
==== Front
Heliyon
Heliyon
Heliyon
2405-8440
Elsevier

S2405-8440(24)12233-5
10.1016/j.heliyon.2024.e36202
e36202
Research Article
A comparison of COVID-19 and post-COVID-19 syndrome among symptomatic and asymptomatic patients in Bangladesh: A retrospective cohort study
Bhowmik Leon
Hasan Md Kutubul
Bristy Tahmina Akter
Etu Sadia Tasnim
Karim Reatul
Mostaid Md Shaki shaki.mostaid@northsouth.edu
⁎⁎
Shill Manik Chandra manik.shill@northsouth.edu
⁎
Reza Hasan Mahmud hasan.reza@northsouth.edu
⁎⁎⁎
Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh
⁎ Corresponding author. manik.shill@northsouth.edu
⁎⁎ Corresponding author. shaki.mostaid@northsouth.edu
⁎⁎⁎ Corresponding author. hasan.reza@northsouth.edu
15 8 2024
30 8 2024
15 8 2024
10 16 e3620217 12 2023
12 8 2024
12 8 2024
© 2024 The Authors
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).
Background

The differentiation between COVID-19 and post-COVID-19 syndromes is not properly defined as some patients remain asymptomatic for post-COVID-19. It can be characterized by several signs and symptoms. Risk factors related to post-COVID-19 remain unsolved. Here we aimed to differentiate post-COVID-19 patients among symptomatic and asymptomatic groups to check the percentage among them and the risk factors for post-COVID-19 and the association of different symptoms.

Methods

This study was conducted in Chittagong division, Bangladesh at different hospitals. Data were collected from the participants either by in person interview or online (email) or mobile phone calls. Follow up was done after 3 months to check the development of post-COVID-19 syndromes. Relevant data were taken, and symptomatic and asymptomatic patients were divided based on the presence and severity of specific symptoms.

Results

Our results showed that 41.88 % patients develop post-COVID-19 symptoms. Fever and Cough were classified as one of the factors of post-COVID-19, followed by dyspnea, fatigue, cough, rhinitis, sore throat, and muscular discomfort. On the other hand, age, respiratory distress, lethargy, duration of illness and severity were classified as risk factors for post-COVID-19. There was a significant difference between symptomatic and asymptomatic patients as only 16.3 % patients showed post-COVID-19 symptoms. Based on the severity grade, 80.7 % of patients had mild COVID-19. We also found that people with ‘B’ positive blood group had a higher chance of developing post-COVID-19 syndrome.

Conclusion

It was concluded that age, duration of illness, presence of respiratory distress, blood group, and disease severity are major risk factors for the development of post-COVID-19 syndrome.

Keywords

COVID-19
post-COVID-19
Symptomatic
Asymptomatic
Risk factors
==== Body
pmc1 Introduction

The recent COVID-19 pandemic has proved that our knowledge of the SARS-CoV-2 virus and its acute and post-acute clinical presentations is still fragmented and needs to be explored thoroughly [1]. On 11th March 2020, the World Health Organization declared COVID-19 as a pandemic [2]. Since then, many scientists worldwide have been working to discover an effective vaccine and a remedy for this deadly disease. Although several vaccines have been developed for this contagious disease and administered to the general population, still a large percentage of people continue to suffer from COVID-19 and post-COVID-19 syndromes, such as long-lasting problems of the respiratory system, cardiovascular system, nervous system, mental health, metabolism, gastrointestinal system, kidney, coagulation regulation, skin, musculoskeletal system, and general health [3].

A number of SARS-CoV-2 patients may have chronic complications from the virus, known as post-COVID-19 diseases or persistent COVID-19 illnesses. These post-COVID-19 symptoms are also known as persistent COVID-19, prolonged COVID-19, long-term COVID-19, post-acute COVID-19, protracted COVID-19, long-term consequences of COVID-19, and chronic COVID-19 [4]. It is well recognized that the post-COVID-19 disease represents several possibly overlapping entities, each with its own set of biological causes, risk factors, and consequences [1]. Despite the recognition of COVID-19 illness as a worldwide health issue, its clinical and epidemiological manifestations are still difficult to assess [5]. The causes of post-COVID-19 syndromes are unclear, and persistent immune activation is hypothesized to be involved [6]. It has been reported that persistent COVID-19 illness may cause many patients to experience adverse symptoms in multiple organs [7,8]. Long COVID-19 shows a range of ongoing health challenges, along with newly developed conditions such as cardiovascular, thrombotic, and cerebrovascular diseases, type 2 diabetes, myalgia, encephalomyelitis, chronic fatigue syndrome (ME/CFS), and dysautonomia, especially postural orthostatic tachycardia syndrome (POTS) [[8], [9], [10], [11], [12], [13]].

