April 10, 2020

Some patients with COVID-19 are testing positive again after discharge, corticosteroids do not appear to benefit patients with SARS-CoV-2

By Denise Baez

NEW YORK -- April 10, 2020 -- In today’s DG Alert, we cover a case series of patients with coronavirus disease 2019 (COVID-19) who had positive reverse transcriptase-polymerase chain reaction (RT-PCR) results days after testing negative and being discharged from the hospital, and the lack of benefit of treating patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with corticosteroids.

A study of 25 patients with COVID-19 who were discharged after negative RT-PCR results showed that 14.5% of them had their RT-PCR results turn positive again 2 to 13 days after discharge, without aggravation of symptoms.

The findings, published in Clinical Infectious Diseases, suggest the need for additional measures to confirm illness resolution in patients with COVID-19.

Jing Yuan, MD, Shenzhen Third People’s Hospital, Shenzhen, China, and colleagues reported that from January 23, 2020, to February 21, 2020, a total of 172 patients with COVID-19 were discharged from their hospital. All patients met the following criteria of hospital discharge in China: (1) normal body temperature for more than 3 consecutive days; (2) significant reduction of respiratory symptoms (cough and expectoration disappeared, normal ranges for interleukin-6 and c-reactive protein, and oxygenation index ≥350); (3) substantial improvement in chest imaging; and (4) at least 2 consecutively negative results of RT-PCR testing separated by at least 24 hours. 

Due to the high risk of reinfection, all discharged patients were required another 14 days of self-quarantine at their home for further observation. The cloacal swab and nasopharyngeal swab samples were both collected from these discharged patients every 3 days for RT-PCR detection of COVID-19 in the same way as they were in hospital. Among the 172 patients, 25 had positive results again. 

The median age of the 25 patients was 28 years, including 6 children younger than 12 years. Most (17 patients) were female. These patients experienced an average of 7.32 ± 3.86 days from their last negative RT-PCR result to turning positive again. All patients were re-admitted to the hospital and within an average of 2.73 days of hospital stay, the RT-PCR results of virus mRNA detection were again negative in both nasopharyngeal swab and cloacal swab samples. Patients were still required to stay in the hospital for a prolonged observation.

Dr. Yuan and colleagues compared data between the 147 patients who were discharged and remained negative with the 25 patients who tested positive again and found no differences in laboratory parameters before leaving the hospital. However, correlation analysis indicated that there was a significant inverse correlation existed between serum D-Dimer level before discharging and the duration of treatment in these 25 patients (r = -0.637, P = 0.002) versus the rest 147 patients. Furthermore, lymphocyte concentrations before these 25 patients leaving the hospital were significantly positively correlated (r = 0.52, P = 0.008) with the time interval for virus reappearing.

“According to our study, it is probable that 2 negative RT-PCR tests 24 hours apart may not be sufficient for viral clearance evaluation,” the authors concluded. “Repeated viral RT-PCR testing separated by prolonged duration like 48 hours is essential to assure that virus has actually cleared and the discharged patients no longer transmitted the virus. On the other hand, we suggested that some immunological parameters such as D-dimer and absolute lymphocyte count, and even antibody test should be combined with RT-PCR negative test as additional measures to assure that infected patients have completely recovered and can be released from quarantine.”

In another study, published in The Medical Journal of Australia, clinicians found no evidence that corticosteroid treatment provided clinical benefit for patients with SARS-CoV-2 without acute respiratory distress syndrome (ARDS).

Lei Zha, MD, Xi’an Jiaotong-Liverpool University, Jiangsu, China, and colleagues analysed data from 31 patients with laboratory-confirmed SARS‐CoV‐2 treated at 2 hospitals in Wuhu, Anhui province (about 500 km from Wuhan) between January 24, 2020, and February 24, 2020. The median age of the patients was 39 years, 64% were male, and 68% had returned from Wuhan, where they were presumed to have contracted the virus.

Comorbid conditions were not frequent in this case series. Only 7 patients had hypertension, 2 had chronic hepatitis B virus (HBV) infection, 1 had diabetes, and 1 had coronary heart disease. Two patients had histories of smoking. On admission, most patients presented with fever, cough, and myalgia or fatigue. Five patients reported diarrhoea and only 4 reported dyspnoea. All patients in the study were classified as having mild disease and none developed ARDS. 

For 29 of the 31 patients, pneumonia was evident on chest CT imaging, including 20 with bilateral involvement. For 2 patients, no abnormalities were evident on chest CT at any point. 

All patients received lopinavir/ritonavir and interferon alfa by inhalation and 11 patients received methylprednisolone 40 mg (once or twice per day) within 24 hours of admission for a median 5 days. 

Patients who received corticosteroid treatment had a higher maximum temperature on admission than patients who did not and more frequently reported clinical symptoms on admission, including myalgia or fatigue and cough. Patients receiving corticosteroid treatment also had higher median c-reactive protein levels and lower median lymphocyte count than patients who did not.

Cox proportional hazards regression analysis indicated no association between corticosteroid treatment and virus clearance time (hazard ratio [HR] = 1.26; 95% confidence interval [CI], 0.58-2.74), hospital length of stay (HR = 0.77; 95% CI, 0.33-1.78), or duration of symptoms (HR = 0.86; 95% CI, 0.40-1.83). 

Interestingly, univariate analysis indicated that virus clearance was slower in 2 patients with chronic HBV (mean difference, 10.6 days).

“Corticosteroids are widely used when treating patients with COVID‐19, but we found no association between therapy and outcomes in patients without acute respiratory distress syndrome,” the authors concluded. “An existing HBV infection may delay SARS‐CoV‐2 clearance, and this association should be further investigated.”

SOURCE: Clinical Infectious Diseases and The Medical Journal of Australia
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