Currently, COVID-19 is spreading rapidly and presenting with different clinical features with different mortality rates worldwide. In the initial days of the pandemic, most of the patients presented with the complaints of lower respiratory tract infection of varying severity, and most of the deaths were also attributable to respiratory failure. As time progressed, more atypical presentations and causes of mortality were encountered according to different age groups. In the present scenario, a surge of COVID-19 cases is expected. Those new cases will also include patients with various problems requiring surgical interventions. In this brief review, we have discussed various presentations and mortality risks of COVID-19 infections in different age groups. We did literature searched on the PubMed database and included studies published in 2019 and 2020. Altogether, 503 articles were retrieved out of which 31 were analyzed to put up this summary. Important atypical findings in neonates and infants were axial hypotonia, drowsiness, moaning sound, intussusception, and late-onset neonatal sepsis with the cause of death being multi-organ failure. Frequently reported comorbidities among children were hydronephrosis, leukemia, and intussusception. Observed risk factors for unfavorable outcome in the adult population were obesity, HIV, tuberculosis, and the intake of immunosuppressive agents in the form of anticancer drugs and steroids. The factors adding to the vulnerability in the elderly population could be enumerated as diabetes, hypertension, ischemic heart diseases, obesity, and cancers.
Keywords: Age group, clinical presentation, COVID-19, mortality, risk factors
|How to cite this URL:|
Prasad C, Dube SK, Rajagopalan V, Chaturvedi A. Influence of patient's age on the clinical presentation, morbidity, and mortality in COVID-19: A brief review. Bali J Anaesthesiol [Epub ahead of print] [cited 2021 Apr 22]. Available from: https://www.bjoaonline.com/preprintarticle.asp?id=297290
| Introduction|| |
Currently, the whole world is facing one of the toughest of their time amid the COVID-19 pandemic. This catastrophe is rapidly spreading worldwide, presenting with different clinical features and mortality rates in different parts of the world. Since the first reported case in December 2019, within 5 months, the spread of the virus has caused over 4.7 million infections and mortality of 0.32 million across the globe.
The United States of America is currently facing the biggest toll of COVID-19 cases and mortality. Centers have analyzed age-wise mortality in the USA. As time is progressing more clarity is added to our insight and more of atypical presentation and cause of mortality are being encountered. It is interesting to know that the presentation and risk factors for adverse outcomes vary widely in different age groups. This information will help us to focus on certain specific issues based on different age groups of COVID-19 patients presenting to us with various surgical problems.
Here, we intend to highlight the different clinical presentations, associated comorbidity, and cause of death in different age groups of COVID-19 affected patients. We shall also be discussing other atypical presentations and mortality risks of COVID-19 in different age groups.
| Methods|| |
In this review, we incorporated studies and reports mentioning risk factors, comorbidities, clinical presentations, and mortalities associated with COVID-19 in different age groups. Medline/PubMed databases were searched for Title/Abstract with the keywords ("risk factors” OR “clinical presentations” OR “mortality” OR “death") AND ("COVID-19” OR “COVID-19” OR “novel coronavirus” OR “sars-cov-2” OR “sars cov 2"). Our research questions were “what are the risk factors for adverse outcome among different age groups in COVID patients,” “what are the comorbidities leading to adverse outcome in COVID patients,” “what are typical and atypical clinical presentations associated to COVID patients” and “what is the death rate in different age groups of COVID patients."
We included studies (randomized control trials, clinical case reports, and correspondence) published in the English language, peer-reviewed journals in 2019–2020. The articles meeting inclusion criteria and posing answer to any of our research questions were included in this review. Review articles, meeting proceedings, waiting for final results and yet recruiting studies were excluded. Altogether 503 articles were retrieved out of which 31 met our inclusion criteria and were analyzed to put up this summary.
