COVID-19 deaths detected in systematic post-mortem surveillance study in Africa

  

View ORCID ProfileLawrence Mwananyanda,  View ORCID ProfileChristopher J. Gill, William MacLeod,  View ORCID ProfileGeoffrey Kwenda,  View ORCID ProfileRachel Pieciak, Zachariah Mupila, Francis Mupeta, Leah Forman, Luunga Ziko,  View ORCID ProfileLauren Etter,  View ORCID ProfileDonald Thea

doi: https://doi.org/10.1101/2020.12.22.20248327

This article is a preprint and has not been peer-reviewed [what does this mean?].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/10.1101/2020.12.22.20248327v1.full.pdf

ABSTRACT

Objectives Limited SARS CoV 2 testing in many African countries has constrained availability of data on the impact of COVID-19 (CV19). To address this gap, we conducted a systematic post-mortem surveillance study to directly measure the fatal impact of CV19 in an urban African population.

Design We enrolled deceased individuals at the University Teaching Hospital (UTH) Morgue in Lusaka, Zambia. We obtained nasopharyngeal swabs for testing via reverse-transcriptase quantitative PCR (RT-qPCR) against the SARS-2 Coronavirus. We stratified deaths by CV19 status, by location, age, sex, and underlying risk factors.

Setting UTH is Zambia’s largest tertiary care referral hospital and its morgue registers ∼80% of Lusaka’s deaths.

Participants Participants of all ages were enrolled if within 48 hours of death and if the next of kin or representative provided written informed consent.

Results We enrolled 372 participants between June and September 2020, and had PCR results for 364 (99.5%). CV19 was detected in 70/364 (19.2%). The median age for CV19+ deaths was 48 years (IQR 36-72 years) and 70% were male. Most CV19+ deaths (51/70, 72.8%) occurred in the community; none had been tested for CV19 antemortem. Among the 19/70 facility deaths, six were tested antemortem. Among the 52/70 CV19 deaths with symptoms data, 44/52 had typical symptoms of CV19 (cough, fever, shortness of breath), of whom only five were tested antemortem. We identified CV19 among seven children; only one had been tested antemortem. The proportion of CV19+ deaths increased with age, but 75.7% of CV19+ deaths were aged <60 years. The five most common co-morbidities among CV19+ deaths were: tuberculosis (31.4%); hypertension (27.1%); HIV/AIDS (22.9%); alcohol use (17.1%); and diabetes (12.9%).

Conclusions Contrary to expectations, CV19+ deaths were common in Lusaka. The majority occurred in the community where testing capacity is lacking. Yet few who died at facilities were tested, despite presenting with typical symptoms of CV19. Therefore, CV19 cases were under reported because testing was rarely done, not because CV19 was rare. If our data are generalizable, the impact of CV19 in Africa has been vastly underestimated.

Competing Interest Statement

The authors have declared no competing interest.

https://www.medrxiv.org/content/10.1101/2020.12.22.20248327v1

White House Covid task force warns of possible new ‘USA variant’ driving spread

 The White House coronavirus task force said there could be a new variant of the virus that evolved in the U.S. and is driving spread, according to a document obtained by NBC News.

The strain variant, in addition to the U.K. variant, is already spreading in communities and may be 50% more transmissible, according to the report that was issued to states on Jan. 3.

The task force said the recent spike in cases has been at nearly twice the rate seen in the spring and summer seasons, according to the report. The U.S. is recording at least 228,400 new Covid-19 cases and at least 2,760 virus-related deaths each day, based on a seven-day average calculated by CNBC using Johns Hopkins University data. The U.S. reported its deadliest day Thursday with more than 4,000 deaths.

“This acceleration suggests there may be a USA variant that has evolved here, in addition to the UK variant that is already spreading in our communities and may be 50% more transmissible,” the report said. “Aggressive mitigation must be used to match a more aggressive virus; without uniform implementation of effective face masking (two or three ply and well-fitting) and strict social distancing, epidemics could quickly worsen as these variants spread and become predominant.”

“It is highly likely there are many variants evolving simultaneously across the globe,” Jason McDonald, a spokesman for the CDC, said in an email to CNBC. He added that there’s a “strong possibility” there are variants in the U.S., but it could be weeks or months before officials identify a particular variant that is “fueling the surge in the United States similar to the surge in the United Kingdom.”

