**3. Results**

From 21 March to 30 September 2020, among the 3056 icddr,b employees working at Dhaka and Matlab centers, 1370 were tested for COVID-19 and 522 (38%) tested positive. Within this period, eight patients (1.5%) had recurrent episodes of COVID-19 infection. Three were excluded due to a short gap (less than 28 days) between previous PCR negativity and subsequent PCR positivity and the absence of any clinical sign/symptoms during their first episode of COVID-19 positivity. None of them had a history of compromised immunity. Of the five remaining patients who fulfilled our criteria for selecting patients to investigate for reinfection, 60% were male. All five cases were 35 to 49 years old with a mean age of 41 years (Table 1). All five cases perceived that the second episode, which occurred after a long recovery time, was a COVID-19 reinfection.


**Table 1.** Clinical characteristics of the COVID-19 cases for both their first and second episodes of illness.

Note: for all patients, we considered the starting date of the illness (first day of symptom onset) as "Day One" (D1). Sign-symptoms: F = fever; H = headache; A=anosmia; J = joint pain; M = malaise; C = dry cough; S = sore throat; HTN = hypertension; DM = diabetes; HT = hypothyroidism; RhA = rheumatoid arthritis. Medications: A = azithromycin 500 mg tablet, once daily for 5 days; D = doxycycline 100 mg capsule, twice daily for 5 days; H = hydroxychloroquine 200 mg tablet, first day—two tab stat., from second day onwards—twice daily for 10 days; Z = zinc 20 mg tablet, twice daily for 14 days; VD = vitamin D3 2000 IU, one tablet on every alternate day for one month; M = montelukast 10 mg tablet, once daily for 10 days; R = rivaroxaban 10 mg tablet, once daily for 45 days; I = ivermectin 6 mg tablet, two tablets on day one only; amoxycillin with clavulanic acid (625 mg), eight hourly for 7 days; moxifloxacin, 400 mg tablet once daily for 7 days; P = tablet prednisolone for two weeks, starting at 16 mg daily for three days and then tapered dose; F = favipiravir 200 mg tablet, 1600 mg twice daily on day 1, 600 mg twice daily on day 2−10.

> The clinical course of the patients over time (onset of symptoms, severity, duration, recovery time) and PCR results are illustrated in Figure 1. Figure 1 clearly demarcates two episodes of COVID-19 illness.

**Figure 1.** Clinical course and the corresponding PCR test results of the five patients with recurrent episodes of COVID-19 infection.

> *3.1. Case Series*

### 3.1.1. Case 1

The first case presented with fever and a cough starting on 13 May (D1; D = day). The nasopharyngeal swab was drawn on 16 May, and the RT-PCR test was COVID-19 positive. The patient had a history of hypertension for three years. The patient reported no contact

with suspected cases. He was advised to home isolate and was treated with azithromycin, ivermectin, doxycycline and zinc tablets (Table 1). He became asymptomatic on D15. On 3 June, his RT-PCR was negative. After a 98-day asymptomatic period, he developed a fever, dry cough and cold on 2 September, and tested positive a second time on 4 September. Case 1 reported attending a meeting at his office and also shopping at a nearby wet market for fish and other groceries in the 14 days before the onset of the second time illness. Although the case reported wearing a mask and using hand sanitizer during these outside visits, he states that these visits may have been the source of COVID-19 exposure. His symptoms persisted for 18 days before full clinical recovery and his RT-PCR was negative 22 days after the second onset of symptoms (24 September). He was well aware of COVID-19 as he read extensively about the infection from different online materials. In terms of vaccination, he was hopeful, assuming that it would continue to reduce the risk of COVID-19 and its severity. His test results are summarized in Table 2.

**Table 2.** Laboratory findings of the COVID-19 cases for both first and second episodes of illness.


\* Influenza virus A and B, respiratory syncytial virus (RSV), parainfluenza (1, 2, 3), human metapneumovirus (hMPV), and adenovirus.

