ALICANTE, SPAIN – Tourists and locals cool off at a crowded El Postiguet Beach during a summer day. Despite summer, there is a surge in Covid, which can be transmitted outdoors, or indoors, as people seek air conditioning (Photo by Marcos del Mazo/LightRocket via Getty Images)LightRocket via Getty ImagesWith this summer’s surge in COVID-19 infections underway, there are some new things to be aware of.***Update: This afternoon, the FDA approved the 2026-2027 season’s new COVID-29 vaccines–with mRNA-based ones from Moderna and Pfizer-BioNTech and a protein-based vaccine from Novavax-Sanofi. Each is based on the dominant XFG variant now in circulation. The vaccine should be available soon–likely within the next two weeks.First is what Michael Hoerger, Ph.D., a Covid mitigation and forecasting expert at Tulane University, describes as “bluewashing,” with the CDC downgrading the colors and rankings on its Covid maps. As he noted, “Much of what was Very High is now “High.” What was High is now “Moderate” or “Low.” Low is “Very Low.” Hoerger continues, “This time, there was no alert and no explanation. Major changes were confined to COVlD, not Influenza A, and not RSV. The CDC made these questionable changes in the middle of rising transmission across most of the country; 15 states already have COVlD outbreaks, and others may soon join the ranks. These are serious ethics concerns that warrant investigative journalism.” Hoerger further notes delayed reporting at High/Very High levels from some monitoring sites and that the CDC does not take this into consideration. His Pandemic Mitigation Collaborative’s PMC Dashboard is my go-to for up to date information on prevalence and risks. Texas is the biggest hot spot now, followed by Alaska, Hawaii, and California. There are at least 24 outbreaks already.Hoerger expects that, “if transmission follows historical patterns, it will peak around Labor Day and then again on New Year’s Eve.VaccinesJust as with annual changes to flu vaccines, the composition of the COVID-19 vaccine needs to change as new variant strains emerge. This year, the target will be the XFG variant, still a descendant of the JN.1 lineage, as was last year’s, which targeted the LP.8.1 variant of the SARS-CoV-2 virus.It is unclear when the FDA will authorize the updated vaccine. They have not responded to my inquiry.Both mRNA (Pfizer and Moderna) and the Sanofi/Novavax will be available–hopefully in September, based on the timing of previous FDA approval. Sanofi notes that their vaccine (“Nuvaxovid”), which is a protein-based alternative to the mRNA ones, demonstrated 100% protection against moderate-to-severe disease during pivotal Phase 3 trials. My experience is that it is less reactogenic and better-tolerated than the mRNA vaccines but that the mRNA ones are more widely available.Who Should Get The COVID-19 Vaccine?Before Robert F. Kennedy, Jr was appointed Secretary of Health, the vaccine was recommended for anyone older than 6 months. Kennedy and his appointees opposed the vaccines for healthy children and pregnant women, bypassing traditional science-based review from the CDC’s Advisory Committee on Immunization Practices. After considerable backlash from the scientific and medical community, Kennedy downgraded the recommendation to “shared decision making” for those younger than 65.Pregnant women have a significantly higher risk of complications including preterm delivery, respiratory failure, and death. Despite his appointing two anti-vax physicians to the ACIP, the American College of Obstetricians and Gynecologists recommends pregnant women be vaccinated to prevent Covid infections.The American Academy of Pediatrics has recommendations for children here, specifically recommending vaccination for kids with asthma, sickle cell, diabetes, obesity, epilepsy, among other underlying diseases, as well as those with family members at risk for severe disease, and anyone whose parent desires their protection from infection. What To Do If You Suspect InfectionFirst, have a low threshold for testing. Many infections now are mild and could be easily dismissed as allergies, a summer cold, or jet lag. If the first test is negative, I would repeat it in 24-36 hours. This is important because the antiviral Paxlovid is most