A recent study demonstrated the majority of individuals who have recovered from COVID-19 regain their physical and functional well-being within a year following the initial infection [14]. However, a subset of these survivors continues to experience morbidity concerns, discomfort, pain, as well as feelings of anxiety or depression, in contrast to individuals who were not affected by COVID-19 [14]. An analysis of over 250,000 electronic health records revealed that over one-third of the individuals exhibited one or more symptoms associated with post-COVID-19 conditions within 3–6 months following initial COVID-19 diagnosis [15,16]. However, it is uncertain whether persistent symptoms and associated abnormalities will be cured entirely or if some may result in life-long impairment. Investigations into the post-COVID-19 condition can be difficult due to several factors, such as the death of the patient, frequent use of non-validated measuring instruments, low rate of patient feedback due to fear of COVID-19 transmission, and data censoring [17]. A significant problem associated with post-COVID-19 conditions is the difficulty of measuring indicators of COVID-19 syndromes, which are different from the usual hospitalizations or deaths [18]. Moreover, due to the lack of biomarkers and diagnostic imaging tests, the pathophysiology of many post-COVID-19 symptoms still remains unclear [18].

Since the first case report of COVID-19 patients, only a few studies have been conducted in Bangladesh, and even the least number of studies have been conducted related to the development of post-COVID-19 syndromes among COVID-19 patients. Also, to the best of our knowledge, most of the previous COVID-19 studies conducted in the Bangladeshi population were limited to Dhaka division. Chittagong is the second largest division in Bangladesh and is a crucial geographic and economic hub, featuring the country's busiest seaport and a major business hub. Due to the high rate of COVID-19 transmission in this area and the ease of follow-up of the native residents of this city, we selected Chittagong as the study location. Moreover, transportation and public movement were limited due to the lockdown and quarantine measures taken by the government during the study period. As a result, we could not conduct the study in other cities of Bangladesh. Therefore, we aimed to investigate the COVID-19 and post-COVID-19 syndromes among Bangladesh's symptomatic and asymptomatic patients residing in Chittagong.

2 Materials and methods

2.1 Study design

We designed a questionnaire to collect information from COVID-19 and post-COVID-19 syndrome patients. We followed a modified version of the questionnaire of a previous study on post-COVID-19 syndromes [19], considering the specific context of our study location. To ensure the validity and relevance of the questionnaire, we consulted with several public health experts for their feedback. Subsequently, we made the necessary modifications to finalize the questionnaire. The study protocol was approved by the Institutional Review Board of North South University (2023/OR-NSU/IRB/1105).

We have used the approved questionnaire to collect data from the participants involved in the study. Upon enrollment, various aspects of patient information were collected, including demographics, signs and symptoms, comorbidities, duration of illness, age, and blood group. To analyze the risk factors associated with COVID-19 and the likelihood of post-COVID-19 development, the patients were categorized into three age groups: less than 40, 40 to 60, and above 60 years of age [19]. After initial selection and data collection, follow up was continued for at least for 3 months, and data were taken from the patients again. Based on the observed features, the patients were divided into three unique severity groups: mild, moderate, and severe [20]. According to these standards, the classification was defined as follows: Patients with symptoms resembling an upper respiratory tract viral infection were under mild disease. These signs included insomnia, a lower body temperature, a dry cough, a sore throat, nasal congestion, lethargy, and headaches. Patients with a mild disease did not exhibit symptoms of severe pneumonia. Patients with moderate disease needed supply of O2, exhibited shortness of breath and pneumonia-like symptoms such as fatigue, cough, chest pain, confusion, or problems in concentration. Individuals having severe disease showed notable symptoms such as tachypnea (rapid breathing) and severe dyspnea (breathing at a rate exceeding 30 breaths per minute) were classified as having severe disease [19,21]. This categorization approach enabled a comprehensive assessment and provided us with a framework to understand the varying levels of severity among the participants based on their symptoms and respiratory distress [22]. Several factors were used to determine clinical improvement, including: body temperature: a sustained recovery to normal body temperature for at least three days; respiratory symptoms: significant decrease in respiratory symptoms, as evidenced by a respiratory rate of 25 breaths per minute and the absence of dyspnea (breathing trouble); maintaining an oxygen saturation level (SpO2) over 93 % without the need for supplementary oxygen breathing aid; hospitalization status: not being hospitalized as a result of any medical ailment, pathology, or clinical assessment. These precise criteria were used as benchmarks to assess the clinical progress of study participants. Meeting these criteria collectively indicated a positive patient health advancement during the COVID-19 recovery phase [23]. Furthermore, individuals were divided into two groups based on specified criteria: those with and those without post-COVID-19 syndrome. According to the World Health Organization (WHO) [24], the categorization was established by the presence or absence of specific symptoms including fatigue, shortness of breath or difficulty breathing, memory, concentration, or sleep problems, persistent cough, chest pain, trouble speaking, muscle aches, loss of smell or taste, depression or anxiety and fever. Individuals showing these symptoms have been identified as having post-COVID-19 syndrome, which indicates that health problems persist after the acute phase of the disease. Those who did not exhibit these symptoms were classified as not having post-COVID-19 syndrome. This categorization aided in the evaluation and comparison of patients with varying recovery histories and probable continuing health concerns [24]. During the COVID-19 period, the individuals were divided into two groups based on the presence or absence of symptoms frequently associated with SARS-CoV-2 infection: symptomatic and asymptomatic. Symptoms such as fever, cough, diarrhea, dyspnea, loss of taste or smell, runny nose, tiredness, and myalgia/arthralgia were included in this classification. The period between the diagnosis and the first occurrence of symptoms, as well as the time needed for the retrieval, were noted. Based on the symptoms observed, the study participants were divided into symptomatic and asymptomatic groups. Participants were asked to answer all study questions comprehensively. A follow-up was done for at least three months after the recovery [24].

