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Covid-19 and its implications on pregnancy

Coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has emerged as a serious global health issue with high transmission rates affecting millions of people worldwide. The SARS-CoV-2 is known to damage cells in the respiratory system, thus causing viral pneumonia. The novel SARS-CoV-2 is a close relative to the previously identified severe acute respiratory syndrome-coronavirus (SARS-CoV) and Middle East respiratory syndrome-coronavirus (MERS-CoV) which affected several people in 2002 and 2012, respectively. Ever since the outbreak of covid-19, several reports have poured in about the impact of Covid-19 on pregnancy. A few studies have highlighted the impact of the viral infection in pregnant women and how they are more susceptible to the infection because of the various physiological changes of the cardiopulmonary and immune systems during pregnancy. It is known that SARS-CoV and MERS-CoV diseases have influenced the fatality rate among pregnant women. However, there are limited studies on the impact of the novel corona virus on the course and outcome of pregnancy.

Figure: commonly observed clinical symptoms of COVID-19 in the general population: Fever and cough, along with dyspnoea, diarrhoea, and malaise are the most commonly observed symptoms in pregnant women, which is similar to that observed in the normal population.

The WHO and the Indian Council of Medical Research (ICMR) have proposed detailed guidelines for treating pregnant women; these guidelines must be strictly followed by the pregnant individual and their families. According to the guidelines issued by the ICMR, the risk of pregnant women contracting the virus to that of the general population. However, the immune system and the body’s response to a viral infection is altered during pregnancy. This may result in the manifestation of more severe symptoms. The ICMR guidelines also state that the reported cases of COVID-19 pneumonia in pregnancy are milder and with good recovery. However, by observing the trends of the other coronavirus infection (SARS, MERS), the risks to the mother appear to increase in particular during the last trimester of pregnancy. Cases of preterm birth in women with COVID-19 have been mentioned in a few case report, but it is unclear whether the preterm birth was always iatrogenic, or whether some were spontaneous. Pregnant women with heart disease are at highest risk of acquiring the infection, which is similar to that observed in the normal population. Most importantly, the ICMR guidelines highlights the impact of the coronavirus epidemic on the mental health of pregnant women. It mentions that the since the pandemic has begun, there has been an increase in the risk of perinatal anxiety and depression, as well as domestic violence. It is critically important that support for women and families is strengthened as far as possible; that women are asked about mental health at every contact.

With the available literature available on the impact of SARS and MERS on reproductive outcome, it has been mentioned that SARS infection did increase the risk of miscarriage, preterm birth and, intrauterine foetal growth restriction. However, the same has not been demonstrated in early reports from COVID-19 infection in pregnancy. According to a study that included 8200 participants conducted by the centre for disease control and prevention, pregnant women may be at a higher risk of acquiring severe infection and need for ICU admissions as compared to their non-pregnant counterparts. However, a detailed and thorough study involving a larger proportion of the population is needed today.

References:

https://www.news-medical.net/news/20210614/COVID-19-in-pregnancy-could-be-less-severe-than-previously-thought-A-Danish-case-study.aspx

https://obgyn.onlinelibrary.wiley.com/doi/10.1111/jog.14696

https://www.nature.com/articles/s41577-021-00525-y

https://www.tandfonline.com/doi/full/10.1080/14767058.2020.1759541

https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/special-populations/pregnancy-data-on-covid-19/what-cdc-is-doing.html

https://economictimes.indiatimes.com/news/india/why-is-covid-19-killing-so-many-pregnant-women-in-india/articleshow/82902194.cms?from=mdr

https://content.iospress.com/download/international-journal-of-risk-and-safety-in-medicine/jrs200060?id=international-journal-of-risk-and-safety-in-medicine%2Fjrs200060

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Nir Hacohen and Marcia Goldberg, Researchers at MGH and the Broad Institute identify protein “signature” of severe COVID-19

Curator and Reporter: Aviva Lev-Ari, PhD, RN

Longitudinal proteomic analysis of plasma from patients with severe COVID-19 reveal patient survival-associated signatures, tissue-specific cell death, and cell-cell interactions

Open AccessPublished:April 30, 2021DOI:https://doi.org/10.1016/j.xcrm.2021.100287

Highlights

  • 16% of COVID-19 patients display an atypical low-inflammatory plasma proteome
  • Severe COVID-19 is associated with heterogeneous plasma proteomic responses
  • Death of virus-infected lung epithelial cells is a key feature of severe disease
  • Lung monocyte/macrophages drive T cell activation, together promoting epithelial damage

Summary

Mechanisms underlying severe COVID-19 disease remain poorly understood. We analyze several thousand plasma proteins longitudinally in 306 COVID-19 patients and 78 symptomatic controls, uncovering immune and non-immune proteins linked to COVID-19. Deconvolution of our plasma proteome data using published scRNAseq datasets reveals contributions from circulating immune and tissue cells. Sixteen percent of patients display reduced inflammation yet comparably poor outcomes. Comparison of patients who died to severely ill survivors identifies dynamic immune cell-derived and tissue-associated proteins associated with survival, including exocrine pancreatic proteases. Using derived tissue-specific and cell type-specific intracellular death signatures, cellular ACE2 expression, and our data, we infer whether organ damage resulted from direct or indirect effects of infection. We propose a model in which interactions among myeloid, epithelial, and T cells drive tissue damage. These datasets provide important insights and a rich resource for analysis of mechanisms of severe COVID-19 disease.

Graphical Abstract

Figure thumbnail fx1

Image Source: DOI: https://doi.org/10.1016/j.xcrm.2021.100287

https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(21)00115-4

The quest to identify mechanisms that might be contributing to death in COVID-19: Why do some patients die from this disease, while others — who appear to be just as ill do not?

Researchers at Massachusetts General Hospital (MGH) and the Broad Institute of MIT and Harvard have identified the protein “signature” of severe COVID-19

Interest was to develop methods for studying human immune responses to infections, which they had applied to the condition known as bacterial sepsis. The three agreed to tackle this new problem with the goal of understanding how the human immune system responds to SARS-CoV-2, the novel pathogen that causes COVID-19.

