SARS coronavirus vaccines protect against different coronaviruses

 Tanushree Dangi, Nicole Palacio, Sarah Sanchez, Jacob Class, Lavanya Visvabharathy, Thomas Ciucci, Igor Koralnik, Justin Richner, Pablo Penaloza-MacMaster

doi: https://doi.org/10.1101/2021.06.01.446491

This article is a preprint and has not been certified by peer review [what does this mean?].

PDF: https://www.biorxiv.org/content/10.1101/2021.06.01.446491v1.full.pdf

Abstract

Although SARS-CoV-2 vaccines have shown efficacy against SARS-CoV-2, it is unclear if they can also protect against other coronaviruses that may infect humans in the future. Here, we show that SARS-CoV-2 vaccination in humans elicits cross-reactive antibodies against other coronaviruses. Our studies in mice demonstrate that SARS-CoV-2 vaccination protects against a common cold coronavirus, and that SARS-CoV-1 vaccination protects against SARS-CoV-2. Similarly, infection with a common cold coronavirus also conferred enhanced protection from subsequent infections with other coronaviruses. Mechanistically, both T cells and antibodies mediated cross-protection. This is the first direct demonstration that coronavirus-specific immunity can confer heterologous protection in vivo, providing a rationale for universal coronavirus vaccines.

Highlights

1. SARS-CoV-2 vaccination elicits cross-reactive antibody against other coronaviruses in humans.

2. COVID-19 patients generate cross-reactive antibody against other coronaviruses.

3. A SARS-CoV-1 vaccine protects against SARS-CoV-2.

4. Prior coronavirus infections improve immune protection following heterologous coronavirus challenges.

Competing Interest Statement

The authors have declared no competing interest.

https://www.biorxiv.org/content/10.1101/2021.06.01.446491v1

Symptomatic Acute Myocarditis in 7 Adolescents Following Pfizer-BioNTech COVID-19 Vaccination

 Mayme Marshall, MD, Ian D. Ferguson, MD, Paul Lewis, MD, MPH, Preeti Jaggi, MD, Christina Gagliardo, MD, James Steward Collins, MD, Robin Shaughnessy, MD, Rachel Caron, BA, Cristina Fuss, MD, Kathleen Jo E. Corbin, MD, MHS, Leonard Emuren, MBBS, PhD, Erin Faherty, MD, E. Kevin Hall, MD, Cecilia Di Pentima, MD, MPH, Matthew E. Oste, MD, MPH, Elijah Paintsil, MD, Saira Siddiqui, MD, Donna M. Timchak, MD, Judith A. Guzman-Cottrill, DO 

DOI: 10.1542/peds.2021-052478

PDF: https://pediatrics.aappublications.org/content/pediatrics/early/2021/06/02/peds.2021-052478.full-text.pdf

Abstract 

Trials of coronavirus disease 2019 (COVID-19) vaccination included limited numbers of children so may not have detected rare but important adverse events in this population. We report seven cases of acute myocarditis or myopericarditis in healthy male adolescents who presented with chest pain all within four days after the second dose of Pfizer-BioNTech COVID-19 vaccination. Five patients had fever around the time of presentation. Acute COVID19 was ruled out in all 7 cases based on negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) real-time reverse transcription polymerase chain reaction (PCR) tests of specimens obtained using nasopharyngeal swabs. None of the patients met criteria for multisystem inflammatory syndrome in children (MIS-C). Six of the 7 patients had negative SARSCoV-2 nucleocapsid antibody assays, suggesting no prior infection. All patients had an elevated troponin. Cardiac magnetic resonance imaging (MRI) revealed late gadolinium enhancement characteristic of myocarditis. All 7 patients resolved their symptoms rapidly. Three patients were treated with non-steroidal anti-inflammatory drugs (NSAIDs) only and 4 received intravenous immune globulin (IVIG) and corticosteroids. This report provides a summary of each adolescent’s clinical course and evaluation. No causal relationship between vaccine administration and myocarditis has been established. Continued monitoring and reporting to the Food and Drug Administration (FDA) Vaccine Adverse Event Reporting System (VAERS) is strongly recommended.

https://pediatrics.aappublications.org/content/pediatrics/early/2021/06/02/peds.2021-052478.full.pdf

Private equity firms buy Medline for reported $34B

 A consortium of private equity firms has reached a deal — reportedly worth about $34 billion — to acquire family-run Medline, the medical supply and equipment company announced Saturday.

The leveraged buyout's value was reported by The Wall Street Journal, which said the acquiring firms — Blackstone Group, Carlyle Group and Hellman & Friedman LLC — had beat out a rival bid from Brookfield Asset Management, a Canadian investing firm.

