On Behalf of the TeamHealth Emerging Infectious Disease Taskforce
Over the last four years each summer has been accompanied by a surge in COVID-19 cases and hospitalizations. This summer follows past patterns with COVID-19 case surges in Europe and the United States. In addition, as concerns grow regarding emerging types of influenza, the CDC has released new guidance on the use of Oseltamivir.
Summer 2024 SARS-CoV-2 Wastewater Detections
The national wastewater surveillance for SARS-CoV-2 detection surged from a level of viral activity of 1.36 on May 4, 2024, 24 to 6.29 by July 13, 2024. This viral activity continued to increase at the time of this writing. Detection of most respiratory viruses, including SARS-CoV-2, in wastewater, tends to precede clinical surges by a few weeks and persist for several weeks following decreases in clinical cases. However, we are still learning how it impacts and correlates with clinical conditions.
Summer 2024 COVID-19 Trends
- In late July, positive COVID-19 tests were at 12.6% nationally, an increase of 1.2% over the previous two weeks. In California, Nevada, Arizona, and Hawaii positive test rates are over 16%.
- In the United Kingdom with COVID-19 positive tests surging from 4% to 14% from March through the end of June.
- COVID-19-related emergency department (ED) visits are reported at 1.6% of all patients seen nationally. This is a percentage increase of 15.7 times from the previous week.
- The proportion of all patients admitted with COVID-19 nationally seems to have hit a peak during week 27 – ending July 6, 2024 – at 2.8%. Although data are incomplete, there is at the time of this production a definite downtrend in COVID-19 admitted patients. As noted previously, admission rates are age-related with individuals age 65 or older accounting for 12.6% of all COVID-19 admissions.
- The mortality rates for COVID-19 cases remain stable at around 0.9%. Most of these fatalities are in the age 65 and older cohort. This is an indicator that although there is a surge in the overall number of cases, there is no clinical evidence of enhanced mortality with the current SARS-CoV-2 variants.
SARS-CoV-2 Variants
The SARS-CoV-2 virus continues to evolve. At the time of this writing, all active variants are of the Omicron lineage. Omicron KP.3 accounts for 32.9% of variants with KP.3.1.1 at 17.7%, KP.2.3 at 12.8%, and another branch LB.1 at 10%.
Recently a deletion of a single amino acid on the SARS-CoV-2 spike protein – amino acid 31 in sequence – has been detected. This segment codes for a serine molecule on the end of the spike – which is now absent in the KP.3 and LB viral lineages.
This genetic loss is the so-called FLiRT or DeFLiRT deletion. Some virologists are suggesting that this altered spike protein may enhance the transmissibility of the FLiRT deleted variants. This is because many of the antibodies produced by COVID-19 vaccines, and naturally, use this serine molecule in the spike protein as an anchor point in binding and neutralization.
The antibodies however should retain most of their effectiveness as there are alternate binding locations. There is no evidence at this time that the FLiRT deletion alters pathogenicity.
These changes in the spike protein can be beneficial to the virus because almost all of the initial immune response against the virus is based on attacking the spike protein. Changing the spike makes these immune attacks less efficient and gives the virus an advantage of immune escape.
However, if the spike changes too much it won’t be able to bind to the ACE-2 receptors of the cell and cause infection. Nature plays a tedious balancing act between too much and too little change in the spike. The evidence thus far is that this amino acid deletion on the spike may confer some increased transmissibility, but probably not much.
Vaccines and Variants
Our current mRNA vaccines based on the XBB.1.5 variant are likely to be effective against the KP and LB variant lineages. However, we will probably see a modified mRNA vaccine released this fall based more on the KP.2 antigens. This updated vaccine – if released – will have its highest impact in protecting elderly and immune-suppressed individuals.
Antivirals and New Variants
Paxlovid™ and Lagevrio – if used – should not lose appreciable efficacy against the KP.2 or LP-related variants. This is based on an analysis of their mechanisms of action as no in vitro or in vivo testing has been done with these variants as of yet.
COVID-19 Changes in Symptoms
Another key function of the spike protein of SARS-CoV-2 is its ability to enter a particular cell and infect it. The spike protein of SARS-CoV-2 first binds to the ACE-2 receptor protein of the respiratory cell to enter and infect that cell. ACE-2 receptors exist in various densities and various structures on different types of cells in the body. The SARS-CoV-2 spike protein will preferentially bind to the ACE-2 receptor it is most adapted for.
As changes in the spike protein occur, such as the FLiRT deletion of serine, this can alter the affinity of that spike protein for a particular type of ACE-2 receptor. Initially, SARS-CoV-2 spikes were configured to bind mostly with upper respiratory cells. That accounted for the preponderance of respiratory symptoms.
As the spike changes, ACE-2 receptors of other cells are becoming at least as likely if not more to bind to the new viral spike. For example, ACE-2 receptors in cells of the gastrointestinal lining are now being bound at a much higher frequency by the newer Omicron variants than with prior variants. As such, a higher incidence of gastrointestinal symptoms in COVID-19 cases is evident.
