This descriptive study was conducted on six cases to explore the efficacy of convalescent plasma therapy for treating COVID-19. According to previous experience with convalescent plasma treatment in SARS and severe influenza[15, 16], the production of endogenous IgM and IgG antibodies peaks at two and four weeks, respectively, after infection. In theory, it should be more effective to use convalescent plasma as soon as possible in the early stage of the disease. However, our study differs from previous convalescent plasma studies on SARS and influenza cases in that we used convalescent plasma during the late stage of disease. The long interval from disease onset to plasma treatment in our study was dictated by the type of patients admitted to Guizhou Jianjunshan Hospital; as a tertiary hospital, the admitted patients have been treated elsewhere before being transferred.
Notably, other treatments may affect the relationship between convalescent plasma and antibody levels, such as antiviral drugs and steroids. Fortunately, we found that in all six cases, convalescent plasma was still clinically beneficial. Patient 1 was in critical condition before receiving the convalescent plasma treatment. While waiting for the convalescent plasma for this patient, we continued to treat her with antiviral drugs and steroids, which clearly stabilized the disease condition, so these treatments likely also contributed to her recovery. There has been much debate about the use of steroids, and it has not been used as a routine treatment from the beginning. Evidence from SARS shows that corticosteroid treatment cannot reduce mortality and it can delay virus clearance. However, systemic corticosteroids may help treat COVID-19 by reducing the excessive lung damage caused by inflammation. The conditions of the six patients in our study had all rapidly deteriorated to ARDS, so they were given intravenous methylprednisolone before convalescent plasma therapy. After patient 1 was given steroid therapy, but before she was given the convalescent plasma, her PaO2/FiO2 underwent a rapid improvement (from 128 to 247), although it did not return to a normal level. After the convalescent plasma treatment, her PaO2/FiO2 further increased to 335. After they were treated with convalescent plasma, the PaO2/FiO2 and lymphocyte count of patients 1, 2, and 3 were close to normal. Additionally, the levels of inflammation markers CRP and IL-6 for these patients decreased significantly, and chest imaging examinations revealed that their lung lesions gradually subsided. The autopsy reports for COVID-19 fatalities are very similar to those for SARS-CoV and MERS-CoV fatalities; they describe diffuse alveolar injury, exudate, and inflammation. ARDS in these patients is partially caused by the cytokine storm and the host immune response. Therefore, the anti-SARS-CoV-2 IgM and IgG in the convalescent plasma treatment not only can directly neutralize the virus, but these anti-inflammatory components can also accelerate the clearance of infected cells to prevent cytokine storms.
It is not surprising that for the patients with recurrence of COVID-19, the minimum time for viral clearance (as assessed by two consecutive negative throat swab tests for SARS-CoV-2 nucleic acid) after the treatment with convalescent plasma is 2 days, and the maximum time is 24 days. However, patient 5 has had consistently positive laryngeal swab test results since receiving convalescent plasma on April 5, 2020 up through the time of writing, May 20, 2020. One possible reason is that the patient’s basic condition and immune system have been poor because this patient suffers from high blood pressure, hyperlipidemia, and type 2 diabetes, and the patient has undergone various operations (e.g., cholecystectomy, hysterectomy, and tonsillectomy). Before infusion of convalescent plasma during the recovery period, his IgM and IgG levels were abnormally low (0.8 g/L and 5.56 g/L, respectively), and his CD4+/CD8+ ratio was 4.34. Another possibility is that the anti-SARS-CoV-2 IgM and IgG in the convalescent plasma treatment were insufficient to neutralize the virus in this patient’s body. Notably, this patient received only one round of convalescent plasma therapy, after which he was treated with antiviral drugs and steroids. We speculate that if another round of convalescent plasma transfusion is given to this patient, the effect of this intervention could be enhanced, speeding up the time until negative results are obtained for laryngeal swab tests of SARS-CoV-2 nucleic acid. Furthermore, a recent report found that antibodies in convalescent plasma administered during the recovery period can help maintain a higher antibody titer and increase the host immune response until the virus infection has cleared.
This study was limited by its small sample size. However, our study population was typical of patients in Guizhou Province, and it included both patients who were treated with plasma therapy during their first SARS-CoV-2 infection and COVID-19 patients who relapsed. Importantly, the treatment of COVID-19 patients with convalescent plasma did not cause any serious adverse effects.