Convalescent plasma

A refractory B cell Non-Hodgkin Lymphoma patient post CD19 CAR-T cell therapy with persistent SARS-CoV-2 infection was administered COVID-19 convalescent plasma. The transfusion was followed by viral clearance. Convalescent plasma was suggested to activate cellular immune responses and thus help to clear SARS-CoV-2 infection. Sample size: 1. 

The treatment was administered to a patient with persistent mild symptoms and viral RNA-positivity. It led to gradual viral clearance and symptom amelioration. There was a temporal viral load increase one week after hospital discharge, which has resolved without any clinical intervention. Sample size: 1. Dosage: 295 ml with a titre of more than 1:100. 

Convalescent plasma administration was associated with improvement in clinical status and markers of cytokine storm in severe COVID-19 patients. This improvement did not translate into reduction of mortality in the treated patients compared to standard of care-only control group, however. Sample size: 30 + 30 control. Dosage: A 500 ml infusion. Primary outcome: Improvement in cytokine storm indicators.

In B-cell depleted COVID-19 patients due to anti-CD20 therapy, convalescent plasma administration was safe and led to viral clearance, clinical and laboratory improvement, even when administered more than 72 hours after symptoms' onset. Sample size: 7. Dosage inforamtion: Anti-Spike IgG titres of 1:100 or higher.

The clinical improvement observed in the majority of the patients and development of detectable antibody responses after the last transfusion suggest that convalescent plasma might be considered as an early treatment option in immunosuppressed patients, with antibody levels after transfusion serving as a predictive marker for treatment success. Sample size: 14. Dosage: 1 (1 case) to 3 (11 cases) transfusions of 200 mL; PRNT50 of 40+.

The sera from COVID-19 convalescent individuals previously infected with SARS-CoV-2 B.1.351 variant were able to neutralize the viral infection by the same variant in vitro. The reduction of neutralizing capacity of these sera against strains that preceded B.1.351 was only 2.3-fold. On the contrary, the neutralization of the B.1.351 strain by sera of convalescent patients infected by the strains from the 1st infection wave declined significantly.

Convalescent plasma administration was associated with clinical improvement and negative SARS-CoV-2 conversion. The administration of convalescent plasma with higher neutralizing antibody titres displayed higher efficacy. None of the patients in the treatment group died, which indicated lower mortality. Sample size: 19 + 43 control. Dosage: 4–5 ml/kg infusion(s).

Patients with haematological malignancies who were administered convalescent plasma 48–72 hours after SARS-CoV-2 infection diagnosis had significantly higher odds of survival and milder course of the infection. Sample size: 23 + 22 control. Dosage: At least one infusion of 200–250 mL.

The sera from convalescent COVID-19 patients collected before D614G (SYSU-IHV), B.1.1.7, and 501Y.V2 strain emergence neutralized SARS-CoV-2 Spike-pseudotyped virus specific for all of the strains, but the neutralization capacity was significantly lower for the 501Y.V2 (“South Africa”) strain.

Combined with

The convalescent plasma from all randomly selected donors had neutralizing anti-nucleocapsid protein (SARS-CoV-2) titres meeting FDA criteria. Cell pre-treatment with convalescent plasma led to significant inhibition of pseudovirus uptake.

Significantly lower number (numerically 48% risk reduction) of older patients with mild COVID-19 who were treated with high-titre (anti-SARS-CoV-2 Spike antibody) convalescent plasma developed severe respiratory disease compared to placebo. Sample size: 80 + 80 placebo. Dosage: 250 mL with anti-Spike titres of more than 1:1000; administered less than 72 hours after symptom onset. Endpoint: Severe respiratory disease onset.

Convalescent plasma administration was safe. Despite the lack of statistical significance, the authors of the study consider numerical decrease in mortality in the treatment group, compared to the control, sufficient to warrant further research of the potential of convalescent plasma treatment in COVID-19 patients. Sample size: 40 + 124 matched control. Dosage: One or more (up to five) infusions of 300 mL. IgG levels had to be detectable. Endpoints: Safety and the length of ICU stay (primary).

The therapy was generaly safe and led to clinical improvement. Sample size: 4 severe + 3 critical severity. Dosage: Neutralizing antibody titres of 1:320 to 1:1,280.

