Introduction

The novel coronavirus disease 2019 (Covid-19), as we know, has raised serious questions among healthcare professionals and the general population alike. Ever since the WHO declared this new virus caused by SARS-CoV-2 as a pandemic, it has been a growing global health concern. As of February 15, 2021, the death toll has reached approximately 2.41 million as against 109,155,627 confirmed Covid-19 cases worldwide (Dong, Du, & Gardner, 2020). At the same time, India's tally of Covid-19 positive cases was 10,925,710 with 155,813 fatalities. Globally, around 81.5 million confirmed cases recovered from the disease, with a recovery rate of 74.66%. In contrast, India's recovery rate was 97.32% of all confirmed cases, i.e.,10,633,025. The number of Covid-19 cases per million for India is projected with a low incidence of 8,030 points per million, as the worldwide figure rose to 14,038 points per million. The global impact of covid-19 and its influence on the disease progression was unmistakable, with astounding statistics.

On the other hand, Mizoram, the second least populous state with 1,097,206 (2011 census), has been the center of attention in its fight against the pandemic (Censusindia.gov.in, 2021). Figure 1 depicted the map of India showing the geographical location of Mizoram in the northeast region. Going into the seventh month since the pandemic and becoming the only Indian state without Covid-19 death, Mizoram recorded its first casualty on October 28, 2020. Earlier on March 25, the state registered its first Covid-19 case. Up until now (as of February 15, 2021), Mizoram reported a total of nine Covid-19 deaths with 4392 confirmed cases, including 3214 males and 1178 females (Government of Mizoram, 2021). A total of 4366 confirmed cases recovered from the disease with a recovery rate of 99.40%.

Currently, there is no scientific record on the clinical characteristics of deceased Covid-19 individuals in Mizoram. The existing literature is equivocal in understanding chronic conditions and mortality risk of Covid-19 as it varies across geographical locations. The diseased condition's ambiguity underlines the need to identify comorbidities and associated risk factors among confirmed Covid-19 dead individuals. This information will undoubtedly be critical in the knowledge and control of mortality these trying times and the future pandemic. The current study evaluates the clinical characteristics and determines the prevalence of comorbidities and associated risk factors in dead Covid-19 individuals.

METHODS

Study oversight

The Institutional Ethical Committee, Hospital and Medical Education, Mizoram approved the study. A total of eight confirmed Covid-19 deaths registered at Zoram Medical College Mizoram, India, till February 14, 2021, were included in the study. Zoram Medical College is a dedicated Covid-19 referral hospital during the pandemic outbreak. The study excluded one confirmed death from outside the state's designated Covid-19 facility.

On April 7, 2020, Zoram Medical College introduces real-time reverse transcription-polymerase chain reaction (RT-PCR) tests to confirm SARS-CoV-2. Subsequently, Covid-19 tests began at nine designated district hospitals on June 12, 2020, with TrueNat machine- Truelab Quattro micro-PCR. Informed consent was taken from the deceased family members, concerned medical authorities, and family physicians.

Participants and Procedures

The study participants were hospitalized after confirmation of Covid-19 positive results on RT-PCR. In the case of a Rapid Antigen Test (RAgT) positive, a nasopharyngeal swab sample on RT-PCR assay was used for a confirmatory test. We collected information about Covid-19 Mizoram statistics from the Government of Mizoram Covid-19portal (Government of Mizoram, 2021) and by direct access of the deceased medical file from the hospital medical record section. In this regard, data were analyzed based on data collection form containing past medical history, ABO blood grouping, the time duration of hospital and Intensive Care Unit (ICU) stay (between admission and death), clinical and laboratory findings, and presenting symptoms upon hospital admission, underlying comorbidities, and complications. Data on the outcome variables were gathered and interpreted by the authors.

Clinical parameters included in the study were arterial blood pressure (systole and diastole), random blood sugar (RBS), heart rate, respiratory rate, oxygen saturation pressure (SpO2), and temperature. Laboratory parameters consisted of liver function test: total protein- albumin and globulin, total bilirubin- direct/conjugated and indirect/unconjugated, aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP); kidney function test: blood urea and serum creatinine; serum electrolytes: sodium and potassium; complete blood count: total White Blood Cells (WBC) and lymphocytes count, hemoglobin (Hb), and Erythrocytes Sedimentation Rate (ESR).

Statistical analysis

The study analyzed the outcome variables between two age groups, i.e., below 60 years (<60) and above 60 years (>60). Categorical variables were denoted as frequency and percentages, and descriptive data of continuous variables as means, standard deviation, median and interquartile range, as appropriate. Continuous variables were analyzed using the Independent 't' test for group comparison. Proportions of categorical variables were determined using the Chi-squared test ( $\square$ 2) and Fisher's exact test, as appropriate. Statistical analysis used was IBM SPSS Statistical software, Version 26.0 (IBM Corp: Armonk, NY, USA).

