key: cord-1017815-1n31zx2j
authors: SAHA, AYAN; AHSAN, MOHAMMED MOINUL; QUADER, TAREK-UL; SHOHAN, MOHAMMAD UMER SHARIF; NAHER, SABEKUN; DUTTA, PREYA; AKASH, AL-SHAHRIAR; MEHEDI, H. M. HAMIDULLAH; CHOWDHURY, ASM ARMAN ULLAH; KARIM, HASANUL; RAHMAN, TAZRINA; PARVIN, AYESHA
title: Characteristics, management and outcomes of critically ill COVID-19 patients admitted to ICU in hospitals in Bangladesh: a retrospective study
date: 2021-04-29
journal: J Prev Med Hyg
DOI: 10.15167/2421-4248/jpmh2021.62.1.1838
sha: dad29e0f69332b3c10197a922d9049d549cacd81
doc_id: 1017815
cord_uid: 1n31zx2j

OBJECTIVES: This study aimed to analyze the epidemiological and clinical characteristics of COVID-19 cases and investigate risk factors including comorbidities and age in relation with the clinical aftermath of COVID-19 in ICU admitted cases in Bangladesh. METHODS: In this retrospective study, epidemiological and clinical characteristics, complications, laboratory results, and clinical management of the patients were studied from data obtained from 168 individuals diagnosed with an advanced prognosis of COVID-19 admitted in two hospitals in Bangladesh. RESULTS: Individuals in the study sample contracted COVID-19 through community transmission. 56.5% (n = 95) cases died in intensive care units (ICU) during the study period. The median age was 56 years and 79.2% (n = 134) were male. Typical clinical manifestation included Acute respiratory distress syndrome (ARDS) related complications (79.2%), fever (54.2%) and cough (25.6%) while diabetes mellitus (52.4%), hypertension (41.1%) and heart diseases (16.7%) were the conventional comorbidities. Clinical outcomes were detrimental due to comorbidities rather than age and comorbid individuals over 50 were at more risk. In the sample, oxygen saturation was low (< 95% SpO2) in 135 patients (80.4%) and 158 (93.4%) patients received supplemental oxygen. Identical biochemical parameters were found in both deceased and surviving cases. Administration of antiviral drug Remdesivir and the glucocorticoid, Dexamethasone increased the proportion of surviving patients slightly. CONCLUSIONS: Susceptibility to developing critical illness due to COVID-19 was found more in comorbid males. These atypical patients require more clinical attention from the prospect of controlling mortality rate in Bangladesh.

The Coronavirus Disease 2019 (COVID- 19) , came into limelight in early December 2019, when some cases of pneumonia were reported in Wuhan, Hubei, China; whose cause following laboratory assessment, was found to be a novel strain of virus belonging to the Coronavirus family and was labelled SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) [1] . The spread of the infection is a rising, rapidly advancing circumstance and due to this whirlwind rate of spread, COVID-19 has been pronounced as a global pandemic by the WHO since March 11, 2020. As of 23 rd September, more than 31.7 million positive cases of COVID-19 have been reported in 217 countries and territories with more than 975,315 deaths. COVID-19 targets the respiratory tract of humans and has similar clinical symptoms to SARS-CoV and MERS-CoV [2] [3] [4] . Typical symptoms experienced by COVID-19 positive individuals include fever, dry cough, fatigue, headache, vomiting, diarrhoea, shortness of breath, myalgia, acute respiratory distress syndrome (ARDS) related symptoms and shock [5] [6] [7] [8] [9] . Previous studies reported that the patients who need intensive care tend to be older in age and male, and about 40% have comorbid conditions, including diabetes, cardiac diseases, hypertension, asthma and other chronic illnesses such as liver or kidney disease [10, 11] . According to the World Health Organization, about 5% COVID-19 patients, who are severe or critically ill require admission to an intensive care unit (ICU) [12] . However, shortages of standard healthcare resources, especially ICU supports are causing the high mortality rate of critically ill patients. The COVID-19 pandemic has imposed an enormous burden and massive challenges to the health care system, especially ICUs, across developed, developing and underdeveloped countries. Likewise, Bangladesh also falls in the category of unfortified countries due to its high population and poor health care system [13] . In Bangladesh, current median age is 26.7 years and mortality rate is 5.52 [14] . Moreover, life expectancy is 73.4 years and a total of 7% of the county's population are senior citizens [14, 15] . Most of these senior citizens, as well as middle-aged people in the country, have comorbidities, such as diabetes (9.7%), asthma (5.2%), hypertension (20%), cardiac disease (4.5%) and chronic pulmonary disease (11.9%), and around 1.3 to 1.5 million cancer patients in the country are vulnerable to COVID-19 [16] [17] [18] [19] . All of these people, who belong to a vulnerable group, may require immediate hospitalisation and intensive care if they contract COVID-19 [11] . Compared to the eight worst affected countries, Bangladesh has the lowest number of COVID-19 ICU beds per 10,000 inhabitants ( Supplementary Fig. 1 ). How the health management system with its poor and limited resources is responding to and tackling critical COVID-19 patients is a matter of inordinate concern. Therefore, it is important for health and government authorities to have information on the clinical features and outcomes of COVID-19 in critically ill cases for them to address the necessities of ICU facilities and prepare for a possible second wave of COVID-19 in Bangladesh. In China, India, Greece and the U.S., similar epidemiological studies have already been conducted sampling COVID-19 patients admitted in the ICU, in order to distinguish COVID-19's clinical implications on patients who had to be admitted in the ICU. Insights obtained from these studies can assist experts to further pinpoint exact management and follow-up medical routines [20] [21] [22] [23] . Therefore, this study aims to investigate the epidemiological and clinical features, disease severity, treatment and clinical outcomes of critical COVID-19 cases in Bangladesh with the goal of portraying a bigger picture of severe clinical manifestations of COVID-19 so that the malleability Bangladesh's health care system can be modified in terms of tackling COVID-19.

