Kevin Kavanagh, MD

As the United States emerges from the COVID-19 pandemic, nobody really wants to hear (and few media outlets report) that the rapid emergence of immune escape COVID-19 variants pose a clear and present danger of a setback. Over three weeks, the percentage of genomic testing which was comprised of the Indian Double Mutation Variant, or Delta Variant, jumped from 1% to 7% in the U.S. The data was derived from 

, a website operated by Scripps Research and funded by the NIC, the Centers for Disease Control and Prevention (CDC) and National Center for Data for Health. (The data are obtained from the World Health Organization’s (WHO) Global Influenza Surveillance and Response System (GISRS) Initiative.) The site contains the most up-to-date information and has state specific data. The site also reports that as of May 27 the Brazilian or Gamma Variant currently comprises 14% of the genomic sequenced specimens in the U.S.

There has been little coverage by the U.S. news media about these emerging variants in the U.S. In the United Kingdom, despite having less than twenty COVID-19 deaths per day, there has been consideration of delaying fully reopening. In regions where the Delta Variant is spreading, advisements have been made to continue to meet outdoors if possible, minimize travel, work from home, abide by social distancing, and for the entire population in the affected region to be tested 

. The strategy of frequent and blanket testing of the whole population is in stark contrast to the lackadaisical approach the U.S. has undertaken regarding these variants.

The best defense against immune escape variants is to become fully vaccinated. It requires 2 doses of the Pfizer or Moderna vaccine to provide protection. Remember, the vaccines were based on the wild type of virus and not the immune escape variants, so the plan is to boost your antibodies and immune response to a very high level.

Immunity from a previous infection may not provide protection from reinfection with an immune escape variant. In the city of Manaus, Brazil, a second wave by the Gamma Variant crushed the city after it was felt to have 

. Studying blood donations, researchers have recently reported that 1 in 6 infected in Manaus with the Gamma Variant were previously infected with the wild type or 

Thus, even if you have already had COVID-19 you still should be vaccinated. There is ongoing research to determine if a single vaccine dose 

, but until this is known for sure, it is recommended that a full vaccination protocol is followed. It has been shown that two doses of a mRNA vaccine will “rapidly induce a much stronger and broader Ab response than 

. And initial reports have found that two doses of the mRNA vaccine offers protection against both the 

Finally, we are flying blind in the U.S. when it comes to the variants. The samples which the U.S. sequences are often from high-risk patients and not necessarily samples from the community, to track spread. Over the last 60 days, Outbreak.info has reported 5800 viral sequences out of approximately 3 million COVID-19 infections in the U.S. This represents only 0.2% of all cases. We should be sampling at least 5% of all COVID-19 cases to adequately track the spread and emergence of variants.

We also must not set the measure of public health success at survival. Too many patients with COVID-19 are developing long-hauler’s syndrome. This has even been reported to occur in 10% to 30% of patients with mild to moderate disease. And although our current mRNA vaccines can prevent the majority of severe COVID-19 cases and deaths caused by immune escape variants, it is unknown if they will prevent long COVID from developing in those who have mild to moderate infections.

As long as the immune escape variants are on the rise in the U.S. and less than half of our population is fully vaccinated, the best advice is to continue public health strategies. Similar to the U.K., this could be a regional advisement, but unfortunately, we are not sequencing nearly enough infections to accurately track the spread of these variants.

And above all, we need to have everyone become vaccinated. That is the best way to stop the spread of the virus and help mitigate the possibility of a truly vaccine evading mutation from occurring.

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As long as the immune escape variants are on the rise in the U.S. and less than half of our population is fully vaccinated, the best advice is to continue public health strategies.

Not Quite Over Yet: COVID-19 Variants on Rise in the U.S.

The Centers for Disease Control and Prevention’s abrupt reversal regarding public masking on May 13, caught all by 

. Not only was it entirely unexpected but it seemed to contradict information generated by the CDC just a few days earlier. On May 7, the CDC affirmed that the SARS-CoV-2 virus is 

, a finding which should have been known over a year ago from numerous case reports involving, cruise ships, restaurants and choirs. As early as July 2020, hundreds of scientists published a letter in 

 to raise awareness of SARS-CoV-2 aerosolization and to encourage strategies to interrupt 

Aerosolized spread makes the wearing of masks an imperative in the control of community spread. In an informal survey of 723 epidemiologists that was conducted between April 28 and May 10, 2021, 80% felt that masks would need to be worn indoors for 

2021, a modeling study was published in the CDC’s 

 that concluded that “an accelerated decline in NPI (public health policies, such as physical distancing and masking) adherence (which encapsulates NPI mandates and population behavior) was shown to undermine vaccination-related gains over the subsequent 2–3 months and, in combination with increased transmissibility of new variants, could lead to surges in cases, hospitalizations, and 

The day before the publication of the modeling study’s dire warning, the CDC abruptly removed mask and physical distancing requirements for those who are 

. Unfortunately, this will probably also result in many unvaccinated individuals unmasking.

