5. Other therapies
The use of convalescent plasma therapy in patients with
COVID-19 is still being debated. Convalescent plasma is a mixture of
inorganic and organic compounds, water and proteins (including albumin,
immunoglobulins, complement, coagulation and antithrombotic factors)
(Rojas et al., 2020). This treatment was formerly evaluated in the
treatment of SARS (Cheng et al., 2005), MERS (Arabi et al., 2016) and
Ebola (Kraft et al., 2015), being associated with a reduction in
fatality rate. For COVID-19, stringent criteria need to be satisfied in
order to be a convalescent donor. Specifically, donors should have the
following characteristics: aged between 18 and 65 years; absence of
infectious symptomatology; a negative test for COVID-19 after 14 days of
recovery (which must be repeated 48 h later and at the moment of
donation) (Tiberghien et al., 2020). The main procedure to obtain plasma
is apheresis, which is based on a continuous centrifugation of blood
from donor. From a single apheresis 400–800 mL of plasma can be
obtained (Bloch et al., 2020). Nowadays, few clinical studies were
concluded and their results could provide new insights regarding to the
effectiveness and safety profile of plasma therapy in COVID-19 patients.
Li l et al. reported the results of an open-label, multicentre,
randomized clinical trial carried out in Wuhan, from February to April
2020. The trial enrolled 103 participants (median age: 70 years) with a
severe form of COVID-19, who were randomized to receive convalescent
plasma in addition to standard treatment (n=52) or the standard
treatment alone (n=51). The effects of both therapies were evaluated as
the time to clinical improvement within 28 days (primary outcome) and on
28-day mortality, time to discharge, and the rate of viral PCR results
turned from positive at baseline to negative at up to 72 hours
(secondary outcomes). According to the study’s results, the convalescent
plasma therapy was not associated with a statistically significant
improvement in time to clinical improvement within 28 days compared with
standard treatment alone. In addition, 2 patients in the convalescent
plasma group experienced adverse events within hours after transfusion.
Due to a decrease in the number of COVID-19 cases in late March, the
study was stopped earlier; this needs to be take in consideration when
the study’s results are interpreted (Li et al., 2020b). Simonovich VA et
al. carried out a randomized controlled trial in 334 hospitalized adult
patients with severe COVID-19 pneumonia, who were randomized to receive
convalescent plasma (n=228) or placebo (n=105) in addition to standard
treatment. Authors evaluated the effects of the therapy in terms of
changes in patient’s clinical status 30 days after the intervention.
Similarly to the previous study, no difference in terms of efficacy was
found between treatments groups at day 30. Regarding to the safety
profile, infusion-related adverse events were detected in 4.8% of
patients in the convalescent plasma group vs. 1.9% of patients in the
placebo group (odds ratio, 2.62; 95% CI, 0.57 to 12.04), even though no
significant differences were found in the overall incidence of adverse
events or serious adverse events (Simonovich et al., 2020). On the other
hand, few small trial or case series reported that the convalescent
plasma therapy might be beneficial in COVID-19 patients. For instance,
Duan K et al. reported that the administration of 200 mL of convalescent
plasma in 10 severe patients brought to a significant improvement in
clinical symptoms along with increase of oxyhemoglobin saturation within
3 days and no severe adverse effects were observed (Duan et al., 2020).
Zhang B et al. presented four critically ill patients with SARS-CoV-2
infection (including a 31-year-old pregnant woman) who received
convalescent plasma and recovered from SARS-CoV-2 infection eventually
and did not experience any serious adverse event (Zhang et al., 2020a).
Lastly, a further case series described the effects of the convalescent
plasma therapy in 5 critically ill patients with COVID-19 and ARDS, who
improved after receiving the therapy (Shen et al., 2020). Despite their
positive results, these studies’ findings (Duan et al., 2020; Shen et
al., 2020; Zhang et al., 2020a) should be interpreted with caution
considering the limited number of patients who were enrolled and the
studies’ designs that did not allow making any comparison. In
conclusion, based on the conflicting evidence currently available, the
use of convalescent plasma needs to be considered as investigational.
Regulatory agencies, such as the FDA, are releasing many documents in
order to guide healthcare providers and investigators in the appropriate
management of plasma therapy in the context of clinical trials (US Food
and Drug Administration, 2020b).
Many studies are currently investigating the effects of vitamin
D in COVID-19 patients (D’avolio et al., 2020). This interest derives
from the evidence suggesting the role of vitamin D in reducing the risk
of cold and acute respiratory infections (Zemb et al., 2020). Many
mechanisms seem to underline this effect, including the effects of
Vitamin D on cellular natural immunity and adaptive immunity through the
decrease in cytokine storm (this effect was observed on interferon γ,
tumor necrosis factor α and CD4+ T cell count (Ali, 2020). In addition,
vitamin D improves the production of antimicrobial peptides in the
respiratory epithelium, potentially reducing the risk of local infection
and it seems to interact with ACE2 (Mitchell, 2020). Pizzini A et al.
investigated the association between of Vitamin D status and COVID-19
presentation among 109 patients, using data from the CovILD registry.
They found that low Vitamin D levels were not associated with poor
clinical and radiological outcomes of COVID-19 (Pizzini et al., 2020). A
further study, which was based on data from the UK Biobank, aimed to
establish whether blood 25-hydroxyvitamin D concentration was associated
with COVID-19 risk or not. Data were available for 348,598 UK Biobank
participants, of which 449 had COVID-19 infection. Authors concluded
that no association was found in terms of potential association between
vitamin D concentrations and the risk of COVID-19 infection (Hastie et
al., 2020). Ultimately, current evidence on a potential correlation
between Vitamin D and COVID-19 is contradictory. Therefore, we should
wait for results from clinical trials, which are currently underway to
evaluate the effects of Vitamin D supplementation on mortality,
morbidity, prevention and treatment of COVID-19
(www.clinicaltrials.gov).
Currently, data on vitamins, mineral supplementation and nutraceuticals
are quite scarce, although some studies are investigating their effects
(Jovic et al., 2020).