Until Covid vax is ready, pneumonia vaccines may reduce Covid deaths

The yearly influenza season threatens to make the COVID-19 pandemic doubly deadly, but I believe that this isn’t inevitable.

There are two commonly given vaccines – the pneumococcal vaccine and the Hib vaccine – that protect against bacterial pneumonias. These bacteria complicate both influenza and COVID-19, often leading to death. My examination of disease trends and vaccination rates leads me to believe that broader use of the pneumococcal and Hib vaccines could guard against the worst effects of a COVID-19 illness.

I am an immunologist and physiologist interested in the effects of combined infections on immunity. I have reached my insight by juxtaposing two seemingly unrelated puzzles: Infants and children get SARS-CoV-2, the virus that causes COVID-19, but very rarely become hospitalized or die; and case numbers and death rates from COVID-19 began varying greatly from nation to nation and city to city even before lockdowns began. I wondered why.

One night I woke up with a possible answer: vaccination rates. Most children, beginning at age two months, are vaccinated against numerous diseases; adults less so. And, both infant and adult vaccination rates vary widely across the world. Could differences in the rates of vaccination against one or more diseases account for differences in COVID-19 risks? As someone who had previously investigated other pandemics such as the Great Flu Pandemic of 1918-19 and AIDS, and who has worked with vaccines, I had a strong background for tracking down the relevant data to test my hypothesis.

Pneumococcal vaccination rates correlate with lower COVID-19 cases and deaths

I gathered national and some local data on vaccination rates against influenza, polio, measles-mumps-rubella (MMR), diphtheria-tetanus-pertussis (DTP), tuberculosis (BCG), pneumococci and Haemophilus influenzae type B (Hib). I correlated them with COVID-19 case rates and death rates for 24 nations that had experienced their COVID-19 outbreaks at about the same time. I controlled for factors such as percentage of the population who were obese, diabetic or elderly.

I found that only pneumococcal vaccines afforded statistically significant protection against COVID-19. Nations such as Spain, Italy, Belgium, Brazil, Peru and Chile that have the highest COVID-19 rates per million have the poorest pneumococcal vaccination rates among both infants and adults. Nations with the lowest rates of COVID-19 – Japan, Korea, Denmark, Australia and New Zealand – have the highest rates of pneumococcal vaccination among both infants and adults.

A recent preprint study (not yet peer-reviewed) from researchers at the Mayo Clinic has also reported very strong associations between pneumococcal vaccination and protection against COVID-19. This is especially true among minority patients who are bearing the brunt of the coronavirus pandemic. The report also suggests that other vaccines, or combinations of vaccines, such as Hib and MMR may also provide protection.

These results are important because in the U.S., childhood vaccination against pneumococci – which protects against Streptococcus pneumoniae bacteria – varies by state from 74% to 92%. Although the CDC recommends that all adults 18-64 in high risk groups for COVID-19 and all adults over the age of 65 get a pneumococcal vaccination, only 23% of high-risk adults and 64% of those over the age of 65 do so.

Similarly, although the CDC recommends at all infants and some high-risk adults be vaccinated against Haemophilus influenzae type B (Hib), only 80.7% of children in the U.S. and a handful of immunologically compromised adults have been. Pneumococcal and Hib vaccination rates are significantly lower in minority populations in the U.S. and in countries that have been hit harder by COVID-19 than the U.S.

Based on these data, I advocate universal pneumococcal and Hib vaccination among children, at-risk adults and all adults over 65 to prevent serious COVID-19 disease.

Left: Combined rates of childhood and adult (over 65) pneumococcal vaccination (out of a possible 200). Right: Cases (per million) population of COVID-19 at about 90 days into the pandemic for 24 nations. Nations with high pneumococcal vaccination rates have low COVID-19 case rates. CC BY-SA

How pneumococcal vaccination protects against COVID-19

Protection against serious COVID-19 disease by pneumococcal and Hib vaccines makes sense for several reasons. First, recent studies reveal that the majority of hospitalized COVID-19 patients, and in some studies nearly all, are infected with streptococci, which causes pneumococcal pneumonias, Hib or other pneumonia-causing bacteria. Pneumococcal and Hib vaccinations should protect coronavirus patients from these infections and thus significantly cut the risk of serious pneumonia.