There are two major concerns. First is too few of the United States’ population have become fully vaccinated. In the United States, only 37% are fully vaccinated, with 48% receiving at least 

. And the rates vary widely between communities, creating pockets that are literally sitting ducks for a major viral outbreak. For example, Kentucky has 36% of its population fully vaccinated but the rates vary widely from a high of 57% in Woodford County to a low of 21% in McCreary and 

Second, there are major variants abroad which are more infectious and may at least partially evade immunity. For example, in Southern India, the N440K immune escape variant is reported to be 10 times more infectious and produces 10 times the viral load than the D614G variant (the dominate 2020 variant in the 

). N440K also has the ability to avoid several monoclonal antibody treatments (C135 and REGN10987) and cause 

Another problematic variant is expected to replace the N44K variant, the Indian (B.1.617) “double mutation” variant. The double mutation variant is named after two of its major mutations (L452R and E484Q) being a combination of those found in the Californian variant and a similar mutation found in the South African 

. The double mutation Variant is also an immune escape variant. It can cause reinfections, along with evading vaccine induced antibodies with “

.” It has a strong foothold in England and is predicted to become the 

. Initial reports are that the double mutation variant is more infectious than the UK variant (B117) and the UK Variant is 70% more infectious and more lethal than the wild type of virus.

Because of the dangers the Indian double mutation variant poses, the World Health Organizatoin has classified it as a 

. The CDC defines a variant of concern as having the attributes of a variant of 

•	Evidence of impact on diagnostics, treatments, or vaccines.
        1.	Widespread interference with diagnostic test targets.
        2.	Evidence of substantially decreased susceptibility to one or more class of therapies.
        3.	Evidence of significant decreased neutralization by antibodies generated during previous infection or vaccination.
        4.	Evidence of reduced vaccine-induced protection from severe disease.
•	Evidence of increased transmissibility.
•	Evidence of increased disease severity.


In view of the above, a more cautious approach would be to wait before unmasking and throwing social distancing to the wind for solid data to be generated in the UK. If just over a third of our population is 

 and the US is invaded by a variant which has twice the infectivity and is more lethal than the last year’s virus (G614D), then the U.S. could be facing an even greater surge in cases, hospitalizations and deaths. To make matters worse, the U.S. has only a rudimentary genomic surveillance detection system for variants. Similar to what happened in the beginning of the pandemic, immune escape variants may spread in the community undetected until it is too late to prevent a major outbreak.

For those vaccinated, laboratory data indicates that there will be some protection with severe cases and deaths being less likely to occur. However, there is little data on the risks of long COVID-19 which can afflict 10% to 30% of individuals with mild to 

. And if a vaccinated individual can develop asymptomatic, mild to moderate infection from an immune escape variant, it is intuitive that they might also spread the virus. And, if the virus spreads, it can also mutate.

 written by Madhukar Pai, an Indian doctor and epidemiologist, and Manu Prakash, summed up the causative factors of India’s current crisis, but may also be a stark warning for the U.S.: “The devastating second wave in India is the result of a perfect storm: a failure to plan for a second wave; premature relaxation of public health measures; large gatherings; insufficient vaccination coverage; and newer variants such as B.1.1.7 and B.1.617 that are highly transmissible and potentially more severe.”

Those of you who advocate reopening at the peril of those who are vaccine hesitant—letting nature decide the fate of the ill-informed—need to remember that survival is not the same as recovery. Many will develop debilitating long COVID, enacting a societal legacy of disregard for humanity, which will impair our health care system for decades to come.

Let’s not be cavalier in our approach to a return to a new normal. Let’s be smart and cautious. Continued masking and social distancing for a few months, possibly just a few weeks, is a small price to pay to assure the safety of our nation.

Those of you who advocate reopening at the peril of those who are vaccine hesitant—letting nature decide the fate of the ill-informed—need to remember that survival is not the same as recovery.

Viewpoint: CDC Might Help COVID-19 Make a Comeback in U.S.

New estimates released this week that uses excess death data collected by the Institute of Health Metrics and Evaluation (IHME) at the University of Washington, and says that 

 people in the United States died from COVID-19, not the 574,043 deaths that have officially been reported.The toll of this pandemic in both deaths and chronic long-hauler disability makes it imperative that we invest the needed resources to stop this virus.

