The 2020-2023 Tridemics of COVID, Influenza, and RSV required all medical professionals to keep up to date with updated legitimate scientific information and with public health/ I.D. experts from whom they can get appropriate information.  The collateral epidemic is one of misinformation (and nefarious disinformation), accompanied by an increasing distrust in medical science (especially public health) and our various healthcare professionals. We all must work hard to remedy this distrust.

A Study estimates 6-times-higher odds of COVID in households amid Omicron

The odds of SARS-CoV-2 infection were 6.2 times greater among household contacts during the Omicron variant wave than during periods dominated by other strains, with rates even higher in children, estimates a study released June 21, 2023, in the CDC’s Emerging Infectious Diseases.

Findings showed COVID-19 infection rates during Omicron 2022-2023 were 35.0% for household contacts and 15.1% for non-household contacts. After adjustment for potential confounding factors, the odds of infection were 6.2 higher among household contacts and 3.6 times greater among other contacts amid Omicron than during the prevariant period.

The WHO & CDC are closely watching some 2023 newer Omicron sub-variants like XBB 1.16, 1.9, 2.3, 1.5, 1.16 (dubbed in the EU as EU1, aka “Arcturus”), many of which have sub-sub-variants, as coronavirus variants of interest globally.  The CDC has seen XBB sub-variants in ~85% of its recently tested US patient sequencing samples as of mid-summer 2023.

The latest (summer 2023) global Omicron XBB sub-sub-variants EG.5.1 (aka Eris) AND BA.2.86 (aka Pirola) contain even more amino acid mutations, hence becoming more likely to escape our immunity (whether from vaccination or natural infection) and are more contagious, but so far seem no more virulent than others. Other sub-variants will likely continue emerging, as is the pattern with coronaviruses.

On April 19, 2023, the FDA and CDC approved a bivalent COVID booster to include newer Omicron XBB variants.  But on June 15 2023 members of the FDA’s Vaccine and Related Biological Products Advisory Committee (VRBPAC) voted unanimously to recommend updating the COVID-19 vaccine composition to a monovalent XBB lineage.  Other US organizations can companies are working to make this happen, possibly by late September.

An interesting UCSF article in Nature 7.19.2023 showed that a small % of people with COVID infection never felt ill because of several possible HLA genotypes which related to memory T calls. Such testing is not yet commercialized.

Reports of summer 2023 US CDC data show slight increases in COVID-19 hospital admissions, emergency department visits, test positivity, and wastewater surveillance indicators.  Only time will tell if these become indicative of a true fall-winter 2023-2024 surge in COVID cases.  Interestingly, wastewater genomic sampling now yields reliable and predictable SARS-CoV-2 variants ahead of community clusters or outbreaks.

Influenza continues to hit “seasonally”, although winter 2022-2023 was a bit milder than the prior few years. Vaccination rates fell significantly among most groups during the 2020-2022 COVID pandemic but are now rising.  The CDC states “influenza viruses (including variants) tested to date are susceptible to the neuraminidase inhibitor drugs oseltamivir, peramivir and zanamivir, and the…endonuclease inhibitor baloxavir”, which can/ should be used for both treatment and prophylaxis where indicated.

Southern Hemisphere influenza viruses (now the SH winter) determine the composition of the Northern Hemisphere (NH) vaccines per the World Health Organization (WHO), which recommends that trivalent vaccines for use in the 2023-2024 NH  influenza season contain the following:

1. For egg-based vaccines:
   • an A/Victoria/4897/2022 (H1N1) pdm09-like virus (updated);
   • an A/Darwin/9/2021 (H3N2)-like virus; and
   • a B/Austria/1359417/2021 (B/Victoria lineage)-like virus.
2. For cell culture- or recombinant-based vaccines:
   • an A/Wisconsin/67/2022 (H1N1) pdm09-like virus;
   • an A/Darwin/6/2021 (H3N2)-like virus; and
   • a B/Austria/1359417/2021 (B/Victoria lineage)-like virus
3. For quadrivalent egg- or cell culture-based or recombinant vaccines (2 A + 2 B strains):
   • the above plus a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.

Recommended strongly is the latest CDC MMWR monograph “Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices -US 2022-2023 Influenza Season”. It is available at https://www.cdc.gov/mmwr/volumes/72/rr/rr7202a1.htm

Respiratory Syncytial Virus (RSV), another common “seasonal” pathogen, disproportionally infects children (especially the very young) and older adults (especially those with chronic medical conditions).  Testing is done via real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) and antigen testing, which is highly sensitive in children but not as much in adults.  The FDA on July 17, 2023, approved the single-shot monoclonal antibody (mAb) nirsevimab (brand name Beyfortus) to protect infants and toddlers. Another mAb product is now being reviewed by the ACIP and CDC for prophylaxis approval.- Unfortunately, no RSV-specific treatment is available yet.

Human MetaPneumoVirus (HMPV) is another respiratory virus that has seen a significant increase in incidence in the US in 2022-2023.  Some of the newest respiratory viral PCR panels often include testing for HMPV.  Symptoms are similar to influenza, COVID, and RSV. Morbidity and mortality are similar to those of influenza. Unfortunately, current science has neither a vaccine, other prophylaxis, nor a specific treatment yet.

Whole Genome Sequencing (WGS) or Targeted Genomic Sequencing (TGS) of coronaviruses isolated from bats and intermediate hosts helps predict evolution into humans, especially as WGS and TGS are now faster and less expensive.  MUSC and Roper use BioFire for respiratory sample sequencing; the CDC uses a Multiplex system, all of which test selected parts of certain viral genomes.

Some good news includes: 1) COVID boosters will likely be monovalent based on the latest sub-variants; 2) the FDA has now approved two single-dose Respiratory Syncytial Virus (RSV) vaccines for adults > 60yo; 3) influenza vaccines will include more types (and newer strain variants) 4) because of evolving vaccine manufacturing technology, future COVID vaccines will likely be a single-shot per year, then hopefully in a few years in combination with seasonal influenza viruses.

Some take-home messages include:

1. Keep updating yourself on respiratory pathogens in your community, state, and nation.
2. Know that COVID coronaviruses continue to mutate, many morphing into less virulent but still highly transmissible variants (not unlike coronaviruses which comprise about 1/5 of common colds).
3. Continue to actively promote folk to keep up to date on all their vaccines (especially COVID boosters).
4. Know how to contact local & state experts for information and advice.
5. Stress that the COVID pandemic is NOT “over” (although the public is over its major effects [i.e., high mortality] and generally has lost interest, but the virus is NOT done with us).

Robert Ball, MD MPH FACP                  

Assistant Adjunct Professor

Department of Public Health Sciences

Medical University of South Carolina

Chair, Charleston County Medical Society Public Health Committee

(843) 709-3779