"Analysis of the Primary Presenting Symptoms and Hematological Findings of COVID19 Patients in Bangladesh"

Background: SARS-Cov-2 infection or COVID-19 is a global pandemic. From the time of identication to till, multiple clinical symptoms and parameters have been identied by the researchers of various countries and regions regarding the diagnosis and presentations of COVID19 disease. In this manuscript, we investigated the primary symptoms and basic hematological presentations of SARS-CoV-2 infection among the Bangladeshi patients. Methodology: We have collected the disease history of mild to moderate degree of COVID19 patients; hematological and biochemical on admission reports of moderate degree COVID19 patients. All of them were tested positive for SARS-CoV-2 by RT PCR in different institutes in Bangladesh. Results: According to this study though COVID19 patients in Bangladesh commonly presented with fever, cough, fatigue, shortness of breath, and sore throat, but symptoms like myalgia, diarrhea, skin rash, headache, Abdominal pain/cramp, nausea, vomiting, restlessness, and a higher temperature of >100 0 F have a greater presentation rate and more frequent than other published studies. CRP and Prothrombin time was found to increase in all the patients. Serum ferritin, ESR, SGPT, and D-Dimer were found increased among 53.85%, 80.43, 44%, and 25% patients respectively. 17.39% of the patients had leucocytosis and neutrophilia. 28.26% of patients presented with lymphocytopenia. 62.52% of patients had mild erythrocytopenia. Conclusion: Despite some similarities, our study has evaluated a different expression in presenting symptoms in the case of COVID19 patients in Bangladesh. CRP, Prothrombin time, serum ferritin, ESR, SGPT, D-Dimer, erythrocytopenia, and lymphocytopenia can be initial diagnostic hematological ndings and assessments for prognosis COVID19 disease. Also, Gender variation has a different scenario of clinical and laboratory appearance in this region.


Methodology:
For the analysis of the presenting symptoms of SARS-CoV-2 infection, we collected the data of COVID19 patients from Chattagram Civil Surgeon's o ce, and the Chakoria Upazila Health and Family Welfare O cer's (UH&FPO) o ce. All the patients were tested positive for SARS-CoV-2 by RT PCR at Bangladesh Institute of Tropical and Infectious Disease (BITID) and Cox's Bazar Medical College Hospital and were treated (either as an outpatient or as inpatient with mild to moderate degree of illness) under different COVID19 dedicated hospitals in Chattagram district, and Chokoria Upazila Health complex. A total of 638 patient's data that were tested positive from May 5th to June 5 th, 2020 were collected. Each of the patients was individually interviewed to nd out the details of the disease symptoms, history, comorbid condition, and associated complaints.
Patients with severe comorbid conditions like severe Bronchial asthma, COPD exacerbation, severe ischemic heart disease, severe uncontrolled diabetes mellitus, advanced renal and hepatic disease, patients with carcinoma, hospitalized and Immuno-compromised patients were not included in this study.
Due to misconception and unreliable statement 127patient's data were discarded. 138 patients had comorbid conditions that affected the presenting symptoms or had existing symptoms from before, so these were also excluded. 53 patients did not respond to our call or unwilling to participate in the study. Following exclusion for symptomatic analysis 320 patients of 13 to 56 years (mean age 35.81 years) of age were included in this study.
To evaluate the hematological changes in the patients we gathered the hematological and biochemical on admission reports of 89 admitted patients (moderate degree COVID19 disease) from May 5th to June 5 th, 2020. This included Hemoglobin level, Erythrocyte Sedimentation rate, total and differential count of WBC, RBC, Platelet, C-Reactive Protein (CRP), SGPT, Serum Ferritin, Prothrombin time, D-Dimer, and Serum creatinine. According to the clinical presentation patients with fever were tested for Dengue NS1 antigen, Dengue IgG & IgM antibody, Salmonella Typhi IgM and IgG antibody, ICT for malaria (Antigen for Plasmodium Falciparum, Vivax, Malaria, and Ovale) and Widal test to exclude Dengue, Malaria, and Enteric fever. Patients who had a chronic comorbid condition and any recent history of hematological, biochemical abnormalities, or chest radiograph abnormality within a period of 30 days were not included in this study. In our observation, all patients with severe diseases had pre-existing comorbid conditions. Therefore only the laboratory ndings of patients with moderate COVID19 disease were collected.
Following exclusion criteria (others as described earlier) 39 patients were excluded from the study. A total of 50 patient's data were included in the analysis. Male 37 males and 13 females of 31 to 59 years of age (mean 42.8 years).
Informed consent was obtained in every case. Ethical committee approval was obtained from Xi'an Jiaotong University. Statistical analysis was done by Graphpad Prism software. T-test was done to see the difference in the values. A P value of < 0.05 was considered signi cant.