Convalescent plasma administration led to clinical improvement in 4 of the 5 patients with protracted COVID-19, impaired humoral immunity, and lacking neutralising antibodies. Dose specification: SARS-CoV-2 neutralising antibody titre of 1:160. Endpoint: Clinical response (temperature of <38°C, Câ€Âreactive protein of <10 mg/l, and hospital discharge within 7 days).

A statistically significantly higher odds of recovery were observed in mild ARDS COVID-19 patients treated with convalescent plasma compared to control. Numerical difference was observed in moderate ARDS patients, as well. No difference was observed in the case of severe ARDS. The sample size was small, however. Sample size: 32 + 32 control. Dosage: An infusion of 600 ml of fresh ABO-identical and RhD-compatible convalescent plasma. Primary outcome: 28-day mortality.

In combination with remdesivir treatment, which was initiated earlier but did not lead to clinical improvement. After the third convalescent plasma infusion, clinical improvement (e. g. in hypoxia and inflammation) was observed in a living donor liver transplant patient who contracted severe COVID-19 during the third postoperative week. Dosage: 200 mL, 230 mL, and 200 mL on days 4,5, and 6 after fever onset, respectively. IgG titres of more than 1:1000.

Significantly higher rate of and shorter time to clinical improvement in moderate and severe COVID-19 patients. Improvement in oxygenation, lymphocyte counts, and CRP levels was detected, as well. Significantly reduced mortality was observed only in the moderate disease treatment group. Sample size: 135 + 233 control. Dosage: 79.3% of patients received 2 infusions of 200 mL 12 hours apart; 20.7% of patients received 1 infusion of 200-400 mL. Endpoint: Time to clinical improvement assessed on day 30 (primary).

Clinical improvement in a COVID-19 patient with severe hypogammaglobulinemia and absence of B cells (with Good syndrome) after administration of convalescent plasma (CP). The CP therapy was initiated on day 71 of symptomatic infection and no previous therapy provided any lasting significant clinical improvement. Dosage: 200 mL twice daily for two days (2 units with titer 1/160 and 2 with 1/40).

Administration of COVID-19 convalescent plasma (together with hemoperfusion sessions and tocilizumab administration) might have contributed to clinical improvement of a 42-year old patient with type 2 diabetes diagnosed with critical COVID-19 pneumonia. Dosage: 2 infusions of 500 mL each.

Preceded by therapeutic plasma exchange. Clinical improvement in symptoms and inflammation markers. Invasive mechanical ventilation could be discontinued in majority of the cases. 28-day mortality was 28.6%. Sample size: 14. Dosage: 500 mL.

Timely administration of convalescent plasma with high titres (≥1:1350) of antibodies targeting RBD of the SARS-CoV-2 spike protein significantly reduced adjusted 28-day mortality and unadjusted 60-day mortality. Sample size: 341 + 594 matched control. Dosage: Mostly single 300 mL transfusion with anti-RBD IgG titer mostly of ≥1:1350.

Improvement in clinical parameters (including oxygenation) in majority of the patients. Sample size: 17. Dosage: 1 unit of 200 mL; 2 units ca. 8 days apart in 3 patients. Antibody titres ranging from 1:400 to 1:6,400.

Early administration of convalescent plasma seems to reduce ventilatory requirements in severe to critical COVID-19 patients. Sample size: 31. Dosage: 250–300 mL.

Lead to reconvalescence, after a failed remdesivir treatment, of a patient infected by a SARS-CoV-2 strain with D484Y substitution in the RNA-dependent RNA polymerase with a a post-rituximab B-cell immunodeficiency and persistent SARS-CoV-2 viremia. Dosage: 4 times 200 mL within 4 days.

Clinical improvement in 2 patients with recurrent gastrointestinal COVID-19-related symptoms. Sample size: 2. Dosage: 200-400 mL.

Treatment resulted in decrease in body temperature, inflammation and the SARS-CoV-2 RNA levels.

