The global deaths due to COVID-19 surpassed 4 million.  The United States has made tremendous progress in the fight against COVID-19. As of July 15, 67.8% of the U.S. population had received at least one dose of a COVID-19 vaccine. At the same time, work remains to be done to reach freedom from the virus. COVID-19 cases are increasing in some parts of the country, and on June 23, 2021, the United States surpassed 600,000 total deaths from COVID-19. Additionally, vaccination rates among people ages 18-29 remain low, and a recent CDC report showed intent to get vaccinated was lowest among adults ages 18-39. Unvaccinated people are at serious risk of getting the virus and spreading it to others. Often within these groups, underlying co-morbidities increase the risk of severe disease in this population.

Nationwide, 58% of new cases are Delta variant. In 47 states and District of Colombia: case numbers are surging. According to Bloomberg, Los Angeles County, home to 10 million Californians, added more than 1,000 new cases for a seventh straight day. With the transmission rate reaching close to a “high” level after hitting a “substantial” pace in a short period of time, Los Angeles is set to require masks be worn indoors again.

According to WHO: Deaths climbed last week after 9 straight weeks of decline; 55,000 lives lost, 3% increase from previous week.

Newly confirmed cases per day have doubled over the past 2 weeks in the U.S.

Vaccine Update:

More than 3.51 billion doses (22.9% of the world population) have been administered across 180 countries, according to data collected by Bloomberg. The latest rate was roughly 30.5 million doses a day.  Since COVID-19 vaccine distribution began in the US on December 14, more than 335 million doses have been administered; fully vaccinating over 48.2% of the total U.S. population.  In the last week of June, an average of 875,452 doses per day were administered.

Multiple studies are indicating that the existing vaccines are performing well with nearly 99% of hospitalizations and deaths from COVID-19 cases occurring in unvaccinated individuals. Furthermore, multiple studies are demonstrating that the immune responses are likely long lasting, potentially years of protection. Moreover, the mRNA vaccines are working well against emerging variants.  Some protection has been lost (66% efficacy) observed with a single shot of the J&J vaccine.  Discussions are underway to expand to two doses with the J&J vaccine if needed to protect against variants.  We may need booster vaccinations in the future, maybe something similar to the annual flu shot as companies periodically update their vaccines to match the prevalent coronavirus variants.  However, no booster recommendations have been recommended to date.

Continued monitoring of the vaccine safety is underway.  Large numbers of the population have been vaccinated with many reports of potential adverse events.  To date there are a few reports of rare vaccinated associated adverse events. Most are minor and consistent with other vaccinations.  Most recently, the CDC has added the potential for chest pain (myocarditis) following vaccination (up to four days) been added to the list of potential known reactions to the mRNA vaccines.  These events are extremely rare, have typically been short in duration, and most do not require medical intervention.  On a daily basis, multiple organizations continue to monitor for any adverse events due to the vaccine.  To date, the evidence demonstrates the benefit of vaccination far exceeds any known adverse events.

Pfizer/BioNTech mRNA vaccine is safe and highly effective (>95%) in adolescents 12 to 15 years of age in both large clinical trials and real-world observational studies. In the clinical trial efficacy was 100%. Moreover there was some protection observed after one dose in this population.  Adverse events were similar to those in older patients, mainly transient fever and injection site pain and occasionally lymphadenopathy. No events related to thrombosis, anaphylaxis, or death were reported.

For those with weakened immune systems, COVID-19 vaccines don’t mean the end of the pandemic.  For those that are in this group, there is no good method to determine if you are protected.  Serology test are not recommended.  Although COVID-19 vaccines work incredibly well for the vast majority of people, roughly 10 million Americans whose immune systems are compromised because of medication or disease may not be well protected. The impact on solid organ transplant patients taking drugs to reject of the transplanted organ. A study from Johns Hopkins University School of Medicine found that only 17% of transplant recipients had antibodies after their first dose of a COVID-19 vaccine, with an additional 35% responding after two shots. Studies are underway to better understand how to protect this special population.

Virus Variants

If a virus had a job description, it would be infect and find new cells which will spill over to other people to infect. When doing this job, viruses make mistakes, random genetic errors and on rare occasion, this change is beneficial.  With one virus entry into a single cell, thousands to millions of errors can occur within one infected cell. With millions of cells infected in a person, the exponential number of viruses made each day places a high probability on variants being generated. The probability is further compounded with 100,000 to 500,000 new cases every day. This is evolution in action and variants are expected to emerge.   Since the start of the pandemic, there have been thousands of document coronavirus mutations. Genetic variants of SARS-CoV-2 have been emerging and circulating around the world throughout the COVID-19 pandemic.  Viral mutations and variants in the United States are routinely monitored (about 6% of the total number of people infected) through sequence-based surveillance, laboratory studies, and epidemiological investigations.  International partners are using similar approaches to understand how the virus is changing.  A US government interagency group developed a Variant Classification scheme that defines three classes of SARS-CoV-2 variants:

• • Variant of Interest– A variant with specific genetic markers that have been associated with changes to receptor binding, reduced neutralization by antibodies generated against previous infection or vaccination, reduced efficacy of treatments, potential diagnostic impact, or predicted increase in transmissibility or disease severity.
  • Variant of Concern– A variant for which there is evidence of an increase in transmissibility, more severe disease (e.g.,  increased hospitalizations or deaths), significant reduction in neutralization by antibodies generated during previous infection or vaccination, reduced effectiveness of treatments or vaccines, or diagnostic detection failures.
  • Variant of High Consequence– A variant of high consequence has clear evidence that prevention measures or medical countermeasures (MCMs) have significantly reduced effectiveness relative to previously circulating variants.

