Long COVID: major findings, mechanisms and recommendations

Abstract

Long COVID is an often debilitating illness that occurs in at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. More than 200 symptoms have been identified with impacts on multiple organ systems. At least 65 million individuals worldwide are estimated to have long COVID, with cases increasing daily. Biomedical research has made substantial progress in identifying various pathophysiological changes and risk factors and in characterizing the illness; further, similarities with other viral-onset illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome have laid the groundwork for research in the field. In this Review, we explore the current literature and highlight key findings, the overlap with other conditions, the variable onset of symptoms, long COVID in children and the impact of vaccinations. Although these key findings are critical to understanding long COVID, current diagnostic and treatment options are insufficient, and clinical trials must be prioritized that address leading hypotheses. Additionally, to strengthen long COVID research, future studies must account for biases and SARS-CoV-2 testing issues, build on viral-onset research, be inclusive of marginalized populations and meaningfully engage patients throughout the research process.

Acute tubulointerstitial nephritis with or without uveitis: a novel form of post-acute COVID-19 syndrome in children

“…We therefore propose that SARS-CoV-2 could prime autoinflammation through molecular mimicry 7 , as reported in other post-COVID-19 long-term symptoms (Long COVID-19). SARS-CoV-2 uses the receptors angiotensin-converting enzyme II (ACE2) and transmembrane protease serine 2 (TMPRSS2) for cell entry and protein S priming, respectively.…”

High number of SARS-CoV-2 persistent infections uncovered through genetic analysis of samples from a large community-based surveillance study

“…Intriguingly, individuals with persistent infections report fewer symptoms later in a persistent infection compared to at their first positive sample, or remain asymptomatic throughout infection, but have more than 50% higher odds of Long Covid compared to a control group. Although the link between viral persistence and Long Covid may not be causal, these results suggest persistent infections could be contributing to the pathophysiology of Long Covid 10,38 , as also evidenced by the observation of circulating SARS-CoV-2 S1 spike protein in a subset of patients with Long Covid months after first infection 39 . The association between persistent infection and Long Covid does not imply that every persistent infection can lead to Long Covid, only 9% of persistently infected individuals reported having Long Covid, nor does it mean that all cases of Long Covid are due to a persistent infection.…”

Autonomic dysfunction and postural orthostatic tachycardia syndrome in post-acute COVID-19 syndrome

“…In mid-2020, a new group of patients, so-called post-COVID-19 long-haulers, emerged. These individuals were constantly tired, incapable of work, often young or middle-aged women, with multiple symptoms, including heart palpitations, tachycardia, orthostatic and exercise intolerance, and chest pain 1 . Many physicians, cardiologists and neurologists realized that some of these symptoms were identical to those of postural orthostatic tachycardia syndrome (POTS), as were patient responses to cardiovascular autonomic tests 2 .…”

“…Recent reports have highlighted this problem by underscoring the place of POTS in the post-COVID-19 landscape 1 , calling for more diagnostic vigilance, greater availability of health-care resources and new therapeutic options. Interestingly, POTS and related conditions, such as mast cell disorders, chronic fatigue and general dysautonomia, are diagnosed more often in the 3 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but can also develop after COVID-19 vaccination.…”