2.2 Data collection

Data were collected from Bangladeshi individuals residing in the Chittagong division of Bangladesh from September 2021 to February 2023. A written informed consent was taken from the participants or their legal guardians. The consent was taken during the initial interview period. While taking the consent, we informed them that we shall contact them to do a follow-up after 3 months.

We have used the validated questionnaire to the collect necessary data from the participants. The first part of the questionnaire was used to assess the problems during COVID, and the second part was used for post-COVID-19 (Suppl. material). The first interview was conducted between 1 and 7 days after a patient tested COVID-19 positive, and the second part was conducted after 90 days. After follow up, patients who developed significant symptoms and needed hospital care were admitted into hospital. We collected all the data from COVID-19 patients in person while they were taking treatment from in patient or outpatient care facilities from hospitals. For the collection of post-COVID-19 data, we communicated with the participants either in person or by email attaching the questionnaire or direct mobile phone calls. Within the study period, the follow-up was done once only.

For this retrospective cohort study, 450 patients diagnosed with COVID-19 and later had a full recovery were chosen. Among them 73 were symptomatic and 376 were non-symptomatic. Post-hoc power calculation was performed using G*Power software which suggested that our sample had 97 % power to detect a medium effect size (d = 0.5) for α = 0.05 [25].

The study aimed to gather accurate and pertinent data from individuals directly impacted by COVID-19, enabling a robust analysis and meaningful insights into the disease's effects and potential risk factors between COVID-19 and post-COVID-19.

2.3 Inclusion and exclusion criteria

The inclusion criteria for the COVID-19 research participants were carefully outlined to ensure the relevance and validity of the study. We have followed the following criteria to select our study population. 1) Bangladeshi patients who tested positive for SARS-COV-2 on RT-PCR swab and/or a serological assay. 2) COVID-19 positive patients who gave their consent were enrolled in the study. 3) After the initial data collection, follow-up was conducted at three-month intervals for each patient. Participants were contacted to find out the presence of specific symptoms based on our pre-defined PCS (Post-COVID Syndrome) criteria. In-person interviews were conducted with all participants who developed post-COVID-19 syndromes by maintaining social distance and other necessary precautions [26]. Efforts were taken to minimize selection bias and information bias.

Furthermore, we excluded individuals who tested negative for COVID-19. Also, during the study, we excluded some participants who did not have any documented health assessment, were unable to understand the study, or had cognitive impairment (Fig. 1) [27].Fig. 1 Study design and collection of participants for the study.

Fig. 1

2.4 Statistical analysis

The normality of data distribution was checked using a Q-Q plot and Shapiro-Wilk test. Independent samples t-test was used to compare between continuous variables, and for not normally distributed data, the Mann-Whitney U test was performed. The chi-square test was used to compare between the categorical variables. The risk ratio was calculated along with 95 % confidence intervals. Furthermore, a binary logistic regression model was used to identify risk factors associated with relevant variables (sex, respiratory distress, lethargy, total duration of illness, severity) in the COVID-19 patient sample. IBM SPSS Statistics for Windows, Version 27.0 were used to perform all statistical analyses. To prevent bias, all study participants were given a unique code number and the analysis was conducted using the double blind method.

3 Results

A total of 450 patients who met the inclusion criteria were included and enrolled in the study. We found that 32 % of all COVID-19 positive patients had some comorbidities. The mean (SD) age of the study population was 38.42 years, and most patients were less than 40 years old. Among the respondents, the male proportion was high (312, 69.20 %) compared to females. Almost 62.70 % people had a fever, and other symptoms were also observed such as changes in mood (56.70 %), cough (57.70 %), general weakness (50.90 %), and loss of taste and smell (46.20 %). Out of all patients, 80.70 % had mild disease, 15.40 % had shown moderate disease, and 4 % had severe disease (Table 1).Table 1 Demographic information on COVID-19 patients, classified according to the presence or absence of post-COVID-19 syndrome.