How scientists launched a study in days to probe COVID-19’s unpredictability

Collecting these specimens required a large team of collaborators from many departments, which worked overtime for five weeks to amass blood samples from 306 patients who tested positive for COVID-19, as well as from 78 patients with similar symptoms who tested negative for the coronavirus.

Alexandra-Chloé Villani

Credit : Alexandra-Chloé VillaniResearch associates at Mass General who worked countless hours to process blood samples for the COVID Acute Cohort Study (from left to right: Anna Gonye, Irena Gushterova, and Tom Lasalle)By Leah Eisenstadt

https://www.broadinstitute.org/news/how-scientists-launched-study-days-probe-covid-19%E2%80%99s-unpredictability

As the COVID-19 surge began in March, Mass General and Broad researchers worked around the clock to begin learning why some patients fare worse with the disease than others

Protein signatures in the blood

https://www.broadinstitute.org/news/researchers-identify-protein-%E2%80%9Csignature%E2%80%9D-severe-covid-19

The study found that most patients with COVID-19 have a consistent protein signature, regardless of disease severity; as would be expected, their bodies mount an immune response by producing proteins that attack the virus. “But we also found a small subset of patients with the disease who did not demonstrate the pro-inflammatory response that is typical of other COVID-19 patients,” Filbin said, yet these patients were just as likely as others to have severe disease. Filbin, who is also an assistant professor of emergency medicine at Harvard Medical School (HMS), noted that patients in this subset tended to be older people with chronic diseases, who likely had weakened immune systems.

Among other revelations, this showed that the most prevalent severity-associated protein, a pro-inflammatory protein called interleukin-6 (IL-6) rose steadily in patients who died, while it rose and then dropped in those with severe disease who survived. Early attempts by other groups to treat COVID-19 patients experiencing acute respiratory distress with drugs that block IL-6 were disappointing, though more recent studies show promise in combining these medications with the steroid dexamethasone.

Hacohen, who is a professor of medicine at HMS and director of the Broad’s Cell Circuits Program:

“You can ask which of the many thousands of proteins that are circulating in your blood are associated with the actual outcome,” he said, “and whether there is a set of proteins that tell us something.”

Goldberg, who is a professor of emergency medicine at HMS:

They are highly likely to be useful in figuring out some of the underlying mechanisms that lead to severe disease and death in COVID-19,” she said, noting her gratitude to the patients involved in the study. Their samples are already being used to study other aspects of COVID-19, such as identifying the qualities of antibodies that patients form against the virus.

SOURCES

Original Research

Filbin MR, Mehta A, et al. Longitudinal proteomic analysis of plasma from patients with severe COVID-19 reveal patient survival-associated signatures, tissue-specific cell death, and cell-cell interactionsCell Reports Medicine. Online April 30, 2021. DOI: 10.1016/j.xcrm.2021.100287.

Adapted from a press release originally issued by Massachusetts General Hospital.

https://www.broadinstitute.org/news/researchers-identify-protein-%E2%80%9Csignature%E2%80%9D-severe-covid-19

https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(21)00115-4

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Cryo-EM disclosed how the D614G mutation changes SARS-CoV-2 spike protein structure.

Reporter: Dr. Premalata Pati, Ph.D., Postdoc

SARS-CoV-2, the virus that causes COVID-19, has had a major impact on human health globally; infecting a massive quantity of people around 136,046,262 (John Hopkins University); causing severe disease and associated long-term health sequelae; resulting in death and excess mortality, especially among older and prone populations; altering routine healthcare services; disruptions to travel, trade, education, and many other societal functions; and more broadly having a negative impact on peoples physical and mental health.

It’s need of the hour to answer the questions like what allows the variants of SARS-CoV-2 first detected in the UK, South Africa, and Brazil to spread so quickly? How can current COVID-19 vaccines better protect against them?

Scientists from the Harvard Medical School and the Boston Children’s Hospital help answer these urgent questions. The team reports its findings in the journal “Science a paper entitled Structural impact on SARS-CoV-2 spike protein by D614G substitution. The mutation rate of the SARS-CoV-2 virus has rapidly evolved over the past few months, especially at the Spike (S) protein region of the virus, where the maximum number of mutations have been observed by the virologists.

Bing Chen, HMS professor of pediatrics at Boston Children’s, and colleagues analyzed the changes in the structure of the spike proteins with the genetic change by D614G mutation by all three variants. Hence they assessed the structure of the coronavirus spike protein down to the atomic level and revealed the reason for the quick spreading of these variants.


This model shows the structure of the spike protein in its closed configuration, in its original D614 form (left) and its mutant form (G614). In the mutant spike protein, the 630 loop (in red) stabilizes the spike, preventing it from flipping open prematurely and rendering SARS-CoV-2 more infectious.

Fig. 1. Cryo-EM structures of the full-length SARS-CoV-2 S protein carrying G614.

(A) Three structures of the G614 S trimer, representing a closed, three RBD-down conformation, an RBD-intermediate conformation and a one RBD-up conformation, were modeled based on corresponding cryo-EM density maps at 3.1-3.5Å resolution. Three protomers (a, b, c) are colored in red, blue and green, respectively. RBD locations are indicated. (B) Top views of superposition of three structures of the G614 S in (A) in ribbon representation with the structure of the prefusion trimer of the D614 S (PDB ID: 6XR8), shown in yellow. NTD and RBD of each protomer are indicated. Side views of the superposition are shown in fig. S8.

IMAGE SOURCE: Bing Chen, Ph.D., Boston Children’s Hospital, https://science.sciencemag.org/content/early/2021/03/16/science.abf2303

The work

The mutant spikes were imaged by Cryo-Electron microscopy (cryo-EM), which has resolution down to the atomic level. They found that the D614G mutation (substitution of in a single amino acid “letter” in the genetic code for the spike protein) makes the spike more stable as compared with the original SARS-CoV-2 virus. As a result, more functional spikes are available to bind to our cells’ ACE2 receptors, making the virus more contagious.


Fig. 2. Cryo-EM revealed how the D614G mutation changes SARS-CoV-2 spike protein structure.