Results: Table 1: A total of 320 patients were included in the study. The patient's ages were 13 to 56 years. 208 (65%) were male and 112 (35%) were female. [ Figure 1A] The Mean age of the patients was 35.81 ± 11.68 years. The mean age of male and female patients was 34.16 ± 11.08 years and 38.89 ± 12.19 years respectively. [ Figure 1B] 129 (40.31%) patients were under hospital and 191 (59.69%) were under home isolation. Out of 320 patients, 262(81.88%) were symptomatic and 58 (18.13%) were asymptomatic. The age of male and female symptomatic patients was 34.15 ± 11.07 years and 38.89 ± 12.19 years. The duration of symptoms was 5.66 ± 3.60 days in general. In the case of male patients, this was 5.72 ± 3.50 days and female was 5.56 ± 4.0 days. [ Figure 1C]  Figure 1D] T-test was not signi cant among the groups. Age group was as following 10 to 20 years 30patients, 21 to 30 years 53 patients, 31 to 40 years 127 patients, 41 to 50 years 71 patients, and 51 to 60 years 39 patients. [ Figure 1E]  Figure   2 A & B] The maximum temperature was found 104 0 F. 220 patients had a history of fever and 100 patients had no fever history. [ Figure 2D] Out of 220 patients presented with fever, 68 patients had temperatures < 100 0 F and 152 presented with > 100 0 F temp. [  Figure 2F]       Figure 3D] Subgroup analysis of patients biochemical evaluation depending on patients gender: CRP and Prothrombin time (PT) was increased in all the male and female patients; increased SGPT level was found among 52.94% male and 25% female; increased serum ferritin level was seen among 68.75% male and 37.5% female; 18.8% male and 100% of female (1 of 1 female patient) had an increased level of serum D-Dimer. [ Figure 3F] Difference between the decrease hemoglobin level (P = 0.0243) and increased SGPT (P = 0.0108) against male and female in the Chisquare test and t-test patients were found signi cant, others are not. [ Figure 3G] Discussion: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 has rapidly evolved as an epidemic outbreak and infected more than six and a half million individuals all over the world. Besides this, billions of others are directly affected by the citizens are affected by measures of social distancing and the socio-economic impact. COVID19 is a systemic infection causing a signi cant impact on the hematopoietic system and hemostasis mechanism. [3] The incubation period of this virus can be up to 14days following exposure. According to the center for disease control and prevention (CDC), the individuals with COVID-19 have had a wide range of symptoms reported ranging from mild to severe illness. These symptoms may appear from the second day till the incubation period. These symptoms may include but not limited to cough, fever, chills, muscle pain, the heaviness of chest, shortness of breath or di culty breathing, sore throat, and loss of taste or smell. Warning signs of COVID-19 include breathing di culty, persistent pain or pressure in the chest, inability to wake or stay awake, sings of central cyanoses like bluish lips or face, and confusion. [4] Multiple studies have reported presenting symptoms of COVID-19 worldwide among which several symptoms are common, but due to geographical locations, these symptoms may differ.
In this study, we analyzed the COVID-19 cases in multiple centers in Bangladesh to assess these symptomatic and hematological variations from the rest of the world. Following exclusion, our study revealed that the primary presenting symptoms of 320 COVID19 patients in treated in multiple centers in Bangladesh include fever, cough, chest tightness, weakness, anorexia, myalgia, diarrhea, nausea, sleep disturbance, headache, sore throat, respiratory distress, rhinorrhea, abdominal pain, rash or skin lesion, vomiting, vertigo, and restlessness. Among these primary presenting symptoms, fever and cough were most common, and vomiting and vertigo were relatively uncommon. Chest tightness and weakness were relatively common in COVID-19 cases but not as much as fever and cough, which was present in the maximum number of cases affected by SARS-CoV-2 [ Figure 2 A & B]. This study can help healthcare professionals in Bangladesh and others to narrow down the suspected COVID-19 affected cases and perform testing accordingly. In Bangladesh, unlike developed countries, real-time reverse transcriptionpolymerase chain reaction (RT-PCR) is the only available test which is recommended by the Institute of Epidemiology, Disease Control and Research (IEDCR) for the healthcare settings. The real-time RT-PCR is of the high value of interest for the detection of COVID19 disease due to its simplicity and speci city. [5][6][7] But unfortunately RT-PCR test has the risk of eliciting false-negative and false-positive results, as the sensitivity and speci city of the RT-PCR test are not 100%. [8] However, a chest computed tomography (CT) was reported 98% and 97% sensitive in two different studies. [9,10] One of the early studies regarding clinical characteristics of COVID-19 done on 1099 patients in china revealed that the most common symptoms were fever, cough, and fatigue which resembles ndings of our study (68.8%, 57.3%, and 41.9%). [ Figure 2 A & B] A study on the systematic review focusing on upper airway symptoms revealed that the common symptoms of COVID19 were fever, cough, and fatigue. [11] These studies with our study con rm that fever and cough are the two most common onset symptoms of  [15] which was also present in the COVID-19 cases found in our study (9.1%). A similar result was also found in the case of rash/skin lesion in this study, which resembles a case study where a young male with full-body rash was a presenting symptom of COVID-19. [16] 16.6% of the patients in our study complained of mild to moderate amounts of abdominal cramp or pain. This nding also similar to a case study reported earlier that the acute abdomen was the early symptom of COVID-19. [17] During the data collection we have noticed 2 severe cases of COVID19 with hemoptysis. As all the severe cases had per existing comorbid conditions, so were not included in his study. We have also observed three cases presented only with anorexia and two cases of severe myalgia later were diagnosed as SARS-CoV-2 infection. As an additional nding, restlessness was complained by 85 (25.63%) of patients this was 34.76% of symptomatic males and 25.51% of the symptomatic females [ Table 2]. Based on our study ndings minimally symptomatic patients or symptoms like abdominal cramp or pain, Myalgia, localize skin lesion or rash, sleep disturbance, and restlessness are important presenting symptoms for this region of COVID19 disease besides common other symptoms.