Northfield, Illinois-based Medline is a major producer and distributor of everything from anesthesia to wheelchairs, beds and lab supplies used in hospitals and other healthcare centers in more than 110 countries. It also sells consumer products including the Curad line.

Medline said in a statement that the company will continue to be privately held and led by the family of Charlie Mills, the chief executive officer, and that it will remain the largest single shareholder.

It said the entire senior management team will remain in place.

Medline, with 28,000 employees worldwide, said it had revenue of $17.5 billion in 2020.

It said it would use the new investment to accelerate international expansion and strengthen its global supply chain.

https://abcnews.go.com/Health/wireStory/private-equity-firms-buy-medical-equipment-giant-medline-78108825

Nearly Half of People With Migraine Don't Seek Care

 Many people with migraine hesitated to seek care, mainly because they chose self-management or were concerned their migraine wouldn't be taken seriously, a population-based survey showed.

Nearly half (45%) of participants in the OVERCOME (U.S.) study hesitated to seek migraine care and of those, 42% did not seek migraine care in the preceding 12 months, reported Robert Shapiro, MD, PhD, of the University of Vermont in Burlington, in a presentation at the American Headache Society virtual meeting.

People who hesitated to get migraine care said they wanted to take care of symptoms on their own (45%) or were concerned their migraine would not be taken seriously (35%), he said. Many who did not seek migraine care experienced at least moderate disability on the Migraine Disability Assessment (MIDAS) test, a measure of the effect of headache attacks on daily school, work, home, or social activities over 3 months.

"Given that nearly half of survey respondents hesitated to seek migraine care, we urgently need to understand the bases for these barriers and promote more effective dialogue between healthcare providers and people with migraine to improve their health outcomes," Shapiro noted.

OVERCOME was a prospective, multi-cohort, web-based survey conducted in a representative U.S. sample in 2018 and 2019. Survey respondents had one or more headache or migraine attack in the past 12 months. Most respondents (94.6%) met criteria based on a validated migraine screener using International Classification of Headache Disorders (ICHD-3) criteria. In addition, 60% had self-reported a migraine diagnosis by a healthcare provider.

Of a total study population of 41,925 people, 39,494 respondents indicated whether they had hesitated to consult for migraine care. Participants who hesitated to get help mainly were female (74%) with an average age of 39. Nearly half (45%) had full-time employment and about a third (32%) had a college degree. Mean BMI was 29.2, and 19.5% currently used marijuana or cannabidiol.

About half (52%) had up to 3 monthly migraine days; 21% had 4-7 days, 13% had 8-14 days, and 14% had 15 days or more. More than 80% had nausea, photophobia, or phonophobia with their attacks. Among participants who felt their migraine would not be taken seriously, most were disabled by migraine on average 1 or more day a week.

Other major reasons people hesitated to get migraine care included not thinking their migraine was serious or painful enough (29%), inability to afford care (29%), inadequate health insurance coverage (21%), and fear of being diagnosed with something serious (19%).

Of participants who eventually did consult for migraine even though they hesitated, factors associated with their decision to get help included a previous migraine diagnosis, moderate or severe disability, and having health insurance.

Several measures may increase migraine consulting and improve health outcomes, Shapiro suggested. "These might include ensuring that an accurate diagnosis of migraine is made, taking migraine seriously -- that is, reducing stigma -- and reducing institutional barriers and costs," he said.

The study had several limitations. Survey data were self-reported and subject to recall and selection bias. In addition, the researchers did not evaluate information about the time lag to consulting.

Disclosures

The study was supported by Eli Lilly.

Shapiro disclosed relevant relationships with Eli Lilly and Lundbeck.

Primary Source

American Headache Society

Source Reference: Shapiro R "Reasons for Hesitating to Consult for Migraine Care: Results of the OVERCOME (US) Study" AHS 2021

Secondary Source

American Headache Society

Source Reference: Reed M, et al "Important Factors Associated With Hesitating to Consult for Migraine Care: Results of the OVERCOME (US) Study" AHS 2021, Abstract P-12.

https://www.medpagetoday.com/meetingcoverage/ahs/92945

CDC director urges teens to get vaccinated after hospitalizations rise

 The U.S. Centers for Disease Control and Prevention director urged teenagers to get vaccinated, as new data from the agency's researchers showed one in three teenagers who were hospitalized due to COVID-19 early this year needed ICU admission. 

  "I am deeply concerned by the numbers of hospitalized adolescents and saddened to see the number of adolescents who required treatment in intensive care units or mechanical ventilation," CDC Director Rochelle Walensky said in a statement on Friday. 

  The rate of hospitalization due to COVID-19 increased among adolescents aged 12 to 17 in April to 1.3 per 100,000 people from a lower rate in mid-March, the CDC said in its Morbidity and Mortality Weekly Report (MMWR). 

