAPR) plus gloves/gown (in negative pressure isolation)
  • Cohorting has begun of inpatients with COVID-19 to a single floor when possible

FAQ

1. What is the sensitivity of the PCR test to diagnose COVID-19?

The sensitivity of a single nasopharyngeal (NP) swab PCR is ~75-80%. Sampling by pooled NP + oropharynx (OP swab likely increases sensitivity by another ~ 10%. The addition of a lower respiratory sample (BAL, endotracheal aspirate) may further increase sensitivity.

2. Should steroids be used in the treatment of severe disease?
Presently, there are insufficient data to recommend steroids during ARDS in the setting of COVID-19. One recent small retrospective study (N=201 hospitalized patients in China ) published by Wu, et al in JAMA Internal Medicine reported 84 (42%) with ARDS, and a 54% mortality among the 84 patients. Some of the risk factors associated in ARDS/mortality included older age, higher neutrophil count and organ dysfunction. Higher fever (>39) was associated with higher risk (1.77) of ARDS and lower mortality rate (0.41) . Among, the 84 patients with ARDS, steroids were used in 31%.The hazard ratio death was lower (0.38, 95% CI 0.20-0.72) in steroid recipients. Despite this association, it is not possible to assess the effect of steroids in absence of a randomized comparison; other studies have also shown prolonged viral shedding in the presence of steroids.

3. What treatment trials are up and going at ZSFG and UCSF hospitals?
We have 2 active trials here; there are many trials ongoing around the world. Both ZSFG and UCSF are participating in an NIH sponsored double blinded, placebo controlled RCT of IV remdesivir (nucleoside analogue that inhibits viral RNA polymerase) given for up to 10 days to hospitalized individuals with COVID-19 (NCT04280705, UCSF PI Luetkemeyer). Patients are eligible if they are have radiographic findings or evidence of hypoxia and are required to have PCR confirmation of COVID-19. More severely ill patients with ARDS may qualify for a study of mesenchymal stromal cells, which may reduce lung injury by targeting several ARDS-triggered pathways to reduce injury and accelerate repair (NCT02097641, UCSF PI Matthay). Please contact the COVID ID service (remdesivir) and Pulmonary/Critical Care (mesenchymal stromal cells) at each site to discuss potential participants or you can reach out to [email protected] or [email protected]

4. Are there any prevention trials for COVID ongoing?
Yes, post-exposure prevention trials are being planned, and some are underway. Chloroquine and hydroxychloroquine (Plaquenil) show robust in vitro activity against the virus causing COVID-19. This mechanism of action is thought to be interference with viral entry. We will be participating in a study using hydroxychloroquine for household contacts of known COVID-19 cases. Expected start date is late April 2020. Lopinavir/ritonavir (Kaletra) has been used for post-exposure prophylaxis during MERS in a small series, and is being actively investigating for both prophylaxis and treatment in COVID-19. There are many trials ongoing around the world investigating other agents with potential COVID-19 activity for post-exposure prophylaxis.

Any questions, please feel free to reach out.

 

 

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COVID-19 DIGEST

From the Infectious Diseases Divisions at UCSF, ZSFGH, and VAMC

Update: March 13, 2020
EPIDEMIOLOGY

Local

As of today, there are 23 confirmed COVID-19 cases and 0 deaths in San Francisco. San Francisco school officials announced yesterday that they are closing Pre-K through Grade 12 schools for 3 weeks. Most, if not all other Bay Area Catholic schools and independent schools have also closed. The Mayor announced temporary housing for homeless persons awaiting COVID testing results or with confirmed cases.

National

Latest US estimates report 1,629 cases and 41 deaths. The president extended travel restrictions to non-US citizens from a majority of European countries (excluding the United Kingdom and Ireland) entering the United States. First in-depth report of US community transmission published in Lancet – household but not HCW transmission in this case. Disembarkation from the Grand Princess Cruise ship docked in Oakland on Monday is still ongoing.