IMAGE SOURCE:  Zhang J, et al., Science

Say the original virus has 100 spikes,” Chen explained. “Because of the shape instability, you may have just 50 percent of them functional. In the G614 variants, you may have 90 percent that is functional. So even though they don’t bind as well, the chances are greater and you will have an infection

Forthcoming directions by Bing Chen and Team

The findings suggest the current approved COVID-19 vaccines and any vaccines in the works should include the genetic code for this mutation. Chen has quoted:

Since most of the vaccines so far—including the Moderna, Pfizer–BioNTech, Johnson & Johnson, and AstraZeneca vaccines are based on the original spike protein, adding the D614G mutation could make the vaccines better able to elicit protective neutralizing antibodies against the viral variants

Chen proposes that redesigned vaccines incorporate the code for this mutant spike protein. He believes the more stable spike shape should make any vaccine based on the spike more likely to elicit protective antibodies. Chen also has his sights set on therapeutics. He and his colleagues are further applying structural biology to better understand how SARS-CoV-2 binds to the ACE2 receptor. That could point the way to drugs that would block the virus from gaining entry to our cells.

In January, the team showed that a structurally engineered “decoy” ACE2 protein binds to SARS-CoV-2 200 times more strongly than the body’s own ACE2. The decoy potently inhibited the virus in cell culture, suggesting it could be an anti-COVID-19 treatment. Chen is now working to advance this research into animal models.

Main Source:

Abstract

Substitution for aspartic acid by glycine at position 614 in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 appears to facilitate rapid viral spread. The G614 strain and its recent variants are now the dominant circulating forms. We report here cryo-EM structures of a full-length G614 S trimer, which adopts three distinct prefusion conformations differing primarily by the position of one receptor-binding domain. A loop disordered in the D614 S trimer wedges between domains within a protomer in the G614 spike. This added interaction appears to prevent premature dissociation of the G614 trimer, effectively increasing the number of functional spikes and enhancing infectivity, and to modulate structural rearrangements for membrane fusion. These findings extend our understanding of viral entry and suggest an improved immunogen for vaccine development.

https://science.sciencemag.org/content/early/2021/03/16/science.abf2303?rss=1

Other Related Articles published in this Open Access Online Scientific Journal include the following:

COVID-19-vaccine rollout risks and challenges

Reporter : Irina Robu, PhD

https://pharmaceuticalintelligence.com/2021/02/17/covid-19-vaccine-rollout-risks-and-challenges/

COVID-19 Sequel: Neurological Impact of Social isolation been linked to poorer physical and mental health

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2021/03/30/covid-19-sequel-neurological-impact-of-social-isolation-been-linked-to-poorer-physical-and-mental-health/

Comparing COVID-19 Vaccine Schedule Combinations, or “Com-COV” – First-of-its-Kind Study will explore the Impact of using eight different Combinations of Doses and Dosing Intervals for Different COVID-19 Vaccines

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2021/02/08/comparing-covid-19-vaccine-schedule-combinations-or-com-cov-first-of-its-kind-study-will-explore-the-impact-of-using-eight-different-combinations-of-doses-and-dosing-intervals-for-diffe/

COVID-19 T-cell immune response map, immunoSEQ T-MAP COVID for research of T-cell response to SARS-CoV-2 infection

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2020/11/20/covid-19-t-cell-immune-response-map-immunoseq-t-map-covid-for-research-of-t-cell-response-to-sars-cov-2-infection/

Tiny biologic drug to fight COVID-19 show promise in animal models

Reporter : Irina Robu, PhD

https://pharmaceuticalintelligence.com/2020/10/11/tiny-biologic-drug-to-fight-covid-19-show-promise-in-animal-models/

Miniproteins against the COVID-19 Spike protein may be therapeutic

Reporter: Stephen J. Williams, PhD

https://pharmaceuticalintelligence.com/2020/09/30/miniproteins-against-the-covid-19-spike-protein-may-be-therapeutic/

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COVID-19 Sequel: Neurological Impact of Social isolation been linked to poorer physical and mental health

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 4/13/2021

Toward Understanding COVID-19 Recovery: National Institutes of Health Workshop on Postacute COVID-19

 

Abstract

Over the past year, the SARS-CoV-2 pandemic has swept the globe, resulting in an enormous worldwide burden of infection and mortality. However, the additional toll resulting from long-term consequences of the pandemic has yet to be tallied. Heterogeneous disease manifestations and syndromes are now recognized among some persons after their initial recovery from SARS-CoV-2 infection, representing in the broadest sense a failure to return to a baseline state of health after acute SARS-CoV-2 infection. On 3 to 4 December 2020, the National Institute of Allergy and Infectious Diseases, in collaboration with other Institutes and Centers of the National Institutes of Health, convened a virtual workshop to summarize existing knowledge on postacute COVID-19 and to identify key knowledge gaps regarding this condition.

Over the past year, the SARS-CoV-2 pandemic has swept the globe, resulting in more than 113 million persons infected and 2.5 million deaths (1). However, the additional toll resulting from long-term consequences of the pandemic has yet to be tallied. Heterogeneous disease manifestations and syndromes are now recognized among some persons after their initial recovery from SARS-CoV-2 infection. Although a standardized case definition does not yet exist for these manifestations, in the broadest sense they represent a failure to return to a baseline state of health after acute SARS-CoV-2 infection. The various terms used to describe this condition have included postacute (or late) sequelae of COVID-19, post-COVID condition or syndrome, long COVID, and long-haul COVID. In this article, we use the general umbrella term of “postacute COVID-19” to refer to multiple disease processes that may have varying degrees of overlap (including but not limited to sequelae of critical illness and hospitalization in persons with COVID-19) and the entity of long COVID, which refers to prolonged health abnormalities in persons previously infected with SARS-CoV-2 who may or may not have required hospitalization. Of note, there is not yet a consensus on terminology, which will likely evolve with a better understanding of this condition.

Reported symptoms are wide-ranging and may involve nearly all organ systems, with fatigue, dyspnea, cognitive dysfunction, anxiety, and depression often described (2–5). Although abnormalities in imaging studies and functional testing have been reported, the long-term clinical significance of some of these findings is not yet clear (367). Postacute manifestations of COVID-19 have been seen in persons of all demographic groups and include reports of multisystem inflammatory syndrome in children (89). Although the epidemiology of the diverse manifestations of postacute COVID-19 is not yet known, the expansive global burden of SARS-CoV-2 infection suggests that the potential public health effects of postacute COVID-19 are significant if even a small proportion of persons with SARS-CoV-2 infection have prolonged recovery or do not return to their baseline health.

