January 13, 2021
“Already, researchers are anticipating mechanisms by which the coronavirus, which mutates quickly, will evade current vaccines. As a result, COVID-19, like influenza, is unlikely to ever go away, even if much of the population is vaccinated.”Dr. Ben Singer, assistant professor of pulmonary and critical care medicine at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician
“We simply cannot stay closed until the vaccine hits critical mass. The cost is too high. We will have nothing left to open. We must reopen the economy, but we must do it smartly and safely.”
President TrumpNew York Governor Cuomo
“The return of concerts, events and the reopening of theaters and venues is all dependent on the COVID-19 vaccine rollout. If everything goes right, this is will occur some time in the fall of 2021.”Dr. Fauci
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- Cases & Tests
- Top 5 States in Cases, Deaths, Hospitalizations & Positivity
- Emerging Variants – 2 Additional Mutations Discovered (!)
- Here’s what to know about the South African and U.K. virus variants (!)
- Why Declining Antibodies Don’t Spell Disaster for Long-Lasting C19 Immunity (!)
- More than half of C19 cases spread by asymptomatic carriers, CDC model shows (!)
- Why C19 pneumonia lasts longer, causes more damage than typical pneumonia
- Scientists identify ‘immune cop’ that detects the coronavirus
- Coronavirus shutdowns have suppressed other viruses, but a rebound is coming
- ‘Pre-existing weaknesses’ hindered the U.S. pandemic response, researchers find
- Pfizer-BioNTech vaccine not affected by mutation seen in contagious coronavirus variant, but questions remain
- How can countries stretch C19 vaccine supplies? Scientists are divided
- New Research Shows Poor Gut Health Connected to Severe C19 – Probiotics May Help Patients (!) (*)
- Study finds 76% of patients hospitalized with C19 have at least one symptom 6 months after falling ill (!)
- Coronavirus can infect neurons and damage brain tissue, study indicates
- For people with type 1 diabetes, CDC Covid guidelines are puzzling
- WHO says herd immunity will not happen in 2021
- This is what an ‘overwhelmed NHS’ looks like. We must not look away
- The Future of the Coronavirus? An Annoying Childhood Infection
N. Linked Stories
- Initial Severity of C19 Is Not Associated With Later Respiratory Complications
- Large study finds higher burden of acute brain dysfunction for C19 ICU patients
- Stanford working on a single shot, room temperature nanoparticle vaccine for C19
- Online Tool Identifies C19 Patients at Highest Risk of Deterioration
- Spikes in Cardiovascular Deaths Shown to Be an Indirect Cost of C19 Pandemic
- Disposable Helmet Designed to Retain Cough Droplets, Minimize C19 Transmission
- Nanoparticle immunization technology could protect against many strains of coronaviruses
- More than half of C19 health care workers at risk for mental health problems
- The odd structure of ORF8: Mapping the coronavirus protein linked to disease severity
- Food insufficiency linked to depression, anxiety during the C19 pandemic
- Study links severe C19 disease to short telomeres
- An augmented immune response explains the adverse course of C19 in patients with hypertension
- New findings help explain how C19 overpowers the immune system
- Search for better COVID vaccines confounded by existing rollouts
- Denmark developing digital C19 “vaccine passport”
- Coronavirus shutdowns have suppressed other viruses, but there will be a rebound
- Best C19 Vaccination Strategies, According To Mathematicians
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A. Pandemic Headlines
(In no particular order)
- WHO warns COVID-19 herd immunity unlikely in 2021, despite vaccines
- Pfizer and BioNTech announced plans to boost production of its COVID-19 vaccine by 50% percent — 2 billion doses — this year
- Johnson & Johnson may seek vaccine approval this month
- Moderna says immunity from its COVID-19 vaccine should last at least a year
- Trump administration wants to widen COVID-19 vaccine distribution, release 2nd doses
- Experts urge caution in delaying the second dose of the vaccine
- Too many states are bungling vaccinations — the feds need to step in
- US to require COVID tests for all international travelers
- A new virus variant is found in Japan
- CDC: No sign of homegrown U.S. coronavirus variant, but scientists need to look harder
- CDC Admits “Most Transmission Occurs At Home”
- NY Gov. Cuomo Reverses: Demands “Reopen The Economy” Amid Dismal NYC Vaccine Rollout
- Hospitalized coronavirus patients still suffer symptoms 6 months post-infection
- L.A. County Tells Residents To Wear Masks Inside Own Homes
- Los Angeles students required to get COVID-19 vaccine before returning to school
- NYC Mayor de Blasio: NYC could run out of COVID shots in 2 weeks
- Bay Area ‘stay-at-home’ order extended indefinitely
- Disneyland joins Dodgers stadium in becoming vaccination site
- Citi Field in NYC to host 24/7 COVID-19 vaccination center
- US hospitalizations hit new records led by California
- Chicago Teachers Union Plans to Mobilize Against Reopening Schools
- Ireland now world’s worst-hit country
- UK Government May Only Let People Out Once A Week
- UK may prevent people from talking to each other in the street and in supermarkets
- The worst is yet to come for Britain’s battle with the virus, officials warn
- Netherlands seeing cautious decline
- Italian Government On Verge Of Collapse Amid Battle Over EU COVID Relief
- England’s Rapid Asymptomatic Testing Could Backfire Over Accuracy
- South Africa struggles with post-holiday spike in COVID-19
- China reports biggest daily COVID-19 case jump in over 5 months
- EU strikes 8th deal to buy vaccine doses
- At COVID-19 ‘breaking point’, Malaysia suspends parliament
- Indonesia’s president receives a Chinese-made vaccine that produced disappointing trial results
- Brazilian researchers find a Chinese vaccine once hailed as a triumph is far less effective than thought
- Temporary morgues set up as UK hospitals run out of space
- China finally allowing WHO scientists in to research COVID-19 origins
- ER nurse gets COVID just days after second dose is canceled
- A Nursing Home Had Zero COVID Deaths. Then, It Vaccinates Residents And The Deaths Begin
- Tribal Elders Are Dying From the Pandemic, Causing a Cultural Crisis for American Indians
- 3 members of family who wore masks, didn’t gather die of COVID-19
- Henry Ford Hydroxychloroquine Shut Down Because They Could Not Find Enough Participants
- Study U.K. Divorces Expected To Surge In A Post-COVID 2021
- Florida puts New York to shame in rational pandemic policies
- NYC couple forged positive COVID-19 results to delay husband’s trial, prosecutors say
- FL teacher charged with spraying students with disinfectant for not wearing masks properly
- CA authorities arrest 182 after busting two ‘superspreader’ events
- Two Gorillas at the San Diego Safari Park Have Tested Positive for COVID-19, First Case Among Great Apes
- Alabama college football fans partied like the pandemic didn’t exist — now officials fear another surge
- Most Japanese citizens think Tokyo Olympics should be canceled or postponed
- This month’s Paris Fashion Week goes totally digital
- Woman caught walking husband on a leash during COVID curfew
B. Numbers & Trends
Note: Unless otherwise noted, (i) all cases/deaths are confirmed cases/deaths that have been reported, (ii) all numbers reported in this update are as of the end of the most recent reporting period, and (iii) all changes reflect changes since the preceding day.
1. Cases & Tests
- Total Cases = 91,988,804
- New Cases (7 day average) = 733,035
- Although the 7 day average of new cases has been increasing rapidly since 12/28, it declined slightly from a record high yesterday (738,453)
- Since 12/28, the 7 day average has increased from 567,710 to 733,035, an increase of 29.1% in only 2 weeks
- Total Cases = 23,368,225
- New Cases (7 day average) = 252,800
- Percentage of New Global Cases = 34.5%
- Although the 7 day average of new cases has been increasing rapidly since 12/29, it declined slightly from a record high yesterday (254,598)
- Since 12/29, the 7 day average has increased from 185,279 to 252,800, an increase of 36.4% in only 2 weeks
- Total Deaths = 1,968,657
- New Deaths (7 day average) = 13,147
- Record high number of new deaths (15,711)
- Record high 7 day average of new deaths
- Total Deaths = 389,559
- New Deaths (7 day average) = 3,384
- Percentage of Global New Deaths = 25.7%
- Record high number of new deaths (4,259)
- Record high 7 day average of new deaths
- Increasing number of new cases indicates that new deaths will also increase
3. Top 5 States in Cases, Deaths, Hospitalizations, ICU Patients & Positivity (1/12)
- Positivity rates are trending down.
- Hospitalizations remain high, but more states are reporting decreases in the number of hospitalized patients.
- Patients in ICU are still increasing, but the growth rate has slowed.
- After peaking at 17.2% on 1/8, the US Positivity Rate remains high, but it fell for the 4th consecutive day to 15.8% on 1/12.
- Overall, only 14 states reported higher positivity rates over the last week (-20 states since 1/5).
- WY leads the US with an average of 66.6% of all tests resulting positive
- Eight states: 7-day positivity rates greater than 40%. (-2 since 1/5)
- Six states: 7-day positivity rates greater than 30%. (-2 since 1/5)
- Eleven states: 7-day positivity rates greater than 20%. (+1 since 1/5)
- Three states (OR, AK, MS): 7-day positivity rates less than 5%. (+1 since 1/5)
- In total, 47 states have 7-day positivity rates greater than 5% (-1 since 1/5)
- Overall, only 14 states reported higher positivity rates over the last week (-20 states since 1/5).
- Hospitalizations in the US decreased slightly to 131,326 patients, down 0.1% over the last week. On 1/12/21, Hospitalizations increased 1,578 patients from the prior day.
- Four states have had increases of hospitalized patients of more than 10% in the past week. (-7 since 1/5)
- CA hospitalizations, 22,665 patients have leveled off are off slightly from its high
- 29 states have more than 1,000 hospitalized patients (-unch since 1/5)
- 30 states saw decreases in the number of hospitalized patients over the past week. (+8 since 1/5)
- Four states have had increases of hospitalized patients of more than 10% in the past week. (-7 since 1/5)
Patients in ICU Trends
- ICU Patients in the US rose 1.8% to 23,881, just short of the all-time high reached on 1/8. On 1/12/21, ICU Patients increased 387 patients from the prior day.
- Five states have seen the number of ICU patients increase by more than 10% since a week ago (-3 since 1/5)
- 28 states have more than 100 patients in ICU, (-2 since 1/5)
- 22 states saw decreases in the number of ICU patients over the past week (-unch since 1/5).
C. New Variants (Mutations) of Coronavirus
1. Emerging Variants – 2 Additional Mutations Discovered
- Expanded sequencing and screening capacity and capabilities have helped identify several emerging variants of the coronavirus (SARS-CoV-2) in the UK (B.1.1.7) and South Africa (B.1.351). More recently, similar variants were detected in Japan and Nigeria.
- The B.1.1.7 and B.1.351 variants have several mutations in the spike protein, which appear to confer increased transmissibility.
- The variant detected in Japan was first identified in 4 travelers from Brazil who arrived at Haneda Airport in Tokyo. The variant identified in Nigeria was first detected in the state of Osun, in specimens dating back to at least August 2020, and preliminary analysis indicates that it is “distantly different” from the B.1.1.7 and B.1.135 variants. Health authorities and researchers are investigating the particular characteristics of the new variants, including any potential effects on transmissibility, disease severity, and vaccine susceptibility.
- Although the variants do not seem to cause increased morbidity or mortality, WHO Director-General Dr. Tedros Adhanom Ghebreyesus stated that the continued emergence of highly transmissible variants is “highly problematic.” While these variants may each exhibit similar mutations and characteristics, it appears that they have all emerged independently.
- The wide geographic distribution of emerging variants is concerning for control efforts, because the emergence and evolution of the virus, including the effects on the virus’ characteristics, are unpredictable. Continued and renewed efforts in genomic surveillance are necessary in order to monitor the geographic spread of existing variants and quickly identify the emergence of new ones.