“Researchers have been monitoring U.S. strains since the pandemic began, including 5,700 samples collected in November and December,” he said. “To date, neither researchers nor analysts at CDC have seen the emergence of a particular variant in the United States as has been seen with the emergence of B.1.1.7 in the United Kingdom or B.1.351 in South Africa.”

Representatives for the Department of Health and Human Services did not return CNBC’s requests for comment.

Few details were provided about the new U.S. strain in the report, including how long it has been circulating. In recent weeks, the U.S. has ramped up its genomic sequences to try and detect other strains.

Dr. Scott Gottlieb, a former commissioner of the Food and Drug Administration, told CNBC on Friday that the new strain the White House task force has found appears to be behaving like the one circulating in the United Kingdom.

But he told “Closing Bell” the new strain isn’t the same as the U.K. one, known as B.1.1.7, adding, “if it was we’d recognize that because we’re looking for it.”

UK strain in several states

Public health officials have been worried about the new strain of the virus found in the U.K. The CDC has identified at least 52 Covid-19 cases with the B.1.1.7 mutation in the U.S., according to data posted on the agency’s website last updated on Thursday. However, the CDC warns that its numbers “do not represent the total number of B.1.1.7 lineage cases that may be circulating in the United States” and may not match the figures reported by local officials.

So far the CDC only shows California, Florida, New York, Colorado and Georgia with cases of the B.1.1.7 variant, but other states like Connecticut, Pennsylvania and Texas announced the arrival of the strain in their states on Thursday.

New York Gov. Andrew Cuomo warned Thursday the new strain from the U.K. could force the state into another economic shutdown if it spreads unchecked and weakens the state’s hospitals.

“In the U.K., it overtook everything in three weeks,” Cuomo said. “If the U.K. spread catches on in New York, hospitalization rate goes up, the hospital staff is sick, then we have a real problem and we’re at shutdown again.”

Vaccines ‘in arms now’

In the task force report issued over the weekend, officials urged states not to delay immunization of those over 65 and vulnerable to severe disease.

“No vaccines should be in freezers but should instead be put in arms now; active and aggressive immunization in the face of this surge would save lives,” the task force said.

A new study from Pfizer found that its vaccine developed with BioNTech appeared to be effective against a key mutation in the U.K. strain as well as a variant found in South Africa.

Michael Osterholm, a member of President-elect Joe Biden’s Covid-19 advisory board, said Tuesday that the U.S. would likely see more new variants of the virus emerge.

Osterholm, an epidemiologist and director of the Center for Infectious Disease Research and Policy at the University of Minnesota, said in an interview with CNBC that the strain that was discovered in the U.K. is “a very big concern.”

“And it’s the first of what will likely be a number of these strains that are emerging as we’re at this point in the pandemic,” he added.

https://www.cnbc.com/2021/01/08/white-house-covid-task-force-warns-of-possible-new-usa-variant-driving-spread.html

Argenx’s cusatuzumab culminates in disappointment

 A big drop in efficacy with Argenx’s CD70-targeting antibody cusatuzumab will be a blow for its licensing partner, Johnson & Johnson. The latest cut of the phase II Culminate data released quietly by Argenx today showed a composite complete remission rate of just 40% among 52 newly diagnosed AML patients who were not eligible for intensive chemotherapy, given the MAb in combination with Vidaza. This is a dramatic fall from the 83% figure released at an event held alongside Ash in 2018, when this study's phase I stage had enrolled just 12 subjects. Those earlier, more impressive data had prompted J&J to part with $500m in cash, which given the waning efficacy signal looks rather expensive. Attention now turns the ongoing phase Ib Elevate study, testing cusatuzumab in combination with Vidaza and Roche/Abbvie’s Venclexta. Elevate has a primary completion date in June, according to clinicaltrials.gov.

Cusatuzumab's waning efficacy in the Culminate trial
	Dec 2018 data (ph1 dose escalation)	Jan 2021 ph2 interim analysis ITT (20mg/kg dose)
Complete remission*	10/12 (83%)	21/52 (40%)
*Including complete remission with incomplete haematologic recovery (CRi). Source: company releases.

https://www.evaluate.com/vantage/articles/news/snippets/argenxs-cusatuzumab-culminates-disappointment

Coronavirus variants 'may lead to false negative results with molecular tests' - FDA

 The U.S. drugs regulator said on Friday genetic variants of COVID-19, including the one found in the UK, could lead to false negative results from some molecular COVID-19 tests, but the risk of the mutations affecting overall testing accuracy is low.