On 3 to 4 December 2020, the National Institute of Allergy and Infectious Diseases, in collaboration with other Institutes and Centers of the National Institutes of Health, convened a virtual workshop (available via videocast at https://videocast.nih.gov/watch=38878 and https://videocast.nih.gov/watch=38879) to summarize existing knowledge on postacute COVID-19 and to identify key knowledge gaps. The speakers and participants included epidemiologists, clinicians, clinical and basic scientists, and members of the affected community. The videocast was open to the general public and had more than 1200 registered participants.

SOURCE

UPDATED on 4/7/2021

‘Beyond a Reasonable Doubt’: COVID-19 Brain Health Fallout Is Real, Severe

Sarah Edmonds

April 07, 2021

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.

START QUOTE

COVID-19 survivors face a sharply elevated risk of developing psychiatric or neurologic disorders in the six months after they contract the virus — a danger that mounts with symptom severity, new research shows.

In what is purported to be the largest study of its kind to-date, results showed that among 236,379 COVID-19 patients, one third were diagnosed with at least one of 14 psychiatric or neurologic disorders within a 6-month span.

The rate of illnesses, which ranged from depression to stroke, rose sharply among those with COVID-19 symptoms acute enough to require hospitalization.  

“If we look at patients who were hospitalized, that rate increased to 39%, and then increased to about just under 1 in 2 patients who needed ICU admission at the time of the COVID-19 diagnosis,” Maxime Taquet, PhD, University of Oxford Department of Psychiatry, Oxford, United Kingdom, told a media briefing.

Incidence jumps to almost two thirds in patients with encephalopathy at the time of COVID-19 diagnosis, he added.

The study, which examined the brain health of 236,379 survivors of COVID-19 via a US database of 81 million electronic health records, was published online April 6 in The Lancet Psychiatry.

High Rate of Neurologic, Psychiatric Disorders

The research team looked at the first-time diagnosis or recurrence of 14 neurologic and psychiatric outcomes in patients with confirmed SARS-CoV-2 infections. They also compared the brain health of this cohort with a control group of those with influenza or with non-COVID respiratory infections over the same period. 

SOURCE

The Effects of Loneliness and Our Brain function: poorer physical and mental health

One review of the science of loneliness found that people with stronger social relationships have a 50 per cent increased likelihood of survival over a set period of time compared with those with weaker social connections. Other studies have linked loneliness to cardiovascular disease, inflammation, and depression.

For loneliness researchers the pandemic has provided an unprecedented natural experiment in the impact that social isolation might have on our brains. As millions of people across the world emerge from months of reduced social contact, a new neuroscience of loneliness is starting to figure out why social relationships are so crucial to our health.

Neural basis of Emotion

Desire for Social Interaction

Are there neurological differences between people who experience short-term isolation and those who have been isolated for long stretches of time? What kinds of social interactions satisfy our social cravings? Is a video call enough to quell our need for social contact, or do some people require an in-person connection to really feel satiated?

START QUOTE

Julianne Holt-Lunstad, a psychology professor at Brigham Young University in the US and the author of two major studies on social isolation and health. “We have a lot of data that very robustly shows that both isolation and loneliness put us at increased risk for premature mortality—and conversely, that being socially connected is protective and reduces our risk,” she says.

START QUOTE

“Trying to investigate isolation or loneliness is not as straightforward in humans. In humans, being lonely is not necessarily correlated with how many people are around you,” says Tomova. She is particularly interested in the impact that the pandemic might have had on young people whose cognitive and social skills are still developing. “I think we will see potentially some differences in how their social behavior developed or things like that,” she says. But as is always the case in the uncertain world of loneliness research, the opposite could be true. “It could also be that most people are fine, because maybe social media does fulfill our social needs really well.”

SOURCE

https://www.wired.co.uk/article/lockdown-loneliness-neuroscience

The Weird Science of Loneliness and Our Brains – Social isolation as been linked to poorer physical and mental health, but scientists are finally starting to understand its neurological impact

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COVID-related financial losses at Mass General Brigham

Reporter: Aviva Lev-Ari, PhD, RN

Based on

Mass General Brigham reports COVID-related financial losses not as bad as expected

By Priyanka Dayal McCluskey Globe Staff,Updated December 11, 2020, 3:02 p.m.

START QUOTE

The state’s largest hospital system on Friday reported the worst financial loss in its history while fighting the COVID-19 pandemic — but still ended the fiscal year in better shape than expected.

Mass General Brigham, formerly known as Partners HealthCare, lost $351 million on operations in the fiscal year that ended Sept. 30. In 2019, the system recorded a gain of $382 million.

The loss, however, is not as great as projected, thanks in part to an infusion of federal aid and patients returning to hospitals in large numbers after the first COVID surge receded.

“2020 is like no other year,” said Peter Markell, chief financial officer at Mass General Brigham, which includes Massachusetts General Hospital, Brigham and Women’s Hospital, and several community hospitals. “At the end of the day, we came out of this better than we thought we might.”

Total revenue for the year remained relatively stable at about $14 billion.

When the pandemic first hit Massachusetts in March, hospitals across the state suddenly experienced sharp drops in revenue because they canceled so much non-COVID care to respond to the crisis at hand. They also faced new costs related to COVID, including the personal protective equipment needed to keep health care workers safe from infection.

Federal aid helped to make up much of the losses, including $546 million in grant money that went to Mass General Brigham. The nonprofit health system also slashed capital expenses in half, by about $550 million, and temporarily froze employee wages and cut their retirement benefits.

Among the unusual new costs for Mass General Brigham this year was the expense of building a field hospital, Boston Hope, at the Boston Convention and Exhibition Center. The project cost $15 million to $20 million, Markell said, and Mass General Brigham is working to recoup those costs from government agencies.

