Long COVID: Complications, Underlying Mechanisms, and Treatment Strategies

Abstract

Long Covid is one of the most prevalent and puzzling conditions that arose with the Covid pandemic. Covid-19 infection generally resolves within several weeks but some experience new or lingering symptoms. Though there is no formal definition for such lingering symptoms the CDC boadly describes long Covid as persons having a wide range of new, recurring or sustained health issues four or more weeks after first being infected with SARS-CoV2. The WHO defines long Covid as the manifestation of symptoms from a "probable or confirmed" Covid-19 infection that start approximately 3 months after the onset of the acute infection and last for more than 2 months. Numerous studies have looked at the implications of long Covid on various organs. Many specific mechanisms have been proposed for such changes. In this article, we provide an overview of some of the main mechanisms by which long Covid induces end-organ damage proposed in recent research studies. We also review various treatment options, current clinical trials, and other potential therapeutic avenues to control long Covid followed by the information about the effect of vaccination on long Covid. Lastly, we discuss some of the questions and knowledge gaps in the present understanding of long Covid. We believe more studies of the effects long Covid has on quality of life, future health and life expectancy are required to better understand and eventually prevent or treat the disease. We acknowledge the effects of long Covid are not limited to those in this article but as it may affect the health of future offspring and therefore, we deem it important to identify more prognostic and therapeutic targets to control this condition.

Keywords: Anxiety; Brain fog; Chronic fatigue syndrome; Cognitive dysfunction; Covid-19; Depression; Long Covid; Post Covid-19 syndrome; Post SARS-CoV2; Postural orthostatic tachycardia syndrome; Pulmonary fibrosis.

Figure 1:. Long Covid as sequelae of acute Covid-19.

Initial hypotheses regarding COVID-19 postulated that age, sex, preexisting comorbidities, and severity of Covid-19 can raise the likelihood of long Covid. However, subsequent studies suggest long Covid can occur regardless of prior comorbidities or severity of acute Covid-19.

Figure 2:

Covid-19 infection affects almost all organs and organ systems are affected resulting in different pathophysiology. Few of the key symptoms and outcome results are shown. This is primarily due to the sequelae of cytokine storm.

Figure 3:

Major clinical complications in long Covid after 12 weeks of initial infection

Figure 4:

Major factors post Covid in the underlying pathophysiology of brain effects in long Covid.

Figure 5:

Potential mechanisms of the effect of SARS-CoV2 infection in the brain that induces chronic inflammation in the neuromuscular junction. This involves mitochondria leading to sarcolemma damage, muscle fibre atrophy and damage. All these result in myopathy.

Figure 6:

Efferent and afferent vagal nerve are critical in gut-brain interaction.

Figure 7:

Key factors involved in the underlying pathophysiology of post/long Covid.