I also found that pneumococcal, Hib and possibly rubella vaccines may confer specific protection against the SARS-CoV-2 virus that causes COVID-19 by means of “molecular mimicry.”

Molecular mimicry occurs when the immune system thinks one microbe looks like another. In this case, proteins found in pneumococcal vaccines and, to a lesser degree, ones found in Hib and rubella vaccines as well look like several proteins produced by the SARS-CoV-2 virus.

Two of these proteins found in pneumococcal vaccines mimic the spike and membrane proteins that permit the virus to infect cells. This suggests pneumococcal vaccination may prevent SARS-CoV-2 infection. Two other mimics are the nucleoprotein and replicase that control virus replication. These proteins are made after viral infection, in which case pneumococcal vaccination may control, but not prevent, SARS-CoV-2 replication.

Either way, these vaccines may provide proxy protection against SARS-CoV-2 infection that we can implement right now, even before we have a specific virus vaccine. Such protection may not be complete. People might still suffer a weakened version of COVID-19 but, like most infants and children, be protected against the worst effects of the infection.

Fighting influenza-related pneumonias during the COVID-19 pandemic

While the specific protection these other vaccines confer against COVID-19 has not yet been tested in a clinical trial, I advocate broader implementation of pneumococcal and Hib vaccination for one additional, well-validated reason.

Pneumococcal and Hib pneumonias – both caused by bacteria – are the major causes of death following viral influenza. The influenza virus rarely causes death directly. Most often, the virus makes the lungs more susceptible to bacterial pneumonias, which are deadly. Dozens of studies around the world have demonstrated that increasing rates of pneumococcal and Hib vaccination dramatically lowers influenza-related pneumonias.

Similar studies demonstrate that the price of using these vaccines is balanced by savings due to lower rates of influenza-related hospitalizations, intensive care unit admissions and deaths. In the context of COVID-19, lowering rates of influenza-related hospitalizations and ICU admissions would free up resources to fight the coronavirus, independent of any effect these vaccines might have on SARS-CoV-2 itself. In my opinion, that is a winning scenario.

In short, we need not wait for a SARS-CoV-2 vaccine to slow down COVID-19.

I believe that we can and should act now by fighting the coronavirus with all the tools at our disposal, including influenza, Hib, pneumococcal and perhaps rubella vaccinations.

Preventing pneumococcal and Hib complications of influenza and COVID-19, and perhaps proxy-vaccinating against SARS-CoV-2 itself, helps everyone. Administering these already available and well-tested pneumococcal and Hib vaccines to people will save money by freeing up hospital beds and ICUs. It will also improve public health by reducing the spread of multiple infections and boost the economy by nurturing a healthier population.

- Robert Root-Bernstein, Professor of Physiology, Michigan State University

https://theconversation.com/until-a-coronavirus-vaccine-is-ready-pneumonia-vaccines-may-reduce-deaths-from-covid-19-147829

1st COVID vaccines 'likely to be imperfect' and 'might not prevent infection'

The first generation of COVID-19 vaccines "is likely to be imperfect" and "might not work for everyone", the chair of the UK Vaccine Taskforce has said.

Writing in The Lancet, Kate Bingham said no vaccine in the history of medicine "has been as eagerly anticipated" and that "vaccination is widely regarded as the only true exit strategy from the pandemic that is currently spreading globally".

But she cautioned against over-optimism and that any vaccine might not work for everyone, or for very long.

"We do not know that we will ever have a vaccine at all," she wrote. "It is important to guard against complacency and over-optimism.

"The first generation of vaccines is likely to be imperfect, and we should be prepared that they might not prevent infection but rather reduce symptoms, and, even then, might not work for everyone or for long."

 

The vaccine taskforce was created by Sir Patrick Vallance, the UK government's chief scientific advisor.

It was set up under the Department for Business, Energy and Industrial Strategy in May 2020, and Ms Bingham reports directly to the prime minister.

In her Lancet article she said that the "strategy has been to build a diverse portfolio across different formats to give the UK the greatest chance of providing a safe and effective vaccine, recognising that many, and possibly all, of these vaccines could fail".

Cabinet minister George Eustice said Ms Bingham's analysis was "probably right".

"A vaccine will be the answer at some point but it is too early to say precisely when that vaccine will come," the environment secretary told Sky News' Kay Burley.

"I know there's some hope there might be something as quickly as Christmas but that's not by any means a certainty.

