Letter to the editor on use of antibodies from convalescent sera in the treatment of moderate and severe Covid-19 infection

To the Editor,

Convalescent plasma (CP) is a form of passive immunization that is used for disease prevention by transferring specific antibodies from a recovered patient to another patient with the same infection. ¹ It has been studied in the treatment of several viral infections with major conflicting results, including the Ebola virus, SARS-CoV1, and MERS-CoV.^2,3,4 More recently, CP usage has been studied widely in the treatment of SARS-CoV2. Similar to previous studies in different outbreaks, the results have been inconsistent. In the recovery and CONCOR-1 trials, there was no difference in mortality nor clinical status at day 28 after CP infusion.^5,6 On the other hand, Joyner et al. and Libster et al. showed that early infusion of high-titer CP may help in preventing clinical deterioration in mild Covid-19 infection.^7,8

Early in the pandemic and due to limited available therapeutic options for Covid-19 infection in Lebanon, we elected to study the efficacy of high-titer CP in moderate Covid-19 infections. A prospective and retrospective cohort study was conducted at the American University of Beirut Medical Center (AUBMC) over 14 months. It included all patients above 18 years presenting to AUBMC for moderate to severe Covid-19 infection. We excluded pregnant women and patients with a predicted survival of less than 2 days. Patients who received CP treatment (cases) in addition to standard therapy were compared to those who received standard therapy alone. The medical records for patients in both groups were reviewed and data related to demographics, medical comorbidities, symptoms upon presentation, the severity of infection on admission, laboratory findings, and treatment received were extracted. The clinical progress and laboratory data were recorded before and after receiving CP. Data were entered into a database using SPSS 29.0 (SPSS Inc, Chicago, IL). Bivariable analysis was conducted to examine the association between demographic and clinical variables with various outcome measures. The chi-square test and the independent samples t-test were used for categorical and continuous variables, respectively. A p-value of less than .05 was considered significant.

We included 23 patients who received CP as cases and 46 patients as controls. The mean age in the cases group (63.4 ± 13.1 years) was more than that in the control group (60.5 ± 15.6). 52% of each group were males and 48% were females. The two groups had no significant difference in baseline demographics and medical comorbidities. Regarding the other Covid-19-related therapeutic options, corticosteroids were more prescribed among cases compared to controls (92% vs 54%). Other treatment options, including remdesivir and tocilizumab, were also more prescribed among cases, albeit with no statistically significant differences. Regarding outcomes, mortality at day 28 was significantly higher among cases (22% vs 4%; p-value = .024). In addition, more patients in the CP group required ICU admission (61% vs 9%), although all the cases who were admitted to ICU received CP after ICU admission. The mean time from Covid-19 infection to CP transfusion was 12.1 days in patients who were admitted to ICU compared with 7.4 days in those who did not require ICU admission (p-value = .015). Among patients who received CP treatment, there was a significant drop in mean CRP level after the infusion (100.7 mg/dl vs 51 mg/dl; p-value < .001). Table 1 summarizes the relevant parameters before and after CP transfusion.

Table 1.

Changes in lab parameters before and after convalescent plasma transfusion.

Variable	Mean before CS	Mean after CS	Difference in means
Temperature, degrees celsius	36.8	36.6	−0.2
CRP, mg/dl	100.7	51.3	−49.4*
AST, units/l	52.7	56.1	2.4
ALT, units/l	41.9	63.4	21.5
Procalcitonin, µg/l	2.3	2.4	0.1
WBC count, per mm3	10319	12183	1864
LDH, units/L	410.8	339.2	−71.6
Pro-BNP, pg/ml	433.0	2096.5	1663.5
D-dimer, ng/ml	2835.0	2322.0	−513.0

Abbreviations: CS = convalescent serum, AST = aspartate aminotransferase; ALT = alanine aminotransferase; WBC = white blood cell; LDH = lactate dehydrogenase; Pro-BNP = pro-brain natriuretic peptide.

*p = .001.

Our study did not show the clinical benefit of CP transfusion in patients with moderate to severe Covid-19 infection. These findings might be explained by the fact that the controls in our study had a milder illness and CP transfusion was done relatively late in the disease. Convalescent plasma therapy should be studied in a larger population early in the course of mild Covid-19 infection in order to determine its utility. However, such an evaluation in a clinical trial or a real world setting has already been complicated by the emergence of new viral variants, a fact that should be taken into consideration when designing future studies.