Infection preventionists need to stress the importance of aerosolization with increased recommendations for N-95 masks and we all need to realize that a prerequisite of reopening a business, school or public venue should be safe ventilation with an increased number of complete air exchanges along with air sanitization.

The new death estimates come as the Centers for Disease Control and Prevention (CDC) yesterday took a major step by clearly articulating three principal modes for 

“The principal mode by which people are infected with SARS-CoV-2 (the virus that causes COVID-19) is through exposure to respiratory fluids carrying infectious virus. Exposure occurs in three principal ways: (1) inhalation of very fine respiratory droplets and aerosol particles, (2) deposition of respiratory droplets and particles on exposed mucous membranes in the mouth, nose, or eye by direct splashes and sprays, and (3) touching mucous membranes with hands that have been soiled either directly by virus-containing respiratory fluids or indirectly by touching surfaces with 

The reason outdoors is 20 times safer than indoors is because aerosols rapidly dissipate with the outdoor air circulation. However, large droplet spread within 6 feet can still occur.

Nowhere is safe inside a poorly ventilated building. The six-foot rule 

N95 masks are of paramount importance for all, especially frontline workers.

Spread also occurs through the eyes. Googles, as commonly worn in other countries, should also be worn, especially in high-risk settings.

Aerosolization of SARS-CoV-2 (the virus which causes COVID-19) is one of its major mechanisms of spread. 

 first covered this topic on April 3, 2020 with the virus spreading rapidly throughout a church choir in 

. Most recently, on March 4, 2021, we again stressed the importance of aerosolization of SARS-CoV-2 in indoor settings and how this is a major 

. This position is supported by a growing number of scientists. The science behind it is sound.

The Proceedings of the National Academy of Sciences reported that, despite being a small droplet, particles up to 100 micros can aerosolize. Viruses in these smaller droplets can survive and float in the air with a half-life of 1.1 hours. And that “These aerosols and droplets are produced by breathing, talking, and coughing, with talking associated with aerosols and the fast-settling droplets with 

Because of the above, on March 4, 2021, we advised that “the CDC needs to articulate firm and harmonized advisements which are consistent across all materials, recommendations and webpages.”

The mindset that you are safe, if you wear a cotton mask and are 6 feet away from someone needs to change. It is not true. SARS-CoV-2 is airborne. And as the third principal mechanism of spread necessitates, we still need to be vigilant regarding contaminated surfaces and wash our hands.

The small viral particle size of 0.1 micron could potentially defeat an N95 mask. However, within as they enter the mask, they are blocked and captured with electrostatic forces and Brownian motion which causes them to collide with and stick to the 

. Thus, it is best to wear an N95 mask. A multiple layered, well-fitted cotton or cloth mask will also afford some protection. Cloth masks are felt to be key in providing good community health and driving the SARS-C0V-2 R0 (pronounced R naught) to less than one; slowing, then stopping the spread of the virus. However, cloth masks may not provide adequate protection for individuals in a high-risk setting. I still do eat indoors at restaurants. As I have stated: “Nowhere is safe in poorly ventilated buildings.”

The CDC’s website also states that spread can be mitigated by “… physical distancing, community use of well-fitting masks (e.g., barrier face coverings, procedure/surgical masks), adequate ventilation, and avoidance of crowded indoor spaces. These methods will reduce transmission both from inhalation of virus and deposition of virus on exposed mucous membranes. Transmission through soiled hands and surfaces can be prevented by practicing good hand hygiene and by environmental cleaning.”

Infection preventionists need to stress the importance of aerosolization with increased recommendations for N-95 masks and we all need to realize that a prerequisite of reopening a business, school or public venue should be safe ventilation.

COVID-19 Model Says 905,289 Died of the Disease in U.S.

One of the most challenging tasks that infection preventionists (IPs) have is the encouragement of patients to follow effective control strategies. There is abundant mixed messaging. Last year, we had the federal government advising individuals to wear masks while the White House blatantly ignored this advice. This year, as pointed out by CNN, the federal government is currently advising vaccinated individuals that they no longer need to wear masks outdoors at small gatherings but President Biden and the White House staff seem to be wearing them everywhere. What gives? No wonder everyone is confused.

Countries such as India and Brazil have adopted the United States’ laissez-faire approach to COVID-19 and are now suffering a similar but far worse fate, having a fragile health care infrastructure and only a fraction of available vaccines.

But it is in these countries where the United States’ conspiracy theories break down and are even shown to be blatantly false. These countries have confirmed many of the assertions made by 

 earlier last year and IPs can use these valuable lessons to help educate the public.

: The pandemic is not a hoax. Anyone now can go on the foreign news services and see the devastation in India, from the piles of empty oxygen tanks to the overflowing makeshift crematoriums. It is easy for some to discount statistics, but not these horrific pictures.