Data collection and analysis
We reviewed all the articles carefully and discarded irrelevant articles, simultaneously took the utmost care to prevent exclusion of relevant studies. Each article was independently reviewed by two authors to assess for eligibility and extraction of relevant data. Data of all the relevant articles were analyzed to prepare this narrative report.
| Results and Discussion|| |
Thirty-one relevant articles extracted from PubMed database were finally included in this review. Data on risk factors, comorbidities, clinical presentations, and mortality were analyzed in different age group wise and a brief report prepared as findings in neonates and infants (up to 1 year of age), children (1 year–18 years), adults (18 years–65 years), and elderly population (>65 years).
As evident from the current literature, the elderly population (>75 years) is having higher mortality, and the majority is of male sex (55.4%). Different COVID-19 case fatality rates across different nations can be attributed to their testing and contact tracing rates. The male preponderance in mortality can be explained by gender-based immunity level and smoking pattern.
The overall case mortality among 72,314 cases in China was reported to be 2.3%, but this increased proportionately with age reaching 8% in 70–79 years of age group and 14.8% in ≥80 years old showing advancing age the most critical risk factor for COVID-19 mortality. However, this can be explained by decreasing immunity and increasing comorbidities such as diabetes, hypertension, atherosclerotic disease, and respiratory impairment. In a study among 191 COVID-19 patients, factors associated with increased mortality were hypertension in 30%, diabetes in 19%, and coronary heart diseases in 8% of cases. Along with the older age group, other risk factors for increased mortality reported by authors were higher admission Sequential Organ Failure Assessment (SOFA) score (SOFA >6.4) and higher D-dimer level (>1 μg/L).
In initial days of the pandemic, most of the patients presented with the complaint of lower respiratory tract infection of varying severity and the typical clinical features were fever (87%), dry cough (60%), fatigue (39%), chest distress (16%), diarrhea (14%), pharyngeal pain (13%), headache (13%), and muscle pain (11%). Most of the deaths were also attributable to respiratory failure initially. As time progressed, some atypical presentations and different risk factors for adverse outcomes in COVID-19 were encountered in different age groups. We summarized the age group wise different presentations and risk factors for adverse outcomes below.
Neonates and infants (up to 1 year-old)
As per the CDC report, COVID-19 mortality among infants has been found to 0.007%. Late-onset neonatal sepsis has been reported in a 3-week-old boy in the USA. On admission, the only remarkable finding was tissue hypoxia. Chest radiography showed bilateral linear opacities and consolidation in the right upper lobe. The child was found to be COVID-19 positive on the 7th day of admission by reverse transcriptase-polymerase chain reaction (RT-PCR) test. The infant was managed successfully with standard pediatric intensive care unit protocol and discharged home on the 9th day of admission.
In Wuhan, China, 10-month old COVID-19 positive infant was diagnosed to have intussusceptions who succumbed to death owing to multi-organ failure. Nathan et al. described atypical clinical features in 4 out of 5 infants admitted in their hospital in Paris, France. All of the four infants were admitted with fever, and all showed neurological symptoms such as axial hypotonia, drowsiness, and moaning sounds. All had cerebrospinal fluid negative for severe acute respiratory syndrome (SARS)-CoV-2 by RT-PCR and responded well to conservative management. A case of an 8-month-old male infant was reported from Milan, Italy, who underwent neurosurgery under general anaesthesia for complex hydrocephalus with shunt malfunction. He presented with the complaint of repeated vomiting along with typical clinical features of COVID-19 like mild fever and dry cough.
Hence, at this stage of the COVID-19 pandemic, it can be inferred that neonates and infants can present with typical clinical features along with atypical ones such as axial hypotonia, drowsiness, moaning sound, intussusception, and late-onset neonatal sepsis with a common cause of death being multi-organ failure. All of these clinical findings were supported by one report in each category [Table 1].
