Effect of coronavirus disease in patients with kidney disease in India

Shashi Prabha Singh1, Preeti Sharma1, Durgesh singh2, Pradeep kumar*1, Rakesh Sharma3, Rachana Sharma4 1Department of Biochemistry, Santosh Medical College and Hospital, Santosh Deemed to be University, Ghaziabad, Uttar Pradesh201009, India 2Department of Anatomy, Government Medical College, Saharanpur, Uttar Pradesh, India 3Department of Biochemistry, Government medical college, Saharanpur, Uttar Pradesh, India 4Department of Biochemistry, TSMmedical college, Lucknow, Uttar Pradesh, India


INTRODUCTION
As now we came to known that novel (SARS-CoV-2) severe acute respiratory syndrome coronavirus 2 is responsible for contagious coronavirus disease 19 (COVID-19) (Sun et al., 2020). These global pandemic infect over 8.5 million people worldwide and over 924951 deaths till mid-September 2020 (World Health Organization, 2020a).
It spreads from a person to another via cough droplets or direct contact. The incubation period of the disease is one to 14 days. As large number of population is affected by this SARS virus, and the clini-cal symptoms of the disease range from minor manifestations like diarrhoea to major manifestations like, septicemia, cardiopulmonary arrest, bilateral pneumonitis, acute respiratory distress syndrome (ARDS) and ultimately death due to loss of immunity and in lammation (Ruan et al., 2020). An outburst of SARS-CoV-2 is mainly seen in senior and people who are already suffering from chronic diseases. COVID-19 mostly occur in those kidney disease patients whose kidney is transplanted or those who are immunosuppressed and undergone hemodialysis. It is assumed that behind high incidence and prevalence of mortality in CKD patients is systemic in lammation (Kurts et al., 2013). In this review article focus on COVID-19 pathogenesis in CKD patients and the association between CKD, immune dysfunction and COVID-19 along with therapy of COVID-19 in CKD.

Pathogenesis of Covid-19 in CKD
Coronavirus disease incubation period is of 1-14 days during which the virus is transmitted, and the subject suffering is generally asymptomatic . COVID 19 is transmitted through close contact from a person to another, and infection occurs mainly through coughing or sneezing (Rubens et al., 2020). COVID-19 virus enters the lungs through a surface receptor ACE2 (angiotensinconverting enzyme 2). It starts infection this shows that there is a strong association between COVID-19 and CKD and inally with RAS (reninangiotensin system) (Gurwitz, 2020). In the RAS pathway, two enzymes, ACE2 and ACE (angiotensinconverting enzyme) play vital roles in pathogenesis. In the RAS pathway angiotensinogen is converted to angiotensin I (AngI) and angiotensin II (AngII) catalyse by renin (secreted in the kidney by the juxtaglomerular cells) and ACE respectively and while the same time ACE2 convert AngII to angiotensin-(1-7) (Ang[1-7]). AngII acts via two receptors: angiotensin II receptor type 1 (AT1R) and angiotensin II receptor type 2 and Ang [1-7] act via MAS receptor. Both angiotensins (AngII and Ang 1-7) exert opposite actions vasoconstrictive and vasodilatory, respectively. AngI regulates ACE and ACE2 formation, and AngII respectively depicted in Figure 1. In lung ACE2: ACE ratio is 1:20, and in kidneys ACE2: ACE ratio is 1:1. Attention should be paid toward drugs that increase ACE2/Ang-(1-7)/Mas or decrease ACE/Ang II/AT1R pathway to treat COVID-19 and understanding the role of ACE2 in the disease (Tan et al., 2018).
In healthy individuals, interferon (IFN) type, I play a major role against infection. Coronavirus may reduce the IFN type I and lead to overproduction of pro-in lammatory cytokines due to which viral load increase limitless, and also thought to play a major role in pathogenesis, as proven by therapeutic trials of both antiviral drugs and neutralising anti-interleukin-6 (IL-6) antibody. Defence against COVID-19 infection is mainly to prevent oxidative stress and in lammation, but if not appropriately regulated effect may be harmful (Dounousi et al., 2006). Lymphocyte, Natural killer (NK) cells, B and plasma cells play a role in defence mechanism by neutralising SARS-CoV-2 and protect tissue from injury. Depletion of Lymphocyte, NK, B and plasma cells is thought to impair antiviral defence. (Giamarellos-Bourboulis et al., 2020) In COVID-19, there is the involvement of complement, and so the use of both strategies the anticomplement C5 and the complement C3 inhibitor, antibody eculizumab and the Amyndas -101 should be triggered respectively (Risitano et al., 2020).

CKD, Immune Dysfunction and Covid-19
Presently, few data are available on CKD and COVID-19. CKD causes persistent systemic in lammation and inally lead to immunosuppression (Figure 2). CKD cause alteration in an immune system characterised by phagocytic B and T cell disturbance and also increased pro-in lammatory cytokines and inally progress towards renal disease (Vaziri, 2012).
In CKD, a neutrophil function is decreased, and inally, an immune disturbance occurs (Martin-Sanchez et al., 2018). Likewise, in advance stage of CKD B lymphocytes increase the rate of apoptosis that may contribute to B lymphopenia, and T cells are activated in an early state. Activated T cells lead to immune dysfunction, apoptosis and inally, infection. (Meier et al., 2002) Persistent in lammation progress CKD and cardiovascular disease (Cohen and Hörl, 2012). There are multiple causative factors of chronic in lammation in CKD, like oxidative stress, infections and haemo dialyses related factors (Haag-Weber and Hörl, 1996). Thus, there is an association in DNA/RNA of microorganism with oxidative stress, serum Creactive protein, cytokines and dialyses (World Health Organization, 2020b). Currently, it is not clear to what extent the coronavirus damages renal cells or whether the cytokine storm syndrome is the cause of kidney injury (Cheng et al., 2020). Knowledge on the involvement of kidney and stages of injury in COVID-19 will be helpful in theranostics of COVID patients.

[1] [2] Immune de iciency and systemic in lammation are the primary manifestations of CKD [3] Relation between CKDco-morbidities [4] therapy
more frequent in hospitalised and 12-fold more frequent in those with ICU admission COVID-19 patients than non admitted patients. The prevalence ratio in ICU patients ranged from 2-to 6.7fold (Chow et al., 2020).

In CKD Treatment of Covid-19
At present, no effective treatment is available for COVID-19.
Treatment of COVID-19 with CKD may be general, supportive and other measures include complications treatment and treatment of secondary infection and if require replacement of kidney.

General management
All COVID-19 patients need an N95 mask and PEP kit to cover the whole body to prevent the transfer of infections to other healthy individuals and quarantined. Early admission of severely ill patients to ICU (intensive care unit) and. PICU in tertiary hospitals along with Supportive care such as bed rest, nutritional and luid support, and maintenance of blood pressure and oxygenation.

Therapy for the virus
There is not any particular therapy for the virus of COVID-19 at present. Chloroquine phosphate show some amount of resistant against COVID-19. COVID 19 can be treatment Successful with remdesivir (World Health Organization, 2020b).

Others treatments
High-volume haemo iltration remove in lammatory cytokines (IL-6). Continuous renal replacement therapy can be used in the treatment of SARS and improved the Organ Failure within seven days in patients with sepsis. Therefore, CRRT may play a role in CKD patients with COVID-19 and sepsis or multiorgan failure syndrome (Chu et al., 2005).

COVID convalescent plasma
COVID convalescent plasma therapy (CCP) is effective to reduce viral load and to prevent further tissue damage in COVID patients before the development of in lammatory life-threatening organ failure (?).