Systemic capillary leak syndrome can affect both vaccinated and post COVID-19 people


Systemic Capillary Leak Syndrome That Can Affect Post COVID And Post Vaccinated Individuals

The review was published on a preprint server and is currently being peer reviewed.


Systemic capillary leak syndrome occurs due to the disruption of endothelial cells, which leads to increased vascular permeability, causing intravascular fluid to leak into the extravascular space and albumin to be retained in the interstitial space [32]. This phenomenon can lead to hypovolemia, peripheral hypoperfusion, and acute renal insufficiency [33].

In viral infections, this condition can be triggered by direct viral toxicity on the endothelial barrier of massive inflammatory mediators secretion [5,34]. This inflammatory response in the lungs leads to pulmonary capillary leak syndrome, which manifests as progressive hypoxemic respiratory failure and acute respiratory distress syndrome (ARDS) [35,36].

The elevation of proinflammatory cytokines and chemokines, like CCL2, IL-1, IL-6, IL8, IL-12, and TNF-α during the SARS-CoV-2 infection has a critical role in damaging the respiratory system and other organs [37]. The most significant injury oc- curs in angiotensin-converting enzyme 2 (ACE2) rich areas, which are entry gates of the virus [38]. On the other hand, the occurrence of SCLS in the settings of COVID-19 vaccines can be attributed to the SARS-CoV-2 spike glycoprotein encoded by the RNA or the viral vector [39].


A great majority of acute SCLSs are preceded by a nonspecific prodrome of the flu- like syndrome [40]. Nonetheless, some acute cases follow an episode of sepsis, anaphylaxis, or even an intense physical exertion [41]. This syndrome is presented with fever, generalized edema, pleural effusions, dyspnea, hypovolaemia, hemoconcentration, pre- renal azotemia, shock, and syncope. Peripheral, periorbital, or facial edema may only be detected [6].

It is a form of vascular leak syndrome defined as the presence of at least two of the following: hypotension, edema, and hypoalbuminemia [42]. However, the chronic form is characterized by fluctuating episodes of diffuse edema, weight gain, and hypoal- buminemia rather than hypotension [43]. Interestingly, consciousness is preserved during the bouts of a chronic SCLS, even in severe attacks [40].


In general, eliminating the precipitating factor is the cornerstone of SCLS management. SCLS is predominantly managed conservatively in the early stages with osmotic drugs, diuretics, colchicine, renal replacement therapy, hemofiltration, and albumin transfusion [50,51].

However, in later phases, surgical drainage might be needed to extract the accumulated fluids from body cavities to restore vital organs function [52]. In order to better manage SCLS, some authorities classify this condition into 4 grades:

grade 1 (hypotension responsive to oral fluid therapy),

grade 2 (intravenous hydration without hospital admission),

grade 3 (life-threatening and requiring ICU admission), and

grade 4 (fatal) [7].

Pulmonary capillary leak syndrome can be managed with oxygen therapy non-inva- sive or invasive mechanical ventilation [53]. Steroids help suppress the hyperinflamma- tory response [54,55], whereas theophylline, beta 2 agonists, aminophylline, lisinopril, montelukast, imatinib, and chronic treatment with IVIg may prevent relapses [50,56,57].

As previously mentioned, Systemic capillary leak syndrome (SCLS) is an uncommon disease defined by the presence of extreme hypotension, hemoconcentration, and hypo- albuminemia due to leakage of plasma fluid and proteins into the interstitial space. SCLS is among the most important immune diseases triggered by the SARS-CoV-2.

According to existing evidence, SARS-CoV-2 infection and COVID-19 vaccination could cause this life-threatening condition. SCLS could lead to severe complications like thromboembo- lism (caused by hemoconcentration and hyperviscosity), renal failure, pericardial effu- sions, tamponade, and cardiac arrest.

Since there are no specific diagnostic criteria and tests for determining SCLS, the diagnosis is excluded. After excluding other causes of hypovolemic shock, the diagnosis of SCLS can be considered on the presence of the clas- sical triad of hypotension, hemoconcentration, and hypoalbuminemia.

A wide range of conditions can be listed as the differential diagnosis for cases of suspected SCLS. The most important ones are septic shock, nephrotic syndrome, anaphylaxis, hereditary angi- oedema, drug reactions, exudative enteropathy, and ovarian hyperstimulation. Early stages of SCLS should primarily be managed conservatively with osmotic drugs, diuret- ics, colchicine, renal replacement therapy, hemofiltration, and albumin transfusion.

While, in later phases, surgical drainage might be needed to extract the accumulated fluids from body cavities to restore vital organs’ function. Since SLCS has been observed in as- sociation with SARS-CoV-2 infection and COVID-19 vaccination, it should be considered a possible diagnosis in COVID-19 patients, and it is advisable to be very cautious and weigh the risks and benefits of vaccination of people with a history of this syndrome.



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