The second surge of COVID, now underway, could hit hospitals’ bottom lines again, though Markell expects a smaller impact this time. One reason is because hospitals are trying to treat most of the patients who need care for conditions other than COVID even while treating growing numbers of COVID patients. In the spring, hospitals canceled vastly more appointments and procedures in anticipation of the first wave of COVID.

Mass General Brigham hospitals were treating more than 300 COVID patients on Friday, among the more than 1,600 hospitalized across the state.

Steve Walsh, president of the Massachusetts Health & Hospital Association, said hospitals across the state will need more federal aid as they continue battling COVID into the new year.

“The financial toll of COVID-19 has been felt by every hospital and health care organization in the Commonwealth,” he said. “Those challenges will continue during 2021.”


Priyanka Dayal McCluskey can be reached at priyanka.mccluskey@globe.com. Follow her on Twitter @priyanka_dayal.

END QUOTE

SOURCE

https://www.bostonglobe.com/2020/12/11/business/mass-general-brigham-reports-covid-related-financial-losses-better-than-expected/?p1=Article_Inline_Related_Box

Integration of Mass General Hospital and Brigham Women’s Hospital was accelerated by the COVID-19 pandemic

Reporter: Aviva Lev-Ari, PhD, RN

BASED on

At Mass General Brigham, a sweeping effort to unify hospitals and shed old rivalries

Executives say greater cooperation is necessary to stay relevant in a dynamic and competitive health care industry. But the aggressive push to integrate is stirring tensions and sowing discontent among doctors and hospital leaders.

By Priyanka Dayal McCluskey and Larry Edelman Globe Staff and Globe Columnist,Updated March 27, 2021, 6:15 p.m.125

https://www.bostonglobe.com/2021/03/27/business/mass-general-brigham-sweeping-effort-unify-hospitals-shed-old-rivalries/?s_campaign=breakingnews:newsletter

START QUOTE

The work of integration was accelerated by the COVID-19 pandemic. As patients flooded hospitals last spring, Mass General Brigham — not each of its individual hospitals — set pandemic policies, from what kind of personal protective equipment health care providers should wear, to which visitors were allowed inside hospitals, to how employees would be paid if they were out sick with the virus.

During the winter surge of COVID, Mass General Brigham officials closely tracked beds across their system and transferred patients daily from one hospital to another to ensure that no one facility became overwhelmed.

And, in the early months of the pandemic, the company dropped the name Partners, which meant little to patients, and unveiled a new brand to reflect the strength of its greatest assets, MGH and the Brigham.

Officials at the nonprofit health system have instructeddepartment heads across their hospitals to coordinate better, so, for example, if a patient needs surgery at the Brigham but is facing a long wait, they can refer that patient to another site within Mass General Brigham.

Some executives want patients, eventually, to be able to go online and book appointments at any Mass General Brigham facility, as easily as they make reservations for dinner or a hotel.

Walls described it like this: “How do we put things together that make things better and easier for patients, and leave alone things that are better where they are?

“We’re not going to push things together that don’t fit together,” he said.

And yet the aggressive pursuit of “systemness,” as executives call it, is taking a toll. Physicians and hospital leaders are struggling with the loss of control over their institutions and worried that the new era of top-down management threatens to homogenize a group of hospitals with different cultures and identities.

Veteran physicians and leaders have been surprised and upset by the power shift that is stripping them of the ability to make key decisions and unhappy with abrupt changes they feel are occurring with little discussion. Most are uncomfortable sharing their concerns publicly.

“If you’re not on the train, you’re getting run over by the train,” said one former Mass General Brigham executive who requested anonymity in orderto speak openly. “It’s not an environment to invite debate.”

Amid the restructuring, senior executives are departing in droves. They include the CEO of the MGH physicians group, Dr. Timothy Ferris; Brigham and Women’s president Dr. Elizabeth Nabel; chief financial officer of the system, Peter Markell; Cooley Dickinson Hospital president Joanne Marqusee; and president of Spaulding Rehabilitation Network, David Storto.

Some also fear the internal discord could hinder Mass General Brigham’s ability to attract talented leaders.

Top executives acknowledge there is angst — “Change is hard,” Klibanski said — but are pushing ahead.

MORE

https://www.bostonglobe.com/2021/03/27/business/mass-general-brigham-sweeping-effort-unify-hospitals-shed-old-rivalries/?s_campaign=breakingnews:newsletter

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The WHO team is expected to soon publish a 300-page final report on its investigation, after scrapping plans for an interim report on the origins of SARS-CoV-2 — the new coronavirus responsible for killing 2.7 million people globally

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 4/1/2021

Coronavirus: More work needed to rule out China lab leak theory says WHO

START QUOTE

The head of the World Health Organization (WHO) has said further investigation is needed to conclusively rule out that Covid-19 emerged from a laboratory in China.

Tedros Adhanom Ghebreyesus said that although a lab leak was the least likely cause, more research was needed.

The US and other countries have criticised China for failing to provide the WHO with sufficient data.

Beijing has always dismissed the allegations of a virus leak.

A report by WHO and Chinese experts released on Tuesday, said the lab leak explanation was highly unlikely and the virus had probably jumped from bats to humans via another intermediary animal.

China has yet to respond to the WHO’s latest statement.

‘All hypothesis on the table’

However the theory that the virus might have come from a leak in a laboratory “requires further investigation, potential with additional missions involving specialist experts,” Dr Tedros said on Tuesday.

“Let me say clearly that as far as WHO is concerned, all hypothesis remain on the table,” he added.

The virus was first detected in Wuhan, in China’s Hubei province in late 2019. An international team of experts travelled to to the city in January to probe the origins of the virus.

The team investigated all possibilities, including one theory that the virus had originated at the Wuhan Institute of Virology. The institute is the world’s leading authority on the collection, storage and study of bat coronaviruses.

International criticism

In response to the WHO report, the US and 13 allies including South Korea, Australia and the UK voiced concern over the findings and urged China to provide “full access” to experts.

The statement said the mission to Wuhan was “significantly delayed and lacked access to complete, original data and samples”.

“Scientific missions like these should be able to do their work under conditions that produce independent and objective recommendations and findings.”

The group pledged to work together with the WHO.

