Human coronaviruses (HCoV) are single-stranded RNA viruses. There are currently four so-called “classic” or “new” coronaviruses, which circulate in winter. They are the cause of moderate respiratory infections in the general population.
However, infections can be more severe in susceptible populations. In particular, HCoVs are involved in 2 to 7% of hospitalizations consecutive to a respiratory infection, in particular in children and the elderly or immunocompromised. Therefore, they belong to the panel of respiratory viruses sought during the routine diagnosis of respiratory infections using molecular biology tools. These so-called circulating coronaviruses are to be distinguished from the two emerging coronaviruses, SARS-CoV and MERS-CoV which are associated with more severe respiratory pathologies.
They are distinguished from other HCoVs by their higher epidemic potential, their greater health impact and their atypical mode of circulation. Like paramyxoviruses and Influenza viruses, coronaviruses should be monitored for their risk of emergence into the human population from an animal reservoir
Clinical manifestations of coronavirus infections
“Classic” and “new” coronaviruses
The “classic” (HCoV-OC43 and HCoV229E) and “new” (HCoV-HKU1 and HCoV-NL63) coronaviruses are generally associated with mild infections of the upper respiratory tract. Coronavirus infections are characterized by non-specific symptoms that vary from patient to patient. In the general population, HCoV infection is most often associated with more or less symptomatic rhinitis or nasopharyngitis. When the infection is symptomatic, the most often described clinical signs are fever, cough, myalgia and nasal congestion.
The pathologies induced by the different HCoVs are similar and the clinical picture alone does not allow them to be distinguished from each other or from other respiratory viruses, such as rhinoviruses, Influenza viruses, metapneumoviruses, respiratory syncytium virus (RSV) or para influenza viruses (PIV). In the elderly, young children and immunocompromised patients, more severe and even fatal respiratory tract infections may be seen.
For example, HCoV-NL63 has been associated with bronchiolitis and broncho-tracheitis, two acute infections of the lower respiratory tract of infants. HCoV-HKU1 was identified for the first time in a patient suffering from pneumonia. Subsequently, it has been associated with community-acquired pneumonia, mainly in the elderly or with an underlying pathology.
During an HCoV infection, moderate enteric pathology (gastroenteritis, diarrhea) is sometimes observed in addition to respiratory pathology. To date, it is not yet clearly defined whether enteric involvement is an indirect consequence of the infection or whether HCoVs have a proven enteric tropism. HCoV have repeatedly been implicated in neurological damage. Several studies already old tend in particular to associate them with multiple sclerosis (MS).
The first speculations as to the implication of a coronavirus in MS date back to the 1980s. Studies were then based on the observation of particles similar to coronaviruses in the brains of patients who died of MS or on the detection of antibodies directed against coronaviruses, particularly HCoV-229E and HCoV-OC43.
More recently, molecular studies have detected the RNAs of these coronaviruses in brain-spinal fluids or in the brains of patients, some of whom had MS or other neurological disorders, but also within a control group. These data suggest a neuroinvasive potential of these coronaviruses, but their implication in the development of neurological pathologies is debated.
Severe Acute Respiratory Syndrome or SARS
The term SARS designates the pathology induced by SARS-CoV. This is a coronavirus which emerged in November 2002 and which circulated pandemic until July 2003. SARS-CoV is characterized by an incubation period of 2 to 14 days. The first symptoms observed are:
- a high fever, above 38 ° C, as well as
- a moderate respiratory syndrome.
- Coughs,
- headache or throat pain and
- general tiredness have also been reported in some patients. In a few days, the symptoms progress, causing an acute respiratory distress syndrome which may require respiratory aid in the most susceptible patients.
During SARS-CoV infection, neutrophilic leukocytes and macrophages infiltrate the lungs and initiate an inflammatory response. The level of pro-inflammatory cytokines increases, while lymphopenia is observed. These phenomena are at the origin of the alterations which occur in the lungs, in particular, of diffuse alveolar damage (DAD). At the same time, a formation of hyaline membranes and edemas is observed. These morphological alterations result in hypoxia.
In a second step, DAD is associated with hyperplasia of type II pneumocytes and with scaly metaplasia, these two characteristics being indicative of a process of scarring of the lungs. The worsening of these histological changes can lead to severe pneumonia and death of the patient. On radiography, unilateral or bilateral condensation of the lungs is observed.
Classic and new coronaviruses
Since the emergence of SARS-CoV in 2002-2003, numerous epidemiological studies of HCoV have been carried out, using increasingly efficient and sensitive serological and molecular tools. In the last epidemiological studies carried out in different countries of Africa, Asia, North and South America, Europe and Australia between 2001 and 2014, an HCoV was detected in 2.1 to 12% respiratory samples subjected to a molecular respiratory diagnosis. HCoVs are responsible for 2 to 7% of hospital admissions following an acute respiratory tract infection, especially in children and the elderly or immunocompromised. These studies highlight seasonal circulation in autumn and winter in temperate regions, where the year is divided into four distinct seasons.