This study's sample comprises 168 COVID-19 patients with definite outcomes who were admitted to Chittagong General Hospital and Chittagong Medical College Hospital (COVID-19 unit) between 1 st April 2020 and 7 th August 2020. The Chittagong General Hospital and Chittagong Medical College Hospital (COVID-19 unit) are specialised hospitals that have been authorised for managing most of the critical COVID-19 patients in the country's economic hub, namely Chattogram city. The epidemiological and demographic data for this study were obtained from the inpatients' files. Approval of this study was provided by the Institutional Review Board (IRB) of Chattogram General Hospital Ethics Committee. In terms of data collection and usage, patients and in some cases, their next of kin (first degree relatives) gave their accord.

Management of all the COVID-19 patients admitted in the ICU were implemented according to the regulations set nationally for COVID-19 management in Bangladesh [24] . Based on clinical symptoms, patients were divided into mild, moderate, severe and critical groups. Most of the severe or critical patients and few moderate ill patients were admitted to the ICU. Those in the severe group have respiratory distress, i.e. a respiratory rate of ≥ 30 beats per minute in a resting state and an oxygen saturation of ≤ 92% SpO2, and those in the critical group experience respiratory failure, Sepsis and shock, thus requiring mechanical ventilation, as well as the combined failure of other organs, which require ICU monitoring and treatment. In both the hospitals combined during the study duration, a total of 1,835 COVID-19 patients were admitted. Of these 1,835 patients, 168 (9.16%) had to be admitted in the ICU and 95 of these 168 ICU patients died. Among the patients who survived, 55.9% (94/168) were in critical condition, 39.9% (67/168) were in severe condition and other 4.2% (7/168) were in moderate condition. The coordinative physicians were accountable for collecting this data from the patients. ARDS was defined according to the Berlin definition [25] , and shock was defined according to the sepsis-3 criteria [26] .

Whether the cases of the sample were positive with COVID-19 was confirmed via a real-time reverse transcription polymerase chain reaction (RT-PCR) assay of respiratory tract samples. Throat swabs were collected and maintained in the viral transport medium. The laboratory test assays for COVID-19 were conducted according to standards set by the World Health Organisation's (WHO). Upper and lower respiratory tract specimens were collected in order to extract SARS-CoV-2 RNA. The RNA was obtained and further tested by means of RT-PCR using the same method that was described previously [20] .

Descriptive statistical analyses were performed to express categorical variables with numbers and proportions. These were then compared using a chi-square test. P values of less than or equal to 0.05 (two-sided) were considered statistically significant. R-script and GraphPad Prism version 7.04 was used to perform all of the statistical analyses and the figure plotting. Patients with at least one type of comorbidity were considered comorbid, and those with no comorbidity were considered non-comorbid patients.

