DISCUSSION
We compare laboratory finding for kidney and liver function between
patients who were recovered from COVID-19 with the died patient during
the same period. To our knowledge, this is the first study that has made
such a comparison. Our goal was to investigate the possible cause of
death other than respiratory failure for the patient with COVID-19.
Many studies conducted to investigate the risk factors for the
development of AKI among COVID-19 patients. Old male gender
(>50 years) have been confirmed to associated with a higher
rate of AKI compared to young and female patients [13]. Another
study concluded that increased ten years of age could be associated with
a >10% increase in the risk of AKI [14]. Besides,
other independent factors related to the development of AKI and
mortality rate in COVID-19 patients include DM, hypertension, WBCs
count, respiratory rate during disease episode, COPD, and previous
history of chronic kidney diseases [15]. These were consistent with
our result in which, died patients were older than recovered patient,
and 76.09% were male. Meanwhile, the respiratory rate at admission was
higher among died patient. The presence of COPD and hypertension could
be the direct cause of death and the causative for AKI (Table 1).
Based on the previous researches and the wide spectrum of the involved
mechanisms, COVID-19 patient with underlying AKI, indeed required
mechanical ventilation and ICU admission and might prognoses with worse
outcomes compared to healthy kidney patients [16]. In this study,
all of them died patients were admitted to the ICU at least two days
before death and died patients’ data were collected for this study a day
before death was reported in the ICU.
Although patients with renal diseases have more risk for infection with
COVID-19, patient infected by SARS-CoV-2 without a history of renal
problems might opposite a burden for severe kidney injury and may
progress to renal failure. Unfortunately, there was a less renal
recovery in patients diagnosed with CVID-19 comparing to the patient
with a negative result for COVID-19 [17]. Furthermore, COVID-19
patients with an advanced stage of AKI (Stage III and more) were
reported to have more than 30% higher incidence for death compared to a
patient with normal or subnormal kidney function [18]. Based on the
previously mentioned facts, our result confirms that the renal function
of died patients was ranged from normal to mild renal insufficiency at
admission and then progressed to critical stage III and IV before death.
Further, the non-significant difference in S.Cr level and eGFR between
the died and recovered patients at admission and the progression of
renal injury that is confirmed by spark elevation in S.Cr
(>2.1 fold), BUN (> 62.2%) and reduction in
eGFR (>62.3%) when we compare renal function test one day
before death with the values obtained on admission. Altogether, these
results indicate an association of AKI and mortality among COVID-19
patients (Table 2). Although studies showed a low rate of renal
replacement therapy for COVID-19 patients with advanced AKI [19],
this result explained by the high rate of mortality in advanced renal
disease among patients suffering from SARS-CoV-2 infection. By this
study, the risk of mortality in COVID-19 patients was strongly related
to AKI (S.CR HR 44.23; 95% CI: 16.34, 119.70, p=0.000) and (BUN 13.04%
versus 2.28%, HR 5.59, 95% CI: 1.86, 16.84, p=0.020) (Table 5, Fig.
3). In this regard, continuous monitoring of renal function with
preventive and supportive therapies of renal disease is crucial for
COVID-19 patients.
Another potential mechanism of AKI involves SARS-CoV-2 related cytokine
storm that is related to immune response deregulations. It is a cytokine
related systemic inflammatory response resulting in a variety of
clinical manifestations such as uncontrolled high fever, CNS
abnormalities, hepatic injury, lymphadenopathy and kidney toxicity
related to the massive release of cytokines such as IFN-c, TNF, IL-1,
IL6 and IL-18, and, if untreated progression to multiple organ failure
(MOF) is almost inevitable [20]. Patient with cardiac comorbidity
(particularly right ventricular failure secondary to COVID-19
pneumonia), or other predisposing factors for hypovolaemia, sepsis or
nephrotoxicity; besides, macrophage activation syndrome, and the
development of microemboli and microthrombi in the context of
hypercoagulability and endotheliitis might lead to kidney and liver
congestion and subsequent AKI and liver injury [21]. The results of
this study confess the role of cytokine storm in the concurrent
deterioration of renal and hepatic functions in COVID-19 patients death.
The liver biochemistry changed dynamically in patients infected by
SARS-CoV-2 during the clinical course. ALT and total bilirubin founded
to be an increase in 28% and 18%, respectively [22], in an early
study in Wuhan, and 53% in a subsequent study [23]. The degree of
acute liver injury was different in COVID-19 patients. The need for ICU
was more prevalent in patient demonstrate high levels of ALT/AST, ALP
and total bilirubin. Furthermore, the prevalence of abnormal liver
biochemistry is high in COVID-19 patients at admission and increased
during the disease course [24]. Importantly, these changes in
hepatic parameters have a potential impact on COVID-19 patients and
independently resulted in admission to ICU. Moreover, many studies
showed that patients with the chronic hepatic disease were more liable
to developed severe COVID-19 [25]. The previous facts are consistent
with our results, in which only bilirubin was significantly higher at
admission among died patients, whereas, just before death, extreme
elevation in AST, ALT, and bilirubin were observed (Table 4, Fig. 2).
Studies were conducted and suggested that abnormal liver function can
result from an infection of bile duct cells by SARS-CoV-2; however,
alkaline phosphatase (ALP) founded not specific for COVID-19 patient as
the bile duct injury-related index [26]. Interestingly, acute liver
injury was believed to be due to the adverse drug reaction in patients
using medication for the severe stage of COVID-19 [27]. Currently,
many reports focus on the systemic inflammation that is associated with
COVID-19 as a cause of liver injury [28]. These confirm our insights
that cytokines storm could be the causative for kidney and liver injury
with subsequent mortality in COVID-19 patients. Although the available
data about the effect of a different antiviral drug on hepatic function,
the use of corticosteroid in COVID-19 patients also seemed to induce
acute hepatic injury [29]. This study was conducted to patients
administered uniform protocol of therapy to exclude the effect of the
drug on the results, taking into consideration the variability in the
duration of therapy and doses used.
Even though no patients had recorded for short-term mortality due to
liver injury, studies were focused on the role of regular hepatic
biochemistry monitoring on hospitalization period and COVID-19 patients
outcome [30]. More importantly, because of a large number of
infected patients recorded daily worldwide, the effect of liver injury
on COVID-19 patient outcomes is valuable, and its predictors can improve
a patient’s health [3].
Therefore, in our study, besides AKI, we focused on the prognostic role
of liver injury in COVID-19 patients and observed significant-high
hepatic parameters indicative for liver injury among patient who are
died.