The present study provides an insight on the clinical and laboratory characteristics of 201 telangana death cases, mostly primary or secondary contacts of infected COVID-19 patients, treated in Gandhi Hospital, Telangana. The mean age of the study group was 56.7years. Earlier two studies from China reported an average age in non-survivors respectively of 65.8 and 70.7 years-old (Du et al. 2020, Du and Tu 2020) whereas a recent European study by Baigi et al. stated that the overall average age in COVID 19 non-survivors was 78.0 years (Biagi et al. 2020). A study by Chen et al (2020) indicated that advanced age is one of the strongest predictors of death in patients with SARS-CoV-2 (Chen et al. 2020). In our study, it was observed that 74.1 % (149) patients were ≥50 years and the mean age of the COVID-19 death cases was lower when compared to the above studies indicating that the age group ≥50 years having a low survival rate in Telangana in comparison to world scenario.
Few studies suggested that though men and women have the same prevalence, men with COVID-19 are more at risk for worse outcomes and death, independent of age (Jin et al. 2020, Li et al. 2020). Male preponderance was observed in our study (147, 71.4%) with 3:1 male-female ratio, reaffirming that COVID-19 was more prevalent in males (Biagi, Rossi et al. 2020, Li et al. 2020).
In a recent study, shortness of breath or dyspnea was found as an independent risk factor leading to death in 74% of fatal patients with COVID-19 (Chen, Liang et al. 2020). Similarly in our study, increased hypoxemia led to dyspnea which may have resulted in 85% COVID-19 deaths. Sore throat was observed in only 4.4% death cases making them least common respiratory symptom. Among the Non-respiratory symptoms, fever (63.1%) was the most common symptom presented which was also observed as common symptoms in various studies in different regions in the world (Guan et al. 2020, Li et al. 2020). Few death cases had underlying comorbidities like asthma and COPD which is in concordance with existing study by Guan et al (2020) which stated that patients with COVID-19 rarely reported as having comorbid respiratory diseases (particularly COPD and asthma) (Guan, Liang et al. 2020). Majority of studies suggested that unlike H1N1 infection, there is no known impact of COVID-19 on mortality in pregnant women with few exceptions (Hantoushzadeh et al. 2020, Pierce-Williams et al. 2020, Schwartz 2020, Zaigham and Andersson 2020). In our study, only one pregnant woman was reported as COVID positive deaths making it difficult to comment on the mortality rate in pregnant women in our population. In our study we also found one death who had preexisting myasthenia gravis (MG). The impact of the presence of this disease on mortality was unclear (Anand et al. 2020).
Irrespective of management of COVID-19 cases, apart from the virus, other factors are also contributing to the death. To understand this, the patterns leading to death in COVID-19 cases are listed in this paper. The median duration from illness onset to dyspnea was 4.23 days (IQR 2–9) which was lower when compared to the latest retrospective study from China which showed median time from illness onset to dyspnea of 5.5 days (IQR 1–9). Grasselli et al (2020) reported a median ICU length period of 9 days (Grasselli et al. 2020) but in our study, we observed that the median ICU stay was 7 days (IQR: 5–11) which was shorter. An overall time taken for a COVID-19 patient to lead to death was published by different research groups who reported that COVID-19 patients had died at an average of 18.5- 28 days, and few reported the median duration from admission to the intensive care unit (ICU) to death as 7 days (IQR 3–11) (Yang et al. 2020) while others reported as 12 days (IQR 8–15) (Zhou et al. 2020). In our study, early deaths have been reported; 2.5% of cases died in 10 days (IQR 5-15) from the time of onset of symptoms, yet the death rate was observed to be lower.
Radiological findings in a recent study by Naeem et al (2020) suggested that chest radiography was more appropriate to follow the progression of the disease (Naeem K 2020). In this study, 65.5% cases presented with a normal chest radiograph while 35.5% showed abnormal findings. A study by Zhou et al (2020) reported the most common finding in COVID-19 non-survivors to be bilateral infiltrates (72%) followed by ground-glass opacity (67%) (Zhou, Yu et al. 2020). In our study, bilateral infiltrates (34.3%) was most common finding.
Among the death cases, several comorbidities recorded of them, three fourth of the patients (76.6%) presented one or more associated disease, whereas only 47 patients (23.4%) had no comorbidities. Earlier studies reported similar findings showing a higher prevalence of coexisting chronic illness in death cases when compared to survivors (Biagi, Rossi et al. 2020, Yang et al. 2020). Considering co-existing conditions, studies by Li et al. and Biagi et al. stated that among that reported comorbidities, hypertension was a common condition among the death cases (Biagi, Rossi et al. 2020, Li et al. 2020). In our study, HTN (60.7%) was the most common condition followed by DM (48.3%). The higher prevalence of hypertension can be attributed to the role of ACE2. The SARS-CoV-2 virus uses the ACE2 receptor to enter in human alveolar epithelial cells (Sakoulas 2020). The altered expression of ACE2 should increase patient susceptibility to viral host cell entry and may partially explain the high prevalence of hypertension in deceased patients. This indicates that investigation of host factors like ACE 2 receptor gene.
According to literature, DM inhibits neutrophil chemotaxis, phagocytosis, and intracellular killing of microbes. Impairments in adaptive immunity, delay in the activation of Th1 cell-mediated immunity and a late hyper-inflammatory response is often observed in diabetics (Hodgson et al. 2015). In our study, DM was the second leading comorbidity recorded. Thus, it is likely that COVID-19 patients with DM may have dull immune responses leading to severe disease condition and may lead to high mortality in this group of people. A study by Kulcsar et al (2020) examined the effects of DM in a humanized mouse model of MERS-CoV infection (Kulcsar et al. 2019). Following MERS-CoV infection, the disease was more severe and prolonged in diabetic male mice and was characterized by imbalances in lymphocyte counts. We also found Lymphopenia in 63% of the cases with comorbidity which is consistent with this finding where patients with COVID-19, peripheral counts lymphocytes were low (Hussain et al. 2020). More death cases need to be assessed to understand the radiological significance in COVID-19 death cases.
A meta-analysis study reported that presence of more than one pre-existing comorbidities were closely related to ARDS, severity and mortality (Hu et al. 2020). According to the New York State Department of Health (Franki 2020), 86% of reported COVID-19 deaths involved at least one comorbidity. In present study, it was observed that pre-exisitng comorbidities increased risk of mortality which was similar to other studies (Ferrando et al. 2020). Considering COVID-19 ARDS patients, this study showed presence of multiple comorbidities in severe ARDS when compare to mild. In this context, the underlying diseases in ARDS COVID-19 patients increases the severity especially those with hypertension and diabetes being the most significant risk factors.