  Among 204 adolescents, who were hospitalized mainly for COVID-19 between Jan. 1 and March 31, 31.4% were admitted to an intensive care unit and about 5% required mechanical ventilation, the agency said. (https://bit.ly/3vOF96u) 

  "Much of this suffering can be prevented," Walensky said. 

  The CDC's latest data was based on a surveillance system of laboratory-confirmed COVID-19–associated hospitalizations in 99 counties across 14 states, covering approximately 10% of the U.S. population. 

  The data adds to previous information showing that hospitalizations due to severe COVID-19 occur in all age groups even though they occur more often in older adults. The CDC released the data as part of the United States' push to vaccinate teenagers with Pfizer Inc and German partner BioNTech SE's vaccine. 

  The shot was authorized for use in 12 to 15 year olds in May. Nearly 50% https://covid.cdc.gov/covid-data-tracker/#vaccinations of the U.S. population, 12 years and older, has been fully vaccinated, according to the agency's data. 

  The increased hospital admission rates in teens may be related partly to the circulation of more infectious variants of the coronavirus and a large number of children returning to schools, the agency said. 

https://finance.yahoo.com/news/u-cdc-director-urges-teens-181905185.html

Computer simulations of brain can predict language recovery in stroke survivors

 At Boston University, a team of researchers is working to better understand how language and speech is processed in the brain, and how to best rehabilitate people who have lost their ability to communicate due to brain damage caused by a stroke, trauma, or another type of brain injury. This type of language loss is called aphasia, a long-term neurological disorder caused by damage to the part of the brain responsible for language production and processing that impacts over a million people in the US.

"It's a huge problem," says Swathi Kiran, director of BU's Aphasia Research Lab, and College of Health & Rehabilitation Sciences: Sargent College associate dean for research and James and Cecilia Tse Ying Professor in Neurorehabilitation. "It's something our lab is working to tackle at multiple levels."

For the last decade, Kiran and her team have studied the brain to see how it changes as people's language skills improve with speech therapy. More recently, they've developed new methods to predict a person's ability to improve even before they start therapy. In a new paper published in Scientific Reports, Kiran and collaborators at BU and the University of Texas at Austin report they can predict language recovery in Hispanic patients who speak both English and Spanish fluently -- a group of aphasia patients particularly at risk of long-term language loss -- using sophisticated computer models of the brain. They say the breakthrough could be a game changer for the field of speech therapy and for stroke survivors impacted by aphasia.

"This [paper] uses computational modeling to predict rehabilitation outcomes in a population of neurological disorders that are really underserved," Kiran says. In the US, Hispanic stroke survivors are nearly two times less likely to be insured than all other racial or ethnic groups, Kiran says, and therefore they experience greater difficulties in accessing language rehabilitation. On top of that, oftentimes speech therapy is only available in one language, even though patients may speak multiple languages at home, making it difficult for clinicians to prioritize which language a patient should receive therapy in.

"This work started with the question, 'If someone had a stroke in this country and [the patient] speaks two languages, which language should they receive therapy in?'" says Kiran. "Are they more likely to improve if they receive therapy in English? Or in Spanish?"

This first-of-its-kind technology addresses that need by using sophisticated neural network models that simulate the brain of a bilingual person that is language impaired, and their brain's response to therapy in English and Spanish. The model can then identify the optimal language to target during treatment, and predict the outcome after therapy to forecast how well a person will recover their language skills. They found that the models predicted treatment effects accurately in the treated language, meaning these computational tools could guide healthcare providers to prescribe the best possible rehabilitation plan.

"There is more recognition with the pandemic that people from different populations -- whether [those be differences of] race, ethnicity, different disability, socioeconomic status -- don't receive the same level of [healthcare]," says Kiran. "The problem we're trying to solve here is, for our patients, health disparities at their worst; they are from a population that, the data shows, does not have great access to care, and they have communication problems [due to aphasia]."

As part of this work, the team is examining how recovery in one language impacts recovery of the other -- will learning the word "dog" in English lead to a patient recalling the word "perro," the word for dog in Spanish?

"If you're bilingual you may go back and forth between languages, and what we're trying to do [in our lab] is use that as a therapy piece," says Kiran.

Clinical trials using this technology are already underway, which will soon provide an even clearer picture of how the models can potentially be implemented in hospital and clinical settings.

"We are trying to develop effective therapy programs, but we also try to deal with the patient as a whole," Kiran says. "This is why we care deeply about these health disparities and the patient's overall well-being."

Story Source:

Materials provided by Boston University. Original written by Jessica Colarossi. Note: Content may be edited for style and length.