Global

There are nearly 138,000 cases of COVID-19 and ~5,000 deaths globally. The situation in Italy continues to be dire, with an increase in cases, deaths and severe strain on the health system and providers. Cases in Iran are rising rapidly, and several high-level government officials have been infected. Cases are continuing to decline in China. *Data from CSSE at Johns Hopkins


DAILY UPDATES

https://www.who.int/emergencies/diseases/novel-coronavirus-2019


PATIENT EVALUATION

COVID-19 PCR testing is ramping up on our campuses. The Chan-Zuckerberg Biohub donated two high-throughput PCR machines. Once the testing on this machine meets CLIA standards (which will take 1-2 weeks), the in-house test capacity is expected to increase to over 200 tests/day. LabCorp, Quest, and ARUP are now live with their COVID-19 PCR tests. As testing becomes more easily available, each of our campuses are updating their screening algorithms, which can be found on the clinical links at the end of this digest.

UCSF health just updated its adult inpatient/ED algorithm. The important changes are:

· Increased test availability: Tests should be ordered per algorithm as “COVID-19 RNA, qualitative.” Approval for testing is no longer required.

· Test collection: Pooled oropharyngeal and nasopharyngeal swabs will be collected in one test. Instructions for collection can be found here.

· Updated PPE guidance: The algorithm now specifies patients requiring “Novel Respiratory Isolation” and those requiring "Respiratory Illness Evaluation without Negative Pressure."

· Discontinuation of isolation: The algorithm now specifies necessary steps.

 

UP-TO-THE-MINUTE DISPATCHES

Patient with Flu and COVID-19: There is a report of a patient in China who presented with LRI symptoms 1 day after returning from a 5-week visit in Wuhan. He tested positive for influenza A but negative for SARS-CoV-2 on a NP swab x 2. He was sent home on oral oseltamivir. One week later, he returned for worsening symptoms. A repeat NP swab and sputum sample was negative for SARS-CoV-2. He required mechanical ventilation. 11 days after his initial presentation, metagenomic sequencing and RT-PCR of BALF and RT-PCR of sputum tested positive for SARS-CoV-2. This case illustrates that (i) SARS-CoV-2 testing may not be initially positive (although we cannot rule out nosocomial transmission) and (ii) although reportedly unusual, patients can be co-infected with both Influenza A and SARS-CoV-2.

Children were infected early during the COVID-19 outbreak in China: A retrospective review of 366 children hospitalized near central Wuhan from January 7-15, 2020 and that were all tested for respiratory pathogens revealed that 23 (6.3%) tested positive for Influenza A, 20 (5.5%) tested positive for Influenza B, and 6 (1.65%) tested positive for SARS-COV2. Age range was 1-7 years old. The most common symptoms in the 6 patients were high fever (6/6), cough (6/6), N/V (4/6). 6/6 had lymphopenia; 4/6 had abnormal chest CT. 1/6 required ICU admission; all were discharged. This study suggests that children were infected early during the epidemic in China.


RESEARCH
COVID-19 RESEARCH UPDATE WITH AN EMPHASIS ON SOME BASIC AND APPLIED VIROLOGY TO HELP UNDERSTAND THIS COVID-19 PANDEMIC

The S (for Surface or Spike, because the protein looks like a spike protruding from the virus) protein of coronaviruses is crucial for the virus to bind to a specific receptor on the host cell, enter into the host cell (which it does by fusing with the host cell membrane. The host cell receptor also defines what cells, tissues, and species can be infected and therefore is considered the best target for vaccine development. Several groups have demonstrated that human angiotensin converting enzyme protein (hACE2) is the receptor for SARS-CoV-2. This protein is expressed in much more in cells of the lower respiratory tract than in the upper respiratory tract, explaining why COVID-19 causes lower respiratory (rather than upper respiratory) tract infections. Mutations that naturally arose in the SARS-CoV-2 S protein during the SARS outbreak that affect the binding affinity of SARS-CoV-2 to hACE2 correlated with the replication, transmissibility, and disease severity of SARS-CoV. Two groups have now published structural studies with SARS-CoV-2 and finds that its S protein binds to hACE2 up to 10 times better than SARS-CoV, possibly explaining the enhanced human-human transmission of SARS-CoV-2. Like the SARS-CoV S protein, the SARS-CoV-2 spike protein is highly glycosylated (ie, it has lots of sugars attached to the protein). These sugar residues are important for the protein to fold correctly, get processed by host proteases, and to be recognized by neutralizing antibodies. The authors were able to visualize the 3D structure of the SARS-CoV-2 S protein and provided evidence that some but not all neutralizing antibodies to SARS-CoV will likely block binding to SARS-CoV-2. This study will hopefully help in the development of an effective vaccine against SARS-CoV-2.

