Immediate and post-COVID complications of symptomatic and asymptomatic COVID-19 patients in Bangladesh: a cross-sectional retrospective study

The COVID-19 pandemic has cost a large number of lives worldwide. Most of the COVID-19 patients recover within two weeks of illness, but many survivors are experiencing different post COVID-19 clinical complications. In this cross-sectional retrospective study, we investigated the immediate and post COVID-19 complications with secondary effects in symptomatic and asymptomatic COVID-19 patients of Bangladesh. A total of 632 patients diagnosed with COVID-19 from December, 2020 to February, 2021 were included in this study. The data were collected by telephone interview with patients consent and reviewing their call records using questionnaire and checklist. Results demonstrate that among the 632 patients, 77.53 % of cases were symptomatic, where fever was the most common symptom (82.24%). The other symptoms were headache (58.16%), sore throat (53.65%), cough (45.51%), weakness (41.22%), breathlessness (40%), loss of smell (37.55%), tastelessness (31.84%), diarrhea (19.39%), and vomiting (14.69%). Comorbidities like asthma, hypertension, diabetes mellitus (DM), cardiovascular disease, and other chronic diseases were pronounced in symptomatic patients. Post COVID-19 complications varied significantly (P<0.05) between the symptomatic and asymptomatic observations. Asthma, hypertension, and diabetes were newly reported in symptomatic patients with the rate of 3.06 %, 2.45 %, and 2.24 %, respectively, while the proportions were 1.41%, 1.41%, and 0.70% for the asymptomatic group. Tiredness, weight loss, hair loss, and insomnia were the most observed post COVID-19 complications found higher in symptomatic patients than in asymptomatic groups. A newly developed visual anomaly was also identified in the symptomatic group (1.42%), which was absent in asymptomatic COVID-19 recovered patients. These findings concluded that post-COVID-19 complications were high in symptomatic and comorbid patients compared with asymptomatic individuals. We hope that this study will contribute in post COVID-19 management and help the concerned authority toward decision making in the treatment of post-COVID-19 complications.


Introduction
Coronaviruses are large, positive-stranded, protein enveloped RNA viruses that are distributed broadly among birds, humans, and other mammals (Weiss and Leibowitz, 2011). A total of seven different species of coronaviruses are found to infect humans. Among them, the species named 229E, OC43, NL63, and HKU1 have been considered inconsequential pathogens causing the -common cold‖ in immunocompetent individuals (Su et al., 2016;Zhu et al., 2019). The other three strains (e.g., SARS-CoV, MERS-CoV, and SARS-CoV-2) are highly pathogenic and sometimes cause fatal illness in the infected individuals (Paules et al., 2020). The recently emerged novel coronavirus (SARS-CoV-2) also known as 2019-nCoV, is zoonotic in origin and was first identified in Wuhan, China in November 2019. This 2019-nCoV genome is 80% identical to the SARS-CoV genome and uses the similar angiotensin-converting enzyme 2 (ACE-2) receptor for viral entry inside the host cells (Zhou et al., 2020;Hoffmann et al., 2020). This viral infection has been confirmed in millions of people and the outbreak has already been declared as a pandemic by WHO in March 2020 (Johns Hopkins Coronavirus Resource Center, 2020;WHO, 2020). In Bangladesh, the first reported COVID-19 infection was on March 8, 2020 (Mina et al., 2020). Although all aged groups are susceptible to this viral infection, the severity and lethality of the disease are much more in older and immune-compromised individuals (Annweiler et al., 2021). A broad spectrum of clinical symptoms are expressed in COVID-19 patients, and the semiology of older patients differs from those encountered younger ones (Carfì et al., 2020). It affects almost every organ system including renal (acute kidney injury), gastrointestinal, endocrine and musculoskeletal, nervous (neuropathy, encephalopathy), cardiovascular, and respiratory system of the body (White-Dzuro et al., 2020;Annweiler et al., 2021). Multiple symptoms like fever, body aches, cough, diarrhea, shortness of breath, etc. have been reported in many patients during COVID-19 infection (Iranmanesh et al., 2021). The post-COVID-19 clinical expressions are still unknown, but some emerging evidence showed that COVID-19 survivors are experiencing medium and long term problems. An Italian study of 143 individuals who had been followed up seven weeks after discharge found that 53% have fatigue, 43% with breathlessness, and 27% having joint pain (Halpin et al., 2021). Similar types of clinical complication were also reported in pathogenic SARS and MERS coronavirus infected patients. Post-COVID complications like post-traumatic stress disorder (PTSD), anxiety, sleepiness, and stress were also observed among the recovered individuals from SARS and MERS (Yuan et al., 2021). Long-term glucometabolic, cardiopulmonary, and neuropsychiatric problems have been reported following infections with coronavirus (Dasgupta et al., 2020). Patients with diabetes, chronic obstructive pulmonary disease (COPD), cardiovascular diseases (CVD), malignancies, hypertension, and other comorbidities are the most susceptible to COVID-19 life-threatening situations (Ejaz et al., 2020). An epidemiological study in Bangladesh found that the recovered individuals experienced some short-term outcomes, including pains and aches (31.8%), anxiety or depression (23.1%) and weakened attention span (24.4%) (Mannan et al., 2021). On the other hand, subclinical lung abnormalities may be associated with asymptomatic COVID-19 patients as identified by CT scan (Oran and Topol, 2020). Research on COVID-19 patients in the Eastern Province of Saudi Arabia demonstrated that abnormal chest radiographs were in 15.5% of asymptomatic and 46% of symptomatic patients (AlJishi et al., 2021). It still remains elusive about the difference in comorbidities and post-COVID-19 complications among the symptomatic and asymptomatic COVID-19 cases in Bangladesh. In this study, we investigated the immediate and long-term secondary effects of symptomatic and asymptomatic COVID-19 patients. Additionally, we compare the post-COVID-19 complications between symptomatic and asymptomatic COVID-19 patients of Bangladesh.