Source: Johns Hopkins COVID-19 Update
2. Here’s what to know about the South African and U.K. virus variants
- In recent weeks, scientists have raised concerns about a coronavirus variant first detected in December in South Africa, noting that this version of the virus may spread more quickly than its cousins, and perhaps be harder to quash with current vaccines.
- Their worries are compounded by skyrocketing C19 cases in the United States and another highly infectious new variant that is driving a surge in Britain.
- Scientists still have a lot to learn about these variants, but experts are concerned enough to warn people to be extra-vigilant in masking and social distancing. Here’s what you need to know:
- The British variant has been found in about 50 countries, including the United States, where dozens of cases have been identified. The South African variant has spread to about 10 countries but has yet to be detected in the United States.
- Both variants carry genetic changes in the virus’s spike protein — the molecule used to unlock and enter human cells — that could make it easier to establish an infection. Researchers estimate that the British variant is about 50% more transmissible than its predecessors. Julian Tang, a virologist at the University of Leicester, said that researchers didn’t yet have a good estimate for how much more contagious the South African variant is.
- There is no evidence that any of the new variants are more deadly on their own, but an uptick in the spread of any virus creates ripple effects as more people become infected and ill. That can strain already overstretched health care systems and undoubtedly lead to more deaths.
- It is unlikely that either variant will completely evade the protective effects of the new Covid vaccines. A recent study, not yet published in a scientific journal, found that the Pfizer-BioNTech vaccine is still effective against a virus carrying a mutation common to both new variants.
- The South African variant does carry genetic changes that could make vaccines less effective: One mutation appears to make it harder for antibodies produced by the immune system to recognize the coronavirus, which means they may be less effective at stopping the variant. But it is “important to note that doesn’t mean vaccines won’t be functionally protective,” said Angela Rasmussen, a virologist affiliated with Georgetown University.
- Vaccines use multifaceted immune responses, and while some antibodies may be confused by the variant, others probably won’t be. In addition, antibodies are only one sliver of the complex cavalry of immune cells and molecules that battle infectious invaders.
- Also, if the virus accumulates more genetic changes, many of the authorized vaccines, including Pfizer’s and Moderna’s, can be adjusted fairly quickly.
Source: New York Times Coronavirus Update
D. New Scientific Findings & Research
1. Why Declining Antibodies Don’t Spell Disaster for Long-Lasting C19 Immunity
- New data suggest that nearly all C19 survivors have the immune cells necessary to fight re-infection.
- The findings, based on analyses of blood samples from 188 C19 patients, suggest that responses to the novel coronavirus, SARS-CoV-2, from all major players in the “adaptive” immune system, which learns to fight specific pathogens, can last for at least eight months after the onset of symptoms from the initial infection.
- “Our data suggest that the immune response is there — and it stays,” LJI Professor Alessandro Sette, Dr. Biol. Sci., who co-led the study with LJI Professor Shane Crotty, Ph.D., and LJI Research Assistant Professor Daniela Weiskopf, Ph.D.
- “We measured antibodies, memory B cells, helper T cells and killer T cells all at the same time,” says Crotty. “As far as we know, this is the largest study ever, for any acute infection, that has measured all four of those components of immune memory.”
- The findings, published in the January 6, 2021, online edition of Science, could mean that C19 survivors have protective immunity against serious disease from the SARS-CoV-2 virus for months, perhaps years after infection.
- The new study helps clarify some concerning C19 data from other labs, which showed a dramatic drop-off of COVID-fighting antibodies in the months following infection. Some feared that this decline in antibodies meant that the body wouldn’t be equipped to defend itself against reinfection.
- Sette explains that a decline in antibodies is very normal. “Of course, the immune response decreases over time to a certain extent, but that’s normal. That’s what immune responses do. They have a first phase of ramping up, and after that fantastic expansion, eventually the immune response contracts somewhat and gets to a steady state,” Sette says.
- The researchers found that virus-specific antibodies do persist in the bloodstream months after infection. Importantly the body also has immune cells called memory B cells at the ready. If a person encounters SARS-CoV-2 again, these memory B cells could reactivate and produce SARS-CoV-2 antibodies to fight re-infection.
- The SARS-CoV-2 virus uses its “spike” protein to initiate infection of human cells, so the researchers looked for memory B cells specific for the SARS-CoV-2 spike. They found that spike-specific memory B cells actually increased in the blood six months after infection.
- C19 survivors also had an army of T cells ready to fight reinfection. Memory CD4+ “helper” T cells lingered, ready to trigger an immune response if they saw SARS-CoV-2 again. Many memory CB8+ “killer” T cells also remained, ready to destroy infected cells and halt a reinfection.
- The different parts of the adaptive immune system work together, so seeing COVID-fighting antibodies, memory B cells, memory CD4+ T cells and memory CD8+ T cells in the blood more than eight months following infection is a good sign.
- “This implies that there’s a good chance people would have protective immunity, at least against serious disease, for that period of time, and probably well beyond that,” says Crotty.
- The team cautions that protective immunity does vary dramatically from person to person. In fact, the researchers saw a 100-fold range in the magnitude of immune memory. People with a weak immune memory may be vulnerable to a case of recurrent C19 in the future, or they may be more likely to infect others.
- “There are some people that are way down at the bottom of how much immune memory they have, and maybe those people are a lot more susceptible to reinfection,” says Crotty.
- “It looks like people who have been infected are going to have some degree of protective immunity against re-infection,” adds Weiskopf. “How much protection remains to be established.”
- The fact that immune memory against SARS-CoV-2 is possible is also a good sign for vaccine developers. Weiskopf emphasizes that the study tracked responses to natural SARS-CoV-2 infection, not immune memory after vaccination.
- “It is possible that immune memory will be similarly long lasting similar following vaccination, but we will have to wait until the data come in to be able to tell for sure,” says Weiskopf. “Several months ago, our studies showed that natural infection induced a strong response, and this study now shows that the responses lasts. The vaccine studies are at the initial stages, and so far have been associated with strong protection. We are hopeful that a similar pattern of responses lasting over time will also emerge for the vaccine-induced responses.”
- The researchers will continue to analyze samples from C19 patients in the coming months and hope to track their responses 12 to 18 months after the onset of symptoms.
- “We are also doing very detailed analyses at a much, much higher granularity on what pieces of the virus are recognized,” says Sette. “And we plan to evaluate the immune response not only following natural infection but following vaccination.”
- The team is also working to understand how immune memory differs across people of different ages and how that may influence C19 case severity.
2. More than half of C19 cases spread by asymptomatic carriers, CDC model shows
- A new model from the Centers for Disease Control and Prevention shows that those who are infected with but show no signs of C19 account for more than half of all coronavirus cases.
- The model, published in JAMA Network Open on Thursday, shows that an estimated 59 percent of all coronavirus cases come from those who are asymptomatic, including 35 percent who are presymptomatic — meaning they initially don’t show symptoms but eventually develop them — and 24 percent who never develop any signs of symptoms of C19.
- “The findings of this study suggest that the identification and isolation of persons with symptomatic C19 alone will not control the ongoing spread of the coronavirus (SARS-CoV-2),” the researchers wrote when describing their findings.
- The model supports the preventative measures experts have recommended for months, such as wearing a face covering and practicing social distancing.
- “The bottom line is controlling the C19 pandemic really is going to require controlling the silent pandemic of transmission from persons without symptoms,” Jay C. Butler, the CDC deputy director for infectious diseases and a study co-author, told the Washington Post. “The community mitigation tools that we have need to be utilized broadly to be able to slow the spread of SARS-CoV-2 from all infected persons, at least until we have those vaccines widely available.”
- Effectively controlling the spread of the virus will requires reducing the risk of transmission from people without symptoms and identifying and isolating people with C19 symptoms, the study authors wrote.
- The findings “suggest that measures such as wearing masks, hand hygiene, social distancing and strategic testing of people who are not ill will be foundational to slowing the spread of C19 until safe and effective vaccines are available and widely used,” the authors wrote.
3. Scientists identify ‘immune cop’ that detects the coronavirus
- Scientists at Sanford Burnham Prebys Medical Discovery Institute have identified the sensor in human lungs that detects the coronavirus (SARS-CoV-2) and signals that it’s time to mount an antiviral response. The study, published today in Cell Reports, provides insights into the molecular basis of severe disease and may enable new strategies for the treatment and prevention of C19.
- “Our research has shown that MDA-5 is the immune cop that’s tasked to keep an eye out for SARS-CoV-2 and call for back-up,” says Sumit Chanda, Ph.D., director of the Immunity and Pathogenesis Program at Sanford Burnham Prebys and senior author of the study. “MDA-5 recognizes replicating viruses in lung cells and activates interferon, the body’s own frontline defender against viral invasion. Without a proper interferon response, viral infections can lead to deadly, out-of-control inflammatory reactions.”
- The new study surveyed 16 viral RNA binding proteins in human lung epithelial cells and identified MDA-5 as the predominant sensor responsible for activating interferon. MDA-5 detects double-stranded viral RNA–a form that the SARS-CoV-2 virus takes when it replicates to spread the infection. Prior to this research, it was known that activating interferon is key to a coordinated immune response to the virus, but the sentinel switch that controls the process was unknown.
- “Understanding the biology of a virus and how it is detected is paramount to controlling infection and disease spread,” says Chanda. “SARS-CoV-2 appears to disable the innate immune arm of our surveillance system, which, in the case of SARS-CoV-2 is controlled by MDA-5, and prevents the activation of interferon. It’s the interferon response that drives the subsequent activation of many genes that exert antiviral activities–and data suggests that we need this activity to control early stages of viral infection and avoid the worst outcomes of C19.
- “Whether our bodies can defeat the virus’s offensive tactics and activate interferon greatly influences the severity of disease. Past studies have shown that interferon responses are higher in patients with mild-to-moderate cases compared to reduced levels in critically ill patients,” adds Chanda.
- “There is still a tremendous need to develop effective therapies for C19 and to prepare for future outbreaks,” says Chanda. “It’s possible that patients who become critically ill are deficient in the interferon signaling pathway. This research opens new avenues toward therapies that enhance the MDA-5 signaling to boost interferon levels early in infection to prevent severe disease.
- “It also creates opportunities to develop C19 vaccines that include an adjuvant(s) to enhance MDA-5 signaling. These would be formulations that use less ‘vaccine’ to minimize toxicity and side effects,” adds Chanda.
4. Why C19 pneumonia lasts longer, causes more damage than typical pneumonia
- Bacteria or viruses like influenza that cause pneumonia can spread across large regions of the lung over the course of hours. In the modern intensive care unit, these bacteria or viruses are usually controlled either by antibiotics or by the body’s immune system within the first few days of the illness.
- But in a study published in Nature on January 11, investigators at Northwestern Medicine show C19 pneumonia is different.
- Instead of rapidly infecting large regions of the lung, the virus causing C19 sets up shop in multiple small areas of the lung. It then hijacks the lungs’ own immune cells and uses them to spread across the lung over a period of many days or even weeks, like multiple wildfires spreading across a forest.
- As the infection slowly moves across the lung, it leaves damage in its wake and continuously fuels the fever, low blood pressure and damage to the kidneys, brain, heart and other organs in patients with C19.
- The severe complications of C19 compared with other pneumonias might be related to the long course of disease rather than more severe disease, the study authors said.
- This is the first study in which scientists analyzed immune cells from the lungs of C19 pneumonia patients in a systematic manner and compared them to cells from patients with pneumonia from other viruses or bacteria.
Drug trial to treat newly discovered targets in C19 pneumonia
- As a result of the detailed analysis, researchers identified critical targets to treat severe coronavirus (SARS-CoV-2) pneumonia and lessen its damage. The targets are the immune cells: macrophages and T cells. The study suggests macrophages – cells typically charged with protecting the lung – can be infected by SARS-CoV-2 and can contribute to spreading the infection through the lung.
- Northwestern Medicine will test an experimental drug to treat these targets in C19 pneumonia patients in a clinical trial early in 2021. The drug to be tested quiets the inflammatory response of these immune cells, thus enabling initiation of the repair process in the injured lung.
