Introduction

Covid-19 is a disease that was a nightmare that struck people around the globe in 2019. First identified and isolated from a patient exposed to the seafood market in Wuhan city, China, in December 2019. It affected the people both physically and mentally. It was recognised as a global epidemic in the year 2020 by the World Health Organisation. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and comes under the family of previously recognised SARS-CoV virus. The virus comes under the family of coronavirus, which is an RNA virus, and the main culprit of the disease is the spike protein, which gives it its name as corona. It was initially thought to be a zoonotic infection specifically originating from bats, but it spreads from human to human.¹ COVID-19 normally affects the respiratory system. Its symptoms are usually a mild flu-like infection, however, it could be pneumonia or severe acquired respiratory distress syndrome(ARDS). Other symptoms are fever, cough, shortness of breath, myalgia, fatigue, loss of taste and smell, and other less common symptoms are sputum production, hemoptysis, headache and diarrhoea. Many patients have developed blood clots after contracting COVID-19, and to date, many published studies have shown a positive association. Thrombosis is a blood clot within blood vessels, and these can limit the flow of blood through arteries, veins or even through capillaries.²

Pathophysiology of COVID-19-associated thrombosis 

Thrombosis is a life-threatening situation in a COVID-19 positive individual. The exact mechanism is not completely understood, but many studies have supported the concept that it is related to immune responses, the coagulation and fibrinolytic pathways and the vascular endothelium all play an important role in blood clot formation. The exact molecular and cellular mechanism is needed to reduce such risks.³

Endothelial dysfunction 

Normally, the endothelial cells form an antithrombotic effect, platelet activation and coagulation. These are mediated with the help of numerous mediators, like chemokines and cytokines. These are disrupted in case of viral and bacterial infection. Angiotensin-converting enzyme 2 (ACE 2) is the receptor that is present in abundance in the lungs and also in the endothelium of blood vessels. Covid 19 usually inhibits these receptors, which can lead to profound cytokine release, overexpression of tissue factors, localised intravascular coagulopathy, dysregulation of the coagulation cascade, and this may lead to thrombosis.^4,5

Cytokine storm and inflammatory response

Numerous inflammatory mediators come into play when a foreign body, especially pathogens, enters our body. Our body has an immune system working to recognise the pathogen, kill the pathogen, repair the tissue and bring the body to the basal state. These are all possible with the help of defence cells and their mediators, such as cytokines and chemokines. There are proinflammatory mediators and anti-inflammatory mediators, and this proper cross-talk will lead to the successful elimination of pathogens. Cytokine storms occur when there is dysregulation of the immune system and causes a hyperinflammatory stage due to excess production of cytokines. This may lead to influenza-like states, leading to hypercoagulability and end-organ failure and even can lead to death of an individual.⁶

Platelet activation and hypercoagulability

Procoagulant activity and antifibrinolytic activity lead to coagulation in COVID-19 patients. COVID-19 associated coagulopathy (CAC) affects multiple organs and tissue sites, such as skin purpura; post-mortem changes in skin (thrombus in the shin also called COVID toe), myocardial infarction and neurological dysfunction. The microthrombi can cause multi-organ failure.⁴

Neutrophil Extracellular Traps(NETs) and thrombosis 

Neutrophils are an important inflammatory mediator, and they release chemokines and cytokines. They also release NET, which is a byproduct of programmed cell death or NETosis. NET is a web-like structure comprising DNA, histones, microbial proteins, oxidant enzymes, coagulants, and complement factors. It has a positive correlation with thrombus, via the expression of functional tissue factor and capturing platelets.⁴ 

Figure 2 - schematic representation of thrombus formation in a COVID-19 patient.⁷

Clinical manifestations of COVID-19-related thrombosis

Thrombosis occurs in the venous, arterial and microcirculatory systems and can involve most of the organs and organ systems.COVID-19-associated thrombosis affects arteries as well as veins. It can also, in turn, affect multiple organs of the body, and the most commonly affected part is the veins. Ischemic stroke, deep vein thrombosis(DVT), pulmonary embolism(PE), limb ischemia, mesenteric ischemia and myocardial infarction. The most common among them are PE and DVT, and they are of venous type, and one of the most common causes of COVID-19 deaths in ICU.⁵

Diagnostic approaches

Most commonly, clinical examination as well as history taking would give a hint to the diagnosis. To confirm COVID-19, Reverse transcriptase PCR (RT PCR) is performed, a swab is taken from the nasopharynx, and PCR is performed: a highly specific and sensitive method. Uncommonly, serological tests and biosensor-related tests are also used. Some imaging modalities are also performed, like chest X-ray and CT scan, to evaluate the severity of the infection.⁸ D dimer is important to assess thrombotic events in a patient with severe COVID-19, so that we can prevent the ailments related to it. 

Management and treatment strategies

The management of DVT is the use of unfractionated heparin(UFH) or Low molecular weight heparin ( LMWH), direct oral anticoagulants (DOACs)and warfarin. LMWH is given for patients with COVID-related thrombosis with no interaction with COVID and direct oral anticoagulants (DOAC) for patients post-hospitalisation.⁹

The treatment of COVID-19 is based on the severity. If it is mild, then antipyretics, mild pain killers, antitussives, and antioxidants are provided.

If it is severe and oxygen saturation is low, then oxygen should be stabilised, and the treatment for pneumonia should be taken according to the severity of pneumonia. of antibiotics, antivirals, steroids, and fluid intake are essential.¹⁰

Summary 

COVID-19 is a viral infection caused by SARS-CoV-2, and it spreads by droplets, with a very high transmission rate. high. It usually affects the lungs, and can lead to pneumonia, it can progress to ARDS, and it can even lead to the death of an individual. It usually causes complications like thrombosis. There are many mechanisms, like endothelial injury, hyperactivity of inflammatory mediators, hyperactivity of factors causing clotting or a decrease in the activity of antifibrinolytic factors. These can cause venous and arterial thrombosis, most commonly PE and DVT. These can be detected by D-dimer in the blood, a marker which helps to detect clots. It usually occurs in severely ill ICU patients, and they should be given anticoagulants, and it should be continued post-hospitalisation. The long-term effect of COVID-19 is CAC, and these clots can be at the microvasculature level also, so proper testing and treatment should be instituted if any symptoms of clotting are encountered. If left untreated, it can cause end-organ failure and may lead to death.