Study design
For this retrospective study, we selected the patients diagnosed with COVID-19 infection by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) assay from December, 2020 to February, 2021. Patients who were tested negative after two consecutive RT-PCR tests at least at a gap of 24 hrs and 28 days prior to the interview date were considered for studying post-COVID-19 complications in individuals. Patients who did not give their consent during the telephone interview were excluded from this study. Furthermore, patients exhibiting no post-COVID-19 complications at an interval of one month after being tested negative were also excluded.

Data collection
All the data for retrospective study were collected by telephone interviews and were recorded in a wellstructured questionnaire which was approved by the Ethical Clearance Committee (ECC) of Noakhali Science and Technology University, Noakhali. The data were stored in a Microsoft Excel file on completion of data collection.

Ethical consideration
Verbal consent was taken from the patients at the beginning of the study. The study protocol was approved by the ECC, Faculty of Science, Noakhali Science and Technology University.

Statistical analysis
The collected data were analyzed using descriptive (frequency counts and percentages) and inferential statistics. T-test was performed to evaluate the association between categorical variables. P-values less than 0.05 were considered significant. All the statistical analyses were carried out by using SPSS Statistics 25 (IBM, Armonk, New York) and Graph-Pad Prism version 8.4.3 (Graph-Pad, San Diego, CA, USA).

Demographic information of COVID-19 positive patients
The demographic profile of symptomatic and asymptomatic COVID-19 patients varied in our study participants (Table 1). Our study was conducted on 632 patients where 77.53% of the patients were symptomatic while the rest of them did not show any symptoms. Among the symptomatic groups, male patients had a higher proportion (70%) compared to females (30%). A similar trend was also observed in the asymptomatic group: male (68 %) and female (32 %) ( Figure 1). The average age of symptomatic and asymptomatic patients was 45.52 ± 17.67 and 41.46 ± 13.27 years, respectively. A substantial difference was found in symptomatic and asymptomatic COVID-19 patients of different age groups (P=0.0029). A higher ratio of symptomatic cases was observed in the age groups of 31-40 (24.49%), 21-30 (22.24%), and 41-50 (18.37%) years ( Figure 2). In this study, O+ve and B+ve blood group patients were more susceptible to COVID-19 infection both in the symptomatic and asymptomatic groups. No significant correlation was observed in symptomatic and asymptomatic COVID-19 patients with smoking, traveling or contract history.

