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ORIGINAL ARTICLE
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A comparative study of the course and outcome in hypoxic COVID-19 patients with and without comorbidities


 Department of Medicine, Smt. Kashibai Navale Medical College and General Hospital, Pune, Maharashtra, India

Date of Submission13-Jan-2021
Date of Decision04-May-2021
Date of Acceptance28-May-2021

Correspondence Address:
Gajanan Balaji Kurundkar,
Department of Medicine, Smt. Kashibai Navale Medical College and General Hospital, Pune, Maharashtra
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mjdrdypu.mjdrdypu_19_21

  Abstract 


Background: Severe acute respiratory illness caused by SARS-CoV-2 has been a health emergency of great concern in the year 2020. This study was undertaken to identify characteristics of hospitalized patients with Coronavirus Disease 19 (COVID-19) and hypoxia in the form of disease course and outcome with special reference to the presence or absence of comorbidities. Materials and Methods: A prospective observational study was conducted at a tertiary hospital recognized as Dedicated COVID Hospital during the period of June 2020 to September 2020. The study included a total of 249 patients of COVID-19 with hypoxia who required oxygen or noninvasive ventilation/invasive ventilation. Patients were divided into two groups as per the presence or absence of comorbidity (175 and 74 patients, respectively). Their clinical and laboratory findings, course in the hospital, and outcomes were noted. Data were analyzed using SPSS software. Results: Among all the study patients, more patients from comorbidity group presented with a N:L ratio >3.5 and raised inflammatory markers (like serum ferritin) than patients in the no comorbidity group. In patients with comorbidities, 47.43% required noninvasive or invasive ventilation as against 18.92% in those without any comorbidities. Development of deranged renal function was noted in 32.57% of patients in the comorbidity group and only 9.46% in the noncomorbid group. All except one death during the study period were in the patients with comorbidities. Conclusion: COVID-19 patients with hypoxia and the presence of comorbidities in this study had more complications and a worse outcome.

Keywords: Comorbidities, coronavirus disease 19, hypoxic, SARS-CoV-2



How to cite this URL:
Wajekar SD, Kurundkar GB, Shah PP, Kadam DB, Bhat SM. A comparative study of the course and outcome in hypoxic COVID-19 patients with and without comorbidities. Med J DY Patil Vidyapeeth [Epub ahead of print] [cited 2021 Dec 6]. Available from: https://www.mjdrdypv.org/preprintarticle.asp?id=323516




  Introduction Top


The world has been going through a pandemic of Coronavirus Disease 19 (COVID-19) caused by SARS-CoV-2 virus in the year 2020. Acute respiratory tract infection-related symptoms including fever, cough, and dyspnea have been reported in many case series. The presentation of patients with COVID-19 can be widely variable, ranging from asymptomatic/minimal symptoms to severe acute respiratory infection including pneumonia, acute hypoxemic respiratory failure to full blown acute respiratory distress syndrome. Involvement of other systems is also observed such as the gastrointestinal symptoms, acute kidney injury (AKI), myocardial dysfunction, and thrombotic/vascular events. Many studies across the world have observed adverse correlation between the presence of comorbid condition and progression, outcome of COVID-19. Higher mortality in patients with COVID-19 may be a direct result of the comorbid condition itself or pathophysiology of COVID-19, highlighting the importance of comorbidity management in COVID-19. Therefore, this study was undertaken to compare clinical and laboratory findings, course in the hospital, complications, and factors affecting outcome in patients of COVID-19 with acute respiratory failure and the presence or absence of comorbidities.

Aims and objectives

The aim and objective of the study were to study the impact of comorbidities on the clinical course, medical complications, and outcome in COVID-19 patients with hypoxia.


  Materials and Methods Top


This prospective observational study was conducted at a tertiary hospital recognized as dedicated COVID Hospital at Pune. The study included 249 patients admitted in the period from June 2020 to September 2020, who met the following criteria.

Inclusion criteria

All hospitalized patients with laboratory-confirmed diagnosis of COVID-19 and SPO2 <94% at rest and/or who required oxygen/noninvasive ventilation (NIV)/invasive ventilation for at least 72 h during hospital stay were included in the study.

Data collection

All patients who met the above inclusion criteria were included in the study. The diagnosis of COVID-19 was confirmed by reverse transcription polymerase chain reaction or rapid antigen test or CB-NAAT for COVID-19 on any of the respiratory specimen as per ICMR guidelines in all patients. Detailed enquiries of the presenting symptoms as well as the physical examination findings were noted. The presence of comorbid conditions was identified as per their medical records, history, physical examination, and investigation reports. For study purpose, patients were divided into two groups as per the presence or absence of comorbid conditions. The various comorbid conditions identified in the patients were as follows.