  Multiple VOIs are being tracked worldwide.  The B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.427 (Epsilon), B.1.429 (Epsilon), and B.1.617.2 (Delta) variants circulating in the United States are classified as variants of concern as of late June 2021.  To date, no variants of high consequence have been identified in the United States.   Currently there are over 50 different COVID variants being tracked that are not listed in the categories above.

   

  Delta variant (India variant)

  The COVID-19 delta variant originally discovered in India is now spreading around the world (over 80 countries have detected the variant), becoming the dominant strain in some countries, such as the U.K., and likely to become so in others.  The CDC has added the variant to the list of “variants of concern”.  The variant now makes up 20% of all new cases in the United States, up from 10% last week. Studies have shown the variant is even more transmissible than other variants (up to 60% more transmissible than the “alpha” variant (UK variant).  Despite being the first to observe the benefits of vaccination, increased cases in Israel are being observed and may be due to the Delta variant(s) and inability to vaccinate 12-15 year olds (n = 600,000) in a timely manner.  Seven-day average of new cases grew from 25 to 72.  No new deaths reported and only 26 of the 729 active cases have been hospitalized.  Reports that 40-50% of new cases were vaccinated. Delta variant appears to be provoking a different range of symptoms but more studies are needed to better understand any differences.

  Delta-like variants are also being detected.  There are further mutations being detected that point to the Delta variant as the parent virus which has further changed during the past few months. Efforts are underway to understand these changes and their impact on transmission.

  Delta Plus Variant

  New and slightly changed version of the highly contagious Delta variant is spreading in the UK, US, and India.  The US has sequenced and confirmed the most number of cases 83 (UK 14, India 40). Other cases have been reported in Canada, Japan, Nepal, Poland, Portugal, Russia, Switzerland, and Turkey. The variant is called B1.617.2.1 or AY.1 or Delta Plus.  It was reported by Public Health England on June 11. However, it was sequenced and identified as early as April 26 and likely has been co-circulating with the Delta variant.  Overall about 200 cases have been identified in 11 countries.  Little is known about the variant, for example if the variant is more or less transmissible than the parent Delta variant.  The Delta Plus variant carries an additional mutation called K417N that the Delta variant does not have in it’s spike protein. The change has been seen in other variants (as far back as Qatar in March 2020) including the Beta variant (South African).  That change has been associated with immune escape features but not necessarily transmission enhancement.  A combination of transmissibility increase and immune escape from existing vaccine-induced or naturally induced immunity will require a booster vaccination campaign.  Estimates are that this will be required as early as the fall or up to 2 years from now.

  Lambda variant

  Recently, the WHO added another COVID mutation, the lambda variant, to its list of variants of interest.  The lambda variant has multiple mutations in the spike protein that could have an impact on its transmissibility, but more studies are needed to fully understand the mutations. The lambda variant has been detected by scientists in South America, including in Chile, Peru, Ecuador and Argentina, thanks to increased genomic surveillance.  In Peru, where it was first identified, the lambda variant now accounts for 82% of new infections. On June 29, 2021 it was detected in the UK in six patient samples. All of these cases are linked to international travel.

  How best to protect yourself and the community

  Viruses mutate when they infect us.  They cannot mutate if they cannot replicate in our cells.  Public health measures and vaccines prevent infection and spread of the virus. The only way to completely stop the virus is to vaccinate to reach herd immunity at global scale, while maintaining behaviors that will reduce transmission and the rise of a variant of high consequence.  Vaccination to achieve herd immunity for the US and world is estimated between 70%-85%.  We are now in a life-and-death contest between vaccination and public health measures verses the virus. The virus is winning this phase of the contest.  Variants and potential future variants threaten to overcome our vaccines and therapeutics.  The existing variants will likely ignite local outbreaks where public health measures are ignored and vaccination rates are low. In time, higher vaccination and prudent public health measures should limit the Covid-19 transmission around the world. Social distancing, mask wearing and following prudent public health practices remains an important component of the defense against COVID-19 and emerging variants. Unvaccinated people, including children >5 years of age, should still wear masks indoors at public events, according to the CDC. Masks on public transportation and by many businesses and state or local governments have utility at protecting us.  Since vaccine rates are low, vaccinations alone won’t significantly lower or stop community transmission.   People need to consider their risk and continue to use masks consistently and physical distance in crowded situations. Moreover, with the rise of variants, asymptomatic infection may be possible in vaccinated individuals.  Masking and social distancing in specific public situations may be important to protect yourself and your immediate community. In short, vaccinated individuals can continue to reduce transmission and protect themselves by masking and social distancing.COVID messaging from WHO, CDC, and state and local health officials has become confusing. Risk of infection remains for all, even vaccinated individuals. Transmission and the goal of the virus, to find more people to infect, means that the path forward is not about individualism but about community.