Mystery of COVID-19 reinfections: Global systematic review and meta-analysis of 577 cases

 Rubaid Azhar Dhillon,  

View ORCID ProfileMohammad Aadil Qamar, Omar Irfan, Jaleed Ahmed Gilani, Usama Waqar, Mir Ibrahim Sajid, Syed Fasial Mahmood

doi: https://doi.org/10.1101/2021.07.22.21260972

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.07.22.21260972v1.full.pdf

Abstract

Background As the COVID-19 pandemic rages on, reports on disparities in vaccine roll out alongside reinfection and reactivation from previously recovered cases have been emerging. With newer waves and variants of COVID-19, we conducted a systematic review to assess the determinants and disease spectrum of COVID-19 reinfection. Methods A comprehensive search covering relevant databases was conducted for observational studies reporting Polymerase Chain Reaction (PCR) confirmed infection and reinfection cases. Quality assessment tool developed by the National Institute of Health (NIH) for assessment of case series was used. Meta-analyses were performed using RevMan 5.3 for pooled proportions of findings in first infection and reinfection with 95% confidence interval (CI). Results Eighty-one studies reporting 577 cases were included from 22 countries. The mean age of patients was 46.2±18.9 years with males accounting for 45.8% of the study population while 179 (31.0%) cases of comorbidities were reported. The average time duration between first infection and reinfection was 63.6±48.9 days. During first infection and reinfection, fever was the most common symptom (41.4% and 36.4%,respectively) whilst anti-viral therapy was the most common treatment regimen administered (44.5% and 43.0%, respectively). Overall, comparable odds of symptomatic presentation and management were reported in the two infections. However, a higher Intensive Care Unit (ICU) admission rate was observed in reinfection compared to first infection (10 vs 3). Ten deaths were reported with 565 patients fully recovering. Respiratory failure was the most common cause of death (7/10 deaths). Seventy-two studies were determined to be of good quality whilst nine studies were of fair quality. Conclusion As the first global-scale systematic review of its kind, our findings support immunization practices given increased ICU admissions and mortality in reinfections. Our cohort serves as a guide for clinicians and authorities for devising an optimal strategy for controlling the pandemic.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

The author(s) received no specific funding for this work.

https://www.medrxiv.org/content/10.1101/2021.07.22.21260972v1

Severity of SARS-CoV-2 reinfections in second wave determines likelihood of mild endemicity

View ORCID ProfileJennie S Lavine,  View ORCID ProfileOttar N Bjornstad,  View ORCID ProfileDaniel Coombs,  View ORCID ProfileRustom Antia

doi: https://doi.org/10.1101/2021.07.21.21260944

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.07.21.21260944v1.full.pdf

Abstract

Immunity to SARS-CoV-2 is building up globally, but will this be sufficient to prevent future COVID-19 epidemics in the face of variants and waning immunity? Manaus, Brazil offers a concerning glimpse of what may come: six months after the majority of the city's population experienced primary infection, a second wave with a new strain resulted in more deaths than the first wave. Current hypotheses for this surge rely on prior immunity waning due to time and antigenic distance. Here we show this hypothesis predicts a severe endemic state. We propose an alternative hypothesis in which individuals infected in the first wave lose protection against transmission but retain immunity against severe disease and show this hypothesis is equally compatible with existing data. In this scenario, the increased number of deaths is due to an increased infection fatality ratio (IFR) for primary infections with the new variant. This alternative predicts a mild endemic state will be reached within decades. Collecting data on the severity of reinfections and infections post-vaccination as a function of time and antigenic distance from the original exposure is crucial for optimizing control strategies.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This work was funded by NIH grants U01 AI150747, U01 HL139483 and U01 AI144616

https://www.medrxiv.org/content/10.1101/2021.07.21.21260944v1

Protesters Rage Across Europe As Lockdown, Vaccination Mandates Begin

 Update (19115ET): Anti-lockdown protests kicked into high gear around the globe on Saturday, including irate Irish protesters:

Bitter Brits:

Pissed-off Parisians:

And incensed Italians, where the country has restricted public access to restaurants and museums to the unvaccinated.

This is what it looked like today in Australia, Milan, London, and France. 

Protests were worldwide today as many are fed up with elites whittling away their freedoms under the guise of COVID. 

*  *  *

Thousands of anti-lockdown demonstrators took to the streets of Sydney and other Australian towns on Saturday to protest new lockdown measures amid a surge of COVID-19 cases in the country.

Dozens were arrested and charged after crowds broke through barriers and clashed with officers, hurling bottles and anything they could get their hands on. 

The unmasked protesters marched from Sydney's Victoria Park to Town Hall. News.com.au estimates 15,000 people took part in the march. Many chanted anti-lockdown slogans and held signs calling for "freedom" and "the truth."