Among the 168 COVID-19 patients admitted in the ICU with a confirmed outcome, 95 (56.5%) of the severely ill patients died in the ICU and the remaining 73 patients (43.5%) were transferred to the isolation ward following improvement (Tab. I). Although 66.7% of the patients were over 50 years old, the highest proportion (28.6%) was between 51 and 60 years old. The proportion of male patients (79.8%) was more than female patients (20.2%). The COVID-19 individuals were into diverse professions and while the 10 (6.0%) of the patients had direct involvement in the healthcare system, most of the patients were from urban areas (65.5%). Persistence of a comorbidity was directly proportional to the state of being admitted in the ICU. As shown in Figure 1A , the proportion of deceased patients was relatively low in the group without comorbidities. Interestingly, the patients who were over 50 years old and had comorbidities comprise 66.3% of the total deaths, with the number of deaths being seven times the number of deaths in the group without comorbidities (Fig. 1B) . About 82.1% (138/168) of patients had at least one coexisting chronic illness, predominantly diabetes (52.4%), hypertension (41.1%) or heart disease (16.7%) (Tab. I). The prevalence of diabetes, hypertension and heart disease in deceased patients was slightly higher (Fig. 1C) . Interestingly, patients with asthma survived well compared to other comorbidities. The most common symptoms experienced by patients were ARDS (133/168; 79.2%), fever (91/168; 54.2%) and coughing (43/168; 25.6%) (Fig. 1D ). The median length of hospital stay was five days, and the median length of ICU stay was four days (Fig. 1E ). The average duration of stay in the ICU was higher in surviving patients. In surviving patients, the median length of hospital stay was eleven days, and the median length of ICU stay was six days (Fig. 1F ). In case of the deceased population of this study, respiratory failure (78/95; 82.1%), diabetes mellitus related complications (30/95; 31.6%), pneumonia (20/95; 21.0%), thromboembolic (4/95; 4.2%) and myocarditis (3/95; 7.4%) were found to be the most prevalent causes of death (Fig. 1G ). The body temperatures for all individuals in the study sample (Tab. II) were measured, and this ranged from 98°F to 102+°F. The vital signs at admission to the ICU were moderate fever ≥ 99°F for 40 patients (71.1%), heart rate ≥ 100 beats per minute for 85 patients (51%) and a respiratory rate of ≥ 25 breaths per minute in 56% of the recorded patients (Tab. II). The patients who had a moderate or high fever (≥ 99°F) tended to have a higher mortality rate than those with a mild or no fever ( Fig. 2A) . Oxygen saturation was low (< 5% SpO2) in 135 patients (80.4%) and the mortality rate of these patients was relatively high (Fig. 2B ). The death rate of patients who had an abnormal heart rate and respiratory rate was higher (Fig. 2C) 133 patients (79%) experiencing severe ARDS. Eighty three out of the 133 severe ARDS patients (62.4%) died (Fig. 2E ).

The laboratory findings of the patients upon admission to the ICU are shown in Figure 2 and Table III were also compared, and it was found that they were essentially identical ( Figure 2F ).

Oxygen therapy was administered in accordance with the patients' oxygen saturation. Over 90% of the (Fig. 3A) . As shown in Figure 3B , the proportion of survived patients was slightly higher with the use of Meropenem, as well as Remdesivir and Dexamethasone, than with the use of Favipiravir or Methylprednisolone. Six patients were treated with Remdesivir and Dexamethasone and only one of them died. The vitamin C, vitamin D and zinc supplements that were commonly used did not show any improved clinical outcomes (Fig. 3C) . [22, [27] [28] [29] . However, the gender propensity of this study's patients (mostly men) is consistent with that of COVID-19 patients in ICUs in Italy, USA and China [27] [28] [29] . The management of patients with several comorbidities is challenging due to their frailty and increased risk of mortality, which is amplified when these comorbid individuals are diagnosed with COVID-19.

The current study has found that older (≥ 50) Bangladeshi male patients with previous comorbidities, such as diabetes, hypertension and heart diseases, are profoundly susceptible to COVID-19, which is comparative to the pattern that has been revealed in China, Italy and New York [8, 27, 29, 30] .