Aim to make C19 like a bad cold
- “Our goal is to make C19 mild instead of severe, making it comparable to a bad cold,” said study co-senior author Dr. Scott Budinger, chief of pulmonary and critical care medicine at Northwestern University Feinberg School of Medicine and Northwestern Medicine.
- “This effort truly represents a ‘moonshot’ in C19 research,” said study co-senior author Dr. Richard Wunderink, professor of pulmonary and critical care medicine at Feinberg and medical director of Northwestern Medicine’s ICU.
C19 unlikely to completely disappear
- C19, like influenza, is unlikely to ever go away, even if much of the population is vaccinated, said senior co-author Dr. Ben Singer, assistant professor of pulmonary and critical care medicine at Feinberg and a Northwestern Medicine physician.
- “Already, researchers at Northwestern and elsewhere are anticipating mechanisms by which this RNA virus, which mutates quickly, will evade current vaccines,” Singer said. “This study will help us develop treatments to reduce the severity of C19 in those who develop it.”
Mortality in C19 patients on ventilators lower than regular pneumonia patients
- The study also revealed why the mortality among patients on a ventilator for C19 was lower than patients on a ventilator due to regular pneumonia, the study reports. An intense conflagration in the lungs (regular pneumonia) has a higher risk of death. Those with C19 pneumonia are sick for a long time, but the inflammation in their lungs is not as severe as regular pneumonia.
- “If patients with C19 are carefully managed and the health care system isn’t overwhelmed, you can get them through it,” Budinger said. “These patients are very sick. It takes a really long time for them to get better. If you have enough beds and health care providers, you can keep the mortality to 20%. When health systems are overwhelmed mortality rates double up to 40%.”
- For the study, scientists performed a high-resolution analysis of the lung fluid of 86 C19 patients on a ventilator and compared it with lung fluid from 256 patients on a ventilator who had other types of pneumonia. Because of the safety concerns, only a handful of groups around the world performed analysis of the immune response in the lungs of patients with C19. As a result, important information about what was killing patients with severe C19 was missing.
5. Coronavirus shutdowns have suppressed other viruses, but a rebound is coming
- Veteran virus trackers say they are chronicling something never before seen — the suppression of virtually every common respiratory and gastrointestinal virus besides the novel coronavirus. They theorize that is largely due to global shutdowns, mask-wearing and a host of other health protocols aimed at stemming the spread of the coronavirus.
- These other viruses — including influenza A, influenza B, parainfluenza, norovirus, respiratory syncytial virus (RSV), human metapneumovirus — all appear to be circulating at or near levels lower than ever previously measured. The same is true for the respiratory bacteria that cause pertussis, better known as whooping cough, and pneumonia.
- In 2019, during the third week of December, before the coronavirus struck the United States, the CDC’s network of clinical labs reported that 16.2 percent of the 29,578 samples tested were positive for influenza A. During the same week in 2020, the rate was 0.3 percent.
- An online map of flu activity maintained by the CDC offers striking visual evidence of the effect. In 2020, for the week ending Dec. 19, the map of the United States is a sea of green, showing “minimal” levels in every state. For the corresponding week in 2019, most states were red (“high”) or deep blue (“very high”).
- As welcome as the absence of these other viruses is during a pandemic, epidemiologists say they see a potentially dangerous consequence after coronavirus cases eventually decline — a rebound that could be frightfully large given the relaxation of social distancing and lowered immunity to other pathogens.
- The possibility of a rebound is not merely theoretical: It appears to be happening already in Australia. Official reports showed historically low levels of flu-like illness among children and adults beginning in May, usually the start of flu season in that hemisphere. The sharp decline in cases came as the country imposed strict shutdown measures. But in the last few months, after the coronavirus was virtually obliterated and the country ended those restrictions, the number of flu cases among children aged 5 and younger began to soar, rising sixfold by December, when such cases are usually at their lowest.
- “That’s an important cautionary tale for us,” Messacar said. “Just because we get through the winter and don’t see much RSV or influenza doesn’t mean we’ll be out of the woods.”
- A breathtaking picture of the extent of the collapse of viral and bacterial infections can be seen in a single chart (shown below) created and maintained by BioFire, a company that provides diagnostic tests for viral and bacterial infections to over 2,500 U.S. health-care providers. The chart shows positivity rates for 13 respiratory viruses and bacteria during the past two years.
- A year ago at this time, nearly 60 percent of samples taken from patients with flu-like symptoms came back positive for one of the pathogens. But beginning in March of this year, when the coronavirus prompted shutdowns and school closings, the percent of samples positive for any other pathogen took a Grand Canyon-worthy plunge, bottoming out in May at about 6 percent. Even now, at the time of year when respiratory infections typically begin to peak, just 18 percent of samples are positive for any respiratory virus or bacteria.
6. ‘Pre-existing weaknesses’ hindered the U.S. pandemic response, researchers find
- How well a country has responded to C19 is not explained by the country’s economic power or scientific capacity, but by how its people relate to one another and their government, according to preliminary findings of a research study.
- “Countries with traditions of acting in concert against social problems, and countries with histories of deference to public authorities, fared better on compliance than countries lacking either or both,” the researchers wrote.
- Investigators compared characteristics of 23 countries on six continents, considering outcomes related to disease burden, economic impact and disparities. In the United States, rated as one of the poorest-performing countries, “the virus ‘exploited’ pre-existing weaknesses” in public health, the economy and politics.
- Before the pandemic, numerous reports and congressional testimony “recognized vulnerabilities that became apparent during C19,” another study found, including threats of viruses emerging from animals, economic disruption, inadequate stockpiles and vulnerability to global supply shortages. For that study, researchers compiled more than 1,200 pre-pandemic records in an expanding online library that was introduced on Tuesday — Health Security Net — in the hopes that it will “inform future planning and response efforts.”
- Another team, studying five countries in Africa, found that national leaders there had quickly recognized the threat from the virus and imposed measures to limit its importation and spread. “That managed to at least curtail the outbreak,” said Wilmot James, a Columbia University research scholar who was one of the study’s principal investigators, “but the impacts on the economies were quite devastating.”
- The Africa Centers for Disease Control and Prevention, a four-year-old institution modeled in part on its U.S. counterpart, was unique in providing technical assistance for an entire continent.
- The research reports were released Tuesday in conjunction with a two-day symposium, the Futures Forum on Preparedness, supported by Schmidt Futures and the Social Science Research Council.
Source: New York Times Coronavirus Update
E. Vaccines & Testing
1. Pfizer-BioNTech vaccine not affected by mutation seen in contagious coronavirus variant, but questions remain
- A mutation found in fast-spreading coronavirus variants does not negate the C19 vaccine from Pfizer and BioNTech, researchers reported late Thursday.
- The result is positive, if expected, evidence that existing vaccines will be able to withstand some mutations to the SARS-CoV-2 coronavirus without losing efficacy. But experts noted that this vaccine and others will still need to be tested against other mutations of concern, and that the new study only looked at one key mutation contained in the variants, not the full variants.
- “We’re working on that part now” in additional studies, Philip Dormitzer, Pfizer’s vice president and chief scientific officer of viral vaccines, told STAT.
- In the study, scientists engineered a version of the virus to include the mutation called N501Y. The mutation is found in variants that seem to transmit faster than other forms of the virus, including one first identified in the United Kingdom that is now spreading in other countries, including the United States.
- The scientists then compared how well blood taken from 20 people who had received the vaccine fended off the mutated form of the virus versus an earlier form. Their finding: there was “no reduction in neutralization activity against the virus” with the mutation, they wrote.
- The study, conducted by scientists at Pfizer and the University of Texas Medical Branch, was posted to a preprint server, meaning it has not been peer-reviewed.
- The concern is that mutations in particular spots in the RNA genome of the virus could change the appearance of certain areas on the virus, making them less recognizable to antibodies elicited by the vaccines.
- In this case, N501Y leads to a change on a key part of the virus’ spike protein, which helps the virus attach to human cells and establish an infection. Portions of the spike protein are prime target sites for antibodies.
- “These data don’t suggest a need for a change, but the mutations are hitting close enough to home that we need to be prepared,” Dormitzer said.
- N501Y seems to help the coronavirus attach to the receptor ACE2 on cells even better than other forms of the virus, meaning people exposed to the virus are more likely to contract it. This could help explain why variants with the mutation seem to be more transmissible.
- In addition to the variant first seen in the U.K., N501Y also appears in a variant identified initially in South Africa. But both the variants contain other mutations as well, so scientists need to test vaccines against the full variants to gauge whether the protection they confer is sustained.
- One key mutation called E484K appears to make the virus less recognizable to certain antibodies and has emerged as a particular concern. That mutation is present in the variant in South Africa, though not the version that first appeared in the U.K.
- Pfizer and its collaborators are in the process of testing its vaccine against the variants. Separately, Moderna — which also has a C19 vaccine authorized in the United States — has said it is conducting similar research.
- Scientists had expected that the vaccines authorized now or in development wouldn’t be taken down by single mutations. For one, antibodies generated by vaccines target multiple parts of the virus, so changes at one site shouldn’t sap the immune system’s ability to recognize the pathogen. Vaccines also induce other parts of the immune system to kick into gear, including fighters called T cells.
- Pfizer has now tested its vaccine against more than a dozen SARS-2 mutations without finding anything alarming, Dormitzer said.
- “I don’t want to be a Pollyanna here … we have to test each one as they come, but so far so good,” he said.
- If anything, a mutation might reduce how well vaccines work, not render them ineffective entirely, experts stress. But they do say it’s possible that the virus will pick up several mutations over time — perhaps years — that could threaten the protection the immunizations provide. In that case, the vaccines would have to be tweaked to match the genetic changes in the virus.
- Scientists and regulators are now trying to figure out at what point they would decide such updates to the vaccines are needed.
2. How can countries stretch C19 vaccine supplies? Scientists are divided
- Amid skyrocketing coronavirus infections, some countries are attempting to stretch limited supplies of C19 vaccines by reducing doses or changing vaccination schedules from those shown to be effective in clinical trials. But data are scarce on the impact of such measures, and scientists are split over whether they are worth the risks.
- “It might be fine,” says virologist Dan Barouch at Harvard Medical School in Boston, Massachusetts. “But we should stick with what’s been proven to work, because we want it to work. We don’t want to be creative for some unclear benefit and then have an unexpected problem.”
- On 30 December, the United Kingdom announced that it would allow doses of two coronavirus vaccines to be administered as many as 12 weeks apart, even though, in clinical trials, the two doses of the vaccine made by Pfizer of New York City and BioNTech of Mainz, Germany, were given to participants about three weeks apart. By delaying the second jab, the government hopes to free up doses to inoculate more people with their first shot during the current surge.
- Similar changes have been discussed in other countries, including the United States. Current US policy is to hold doses of the vaccine in reserve to guarantee recipients a second shot, but the transition team of president-elect Joseph Biden is reportedly considering an end to that. And Moncef Slaoui, head of the country’s Operation Warp Speed coronavirus-vaccine effort, has suggested that one vaccine — developed by Moderna of Cambridge, Massachusetts, and the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland — could be given at half the dose used in its largest clinical trial.
- “These are all reasonable questions to consider and evaluate in clinical trials,” said Stephen Hahn, chief of the US Food and Drug Administration (FDA), in a statement released on 4 January. “However, at this time, suggesting changes to the FDA-authorized dosing or schedules of these vaccines is premature and not rooted solidly in the available evidence.”
- Many vaccines consist of multiple jabs — the first to trigger an initial immune response to certain proteins produced by a virus or bacterium, and later booster shots calling the immune system’s memory cells into action. It usually takes weeks for these memory cells to be generated. Over time, the immune system also broadens its response, developing memory cells capable of responding not only to specific proteins, but also to some variants of them. This means that a later booster shot is sometimes more effective, says immunologist Akiko Iwasaki at Yale University in New Haven, Connecticut: “Immunologically speaking, it may even help to delay a little.”