Footage on social media shows thousands of demonstrators marching through Sydney's downtown area. 

There was a significant police presence, including mounted police and riot control officers in response to what authorities said was an "unauthorized protest." 

The demonstrators defied restrictions on non-essential travel and mass public gatherings that could be extended through October. 

The Greater Sydney area has been locked down for a month as infections rise.  

Protesters were also seen in Melbourne and Adelaide. 

There's discontent with Australians being forced into lockdowns again as an outbreak of the delta variant began last month. 

Protests are not limited to Australia. New COVID rules have been implemented across Europe as Delta infections flare-up, which demonstrators in France and Greece recently took to the streets. The UK has even triggered widespread panic through a new app that notified tens of thousands of people they must quarantine for ten days because of possible exposure. 

Multiple US cities are now requiring people to wear masks indoors amid surging cases. 

https://www.zerohedge.com/political/thousands-join-anti-lockdown-protests-australia-amid-new-restrictions

In 60 days, most insurers must cover HIV prevention drugs, related services with no cost-sharing

 The federal government issued guidance Monday stating that almost all health insurers must cover HIV prevention drugs — such as Gilead’s Truvada and Descovy — with no cost-sharing, as well as associated lab testing and follow-up visits.

Insurers were already required to quit charging out-of-pocket fees for the drugs, called HIV Preexposure Prophylaxis (PrEP), by January of this year. But now insurers have 60 days to comply with the additional requirements, including no-cost services like baseline and follow-up testing, as well as monitoring, according to the guidance.

The news comes about two years after the US Preventive Services Task Force granted an “A” rating to PrEP treatments, requiring clinicians to offer “effective antiretroviral therapy to persons who are at high risk of human immunodeficiency virus (HIV) acquisition.”

Truvada was approved back in 2004 to treat HIV, and was sanctioned by the FDA as a preventative treatment in 2012. According to the CDC, daily PrEP reduces the risk of getting HIV via sexual intercourse by more than 90%.

AIDS activists, lawmakers and patients have criticized Gilead over the years regarding the price of Truvada, which cost nearly $2,000 for a one-month supply without insurance back in 2020. In May 2019, advocacy organization Health GAP testified to the US House committee on oversight and reform that generic versions in other countries were being sold for as little as $6 per month.

“While under-utilization of PrEP is caused by multiple factors, it is clear that price is a barrier that inhibits broad access,” the group said.

Gilead spent a priority review voucher to clear Descovy for PrEP back in 2019, just before Truvada generics were set to hit the market in 2020. Last year, Gilead’s HIV products raked in $16.9 billion, up 3% from 2019. Teva launched the first generic version of Truvada in October, charging $48.51 per tablet.

In November 2020, the HIV+Hepatitis Policy Institute reported that come 2021, “many plans” would not be in compliance with the legal requirement to offer PrEP treatment without cost-sharing, and urged insurers to take corrective action.

“The HIV community and public health leaders have been working for years to get to the day when insured people who are at risk of HIV can access PrEP without cost-sharing,” executive director Carl Schmid said at the time. “Unfortunately, it appears that some insurers and insurance regulators do not share our enthusiasm. I hope that will be corrected immediately.”

While PrEP will soon be readily available for insured patients, uninsured patients could still be left with no protection. According to an NBC News report, Gilead provides PrEP for free to lower-income people who aren’t insured, but it doesn’t cover associated services. And, safety net clinics are set to lose $100 million in annual HIV prevention funds due to a recent decision by Gilead.

https://endpts.com/in-60-days-most-insurers-will-be-required-to-cover-hiv-prevention-drugs-and-related-services-with-no-cost-sharing/

Pfizer, BioNTech team with South African manufacturer, but only on fill-finish

 The manufacturing expansion into Africa continued Wednesday with Pfizer and BioNTech’s announcement that the two companies signed on with the Biovac Institute to manufacture its Covid-19 vaccine to distribute throughout Africa. But while the continent is in dire need of doses, vaccines from the expansion won’t be available until the start of next year.

Biovac will only handle distribution and fill-finish duties. Drug substance for these batches will come from European facilities. When fully operational, the facility will pump out 100 million doses a year, set to be evenly distributed among the 55 member states of the African Union.

The announcement marks the fourth continent that the vaccine will be manufactured in, at over 20 facilities. Technical transfer, on-site development and equipment installations are all already underway, Pfizer said.