effective taken early, as is metformin.Medicines To Reduce Illness Or Prevent Long CovidPaxlovidIn those at high risk and who are unvaccinated, “Paxlovid significantly reduced the proportion of people with Covid-19 related hospitalization or death” by 88% compared to placebo.But for those who are vaccinated, there is no benefit in reducing hospitalization or death, even among the elderly. UpToDate, a medical treatment guide, recommends treatment for those older than 75 or with significant underlying disease. Benefit was limited to those at high risk and was predominantly a small reduction in illness duration.A recent study — a small but well-done, double-blind, randomised placebo-controlled trial showed patients who received Paxlovid (nirmatrelvir–ritonavir) had a significantly lower risk of being symptomatic at 3 months (26%) compared with those receiving placebo (43%).The cost of Paxlovid is $1400-$1500 with some patient assistance programs available.MetforminCuriously, the UpToDate authors do not recommend metformin. A recent meta-analysis concluded that the drug provided “modest benefit in reducing hospitalisation, ED visits, or mortality” but that the findings were inconclusive.I’ve long recommended metformin to help prevent long Covid, largely based on Carolyn Bramante’s studies. Her first study showed a 41% reduction in the incidence of long Covid, compared with placebo, when started early.In the May 2024 “COVID-OUT” study, Bramante’s group showed the SARS-CoV-2 viral load was cut 3.6-fold with metformin compared to placebo. The odds of severe COVID-19 were reduced by 55% and of long COVID by 65% if metformin was started less than four days from symptom onset. The RECOVER trial extended the finding to patients with diabetes, and showed a 13% to 21% lower incidence of long COVID or death.They also found that metformin reduces viral load and pro-inflammatory molecules that contribute to clotting in Covid infections.Metformin is a pretty benign drug—its main side effects are GI upset, and it is better tolerated when titrated up. It is relatively inexpensive, $10-30 for a 60-day supply (500 mg dose).The main problem I’ve encountered is hearing that providers are refusing the request for a 2-week course of metformin, because “it’s just for diabetes.”Azelastine/AntihistaminesAzelastine is a nasal antihistamine spray. In a 450-patient randomized, controlled, double-blind trial, it significantly lowered the incidence of subsequent COVID-19 infection to (2.2%) compared with the placebo group (6.7%). It also reduced the risk of rhinovirus (cold) infections. It’s thought to work by blocking the viral receptor in the nose.In preliminary data from the University of Florida, researchers found diphenhydramine (Benadryl), hydroxyzine (Atarax), and azelastine to inhibit coronavirus infection of cells. Fexofenadine (Allegra), cetirazine (Zyrtec), and loratadine (Claritin) are similar H1 receptor blockers, but there is not data yet as to their efficacy.Famotidine, an H2 blocker, reduces the severity and mortality of Covid infections in some studies.Ensitrelvir/Post-exposure prophylaxisThe latest advance regarding Covid is Ensitrelvir (brand name Xocova), a protease inhibitor. The SCORPIO-PEP clinical trial was a double-blind, randomised, placebo-controlled trial assessing the drug for Post-exposure prophylaxis of household members of someone with acute Covid.The incidence of COVID-19 was lower in the ensitrelvir group than in the placebo group by 67%.While the drug is approved to prevent Covid, its cost may be prohibitive to many. Ensitrelvir costs $1421 through GoodRx. Shionogi is developing a financial assistance program for those who are uninsured. Patients with commercial insurance may be eligible for having no copayment; the terms are outlined here.Bottom Line On ProtectionIan Mackay’s Swiss Cheese COVID-19 Defense modelCourtesy Ian M. Mackay, PhDAs Australian virologist and educator Ian Mackay showed us early on, Covid prevention requires the Swiss cheese model of protection, with multiple layered components. To this fine illustration, with masking, ventilation, and vaccination as the base, we could consider azelastine for prevention.We can now add metformin, Paxlovid, and ensitrelvir to help prevent progression to long Covid.