: Herd immunity without a vaccine is not an option. The devastation’s case count and body toll in India has no end in sight, and no one is effectively counting. Patients have been turned away from overflowing facilities and testing infrastructure has collapsed. Unfortunately, the situation is still getting worse, and cases are skyrocketing. Attempts to achieve herd immunity carry too heavy a price and affords the virus ample opportunity to mutate. India has already cultivated a “double mutation” (B.1.617) variant which possesses two very worrisome spike 

, making it more infectious and capable of 

. With the virus ever mutating and large segments of the public vaccine adverse, many experts now believe we will never truly reach herd immunity in the 

: Hydroxychloroquine does not work. One of the prevalent misinformation campaigns involves around countries with high rates of malaria had low rates of COVID-19. The theory was that large segments of the public were taking hydroxychloroquine as a prophylaxis for malaria. This theory was widely circulated despite having multiple negative randomized controlled trials being not able to demonstrate hydroxychloroquine effectiveness in 

. India serves as a testament to the fallacy of this assertion.

: Large outdoor gatherings can spread the virus. Similar to the US, India had very large outdoor gatherings during the pandemic where Individuals were packed together in large political and 

. Insanity is doing the same thing multiple times and expecting a different result. That is what I fear is happening here. Yes, outdoors is safer than indoors, but not in crowded conditions. Both are dangerous.

: The pandemic is a world problem. Controlling the pandemic in just one country is highly problematic. With abundant readily accessible means of travel, the virus can easily enter a country being carried by asymptomatic individuals seeking a safe haven from the devastation of COVID-19. Snuffing out variants as they arise in foreign countries as opposed to on our soil is preferable. We adopted this strategy with international terrorism but for viruses we became isolationists with massive reductions in the CDC’s 

. We need to increase funding for both supplies and boots on the ground in foreign countries with dangerous emerging pathogens.

: The virus rules. Political posturing, repeated denials and displays of hubris will not stop this virus. It is a relentless pathogen which is out to win. No amount of fudging case definitions with requiring a positive test or not counting deaths from COVID-19 heart and kidney disease can cover up the enormity of the pandemic.

So, what should we advise with all the mixed messaging? Recently the CDC has stated one can exercise outdoors without a mask, with your household. I am not sure this helps much, since I assumed you could do this anyway, even indoors. The not needing to wear a mask outdoors in small gatherings but having to wear one in large gatherings is confusing for individuals. First of all, the size of the gathering is not defined. This appears to be based more upon what is safe for the community not safety for the individual. And with the new variants, we really do not know what precautions are necessary to prevent spread.

What we do know is that SARS-CoV-2 spreads by both droplet and 

 Most policymakers have only focused on droplet spread. Indoors, researchers at MIT have published in the 

Proceedings of the National Academies of Science

 that because of aerosolization, no one can be truly safe in an indoor setting with poor ventilation. Sixty feet offers no better protection 

. Outdoors, aerosolized particles rapidly dissipate, making it safer, up to 

. But droplet spread (within 6 feet) can still readily occur.

Thus, policymakers have falsely equated outdoor safety, produced by the rapid dissipation of aerosols, with safety from droplets and have ill-advised not wearing masks at some outdoor events. This may be effective in suppressing community spread, but it will not afford adequate protection for the individual.

Real life advice which I would give: Avoid indoor settings and if you have to go inside, wear a mask; outdoors stay at least 6 feet away from others and wear a mask if you want maximum assurance of not catching COVID-19. With the new immunity avoiding variants, vaccinations may provide protection from severe disease and death; and will help but not necessarily prevent infections. Survival is a low bar for community health. Ten to thirty percent of mildly affected individuals can develop long-haulers 

. And, it must be remembered that the more we spread the virus, even asymptomatically, the more it will mutate.

I believe that if we all would have followed public health strategies last year, we would be largely out of the pandemic and suppressing minor outbreaks with case tracking. With the emerging immunity avoiding variants and the high rate of SARS-CoV-2 in our population, the best advice is for all of us is to become vaccinated, wear a mask, avoid indoor settings and socially distance from others not in your households.

What happens in India, or anywhere else in the world, doesn't stay there. The longer COVID-19 hangs around, the more chance it has of mutating into a variant that the vaccines won't stop.

Kevin Kavanagh, MD

Articles

Not Quite Over Yet: COVID-19 Variants on Rise in the U.S.

Viewpoint: CDC Might Help COVID-19 Make a Comeback in U.S.

COVID-19 Model Says 905,289 Died of the Disease in U.S.

Infection Preventionists Must Ward Off a COVID Comeback