In Bangladesh, most people diagnosed with diabetes are from urban areas, and the prevalence of diabetes is highest among those aged from 55 to 59 years [31] . The presence of comorbidity might explain COVID-19's severity in Bangladeshi patients aged 51 to 60 years. Another finding from this study was that patients with asthma survived well compared to other comorbidities. As with other viruses, SARS-CoV-2 triggers asthma exacerbations, which is why asthma is listed as a risk factor for COVID-19 related morbidity. However, this study's finding is consistent with that of Leonardo Antonicelli et al. (2020) , who found that asthma seems to play a minimal role in clinical severity [32] . ARDS (79.2%) was found to be the most prominent symptom within the study sample upon admission to the ICU, and this was also reflected in patients described in reports from China, USA and Europe [8, 27, 28] . Other noteworthy symptoms are fever (8.40%) and coughing (7.70%), and the results obtained by this study align with the trends concerning high prevalence seen in other countries [27] [28] [29] . Intestinal signs and symptoms, such as diarrhoea, were rarely developed by the patients in this study. Majority of the study population had to rely upon supplemental oxygen while being cared for in the ICU. The cause of their inclination towards supplemental oxygen was severe to moderate ARDS which was indicated by their low oxygen saturation levels. In cases with depleting oxygen saturation, Oxygen therapy by highflow nasal cannula (HFNC) and mechanical ventilators provide higher efficacy in the matter of additional oxygen support [33, 34] . However, given the spike in COVID-19 cases, the demand of HFNC has increased substantially because HFNC has been found to improve therapy by reducing the requirement of invasive ventilation [33] . Unfortunately, during the initial stages of this study HFNC could not be provided to the participating population and ventilators were limited as well which deprived patients of the support of mechanical ventilation when needed. This scarcity of proper ventilation might explain the prevalence of a high mortality rate in patients with a moderate to high fever and a low oxygen saturation. Therapeutic plasma exchange has been recommended as a treatment measure for patients with severe COVID-19; however, this study found that therapeutic plasma exchange had no significant impact on the improvement of critically ill patients. According to a recent study, therapeutic plasma exchange can be effective in critically ill patients if it can be applied within the first week of symptom onset [35] . Unfortunately, most of the patients in the current study were admitted to the ICU in a critical condition due to the lack of available ICU beds. Therefore, it may have been too late for convalescent plasma therapy to have an effective impact.

To the extent of the author's knowledge, so far, this study is the only study on the medicine administered to critically ill COVID-19 patients in Bangladesh. Currently, there is no recommended treatment for COVID-19 infection in careful supportive care [36] . In this study, 97.6% of patients received antibacterial agents, 56% received antiviral therapy and 88.7% received anti-inflammatory drugs. Even though the antiviral drug Favipiravir was the mostly used antiviral drug, the survival rate was higher among the patients who had been given Remdesivir. Favipiravir concentrations become lower in critically ill patients than in healthy subjects, which might be one reason why Favipiravir is less effective [37] . Several countries, such as Japan, Taiwan and USA, and the European Union (EU) suggest the conditional use of Remdesivir to treat critical patients [38, 39] . Therefore, Remdesivir can be a better choice over Favipiravir in providing aid to COVID-19 individuals.

A recent report suggests that glucocorticoids may also minimize severe clinical outcomes in critical COVID-19 patients with ARDS [40] . The current study finds that Dexamethasone has comparatively better clinical outcomes than Methylprednisolone. According to a large clinical trial conducted in the United Kingdom (UK), Dexamethasone reduced deaths by about one-third in critical COVID-19 patients who were on ventilator support [41] . In this study, only one out of six patients who were treated with both Remdesivir and Dexamethasone died. However, further studies with larger sample sizes are required to evaluate the effectiveness of the combined use of Remdesivir and Dexamethasone.

Although the findings of this study were significant, limitations were also in order. Firstly, laboratory data collection to conduct a broad and extensive study was inevitably challenging as the laboratory results were not systematically collected. Secondly, the evaluated data was extracted retrospectively from patients' medical files and not all laboratory tests were conducted on all patients. Thirdly, because of the study's objective to identify the critical care needs of patients with the greatest severity of illness, the sample size is small. Therefore, more thorough assessment of comorbidities in larger samples of critical Bangladeshi patients with COVID-19 and future studies are required. Despite these limitations, this study represented the largest cohort of critically ill COVID-19 patients from Bangladesh reported to date.

To summarize, parallel to the data obtained from studies conducted in other countries, there is an elevated prevalence of comorbidities, such as diabetes, hypertension and heart diseases, in a profuse number of COVID-19 patients with critical expositions who are hospitalised in Bangladesh.

Since this cohort is more vulnerable in terms of COVID-19 related morbidity and mortality, besides implementing an effective policy for the prevention and control of the disease in general, the authorities should pay more attention to these atypical patients. In conclusion, the findings reported here provide important context for effective strategies for the provision of comprehensive health care to critically ill COVID-19 patients. However, future studies with larger sample sizes are needed in order to assess the risk factors and associated clinical outcomes in a broader sense.

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Funding sources: this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.The authors would like to acknowledge all patients and fellow healthcare workers for providing excellent patient care at considerable personal risk.

The authors declare no conflict of interest. 

Supplementary Fig. 1 . The number of COVID-19 ICU beds available for every 10,000 inhabitants of Bangladesh and other countries worse affected by COVID-19. USA, United States of America; UK, United Kingdom [9, 14, [42] [43] [44] [45] [46] [47] .