Table 1Variables	Total population	Group 1a	Group 2b	p value	x2	df	RR (95 % CI)	
n = 450	n = 266	n = 184	
Age(years), mean (SD)	38.42 (13.69)	37.83(14.06)	39.27(13.12)	0.252c	67.95a	61		
Age<40 years, mean (SD)	28(61.55)	168(63.15)	109(59.23)	0.670	27.06a	27		
Age = 40–60 years, mean (SD)	138(30.66)	79(29.69)	59(32.06)	27.80a	19		
Age>60 years, mean (SD)	35(7.78)	19(7.14)	16(8.70)	10.97a	12		
Sex(male), n%	312(69.20)	179(67.30)	133(72.28)	0.26	1.27a	1	1.15	
(0.87–1.78)	
Total duration of illness (days) median, (IQR)	15(14–22)	15(13–20)	20(14–28)	<0.001d				
Fever, n%	282(62.70)	168(63.20)	114(62)	0.79	0.67a	1	1.03	
(0.82–1.30)	
Fatigue, n%	87(19.30)	39(14.70)	48(26.10)	0.003	9.104a	1	0.68	
(0.54–0.86)	
Dyspnea, n%	67(14.90)	35(13.20)	32(17.40)	0.22	1.54a	1	0.83	
(0.63–1.10)	
Joint Pain, n%	48(10.70)	26(9.80)	22(12.0)	0.46	0.54a	1	0.88	
(0.63–1.22)	
Chest Pain, n%	55(12.20)	18(6.80)	37(20.10)	<0.001	18.05a	1	0.55	
(0.44–0.69)	
Cough, n%	246(54.70)	134(50.40)	112(60.90)	0.28	4.83a	1	0.78	
(0.62–0.98)	
Loss of Taste and Smell, n%	208(46.20)	114(42.90)	94(51.10)	0.09	2.96a	1	0.82	
(0.66–1.03)	
Rhinitis, n%	91(20.20)	44(16.50)	47(25.50)	0.02	5.46a	1	0.74	
(0.58–0.94)	
Red Eyes, n%	7(1.60)	3(1.10)	4(2.20)	0.38	0.78a	1	0.71	
(0.37–1.36)	
Lack of Appetite, n%	12(2.70)	4(1.50)	8(4.30)	0.07	3.39a	1	0.60	
(0.39–0.91)	
Sore Throat, n%	87(19.30)	46(17.30)	41(22.30)	0.19	1.74a	1	0.84	
(0.65–1.08)	
Vertigo, n%	34(7.60)	18(6.80)	16(8.70)	0.45	0.58a	1	0.86	
(0.59–1.25)	
Diarrhea, n%	61(13.60)	31(11.70)	30(16.30)	0.16	2.01a	1	0.81	
(0.61–1.07)	
General Weakness, n%	229(50.90)	121(45.50)	108(58.70)	0.01	7.59a	1	0.73	
(0.58–0.95)	
Muscle Weakness, n%	39(8.70)	13(4.90)	26(14.10)	<0.001	11.74a	1	0.58	
(0.45–0.74)	
Muscle Pain, n%	88(19.60)	44(16.50)	44(23.90)	0.05	3.76a	1	0.77	
(0.61–0.99)	
Jaundice, n%	2(0.40)	1(0.40)	1(0.50)	0.79	0.69a	1	0.82	
(0.20–3.28)	
Heart Disease, n%	3(0.70)	1(0.40)	2(1.10)	0.36	0.83a	1	0.61	
(0.27–1.37)	
Respiratory Disease (Asthma/COPD), n%	29(6.40)	14(5.30)	15(8.20)	0.22	1.51a	1	0.78	
(0.54–1.12)	
Stroke and Cardiovascular Disease, n%	4(0.90)	0(0.0)	4(2.20)	0.016	5.83a	1	0.40	
(0.36–0.45)	
Diabetes, n%	4(0.90)	1(0.40)	3(1.60)	0.16	1.94a	1	0.54	
(0.30–0.96)	
Kidney Disease, n%	1(0.20)	0(0.00)	1(0.50)	0.23	1.45a	1	0.41	
(0.37–0.46)	
Needle pain in arms and legs, n%	2(0.40)	2(0.80)	0(0.0)	0.24	1.39a	1	0.59	
(0.45–0.64)	
Hearing Problem, n%	5(1.10)	2(0.80)	3(1.60)	0.38	0.75a	1	0.68	
(0.329–1.39)	
Hair Loss, n%	14(3.10)	8(3.0)	6(3.30)	0.88	0.023a	1	0.95	
(0.52–1.76)	
Skin Disease, n%	11(2.40)	5(1.90)	6(3.30)	0.35	0.87a	1	0.74	
(0.73–1.29)	
Depression, n%	36(8.0)	12(4.50)	24(13.0)	0.001	10.76a	1	0.58	
(0.45–0.75)	
Insomnia, n%	26(5.80)	14(5.30)	12(6.50)	0.57	0.32a	1	0.88	
(0.57–1.35)	
Anxiety, n%	108(24)	62(23.30)	46(25.0)	0.68	0.17a	1	0.95	
(0.74–1.22)	
Suicidal Tendency, n%	60(13.30)	30(11.30)	30(16.30)	0.12	2.38a	1	0.79	
(0.59–1.05)	
Inability to Concentrate, n%	10(2.20)	3(1.10)	7(3.80)	0.06	3.59a	1	0.58	
(0.38–0.88)	
Memory Lapses, n%	17(3.80)	2(0.80)	15(8.20)	<0.001	16.39a	1	0.442	
(0.36–0.55)	
Changes in Mood, n%	255(56.70)	154(57.90)	101(54.10)	0.53	0.40a	1	1.08	
(0.86–1.34)	
Comorbidities, n%	144(32)	75(28.19)	69(37.50)	0.40	4.33a	1	1.53 (1.02–2.28)	
Severity Gradee	
Mild, n (%)	363(80.70)	232(87.20)	131(
71.20)	<0.001				
Moderate, n (%)	69(15.40)	24(9.10)	45(24.50)	<0.001				
Severe, n (%)	18(4.0)	9(3.40)	9(4.90)	0.43				
Blood Groupf	
A+	98(21.80)	54(20.30)	44(23.90)	0.79	3.88a	7		
AB+	69(15.30)	36(13.50)	33(17.90)	
B+	125(27.40)	78(29.30)	47(25.50)	
O+	92(20.40)	55(20.70)	37(20.10)	
A-	38(38.40)	24(9.0)	14(7.60)	
AB-	10(2.20)	7(2.60)	3(1.60)	
B-	8(1.80)	5(1.90)	3(1.60)	
O-	10(2.20)	7(2.60)	3(1.60)	
RR, relative risk; CI, confidence interval; SD, standard deviation; IQR, interquartile range.

