To date, the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in over 142.2 million cases and over 3 million deaths worldwide.
To mitigate the impact of any infectious disease, it is necessary to understand how its causative pathogen is transmitted as well as its clinical features. As has been observed since the onset of the current pandemic, COVID-19 has exhibited a wide range of clinical features and disease outcomes. Despite many studies focusing on its risk factors and the clinical features, important factors of mortality rate in COVID-19 are not yet sufficiently understood.
To explore these features, an interdisciplinary team of researchers has investigated important factors and their influence on a COVID-19 patient’s death. In this study, the team suggests that they have presented some features investigated for the first time. The team’s findings were recently released medRxiv* on the preprint server.
The study showed a significant association between mortality and certain risk factors like old age, headache, chest pain, respiratory distress, low respiratory rate, oxygen saturation less than 93%, need for mechanical ventilation, evidence from CT, hospitalization intake and histories of hypertension, neurological disorders, or any cardiovascular diseases.
Contrastingly, they observed no significant association between mortality and gender, fever, myalgia, dizziness, seizure, abdominal pain, nausea, vomiting, diarrhea or anorexia.
The researchers said that this study might help in the better management of COVID-19 patients clinically.
COVID-19 often manifests with fever, a continuous dry cough and shortness of breath. Chest X-rays generally demonstrate ground-glass opacity and multiple mottling in patients who develop COVID-19-related pneumonia.
Other clinical observations typically found in COVID-19 patients include decreased eosinophils and lymphocyte counts; lower median hemoglobin values, and enhanced neutrophil counts; WBC and serum levels of alanine aminotransferase (ALT); aspartate aminotransferase (AST); lactate dehydrogenase (LDH); and C-reactive protein (CRP). In the case of severe COVID-19 patients, initial CRP serum levels are considered an independent predictor.
As the angiotensin-converting enzyme 2 (ACE2) receptors of the viral spike protein are widely expressed in various organs, the SARS-CoV-2 infection can cause (along with lung damage) gastrointestinal, liver, kidney, central nervous system, cardiovascular and ocular damage. In the case of acute respiratory distress syndrome (ARDS), patients' conditions deteriorate rapidly with the ‘cytokine storm,’ leading to fatal multiple-organ failure.
Elevated D-dimer levels, reflecting the risk of disseminated coagulopathy in patients with severe COVID-19, are also found with increased severity.
Previous studies on the risk factors and outcomes related to COVID-19 have targeted diabetes, heart injury, and high-dose corticosteroid use, healthcare resource availability, Selenium status, cardiac injury markers, statin use, ICU admission, nutrition status, and also air pollution levels.
However, the researchers note that a comprehensive list of clinical features associated with COVID-19 mortality has not yet appeared in the existing literature. They have aimed to address this, and believe the effect of some risk factors and associated symptoms of COVID-19 mortality have been investigated in their study for the first time.
The study was conducted between March 2020 to November 2020, and included a cohort of 3,008 patients with COVID-19; most of them of Iranian nationality (94.5%), and the rest were Afghan nationals (5.5%).
The researchers found that while gender did not affect mortality, there was a significant difference between mortality and the age of patients, infection time, and the hospitalization ward (isolated ward, intensive care unit, normal ward).
They found that there was a significant difference between mortality and headache in patients infected with COVID-19. Presentation of chest pain, decreased level of consciousness, respiratory distress, oxygen saturation less than 93%, lower respiratory rate and need for mechanical ventilation were significantly associated with COVID-19 related mortality.
The researchers tabulated the effect of different features (early symptoms) on mortality rates. Most of the key factors agreed with previous observations. The researchers noted that the following did not associate with COVID-19-related mortality: opium addiction, smoking status, pregnancy, diabetes mellitus, underlying cancer, liver disease, lung disease, asthma, kidney disease, chronic hematological diseases, other chronic diseases, and receiving immunosuppressive medicines.
However, they reported that underlying cardiovascular disease, hypertension and neurological diseases were associated with COVID-19 related mortality.
The researchers observed a significant association between COVID-19 mortality and age in the context of immune impairment and the enhanced possibility of developing cardiovascular and respiratory diseases in old age.
Notably, they observed no relationship between mortality of COVID-19 and cancer – a finding in discrepancy with some previous studies. This finding could be because of the alternate populations under observation in this study.
The researchers caution that while this study has highlighted some important features of COVID-19 mortality, its geographical and demographic scope is limited. Factors associated with mortality may differ in other regions.
The team’s findings may help facilitate further research in the area to corroborate or refine its findings. They may also help clinicians to better manage, triage and care for COVID-19 patients with clinical features associated with serious disease outcomes.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
- Rahimeh Eskandarian, Zahra Alizadeh Sani, Mohaddeseh Behjati, Mehrdad Zahmatkesh, Azadeh Haddadi, Kourosh Kakhi, Mohamad Roshanzamir, Afshin Shoeibi, Roohallah Alizadehsani, Sadiq Hussain, Fahime Khozeimeh, Vahideh Keyvani, Abbas Khosravi, Saeid Nahavandi, Sheikh Mohammed Shariful Islam. Identification of clinical features associated with mortality in COVID-19 patients. medRxiv 2021.04.19.21255715; doi: https://doi.org/10.1101/2021.04.19.21255715, https://www.medrxiv.org/content/10.1101/2021.04.19.21255715v1