List of comorbidities

List of comorbidities were Age ≥55 years, diabetes mellitus (DM), hypertension, cardiovascular disease (CVD) (ischemic heart disease and cardiomyopathy), chronic obstructive pulmonary disease (COPD), asthma, prior stroke, malignancy, chronic kidney disease, and immunosuppressed status.

All patients received treatment as per the standard protocol by the treating physicians. Patients' clinical course was observed for the progression of symptoms, development of new symptoms or physical findings, development of medical complications including organ failure, and requirement of organ support such as noninvasive or invasive ventilation and hemodialysis. Their outcome in the form of discharge or death was noted.

Statistical analysis

Data were presented in the form of tables and charts and analyzed using suitable tests such as Chi-Square test and unpaired t-test with the help of IBM SPSS software for Windows version 27.0.1 (IBM Corp., Armonk, N. Y., USA).


  Results Top


A total of 249 patients were included in this study; out of which 160 (64.26%) were male and 89 (35.64%) were female (male: female = 1.79:1). Out of these 249 patients, 175 (70.28%) had one or more comorbidities (114 males and 61 females, male: female = 1.87:1), the minimum age 23 years, maximum age 96 years, with the mean age of 62.33 ± 13.39. Among the others without comorbidity were 74 (29.72%) patients (46 males and 28 females male: female = 1.64:1), the minimum age 14 years and maximum age 54 years, with the mean age of 38.70 ± 9.23 [Graph 1].



The common comorbidities were age ≥55 years, hypertension, and DM. All patients belonged to moderate or severe or critical category. Most of them presented with fever and respiratory symptoms. All of them required oxygen or noninvasive ventilation or invasive ventilation for at least 72 h during hospitalization [Graph 2].



Clinical and laboratory characteristics at time of presentation

Clinical and laboratory findings on day 1 of admission are summarized in [Table 1]. Striking observation was that more patients with comorbidities had N:L ratio >3.5 and raised inflammatory markers (such as serum ferritin) as against patients without comorbidities.
Table 1: Baseline characteristics on day one of hospitalisation

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Out of total 249 patients who were included in the study, 97 patients received noninvasive or invasive ventilation. Complications such as respiratory failure requiring noninvasive or invasive ventilation, deranged renal functions, raised cardiac enzymes, and thrombotic events were higher in patients with comorbidities. All five patients who required hemodialysis were from comorbidity group. The association of the presence of comorbidity and requirement of noninvasive/invasive ventilation was statistically significant. The presence of comorbidity and development of deranged renal function was of statistical significance [Table 2].
Table 2: Complications during hospital stay as per the presence or absence of comorbidities

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Outcome

Total 38 deaths were recorded in the hospital during the study period. Most of them (37) had one or more comorbidities. Higher mortality in comorbid group was statistically significant (P = 0.0000722). Mortality was also significantly higher in patients who had comorbidities and developed acute respiratory failure requiring noninvasive or invasive ventilation as compared to those without comorbidities and requiring ventilation (P = 0.00794). There was no significant difference in mortality in males and females (P = 0.83044; odds ratio [OR] = 1.0832 [0.523; 2.239]). Age ≥55 years was the single most important determinant of adverse outcome in our study, followed by others such as DM and hypertension. The adjusted odds of mortality are shown in [Table 3].
Table 3: Effect of comorbidities on mortality in overall study population

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  Discussion Top


A series of acute atypical respiratory diseases was first noted in the Wuhan province of China in December 2019, which later spread to other parts of the country and the world, and was later declared as a pandemic by the World Health Organization.[1],[2] The novel virus has been named as SARS-CoV-2 due to its high homology to SARS-CoV, and the disease caused by this virus is termed as COVID-19.[3] SARS-CoV-2 virus primarily affects the respiratory system, but other organ systems are also involved. The modes of presentation are varied, with patients being asymptomatic to having minimal symptoms, to having acute hypoxemic episodes to progressing to a full-blown acute respiratory distress syndrome.[4]

Our study included all sick and critically ill patients admitted with COVID-19. All patients required oxygen or noninvasive ventilation or invasive ventilation for correction of hypoxia during the course of hospitalization, for at least 72 h. Time frame of 72 h was observed to maintain uniformity in all patients with respect to clinical features and also to account for time required for laboratory diagnosis of COVID-19. The study included patients from all age groups and various comorbid illnesses. Their general laboratory characteristics such as mean hemoglobin and white blood cell on admission were comparable. However, more patients from the comorbidity group had N:L ratio >3.5 and raised inflammatory markers. Mean N:L ratio was higher in the comorbid group. In a study of multiple biomarkers in COVID-19 by Tjendra et al., similar observations were noted. They identified number of laboratory parameters including decreased lymphocyte count, and increased NL ratio, C-reactive protein, ferritin, interleukin (IL)-6, IL-10 as the important determinants of disease severity.[5] Malik et al. published a meta-analysis of 32 studies and concluded that lymphopenia and elevated inflammatory markers are associated with more severity of COVID-19.[6]

