Angelica Giambelluca1, Alessandro Gallo2
1 Giornalista professionista in ambito medico e sanitario
2 Direttore Generale Springer Healthcare Italia
The vast majority of individuals who contracted COVID-19 eventually fully recover. However, even after mild or asymptomatic infection, a relatively significant number of subjects may experience a variety of symptoms, sometimes for months, even when testing negative to COVID-19. The exact prevalence of this phenomenon is unknown, due to the high heterogeneity across studies. A recent study conducted in the Netherlands (1) prior to the 2022 Omicron waves provides a credible estimate. Based on the evidence of a follow of thousands of individuals, matched by age and sex with uninfected controls, the ensuing estimated was 12.7% (i.e.1 in 8 people who had Covid may have developed the condition).
This is Long COVID, and people who experience it sometimes are referred to as “long-haulers.” Long COVID main symptoms are fatigue, mental fog, loss of taste and smell, breathlessness and cognitive dysfunction (i.e. confusion, forgetfulness, or lack of mental focus and clarity). Long COVID-19 conditions can affect a person’s ability to perform daily activities such as going to work or attending classes at school.
Until recently, it was unclear whether COVID vaccination – which proved effective in limiting transmission and virulence of infection – was equally effective in preventing Long COVID. Some recently published studies show how vaccination can help limiting the onset and severity of these symptoms, especially with two (or three) doses on vaccination.
What is the timeline for Long COVID and what does this imply?
Reviewing published literature on scholarly journals, there are diverging views on what can be clinically considered “Long COVID”. NICE (2) provides this definition: “Ongoing symptomatic COVID-19 Signs and symptoms of COVID 19 from 4 weeks up to 12 weeks. Post-COVID-19 syndrome Signs and symptoms that develop during or after an infection consistent with COVID 19, continue for more than 12 weeks and are not explained by an alternative diagnosis.”
According to a study published by the British Medical Journal (3), a patient can be considered affected by Long COVID when infection symptoms persist more than four weeks after the last negative diagnostic test. According to a study published in Nature (4), this condition can last for many months and involve up to 50% of individuals who were affected by COVID-19. Despite such large scale impact, knowledge about such condition is still limited.
Most frequent symptoms include:
- “mental fog” (memory and concentration problems)
- loss of smell and taste
- respiratory and cardiological occurrences
- neurological disorders
- anxiety and stress
To date, it remains to be ascertained whether such condition is a consequence of direct damage caused to one or more organs, or if such clinical impact was triggered by virus as an immune response directed against organs and tissues, as if it were an autoimmune reaction. Elderly individuals, primarily female, overweight, with comorbidities represent the main groups at risk of developing Long COVID.
Vaccines and Long COVID
In the abovementioned BMJ observational study, researchers tried to understand if vaccination could somehow limit the onset of Long COVID. Approximately 30,000 adults residing in the UK with a history of COVID-19 prior to their vaccination and managed at home (not in hospital or other health facilities) were monitored between February to September 2021.
The main objective of the study was detecting Long COVID symptoms for at least twelve weeks following a SARS-CoV-2 infection.
The analysis found that the chances of experiencing Long COVID symptoms decreased by an average of 13% after the first jab. The administration of a second jab was associated with further decrease probability (9%) of a Long COVID onset.
As a matter of fact, further research is needed to assess the association of vaccination to Long COVID onset. Specifically, a more in-depth analysis is required to understand the impact of the Omicron variant and any other sub-variant, the effect of boosters and reinfections. Additional research is required to understand the biological mechanisms underlying symptom improvements following vaccination.
An Italian study published in JAMA
With three jabs, protection against Long COVID seems to be even more effective. This is the result of a recently published Italian research (5). The authors, Professor Maria Rescigno, Head of the Humanitas Mucosal and Microbiota Immunology Laboratory and Dr. Elena Azzolini, Deputy Medical Director of Humanitas, in collaboration with Prof. Alberto Mantovani, scientific director of the hospital, showed how unvaccinated individuals are the most exposed group to Long COVID (41.8%), compared to a mere 16% of those who were vaccinated with 3 doses.
This research provides, a clear “snapshot” of how the immune system of the hospitalized subjects performed between March 2020 to April 2022, throughout the various variant waves, including the effects of the vaccination campaign (including the third jab and the fourth for the most fragile groups).
- Ballering AV, van Zon SKR, Olde Hartman TC, Rosmalen JGM; Lifelines Corona Research Initiative. Persistence of somatic symptoms after COVID-19 in the Netherlands: an observational cohort study. Lancet. 2022 Aug 6;400(10350):452-461.
- National Institute for Health and Care Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN) and Royal College of General Practitioners (RCGP), COVID-19 rapid guideline: managing the longterm effects of COVID-19 [Internet1 March 2022 https://www.nice.org.uk/guidance/ng188/resources/covid19-rapid-guideline-managing-the-longterm-effects-of-covid19-pdf-51035515742 (last access 5 September 2022)
- Ayoubkhani D, Bermingham C, Pouwels KB, Glickman M, Nafilyan V, Zaccardi F, Khunti K, Alwan NA, Walker AS. Trajectory of long covid symptoms after covid-19 vaccination: community based cohort study. BMJ. 2022 May 18;377:e069676.
- Blomberg B, Mohn KG, Brokstad KA, Zhou F, Linchausen DW, Hansen BA, Lartey S, Onyango TB, Kuwelker K, Sævik M, Bartsch H, Tøndel C, Kittang BR; Bergen COVID-19 Research Group, Cox RJ, Langeland N. Long COVID in a prospective cohort of home-isolated patients. Nat Med. 2021 Sep;27(9):1607-1613
- Azzolini E, Levi R, Sarti R, Pozzi C, Mollura M, Mantovani A, Rescigno M. Association Between BNT162b2 Vaccination and Long COVID After Infections Not Requiring Hospitalization in Health Care Workers. JAMA. 2022 Aug 16;328(7):676-678.