a Group 1 patients who did not develop post-COVID-19 syndrome.

b Group 2 patients who developed post-COVID-19 syndrome.

c Independent sample t-test.

d Non-parametric test, Mann–Whitney U test.

e Disease severity at presentation: Mild (No need oxygen) Moderate (Need oxygen, Shortness of breath and Pneumonia like Symptoms Like Fatigue, cough, Chest pain, Confusion or problem in concentration) Severe- Rest of the data is counted as severe.

f Disease severity presentation among blood groups.

A significant number of patients 184 (40.88 %) reported experiencing at least one symptom related to post-COVID-19 syndrome (PCS), while the remaining 59.11 % (266 patients) did not exhibit any complications following their recovery from COVID-19. Among those with post-COVID-19 syndrome, the most prevalent symptoms were fever (62 %), followed by cough (60.90 %), general weakness (58.70 %), alterations in mood (57.90 %), and loss of taste and smell (51.10 %).

The median total duration of illness was 15 days, whereas in post-COVID-19 syndrome developing patients it was 20 days. The difference in the interquartile range (IQR) between patients with PCS and those without PCS was statistically significant (p < 0.001).

There was no gender bias in the development of post COVID-19 syndromes (χ2 = 1.27, 95 % CI = 0.90–1.78, P = 0.26) (Table 1). We found that Fatigue requires more time for clinical improvement (χ2 = 9.10, 95 % CI = 0.54–0.86, P = 0.003), followed by Chest pain (χ2 = 18.05, 95 % CI = 0.44–0.69, P < 0.001), Rhinitis (χ2 = 5.46, 95 % CI = 0.58–0.94, P = 0.02), Lack of appetite (χ2 = 3.39, 95 % CI = 0.40–0.91, P = 0.07), Muscle weakness (χ2 = 11.74, 95 % CI = 0.45–0.74, P < 0.001), Stroke and cardiovascular disease(χ2 = 5.84, 95 % CI = 0.36–0.45, P = 0.02) and Memory lapses (χ2 = 16.39, 95 % CI = 0.36–0.55, P < 0.001). The severity grade was also significant for mild (p < 0.001) and moderate (p < 0.001) (Table 1).

After analyzing the blood groups of the patients, we observed that individuals with ‘A’ negative blood type had the highest likelihood of developing COVID-19, accounting for 38.40 % of the cases. This was followed by ‘B’ positive individuals at 27.40 %, ‘A’ positive at 21.80 %, ‘O’ positive at 20.4 %, and ‘AB’ positive at 15.30 %. However, the situation changed when it came to developing post-COVID syndrome (PCS). Among those who recovered from COVID-19, we found that ‘B’ positive individuals had a higher tendency to develop PCS, with a rate of occurrence of 27.40 % while ‘A’ positive, ‘O’ positive and ‘AB’ positive individuals had a rate of 23.90 %, 20.10 % and 17.9 % of PCS respectively. (Table 1).

Among the participants who developed post-COVID-19 syndrome, 16.30 % were grouped as symptomatic and 83.70 % were asymptomatic. Fatigue was common in both groups, followed by muscle pain (32.90 %), respiratory disease (12.30 %) and inability to concentrate (24.70 %). On the contrary, general weakness was less prone symptomatic patients, followed by skin disease (5.90 %), depression (8.20 %), anxiety (1.40 %), suicidal tendency (13 %) and memory lapses (13.30 %) (Table-2).Table 2 Spectrum of post COVID-19 symptomatic and asymptomatic complications among positive patients.