As the continent has been left behind in the race between countries to inoculate its residents, drugmakers have made moves to play catch-up, particularly after being spooked by President Joe Biden’s declaration that his administration supported vaccine intellectual property waivers. Moderna’s only involvement in Africa has come in the form of a distribution agreement with Dubai-based Magenta Investments, a company which has dealings in both the Middle East and Africa. In March, J&J made 220 million doses of the shot available to the African Vaccine Acquisition Trust, but no announcements surrounding manufacturing have been made.

The WHO and CDC have both thrown support at a South African consortium to establish a Covid-19 mRNA vaccine technology transfer hub that will, in theory, allow for the sharing of IP to train manufacturers and learn the process.

But the demand for doses is urgent; nearly all vaccines used in Africa are imported and only about 1% of people on the continent have been fully vaccinated. The Covid-19 pandemic isn’t the first time Africa has been neglected by the pharmaceutical industry, but it’s the latest example.

“As we and many others have long said, sharing Covid-19 tech and manufacturing is only way to move toward equity. huge un-tapped African capacity and expertise,” Georgetown global health professor Matthew Kavanagh tweeted Wednesday. “Past time to use state power to compel sharing. Today, companies show they will not do right without it.”

The contract was awarded to the Biovac Institute after a selection process that factors in compliance, quality and safety track record, among other things. Pfizer has worked with Biovac since 2015, when the two joined forces for fill-finish duties and distribution of Prevenar 13, an intramuscularly injected jab to prevent infections such as pneumonia and meningitis.

“From day one, our goal has been to provide fair and equitable access of the Pfizer-BioNTech COVID-19 Vaccine to everyone, everywhere,” Pfizer CEO Albert Bourla said in a statement. “Our latest collaboration with Biovac is a shining example of the tireless work being done, in this instance to benefit Africa. We will continue to explore and pursue opportunities to bring new partners into our supply chain network, including in Latin America, to further accelerate access of COVID-19 vaccines.”

Pfizer-BioNTech’s jab is still awaiting full approval from the FDA. It’s currently available under the Emergency Use Authorization.

In May, the EU backed an effort to expand manufacturing in Africa. Three locations were being considered, including the Institut Pasteur in Senegal, and in Rwanda and South Africa.

https://endpts.com/pfizer-and-biontech-team-up-with-south-african-manufacturer-but-it-will-only-handle-fill-finish/

Long-Awaited Elizabeth Holmes Documentary Set to Air on Hulu After Fraud Trial Begins

 As disgraced Theranos founder Elizabeth Holmes awaits her day in court, a long-awaited documentary series focused on the Stanford dropout who became a billionaire before losing it all is set to air on streaming service Hulu.

Hulu first announced the serial documentary in 2019. At the time, Saturday Night Live star Kate McKinnon had been tapped to star in the series as Holmes, but has since been recast to star Amanda Seyfried, Dark Daily reported. The series will be titled “The Dropout,” which references Holmes’ departure from Stanford at the age of 19 to found Theranos. “The Dropout,” which took its name from an ABC News podcast about Holmes, is set to stream this fall. Holmes is scheduled to head to court on Aug. 31 for fraud charges related to her role as CEO of the now-defunct Theranos. No drop date has yet been announced for the documentary.

Holmes has become a fascinating subject for documentarians. In addition to the ABC podcast about the life of Holmes, which included a deep dive into Holmes’ childhood in Texas where she was described as “disconnected” and dogged in her determination, HBO also aired a documentary called “The Inventor: Out For Blood In Silicon Valley.”

In addition to documentaries, a feature film in the works had attached Jennifer Lawrence in the title role. That film had been titled “Bad Blood” and was based on the seminal book of the same name written by The Wall Street Journal’s Pulitzer Prize-winning investigative journalist John Carreyrou, who first broke the story about Theranos and the problems with its diagnostics development equipment.

Holmes had been set to go to trial more than a year ago to face the fraud charges brought by the U.S. government, but the trial was delayed by the COVID-19 pandemic. Holmes, along with former Theranos president Ramesh “Sunny” Balwani, were charged with multiple counts of fraud in 2018. According to the government, from 2013 to 2015, Holmes and Balwani raised more than $700 million from investors in a manner that the U.S. Securities and Exchange Commission called “years-long fraud.”

During this time, they exaggerated or lied about the efficacy of the company’s proprietary technology and the state of its finances, according to the federal complaint. Additionally, Theranos also made false claims about its relationship with the Department of Defense as well as its regulatory status with the U.S. Food and Drug Administration during that time period. During fundraising efforts, Holmes and Balwani touted the technology’s efficacy and promise, but never produced any supporting evidence in peer-reviewed publications. Theranos largely relied on the personality of Holmes to push the false narrative about the technology. Based on the alleged fraudulent promises made to investors, the valuation of Theranos swelled to $9 billion. That made Holmes one of the youngest billionaires in the United States.