"And it's also the case, it always is with a vaccine, you don't know precisely what level of protection it will deliver. Some of them deliver full protection, some don't."

Ms Bingham's article came as a review of coronavirus vaccine research called for a standardised approach to assessing the effectiveness of all potential COVID-19 inoculations.

Publishing their conclusions in The Lancet Infectious Diseases journal, researchers from the University of Oxford said a meaningful comparison of different candidates is required to ensure only the most effective vaccines are deployed.

Dr Susanne Hodgson, of the University of Oxford, who is the lead author of the review, said: "It is unlikely that we will see a single vaccine winner in the race against Covid-19.

"Different technologies will bring distinct advantages that are relevant in different situations, and additionally, there will probably be challenges with manufacturing and supplying a single vaccine at the scale required, at least initially.

"Taking a standardised approach to measuring the success of vaccines in clinical trials will be important for making meaningful comparisons, so that the most effective candidates can be taken forward for wider use."

There are more than 200 vaccine candidates in development around the world, with 44 in clinical trials.

Of the 44, nine are in the phase three stage of clinical evaluation and are being given to thousands of people to confirm safety and effectiveness.

https://news.sky.com/story/coronavirus-first-covid-vaccines-likely-to-be-imperfect-and-might-not-prevent-infection-says-taskforce-boss-12116593

Treatment with Zinc Associated with Reduced In-Hospital Mortality in COVID-19 Patients

Jennifer A. frontera, Joseph O. Rahimian, Shadi Yaghi, Mengling Liu, Ariane Lewis, Adam de Havenon, Shraddha Mainali, Joshua Huang, Erica Scher, Thomas Wisniewski, Andrea B. Troxel, Sharon Meropol, Laura J. Balcer, Steven L. Galetta

DOI: https://doi.org/10.21203/rs.3.rs-94509/v1

PDF: https://www.researchsquare.com/article/rs-94509/v1.pdf

ABSTRACT:

Background: Zinc impairs replication of RNA viruses such as SARS-CoV-1, and may be effective against SARS-CoV-2. However, to achieve adequate intracellular zinc levels, administration with an ionophore, which increases intracellular zinc levels, may be necessary. We evaluated the impact of zinc with an ionophore (Zn+ionophore) on COVID-19 in-hospital mortality rates.

Methods: A multicenter cohort study was conducted of 3,473 adult hospitalized patients with reverse-transcriptase-polymerase-chain-reaction (RT-PCR) positive SARS-CoV-2 infection admitted to four New York City hospitals between March 10 through May 20, 2020. Exclusion criteria were: death or discharge within 24h, comfort-care status, clinical trial enrollment, treatment with an IL-6 inhibitor or remdesivir. Patients who received Zn+ionophore were compared to patients who did not using multivariable time-dependent cox proportional hazards models for time to in-hospital death adjusting for confounders including age, sex, race, BMI, diabetes, week of admission, hospital location, sequential organ failure assessment (SOFA) score, intubation, acute renal failure, neurological events, treatment with corticosteroids, azithromycin or lopinavir/ritonavir and the propensity score of receiving Zn+ionophore.  A sensitivity analysis was performed using a propensity score-matched cohort of patients who did or did not receive Zn+ionophore matched by age, sex and ventilator status.

Results: Among 3,473 patients (median age 64, 1947 [56%] male, 522 [15%] ventilated, 545[16%] died), 1,006 (29%) received Zn+ionophore. Zn+ionophore was associated with a 24% reduced risk of in-hospital mortality (12% of those who received Zn+ionophore died versus 17% who did not; adjusted Hazard Ratio [aHR] 0.76, 95% CI 0.60-0.96, P=0.023). More patients who received Zn+ionophore were discharged home (72% Zn+ionophore vs 67% no Zn+ionophore, P=0.003) Neither Zn nor the ionophore alone were associated with decreased mortality rates. Propensity score-matched sensitivity analysis (N=1356) validated these results (Zn+ionophore aHR for mortality 0.63, 95%CI 0.44-0.91, P=0.015). There were no significant interactions for Zn+ionophore with other COVID-19 specific medications.