We considered age ≥55 years as one of the important comorbidities as many studies have previously reported increased mortality in the age group of ≥55 years. Among all these sick patients, comorbidity group had more than 2.5 times as many patients as in the noncomorbidity group. Yang et al. and Sanyaolu et al. published two systematic reviews and meta-analyses of many studies. Both meta-analyses concluded that age and other comorbidities are clearly risk factors for the development of severe COVID-19 and also noted association of higher mortality in those with comorbidities.[7],[8] A number of comorbid conditions such as DM, hypertension, and CVD tend to increase with age. Chronic diseases often feature proinflammatory state, and attenuation of the innate immune response which may make these individuals more susceptible to disease complications.

A Systemic Review and Meta-Analysis by Wang et al. showed that COVID-19 patients with hypertension or CVD have an approximately 3–4-fold higher risk of developing severe disease. Their study also suggested AKI to be a major risk factor for an increased mortality rate among COVID-19 patients.[9] Analysis of 1590 patients of COVID-19 by Guan et al. suggested that patients with comorbidities had a greater disease severity as compared to those without any comorbidity, and also that the presence of two or more comorbidities correlated with a greater disease severity of COVID-19.[10] A retrospective multicenter cohort study was performed by Harrison et al. on more than 31,000 patients in the United States to study the effect of comorbidities on COVID-19. They observed that older age, male sex, and comorbidities were associated with increased mortality in COVID-19.[11] Jain et al. published a retrospective study of 425 COVID-19 patients. They identified few poor prognostics factors such as age, DM, and CVD.[12] As our study included more sick patients, the odds are slightly different than those reported by them.

Mechanism of more serious injury in COVID-19 due to the presence of comorbidities is being studied all over the world. There may be exaggerated pro-inflammatory cytokine expression in diabetes, which could contribute to the cytokine storm. Dysregulation of angiotensin-converting enzyme-2 (ACE II) receptors may also be responsible for more severe disease in diabetes.[13],[14],[15]

The specific pathogenesis of hypertension and CVD that may lead to more severe COVID-19 is not yet clearly understood. The imbalance of cytokines and dysregulation of ACE II receptors could be possible reason for the correlation between hypertension and severe COVID-19.[16]

The pathogenesis of kidney injury in COVID-19-infected patients is likely to be multifactorial. Possible factors are direct virulence of SARS-CoV-2, other secondary insults such as renal medullary hypoxia, cytokine storms, hypo/hypervolemia, secondary infections, and drug-associated nephrotoxicity.[17]

Since the number of comorbid conditions steadily increases with age, this could be another logical explanation for the increased mortality in older patients. These comorbid conditions themselves may be responsible for an adverse clinical course and increased mortality due to COVID-19. Decreased immunity due to advanced age makes them susceptible for COVID-19.[18]

The adjusted OR of age, DM, and hypertension considering this overlap has been represented in [Table 3].


  Conclusion Top


COVID-19 patients with hypoxia and the presence of one or more comorbidities in this study had more complications and a worse outcome. The study highlights the impact of comorbidities on the clinical course and outcome of COVID-19. Individuals with comorbidities should take more precautions to avoid getting exposed to COVID-19. This study also suggests that the medical management of comorbid conditions may perhaps have a significant impact on the clinical outcome of diseases like COVID-19.

Limitations of study

Our study was a single-center observational study including a limited number of patients spread over a period of approximately 4 months. The patients included in our study had experienced significant hypoxia requiring correction by either oxygen, NIV, or invasive ventilation for at least 72 h. Therefore, the results will be applicable to a similar group of patients. There were only a few patients with some other comorbidities such as ischemic heart disease, asthma/COPD, and hematological disorders [as represented in [Graph 1]. Due to a relatively smaller proportion of patients having these comorbidities, the data were not considered to be sufficient for statistical analysis of these comorbidities. A large multicenter study will definitely be helpful to improve medical understanding on this topic.

Acknowledgment

We acknowledge the contribution of the medical and paramedical staff for their efforts in managing the COVID-19 patients, as well as those who helped us for the compilation of the data.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Guan WJ, Liang WH, Zhao Y, Liang HR, Chen ZS, Li YM, et al. Comorbidity and its impact on 1590 patients with COVID – 19 in China: A nationwide analysis. Eur Respir J 2020;55:2000547 [https://doi.org/10.1183/13993003].  Back to cited text no. 10
    
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    Tables

  [Table 1], [Table 2], [Table 3]



 

 
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