The U.S. Food and Drug Administration (FDA) said it has alerted lab staff and healthcare providers to the possible false negative results and has asked them to consider such results in combination with clinical observations, and use a different test if COVID-19 is still suspected. (bit.ly/3ost0R6)

The more contagious variant of COVID-19 that has swept through the United Kingdom has been reported in at least five U.S. states, National Institutes of Health Director Francis Collins said this week.

Scientists have said newly developed vaccines should be equally effective against the new variant.

Thermo Fisher Scientific Inc’s TaqPath COVID-19 combo kit and Applied DNA Sciences’ Linea COVID-19 assay kit were found to have significantly reduced sensitivity due to certain mutations, including the B.1.1.7 variant or the so-called UK variant, according to the agency.

However, the detection patterns of both tests may help with early identification of new variants in patients, the FDA said.

The performance of Mesa Biotech’s Accula test can also be impacted by the genetic variants, the health regulator added.

Mesa said its test would tolerate the genetic variation presented by the new strain and that it should not have an impact on clinical performance of the test.

Britain said in December rapid lateral flow tests being deployed in the country’s mass-testing program can identify the variant, while Roche said its molecular test for COVID-19 was unlikely to be affected by the mutant strain of the virus.

https://www.reuters.com/article/us-health-coronavirus-testing/coronavirus-variants-may-lead-to-false-negative-results-with-molecular-tests-fda-idUSKBN29D2IZ

Older Americans scramble for COVID-19 shots as some U.S. states broaden access

 At Don's Pharmasave in Louisiana's rural Avoyelles parish, pharmacist Constance Rabalais and colleagues have had to come up with their own policies and procedures for doling out their first 100 COVID-19 vaccine doses amid overwhelming demand.

More than a dozen states looking to deploy unused coronavirus vaccines are starting to give shots to older members of the general population while others have not, meaning protection for more than 20 million Americans aching to hug their grandchildren may depend on where they live.

“We're glad to get it out. We just wished we’d had a little more time to understand the scheduling and appointment process,” Rabalais said.

States have received 21 million doses since the Food and Drug Administration in December authorized two vaccines - from Pfizer Inc with partner BioNTech SE and Moderna Inc - but only about 6 million have been administered.

Healthcare workers and people in nursing homes have been at the front of the line. But states left to distribute vaccines with little federal funding or direction are now plotting their own courses of action.

“It has created a situation where it’s confusing to the public," said Jen Kates, a senior vice president at Kaiser Family Foundation. "Even within states, if you live in one county you may have a different priority than if you live in another county."

Texas, Louisiana, North Carolina, Mississippi, Colorado, West Virginia, Alabama, Alaska, Arizona, Michigan, Florida, Georgia, Oklahoma, Indiana, Wyoming and Tennessee have either begun or will allow the vulnerable older generation to get shots this week or next in some or all counties.

In Texas, Florida and Georgia people over 65 are eligible for a shot, while West Virginia and Indiana are limiting the vaccine to those over 80.

Other states are holding off on moving into the next phase until more healthcare workers and nursing home residents are vaccinated, or have not yet announced a timeline for the general population.

The Trump administration has conceded that the biggest vaccination campaign in history aimed at stopping the deadly pandemic is off to a slower than hoped for start.

The government has advised states to expand eligibility and said it would start pushing vaccines directly to pharmacies this week.

President-elect Joe Biden wants to release the doses being held back for second shots into the supply, his spokesman said on Friday. Such a move would require that manufacturing is consistent enough to supply required second doses on schedule.

“I think the overarching goal of getting all eligible people vaccinated has to take precedence,” said Amesh Adalja, senior scholar at The Johns Hopkins Center for Health Security. “We can’t let an overly dogmatic adherence to priority groups to cause inefficiencies in vaccine administration.”

Distributing doses at pharmacies could help speed the process, but risks wasted doses, fraud, and confusion among the pubic, experts said.