Post-COVID-19 complications in positive patients
Post-COVID-19 complications varied significantly (P<0.05) among the symptomatic and asymptomatic observations (Table 3). Interestingly, the number of comorbid patients was higher in the symptomatic group than in the asymptomatic. Asthma, hypertension, and diabetes mellitus were newly reported in 3.06 %, 2.45 %, and 2.24 %, respectively of symptomatic patients, while the proportions were 1.41%, 1.41%, and 0.70% for the asymptomatic group. Tiredness, weight loss, hair loss, and insomnia were the most observed post-COVID-19 complications found in both symptomatic and asymptomatic group; (12.45 % and 4.22%), (9.18% and 4.93%), (5.92% and 4.22%), and (5.71% and 4.22%) respectively. Among other complications, chronic disease, allergy, mental confusion, sleepiness, chest pain, cough, anorexia, irritable mood, nausea, and dyspepsia were reported in both symptomatic and asymptomatic COVID-19 positive patients after recovery. No visual anomaly was reported in asymptomatic patients, but 1.42% of the symptomatic individuals developed a visual problem (Table  3).

Discussion
The highly contagious COVID-19 disease caused by SARS-CoV-2 primarily infects the respiratory tract cells and can develop mild to severe interstitial pneumonia and acute respiratory distress syndrome (ARDS) (Zou et al., 2020;Weiskopf et al., 2020). However, SARS-CoV-2 also affects other cells of different systems like central nervous, cardiovascular, musculoskeletal, and gastrointestinal system where ACE-2 receptors are widely expressed (Gheblawi et al., 2020;Candan et al., 2020;Hamming et al., 2004). Although several reports have been found on COVID-19 complications, however, the long-term effects have not been fully understood yet due to its short history of emergence. In this study, we present the immediate and long-term clinical features of the COVID-19 patients reported from Bangladesh. The majority of the patients were in two groups, namely symptomatic and asymptomatic. A total of 632 COVID-19 positive participants (mean age ± SD=45.66 ± 17.63 years) were included in this current study, where the most patients were symptomatic (77.53%). Figure 1 showed the total ratio of male and female patients in both symptomatic and asymptomatic groups. A significant difference was found in symptomatic and asymptomatic COVID-19 patients of different age groups. A higher prevalence of COVID-19 positive was observed in the age group ranging from 21-30. In contrast, a lower prevalence of COVID-19 positive was detected in the age group ranging from 0-10 and 11-20 (Table 1). This finding indicates the children are prone to benign COVID-19 infection than older people. Moreover, the majority of the symptomatic patients were above 30 years old (70.61%) (Figure 2). Results of this study also provided compelling evidence that blood groups had a significant relationship with the patients being asymptomatic or symptomatic. The majority of the symptomatic (46.73 %) and asymptomatic (51.41 %) COVID-19 patients belonged to O+ve blood group. The other's with B+ve and A+ve groups were also highly susceptible to COVID-19 both in symptomatic and asymptomatic patients (Table 1). This might be due to B+ve and O+ve blood groups are the most common blood group among Bangladeshis (Dipta et al., 2011). We did not find any significant relation between the symptomatic and asymptomatic patients with smoking history. However, our study reported that 3.47% and 3.52% of symptomatic and asymptomatic individuals with COVID-19 infection had travel history and didn't show any significant difference in patients falling into each group (Table 1). From our study, we observed one or more clinical symptoms in the symptomatic COVID-19 patients. The most common clinical complication observed in symptomatic COVID-19 patients is fever (82.24%) followed by headache (58.16%), sore throat (53.65%), cough (45.51%), weakness (41.22%), breathlessness (40%), loss of smell (37.55%), tastelessness (31.84%), diarrhea (19.39%), and