During pretrial arguments earlier this year, Holmes denied destroying evidence related to the company’s blood tests. The prosecution had alleged that Holmes and the Theranos team destroyed a database called the Laboratory Information System (LIS) in 2018. The LIS contained three years’ worth of accuracy and failure rates of Theranos tests. In its arguments, the prosecution said the database included evidence that Theranos’ technology did not work as promised and had a failure rate of 51.3%. At the time, the government said the tests “were so inaccurate, it was essentially a coin toss whether the patient was getting the right result. The data was devastating.”

Last year the judge overseeing the Holmes trial dismissed some added charges against the duo that expanded existing wire fraud charges. Additional fraud charges were dropped by the judge in February of 2020.

https://www.biospace.com/article/long-awaited-elizabeth-holmes-documentary-set-to-air-on-hulu-after-fraud-trial-begins/

Lisa Stockman Mauriello Receives First ALS Med Treatment

 Late Thursday evening, it was announced that Lisa Stockman Mauriello had received her first treatment of Amyotrophic Lateral Sclerosis (ALS) drug, tofersen. After months of advocacy, the moment was bittersweet for the Mauriello family and the supporters who have been drawn to Lisa's plight, as only time will tell whether the medicine will have an impact on her condition at this late stage. 

On June 25, Biogen opened applications for its hard-won compassionate use program for the drug, an antisense oligonucleotide (ASO) which targets a mutation in the superoxide dismutase 1 (SOD1) gene, believed to be the genetic driver in a familial form of the disease called SOD1-ALS. Tofersen is being co-developed by Biogen and collaborator, Ionis Pharmaceuticals.

In phase one of the two-part early access program (EAP), access to tofersen is being granted on an individual basis to SOD1-ALS patients with the most rapidly progressing disease, classified as an ALS Functional Rating Scale - Revised (ALSFRS-R) slope decline greater than or equal to two points per month. Then, if safety and efficacy data are positive, Biogen will offer the drug to the broader SOD1-ALS population in Fall, 2021.

Phase one launched last week after patients who had been on placebo in the pivotal phase III VALOR study were transitioned to active therapy. 

During a time when Americans have come face-to-face with their own mortality, Stockman Mauriello’s petition to receive access to tofersen through the “Right-to-Try” act sparked the compassion of a nation.

Stockman Mauriello suffers from a particularly devastating AD5 variant of SOD1-ALS, which typically kills patients within 12 months of the diagnosis. The New Jersey mother of three began exhibiting symptoms nearly one year ago, in August of 2020.

“We are thankful that Lisa finally got access to Tofersen - and that it happened within a week of the start of the EAP program. It was a fantastic belated birthday present,” Bob Mauriello told BioSpace. Lisa's birthday was on July 15.  “Our hope is that this is the beginning of a new day for ALS SOD1 patients and hopefully, it will lead to positive changes in the way that experimental drugs are developed and approved.”

While ultimately ceding to the pressure of over 100 000 petitioners and vocal criticism from the ALS community, Biogen did not compromise on its primary ethical argument.

BioSpace originally reported that the neurodegenerative disease leader was uncomfortable offering Tofersen more broadly while a control group of patients was still receiving a placebo in the 2:1 randomized trial. As of mid-July, Biogen stated that these patients would have transitioned to active therapy.

“We do not believe it is fair to ask participants in this study to continue to receive placebo while other SOD1-ALS patients are offered access to tofersen, but we do believe that access could be provided as soon as the placebo-controlled study has ended. However, until the safety and efficacy have been established, we will prioritize early access for a subset of the most rapidly progressing patients with this rare, severe disease,” Biogen said in a statement announcing the early access program.

Former Biogen senior vice president of corporate affairs, Daniel McIntyre, weighed in on the matter.

“The effort to support Lisa Mauriello has never been about simply giving her tofersen to the detriment of others. It’s true that the research sponsor’s first obligation is to those in the trial, which is why Lisa has asked to be randomized in the same manner as those participating in the VALOR trial,” McIntyre told BioSpace. “This started together as help for Lisa but not ONLY for Lisa, and arguments focused on trial participants on placebo does a disservice to both Lisa and other members of the ALS community who are seeking a more transparent, humane and accountable system that works for everyone.” 

In Thursday’s statement, The Mauriellos went on to thank, among others, the ALS community and Lisa’s physician, Dr. Neil Shneider.

“Sadly, there are few expanded access programs for promising #ALS therapies, so this is an important step," the family said in a statement. "We appreciate that Biogen finally agreed to offer this program and accelerated the timeline. While we wish this all would have occurred sooner, we are glad the day has finally come." 

https://www.biospace.com/article/lisa-stockman-mauriello-receives-first-tofersen-treatment-updated/