Children (1–18 years)
The Centers for Disease Control and Prevention stated that the mortality among children in the USA lies between 0.004% and 0.1%. Lu et al. studied 1391 children at Wuhan Children Hospital, out of whom 171 (12.3%) were positive for SARS-CoV-2. The median age of infected children was 6.7 years and most of them presented with typical clinical features such as fever, cough, and pharyngeal erythema. Twenty-seven (15.8%) patients did not have clinical or radiological findings of pneumonia, 12 (7%) children had radiological features of pneumonia without clinical features of infection, and lymphopenia was found in 6 (3.5%) patients. Three patients required intensive care support and mechanical ventilation, all of them had comorbidities: Hydronephrosis, leukemia, and intussusception. They reported low susceptibility and lower transmissibility among children.
In another study at Wuhan, 6 out of 366 in-hospital children were found to be positive for SARS-CoV-2, the median age being 3 years. All of them had a fever and dry cough whereas both pneumonia and lymphopenia were found in four patients. One of them was admitted to the intensive care unit and given immune globulin therapy. As most of the schools over the globe are closed, young children are contained at homes. Inconsistent fear of the coronavirus leads to dramatic behavior modification such as excessive house cleaning and misuse of cleaning products. Overexposure of these harmful chemical substances (quite a few of them can be toxic) can add to the morbidity and mortality of children amid the pandemic.
Thus, the reported comorbidities among 1–18-year age were hydronephrosis, leukemia, and intussusception, whereas poisoning can be an indirect cause of mortality. However, the existence of asymptomatic COVID-19-positive children cannot be denied. Lymphopenia was reported in two articles, while an article mentioned hydronephrosis, leukemia, and intussusception.
Adults (18–65 years)
In adults, the mortality rate remains at 0.10% to 12.25%. The curve keeps on steeping with the advancement of age. Apart from the risk factors previously explained such as low immunity, hypertension, diabetes, coronary heart diseases, and respiratory impairment in the elderly population, many more risk factors are being defined temporally. In a retrospective case series of 393 patients (median age 62.2 years), 35.8% of patients had obesity, and the reported mortality was 10.2%. Obesity, elevated liver function test values and inflammatory markers (ferritin, d-dimer, C-reactive protein, and procalcitonin) were suggested to be risk factors for the need for invasive mechanical ventilation and mortality.
Tuberculosis and HIV are independent risk factors for high mortality, especially in more prevalent geographical areas like Africa. Tuberculosis is an issue throughout the world. Nevertheless, in Africa, the tuberculosis epidemic is driven by HIV, and HIV-tuberculosis co-infection largely influences mortality. Low immune status HIV patients are vulnerable to tuberculosis and so also to COVID-19.
Malignancies are important risk factors for unfavorable outcomes in COVID-19 patients, and immunosuppressive effects of ongoing anticancer drugs can be one of the reasons for this. Management of COVID-19 was described in 39 years male patient with a history of non-Hodgkin lymphoma and chronic lymphoid leukemia. Transplant recipients pose an exceptionally high risk for adverse outcomes in the setting of COVID-19. In one study, out of 34 SARS-CoV-2 positive kidney recipients (median age 60 years), 11 (39%) patients required mechanical ventilation, and 9 (26.5%) patients died. Immunosuppressive agents, especially anti-thymocyte globulin, were attributed to this adverse effect.
The adult population has presented with the same typical clinical features in most of the cases, but few atypical presentations are worth discussing. Recently, five SARS-CoV-2 positive patients (all <50 years) were reported to present with neurological symptoms in the USA, and all were diagnosed to have large vessel stroke. The proposed mechanism was coagulopathy and endothelial dysfunction, but precise pathogenesis is still elusive. Delay in timely initiating treatment because of fear of hospital-acquired COVID-19, causing a decrease in the rate of intravenous thrombolysis by 26% and an increase in primary mechanical thrombectomy by 41%.
