As of March 24, 2020, novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for 379,661 infection cases with 16,428 deaths globally, and the number is still increasing rapidly. Herein, we present four critically ill patients with SARS-CoV-2 infection who received supportive care and convalescent plasma. Although all four patients (including a pregnant woman) recovered from SARS-CoV-2 infection eventually, randomized trials are needed to eliminate the effect of other treatments and investigate the safety and efficacy of convalescent plasma therapy
A recent retrospective review of 72,314 SARS-CoV-2-infected cases by the China CDC showed that 5% of cases were critical illness characterized by respiratory failure, septic shock, and/or multiple organ dysfunction or failure.Around 48% of patients infected with SARS-CoV-2 had comorbid conditions, commonly cardiovascular diseases and diabetes.Older adults with underlying diseases were more likely to have a higher Sequential Organ Failure Assessment score and higher risk of death. The treatment of SARS-CoV-2 infection faces compelling challenges. To date, no therapeutics have yet been proven effective for the treatment of the critical illness except for supportive care, including treatment with antiviral drugs, corticosteroids, immunoglobulins, and noninvasive or invasive mechanical ventilation. The most critically ill patients infected with SARS-CoV-2 have elevated levels of infection-related biomarkers and inflammatory cytokines, indicating potential bacterial coinfection caused by a dysregulated immune system. Antibacterial drugs are therefore given to these patients. Management of critical SARS-CoV-2 infection is not different from management of most viral pneumonia causing respiratory failure. The principal feature of patients with the critical illness is the development of ARDS. ECMO is recommended by World Health Organization interim guidelines to support eligible patients with ARDS, while the use of which is restricted to specialized centers globally and technology challenges.
In this study, two patients were treated with ECMO, but the efficacy was mixed. Apart from ARDS, other life-threatening conditions including septic shock and multiple organ dysfunction or failure may occur in a substantial proportion of patients with SARS-CoV-2-related critical illness, the management of which is according to current evidence-based guidelines.In China, if the current therapeutic strategies are not satisfactory for critically ill patients, physicians might turn to convalescent plasma transfusion based on the Pneumonitis Diagnosis and Treatment Program for SARS-CoV-2 infection (Trial Version 7). Convalescent plasma has been used as a last resort to improve the survival rate of patients with severe acute respiratory syndrome infection. Previous evidence has proven that convalescent plasma treatment can significantly reduce the relative risk of mortality of patients, which may be because antibodies from convalescent plasma might suppress viremia. The level of SARS-CoV-2 neutralizing antibodies in donor plasma could be important for the effectiveness of intervention. However, the level of neutralizing antibodies in donor plasma before transfusion cannot be determined. In this study, three patients were tested for either virus load or antibodies IgM and IgG. In the first case, SARS-CoV-2 virus load after convalescent plasma transfusion significantly dropped (from 55 × 105 to 3.9 × 104 to 180 copies/mL). Among the four patients, the time from transfusion to negative RT-PCR test results ranged from 3 to 22 days. The third and fourth cases produced anti-SARS-CoV-2 IgG approximately 14 days after convalescent plasma transfusion. Patients who survive critical illness might mount higher antibody responses, which can persist for longer periods compared with those with nonsevere disease. The antibody levels, however, are confounded by other treatments, such as antiviral drugs, steroids, and IV immunoglobulin. A recent animal model indicated that antibodies produced from SARS-CoV-2 infection could protect from subsequent exposures.
Our results indicate convalescent plasma might be a potential therapy for critically ill patients infected with SARS-CoV-2. We observed no serious adverse reactions associated with the transfusion of convalescent plasma. However, the relative contributions of supportive care, investigational therapies, and patient’s immune response on survival could not be determined. Whether convalescent plasma and/or supportive care provide any clinical benefit is unknown. The safety and efficacy of convalescent plasma transfusion in patients infected with SARS-CoV-2 should be studied within the context of a well-designed clinical trial.
Reference & Source information: https://journal.chestnet.org/
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