- This might be especially true for vaccines that use harmless viruses to shuttle the genetic code for coronavirus proteins into cells, says Hildegund Ertl, an immunologist at the Wistar institute in Philadelphia, Pennsylvania. Cells read the code and make the coronavirus protein, triggering immune responses against it. But the immune system might also generate antibodies against the harmless vector virus. If the booster is administered while levels of those antibodies remain high, the vector could be neutralized before it has a chance to deliver its cargo.
- Vaccines that use viral vectors include Sputnik V, from Russia, and the vaccine developed by AstraZeneca of Cambridge, UK, and the University of Oxford, UK. Large clinical trials of the AstraZeneca vaccine, which has been authorized in the United Kingdom and India, among other countries, waited anywhere from one to three months before administering the booster shot, and the data suggest that longer intervals improved results, says Ertl. “I’m delighted that the UK is going to wait longer,” she says.
- But Ertl and others say it is less clear how a longer interval might change the effectiveness of RNA vaccines such as those made by Pfizer and Moderna. These vaccines do not rely on viruses to ferry genetic material into cells, and they cause cells to produce the coronavirus protein for only a few days after vaccination. Clinical-trial data suggest that recipients derive significant protection from the first dose of these vaccines, but most study participants received their second shot within a month, and little is known about the length of the immune response in the few who did not receive a second dose.
- Some researchers are also worried about the impact of the longer dosing interval on the coronavirus itself. Immunologist Florian Krammer at the Icahn School of Medicine at Mount Sinai in New York City says that people who receive a single dose of an RNA vaccine produce relatively low levels of antibodies, and he fears that this could encourage the emergence of viral variants that are resistant to vaccines.
Blocking viral evolution
- Not everyone agrees. Sarah Cobey, who studies the evolution of viruses and immunity at the University of Chicago in Illinois, points out that natural infections can also generate fairly low antibody levels. If single doses of vaccine can reduce the number of natural infections, they might cut the risk of resistance evolving, she says.
- And Cobey notes that although some variants might be partially resistant to vaccines, they are unlikely to render the shots completely ineffective. The body produces a mix of antibodies targeting different regions of a foreign protein; it will be difficult for a slowly evolving virus such as SARS-CoV-2 to mutate so that none of those antibodies recognize it while still retaining its ability to infect human cells. Meanwhile, the many further vaccines currently in the pipeline could provide fresh weapons against future coronavirus variants. “It’s a very serious thing to be sacrificing people now because you’re afraid that you won’t be able to handle a strain in the future,” she says. “If I were to place a bet, I would be doing what the UK is doing.”
F. Improved & Potential Treatments
1. C19 drug prospects boosted by discovery of short form of ACE2
- The coronavirus (SARS-CoV-2) enters nose and lung cells through binding of its spike protein to the cell surface protein angiotensin converting enzyme 2 (ACE2).
- Now a new, short, form of ACE2 has been identified by Professor Jane Lucas, Professor Donna Davies, Dr Gabrielle Wheway and Dr Vito Mennella at the University of Southampton and University Hospital Southampton NHS Foundation Trust.
- The study, published in Nature Genetics, shows that as well as the longer form of ACE2 used by SARS-CoV-2, a shorter form of ACE2 exists that lacks the SARS-CoV-2 binding site.
- Naturally occurring antiviral proteins called interferons have shown promise in treating C19. However, previous studies have shown that interferons increase levels of ACE2 – casting doubts over the potential for such treatments, with the possibility that increased ACE2 could see these drugs actually worsen C19 impacts.
- But this latest research shows that it is predominantly the short ACE2, which lacks the viral binding site, that is increased in response to interferons. Since levels of the longer form of ACE2 remain unchanged, interferons do not appear to boost entry points for the virus, supporting their use in treating C19 patients.
- As a result, a shadow over the promising inhaled interferon beta C19 therapy has been cleared with the discovery that although it appears to increase levels of ACE2 protein – coronavirus’ key entry point into nose and lung cells – it predominantly increases levels of a short version of that protein, which the virus cannot bind to.
- This helps to explain the hugely promising results for a trial of an inhaled interferon beta treatment for C19 patients, developed in Southampton by a team led by Professor Tom Wilkinson of the University of Southampton.
- This research gives a new insight into this short form of ACE2, and shows how it has a very different role to the longer form of ACE2 that acts as entry point for SARS-CoV-2.
- Short ACE2 lacks the binding site for SARS-CoV-2, so it cannot be used as an entry point for the virus. Instead, its regulation by interferons suggests it may be involved in the body’s anti-viral response.
- As the researchers showed that short ACE2 does not increase in response to SARS-CoV-2 infection, it is unlikely to be involved in the body’s immune response to C19, but it did increase in response to another common respiratory virus.
- These results will enable researchers to distinguish between these two forms of ACE2, knowledge which could prove invaluable for developing more sophisticated treatments for C19 patients.
- Professor Jane Lucas, Professor of Paediatric Respiratory Medicine at the University of Southampton and Honorary Consultant Paediatric Respiratory Medicine at University Hospital Southampton and one of the lead authors for the study, said:
- “We were excited to discover a new form of ACE2, and became even more interested when we realized that may be protective against SARS-CoV-2 in the airways rather than an entry site for infection. We believe this may have important implications for managing C19 infection and we are starting further studies to investigate this further.”
G. Concerns & Unknowns
1. New Research Shows Poor Gut Health Connected to Severe C19 – Probiotics May Help Patients
- Severe cases of C19 often include GI symptoms
- Chronic diseases associated with severe C19 are also associated with altered gut microbiota
- A growing body of evidence suggests poor gut health adversely affects prognosis
- If studies do empirically demonstrate a connection between the gut microbiota and C19 severity, then interventions like probiotics or fecal transplants may help patients
- People infected with C19 experience a wide range of symptoms and severities, the most commonly reported including high fevers and respiratory problems. However, autopsy and other studies have also revealed that the infection can affect the liver, kidney, heart, spleen — and even the gastrointestinal tract.
- A sizeable fraction of patients hospitalized with breathing problems also have diarrhea, nausea and vomiting, suggesting that when the virus does get involved in the GI tract it increases the severity of the disease.
- In a review published this week in?mBio,?microbiologist Heenam Stanley Kim, Ph.D, from Korea University’s Laboratory for Human-Microbial Interactions, in Seoul, examined emerging evidence suggesting that poor gut health adversely affects C19 prognosis. Based on his analysis, Kim proposed that gut dysfunction — and its associated leaky gut — may exacerbate the severity of infection by enabling the virus to access the surface of the digestive tract and internal organs. These organs are vulnerable to infection because they have widespread ACE2 — a protein target of SARS-CoV-2 — on the surface.
- “There seems to be a clear connection between the altered gut microbiome and severe C19,” Kim said.
- Studies have demonstrated that people with underlying medical conditions including high blood pressure, diabetes and obesity face a higher risk of severe C19. Risk also increases with age, with older adults most vulnerable to the most serious complications and likelihood of hospitalization. But both of these factors — advanced age and chronic conditions — have a well-known association with an altered gut microbiota. This imbalance can affect gut barrier integrity, Kim noted, which can allow pathogens and pathobionts easier access to cells in the intestinal lining.
- So far, the link between gut health and C19 prognosis hasn’t been empirically demonstrated, Kim noted. Some researchers have argued, he said, that unhealthy gut microbiomes may be an underlying reason for why some people have such severe infections.
- What studies have been done hint at a complicated relationship. A study on symptomatic C19 patients in Singapore, for example, found that about half had a detectable level of the coronavirus in fecal tests — but only about half of those experienced GI symptoms. That study suggests that even if SARS-CoV-2 reaches the GI tract, it may not cause problems. Kim also noted that a person’s gut health at the time of infection may be critical for symptom development.
- Many recent studies have found reduced bacterial diversity in gut samples collected from C19 patients, compared to samples from healthy people. The disease has also been linked to a depletion of beneficial bacterial species – and the enrichment of pathogenic ones. A similar imbalance has been associated with influenza A infection, though the 2 viruses differ in how they change the overall microbial composition.
- The depleted bacterial species associated with C19 infection include some families that are responsible for producing butyrate, a short-chain fatty acid, which plays a pivotal role in gut health by reinforcing gut-barrier function.
- Kim said he started analyzing the studies after realizing that wealthy countries with a good medical infrastructure — including the United States and nations in Western Europe — were among the hardest hit by the virus. The “western diet” that’s common in these countries is low in fiber, and “a fiber-deficient diet is one of the main causes of altered gut microbiomes,” he said, “and such gut microbiome dysbiosis leads to chronic diseases.”
- The pathogenesis of C19 is still not fully understood. If future studies do show that gut health affects C19 prognosis, Kim argued, then clinicians and researchers should exploit that connection for better strategies aimed at preventing and managing the disease. Eating more fiber, he said, may lower a person’s risk of serious disease. And fecal microbiota transplantation might be a treatment worth considering for patients with the worst cases of C19.
- The problem with gut health goes beyond C19, though, he said. Once the pandemic passes, the world will still have to reckon with chronic diseases and other problems associated with poor gut health.
- “The whole world is suffering from this C19 pandemic,” Kim said, “but what people do not realize is that the pandemic of damaged gut microbiomes is far more serious now.”
Also see: Gut Microbiome May Influence C19 Severity and Immune Response – Also Implicated in “Long COVID”
2. Study finds 76% of patients hospitalized with C19 have at least one symptom 6 months after falling ill
- 76% of C19 patients have at least one symptom six months after symptom onset.
- Fatigue or muscle weakness is the most common symptom, with sleep difficulties and anxiety or depression also frequently reported.
- Lower antibodies against C19 in patients six months after becoming ill compared with during acute infection raises concerns about the possibility of re-infection.
- More than three quarters of C19 patients have at least one ongoing symptom six months after initially becoming unwell, according to research published in The Lancet.
- The cohort study, looking at long-term effects of C19 infection on people hospitalised in Wuhan, China, reveals that the most common symptom to persist is fatigue or muscle weakness (63% of patients), with patients also frequently experiencing sleep difficulties (26%). Anxiety or depression was reported among 23% of patients.
- Patients who were severely ill in hospital more often had impaired lung function and abnormalities detected in chest imaging – which could indicate organ damage – six months after symptom onset.
- Levels of neutralizing antibodies fell by more than half (52.5%) after six months in 94 patients whose immune response was tested at the peak of the infection, raising concerns about the possibility of being re-infected by the virus.
- Little is known about the long-term health effects of C19 as few follow-up studies have so far been carried out. Those that have been conducted looked only at a small number of cases over a short follow-up period (typically around three months after discharge).
- Professor Bin Cao, from National Center for Respiratory Medicine, China-Japan Friendship Hospital and Capital Medical University, said: “Because C19 is such a new disease, we are only beginning to understand some of its long-term effects on patients’ health. Our analysis indicates that most patients continue to live with at least some of the effects of the virus after leaving hospital, and highlights a need for post-discharge care, particularly for those who experience severe infections. Our work also underscores the importance of conducting longer follow-up studies in larger populations in order to understand the full spectrum of effects that C19 can have on people.”
- The new study included 1,733 C19 patients who were discharged from Jin Yin-tan Hospital in Wuhan, China, between January 7th and May 29th 2020. Patients had a median age of 57 years. Follow-up visits were done from June 16th to September 3rd, 2020, and the median follow-up time was 186 days.
- At follow-up, 76% of patients (1,265/1,655) reported at least one ongoing symptom. Fatigue or muscle weakness was reported by 63% (1,038/1,655), while 26% (437/1,655) had sleep difficulties and 23% (367/1,733) experienced anxiety or depression.
- Of the 390 patients who underwent additional testing, 349 completed the lung function test (41 were unable to complete the test due to poor compliance). Patients with more severe illness commonly had reduced lung function, with 56% (48/86) of those at severity scale 5-6 (who required ventilation) experiencing diffusion impairment – reduced flow of oxygen from the lungs to the bloodstream. For patients at severity scale 4 (who required oxygen therapy) and those at scale 3 (who did not require oxygen therapy) the figures were 29% (48/165) and 22% (18/83), respectively.
