|Ahead of print publication
Eight hospitalized patients with COVID-19
Purvesh Agrawal1, Nidhi Khandelwal2
1 Department of Medicine, INHS Patanjali, Karwar, Karnataka, India
2 Department of ENT, INHS Patanjali, Karwar, Karnataka, India
|Date of Submission||12-Apr-2020|
|Date of Decision||16-Apr-2020|
|Date of Acceptance||19-Jul-2020|
|Date of Web Publication||25-Aug-2020|
Department of Medicine, INHS Patanjali, Karwar - 581 308, Karnataka
Source of Support: None, Conflict of Interest: None
In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China and has spread globally, creating a pandemic. Information about the clinical characteristics of infected patients is limited. We hereby report the initial experience (clinical features and management) of COVID-19 cases in India. Among the first eight patients diagnosed with SARS-CoV-2 infection in Uttara Kannada district, clinical presentation was frequently a mild respiratory tract infection. Only one of eight patients required supplemental oxygen. Although we cannot draw any conclusions on the basis of these very few cases, available data indicate considerable variability among different countries in the proportion of severe cases of COVID-19 among those testing positive.
Keywords: Azithromycin, bacille Calmette-Guérin vaccination, hydroxychloroquine, reverse transcription polymerase chain reaction, severe acute respiratory syndrome coronavirus 2
| Introduction|| |
The novel coronavirus has affected nearly all continents. At the time of writing, novel coronavirus has brought life to near standstill in almost every part of the world. At the start of March 2020, India also started experiencing increase in the diagnosed cases. During these past weeks, eight patients have been admitted with a diagnosis of COVID-19, and another 200 patients have been assessed in the COVID assessment clinic at this secondary care naval hospital now designated as COVID hospital. Data were collected from March 25, 2020, to April 28, 2020.
| Protocol|| |
All suspect cases in Uttara Kannada district were tested with reverse transcription polymerase chain reaction (RT-PCR) at district hospital. While the district authorities were in the process of setting up of COVID facility, our hospital was tasked with the treatment of COVID-positive cases.
Routine investigations such as complete blood cell count, renal and liver function test, and measurement of C-reactive protein were performed. All patients received supportive therapy. When saturation as measured by pulse oximeter dropped below 90%, they received supplemental oxygen. Empirical broad-spectrum antibiotics were administered to patients clinically suspected of having community-acquired pneumonia. Hydroxychloroquine (HCQ) orally for 5–10 days was prescribed to all confirmed COVID-positive patients. Azithromycin was added based on normal QTc in baseline electrocardiogram (ECG). Corticosteroids were avoided, reflecting increased mortality with their use in severe influenza. Nasopharyngeal swabs were collected only 14 days after first positive sample for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as per the ICMR guidelines.
| Case Reports|| |
The main clinical characteristics of the eight COVID-positive patients at hospital admission are presented in [Table 1].
Patient 1 was a 42-year-old male who had a recent history of travel to Dubai. He had fever and flu-like symptoms. Initial metabolic workup was suggestive of mild lymphopenia and thrombocytopenia. There were no abnormalities on chest X-ray. Fever resolved within 3 days. The patient became asymptomatic on day 10. Alanine aminotransferase (ALT) levels returned to normal by day 12. His nasopharyngeal swabs were collected after day 14 according to the protocol. He was discharged on April 7 following two negative nasopharyngeal swabs for SARS-CoV-2 by RT-PCR.
Patient 2 was a 64-year-old man with recent travel history. He flew back from Dubai to Mumbai on March 17, 2020. Comorbidities included hypertension and diabetes type 2. He had mild cough, fatigue, myalgia, and fever for 4 days. He also complained of mild diarrhea. His daily ECGs were within normal limits. He was continued on antihypertensive medications and euglycemia achieved with subcutaneous insulin regimen. Chest X-ray was normal. After full recovery, he was discharged on April 7.
Patient 3 (patient 2's wife) was a 56-year-old female and was diagnosed with COVID-19 on March 28, 2020. She had high-grade fever and diarrhea from March 22. She then developed progressive breathlessness and cough over the next 2 days. HCQ was started with a loading dose. Oral azithromycin was added as part of protocol. Broad-spectrum antibiotics were started for a possible superinfection. High-flow supplemental oxygen was continued to achieve saturation >94%. PA view Chest radiograph showed bilateral peripheral ground glass opacities as shown in [Figure 1]. Facility to safely mobilize a COVID-positive patient for computed tomography (CT) scan was not feasible at our center. Hence, a CT scan was deferred. The patient showed clinical improvement over the next 5 days and was subsequently taken off supplemental oxygen. She was discharged following two negative nasopharyngeal swab tests for SARS-CoV-2 on April 12.
|Figure 1: Chest x ray PA view – Bilateral peripheral ground glass Opacities|
Click here to view
Patients 4 and 5 were admitted to hospital early after the onset of the symptoms. Patient 4 (patient 2 and 3's daughter), a 25-year-old female, was diagnosed with COVID-19 on March 28, 2020, at district hospital. She had sore throat and fever from March 24, with no abnormalities on the chest X-ray. Patient 5 (patients 2 and 3's daughter and patient 4's sister), a 22-year-old female, was diagnosed with COVID-19 on March 28, 2020. She had mild fever with sore throat and dry cough from March 27. She also complained of diarrhea. Her chest X-ray was normal. Both had spent the past week with patients 2 and 3. They improved clinically with routine treatment and were discharged on April 12.