Conclusions: Zinc with an ionophore was associated with increased rates of discharge home and a 24% reduced risk of in-hospital mortality among COVID-19 patients, while neither zinc alone nor the ionophore alone reduced mortality. Further randomized trials are warranted.

https://www.researchsquare.com/article/rs-94509/v1

Aldeyra Has 'Catalayst-Rich' 12 Months Ahead, Jefferies Says In Bullish Initiation

Shares of Aldeyra Therapeutics Inc ALDX 5.86%, a company focusing on immune-mediated diseases, are primed for further upside, according to a Jefferies analyst. 

The Aldeyra Analyst: Kelly Shi initiated coverage of Aldeyra shares with a Buy rating and $24 price target.

The Aldeyra Thesis: Aldeyra's lead asset reproxalap has substantial opportunity in ocular inflammatory dry eye disease and allergic conjunctivitis, Shi said in a Friday initiation note. 

With market dominant brands such as Allergan's Restasis and Novartis AG's NVS 0.03% Xiidra having pitfalls such as slow onset of drug action and a suboptimal patient experience, there is an unmet need in moderate-to-severe dry eye patients on chronic therapies, the analyst said.

Aldeyra's reproxalap has shown a differentiated product profile to date, suggesting commercial competitiveness if approved, she said. 

Two Phase 3 data releases in the first half of 2021 should serve as major catalysts, Shi said.

"Other progress from Aldeyra's immune-disease focused pipeline in rare ocular disorders, autoimmune diseases, oncology, and Covid set up a catalyst-rich 12 mos to offer further upside." 

https://www.benzinga.com/analyst-ratings/analyst-color/20/10/18146570/aldeyra-has-catalayst-rich-12-months-ahead-jefferies-says-in-bullish-initiation

Oregon may become first state to decriminalize hard drugs

• Besides casting their votes for the presidential election, voters in Oregon this week will decide on decriminalizing hard drugs via a ballot initiative called Measure 110.
• The bill would decriminalize personal possession of less than one gram of heroin or methamphetamine; two grams of cocaine; 12 grams of psilocybin mushrooms; 40 doses of LSD, oxycodone or methadone; and one gram or five pills of MDMA.
• Instead of being arrested, going to trial and facing possible jail time, users would have the option of paying $100 fines or attending new, free addiction recovery centers.
• The facilities would be funded by retail marijuana tax revenues collected by the state, which is in excess of $45M annually.
• Oregon was the first state in the U.S. to decriminalize marijuana possession in 1973, and later approved medical use in 1998 and recreational use in 2014.
• Oregon's measure is backed by the Oregon Nurses Association, the Oregon chapter of the American College of Physicians and the Oregon Academy of Family Physicians.
• Opponents include two dozen district attorneys, who have said the measure "recklessly decriminalizes possession of the most dangerous types of drugs (and) will lead to an increase in acceptability of dangerous drugs."
• Countries including Portugal, the Netherlands and Switzerland have already decriminalized possession of small amounts of hard drugs.
• https://seekingalpha.com/news/3629362-oregon-may-become-first-state-to-decriminalize-hard-drugs
  

Travelers to New York will need a negative COVID-19 test - Cuomo

• Doing away with the Tri-State Travel Advisory, Governor Andrew Cuomo is now requiring people coming to New York to test negative, with the exception of residents from the contiguous states of New Jersey, Connecticut and Pennsylvania.
• Travelers will be required to get tested for COVID-19 three days before arriving in the Empire State. They will then need to quarantine for three days once they arrive, and get tested again on the fourth day. Should the test come back negative, they could exit quarantine. If a person chooses not to get tested, they must quarantine for 14 days.
• New York residents returning from travel under 24 hours outside the state do not need to take a test before coming back, however, they must take a test after returning.
• It's still not clear how the measures will be strictly enforced, but according to data released Saturday by Johns Hopkins, the U.S. added 99,321 coronavirus cases and 1,030 deaths to its tally on Friday, as infections continued to climb across the nation.
• https://seekingalpha.com/news/3629349-travelers-to-new-york-will-need-negative-covidminus-19-test-cuomo
  

NOVO NORDISK Gets a Buy rating from Bernstein

In a research note published by Wimal Kapadia, Bernstein advises its customers to buy the stock. The target price is set at 460 versus 470 DKK.

https://www.marketscreener.com/quote/stock/NOVO-NORDISK-A-S-1412980/news/NOVO-NORDISK-Gets-a-Buy-rating-from-Bernstein-31655650/