This is a retrospective study with two groups of patients that received CCP: Group A, formed by patients that received compassionate CCP, from January to May 2021, n = 94, and Group B formed by patients from a previous clinical study, from March to October 2020, n = 47. Most of the participants were male, with mean age above 60 years and with comorbidities, a population under higher risk of hospitalization and ICU admission [14]. Group B was different from group A in that group B had a higher percentage of patients in ICU on the day of transfusion and a higher WHO ordinal scale on Day 0, suggesting more severity. As showed in Table 1, all characteristics of the CCP intervention were different between the groups.
Inflammation has been a problem for the treatment of COVID-19, including the use of CCP[6]. Table 2 shows that the value of the hemoglobin was different between the groups on the days 0 and day 5. Despite the median being in the normal range, it is important to mention that the minimum value in the total group was 7.9 mg/dL on day 0 and 7.6 mg/dL on day 5, probably because the anemic hypoxia as was already described in COVID-19 infection[15]. The groups were different between the lymphocyte count, with a median of 805 cell/µL on day 0 and 1069 cell/µL on day 5. Lymphopenia is believed to represent a defective response to the virus, and it was already associated with mortality and ICU admission[7]. There was no difference between the groups A and B when comparing the NLR, nevertheless the median of both were above 11, a value predictive of ARDS[16]. Moreover, neutrophil to lymphocyte ratio can be a significant predictor of severe disease when collected on the day of admission[17], however our data were collected on the day of the transfusion. Thrombocytopenia can be detected in COVID-19 patients [18], however the median from day 0 and from day 5 were in normal range for both groups.
Despite there being no difference between the groups on day 0 and day 5, the median of the C-RP ( 95.1 mg/L) on day 0 was approximately 19 times the normal range, a value lower than what was found in a study comparing WHO ordinal scale and risk categories, where the values were: 131 (75–220) mg/L for patients with 5 points and 141 (79–228)] mg/L for those with 6 points[12]. Notwithstanding, our findings about C-RP were superior to the threshold cut-off of C-RP ≥ 40 mg/L that was considered a predictor of mortality [19]. In the same way, the value of NMR ≥ 17.75 was a predictor of in-hospital mortality in seriously ill patients with COVID-19 with a sensitivity of 81.48%[20], and in our groups the mean was superior to this value on day 0.
The percentage of mean variation of the WHO ordinal scale was negative in group B, suggesting that these patients, who had a higher duration of symptoms (Table 1), showed a better clinical improvement. Despite these differences between the groups, patients in group B presented a higher mean of days in ICU and on mechanical ventilation. However, although CCP was well tolerated, it did not show any influence on the outcomes, even in different volumes, titles of nAbs and time from hospitalization to transfusion. This agrees with a study that found that convalescent plasma did not reduce the risk of intubation or death at 30 days in hospitalized patients with COVID-19[21]. Also, a recent review by Cochrane found that CCP did not reduce all-cause mortality at up to day 28, had little to no impact on need for invasive mechanical ventilation or death, and had no impact on whether participants are discharged from hospital [22].
As showed in Tables 5, 6 and 7, dialysis was a factor that influenced the number of days of hospitalization, ICU and mechanical ventilation. Damage to the renal system, the cause of kidney failure, can be caused by virus tropism and the incidence of acute kidney injury in COVID-19 patients could be as high as 25% [23], achieving 45% in ICU patients and affecting mortality[24, 25]. Acute renal injury was also associated with adverse outcomes in general ICU patients, such as increased length of stay as well as short-term and long-term mortality [26, 27]. Higher WHO ordinal scale on day 0 showed a negative impact in the number of days of hospitalization, ICU discharge and reduced the risk of mechanical ventilation discontinuation. This information, as far as we can determine, is new in the literature.
Our study contributes with more knowledge about COVID-19. As with other authors, we agree that the CCP has a similar safety profile as standard plasma and could be implemented at the onset of future infectious disease outbreaks[5]. Moreover, our patients had high levels of C-RP, reflecting an inflammatory state that could impair the response to treatments [6]. Corticosteroids, that were used for the majority of patients, could interfere with antibody function and also affecting the results of CCP [5].
To conclude, we have to mention the possible bias. This is a retrospective study, with a limited number of patients and without a control group. All patients were under clinical support and had received other types of treatment, such as heparin, antiviral agents or antibiotics during hospitalization.