- Patients with more severe disease performed worse in the six-minute walking test (which measures the distance covered in six minutes), with 29% of those at severity scale 5-6 walking less than the lower limit of the normal range, compared with 24% for those at scale 3, and 22% for scale 4.
- The authors also found that some patients went on to develop kidney problems post-discharge. As well as the lungs, C19 is known to affect other organs, including the kidney. Lab tests revealed that 13% (107/822) of patients whose kidney function was normal while in hospital had reduced kidney function in follow-up.
- Follow-up blood antibody tests from 94 patients after six months revealed that levels of neutralising antibodies were 52.5% lower than at the height of infection. The authors say this raises concerns about the possibility of C19 re-infection.
- As the number of participants with antibody test results both at acute phase and follow-up was limited, larger samples are needed in future to clarify how levels of antibodies against the virus change over time. Further work is also needed to compare differences in outcomes between inpatients and outpatients, as patients with mild C19 symptoms who stayed in temporary Fangcang shelter hospitals were not included in the study.
- Impaired lung function and exercise capacity observed in the study cannot be directly attributed to C19 as baseline data for these are unavailable. Due to the way the data was analysed, it also was not possible to determine if symptoms reported during follow-up were persistent following the infection, worsened after recovery, or occurred post-discharge.
- Writing in a linked Comment, Monica Cortinovis, Norberto Perico, and Giuseppe Remuzzi, from the Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Italy, who were not involved in the study, remark on the uncertainty regarding the possible long-term impacts of C19 on health, saying: “Unfortunately, there are few reports on the clinical picture of the aftermath of C19. The study by Huang and colleagues in The Lancet is therefore relevant and timely.”
- Echoing the study authors’ calls for further research, they add: “Even though the study offers a comprehensive clinical picture of the aftermath of C19 in hospitalised patients, only 4% were admitted to an intensive care unit (ICU), rendering the information about the long-term consequences in this particular cohort inconclusive. Nonetheless, previous research on patient outcomes after ICU stays suggests that several C19 patients who were critically ill while hospitalised will subsequently face impairments regarding their cognitive and mental health and/or physical function far beyond their hospital discharge.”
3. Coronavirus can infect neurons and damage brain tissue, study indicates
- Using both mouse and human brain tissue, researchers at Yale School of Medicine have discovered that the coronavirus (SARS-CoV-2) can directly infect the central nervous system and have begun to unravel some of the virus’s effects on brain cells. The study, published today in the Journal of Experimental Medicine (JEM), may help researchers develop treatments for the various neurological symptoms associated with C19.
- Though C19 is considered to primarily be a respiratory disease, SARS-CoV-2 can affect many other organs in the body, including, in some patients, the central nervous system, where infection is associated with a variety of symptoms ranging from headaches and loss of taste and smell to impaired consciousness, delirium, strokes, and cerebral hemorrhage.
- “Understanding the full extent of viral invasion is crucial to treating patients, as we begin to try to figure out the long-term consequences of C19, many of which are predicted to involve the central nervous system,” says Akiko Iwasaki, a professor at Yale School of Medicine.
- Many questions remain to be answered, including whether SARS-CoV-2 can infect neurons or other types of brain cells. To address this question, a team led by Iwasaki and co-senior author Kaya Bilguvar, an associate professor at Yale School of Medicine, analyzed the ability of SARS-CoV-2 to invade human brain organoids, miniature 3D organs grown in the lab from human stem cells. The researchers found that the virus was able to infect neurons in these organoids and use the neuronal cell machinery to replicate. The virus appears to facilitate its replication by boosting the metabolism of infected cells, while neighboring, uninfected neurons die as their oxygen supply is reduced.
- SARS-CoV-2 enters lung cells by binding to a protein called ACE2, but whether this protein is present on the surface of brain cells is unclear. The Yale team determined that the ACE2 protein is, in fact, produced by neurons and that blocking this protein prevents the virus from human brain organoids.
- SARS-CoV-2 was also able to infect the brains of mice genetically engineered to produce human ACE2, causing dramatic alterations in the brain’s blood vessels that could potentially disrupt the organ’s oxygen supply. Central nervous system infection was much more lethal in mice than infections limited to the lungs, the researchers found.
- Finally, the researchers analyzed the brains of three patients who succumbed to C19. SARS-CoV-2 was detected in the cortical neurons of one of these patients, and the infected brain regions were associated with ischemic infarcts in which decreased blood supply causes localized tissue damage and cell death. Microinfarcts were detected in the brain autopsy of all three patients.
- “Our study clearly demonstrates that neurons can become a target of SARS-CoV-2 infection, with devastating consequences of localized ischemia in the brain and cell death,” Bilguvar says. “Our results suggest that neurologic symptoms associated with C19 may be related to these consequences, and may help guide rational approaches to the treatment of C19 patients with neuronal disorders.”
- “Future studies will be needed to investigate what might predispose some patients to infections of the central nervous system and to determine the route of SARS-CoV-2 invasion into the brain and the sequence of infection in different cell types within the central nervous system that will help validate the temporal relationship between SARS-CoV-2 and ischemic infarcts in patients,” Iwasaki adds.
4. For people with type 1 diabetes, CDC Covid guidelines are puzzling
- The CDC’s recommendations for who ought to get a C19 vaccine when are causing confusion among people with diabetes.
- Those with the type 1 form of the disease are lower down on the priority list than those with type 2.
- People with type 2 will get vaccinated right after health care and other essential workers, as part of Phase 1. But people with type 1 are in Phase 2, even though data show that these people have just as much risk — if not more — of dying from C19 as those with type 2 diabetes.
- CDC guidelines rank a person with type 2 diabetes as someone “at increased risk” of more severe illness from C19, while those with type 1 diabetes “might be at an increased risk.”
- Those recommendations differ from the U.K.’s, which place patients with either type of diabetes in the same risk category. STAT has more here.
H. The Road Back?
1. What path will the US follow? Ireland presents a cautionary tale
- For the past year, I’ve been consumed with how Covid numbers are used/manipulated to create political narratives. From China to WHO to don’t-test-don’t-tell to Covid Trutherism in all its forms … that’s been the windmill I’ve tilted at for almost 12 months now.
- Last week I became consumed by a new twist on all this – Covid numbers that were being largely ignored. Insane infection numbers coming out of the UK and Ireland, apparently driven by a new virus strain, that we acknowledged over here but didn’t seem to be too mussed about. Daily new reported cases in Ireland are shown in the chart below.
- It reminded me of the Covid numbers coming out of Italy last February. Was Europe once again our crystal ball? Were we once again going to ignore THAT?
- And when I say “insane infection numbers” I mean a 30x spike in Covid cases in Ireland over the span of two weeks in late December, where the R number – the basic reproductive rate of the disease – went from something around 1.2 to something around 3. Where you suddenly went from a few hundred new Covid cases every day to more than six thousand cases every day. All in a country the size of Alabama (which, btw, currently has about 4 thousand cases every day).
- So I’ve been trying to figure out what happened in Ireland, and whether it could happen here.
- To do that I had to research this new UK-variant of the virus. I had to research the way in which Covid is explosively spreading in Ireland, and whether that was similar or different to the US. I had to research what it MEANS to have an R-number go from 1.2 to 3. And finally I had to dig into why this ‘Ireland Event’ was not being discussed by US Covid missionaries (to use an Epsilon Theory term) like Scott Gottlieb or Tony Fauci.
- I’ll start with the conclusion.
- I believe there is a non-trivial chance that the United States will experience a rolling series of “Ireland events” over the next 30-45 days, where the Covid effective reproductive number (Re not R0) reaches a value between 2.4 and 3.0 in states and regions where a) the more infectious UK-variant (or similar) Covid strain has been introduced, and b) Covid fatigue has led to deterioration in social distancing behaviors.
- A single Ireland event is a disaster. A series of Ireland events on the scale of the United States is catastrophic. If this were to occur, I’d expect to see a doubling of new Covid cases/day from current levels in the aggregate (today’s 7-day average is 240k/day), peaking somewhere around 500,000 new daily cases before draconian economic shutdowns (more severe than anything we’ve seen to date) would occur in every impacted major metro area. Hospital systems across the country would be placed under enormous additional strain, leading to meaningfully higher case fatality ratios (CFRs) as medical care was rationed. Most critically, this new infection rate would far outpace our current vaccine distribution capacity and policy. Assuming that vaccines are preferentially administered to the elderly, aggregate infection fatality ratios (IFRs) should decrease, but the overall burden of severe outcomes (death, long-term health consequences) would shift to younger demographics.
- Current US government policy rejects the possibility of an Ireland event, largely because of what I believe is a politically-motivated analysis by the CDC that models more than 100 million Americans already possessing Covid antibodies, prior to any vaccination effort. Using data from flu monitoring programs in prior years, the CDC models project that 70 MILLION Americans have already gotten sick with symptomatic Covid, but decided to just write it off as a bad cold and never got tested. I am not making this up.
- Add in another 10 million or so Americans who the CDC models as having already had asymptomatic Covid, add in the 23 million Americans who we know have had Covid, and voila! – per the CDC, one-third of the American population is already effectively immunized against getting Covid in the future. And obviously enough, if >30% of Americans are already effectively immunized against Covid because they’ve already gotten sick, then it’s very difficult to hit the Re numbers of 2.4 – 3.0 that Ireland is currently experiencing.
- I think this model is wrong, and I think the CDC knows that it’s wrong.
- I think it’s wrong because the 2021 behavior of someone who thinks they might have Covid is very different from the 2015 behavior of someone who thought they might have had the flu, but the CDC assumes it is the same in their models. You don’t ignore Covid. You don’t just brush it off. I’d say that no one just brushes off Covid symptoms the way they might have brushed off flu symptoms in the past, but of course that’s not true. I’m sure there are millions of Americans who have, in fact, had symptomatic Covid and ignored it, particularly in spring and early summer when our national testing capability was pathetic. But 70 MILLION Americans? Twenty percent of ALL Americans? More than three times the number of known Covid cases? C’mon, man.
- I think the CDC knows this model is wrong because if it were true – if they actually thought that one-third of Americans were already effectively immunized by having Covid antibodies – this would be an ENORMOUS factor in determining vaccination policy. Otherwise, you are going to be wasting one-third of your precious supply of vaccines on people who don’t need it.
- I think the CDC knows this model is wrong because if it were true, how do you make sense of Covid hospitalization rates?
- Again, were there millions of undiagnosed and “brushed-off” Covid cases in the spring and early summer when Covid testing was ridiculously sparse? Absolutely. But unless you’re prepared to say that either the SARS-CoV-2 virus is much more dangerous today than it was in the spring or that hospital Covid admission policies are much more lenient today than they were in the spring, I think it is impossible to reconcile actual Covid hospitalization data on 23 million symptomatic-and-diagnosed Covid cases with a model of 70 million symptomatic-but-undiagnosed Covid cases.
- But this CDC model is why prominent Covid like Scott Gottlieb and Tony Fauci have said that they expect daily case numbers to decline from here on out, not accelerate, and this is why I think a potential Ireland event is NOT priced into any mainstream market expectations or political expectations for 2021.
- Unfortunately, once it becomes apparent that an Ireland event is occurring, it’s too late to stop it.
- In our human-scale, linear world, we experience exponential growth like this: nothing, nothing, nothing … case, case, case … cluster, cluster, cluster … BOOM! But by the time we start to really pay attention to an exponential growth process – typically at the cluster stage – the process is already too entrenched to stop it, absent incredibly harsh social measures like you see China reinstating today in Shijiazhuang, a city of 11 million. No government in the West is prepared to even talk about these measures, much less implement them. So we’re always surprised by the BOOM. If an Ireland event occurs here, it will be no exception.