There also seems to be a cyclical variation every two to three years of the different HCoVs. Overall, HCoV-OC43 and HCoV-NL63 are the most commonly detected coronaviruses. This tendency can be associated with a possible immune protection of HCoV-NL63 against HCoV229E on the one hand and HCoV-OC43 against HCoV-HKU1 on the other hand, due to their belonging to the same genus (Alphacoronavirus and Betacoronavirus respectively).
HCoV-NL63 and HCoV-OC43 are the coronaviruses encountered early in childhood. Most children get seroconversion to these coronaviruses before the age of 3. The individuals in whom these viruses are most commonly detected are young children, the elderly and caregivers. However, the induced pathology being mainly benign, each individual is likely to meet one of these viruses without being the subject of a viral diagnosis. Indeed, in 2008, Severance et al. it is highlighted that more than 90% of a group of 196 adults representative of the general population was exposed to HCoV-OC43, -229E and -NL63, while a lower proportion of 59.2% was exposed at HCoV-HKU1
Covid 19 and its thromboembolic form
Covid 19 is currently a global health problem with health, safety, economic and social implications. The causative agent is SARS-COV2, a strain that appeared in December 2019 at WUHUN and has spread in pandemic mode.
The virus has a very high contagion potential, it can spread quickly according to an exponential model contaminating thousands of people in the absence of barrier measures and means of strict containment. The disease is highly contagious. No country is spared.
Why does SARS-COV 2 have frequent thromboembolic complications?
We have recently been able to understand the mechanism of lesion of SARS COV2, thanks to the results of autopsies made by the Italians and which have been published recently.
SARS COV 2 has a vascular tropism, it attacks the endothelial cell (the cells of the vascular wall). It attaches to cells thanks to its protein Spike (major immunological determinant of the virus). The cellular receptors are the angiotensin receptors These receptors are overexpressed in hypertensive patients, which explains the serious forms observed in hypertension.
Cell lesions caused by the virus resemble diffuse vasculitis, mainly affecting the vascular wall of the lungs, causing a shunt effect.
It is therefore not a classic ARDS observed during classic pneumonitis, which explains the high mortality rate in intensive care, it is therefore advisable to change your therapeutic attitude and not to resort to intubation early Endo tracheal, Indeed, non-invasive ventilation could be an interesting alternative that can prevent the worsening of lung damage caused by mechanical ventilation.
Pulmonary embolisms and micro thromboses are also observed in the pulmonary level but also in the brain, liver, kidneys and intestines, which explains the multi-visceral manifestations of the pathology. Frostbite lesions have recently been described, vascular skin lesions have been implicated.
The virus causes a prothrombotic state at the vascular level and diffuse endothelial lesions predominant at the pulmonary level.
This new explanation of the disease will allow us to move towards new therapeutic avenues. Hydroxychloroquine therefore largely finds its place especially at an early stage (Hydroxy chloroquine is recommended in the treatment of certain vasculitides).
Thromboembolic prophylaxis could prevent these complications, see effective anti-coagulation in patients at high risk (in obese, hypertensive patients and patients with a history of cancer) and in severe forms.
I think that patients with COVID 19 should be put on early anticoagulant therapy as a preventive, or even curative, treatment for patients at risk in combination with hydroxychloroquine and AZITHROMYCINE.
What are the effective collective protection and prevention measures?
Total and strict confinement is the best means of collective protection and prevention. Tunisia adopted this strategy since March 22, 2020, when the country recorded 54 cases of COVID 19 + with an increase of 15 cases in 24 hours. However, the strict application of the containment policy appears to be difficult in practical terms. Indeed, the economic and social consequences are significant. Total confinement also has negative psychological repercussions for the mental health of the population and induces sequelae of post-traumatic stress.
Total containment should not be the only means of combating this disease and should not exceed 60 days in all cases.
The compulsory wearing of a mask by the population makes it possible to effectively control the spread of the virus (the case of South Korea). This strategy makes it possible to shorten the period of strict confinement and to introduce progressive deconfinement without taking the risk of having a second endemic peak.
Hence our approach to diagnose and treat COVID 19 + patients, a strategy that could be adopted within the framework of a national health policy, led by the high national council to fight COVID 19.
Finally
COVID 19 is a serious disease caused by SARS COV2, manifested clinically as systemic vasculitis. Early thromboprophylaxis in infected patients, see effective anticoagulation, in combination with hydroxychloroquine and AZITHROMYCINE could prevent the transition to serious forms and thromboembolic complications, which can reduce mortality in patients with COVID19.