NIH has issued their policy and information on COVID-19-related potential delays for grant applications, progress reports, meeting etc
1. FAQs regarding proposal submission and award management
2. Policy regarding late applications due to COVID-19

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COVID-19 DIGEST

From the Infectious Diseases Divisions at UCSF, ZSFGH, and VAMC

Update: March 10, 2020
EPIDEMIOLOGY

Local

As of today, there are 13 confirmed COVID-19 cases and 0 deaths in San Francisco; the Department of Public Health (DPH) is providing daily updates. Santa Clara County has reported 43 cases, and the first death in a woman in her 60s. To reduce the pace of spread of COVID-19, the SFDPH recommends rescheduling or cancelling non-essential events and that vulnerable populations refrain for attending events of 50 or more persons. Starting Wednesday, Santa Clara County is banning events of over 1,000 persons until the end of the month.

National

Latest US estimates are 647 cases and 25 deaths. Yesterday, New York State reported an increase in cases—173 total to date with eight hospitalizations. The National Guard is sending troops to assist in testing and setting a “containment area” in New Rochelle, NY until March 25, where a cluster of cases has been detected. The Grand Princess Cruise ship docked in Oakland yesterday, and disembarkation will occur over the next few days under Federal guidance.

Global

There are nearly 120,000 cases of COVID-19 and 4,200 deaths globally. The epidemic in Italy is not abating-- 9,173 cases and 463 deaths to date. Yesterday, Italy announced all forms of public gathering for the entire country would be put on hold, and non-essential travel was being restricted until April 3. A overview presented virtually at CROI 2020 details the global arc of the virus.


DAILY UPDATES

https://www.who.int/emergencies/diseases/novel-coronavirus-2019


PATIENT EVALUATION
COVID-19 PCR testing went live at UCSF Medical Center yesterday. They are able to run 20-40 tests per day and are hoping to quickly escalate to over 100 samples per day within the next week. As testing become more widespread, each of our campuses are updating their screening algorithms. LabCorp, Quest, and ARUP are now live with their COVID-19 PCR tests.


EDUCATION
The Cross-campus ID Task Force can provide updates by ID faculty on COVID-19 to your department, division or team in varying formats: a 15-minute talk, a Grand Rounds, a Q&A session or another format that might suit your group. For more information or to schedule a session, please contact us.


RESEARCH
A study of 181 confirmed cases of SARS-CoV-2 infection found that the median incubation period was 5.1 days and that 97.5% of patients will develop symptoms within 11.5 days of infection. A clearer understanding of incubation period helps providers make best decisions on quarantine to prevent spread. Although it is believed that respiratory droplets are the primary mode of transmission of infection, patients have been noted to have stool with positive PCR testing for SARS-CoV-2. Researchers identified an asymptomatic child with stool positive for SARS-CoV-2 PCR 17 days after last exposure. Transmission is primarily via virus-laden droplets and implications of asymptomatic stool carriage as a vector for transmission is unclear.


FREQUENTLY ASKED QUESTIONS

1.What is the difference between SARS-COV2 and COVID-19?
SARS-COV2 (the virus) stands for Severe Acute Respiratory Syndrome – Coronavirus. COVID-19 (the disease) stands for Coronavirus Disease first reported in 2019.

2. Which patients are at highest risk for death from COVID-19?
Based on data from a large study in China of 72,314 infected patients, case fatality was 2.3% in all patients. However, risk of death increased with increasing age in years 0-39 (0.2%), 40-49 (0.4%), 50-59 (1.3%), 60-69 (3.6%), 70-79 (8%), and >79 (14.8%) and for patients with cardiopulmonary disease, diabetes, hypertension, and cancer.

3. What are the most common laboratory abnormalities you should expect to see in patients with COVID-19 pneumonia?
In two recent studies describing clinical characteristics of patients from China with COVID-19 pneumonia (Guan W et al and Chen N et al), leukocytosis was uncommon and leukopenia (30-45%) and lymphopenia (33-85%) were frequently seen. C-reactive protein was elevated in most (60.7%) patients while procalcitonin was unlikely elevated (5.5%).