RESULTS

Estimating mortality rate of Covid-19

The proportion of Covid-19 Case Fatality Rate (CFR) was calculated as the total number of Covid-19 deaths divided by the total number of confirmed Covid-19 cases, multiplied by 100 (World Health Organization, 2020).

$Case Fatality Rate (CFR, in \%)=\frac{Number of deaths from disease}{Number of confirmed cases of disease}\times 100$

The crude mortality rate or the crude death rate (CDR) measures the probability that an individual is likely to die from the disease in a given population. It was calculated in percentages as the total number of Covid-19 deaths divided by the total population, multiplied by 1,000,000.

The proportion of CFR, CDR per million, recovery rate, cases per million, and the projected total population for the World, India, and Mizoram, i.e., 7.674 billion, 1.366 billion, and 1,238,244 respectively, are given in Table 1. Similarly, as of February 15, 2021, the total number of confirmed Covid-19 cases and the total number of confirmed Covid-19 deaths Worldwide, India and Mizoram are presented in the table. The case fatality rate in Mizoram was 0.2%, 1.4% in India, and 2.2% worldwide. The crude death rate was significantly lower in Mizoram (07.27% per million) compared to India (114.03%) and the World (314.05%). Concerning India (97.32%) and the World (74.66%), Mizoram recorded a high recovery rate of 99.40% as of February 15, 2021. Covid-19 confirmed cases per million; the Worldwide figure was 14038, 8030 for India and 3547 for Mizoram. Figure 2 projected estimation of Covid-19 mortality rate.

Age group-specific demography, clinical characteristics, and laboratory findings among Covid-19 deceased

The decedents' mean age was 62.88 years, 60.71 for males and 78 for a female, with a standard deviation (SD) ± 18.658 and Inter-quartile range (IQR) = 44-78. The age group between 65 and 84 years has the most casualties and the highest percentage (50%) of other age groups as shown in Table 2. The death percentage >60 was significantly higher, with 62.5% compared to 37.5% in <60. It is apparent from the analysis that the rate of Covid-19 fatalities increases with increasing age. Males (87.5%) had a significantly higher number of Covid-19 deaths than females (12.5%). Half of the decedents had blood group B, the most dominant among blood ABO groupings. Blood group type A and AB followed, with 37.5 and 12.5 percent, respectively, and no casualties with blood group O. In the age group <60, the median time intervals for hospital and ICU between admission and death were 18 days, each with SD±7.57 days, respectively. The median lengths of hospital and ICU stay in the age group >60 were 15±6.42 and 11±5.72 days. As shown in Table 3, the total median lengths of hospital and ICU stay were 15.50±6.45 and 11±6.36 days, respectively. The study compares the specific age group >60 and <60 with the deceased individuals' clinical characteristics. Based on the clinical findings upon arrival to hospital, we found no significant differences on the parameters of systolic blood pressure (P = 0.65), diastolic blood pressure (P = 0.61), random blood sugar (P = 0.61), heart rate (P = 0.06), respiratory rate (P = 0.97) and oxygen saturation pressure (SpO2) (P = 0.28) and temperature (P = 0.71).

Table 4 presented the comparison between age groups (<60 and >60) and presenting symptoms. Fever was the most common presenting symptom seen in 75% of decedents with Covid-19 pneumonia, comprising 50% and 25% in the age group <60 and >60, respectively. Shortness of breath/ difficulty breathing (62.5%), cough/ sore throat (50%) followed. Among others, generalized weakness/ fatigue/ myalgia, chest pain, delirious/ decreased levels of consciousness, headache, and diarrhea/ abdominal pain represented the minority of the

deceased individuals. Hypertension (>60 = 50%) and diabetes mellitus (>60 = 37.5%) were the most common comorbidities with 62.5%, and their concurrence accounts for 87.5% of the decedents. Cardiovascular disease followed with 25%, and 75% reported having any underlying chronic conditions.

The less common comorbidities reported were chronic liver disease, pulmonary tuberculosis, neuro-cerebral atrophy/ dementia, and immuno-compromised states. The elderly population (>60) was more susceptible to develop underlying comorbidities compared to the younger age group (<60).

As demonstrated in Table 4, acute respiratory failure and cardiovascular conditions were the most common complications. Both contributing 87.5% each, and more prevalent among the elderly population (>60) than with the younger age group (<60). Hyper-glycemia was associated with 37.5%; acute liver failure, jugular venous pressure, and neurologic conditions with 25% each. Acute kidney failure, dyslipidemia, pulmonary tuberculosis, secondary bacterial infection, and urinary tract infection collectively contributed 62.5% of the decedents.

