SARS-CoV-2 Reinfections and Long COVID in the Post-Omicron Phase of the Pandemic

Abstract

We are reviewing the current state of knowledge on the virological and immunological correlates of long COVID, focusing on recent evidence for the possible association between the increasing number of SARS-CoV-2 reinfections and the parallel pandemic of long COVID. The severity of reinfections largely depends on the severity of the initial episode; in turn, this is determined both by a combination of genetic factors, particularly related to the innate immune response, and by the pathogenicity of the specific variant, especially its ability to infect and induce syncytia formation at the lower respiratory tract. The cumulative risk of long COVID as well as of various cardiac, pulmonary, or neurological complications increases proportionally to the number of SARS-CoV-2 infections, primarily in the elderly. Therefore, the number of long COVID cases is expected to remain high in the future. Reinfections apparently increase the likelihood of long COVID, but less so if they are mild or asymptomatic as in children and adolescents. Strategies to prevent SARS-CoV-2 reinfections are urgently needed, primarily among older adults who have a higher burden of comorbidities. Follow-up studies using an established case definition and precise diagnostic criteria of long COVID in people with or without reinfection may further elucidate the contribution of SARS-CoV-2 reinfections to the long COVID burden. Although accumulating evidence supports vaccination, both before and after the SARS-CoV-2 infection, as a preventive strategy to reduce the risk of long COVID, more robust comparative observational studies, including randomized trials, are needed to provide conclusive evidence of the effectiveness of vaccination in preventing or mitigating long COVID in all age groups. Thankfully, answers not only on the prevention, but also on treatment options and rates of recovery from long COVID are gradually starting to emerge.

Patients with unmet social needs are at higher risks of developing severe long COVID-19 symptoms and neuropsychiatric sequela

“…A recent prospective study demonstrates similar findings, in which patients with high respiratory symptomatic burden 3-months post-COVID were associated with high disease severity 40 . Previous studies have reported individuals with mild symptoms from SARS-CoV-2 infection (i.e., not requiring hospitalization) or asymptomatic infection may also be susceptible to general and neurological PASC 41 – 43 .…”

Seroprevalence of IgM/IgG and Neutralizing Antibodies against SARS-CoV-2 in Unvaccinated Young Adults from Mexico Who Reported Not Having Had a Previous COVID-19 Infection

“…The above is important because asymptomatic cases have the potential to perpetuate infections among vulnerable individuals or those who might eventually develop symptomatic disease. Moreover, this is crucial considering studies suggesting that reinfections could elevate the long-term risk of COVID-19, albeit to a lesser extent in mild or asymptomatic infections [ 31 ].…”

The knowns and unknowns of long COVID-19: from mechanisms to therapeutical approaches

“…In addition to host factors such as immunity status, comorbidities, vaccination status etc., Long COVID is also influenced by the virus, including strain/variant ( 180 ). Therefore, it is important to distinguish between long COVID infections with the wild type virus and subsequent variants.…”