Table 2Characteristics	Total Patients n = 450	Symptomatic Patents	Asymptomatic Patients	
n = 73(16.3) n (%)	n = 376(83.7) n (%)	
Fatiguea	23(5.10)	23(31.50)	0	
Dyspneab	13(2.90)	11(15.20)	2(0.50)	
Joint Pain	16(3.60)	3(4.10)	13(3.50)	
Chest Pain	13(2.90)	4(5.50)	9(2.40)	
Coughc	3(0.70)	3(4.10)	0	
Loss of Taste and Smell	1(0.10)	1(1.40)	0	
Rhinitis	8(1.80)	8(11)	0	
Red Eyes	8(1.80)	1(1.40)	7(1.90)	
Lack of Appetite	6(1.30)	0	6(1.60)	
Sore Throat	9(2.0)	9(12.30)	0	
Vertigo	8(1.80)	0	8(2.10)	
Diarrhea	6(1.30)	5(6.80)	1(0.30)	
General Weakness	118(26.30)	16(21.90)	102(27.10)	
Muscle Weakness	28(6.20)	24(32.90)	4(1.10)	
Muscle Pain	28(6.20)	24(32.90)	4(1.10)	
Jaundice	1(0.20)	1(1.40)	0	
Tuberculosis	1(0.20)	0	1(0.30)	
Heart Disease	4(0.90)	1(1.40)	3(0.80)	
Respiratory Disease (Asthma/COPD)	16(3.60)	9(12.30)	7(1.90)	
Stroke and Cardiovascular Disease	8(1.80)	3	5(1.30)	
Diabetes	3(0.70)	1(1.40)	2(0.50)	
Needle pain in arms and legsd	10(2.20)	3(4.10)	7(1.90)	
Hearing Problem	8(1.80)	4(5.50)	4(1.10)	
Hair Loss	41(9.10)	12(16.40)	29(7.70)	
Skin Disease	26(5.80)	4(5.50)	22(5.90)	
Depression	36(80)	5(6.80)	31(8.20)	
Insomniae	16(3.60)	7(9.60)	9(2.40)	
Anxiety	48(10.70)	9(12.30)	39(10.40)	
Suicidal Tendency	62(13.80)	13(17.80)	49(13)	
Inability to Concentrate	75(16.70)	18(24.70)	57(15.20)	
Memory Lapsesf	61(13.60)	11(15.10)	50(13.30)	
Changes in Mood	7(1.60)	2(2.70)	5(1.30)	
a This condition refers to a significant decrease or limitation in one's ability to participate in the activities they used to do before becoming ill. It lasts for more than six months and is accompanied by intense fatigue. Importantly, this fatigue is not due to overexertion and cannot be significantly relieved by rest. Additionally, it is not a lifelong condition but rather has emerged recently or is clearly identifiable as a new condition.

b This refers to experiencing a sense of respiratory discomfort or difficulty in breathing during physical activities that would not typically cause such discomfort.

c Coughing for >1 h or ≥3 coughing episodes in 24 h.

d Unpleasant sensation of tingling or prickling, usually felt in the arms, legs, hands or feet.

e Persistent difficulty with sleep initiation, duration, consolidation, or quality.

f A pathological condition when a patient forgets things that should be remembered.

Overall, we found that individuals with fatigue (χ2 = 9.10, 95 % CI = 0.54–0.86, P = 0.003) have a slightly increased risk of developing post-COVID-19 syndrome. Additionally, dyspnea (RR = 0.83), cough (RR = 0.76), rhinitis (RR = 0.73), sore throat (RR = 0.84), and muscular discomfort (RR = 0.77) emerge as risk factors for post-COVID-19 syndrome development. As shown in Table-1, respiratory distress (χ2 = 1.51, 95 % CI = 0.54–1.12, P = 0.22) had a weaker connection with the emergence of post-COVID-19 symptoms.

We utilized logistic regression analysis to evaluate the risk factors related to post-COVID-19 problems (Table 3). The findings show that numerous crucial parameters are statistically significant in predicting the development of post-COVID-19 symptoms. Gender did not have a significant association with the development of post-COVID-19 symptoms (Odd Ratio = 0.79, 95 % CI = 0.52–1.19, P = 0.26). Individuals experiencing respiratory distress had a significantly lower likelihood of developing post-COVID-19 complications (Odd Ratio = 0.35, 95 % CI = 0.22–0.57, P < 0.001). Participants with lethargy showed a considerably higher incidence of post-COVID-19 issues (Odd Ratio = 62.25, 95 % CI = 8.44–458.98, P < 0.001). Total duration of illness was related with an increased risk of post-COVID-19 problems (Odd Ratio = 0.69, 95 % CI = 1.03–1.07, P < 0.001). Patients with more severe COVID-19 symptoms were also at a higher risk of having post-COVID-19 problems (Odd Ratio = 2.84, 95 % CI = 1.75–4.62, P < 0.001). In conclusion, our data highlight the importance of these characteristics in predicting post-COVID-19 problems, with respiratory distress and lethargy having opposite effects on risk. The duration of sickness and the intensity of the initial COVID-19 presentation were also identified as important factors in predicting the development of post-COVID-19 symptoms. These identifications can help with risk assessment and patient care measures.Table 3 Risk factors for COVID-19 patients (binary logistics regression analysisa).

Table 3Variables	Reference Category	Bd	SEe	Waldf	p value	Odd Ratio	95 % CI	
Sex	Female	−0.24	0.21	1.27	0.26	0.78	0.52-1.19	
Respiratory Distressb	Absence	−1.05	0.25	17.88	<0.001	0.35	0.217-0.57	
Lethargy	Absence	4.13	1.02	16.43	<0.001	62.25	8.44–458.98	
Total Duration of Illness		0.10	0.01	20.96	<0.001	0.69	1.03-1.07	
Severityc	Mild	1.05	0.25	17.88	<0.001	2.84	1.75-4.62	
Constant		−0.572	0.11	27.35	<0.001	0.57		
a Independent variables: sex, age, all COVID-19 symptoms, severity of COVID-19, severity conversion, persistent positivity, total duration of illness, patient suffering for <7 days and >14 days; Omnibus test of model coefficient, 0.00; Nagelkerke R square, 0.26; Hosmer–Lemeshow test, 0.83; Step 7, sensitivity 60 %, specificity 79 %.