Table 3 presented the means and SD between the age groups (<60 and >60) with the total means and p-value of laboratory parameters. There were no significant differences (P>0.05) between the groups and laboratory parameters, except for alkaline phosphatase, which was significant at P<0.05 (P = 0.002). The average means of aspartate transaminase (AST) and alanine transaminase (ALT) were raised substantially above the upper limit. Similarly, serum creatinine and blood urea levels were elevated, including total white blood cells (WBC) and erythrocytes sedimentation rate (ESR). There was a marked reduction in lymphocyte count, complete protein, and albumin levels.

DISCUSSION

There is a shortage of information and scientific evidence in the north-eastern part of the country and most parts of India. With the rising high number of confirmed cases (10.9 million) and deaths (155,813) in India, the well-being of public health needs considering prospects. Currently, the diseased mechanism is still unknown.

Hence, information on the clinical characteristics and laboratory findings of deceased Covid-19 patients could assist in timely intervention, early diagnosis, and prognosis of Covid-19. The study findings could potentially counteract the detrimental effects of diseased progression and severity of disease infection.

This study emphasized the demography, time intervals between hospital and ICU admission to death, clinical and laboratory findings, symptoms, complications, and comorbidities of deceased Covid-19 individuals.

Age is one of the common risk factors for Covid-19 fatality. In our study, the proportion of covid-19 death was higher in the age group above 60 years (62.5%) than below 60 years of age (37.5). The mortality risk of Covid-19 significantly increases with increasing age. Based on data collected from 45 nations, the age-specific mortality rate among

>60 years was significantly higher and is consistent with other European populations (O’Driscoll et al., 2021). The increased risk of Covid-19 deaths with increasing age could be due to the high prevalence of underlying comorbidities and more susceptibility to infection because of an inadequate immune response (Verity & Okell, 2020).

Our study comprised a higher proportion of Covid-19 deaths in males (87.5%) than their female counterparts (12.5%). One study reported the mortality risk for men to be more than doubled compared to women (Pastor-Barriuso & Pérez-Gómez, 2020). According to a survey, gender bias on sex hormones and X chromosomes may play a pivotal role in reduced mortality among women. Females have the innate ability to protect the X chromosomes (single X chromosomes in males) following exposure to infectious disease. Women possessed a more robust immune response to pathogens like SARS CoV-2, suggesting its comparatively low female fatality rate (Li, Jerkic, Slutsky, & Zhang, 2020).

Figure 2 provides information on estimating the Covid-19 mortality rate in Mizoram, across India and the World. The proportion of mortality rate (CFR-0.2 and CDR per million- 7.27) for Mizoram was comparatively lower than the rest of the World. The current global Covid-19 fatality rate of 2.2% is relatively low compared to 30% and 10%, respectively, for Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS) (Petrosillo, Viceconte, Ergonul, Ippolito, & Petersen, 2020). In the study, individuals with blood group B have the highest prevalence of Covid-19 mortality with 50%, followed by blood group A (37.5%) and zero fatality for blood group O. Studies have shown that persons with blood group type A and type B are more vulnerable to Covid-19 infection. In contrast, blood group O has the slightest chance of developing the novel coronavirus. No correlation existed between ABO blood groups with the severity of SARS CoV-2 infection (Samra, Habeb, & Nafae, 2021).

The median time interval of hospital stay (from admission to death) was 15.5 days and 11 days for ICU stay. The length of hospital stay was consistent with other countries ranging between 4 and 16 days (Chen & Wu, 1091; Yang et al., 2020). The median for both hospital and ICU stays (15 and 11 days) was shorter in duration among >60. The elderly population is at increased risk of developing a severe infection, worst outcome, and death from Covid-19. Moreover, the risk factors for ICU admission include age (>60), gender (male), and multi-comorbidities. The concurrence of multiple comorbidities among the male and older age group was strongly associated with increased risks for Covid-19 mortality than the younger age group (Chen et al., 2020). All the decedents in the study were ICU admitted, where 87.5% required mechanical ventilators. Other studies from New York City and the United Kingdom, with 89.9% and 88.5%, recorded a high proportion of ICU admitted patients requiring mechanical ventilators (Richardson, 2020; Wunsch, 2020).

The most prevalent comorbidities associated with Covid-19 deaths include hypertension, diabetes mellitus, and other chronic diseases, were consistent with our study (Javanmardi, Keshavarzi, Akbari, Emami, & Pirbonyeh, 2020; Wortham & Lee, 2020). In Mizoram, both hypertension with 62.5% (12.1% <60; 50% >60) and diabetes mellitus with 62.5% (25% <60; 37.5 >60) was the most prevalent comorbidities associated with deceased individuals. Altogether, 87.5% (25% <60; 62.5 >60) of the decedents had either hypertension or diabetes mellitus or both. 75% of the deceased had at least one of the underlying comorbidities. The death rate was registered 12 times higher in patients with pre-existing comorbidities than without (CDC, 2020). In other countries, a substantial proportion of around 70% to 90% of Covid-19 deceased had at least one of the underlying comorbidities (Guan & Liang, 2020; Pachiega & Afonso, 2020).