4. Has lung transplantation been used as a treatment for patients with COVID-19 pneumonia?
Yes, in China there have been two lung transplants performed for patients with COVID-19 disease. Both these patients had been on ECMO and had failed to improve.

5. How does SARS-COV2 cause respiratory failure?
The pathogenesis of SARS-COV2 is poorly understood. It is thought that the virus is able to infect respiratory epithelial cells via binding to the angiotensin converting enzyme (ACE) 2 receptor. Once it infects the cells, immune-mediated attack of virally infected cells may be a driver of clinical disease. In fact, researchers in China are studying the IL-6 receptor blocker, tocilizumab, as a possible therapy. Tocilizumab has been used for the treatment of “cytokine storm” in patients being treated with CAR T-cells.

 

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COVID-19 DIGEST

From the Infectious Diseases Divisions at UCSF, ZSFGH, and VAMC

Update: March 6, 2020
EPIDEMIOLOGY

Local

The situation is evolving rapidly with 2 confirmed community-transmitted hospitalized cases in San Francisco announced yesterday, and many suspected cases under evaluation. Public health officials are working around the clock discussing and expanding community mitigation strategies. City and health officials are also working diligently and collaboratively to insure health care worker safety as our response is intensified.

National

More cases COVID-19 are now being recognized around the United States. As of today, there are 233 cases and 14 deaths. There have been notable increases in the Los Angeles area, as well as New York. Many of the deaths have been in elderly persons, and in particular, elderly residential group facilities. There have been no deaths among children in the US to date.

Global

We’ve reached over 100,000 cases of COVID-19 globally. Cases from India are now being increasingly reported. It is somewhat encouraging that new cases from China are starting to decrease, but the burden there remains high. Health care workforce shortage remains a great challenge there-- more than 3000 physicians in China have been infected and at least 22 have died—underscoring the importance of us putting the resources needed to insure health care work safety from the start.

DAILY GLOBAL UPDATES:
https://www.who.int/emergencies/diseases/novel-coronavirus-2019


PATIENT EVALUATION

Increased access to COVID-19 laboratory testing is actively happening in San Francisco with a revision of the recommended isolation and testing algorithms. Each of our campuses are updating their screening algorithms, which can be found on the clinical links at the end of this digest. LabCorp has launched a COVID-19 PCR test as of today and Quest will have a test available by Monday.


EDUCATION

The UCSF ID COVID-19 Task Force can provide updates by ID faculty on COVID-19 to your department, division or team in varying formats: a 15-minute talk, a Grand Rounds, a Q&A session or another format that might suit your group. For more information or to schedule a session, please contact Chesa Cox at [email protected].


RESEARCH

Scientists are busy sequencing the virus and sharing on a common platform – https://nextstrain.org/ncov

There was recognition of 2 separate strains reported yesterday (“L” and “S”) and a suggestion that there was correlation with clinical outcomes—but much more information on this possible association and what it means is needed. UCSF is in the process of validating a SARS-CoV2 PCR assay and this should be completed in the coming week with an estimated turnaround of 20 samples per day. Steve Miller, Director of the UCSF Microbiology Lab, is leading this effort. There is also ongoing work at Moffitt to bring online a higher throughput commercial PCR instrument and a CRISPR/Cas12a-based diagnostic test in the upcoming weeks.


FREQUENTLY ASKED QUESTIONS

1. What is the risk of COVID-19 in pregnancy?
Based on the limited available data it does not appear that pregnant women are more susceptible to COVID-19 and clinical presentation in pregnancy has been similar to that of non-pregnant patients. Reported complications rates to date are much lower than seen previously with SARS, but there have been reports of fetal distress and preterm delivery in some cases. There has not been convincing evidence of intrauterine maternal to child transmission, however infants born to a mother with known infection are clearly at risk and appropriate infection control measures to prevent transmission post-partum are warranted.

See Lancet and ACOG articles for more information

2.Can asymptomatic people test positive for COVID-19 and if so, are they infectious?

