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Convalescent plasma (CP) with neutralizing antibodies (IgG and IgM) has a long history of treating severe viral illnesses, having been used recently for SARS, MERS, and the 2009 H1N1 pandemic. In these infections, CP showed statistically significant reductions in mortality over placebo and the safety profile was excellent. This sets the scene and provides the rationale for the prevention and treatment of SARS-CoV2 infections with CP. However, the jury remains out on the overall effectiveness of CP in COVID-19. There are several good cases series in the literature that describe significant clinical, biochemical and radiological improvements in patients with severe COVID-19 following CP transfusions, together with rapid reductions in viral loads. For example, see the papers by Duan et al. 2020 (PNAS 2020 117(17): 9490–9496) and Shen et al. (JAMA 2020 323(16):1582:1589). However, case reports have limitations. For example, without a control group, it is impossible to know whether these patients would have improved anyway. In addition, these patients received various concomitant anti-viral and immunomodulatory therapies, so the specific contribution of CP to the outcomes is unknown. Thus, we await the results of the many RCTs currently running with CP – with and without other therapies. There are RCTs in different severity levels of the COVID-19 illness, in healthcare workers as prophylaxis, and in paediatrics.
This question is now answered with second small ‘waves’ of COVID-19 infections in many countries as social distancing restrictions are lifted, notably Germany and South Korea. Reproduction rates are > 1, indicating the number of infections is growing again. The size of second waves in various areas will be dependent on many factors, but a worrying lack of ‘herd immunity’ means that most people are still susceptible to the infection. More than 99% of patients post COVID-19 have antibodies against SARS-CoV2, so they should be spared from a second wave. However, there are still questions regarding the quality of this immunity and for how long it lasts, although significant cases of re-infection are very rare. The pathway to long-term global control COVID-19 is difficult, even if second waves are avoided in some countries. Thus, the intense efforts to make vaccines against SARS-CoV2 which would eradicate COVID-19 by artificially generating herd immunity.