#### 3.1.2. Case 2

The second case was a research assistant. She reported malaise on 19 May (D1). Two days later, her RT-PCR test was found to be positive. She had no other comorbidity. She went only to her workplace in the past 14 days before the onset of symptoms. The patient reported no contact with suspected cases. She was advised to home isolate. Her ECG, blood pressure and oxygen saturation were within normal limits. She became asymptomatic after D10 (27 May). She was tested again on D25 (12 June) and her RT-PCR test was negative. Case 2 reported that she went to the office regularly after being PCR negative. She used public transportation to and from work as well as on field trips. After a 92-day asymptomatic period, she developed a sore throat, fever, dry cough and a headache on 27 August. She was retested on 1 September and was found to be RT-PCR positive for the second time. No family members or any close contacts were positive for coronavirus within this time frame. She reported that she might have unknowingly been exposed to someone who is COVID-19 positive while traveling or engaging with patients and their caregivers at her workstation. For the second episode of illness, she was again treated at home with oral medication (Table 1). Her symptoms persisted for 21 days and her RT-PCR test was found to be negative on 21 September (Table 1). Influenza H3 coinfection was discovered in her second respiratory specimen. Since she received basic biosafety training from her office, she was well aware of COVID-19 transmission including person-to-person infection and through respiratory droplets in the air. She also shared an interest in the COVID-19 vaccine, which she hopes would benefit both her family and community.

#### 3.1.3. Case 3

Case three was a hypertensive physician who reported a fever, headache and sore throat on 28 May (D1). Two days later, his PCR sample was found to be positive. He was isolated at home. Four days later, he became symptom-free. On 19 June, his follow-up sample was found negative. He was asymptomatic for the next 70 days. He reported fever, cold and low oxygen saturation (self-reported at 93%) on 12 August, and again was found to be PCR positive on 16 August. The case reported that within the past 14 days of his second episode, he had interaction with two COVID-19 relatives. During this second episode, he was tested for CBC, CRP, D-Dimer, LDH, a CT scan, and an echocardiogram. All were within normal limits except that a ground-glass appearance was evident on the chest CT and the CRP was elevated. After 12 days of illness, he became asymptomatic on 24 August (D90). On 29 August (D94) his PCR test was found to be positive. He was advised to isolate for another week without additional treatment and no further PCR testing was recommended. He reported having direct contact with COVID-19 positive patients and visiting them in the hospital is the riskiest way to acquire COVID-19 infection compared to exposure to an open environment like a wet market or workplace. He has a very positive attitude towards vaccinations.

#### 3.1.4. Case 4

Case four was an account officer with a history of recurrent asthma. He developed a fever on 1 June (D1) and tested positive for COVID-19 on 3 June. His fever subsided after three days. His next scheduled PCR test was negative on 25 June. Due to the nature of the job, case 4 reported that he frequently went to his office in the preceding 14 days using office transportation and also visited local markets for shopping. Eighty-five days after the relief of symptoms, he reported fever and cough on 29 August and was found PCR positive on 1 September. The staff clinic prescribed ivermectin, doxycycline, zinc for the second illness. His fever subsided 3 days after onset, but a dry cough persisted for seven days. On 21 September, his scheduled PCR test was negative. During his second episode, he was co-infected with influenza H3. His detailed treatment history and laboratory findings are depicted in Tables 1 and 2. He had a basic understanding of how the virus spreads. For COVID-19 prevention, he emphasized handwashing with soap or sanitizer on a regular basis, maintaining social distance, and wearing a mask outside. He desired to ge<sup>t</sup> a COVID-19 vaccine as soon as possible to protect himself and safeguard his family.

### 3.1.5. Case 5

Case five was a young doctor working at the Matlab hospital. She reported to the staff clinic on 9 May with a sore throat and cough starting on 7 May 2020. Both her father and son were previously diagnosed as COVID-19-positive and she was a close contact. On 12 May, her PCR test result was found positive. She was isolated at home and treated with azithromycin, hydroxychloroquine and zinc tablets. Fourteen days after initial positivity, consecutive tests, 24 h apart, were found to be negative. After a prolonged asymptomatic period (113 days), she was tested again, given she was unknowingly in close contact with a COVID-19-positive nurse at work in the preceding week. On 16 September, she tested positive for a second time. Two days after the second diagnosis, she reported a very severe headache, chest pain and a sore throat. She measured her oxygen saturation and it was low (90%). She was subsequently admitted to icddr,b hospital on 20 May. Her ECG, Chest X-ray, and D-dimer levels were tested and found to be within normal limits. As her symptoms improved over the day, she was discharged in the evening on the same date for home isolation. She also self-medicated with rivaroxaban tablets for the prevention of thrombotic events. She reported relief from symptoms on 23 September. Her follow-up PCR test conducted after 21 days was negative on 6 October. She reported that overconfidence, accompanied by carelessness, was the primary reason for getting the infection from a contaminated surface, or direct or indirect interaction with a COVID-19 positive individual. She reported that taking precautions such as using masks, gloves, hand sanitization, and

maintaining a safe distance can reduce some risk of this infection. She was very enthusiastic about the COVID-19 vaccination because she thought it would minimize the risk of getting this disease.