Former US President Donald Trump was among those who supported the theory that the virus might have escaped from a lab.

WHO investigation team leader, Peter Ben Embarek said on Tuesday his team had felt under political pressure, including from outside China but said he was never pressed to remove anything from the team’s final report.

He also confirmed his team had found no evidence that any laboratories in Wuhan were involved in the outbreak.

MORE …

SOURCE

https://www.bbc.com/news/world-asia-china-56581246

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Ex-CDC Director Robert Redfield believes COVID-19 came from Wuhan lab

By Lia Eustachewich

March 26, 2021 | 10:03am | Updated

START QUOTE

The former director of the Centers for Disease Control and Prevention believes the virus that causes COVID-19 escaped from a lab in Wuhan, China, according to a new interview.

Robert Redfield told CNN on Friday that it was his “opinion” that SARS-CoV-2 — the new coronavirus responsible for killing 2.7 million people globally — did not evolve naturally.

“I’m of the point of view that I still think the most likely etiology of this pathology in Wuhan was from a laboratory — escaped,” said Redfield, who led the CDC during the height of the pandemic. “Other people don’t believe that. That’s fine. Science will eventually figure it out.”

Researchers believe the deadly and highly transmissible strain of coronavirus behind the global pandemic mutated from a virus that infects animals — namely, bats — to one that sickens humans.

But some believe the virus was somehow released from the Wuhan Institute of Virology — which is the only lab in China authorized to study the most dangerous known pathogens, according to Axios.

“It’s not unusual for respiratory pathogens that are being worked on in a laboratory to infect the laboratory worker. … That’s not implying any intentionality,” Redfield said. “It’s my opinion, right? But I am a virologist. I have spent my life in virology.

“I do not believe this somehow came from a bat to a human and at that moment in time, that the virus came to the human, became one of the most infectious viruses that we know in humanity for human-to-human transmission.”

Redfield said usually when a virus jumps from animals to humans, “it takes a while for it to figure out how to become more and more efficient in human-to-human transmission.”

SOURCE

START QUOTE

What they’re saying: “I’m of the point of view that I still think the most likely etiology of this pathology in Wuhan was from a laboratory. Escaped. Other people don’t believe that. That’s fine. Science will eventually figure it out,” Redfield told CNN’s Sanjay Gupta.

  • “It’s not unusual for respiratory pathogens that are being worked on in a laboratory to infect the laboratory worker. … That’s not implying any intentionality. It’s my opinion, right? But I am a virologist. I have spent my life in virology,” he continued.
  • “I do not believe this somehow came from a bat to a human and at that moment in time that the virus came to the human, became one of the most infectious viruses that we know in humanity for human-to-human transmission.”

Between the lines: Lab accidents in the U.S. are not especially rare, as USA Today’s Alison Young noted in a recent opinion piece arguing why the Wuhan lab theory cannot be ruled out. The CDC itself experienced a possible contamination in a lab where it was making COVID-19 test kits early in the pandemic.

What to watch: The WHO team is expected to soon publish a 300-page final report on its investigation, after scrapping plans for an interim report amid mounting tensions between the U.S. and China.

SOURCE

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McKinsey experts on COVID-19: Implications for business

 

https://www.mckinsey.com/business-functions/risk/our-insights/covid-19-implications-for-business?cid=other-eml-alt-mip-mck

Reporter on Highlights: Joel T. Shertok, PhD

JTS – 11/17/20

 

  • COVID-19-vaccine trial: a leading candidate has an efficacy rate of about 90 percent.
  • The gap between incoming and outgoing Treasury funds may reach $30 trillion soon.
  • Our latest research shows a particularly effective bridge for governments to consider: real estate.
  • Many businesses will embrace sustainability; voluntary carbon markets can help them reach their goals.
  • China, the world’s growth engine for the past 25 years, has come back
  • Consumer behavior has changed, pockets of growth are shifting, and leadership and management practices are in flux
  • Likely Pandemic scenarios:
  • A muted recovery
  • A prolonged and insufficient recovery
  • As the unrelenting COVID-19 pandemic rolls on, the future isn’t what it used to be: what used to be a simple idea now comes freighted with caveats, assumptions, and speculations.
  • The auto industry is one of the world’s largest and has been devastated by the pandemic: sales may drop by 20 to 30 percent in 2020, and we estimate that profits will fall by $100 billion.
  • The US restaurant industry has given many iconic brands to the rest of the world. But today, the sector is in trouble.
  • People don’t order sides, appetizers, and desserts as frequently when they’re ordering for delivery—but as leaders know, those items are often the difference between profit and loss.
  • For banks, the pandemic has changed everything. Risk-management teams are running hard to catch up with cascades of credit risk, among other challenges.
  • Ethnic minority groups have made progress. But the COVID-19 crisis threatens that progress;
  • All ethnic-minority groups have higher age-adjusted COVID-19-related death rates than white people do.
  • In the middle of the deepest recession in memory, stock markets are reaching new highs. Why the disconnect?
  • Many investors still take a long-term perspective; they are looking ahead to the end of the pandemic.
  • Another factor: five big-tech companies now make up 21 percent of the S&P 500,
  • The overall stock market can do relatively well even when employment and GDP are severely depressed.
  • Companies can expect a disruption to their production lines of one to two months—a very long time.
  • The effects of the COVID-19 crisis have exacerbated gender disparities and their implications for women at work, especially for mothers, female senior leaders, and Black women across America.
  • The exodus might include as many as two million women. That would raise a significant barrier to achieving gender parity in leadership roles in years to come.
  • The global economic contractions resulting from the COVID-19 pandemic have far exceeded those of the Great Recession that ended in 2009 and have occurred at a much faster rate, hitting all sectors and many of the world’s largest employers.
  • Two important issues facing healthcare providers. First, similarities in flu and COVID-19 symptoms could lead to a threefold spike in demand for COVID-19 testing as flu season in the Northern Hemisphere approaches.
  • Second, the crisis has also led to a surgical backlog for elective procedures because of lack of hospital capacity, workforce shortages, and new safety protocols.