b Shortness of breath, respiratory rate >25 breath/min, or oxygen saturation <93 %.

c Disease severity at presentation: mild symptoms of upper respiratory tract viral infection, including mild fever, cough (dry), sore throat, nasal congestion, malaise, headache, muscle pain, anosmia, or malaise; moderate respiratory symptoms such as cough and shortness of breath without signs of severe pneumonia (tachypnea >30 breaths/min and hypoxia: SpO2 <90 % on room air).

d This is the coefficient for the constant (also called the “intercept”) in the null model.

e This is the standard error around the coefficient for the constant.

f The Wald chi-square value.

4 Discussion

The study included 450 individuals diagnosed with COVID-19 from Chittagong, Bangladesh. We found that 40.88 % of individuals exhibited at least one symptom of post-COVID-19 syndrome and most patients developed it after 2–3 week following the initial recovery. Fever, cough, changes in mood, general weakness, loss of taste and smell, rhinitis, anxiety, muscle pain, fatigue, sore throat, and dyspnea were the most common symptoms in patients (Fig. 2). Moreover, we identified that age, respiratory distress, lethargy, duration of illness and severity of disease may act as risk factors for post-COVID-19. Many of the symptoms were very similar to that developed during the acute phase of COVID-19 [28]. The symptoms were inconsistent, and some individuals experienced symptoms from both COVID-19 and post-COVID-19 syndrome. In addition, we found that a large number of patients did not recover properly and showed long-term symptoms. We have also observed that 37.50 % of patients who had comorbidities, developed post-COVID-19 syndrome (Table 1). This is similar to a previous study conducted in Bangladesh which revealed that 38 % patients who developed post-COVID-19 conditions had comorbidities [29].Fig. 2 Comparison between COVID-19 and post-COVID-19 symptoms.

Fig. 2

Several reports have suggested that many patients did not return to the normal healthy life after recovery from COVID-19, and post-COVID-19 symptoms were still affecting multiple organs of the body [30,31]. Age is thought to be an important factor as the pattern and magnitude of post-COVID-19 syndromes varies in people from different age groups [30,31]. In our study, we have divided patients into three age groups. Among the groups, people aged 40 years or younger showed more susceptibility to develop post-COVID-19 syndromes whereas age group greater than 60 showed less susceptibility (Table 1). This finding is similar to a previous report where they reported that people of older age were less prone to develop post-COVID-19 syndromes [19]. However, another study conducted in the USA reported that people aged 55 years or older were more prone to develop post-COVID-19 syndromes (62 %), while people aged below 55 developed less post-COVID-19 syndromes (38 %) [32]. In our study, most of the participants were from the younger age group (61.55 %) and only 7.78 % were from older age group. This discrepancy in post-COVID-19 syndrome among different age groups may be due to ethnic differences and access to medical services, hospitalization, environmental factors, and lifestyle. Many elderly people in Bangladesh who develop post-COVID-19 syndrome may be unaware of the complications due to lack of education and may not visit the health care facilities and thus go unnoticed.

There are several factors that can justify the higher prevalence of post-COVID-19 syndromes in elderly population such as weakened immune system, preexisting comorbidities, reduced lung function, delayed immune response, inflammatory response and longer exposure [[33], [34], [35], [36]]. In Bangladesh, only 9.28 % of the total population are aged 60 or above whereas in western countries the percentage of elderly population is significantly high (USA 16 %, Japan 28.20 %, Germany 21.40 %, Italy 22.80 %, United Kingdom 18.30 %) [37,38]. This may be a reason behind reduced number of mortalities related to COVID-19 in elderly people from Bangladesh. Moreover, environmental and socio-economic factors can play a role that need to be investigated in future studies.

In the present study we divided the participants into three categories: patients with mild, moderate and severe symptoms. We found that, 71.20 % population showed mild symptoms (Table 1). In previous studies, researchers found that people having mild symptoms exhibited cell alterations, including exhausted T cells and reduced CD4+ and CD8+ effector memory cell numbers [8,39,40]. One previous study that compared individuals with long COVID to both uninfected individuals and those who had COVID-19 without developing long COVID found significant changes in immune cell profiles [8]. The study also reported elevated levels of non-classical monocytes, activated B cells, double-negative B cells, and CD4+ T cells that secreted IL-4 and IL-6 in long COVID patients [8]. In contrast, reduced numbers of conventional dendritic cells and exhausted T cells was observed in this group [8]. Additionally, individuals with long COVID exhibited low cortisol levels, and this analysis was conducted at a median of 14 months after the initial infection [8]. In our study, the median of total duration of illness, (IQR) was 15 days, which increased to 20 days in post-COVID-19 patients (Table 1). This aligns with findings from previous studies [19,40].

We found that the common post-COVID-19 symptoms were fatigue, cough, weakness, mood changes which are prevalent, and more, often appearing weeks after recovery. Moreover, we found multi-organ impact of SARS-CoV-2, affecting not only the lungs but also cardiovascular, neurological, and kidney systems. Understanding these effects is crucial for managing post-COVID-19 conditions [41].