Some states have internet portals for vaccine sign-ups, which may be challenging to access for those without internet. Other states have no centralized sign-up system at all, Kaiser's Kates said.

PHONES RINGING OFF THE HOOK

Rabalais said the phones have been ringing of the hook at her pharmacy with its staff of three, and that the store has done little besides organizing the vaccine rollout and navigating the state’s vaccine registry.

Erin Zwiener, a Democratic representative in the Texas state legislature, said the haphazard vaccine rollout echoes earlier phases of the pandemic, when testing and personal protective gear were scarce, and that ultimately the state’s poor will bear the brunt.

“My big concern is because we are so intensely privatizing this rollout and relying on pharmacies, we really are giving our wealthier folks more access to this vaccine,” she said.

Florida's Seminole county has set up vaccination clinics and wants to distribute in pharmacies next, but has not been told when it will receive more doses or how many, said Alan Harris, an emergency manager for the county.

Even though Texas broadened access, some hospitals and pharmacies are still prioritizing healthcare workers. That has led to confusion and frustration among the general public who thought doses were more widely available.

At multiple Brookshire Brothers stores, a Texas and Louisiana grocery and pharmacy chain, an automated message tells customers the stores' vaccine waiting lists are full.

Wimberley Pharmacy, an independent store in Wimberley, Texas, said they received thousands of calls from members of the general public after the state posted locations with vaccine supply on a public website to help Texans find shots nearby.

The store's first 100 doses went quickly to healthcare workers and first responders. The next batch of doses they receive will be open to the general public.

Said the store's manager Cody Gass: “We definitely don't have any sitting around."

https://www.marketscreener.com/quote/stock/MODERNA-INC-47437573/news/Moderna-Older-Americans-scramble-for-COVID-19-shots-as-some-U-S-states-broaden-access-32150215/

Janssen reports adverse event in Brazil COVID-19 trial unrelated to vax

 Brazilian health regulator Anvisa said on Friday that the Janssen unit of Johnson & Johnson had reported an adverse event suffered by a Brazilian volunteer in a Phase III trial for its COVID-19 vaccine.

Anvisa said Janssen and researchers found that the adverse event was not related to the vaccine. The agency said the trial will not have to be suspended, given that they were no longer recruiting new volunteers.

https://www.marketscreener.com/quote/stock/MODERNA-INC-47437573/news/Janssen-reports-adverse-event-in-Brazil-COVID-19-trial-unrelated-to-vaccine-32150561/

Biden Plans to Release Nearly All Available Covid-19 Vaccine Doses

 President-elect Joe Biden will seek to release nearly all available coronavirus vaccine doses to accelerate distribution, his transition team said Friday, in a shift from the Trump administration's policy of holding back stock for second doses.

"The president-elect believes we must accelerate distribution of the vaccine while continuing to ensure the Americans who need it most get it as soon as possible," said TJ Ducklo, a spokesman for Mr. Biden's transition. "He supports releasing available doses immediately, and believes the government should stop holding back vaccine supply so we can get more shots in Americans' arms now."

Mr. Ducklo said Mr. Biden, who will be inaugurated on Jan. 20, will release additional details about his vaccine distribution plans next week. They include establishing federally run vaccination sites, as well as mobile units that can travel to rural and underserved areas, and the launch of a national public awareness campaign around vaccine safety and guidelines, said incoming White House press secretary Jen Psaki.

The announcement comes as the U.S. and many other countries are struggling to ramp up vaccination programs. The Trump administration had promised to vaccinate 20 million people by the end of 2020.

The administration has been holding back about half of the vaccination doses for second shots. The administration has distributed 21.4 million vaccination doses from Moderna Inc. and Pfizer Inc. with BioNTech SE, and 5.9 million people have received the first dose as of Jan. 7, according to the Centers for Disease Control and Prevention.

"Vaccines give us hope, but the rollout has been a travesty," Mr. Biden told reporters in Wilmington, Del., on Friday.

Some medical authorities, including the U.S. Food and Drug Administration, have said delaying the second dose of the vaccine is potentially detrimental to public health. A Biden transition official said the president-elect is confident that manufacturers can produce enough vaccines to deliver second doses in a timely manner, while adding Mr. Biden will use the Defense Production Act to boost supply.