In one study, some form of neurological features were found during the course of treatment in 84% (median age 63 years) of patients, i.e., agitation (69%), corticospinal tract signs (67%) and dysexecutive syndrome (36%). Five SARS-CoV-2 positive cases from three different hospitals of northern Italy were reported to present with Guillain–Barre syndrome (GBS) posing similar onset and clinical course as associated with other infective organisms such as Campylobacter jejuni, Epstein–Barr virus, Cytomegalovirus, and Zika virus. One possible association of SARS-CoV-2 and GBS has also been reported in 61 years old female patient. Previously, GBS has also been reported with Middle East respiratory syndrome coronavirus (MERS-CoV). High risk of venous thromboembolism was found in 40% of admitted COVID-19 patients and they are said to have a more unsatisfactory outcome. An increase in suicide rate has also been anticipated to have an impact on unemployment in young adults.
Thus, to summarize the risk factors for an unfavorable outcome in the adult population are obesity, HIV, tuberculosis, and the intake of immunosuppressive agents in the form of anticancer drugs and steroids. Atypical clinical presentations in this age group can be neurological conditions such as stroke and GBS. Stroke and neurological features were reported by one author each while GBS was mentioned in two articles [Table 1].
The elderly population (>65 years of age)
The major chunk of mortality so far has been linked to this age group, approximately 79%. This age group is already vulnerable due to the strong association with previously described risk factors. Malignancies need a special mention here because, in one report, out of 355 COVID-19 deaths (mean age 79.5 years), 87 (24.5%) had active cancers along with diabetes in 35.5% and ischemic heart diseases in 30% of the patient population.
Emphasis must be given to the burden of anticancer drugs on the already immunocompromised status and underlying comorbidities in this vulnerable age group. Three out of six COVID-19 positive postliver transplant patients (>65 years) died at one center and all had obesity, diabetes, hypertension. In another study, 9 (23%) out of 39 postliver transplant COVID-19 patients succumbed to death due to respiratory failure, among them 44% had diabetes, 44% had hypertension, and 33% cases had obesity.
Apart from all the clinical presentations described earlier myocarditis and coagulopathy had been primarily described in this age group. Myocarditis linked to COVID-19 has been postulated in a 69 years old male after ruling out other common infective causes of it, i.e., parvovirus B19, human herpesvirus, Epstein–Barr virus, Enterovirus, Cytomegalovirus, adenovirus, HIV, and hepatitis C virus. A causal association of immune thrombocytopenic purpura (ITP) was postulated in a 65-year-old female COVID-19 patient who was a known case of hypertension and autoimmune hypothyroidism. The patient developed all the classical clinical features of ITP during COVID-19 treatment, including limb purpura and subarachnoid micro-hemorrhage. Antiphospholipid syndrome was diagnosed in a case of 69-year-old COVID-19 male patient who presented with bilateral lower limb and left-hand finger ischemia along with typical complaints such as fever, cough, headache, and diarrhea.
Hence, the factors adding to the vulnerability of this age group can be enumerated as diabetes, hypertension, ischemic heart diseases, obesity, and cancers. Atypical clinical presentations are myocarditis and coagulopathy in the form of ITP (limb purpura and subarachnoid micro-hemorrhage) and antiphospholipid syndrome. Acute respiratory failure is a ubiquitous mechanism of death in this age group. All the atypical presentations were supported by one report in each category [Table 1].
| Conclusion|| |
There is a continuous change in the clinical presentations of COVID-19. Various new risk factors and clinical presentations are being defined regularly. This rapidly changing clinical behavior of the pandemic keeps on engaging medical science in modifying and re-modifying medical infrastructure and policies. Hence, the practicing clinicians need to remain updated through the latest literature and other methods like seminar or webinar, which will be useful in the successful management of these patients.
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Conflicts of interest
There are no conflicts of interest.
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Surya Kumar Dube,
Department of Neuroanaesthesiology and Critical Care, 7th Floor, Neurosciences Center, All India Institute of Medical Sciences, New Delhi - 110 029
Source of Support: None, Conflict of Interest: None