Fatigue has been reported as the first symptom of post-COVID-19 [16,42]. It is related to the neurological system followed by memory loss, disorder sleep and cognitive impairment [8]. In this study, 31.50 % patients exhibited fatigue from post-COVID-19 and all of them belonged to the symptomatic cohort (Table 2). The reason behind developing fatigue is still unknown but it is suggested that COVID-19 causes imbalance in the natural immune response and people may experience fatigue [43]. A study conducted in UK found that fatigue affects the daily life activities and scores similar or worse comparing with cancer related anemia or severe kidney disease patients [8]. In addition, muscle pain and muscle weakness are also highly prevalent in post-COVID-19 as 32.90 % patients experienced these symptoms. In our study, 26.10 % patients developed dyspnea (Table 1). Previous studies suggested that dyspnea is prevalent in post-COVID-19 and decreased in the year following recovery from SARS-CoV-2 [[44], [45], [46], [47]].

Cough (60.90 %) is the most common symptom in post-COVID-19 (Table 1, Fig. 2). Although it is not identified why cough dominates the post-COVID-19 syndromes but it is often accompanied by various manifestations affecting multiple systems, suggesting the presence of either multifactorial underlying pathogenesis or shared mechanisms contributing to these symptoms. Moreover, dyspnea also contributes to post-COVID-19 syndromes. In our study, 17.40 % of participants developed dyspnea as a symptom of post-COVID-19. A previous study conducted in the Chinese population suggested that after recovery from COVID-19 patients the diffusion process is reduced by almost 30 % [48]. COVID-19 mainly affect the lung and so cough and dyspnea are highly likely to occur.

Post-COVID-19 manifests several complications such as neuropsychiatric, cardiovascular, musculoskeletal, dermatologic, pulmonary, hematologic, gastrointestinal, renal, and endocrine system [49,50]. In this study, we have found that it mainly affects the pulmonary, neuropsychiatric and musculoskeletal system. This study also reveals that gender, respiratory distress, lethargy, total duration of illness, and severity are the risk factors for post-COVID-19, which is in line with previous studies (Table 3) [19]. We found that male is more prone to develop post-COVID-19 syndromes. However, a previous study suggested that women had a 3-folds higher risk of developing post-COVID-19 [51]. It is important that patients with specific risk factors, in particular, should be extra cautious about their health. Specially, individuals experiencing symptoms such as fatigue, dyspnea, cough, general weakness, muscle weakness, muscle pain, and those with pre-existing kidney disease needs special attention and care.

Our study has several limitations. The number of patients included is not sufficiently large to detect small effects in COVID-19 patients. Moreover, the pandemic related lockdown measures posed challenges in data collection and robust assessment. Although we maintained a 3-months follow-up for our patients, it is evident that extended follow-up periods are required to obtain data that is not only more accurate but also reflective of the enduring impact of COVID-19. Longitudinal studies with larger sample size and different ethnicities are thus warranted. The results of our study should be validated in studies with larger sample size and caution should be taken for generalizability of the results in population from different ethnicity.

5 Conclusion

In conclusion, we can say COVID-19 and post-COVID-19 symptoms reveal different patterns that emphasize the dynamic character of the viral infection. The classical symptoms of COVID-19 consist of fever, fatigue, cough, loss of taste and smell, overall weakness, changes in cognition, and respiratory distress but the post-COVID-19 phase, also known as post-acute COVID-19 syndrome has a distinctive clinical character. This phase offers a broader range of symptoms, including emerging multisystem presentations and those seen during the acute phase. Continuous long-term monitoring is thus necessary to get a better understanding of the risk factors and management of COVID-19.

Funding

The authors did not receive any specific funding for this study.

Data availability statement

Data will be made available on request.

Ethics

All study participants signed informed consent forms and the study protocol was approved by the Institutional Review Board of North South university (Approval ID: 2023/OR-NSU/IRB/1105).

CRediT authorship contribution statement

Leon Bhowmik: Writing – original draft, Investigation, Formal analysis. Md Kutubul Hasan: Writing – original draft, Investigation, Formal analysis. Tahmina Akter Bristy: Writing – original draft, Investigation, Formal analysis. Sadia Tasnim Etu: Writing – original draft, Investigation, Formal analysis. Reatul Karim: Writing – review & editing, Visualization, Validation, Software, Data curation. Md Shaki Mostaid: Writing – review & editing, Visualization, Validation, Software, Data curation. Manik Chandra Shill: Writing – review & editing, Supervision, Project administration, Conceptualization. Hasan Mahmud Reza: Writing – review & editing, Visualization, Validation, Project administration.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Appendix A Supplementary data

The following is the Supplementary data to this article:Multimedia component 1

Multimedia component 1

Acknowledgement

The authors would like to thank the study participants for participating in the study. Moreover, we thank their family members, doctors, nurses, and hospital management for their cooperation in data collection procedure.

Appendix A Supplementary data to this article can be found online at https://doi.org/10.1016/j.heliyon.2024.e36202.
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