The Biden team's decision won't change the timing interval between first and second doses, according to a person familiar with the administration's planning.

The release of more vaccination doses could further strain some states that have for months been calling for more funding from the Trump administration and Congress to help them staff up and handle administration of the shots.

Congress in December approved a vaccine relief package that includes about $8 billion for states. But some states may have to hire and train staff, which some public health officials have said can take five to six weeks.

"Public health has been scaled up to deal with it, but vaccine allocation has not gone up," said Claire Hannon, executive director of the Association of Immunization Managers, which works with states and territories on immunization. "We keep thinking it's going to ramp up and it isn't."

Mr. Biden said Friday he will seek a significantly larger coronavirus relief package upon taking office, which would include more funding for local and state officials as they grapple with the pandemic and vaccine distribution. "The price tag will be high," Mr. Biden said.

A Pfizer spokeswoman said the company is confident in its ability to deliver 200 million doses of the vaccine to the U.S. government by the end of July.

"We are committed to collaborating with the Biden administration on common-sense solutions to the challenges in vaccine distribution so that as many Americans as possible have access to our vaccine as quickly as possible," the spokeswoman said.

Mr. Biden will get his second dose of the vaccine next week, his incoming White House press secretary Ms. Psaki said Friday. He received his first dose last month before cameras in a bid to instill public confidence in the vaccine. Ms. Psaki said the vaccine was also being administered to other top officials who will be close to the president-elect in the administration.

News of the Biden administration's release plan was first reported by CNN.

The release plan follows a letter from a group of Democratic governors to Health and Human Services Secretary Alex Azar and Operation Warp Speed Chief Operating Officer Gen. Gustave Perna asking the federal government to immediately begin distributing reserved doses.

Mr. Biden has promised a more robust response to steering the nation out of the coronavirus pandemic, which has infected more than 21 million people across the U.S. and claimed more than 360,000 lives.

The decision could help increase the number of people who receive the vaccine. But it also raises the risk of not having reserves to provide booster shots and could strain some states that lack the staffing or infrastructure to meet potential demand.

Some state public health officials said they haven't yet received information from Mr. Biden's transition team on changes to the vaccine rollout that may be planned, which they say they need to anticipate any hiring or workflow changes.

U.S. Department of Health and Human Services leaders who have been overseeing the coronavirus response team are preparing to leave, and some staff who handle communication and coordination have been told they will be replaced after they offered to stay in their roles to help during the transition. Concerns are mounting that the vaccine rollout could be further disrupted by the changeover, according to two people familiar with the planning.

"If President-elect Biden is calling for the distribution of vaccines knowing that there would not be a second dose available, that decision is without science or data and is contrary to the FDA's approved label," said Michael Pratt, a spokesman for Operation Warp Speed.

"If President-elect Biden is suggesting that the maximum number of doses should be made available, consistent with ensuring that a second dose of vaccine will be there when the patient shows up, then that is already happening," he added. "Second-dose management was always about ensuring supply-chain availability."

The vaccine rollout has been sluggish. Dr. Anthony Fauci, the U.S. government's top infectious-diseases official, said this week that the U.S. will soon be able to give one million vaccinations a day. But even that stepped-up pace would put the country on track to fully immunize 80% of the population by June of 2022.

"We really should be at at least three million a day," said Ashish Jha, dean of the Brown University School of Public Health, who on Friday praised the decision to release more of the second doses.

Pressure has been growing from public-health officials and Democratic state leaders to release the second doses, and the urgency has risen because a new, more transmissible strain of the virus has been found in the U.S. California Democratic Gov. Gavin Newsom and New York Gov. Andrew Cuomo, also a Democrat, this week pressed HHS to release second doses.

The White House coronavirus task force this week had discussed possible changes to the vaccine rollout, including whether more vaccines should be sent to states that are making more rapid progress on getting shots administered, according to a person familiar with the discussions.

They also discussed possibly allowing second shots to be given at five or seven weeks after the first, instead of at three or four weeks, the person said. The decision to hold back second doses wasn't made by the task force, the person said.

https://www.marketscreener.com/quote/stock/MODERNA-INC-47437573/news/Biden-Plans-to-Release-Nearly-All-Available-Covid-19-Vaccine-Doses-4th-Update-32151026/