- A full-blown Ireland event is driven by both the more virulent UK-strain AND a deterioration in social distancing behaviors. Either taken alone is bad enough. It’s the combination, though, that creates a regional superspreader event. Irish health authorities estimate that their starting point for Covid Re was something between 1.1 and 1.3 (meaning that, on average, one person infected with the SARS-CoV-2 virus would pass it along to 1.1 – 1.3 new people). They blame deteriorating masking/social distancing for the majority of their “event” (say, a 0.9 – 1.1 increase in the Re number), and the UK-variant for the balance (say, a 0.5 – 0.7 increase in Re).
- This is very much in line with the latest research from Public Health England, which estimates that the UK-variant Covid virus is approximately 40% more infectious than the baseline virus. Notably, the UK-variant is, relatively speaking, significantly more infectious than the baseline virus for “close contacts” (not face-to-face, up to 2 meters apart) rather than “direct contacts”, meaning that the UK-variant virus is particularly successful at bridging the air gap between strangers or short-duration contacts in an indoor space. This is … ummm … troubling. As lax as we all have gotten with our mask wearing and our social distancing outside of the home, the UK-variant virus dramatically reduces the margin of error we have with mask wearing and social distancing outside of the home.
- For the same reasons that we humans typically don’t recognize an exponential growth process prior to the cluster, cluster, cluster stage, we have an even harder time appreciating the impact of even a small increase in the effective reproduction rate of Covid. A 40% increase in Re has an enormous impact on how many people will be infected by Covid. For example, let’s assume that the current Re for the United States is something like 1.4 (I think it’s probably higher than that in areas like SoCal, and going up everywhere as Covid fatigue takes hold). With a 5-day infection cycle (assume you pass along the virus to 1.4 new people within 5 days of contracting the virus yourself, i.e. before you become symptomatic), a single Covid case will result in a grand total of 2,296 Covid infections over a 100-day period. Now let’s increase that Re by 40%, so that it’s not 1.4 but is 2.0 … now that single Covid case will result in more than 2 MILLION total Covid infections over a 100-day period.
- This is the power of exponential growth. The numbers get silly … I mean, take that Re up to 3.0 (the high end of the current Ireland estimate), and a single Covid case will result in 5.2 BILLION total cases over a 100-day period, about 60% of the entire human population on the planet. Obviously our social behaviors around the disease would change dramatically well before we got to that point. But the real challenge of all this from a social behavior perspective is the nothing, nothing, nothing … case, case, case … cluster, cluster, cluster … BOOM! nature of any exponential growth process.
- That Re of 2.0 that results in 2 million total infections from a single Covid case over 100 days? On Day 30 there are only 127 total cases. Not noticeable at all. On Day 50 there are just over 2,000 total cases. Barely noticeable. Let’s say you’re an elected political leader. Are you really going to take the steps that are necessary to stop this process – like shutting down domestic travel to and from an infected area, like physically quarantining entire cities – over a few hundred cases? Not a chance. Even if you’re right … even if you prevent a catastrophic outcome through your actions on Day 30 or Day 50 … your voters will never know that you were right. They will only experience the lockdown pain, and they will never credit you for the catastrophe averted.
- I think we’re already at Day 30 in a dozen states. I suspect we’re already at Day 50 in a few.
- So look, maybe I’m wrong about all this. Maybe we’re already well along the path to herd immunity, and one-third of Americans currently have Covid antibodies through prior exposure, just like the CDC models say. Maybe we’ll all rediscover that old-time religion when it comes to mask wearing and social distancing outside of the home. Maybe governors and the new Administration will focus on containing the UK-variant through domestic travel restrictions. Maybe we’ll wake up tomorrow with a new urgency about vaccine distribution.
- Maybe. But my spidey-sense is really tingling on this one.
I. Innovation & Technology
1. Detecting C19 Antibodies in 10–12 Seconds With a 3D Printed Test Chip
An image of the C19 test chip made by aerosol jet nanoparticle 3D printing.
- Researchers at Carnegie Mellon University report findings on an advanced nanomaterial-based biosensing platform that detects, within seconds, antibodies specific to the coronavirus (SARS-CoV-2). In addition to testing, the platform will help to quantify patient immunological response to the new vaccines with precision.
- The results were published recently in the journal Advanced Materials. Carnegie Mellon’s collaborators included the University of Pittsburgh (Pitt) and the UPMC.
- The testing platform identifies the presence of two of the virus’ antibodies, spike S1 protein and receptor binding domain (RBD), in a very small drop of blood (about 5 microliters). Antibody concentrations can be extremely low and still detected below one picomolar (0.15 nanograms per milliliter). This detection happens through an electrochemical reaction within a handheld microfluidic device which sends results almost immediately to a simple interface on a smart phone.
- “We utilized the latest advances in materials and manufacturing such as nanoparticle 3D printing to create a device that rapidly detects C19 antibodies,” said Rahul Panat, an associate professor of mechanical engineering at Carnegie Mellon who uses specialized additive manufacturing techniques for research ranging from brain-computer interfaces to biomonitoring devices.
- An additive manufacturing technology called aerosol jet 3D printing is responsible for the efficiency and accuracy of the testing platform. Tiny, inexpensive gold micropillar electrodes are printed at nanoscale using aerosol droplets that are thermally sintered together. This causes a rough, irregular surface that provides increased surface area of the micropillars and an enhanced electrochemical reaction, where antibodies can latch on to antigens coated on the electrode. The specific geometry allows the micropillars to load more proteins for detection, resulting in very accurate, quick results.
- The test has a very low error rate because the binding reaction between the antibody and antigen used in the device is highly selective. The researchers were able to exploit this natural design to their advantage.
- The results come at an urgent time during the C19 pandemic. “Because our technique can quantify the immune response to vaccination, it is very relevant in the current environment,” Panat said.
- Panat collaborated with Shou-Jiang Gao, leader of the cancer virology program at UPMC’s Hillman Cancer Center and professor of microbiology and molecular genetics at Pitt. Azahar Ali, a researcher in Panat’s Advanced Manufacturing and Materials Lab, was the lead author of the study.
- Rapid diagnosis for the treatment and prevention of communicable diseases is a public health issue that goes beyond the current C19 pandemic. Because the proposed sensing platform is generic, it can be used for the rapid detection of biomarkers for other infectious agents such as Ebola, HIV, and Zika.
- Such a quick and effective test could be a game-changer for controlling the spread of diseases.
J. Projections & Our (Possible) Future
1. WHO says herd immunity will not happen in 2021
- WHO chief scientist Soumya Swaminathan said Monday that herd immunity to the coronavirus would not be achieved in 2021, despite the growing availability of vaccines.
- Mitigating factors to herd immunity include limited access to vaccines in developing countries, skepticism about vaccination and the potential for virus mutations, according to health experts.
Making progress, but vaccines ‘take time’
- “We are not going to achieve any levels of population immunity or herd immunity in 2021,” Swaminathan told a briefing, while emphasizing that measures such as physical distancing, handwashing and wearing masks continue to be necessary in containing C19’s spread for the rest of the year.
2. This is what an ‘overwhelmed NHS’ looks like. We must not look away
- England currently has more than 30,000 patients in hospital with C19. This is 62% more than at the first peak in April. Chris Whitty wrote in the Sunday Telegraph that the NHS faces the “most dangerous situation in living memory” and hospitals could be overwhelmed within two weeks. The London mayor, Sadiq Khan, declared a Covid emergency in the capital, warning that its NHS was already overwhelmed. Each new day of record admissions turns the screw on frontline staff. The problem is that while the NHS, government ministers and scientists are all sounding the alarm, there is also a reluctance to spell out exactly what this means.
- This is an account of what it truly means for a hospital to be “overwhelmed”. It is gleaned from years of working with intensive care clinicians and hearing from doctors across the country. Much of this is happening already, but we have not yet seen the worst.
- The danger is not of a sudden collapse, but an escalation of worsening care for patients and increasing pressure on staff. First, care that is not immediately essential is postponed: operations such as hip or knee replacements, scans or check-ups for chronic diseases such as diabetes or heart disease. This will mean that some people get sicker in the future because they missed out on care now. Others will have new cancers or heart disease missed for several months. This is already happening.
- Then, as beds become scarce, capacity is expanded, particularly in intensive care units. This has meant finding and converting space – separated from non-Covid areas – for very sick patients, but also finding a way to staff them in an already stretched NHS. Intensive care is exactly that: intensive. There should be one specialised ICU nurse to every one or two patients. There are only a limited number of ICU-trained nurses, and acutely ill Covid patients are severely sick, even compared with other ICU patients.
- As capacity is extended, ICU nurses are each allocated more patients to look after. This is already happening. With staffing stretched to as many as four patients to each ICU nurse, non-specialist nursing and clinical staff are drafted in to help. By this point, staff are exhausted from working as many shifts as possible with little time off. It is almost inevitable that care suffers. Small mistakes creep in and warning signs are missed. Most errors, perhaps all, will be caught and corrected. But it might then take longer for some patients to recover. It is incredibly distressing for clinical staff who cannot provide the level of care they wish to.
- Then there’s the question of oxygen. Hospitalised Covid patients need help breathing. This can be a simple face mask that provides extra oxygen, a tight-fitting mask that uses pressure to force oxygen into lungs, or tubes doing the breathing for you in ICU. But the pipes in the hospital walls that deliver oxygen to each bed were not designed to be used by hundreds of patients at the same time. If this facility is breached, the whole system fails. This catastrophic scenario – where the oxygen stops being delivered to patients and many die – happened recently in Egypt.
- It should never get to that stage – hospitals are constantly monitoring their oxygen supplies – but some hospitals in England are very oxygen-stressed, and this can affect decisions about care.
- As for logistics, patients will keep arriving without enough beds to accommodate them, which is already happening in London and the south-east. Ambulances have had to queue for hours outside hospitals, waiting for a bed to become available. While they care for patients in the hospital queue, they are unable to pick up new patients so waiting times for ambulances get longer. A paramedic outside London told me that because of the queues, they are now attending to only half as many patients each shift as usual.
- More and more ambulance and hospital staff are off sick from Covid and physical or mental burnout, putting further strain on the system. So far, other hospitals in England have been able to relieve some of the pressure by taking patients from London and the south-east, but as admissions rise across the country that option diminishes. Heart attack or stroke patients might die at home waiting for an ambulance, or inside the vehicle as they wait for a bed to become free.
- The final stage, which London is now approaching, is where patient care is not just compromised but cannot be delivered. This won’t be dramatic and public – you won’t see patients refused entry to hospital or bodies on the street. It will take the form of doctors being forced to make impossible decisions about which patient can best benefit from a single spare ICU bed when many need one, or how long to wait for a very sick patient to improve before having the conversation with the family about withdrawing care.
- This is called rationing. The NHS will speak about it as the ultimate warning, but it is very wary about saying exactly how those decisions would actually get made. The British Medical Association has published guidelines, but much is left up to individual hospitals and doctors. Senior doctors I know have been close to tears at the thought of making those decisions. Many are scared of being blamed afterwards.
- The strain on the NHS will get worse over the next few weeks. If we are very lucky, we will avoid the worst scenarios outlined here. We can each contribute by reducing our contact with others as much as possible, wearing masks, opening windows, keeping distance.
3. The Future of the Coronavirus? An Annoying Childhood Infection
- As millions are inoculated against the coronavirus, and the pandemic’s end finally seems to glimmer into view, scientists are envisioning what a post-vaccine world might look like — and what they see is comforting.
- The coronavirus is here to stay, but once most adults are immune — following natural infection or vaccination — the virus will be no more of a threat than the common cold, according to a study published in the journal Science on Tuesday. Read the study here.
- The virus is a grim menace now because it is an unfamiliar pathogen that can overwhelm the adult immune system, which has not been trained to fight it. That will no longer be the case once everyone has been exposed to either the virus or vaccine.
- Children, on the other hand, are constantly challenged by pathogens that are new to their bodies, and that is one reason they are more adept than adults at fending off the coronavirus. Eventually, the study suggests, the virus will be of concern only in children younger than 5, subjecting even them to mere sniffles — or no symptoms at all.