Several asymptomatic persons tested positive for COVID-19 and were the presumed sources of transmission to close contacts. In one case, the chest CT was normal; the person never developed symptoms and cleared COVID on subsequent testing. The second case appears to have transmitted COVID during the incubation period prior to developing symptoms. These cases raise important questions about how much transmission is driven by those without symptoms, what the relationship is between viral load and infectiousness, and what the implications of this will be for control of this epidemic

3.How many negative tests are enough to demonstrate that a person is no longer infected and infectious?
The current guidance is for two sequential negative PCR tests and clinical improvement for discharge from hospital or quarantine. Post-clinical viral shedding may occur and is under study.

 

If you have further questions, please feel free to reach out and we can direct your query appropriately. UCSF is maintaining a microsite with updates as well.

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COVID-19 DIGEST

From the Infectious Diseases Divisions at UCSF, ZSFGH, and VAMC

Update: March 3, 2020

EPIDEMIOLOGY

Local

There is clear evidence for community transmission in the Bay Area—cases where there is no known direct link to travel or to infected persons. Five new diagnosed patients including two East Bay Health workers were announced over the weekend. This was expected and not surprising, given what is currently known about COVID-19 transmission and circulation. San Francisco’s outstanding Public Health Department is monitoring and responding to our local situation.

National

Cases of COVID-19 are now being recognized around the United States. There have been 105 cases in 15 states. California is reporting the largest number of new cases (20). Washington State has sadly reported 9 fatalities as of today. Many of these deaths were associated with transmission in a nursing home setting.

Global

Over 90,000 cases of COVID-19 have been reported in > 70 nations. In Europe, cases are now being detected in many countries beyond Italy, and various measures are being taken in these countries to mitigate spread. Some countries have already called for cancelling events where more than 1,000 persons gather; museums, such as the Louvre in Paris, are temporarily closed. Many large meetings—including those in medicine, science and tech—are being cancelled and are choosing to share conference information digitally. An overview of the global situation is updated daily here:

Daily Updates:
https://www.who.int/emergencies/diseases/novel-coronavirus-2019


PATIENT EVALUATION

SF Public Health Department lab is actively testing specimens for COVID-19. Each of our campuses are updating their screening algorithms and testing capacity. 


EDUCATION

The UCSF Task Force can provide updates by ID faculty on COVID-19 to your department, division or team in varying formats: a 15-minute talk, a Grand Rounds, a Q&A session or another format that might suit your group. Please contact us if interested.


RESEARCH

Treatments and vaccines are areas of active and intense investigation. There is no proven antiviral treatment for COVID-19. Several antimicrobial agents may have activity against COVID, including both experimental and FDA approved drugs. One promising agent is remdesivir, an investigational nucleotide analogue under active investigation for COVID-19 in two phase 3 randomized open label studies enrolling in Asian countries and a Phase 2 double blinded, placebo controlled NIH-funded study actively enrolling in the U.S. at Univ. of Nebraska Medical Center. This trial has potential to expand to other sites. Remdesivir is also available through compassionate use from Gilead Sciences for qualifying patients on a case-by-case basis.

An electron microscope image showing particles of the new coronavirus being released from an infected cell. Image credit: The University of Hong Kong


FREQUENTLY ASKED QUESTIONS

1. What is the increased risk for disease acquisition or mortality for persons on immune suppression?

Although there are limited data on this, medical comorbidities including malignancy have been associated with higher risks for severe outcomes (data from China). In other coronaviruses, immunocompromised patients may show fewer symptoms at onset but later have more severe disease; it is not known if this is the case with COVID-19. There are no data to determine if people living with HIV specifically are at greater risk of COVID-19 acquisition or more severe disease.

2. What do we know about COVID-19 spread to children?

In Germany, a schoolteacher fell ill with COVID-19 pneumonia. Of the 114 children exposed to this teacher, 100 were tested. Four children in this classroom have subsequently developed COVID-19 with mild symptoms. There are school closings in Europe where teachers have fallen ill with the disease, but no reported deaths among children.

3. Can COVID-19 relapse?

There have been reports from China, Japan, and the US of persons who tested positive weeks after recovering from COVID-19 disease. There is insufficient information at the present time to interpret these reports, which could represent assay error, prolonged waxing/waning viral shedding, true reinfection or true relapse. This is an area of active investigation.

 

If you have further questions, please feel free to reach out and we can direct your query appropriately. UCSF is maintaining a microsite with updates as well.