Covid-19 pneumonia was associated with each of the decedents. The incidence of fever was three-fourths, shortness of breath three-fifths and half of the deceased had cough/ sore throat, which was coherent with previous studies. Other studies reported the less common symptoms, viz. generalize weakness/ fatigue/ myalgia, chest pain, decreased consciousness/ delirious, headache, diarrhea/ abdominal pain. The elderly and male population have a higher proportion of the most common Covid-19 symptoms (Chen et al., 2020; Huang & Wang, 2020; Wang et al., 2020). Upon hospital arrival, vital signs were monitored on systolic/ diastolic blood pressure, heart rate, respiratory rate, SpO2, and temperature. Objective characteristics on mean arterial pressure, tachycardia, tachypnoea, and oxygen requirement levels did not vary between the advanced and the younger age groups. These clinical findings were similar to a retrospective study of Covid-19 patients with acute respiratory distress syndrome (Shah et al., 2020). Neurological effects like altered consciousness, delirium, seizures, and encephalopathy were reported, as with another research (Ellul et al., 2020). The potential deterioration of the blood-brain barrier enables toxic substances and chemicals to enter the brain. The subsequent impairment of brain function attributable to unknown markers' inflammation causes neurological characteristics seen in several Covid-19 patients.

Our study did not indicate differences between the age groups and laboratory parameters, except for alkaline phosphatase (P = 0.002), where the significant difference was related to previous findings (Wang et al., 2020). Laboratory profile abnormalities with SARS CoV-2 were like the earlier SARS CoV infection (Wang et al., 2020). Research findings demonstrated a significant correlation between laboratory abnormalities and Covid-19 severity (Guan et al., 2020). The study noted an abnormal liver function profile of aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP). The AST and ALT levels were raised substantially above the reference range, indicating higher probabilities of Covid-19 disease progression to severity. A recent study reported the high prevalence of acute liver disease in 64% and 73% of hypertension and diabetes mellitus. 25% of the deceased had acute liver disease, explaining the high proportion of hypertension (62.5%) and diabetes mellitus (62.5%). Furthermore, the clinical attribute of severe Covid-19 pneumonia is the focal endpoint, necessitating ICU admission with mechanical ventilator support (Cai et al., 2020). Numerous studies reported elevated serum blood creatinine and urea nitrogen levels compatible with our study. The high levels of these laboratory findings in acute kidney disease suggest an increased risk of Covid-19 severity and death (Chen et al., 2020; Yang et al., 2020). The decreased lymphocyte count and increased ESR indicate disease severity and worst outcome in Covid-19 (Hui & Zumla, 2019). Covid-19 acts on T-lymphocytes, bringing about changes in the immune response. The study registered a subsequent reduction of lymphocyte counts and increased WBC levels. The levels of lymphocytes and albumin could provide early diagnostic and prognostic factors, as the decreased levels signify the severity of Covid-19 (Li, Liu, & Huang, 2020).

Limitations

There are some limitations. First, the study consisted of only eight deceased individuals from the dedicated Covid-19 hospital, Zoram Medical College, Mizoram. The study excluded one death occurring outside the designated facility. Notwithstanding the nominal sample size, the study's primary purpose was to provide documented information to identify the prevalence of comorbidities and associated risk factors of Covid-19 deceased. Hence, the small sample size could limit the outcome's viability, bias the study results, or misinterpret the results. Second, there were variations in the documentation of the patient's medical profile. Data were extracted as appropriate in some cases, owing to an incomplete laboratory profile test: preliminary or brief medical history, clinical symptoms, and findings upon hospital arrival complicated data entry.

Conclusion

This study evaluates the status of Mizoram on the disease prevalence of comorbidities and risk factors of Covid-19. Based on the findings, the mortality risk of Covid-19 increases with advanced age, male gender, and pre-existing comorbidities. The most prevalent comorbidities are hypertension and diabetes mellitus, and their coexistence accounts for nearly nine-tenth of the deceased. Fever and respiratory symptoms (dyspnoea, cough/sore throat, chest pain) are the common presenting symptoms at the onset of Covid-19 pneumonia.

Acknowledgement

The authors acknowledge the Covid-19 team of doctors and healthcare workers from the dedicated Covid-19 hospital, Zoram Medical College, Mizoram. The authors thank the management staff who helped immensely in carrying out the research work.

Funding Support

The authors declare that they have no funding support for this study.

Conflict of Interest

The authors declare that they have no conflict of interest for this study.