- In other words, the coronavirus will become “endemic,” a pathogen that circulates at low levels and only rarely causes serious illness.
- “The timing of how long it takes to get to this sort of endemic state depends on how quickly the disease is spreading, and how quickly vaccination is rolled out,” said Jennie Lavine, a postdoctoral fellow at Emory University in Atlanta, who led the study.
- Dr. Lavine and her colleagues looked to the six other human coronaviruses — four that cause the common cold, plus the SARS and MERS viruses — for clues to the fate of the new pathogen.
- The four common cold coronaviruses are endemic, and produce only mild symptoms. SARS and MERS, which surfaced in 2003 and 2012, respectively, made people severely ill, but they did not spread widely.
- Reanalyzing data from a previous study, they found that the first infection with common cold coronaviruses occurs on average at 3 to 5 years of age. After that age, people may become infected again and again, boosting their immunity and keeping the viruses circulating. But they don’t become ill.
- The researchers foresee a similar future for the new coronavirus.
- Depending on how fast the virus spreads, and on the strength and longevity of the immune response, it would take a few years to decades of natural infections for the coronavirus to become endemic, Dr. Lavine said.
- Without a vaccine, the fastest path to endemic status is also the worst. The price for population immunity would be widespread illness and death along the way.
- Vaccines completely alter that calculus: The faster people can be immunized, the better. An efficient vaccination rollout could shorten the timeline to a year, or even just six months, for the coronavirus to become an endemic infection.
- Still, the vaccines are unlikely to eradicate the coronavirus, Dr. Lavine predicted. The virus will become a permanent, albeit more benign, inhabitant in our environment.
- Other experts said this scenario was not just plausible but likely.
- It is more plausible that the vaccines will prevent illness — but not necessarily infection and transmission, he added. And that means the coronavirus will continue to circulate.
- “It’s unlikely that the vaccines we have right now are going to provide sterilizing immunity,” the kind needed to prevent infection, said Jennifer Gommerman, an immunologist at the University of Toronto.
- Natural infection with the coronavirus produces a strong immune response in the nose and throat. But with the current vaccines, Dr. Gommerman said, “you’re not getting a natural immune response in the actual upper respiratory tract, you’re getting an injection in the arm.” That raises the likelihood that infections will still occur, even after vaccination.
- Ultimately, Dr. Lavine’s model rests on the assumption that the new coronavirus is similar to the common cold coronaviruses. But that assumption may not hold up, cautioned Marc Lipsitch, an epidemiologist at the Harvard T.H. Chan School of Public Health in Boston.
- Another plausible scenario, he said, is that the virus may come to resemble the seasonal flu, which is mild some years and more lethal in others. New variants of the coronavirus that evade the immune response may also complicate the picture.
- “Their prediction of it becoming like common cold coronaviruses is where I’d put a lot of my money,” Dr. Lipsitch said. “But I don’t think it’s absolutely guaranteed.”
1. Some Good News On Hospitalizations
- A little over two weeks ago we showed that despite the continued rise in covid cases in the US, where BofA calculated that the 7-day average of new US cases hit a new record high of 241,600 yesterday with daily Covid-related deaths at 3,190 and hospitalizations at 4,840 at new highs, having risen 20% over the past week…
- … the trend in US hospitalizations was decidedly optimistic, with the second derivative of hospitalizations – or the daily number of new admission – continuing to moderate with the weekly increase well below 10,000 versus the peak of near 15,000 almost two weeks ago.
- As a reminder, in Mid-December, we reported why according to Goldman, covid-related hospitalizations are about to tumble – just as Biden gets inaugurated – as more vaccinations are rolled out, and the latest data validates this.
- To be sure, despite the increase in absolute terms, the hospitalization rate as a percentage of daily new infections has remained remarkably steady as the following charts from JPMorgan show:
- And while select hospital systems are indeed nearing overcrowded levels – which are due to numerous other factors in addition to covid – as the following chart of the ten most overcrowded hospital systems shows…
- … even Bloomberg now writes that “the pace of C19 hospitalizations in the Northeast is showing some preliminary signs of easing, adding to hopeful indicators in the Midwest, where the latest viral wave began.“
- According to the report, the number of people currently hospitalized with C19 in the Northeast was 21,494 as of Sunday, up 0.8% from a week earlier, the smallest seven-day percentage increase since Sept. 25, according to Covid Tracking Project data.
- Bloomberg’s admission that contrary to widespread fears that covid would crush the US hospital system comes as the virus is now raging once again primarily across the Sun Belt and as many states are finding tremendous challenges with the vaccine rollout.
- Based on U.S. Census Bureau definitions for each region, hospitalizations are up 6.1% in the past week in the South; up 4% in the West; and down 4.2% in the Midwest.
- And some more good news according to the Covid Tracking Project, as reported by Bloomberg: no states posted record cases on Sunday, but weekends are typically slower reporting periods.
- Finally, according to Bloomberg, Arizona now leads the nation in people currently hospitalized with the virus per capita, with 685 per million residents.
L. Practical Tips & Other Useful Information
1. Should You Go to the ER for That?
- With emergency rooms and ICUs across the country overloaded, a trip to the hospital can mean greater pandemic-related risks. According to the Covid Tracking Project, more than 132,000 people are in hospital with C19, with the majority of states reporting record hospitalizations. That affects not just emergency departments but staffing and space throughout entire hospitals, which usually isolate Covid patients to prevent infection.
- That is complicating the decision to go to the emergency room. Here’s what doctors and other medical authorities advise.
When are urgent-care clinics the best option?
- If you aren’t experiencing heart attack or stroke symptoms, some lesser emergencies may be easier addressed outside the ER, said Andra Blomkalns, chair of the emergency medicine department at Stanford University. This is critical if hospitals in your area are near capacity. “If you have a sprained ankle, it’s probably not the time to go to the hospital,” she said. Many urgent-care clinics also post waiting times and can do sutures, X-rays and other diagnostic testing.
- Remember that your gut reaction can be misleading. Research shows that people can’t always judge whether they are experiencing a health emergency, said Charleen Hsuan, professor of health policy and administration at Pennsylvania State University, adding, “in general, patients aren’t necessarily good at telling when something is a real emergency or not.”
Which area of the hospital poses the most risk to non-Covid patients?
- As Covid patients pour in, separating them from ER arrivals with non-Covid-related emergencies is getting more difficult, said Sarah Nafziger, vice president for clinical support services at the University of Alabama at Birmingham Hospital. Many hospitals, including Dr. Nafziger’s, have created separate entrances and waiting areas, but such measures help only so much amid the onslaught of patients. “They don’t come in wearing a label: ‘I have Covid’ or ‘I don’t,’ ”she said.
If you can choose among ERs and have more than minutes to spare, what can you do before heading to a hospital?
- If your doctor has admitting rights at a particular hospital, call to see whether you should come in and inquire about crowds, said Eugene Litvak, president of the Institute for Healthcare Optimization, a nonprofit in Newton, Mass. Many hospitals post ER waiting times online or can estimate them over the phone. Also, consider the size of the hospital, especially if you end up needing intensive care. “Larger hospitals have better resources and typically smaller hospitals have much fewer ICU beds that are critical nowadays,” he said.
What should you learn before going to a hospital for surgery?
- In general, you should get a sense of current staffing levels as well as resources after surgery. Pre-pandemic research shows that a nurse-to-patient ratio of 1:5 or 1:4 can result in better care for the patient, said Mr. Litvak, who is also an adjunct professor at the Harvard T.H. Chan School of Public Health. Covid patients are clustered in hospitals and staying longer, so they are drawing resources from other departments, he said, but nursing staff can’t move back and forth, tending to Covid and non-Covid patients. You might ask your doctor whether surgeries are scheduled evenly throughout the week or concentrated on certain days, which can limit space in recovery areas on some days, he said.
- A hospital’s website might also alert patients to any pandemic-related changes to procedures, Dr. Hsuan said. She warned that quality ratings for hospitals haven’t been updated to reflect operations during the pandemic.
How can you ensure the best care amid reports of doctors and staff being stretched thin?
- Beyond tracking hospital-occupancy rates, there is no way to tell if a particular medical provider feels overworked. Hospitals don’t release information on when they rotate staff to provide time off between shifts. “To some degree you have to have some faith in the system,” Dr. Blomkalns said. “Physicians are used to staying up nights, studying hard and being challenged on the job—and this is what we all trained to do.”
What can you do once at the hospital?
- Social distancing, masks and hand-washing are critical. Most hospitals don’t allow cloth masks and will ask patients to wear surgical ones during their stay. According to Dr. Nafziger, while some health-care workers have been vaccinated, the shots haven’t yet had an effect on the hospital population overall. “It doesn’t mean that hospitals are any safer right this minute,” she said.
M. Johns Hopkins COVID-19 Update
January 12, 2021
1. Cases & Trends
- The WHO C19 Dashboard reports 89.71 million cases and 1.94 million deaths as of 11:45am EST on January 12. Following 2 weeks of decreased global incidence and mortality, coinciding with holidays around the world, the WHO reported new record high weekly totals for both C19 incidence and mortality. The WHO reported 4.95 million new cases last week, a nearly 20% increase over the previous week. The WHO also reported 85,653 deaths last week, an 11% increase over the previous week.
- The US CDC reported 22.32 million total cases and 373,167 deaths. On January 8, the US reported 314,093 new cases, becoming the first country to surpass 300,000 new cases in a single day. To our knowledge, the US remains the only country to report more than 100,000 new cases in a single day. The US is now averaging 244,702 new cases per day, the highest daily incidence to date and nearly 1 million new cases every 4 days. The US reported a new record for single-day mortality* as well, with 4,180 deaths reported on January 7. The average daily mortality surpassed 3,000 deaths per day for the first time since the onset of the pandemic. The current average of 3,214 is 12.5% higher than the peak mortality during the United States’ initial surge, corresponding to nearly 10,000 deaths every 3 days.
- The US CDC reported 25.48 million vaccine doses distributed and 8.99 million doses administered (35.3%). These include 4.24 million doses distributed for use in long-term care facilities, of which 937,028 (22.1%) have been administered.
- Distribution of SARS-CoV-2 vaccines continues to scale up nationwide, but the speed at which states are administering vaccinations varies widely. Among US states, all but 7 (and Washington DC) have received between 6,000 and 8,000 doses per 100,000 population from the federal government, illustrating that allocation has been largely consistent nationwide. Arkansas; Hawai’i; Maine; New Mexico; Vermont; Washington, DC; and West Virginia have received between 8,000 and 9,000 doses per 100,000 population, and Alaska has received 18,092 doses per 100,000 population, more than double the per capita total received by any other state.
- While the per capita distribution is relatively consistent between states, vaccine administration is a much different story. Most US states have administered between 2,000 and 4,000 doses per 100,000 population. Among those states reporting higher vaccination coverage, Alaska (4,788); Maine (4,088); Vermont (4,128); Washington, DC (4,141); and West Virginia (5,376) are among those that have administered the most vaccine doses per capita. Connecticut is reporting 4,128 vaccines per 100,000 population, and North and South Dakota are reporting 5,100 and 5,451, respectively. On the other end of the spectrum, 9 states are reporting fewer than 2,000 vaccinations per 100,000 population, including Arkansas (1,355) and Georgia (1,346) with fewer than 1,500. Alabama (23.4%) and Arizona (24.5%) are also reporting fewer than 25% of doses administered. 10 states have administered more than half of their received doses. North and South Dakota are the top 2 states, with 72.6% and 70.0%, respectively.
- The Johns Hopkins CSSE dashboard reported 22.71 million US cases and 378,457 deaths as of 1:30pm EST on January 12.
