By Gary Evans, Medical Writer
Healthcare workers and millions of other Americans are suffering from the ghost of COVID-19, a seemingly endless or remittent continuation of a disturbing panoply of symptoms that could have been lifted from Dante’s Inferno: cognitive decline, chronic pain, shortness of breath, intense fatigue, and neurological attacks on the body’s organs.
This is long COVID, about which there is little consensus on diagnosis, treatment, and prognosis. However, evidence is accumulating suggesting vaccination can prevent or reduce the impact of long COVID.
“Long COVID can include a wide range of ongoing health problems; these conditions can last weeks, months, or years,” the CDC stated. “Long COVID occurs more often in people who had severe COVID-19 illness, but anyone who has been infected with the virus that causes COVID-19 can experience it. People who are not vaccinated against COVID-19 and become infected may have a higher risk of developing long COVID compared to people who have been vaccinated.”1
As of May 8, 2023, the CDC reported 27% of people who have contracted COVID reported developing long COVID.2 As of that same date, 10% of people who had previously contracted COVID were currently suffering long COVID. Of that population, 24% reported “significant activity limitations.” Of course, these numbers are ever shifting — recoveries, new cases, and to some extent, the definitions of symptoms and their duration.
The current CDC definition is necessarily broad, reading in part as the aforementioned signs, symptoms, and conditions that continue or develop after initial SARS-CoV-2 infection and last four weeks or longer.
“[Long COVID] may be multisystemic, and may present with a relapsing-remitting pattern and progression or worsening over time, with the possibility of severe and life-threatening events even months or years after infection,” the CDC stated. “Long COVID is not one condition. It represents many potentially overlapping entities, likely with different biological causes and different sets of risk factors and outcomes.”3
With this entanglement as our starting point, any attempt to winnow out long COVID prevalence among healthcare workers invites one up a steep and thorny path. One of the latest studies to address this question was conducted by Alex Marra, MD, an infectious disease physician at Hospital Israelita Albert Einstein in São Paulo, Brazil.
Case-Control Study in Brazil
Marra and colleagues conducted a case-control study among healthcare workers with confirmed symptomatic COVID-19 working in a Brazilian healthcare system between March 1, 2020, and July 15, 2022. Overall, of 7,051 workers diagnosed with COVID-19, 1,933 developed long COVID. They were compared to a control group of 5,118 who did not report these aftereffects.4
Cases were defined as those with long COVID according to the CDC definition. Hospital Employee Health asked Marra if his findings in Brazil could be extrapolated to U.S. healthcare workers.
“With the ongoing COVID-19 pandemic, a considerable proportion of individuals who have recovered from COVID-19 infection have long-term symptoms involving multiple organs and systems,” Marra says. “It is difficult to say that the same proportion of U.S healthcare workers will have similar rates of long COVID.”
Since the beginning of the pandemic, medical workers at the Brazilian hospital had access to free SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) testing. When they became available, the hospital offered COVID-19 vaccines, including Oxford-AstraZeneca, CoronaVac, Pfizer/BioNTech, and Janssen.
“Healthcare personnel [HCP] were required to notify the employee health clinic if they tested positive for SARS-CoV-2,” Marra and colleagues wrote. “HCP with a laboratory-confirmed COVID-19 by RT-PCR were assessed by the employee health clinic at one, three, and six months after the first infection via in-person appointment, telephone appointment, or emails.”
Interestingly, the Brazilian medical workers were much more likely to develop long COVID after infection with the original Wuhan strain or the first variant, alpha. This is thought to suggest naïve population immunity through lack of natural infection or vaccination, which came into play later reduce the number of long COVID cases during the delta variant and omicron variant surges.
“Most of those with long COVID had three or more signs or symptoms (52%), whereas 644 had one infection (33%) and 288 (15%) had two infections,” Marra and colleagues reported. “The most common symptoms were headache (53%), followed by joint and muscle pain (47%), and nasal congestion (45%).”
The Vaccine Effect
The primary protective factor was receiving four doses of vaccine before infection.
“We revealed that receiving four doses of COVID-19 vaccinations before infection was protective against long COVID, although a dose-response effect was not detected, which could have been due to the small sample size, creating an unbalanced comparison between vaccinated and unvaccinated,” Marra and colleagues concluded.
With the U.S. public widely underimmunized — particularly with the current bivalent vaccine — it bears repeating that COVID-19 vaccination likely prevented a lot of long COVID cases that might have otherwise occurred. Marra and colleagues also published another study in this regard, finding that vaccination — particularly before infection — blunted onset of long COVID.5
“That study indicates that despite low efficacy [against infection], COVID-19 vaccines effectively reduce long COVID symptoms caused by circulating SARS-CoV-2 variants,” Marra tells Hospital Employee Health. “The vaccines are more effective when administered before infection. However, the vaccines provide some level of protection [against long-COVID] to individuals who were immunized post-infection.”
That raises the issue of the discontinuation of the federal mandate to immunize healthcare workers for COVID-19, although the better likelihood of preventing long COVID would seem to be a strong selling point for voluntary shots.
