Long COVID-19 and New Variants: Sounding a Continuing Alarm

Kevin Kavanaugh, MD

The news regarding the SARS-CoV-2 pandemic has been very concerning on 2 fronts. The first is the recent evidence regarding the immune-escape properties of the newly surging variants BA.4 and BA.5, and the second concerns the growing dangers of long COVID-19.
 
The potential for infection or reinfection or breakthrough infection with BA.4 and BA.5 is alarmingly high. Yes, this viewpoint is sounding an alarm. Two recent news articles from The Times of Israel and the Independent have reported rising rates in Israel and the United Kingdom, with increases in hospitalizations. These reports are supported by recent laboratory evidence published in the New England Journal of Medicine which found that “…data show that the BA.2.12.1, BA.4, and BA.5 subvariants substantially escape neutralizing antibodies induced by both vaccination and infection.”
 
In addition, the BA.4 and BA.5 variants " In addition, the BA.4 and BA.5 variants may be the most infectious variants to date. "Infectivity can have more of an impact on society than a high case fatality rate. As evidenced by the United States’ COVID-19 death data, an individual’s chances of dying from Omicron (BA.1) variant was greater than from the Delta variant. Participating in high-risk activities during Omicron was more likely to result in a severe outcome and death. For those individuals who had infection or vaccine-induced immunity, once infected with BA.1, the disease may have been milder. However, for others, BA.1’s lethality was comparable to previous variants.

Even as many of our policymakers have focused on deaths, long COVID-19 is continuing to take a toll on society by impacting multiple organ systems. Long COVID-19 has been found to occur in 30% of patients treated for COVID-19, and up to 70% have symptoms of brain fog, memory, or other cognitive problems. It also can have a profound impact on the heart and other organs. Also, long COVID-19 is responsible for approximately doubling COVID-19 deaths with 8.39 per 1000 additional deaths occurring after the acute infection. In addition, now biomarkers are starting to emerge in patients who have long COVID-19. A report from Harvard Medical School found viral antigens in the serum of long COVID patients up to a year after their acute infections, which may indicate an ongoing subacute active infection. Noted in a report from Australia, investigators identified biomarkers associated with kynurenine pathway activation in those patients who suffer from long COVID-19 with cognitive decline.
 
Even more concerning is the report that vaccines provide suboptimal protection for most long COVID-19 symptoms, specifically:

• Beyond 30 days after the acute illness, the risk of death after a breakthrough infection is significantly decreased compared to an infection in an unvaccinated individual (HR= 0.66, or a 34% decrease in risk). However, there is a lesser effect on other delayed sequelae (HR = 0.85, or a 15% decrease in risk).

• Compared to non-infected controls, patients with breakthrough infections “exhibited increased risk of death and post-acute sequelae in the pulmonary and several extrapulmonary organ systems.” This was also observed in non-hospitalized patients.

• Compared to non-vaccinated SARS-CoV-2 patients, patients with breakthrough infections also showed a lower risk of death and post-acute sequelae. The risk reduction was more evident in hospitalized patients.

• But the burden of disease in those patients with breakthrough infections is not trivial. Vaccination only partially reduces risks and has the same range of long COVID-19 involving several organ systems “including cardiovascular, coagulation, and hematologic, gastrointestinal, kidney, mental health, metabolic, musculoskeletal, and neurologic disorders.”

But most concerning is that repeated infections are reported to have an additive effect, resulting in a stepwise progression of disease with each infection. Presumably, this is due to added damage to the involved organs.
 
All the studies regarding long COVID-19 have data acquisition periods before the BA.4 and BA.5 variant—a variant which may be even more problematic.
 
Thus, the world has a highly infectious variant, having an uncertain case fatality rate, but with overseas reports of increased hospitalizations. This, combined with disturbing new data on long COVID-19, dictates we need to be on the side of caution and maintain strong public health guidance, including the use of N95 masks along with improving ventilation in all indoor settings. Vaccinations, although weakening, are still advisable since they are low risk and may still make the difference between hospitalization and death and being treated at home. Medical professionals and infection preventionists (IPs) know how this virus spreads and how to mitigate its impact. Now, more than ever, it is important they maintain strong messaging which encourages the following of public health measures.