2. US VACCINATION
- As vaccination efforts continue in the US, operational and policy challenges continue to emerge, some of which are slowing progress. One of the biggest issues with the US vaccination effort is the national distribution system. Under the current plan, the federal government is reserving approximately half of the available vaccine doses in order to ensure that enough supply is available to provide second doses to all vaccinees. In order to speed the United States’ C19 vaccination progress, US President-Elect Joe Biden announced that he intends to release essentially all of the remaining federal inventory soon after taking office. The stated goal of administering 100 million vaccinations in the first 100 days of his term would be a tremendous achievement, particularly considering the US has administered fewer than 10 million doses in slightly less than a month.
- Efforts are ongoing to establish plans to provide states with additional information regarding future shipments that will enable vaccinators to improve scheduling and administration, but many challenges remain. Even if the federal government increases the distribution to states, there are still many barriers to increasing the pace of vaccination at the local level.
- Notably, the Biden Administration plan will not delay the second dose, like in some other countries. The aim is to increase the speed at which the first doses are administered and to provide increased transparency regarding the timing of future shipments to improve planning at the local level. Following the Biden Administration announcement, the US Department of Health and Human Services is expected to announce that the federal government will begin distributing the reserved vaccine doses prior to President-Elect Biden taking office.
- As we covered previously, the European Medicines Agency (EMA) updated its guidance for the Pfizer/BioNTech vaccine to recommend the use of “low dead-volume” syringes in order to enable vaccinators to draw an extra, sixth dose from vaccine vials. Reports emerged early in the US vaccination effort that some Pfizer/BioNTech vials contained enough vaccine for a sixth (or sometimes seventh) dose; however, a report published by Politico indicates that some of the syringes distributed nationwide by Operation Warp Speed are not the kind that enable vaccinators to draw extra doses. The syringes are distributed along with the vaccine as part of “ancillary supply kits,” and federal officials are reportedly working on a solution to provide syringes with a smaller “dead-volume” that could increase the number of available doses.
- At 1 extra dose of vaccine per vial, the overall capacity could increase by 20%, which could translate to an extra 5 million doses, based on the current national distribution. A representative from the American Hospital Association indicated that the syringes included with the most recent distributions of the vaccine have a larger “dead-volume,” which is resulting in fewer doses of the vaccine compared to earlier shipments, posing challenges in terms of ensuring enough vaccine is available to provide individuals with the second dose.
- A representative for the American Pharmacists Association noted that the federal tracking system is based on the number of vials distributed, not the number of doses administered, so hospitals that receive the same number of vials may not have enough vaccine to provide everyone with a second dose, if they are not able to draw extra doses from each vial like they did previously.
Mass Vaccination Events
- As vaccination efforts scale up nationwide, including expanded eligibility, state and local public health and healthcare officials are proceeding with plans to establish mass vaccination capacity. Some of these efforts are leveraging space available at large venues—such as stadiums, convention centers, and fairgrounds—which can provide space for many vaccinators that can process large crowds quickly. For example, Los Angeles, California, is converting Dodger Stadium from a mass testing site to administer vaccinations. California is reportedly also establishing mass vaccination sites at Disneyland Resort (Anaheim), Petco Park (San Diego), and CalExpo fairgrounds (Sacramento).
- In San Antonio, Texas, health officials began administering vaccinations at the Alamodome, where they expect to be able to vaccinate 30,000 people per week. With its regular season over, and most teams no longer playing, the NFL (football) is encouraging teams to make their stadiums available to serve as vaccination sites. While these large sites provide the space needed to administer vaccinations rapidly, many barriers still remain, including the logistics of transporting and storing vaccines and the need for additional personnel who are trained and qualified to administer vaccinations.
3. VACCINATING RECOVERED INDIVIDUALS
- Since the onset of the pandemic, health experts and officials have studied the role of immunity conferred by natural infection. While reports of are relatively rare, the potential for reinfection does exist. In light of this risk, the US CDC emphasizes that individuals who were previously infected and recovered should still get vaccinated due to the “severe health risks” and uncertainty regarding the duration of natural immunity. Additionally, the degree of natural immunity “varies from person to person.” The duration of the immunity conferred by vaccination remains uncertain as well, but research is still ongoing via clinical trials. Depending on the duration of immunity following vaccination, it may be necessary for individuals to receive regular boosters to provide longer-term protection.
4. SHORTENED QUARANTINE
- In December 2020, the US CDC updated its C19 quarantine guidance to offer several options that allow individuals to shorten their 14-day quarantine period following a known exposure to SARS-CoV-2. Specifically, individuals who are unable to quarantine for the full 14 days can end their quarantine after 10 days if they exhibit no symptoms or after 7 days if they test negative on Day 5 or later. The CDC’s MMWR published 2 recent studies that provide analysis of the transmission risk associated with shorter quarantine periods.
- The first study was conducted by the US CDC C19 Response Team and the C19 Collegiate Athlete Testing Group, in collaboration with researchers from several US universities. The researchers evaluated SARS-CoV-2 testing data for 1,830 US college athletes who were quarantined and tested after exposure to known C19 cases.
- Among these athletes, 458 (25%) tested positive at some point during their quarantine period, including 137 who never reported C19 symptoms. Among 620 athletes with positive tests*, 303 (48.9%) had positive tests by Day 2 of quarantine and 453 (73.1%) by Day 5. For those who had a negative test on Day 5, the researchers estimate the risk of testing positive after that point to be 26.9%, including 14.2% after Day 7 and 4.7% after Day 10. Notably, however, 26 of the 29 athletes that tested positive on Days 11-14 were not tested at all prior to that point, so it is possible that they would have tested positive on earlier tests, had they been conducted.
- Officials from the Vermont (US) Department of Health issued recommendations for a shorter quarantine period in May 2020, 7 months before the US CDC update. The Vermont policy stated that individuals could conclude their quarantine period if they tested negative on or after Day 7, based on data indicating that approximately 75% of C19 patients developed symptoms within 7 days of exposure.
- The researchers analyzed test results for 2,200 contacts of known C19 cases who were tested on Days 7-10 after exposure, collected in May-November 2020. In total, 87 (4%) of these individuals tested positive on Days 7-10, including 24 (25%) who were asymptomatic at the time of testing. The researchers also present data on the results for subsequent testing for a subset of these individuals.
- Among those who initially tested negative, 262 were tested again within 7 days—154 initially tested on Day 7 and 108 initially tested on Days 8-10. None of those individuals tested positive on the second test, providing evidence that there is relatively low risk of becoming infectious after a negative test later in the quarantine period. This study included data from a small proportion of individuals who ended their quarantine early, but it does provide some evidence that the risk of becoming infectious late in the quarantine period is relatively low.
5. UK TRAVEL SCREENING & TESTING
- With the emergence of the B.1.1.7 variant of SARS-CoV-2, the UK has strengthened travel restrictions and increased testing volume. Many countries have implemented their own travel restrictions to decrease the number of travelers arriving from the UK, including some in response to the new variant. The UK, already struggling to keep up with increased incidence believed to be linked to the B.1.1.7 variant, has also implemented strict travel guidance to prevent the entry of other variants, including the B.1.351 variant.
- Anyone entering the UK by plane, boat, or train must now present a negative SARS-CoV-2 test, taken within 72 hours of departure, before they are permitted to enter the country. Travelers also must fill out a passenger locator form prior to their arrival in order to facilitate contact tracing efforts while they are in the UK. Failure to complete the passenger locator form could result in fines up to £500.
6. TRANSMISSION ON AIRCRAFT
- A study published in the US CDC’s Emerging Infectious Diseases journal describes in-flight transmission of SARS-CoV-2 among passengers on a flight from Dubai, UAE, to Auckland, New Zealand—with a stop in Kuala Lumpur, Malaysia. Upon arrival in New Zealand, all passengers were subjected to mandatory 14-day quarantine, with testing conducted at approximately Day 3 and Day 12. Testing identified 7 SARS-CoV-2 infections among the passengers, including 5 that tested negative prior to their departure.
- Genomic analysis of specimens collected from each passenger found that the viral genome in 6 of the 7 passengers was identical, with 1 mutation present in the seventh passenger. Combined with the timeline of symptoms and positive tests, this suggests that the infection was transmitted among the passengers, rather than from multiple sources prior to travel. While testing negative prior to travel will likely decrease the number of imported cases, by denying travel for those who are already infectious, negative tests only indicate the current state of infection and cannot detect individuals who will be infectious after that point. Travel screening can mitigate the risk of importing cases or transmission during travel, but it cannot prevent them.
7. HIGH-TITER CONVALESCENT PLASMA
- A study published in The New England Journal of Medicine, conducted on behalf of the Fundación INFANT–C19 Group, evaluated convalescent plasma with a high IgG titer as a C19 treatment. The randomized, double-blind, placebo-controlled trial included 160 patients in Argentina aged 75 years or older or aged 65-74 years with at least 1 pre-existing condition associated with elevated risk of severe C19 disease and death.
- The convalescent plasma used in the treatment group included “antibody concentrations in the upper 28th percentile,” and the study participants were divided equally between the treatment and placebo groups (80 in each). The treatment group exhibited a 48% relative reduction in risk of severe respiratory disease compared to the placebo group—13 patients (16%) in the treatment group compared to 25 patients (31%) in the placebo group. Additionally, few patients in the treatment group died than in the placebo group, 2 (2%) compared to 4 (5%), but this result was not statistically significant. No adverse events were reported in either group.
8. LONG-TERM HEALTH EFFECTS
- Evidence continues to emerge on the many and varied long-term health effects of C19. Research has already established correlation between C19 disease and certain cardiac, respiratory, and neurological conditions, but it is still unclear for how long these “long COVID” symptoms may persist. A study published in The Lancet followed 1,733 recovered C19 patients from Wuhan, China, who were initially recovered between January and May. Among these patients, 76% reported at least one symptom 6 months after their recovery, including muscle weakness or fatigue (63%), difficulty sleeping (26%), and hair loss (22%).
- Additionally, 23% of the participants reported anxiety or depression, and 27% reported persistent pain or discomfort. The odds of having persistent symptoms was statistically higher among participants with severe disease—i.e., requiring high-flow nasal cannula oxygen, non-invasive ventilation, or invasive mechanical ventilation—compared to patients who did not require any oxygen therapy (OR= 2.42).
- Data collection on “long COVID” patients must continue for the foreseeable future to track whether or when these symptoms resolve. The persistence of months- or years-long C19 medical sequelae has significant implications for medical care and public health initiatives in the future, potentially long after the end of the pandemic.
- Mechanical ventilation has been previously associated with an increased risk of acute brain dysfunction, and a study published in Lancet: Respiratory Medicine investigated delirium and coma across critically ill C19 patients. The study included 2,088 adult C19 patients across 69 intensive care units (ICUs) across 14 countries. Patients with a history of mental health issues, neurological conditions, drug overdose, brain damage, blindness, and deafness were excluded. Within the cohort, 1,397 of patients were mechanically ventilated during the same day of ICU admission, and an additional 430 patients were mechanically ventilated at some other time during hospitalization.
- The researchers evaluated risk factors associated with coma or delirium within 21 days of ICU admission. Invasive mechanical ventilation and the use of restraints as well as the prescription of benzodiazepine (sedative), opioids, vasopressors, or antipsychotic medications were significantly associated with increased risk of delirium the following day. Notably, family visitation, whether in-person or virtual, was significantly associated with a lower risk of delirium (OR= 0.73). The researchers recommended that clinicians avoid continuous infusions of benzodiazepine and use alternative options for sedation. Authors also recommended that care providers arrange safe and appropriate family visitation, either in person or virtually.
10. mRNA VACCINE PLATFORM
- Following the success of the mRNA platform used in its SARS-CoV-2 vaccine, Moderna announced that it is expanding its mRNA vaccine development efforts. The 3 new programs will leverage the mRNA technology, successfully demonstrated to be effective in combating SARS-CoV-2, for other pathogens. Moderna will be expanding its research portfolio with 3 mRNA vaccine efforts for seasonal influenza, 2 for HIV, and 1 for Nipah virus, and it already has ongoing mRNA vaccine development efforts for a number of other pathogens. Beyond vaccines, Moderna is also expanding its mRNA research for therapeutics.