SOURCE

https://www.mckinsey.com/business-functions/risk/our-insights/covid-19-implications-for-business?cid=other-eml-alt-mip-mck

 

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Approaches and Solutions for Management of the COVID Pandemic

Reporter: Aviva Lev- Ari, PhD, RN and Stephen J. Williams, PhD  
 
 
 
 
 
October 8, 2020 N Engl J Med 2020; 383:1479-1480 DOI: 10.1056/NEJMe2029812

 

Dying in a Leadership Vacuum

CONTINUE TO READ AT THE SOURCE N Engl J Med 2020; 383:1479-1480 DOI: 10.1056/NEJMe2029812   Janice Hopkins Tanne. (2020) Covid 19: NEJM and former CDC director launch stinging attacks on US response. BMJ, m3925. BMJ 2020;371:m3925

Covid 19: NEJM and former CDC director launch stinging attacks on US response

Janice Hopkins Tanne Author affiliations

The US is “dying in a leadership vacuum,” in responding to the covid-19 pandemic, the New England Journal of Medicine has said in an editorial.

“Our leaders have failed. They have taken a crisis and turned it into a tragedy,” the NEJM editors said. US leaders are “dangerously incompetent,” have undercut trust in science and in government,” and should be voted out,1 the journal said.

The intervention came as a former director of the Centers for Disease Control and Prevention (CDC) suggested the current CDC director should update staff in writing about the agency’s failings, apologise, and resign.23

The US leads the world in the death rate from covid-19, which is far higher than larger countries and those with less sophisticated technology and health services, the editors said.

“We have failed at almost every step,” they wrote, describing problems with supplies of personal protective equipment, delays in testing, and failure to employ quarantine, isolation, and social distancing appropriately and quickly. Government inaction has led to business losses and unemployment.

Earlier, William Foege, former director of the CDC and a leader in smallpox eradication, criticised the US response and the failure of the CDC. He sent a letter to Robert Redfield, the current CDC director, asking him to write to CDC employees describing the White House’s failure to put the CDC in charge of the covid-19 pandemic and then resign. A letter, he wrote, would be on the record.

Foege called the US response to the pandemic “a slaughter and not just a political dispute” that had turned the CDC’s reputation from “gold to tarnished brass.”

Foege is emeritus presidential distinguished professor of international health at Emory University. He was director of the Carter Center’s Task Force for Child Survival and senior medical advisor to the Bill and Melinda Gates Foundation. President Barack Obama awarded him the Presidential Medal of Freedom, the nation’s highest civilian honour, in 2012. His private letter, written on 23 September, was published by USA Today on 7 October.

Redfield, a virologist with expertise in HIV/AIDS and a clinician, served in the US Army’s medical corps. He co-founded the University of Maryland’s Institute of Human Virology and was chief of infectious diseases at the university’s medical school.

Foege wrote, “You don’t want to be seen, in the future, as forsaking your role as servant to the public in order to become a servant to a corrupt president. You could send a letter to all CDC employees (a letter leaves a record and avoids the chance of making a mistake with a speech) laying out the facts. The White House will, of course, respond with fury. But you will have right on your side. Like Martin Luther, you can say, ‘Here I stand, I cannot do otherwise.’”

Among the truths that need to be faced, Foege said, are that, despite White House spin attempts, the failure of the US public health system is because of “the incompetence and illogic of the White House programme.”

The White House failed to put the CDC in charge of the pandemic, violating rules of public health so that “people and the media go to the academic community for truth, rather than to CDC,” Foege’s letter says. Unlike former responses to health crises, there has been no federal plan, “resulting in 50 states developing their own plans, often in competition.”

The need to form coalitions to fight the pandemic “has been ignored as the president thrives instead on creating divisions, and the need for global cooperation has been squandered by an ‘America first’ policy. The best decisions are based on the best science while the best results are based on the best management. The White House has rejected both science and good management,” Foege wrote.

Foege, the CDC, Redfield, and the White House have not publicly commented on the letter.

References
  SOURCES for the NEJM https://www.nejm.org/doi/full/10.1056/NEJMe2029812?query=recirc_mostViewed_railB_article https://www.nejm.org/doi/full/10.1056/NEJMe2029812#.X39d2y9tN84.twitter Janice Hopkins Tanne. (2020) Covid 19: NEJM and former CDC director launch stinging attacks on US response. BMJ, m3925. BMJ 2020;371:m3925

Covid 19: NEJM and former CDC director launch stinging attacks on US response

BMJ 2020371 doi: https://doi.org/10.1136/bmj.m3925 (Published 08 October 2020) Cite this as: BMJ 2020;371:m3925   References
  1. Johns Hopkins University Coronavirus Resource Center. COVID-19 dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (https://coronavirus.jhu.edu/map.html. opens in new tab).

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  2. Total number of COVID-19 tests per confirmed case, September 14, 2020. Our World in Data (https://ourworldindata.org/grapher/number-of-covid-19-tests-per-confirmed-case. opens in new tab).

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  3. McGinley L, Abutaleb L, Johnson CY. Inside Trump’s pressure campaign on federal scientists over a Covid-19 treatment. Washington Post. August 302020 (https://www.washingtonpost.com/health/convalescent-plasma-treatment-covid19-fda/2020/08/29/e39a75ec-e935-11ea-bc79-834454439a44_story.html. opens in new tab).

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  4. Haberman M. Trump admits downplaying the virus knowing it was ‘deadly stuff.’ New York Times. September 92020 (https://www.nytimes.com/2020/09/09/us/politics/woodward-trump-book-virus.html. opens in new tab).