Patients 6 and 7 were asymptomatic contacts of patient 1. Their throat swabs for SARS CoV-2 were collected on March 27 as a part of active surveillance and contact tracing measures after patient 1 was tested positive. After confirmation of COVID-19 diagnosis for both these patients, they were admitted to the hospital on March 31 for observation and possible management. Both the cases had mild disease, which resolved with symptomatic treatment. Both were discharged on April 15.
Patient 8 was a 25-year-old male who had recent history of travel to Delhi. He was tested for COVID on April 12, after his spouse who presented with complaints of cough and fever was found positive. He was diagnosed with COVID-19 on April 14, 2020. He had only mild diarrhea as a presenting complaint. There were no abnormalities on chest X-ray. He was discharged following two negative nasopharyngeal swab tests for SARS-CoV-2 on April 28.
The most common symptoms at illness onset were fever, cough, headache, myalgia or fatigue, and diarrhea. Only one patient developed shortness of breath. On admission, the blood counts of two of the eight (25%) patients showed leukopenia (white blood cell count < 4 × 109/L). Levels of ALT increased in only one patient (12.5%).
One patient with moderate-to-severe disease was given HCQ + azithromycin combination along with empirical IV antibiotics. None of the patients received systematic corticosteroid. At this point, all eight patients have been discharged and no patients had died. Fitness for discharge was based on clinical and radiological clearance with viral clearance in samples from the nasopharynx which were collected only 14 days after the first positive sample date of respective patients.
| Discussion|| |
Available data indicate considerable variability among different countries in the proportion of severe cases of COVID-19 among those testing positive. Likewise, clinical features of early cases of COVID-19 in Wuhan were not the same as those in other areas of China. This phenomenon was also apparent during the transmission of Middle East respiratory syndrome (MERS)-CoV. The global case mortality of MERS-CoV was about 40%, whereas the mortality from second-generation MERS-CoV was about 20%., At our hospital, most patients had mild symptoms, and only a one case had dyspnea. No patients needed admission to the intensive care unit. The laboratory test results showed that the patients also experienced mild illness.
Two studies have proposed that universal bacille Calmette-Guérin (BCG) vaccination policy is correlated with reduced mortality rates due to COVID-19., Both studies recommend further testing of the hypothesis that BCG vaccine probably offers protection against COVID-19, through randomized controlled trials to determine how fast a BCG induced protective immune response to COVID-19 develops. The protection offered by BCG vaccine to SARS-CoV-2 has been attributed to its nonspecific effects (NSEs). The range of NSEs include a reduction in the incidence of respiratory tract infections in children, antiviral effects, and reduced viremia in experimental animals. For several viruses such as respiratory syncytial virus, yellow fever, herpes simplex virus, and human papilloma virus, a favorablein vitro orin vivo effect has indeed been observed in various studies.
Chloroquine inhibits replication of several intracellular microorganisms including coronaviruses invitro. Chloroquine blocks viral infection by increasing endosomal pH and interfering with the glycosylation of cellular receptor of SARS-CoV. HCQ is very similar to chloroquine except an additional hydroxy moiety in one terminal. HCQ is less permeable to blood–retinal barrier due to addition of additional hydroxyl molecule. There is a lesser risk of retinal toxicity with HCQ compared to chloroquine as it allows faster clearance from retinal pigment cell. HCQ has been a proven disease-modifying anti-inflammatory agent which helps in decreasing production of proinflammatory markers and cytokines. Whether HCQ has a role to play in treatment of cytokine storm associated with severely sick patients of COVID-19 is a matter of further research.
Studies suggest a synergistic effect of the combination of HCQ and azithromycin. Azithromycin has been shown to be activein vitro against Zika and Ebola viruses,, and to prevent severe respiratory tract infections when administrated to patients suffering viral infection. This finding should be further explored to know whether a combination is more effective especially in severe cases.
| Conclusion|| |
Among the first eight patients diagnosed with SARS-CoV-2 infection in Uttara Kannada district, clinical presentation was frequently a mild respiratory tract infection. Whether BCG vaccination policy is correlated with reduced severity/mortality due to COVID-19 is a matter of further research. Considering the potentially favorable benefit–risk balance, HCQ + azithromycin combination could be useful in the current context of COVID-19 outbreak. On the basis of our data, we cannot draw any conclusions. However, we believe that these findings will contribute to better understanding of the disease.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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