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Journal Reference:

1. Uli Grasemann, Claudia Peñaloza, Maria Dekhtyar, Risto Miikkulainen, Swathi Kiran. Predicting language treatment response in bilingual aphasia using neural network-based patient models. Scientific Reports, 2021; 11 (1) DOI: 10.1038/s41598-021-89443-6

https://www.sciencedaily.com/releases/2021/06/210604213613.htm

COVID treatment guidelines may contribute to rise in black fungus in India

 One of the more recent and worrying consequences of COVID-19 in India is the emergence of mucormycosis and other fungal co-infections.

Media reports use black, white and yellow fungus to refer to mucormycosis, aspergillosis, candidiasis and cryptococcosis. Together, they are referred to as invasive fungal infections, and they usually infect people with an impaired immune system, or with damaged tissue.

Some 12,000 cases of mucormycosis have been reported across the country in recent months.

These are said to have been caused by misuse of steroids and antibiotics (which impair our ability to fight these fungal infections) in COVID treatments, and high numbers of patients with poorly controlled diabetes where tissue is damaged.

Mucormycosis most commonly manifests in the nose and sinuses, but from there can spread to the eyes, lungs and brain. It also affects other organs including the skin.

Wide-scale shortages of Amphotericin B, the mainstay therapy for mucormycosis, are being reported. Citizens have had to turn to social media and courts to procure the medicine.

The central government has granted approval to five companies to produce the drug, in addition to the six that already do so.

Could the situation have been averted? Perhaps, if the government had considered recent evidence and issued clear guidelines on using steroids and antiobiotics in treating COVID-19.

What we knew before the second wave

Over the last year, COVID-19-associated invasive fungal infections have been reported from across several countries. In India, they were reported as early as April last year, during the first wave.

These infections have also been reported during previous epidemics such as SARS in 2003.

The infection is often fatal. Deaths due to the fungal infection in previous coronavirus outbreaks such as SARS ranged from 25% to 73%.

Antibiotic guidelines in India

The two most recent versions of COVID treatment guidelines in India (June 27, 2020 and May 24, 2021) rightly state antibiotics should not be prescribed routinely.

Instead, they urge doctors to consider "empiric" antibiotic therapy as per a "local antibiogram" when COVID patients have moderate secondary infections. Empiric antibiotic therapy implies making a diagnosis based on what the literature says is the most likely pathogen (or bug) causing the infection. Antibiograms are sent out to hospitals periodically and they describe the current infections circulating in the area and which antiobiotics work against them.

For severe secondary infections, the guidelines suggest conducting blood cultures to check which antibiotic might work, ideally before the medication is started.

An empirical approach can work effectively only if a majority of COVID facilities treating moderate cases have access to local antibiograms. If they don't, doctors will usually end up prescribing broad-spectrum antibiotics. Broad-spectrum antiobiotics kill a range of bugs, rather than a specific one, which is risky because they can also kill the good bugs we use to fight off things like fungal infections.

A study of ten Indian hospitals found 74% of patients with secondary infections during the first wave were given antibiotics the World Health Organization has said should be used sparingly, and another 9% received antibiotics that were not recommended.

The guidelines should advise the same procedure for moderate and severe cases, that is, to conduct blood cultures before starting patients on antimicrobial therapy to ensure the antibiotics will work, and that they won't lead to a secondary fungal infection.

Steroid dosage too high

One of the recommended COVID treatments of the National Institute of Health in the US is 32mg a day of the steroid methylprednisolone.

In March 2020, Indian guidelines for treatment recommended 1-2mg methyprednisolone per kilo of body weight for patients with severe symptoms (so 70-140mg for a 70kg person).

This was updated in June 2020 with a lower dose of methylprednisolone (35–70mg per day for a 70kg person) for three days for moderate cases and the original recommended dose (70–140mg per day for a 70kg person) for five to seven days for severe cases.

The most recent guideline of April 2021 does not alter the dosage per day but recommended an increased duration of therapy, five to ten days, for both moderate and severe cases.

Despite that, the Indian recommendation still works out to a wide range across moderate and severe categories—from a low of about 35 mg to a high of 140 mg (for a 70kg person). This is in sharp contrast to the 32mg (total daily dose) recommendation in the US.

Indian government spokespersons have attributed the rise in fungal infections to the fact doctors in the country may have irrationally used steroids.

But given the government's own guidelines for steroid use are so much higher than in other countries, there should be analysis into whether this may be contributing to the significant rise in fungal infections.

Those findings would have profound implications on India's pandemic management.

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India doctors warn of deadly fungal infection in COVID-19 patients

https://medicalxpress.com/news/2021-06-covid-treatment-guidelines-contributing-black.html