Seasonal Variation of COVID-19
COVID-19 infections continue to intermittently surge in populations globally. Although most respiratory viruses such as influenza and respiratory syncytial virus (RSV) have taken on distinct seasonal patterns – surging primarily during the winter months – SARS-CoV-2 has not. This makes predicting when the next surge of COVID-19 will occur, problematic.
Why Do Viruses Develop Seasonality?
It is thought that most respiratory viruses surge in the winter months due to imposed environmental conditions that enhance transmission. These include crowding together inside, heated dry air impacting airway epithelium, seasonal alterations in immunity, and hormonal changes due to decreased natural illumination. It may be that SARS-CoV-2 is simply less impacted by these factors.
What Has Changed Environmentally?
Environments have recently been much hotter in most locations globally than in the past. This is resulting in fewer outside large venue events, and more crowded inside air-conditioned events. Similar to winter heating, condenser-based air conditioning significantly dries the air and respiratory epithelium making viral infection more likely.
Crowding always has the effect of enhancing the spread of communicable airway viruses. People are also less likely to follow public health measures such as masking, social distancing, and hand washing during the hot summer. Additionally, condenser-based air-conditioning has been noted to increase airborne viral particles in closed venues.
These points may be part of the reasons the Southern and Southwestern United States is seeing an enhanced number of COVID-19 cases.
Or these “summer surges” of COVID-19 could be due to other factors that remain unidentified. We have to recall that humans have only been dealing with this virus since 2019. We both have a lot to “learn” about each other. SARS-CoV-2 is endemic in the human population, but it is still seeking a more stable relationship with us.
Healthcare Provider Return-to-Work Guidance
Another important question currently is about healthcare provider (HCP) return-to-work (RTW) post-COVID-19 guidance. The approaches used during the peak of the pandemic for HCP RTW probably do not make sense given the current changes in COVID-19 prevalence and pathogenicity. No additional guidance from the CDC or other organizations has been delivered since the emergence and dominance of SARS-CoV-2 Omicron lineages.
As such, healthcare institutions and providers have increasingly had to rely on consensus practices along with any new science when making local HCP RTW recommendations.
In summary, the following can be stated about HCP RTW guidance.
- Members of the general population can go back to work 24 hours after fever subsides.
- The last general guidance from the CDC on HCP RTW recommends seven days after symptom onset and at least 24 hours since the last fever with improving symptoms. There are other caveats to this recommendation as well.
- The seven-day guidance is based on previous disease prevalence and virulence information and has not been updated since September of 2022.
- Many healthcare facilities have already modified their guidelines for HCP RTW using a stratified approach to follow similar patterns as the general population EXCEPT when the HCP routinely cares for high-risk patients – age≥65 and/or immunocompromised.
Oseltamivir for Treatment and Prophylaxis of HPAI A(H5N1) and Other Influenza
On July 22, 2024, the CDC released a revision of the Emergency Use Instructions (EUI) for using Oseltamivir in the setting of certain active Influenza infections. In addition, they have added guidance for the use of this antiviral in Post Exposure Prophylaxis (PEP) for various high-risk types of Influenza A.
These changes include Oseltamivir use for any Influenza A viruses that are classified as “pandemic” by the WHO or CDC or those classified as “Novel Influenza A viruses with pandemic potential.” Importantly this now includes Highly Pathogenic Avian Influenza (HPAI) A(H5N1) exposures.
What are the Major Changes for Oseltamivir?
The CDC EUI provides information on the recommended uses of Oseltamivir that differ from or go beyond the previous package insert in the following areas:
- Initiation of treatment may be started after 48 hours from symptom onset.
- Treatment of severely ill hospitalized patients, including longer courses of treatment (e.g., 10 days) maybe used based on clinical judgment.
- A higher total daily dose with a flexible duration for PEP is now recommended. The EUI-recommended dosing regimen in most cases is twice daily for five or 10 days in asymptomatic close contacts of a confirmed or probable novel influenza A case or asymptomatic persons exposed to animals infected with HPAI A(H5N1) or other novel Influenza A viruses.
- Treatment of term neonates under two weeks of age may be considered.
- PEP in neonates and infants less than one year of age may be considered.
- Treatment and PEP dosing regimens for preterm neonates and infants are provided.
The full EUI guidance is provided in the references for this post.
Closing
The SARS-CoV-2 virus continues to cause severe cases of COVID-19 globally. Both Europe and the United States have reported a summer surge in positive tests and admissions. Fortunately, the mortality rates remain stable indicating that the pathogenicity of the virus has not significantly changed. Unfortunately, the high mortality rates for older patients remain.
Although updated COVID-19 vaccines are likely to be released this fall, the current Omicron XBB. 1.5-based mRNA vaccines remain effective. Unvaccinated elderly or other high-risk individuals should not wait for the updated vaccines but rather receive a current COVID-19 vaccine series now.
Although the SARS-CoV-2 virus continues to evolve, recent changes to the spike protein – the co-called FLiRT deletion – is not likely to impact either vaccine immunity or the efficacy of available antivirals.
Influenza viruses also continue to evolve. New guidance from the CDC enhances the use of Oseltamivir in the setting of dangerous and novel influenza virus infections. The guidance also expands the use of this antiviral in PEP.
As always, detailed information on these topics is available in the references for this post.