According to our study males have a higher infection rate than females 208 (65%) & 112 (35%). [ Figure   1A] Also only 18.12% of patients were asymptomatic whereas symptomatic cases were 81.88%. [ Figure  2C] This is due to lack of test availability and also tests were made available only to the de nite symptomatic patients or those who have radiological or laboratory ndings suggestive of SARS-CoV-2 infection. The duration of symptoms had no variation depending on gender and age. [Figure 1 C, Fig. 2F] Male patient's home isolation and treatment number are higher than the female patients. [ Figure 1D] Incase of age group 31 to 40 years are the most affected n = 127/320 and 10 to 20 are the least n = 30/320. [ Figure 1E] Cases with or without fevers were high 68.75% and 31.25% compare to Wei-jie Guan et al. [11] Duration of fever has no signi cant difference regarding presenting temperature. [ Figure 1F] But temperature > 100 0 F was relatively higher then < 100 0 F 47.5% and 21.25% of total patients, this is 152 (69.09%) and 68 (30.90%) [ Table 1] of patients with fever and does not correlate with the other study. [11] Male patients were more affected with cough than female and dry cough was more common than sputum. [ Figure 2E] Fever, weakness, anorexia, Myalgia, nausea, headache, breathing di culty, vomiting, and restlessness were more prominent in the case of male than female patients. [ Table 2, Fig. 3A & B] Chest tightness, sore throat, skin lesion/rash, and vertigo were more common in female patients. [ Table 2, Fig. 3A  and an early and prolonged pharmacological thromboprophylaxis with Low molecular weight heparin (LMWH) is highly recommended. [18] We  Figure 3F] Analysis of biochemical values according to gender revealed differences between males and females in a few parameters. Increased levels of SGPT and S. Ferritin were found among males, and increased levels of D-Dimer were found among females (One in one patient). [ Figure 3E] There were no differences in the levels of CRP and prothrombin times between males and females in patients with COVID-19. [ Figure 3E] Hemoglobin count was decreased in the case of males (71.42%) than females (36.36%), though RBC count was normal in all the males and decreased among 27.27% of female patients. [ Figure 3D] Difference between the decrease hemoglobin count and increased SGPT against male and female patients was found signi cant. [ Figure 3G] All these suggests us to provide more attention towards gender in cease of laboratory ndings for COVID19 diagnosis and prognosis One of our important observations was in delay in diagnosis and therefore treatment from the time of appearance of symptoms, 5.67 ± 3.56 days. [ Figure 1C] This is probably explained by delay in publishing test results (2 to 3days from sample collection) unwilling to take tests by patients due to testing and social hazards, and strict indications followed for the PCR test (Fever, breathing di culty, chest discomfort, Chest X-ray ndings, and associated hematological ndings) by the COVID19 tertiary center doctors due to limited resources.

Conclusion:
According to this study COVID19 patient in Bangladesh though has similarity with the presenting symptoms like fever, cough and berating complaints, but symptoms like myalgia, diarrhea, skin rash, headache, Abdominal pain/cramp, nausea, vomiting, restlessness, and a higher temperature of > 100 0 F have a greater presentation rate and more frequent even as an isolated presentation of SARS-CoV-2 Consent to participate: Informed written consent was taken in every case. In the case of bellow 16yeras old participants written informed consent was obtained from a parent or guardian.