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Related Articles

 

Other related articles published in this Open Access Online Scientific Journal include the following EIGHT topics we cover since March 14, 2020 on LPBI Group’s Coronavirus PORTAL

https://pharmaceuticalintelligence.com/coronavirus-portal/

Eight COVID-19 Topics Covered and Lead Curators are:

  1. Breakthrough News Corner
  2. Development of Medical Counter-measures for 2019-nCoV, CoVid19, Coronavirus
  3. An Epidemiological Approach Stephen J. Williams, PhD and Aviva Lev-Ari, PhD, RN Lead Curators – e–mail Contacts: sjwilliamspa@comcast.net and avivalev-ari@alum.berkeley.edu
  4. Community Impact Stephen J. Williams, PhD and Irina Robu, PhD Lead Curators – e–mail Contacts: irina.stefania@gmail.com and sjwilliamspa@comcast.net
  5. Economic Impact of The Coronavirus Pandemic Dr. Joel Shertok, PhD Lead Curator – e–mail Contact: jshertok@processindconsultants.com
  6. Voices of Global Citizens: Impact of The Coronavirus Pandemic, Gail S. Thornton, M.A. Lead Curator – e–mail Contact: gailsthornton@yahoo.com
  7. Diagnosis of Coronavirus Infection by Medical Imaging and Cardiovascular Impacts of Viral Infection, Aviva Lev-Ari, PhD, RN Lead Curator e-mail contact: avivalev-ari@alum.berkeley.edu
  8. Key Opinion Leaders Followed by LPBI Aviva Lev-Ari, PhD, RN and Dr. Ofer Markman, PhD Lead Curators e-mail contacts: oferm2015@gmail.com and avivalev-ari@alum.berkeley.edu

 

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The lessons from the Covid-19 response, according to Anthony Fauci

Reporter : Irina Robu, PhD

 

UPDATED on 10/18/2020

 

 

Since COVID-19 was declared an international pandemic, the world has learned difficult lessons according to Dr. Anthony Fauci. They are as follows:

  • Don’t understand the impact of the pandemic. Don’t ever estimate [an outbreak] as it evolves and don’t try to look at the rosy side of things.
  • Always do scientifically sound research.
  • Adapt to new information. If you look at what we knew in February compared to what we know now [about Covid-19], there really are a lot of differences. The role of masks, the role of aerosol, the role of indoor vs. outdoors, closed spaces. You’ve just got to be humble enough to realize that we don’t know it all from the get-go and even as we get into it.
  • Address existing health care disparities. There is a high number of hospitalizations with COVID within African-American and Latin community.

SOURCE

https://www.statnews.com/2020/09/10/anthony-fauci-lessons-learned-covid19-pandemic

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From AAAS Science News on COVID19: New CRISPR based diagnostic may shorten testing time to 5 minutes

Reporter: Stephen J. Williams, Ph.D.

 

 

 

 

 

 

 

 

 

A new CRISPR-based diagnostic could shorten wait times for coronavirus tests.

 

 

New test detects coronavirus in just 5 minutes

By Robert F. ServiceOct. 8, 2020 , 3:45 PM

Science’s COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.

 

Researchers have used CRISPR gene-editing technology to come up with a test that detects the pandemic coronavirus in just 5 minutes. The diagnostic doesn’t require expensive lab equipment to run and could potentially be deployed at doctor’s offices, schools, and office buildings.

“It looks like they have a really rock-solid test,” says Max Wilson, a molecular biologist at the University of California (UC), Santa Barbara. “It’s really quite elegant.”

CRISPR diagnostics are just one way researchers are trying to speed coronavirus testing. The new test is the fastest CRISPR-based diagnostic yet. In May, for example, two teams reported creating CRISPR-based coronavirus tests that could detect the virus in about an hour, much faster than the 24 hours needed for conventional coronavirus diagnostic tests.CRISPR tests work by identifying a sequence of RNA—about 20 RNA bases long—that is unique to SARS-CoV-2. They do so by creating a “guide” RNA that is complementary to the target RNA sequence and, thus, will bind to it in solution. When the guide binds to its target, the CRISPR tool’s Cas13 “scissors” enzyme turns on and cuts apart any nearby single-stranded RNA. These cuts release a separately introduced fluorescent particle in the test solution. When the sample is then hit with a burst of laser light, the released fluorescent particles light up, signaling the presence of the virus. These initial CRISPR tests, however, required researchers to first amplify any potential viral RNA before running it through the diagnostic to increase their odds of spotting a signal. That added complexity, cost, and time, and put a strain on scarce chemical reagents. Now, researchers led by Jennifer Doudna, who won a share of this year’s Nobel Prize in Chemistry yesterday for her co-discovery of CRISPR, report creating a novel CRISPR diagnostic that doesn’t amplify coronavirus RNA. Instead, Doudna and her colleagues spent months testing hundreds of guide RNAs to find multiple guides that work in tandem to increase the sensitivity of the test.

In a new preprint, the researchers report that with a single guide RNA, they could detect as few as 100,000 viruses per microliter of solution. And if they add a second guide RNA, they can detect as few as 100 viruses per microliter.

That’s still not as good as the conventional coronavirus diagnostic setup, which uses expensive lab-based machines to track the virus down to one virus per microliter, says Melanie Ott, a virologist at UC San Francisco who helped lead the project with Doudna. However, she says, the new setup was able to accurately identify a batch of five positive clinical samples with perfect accuracy in just 5 minutes per test, whereas the standard test can take 1 day or more to return results.

The new test has another key advantage, Wilson says: quantifying a sample’s amount of virus. When standard coronavirus tests amplify the virus’ genetic material in order to detect it, this changes the amount of genetic material present—and thus wipes out any chance of precisely quantifying just how much virus is in the sample.

By contrast, Ott’s and Doudna’s team found that the strength of the fluorescent signal was proportional to the amount of virus in their sample. That revealed not just whether a sample was positive, but also how much virus a patient had. That information can help doctors tailor treatment decisions to each patient’s condition, Wilson says.

Doudna and Ott say they and their colleagues are now working to validate their test setup and are looking into how to commercialize it.

Posted in:

doi:10.1126/science.abf1752

Robert F. Service

Bob is a news reporter for Science in Portland, Oregon, covering chemistry, materials science, and energy stories.

 

Source: https://www.sciencemag.org/news/2020/10/new-test-detects-coronavirus-just-5-minutes

Other articles on CRISPR and COVID19 can be found on our Coronavirus Portal and the following articles:

The Nobel Prize in Chemistry 2020: Emmanuelle Charpentier & Jennifer A. Doudna
The University of California has a proud legacy of winning Nobel Prizes, 68 faculty and staff have been awarded 69 Nobel Prizes.
Toaster Sized Machine Detects COVID-19
Study with important implications when considering widespread serological testing, Ab protection against re-infection with SARS-CoV-2 and the durability of vaccine protection

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