“Requiring healthcare personnel to be vaccinated is aimed at reducing the risk of transmission in healthcare settings and protecting vulnerable patients who may have compromised immune systems or other health conditions,” Marra explains. “It is a precautionary measure to ensure the safety and well-being of both patients and healthcare workers. However, it is important to note that the risk of long COVID after breakthrough infection, while lower than in unvaccinated individuals, cannot be completely ruled out. Long COVID can occur in some cases even after a mild or asymptomatic infection. The exact risk and factors contributing to long COVID are still being actively researched.”
There have been some predictions that a post-pandemic of chronic long COVID will afflict millions of people globally. “While a significant number of individuals with COVID-19 may experience long-lasting symptoms, it is unclear at this point how many will develop chronic diseases as a direct result of long COVID,” Marra says. “Research is ongoing to better understand the underlying mechanisms, risk factors, and long-term outcomes of long COVID, which can vary widely among individuals, with some experiencing milder symptoms that resolve over time. Additionally, vaccination efforts and other public health measures may help mitigate the long-term impact of COVID-19.”
Thus, long COVID could drive the creation of new treatments and vaccines, even if SARS-CoV-2 is contained to an endemic virus.
Healthcare workers should know the bivalent vaccine will be discontinued and replaced by a new vaccine, likely in September. The effectiveness of the current bivalent vaccine is waning against the latest iterations of omicron subvariants. On June 15, FDA advisors voted unanimously to approve a new monovalent vaccine for the fall containing the currently predominant omicron subvariant XBB.1.5. The current bivalent vaccine probably will be scuttled soon to clear a sufficient period before receiving the new vaccine.
The FDA’s Vaccines and Related Biological Products Advisory Committee decided to go all in on XBB.1.5, in part because it has demonstrated cross-reactivity against the other XBB subvariants of omicron. As of June 10, XBB.1.5 comprised 40% of the circulating SARS-CoV-2 variants in the United States, with a host of related subvariants trailing it.
“We may well find in the next month the XBB.1.16 or XBB.2 become more dominant than XBB.1.5,” said FDA committee member Stanley Perlman, MD, PhD, of the University of Iowa. “But that doesn’t matter because we have good data that there’s good cross-reactivity within the S protein and other parts of the virus. This should work just fine.”
For the first time since the COVID-19 vaccines were developed, the original Wuhan strain will not be included, underscoring how much of a viral changeling SARS-CoV-2 has become. This original safety net, which is credited with inducing some of the original deep-set immunity in T and B cells that curbed severe infections and deaths, has long been overtaken by the rapidly evolving variants that followed it.
Including the original strain that arose from China in 2019 would only dilute the potency of the new monovalent XBB.1.5. Furthermore, immunizing against the Wuhan strain again could undermine vaccine efficacy by the phenomenon of “imprinting,” wherein the immune system is distracted by recognizing and responding to an old viral enemy.
An FDA background document for the meeting stressed the continued evolution of SARS-CoV-2 creates the possibility for “increased transmissibility and adaptation to the host.”6
As has been suspected in the emergence of omicron, immune escape variants may be selected out in prolonged infections in immune-compromised hosts. “Thus far, the impressive plasticity, especially in spike, suggests that the virus can continue evolving by both incremental (drift-like) and saltatory (shift-like) modes, underscoring the importance of ongoing global surveillance,” the FDA stated.
While it must be cleared by the CDC’s Advisory Committee on Immunization Practices (ACIP), the new COVID-19 vaccine is expected to be released sometime in September. ACIP will discuss whether this vaccine should be given to everybody or a subset of people, but healthcare workers will no doubt be included as a priority. Preventing long COVID and its horrific manifestations should be reason enough for most healthcare workers to roll up their sleeves.
REFERENCES
- Centers for Disease Control and Prevention. Long COVID or post-COVID conditions. Updated Dec. 16, 2022.
- National Center for Health Statistics. Long COVID Household Pulse Survey. Last reviewed May 17, 2023.
- COVID.gov. What is long COVID? 2023.
- Marra AR, Sampaio VS, Ozahata MC, et al. Risk factors for long coronavirus disease 2019 (long COVID) among healthcare personnel, Brazil, 2020-2022. Infect Control Hosp Epidemiol 2023 Jun 5;1-7. doi: 10.1017/ice.2023.95. [Online ahead of print].
- Marra AR, Kobayashi T, Suzuki H, et al. The effectiveness of coronavirus disease 2019 (COVID-19) vaccine in the prevention of post–COVID-19 conditions: A systematic literature review and meta-analysis. Antimicrob Steward Healthc Epidemiol 2022;2:e192.
- Food & Drug Administration. FDA Briefing Document: Vaccines and Related Biological Products Advisory Committee Meeting: Selection of strain(s) to be included in the periodic updated COVID-19 vaccines for the 2023-2024 vaccination campaign. June 15, 2023.
Healthcare workers and millions of other Americans are suffering from the ghost of COVID-19, a seemingly endless or remittent continuation of a disturbing panoply of symptoms that could have been lifted from Dante’s Inferno: cognitive decline, chronic pain, shortness of breath, intense fatigue, and neurological attacks on the body’s organs. This is long COVID, about which there is little consensus on diagnosis, treatment, and prognosis. However, evidence is accumulating suggesting vaccination can prevent or reduce the impact of long COVID.
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