Significantly reduced increase in supplemental oxygen requirement and increased rate of survival (for a 1:4 matched control; numerical for a 1:2 matched control). No severe transfusion-related adverse effect were noted. The receivers of convalescent plasma group were more frequently treated with anticoagulants than those in the control group. Sample size: 39 + 78 (1:2 matched control) + 156 (1:4 matched control). Dosage: 2 units of 250 ml (usually from the same donor); anti-spike IgG titers of ≥1:320 on the MSH-ELISA.

Some solid organ transplant patients infected with SARS-CoV-2 may benefit from convalescent plasma treatment, especially in the case of early administration. Further verification is needed, however. Sample size: 13. Dosage: Two units of 500 mL total.

A 9-week-old female with trisomy 21 and a heart defect, non-responsive to remdesivir treatment, manifested clinical improvement after convalescent plasma transfusions. Dosage: 2 aliquots of CP (10 mL/kg per aliquot).

Patients may benefit from treament with convalescent plasma with higher anti-S1 (SARS-CoV-2) levels. Sample size: 49. Dosage: 200 ml (additional 200 ml after 24 hrs if well-tolerated). Endpoint: Clinical improvement at day 14 (alive, not mechanically ventilated, recovered or mild to moderate COVID-19).

Critically ill paediatric patients may benefit from convalescent plasma infusion. The treatment was not associated with elimination of endogenous antibody response or antibody-dependent enhancement. Donor plasma with higher antibody titres provided a more pronounced clinical improvement. Sample size: 4. Dosage: 2-4 mL/kg.

In patients with prolonged positivity for the SARS-CoV-2 RNA, the convalescent plasma treatment may help eliminate virus and shorten the length of hospital stay. Sample size: 27. Dosage: 400 ml median total volume.

Combined with UC-MSCs, a possible synergy in inducing clinical and laboratory improvement was observed. Sample size: 1. Dosage: 400 ml total in two infusions, one day apart; anti-SARS-CoV-2 titer of >1:160. 

reduced duration of infection and death rate

early indicators suggest that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19

hyperimmune plasma (neutralizing antibodies titer ≥1:160)

non-intubated patients may benefit more than those requiring mechanical ventilation

convalescent plasma obtained from donors with confirmed SARS-CoV-2 infection and had been symptom free for 14 days

Plasma from individuals previously infected with a non-omicron strain had a substantially reduced or no capacity to neutralize the omicron variant of SARS-CoV-2 in vitro. 

Omicron variant was significantly less sensible to neutralization by antibodies present in plasma of convalescent individuals. 

In the case of majority of convalescent patients, the sera were not capable to neutralize SARS-CoV-2 Omicron Spike-pseudotyped virus in vitro. Slightly higher titres (still 37x lower compared to the Wuhan strain) were observed in the sera of convalescent patients who had been previously hospitalized due to COVID-19. 

The antibody titres in convalescent plasma were lower compared to the titres in the case of active critical infections; nevertheless, administration of convalescent plasma led to increase of the titres in the sera of critically ill ICU patients. The translation of this development into an improvement in clinical outcome was limited, however. Sample size: 8. Dosage: Three infusions of 200–280 ml, two days apart. Primary outcome: Humoral immune response.

B.1.351 (South Africa) variant of SARS-CoV-2 is 9.4-fold more resistant to neutralization by convalescent plasma compared to the wild type. 

No significant difference in the clinical outcomes between the treatment and the placebo group. Sample size: 228 + 105 placebo. Dosage: 500 mL (median) with median anti-SARS-CoV-2 antibody titre of 1:3200. Endpoints: Clinical status on an ordinal scale 30 days after the intervention (primary); clinical status on the ordinal scale at days 7 and 14,  the time to hospital discharge, the time to ICU discharge, the time to improvement in at least two categories on the ordinal scale, the time to death, and the time to recovery (secondary).

The use of convalescent plasma was not associated with reduction of primary outcome in moderate COVID-19 patients. Improvement was observed in some of the secondary outcomes (shortness of breath, fatigue, negative SARS-CoV-2 RNA conversion) at day 7. Sample size: 235 + 229 control. Dosage: Two doses of 200 mL 24 hours apart. Endpoint: Progression to severe disease or death within 28 days post-enrolment (primary).

Convalescent plasma administration in critically ill COVID-19 patients did not lead to a statistically significant improvement of respiratory status within 28 days, all-cause mortality at day 28 or viral clearance. Sample size: 40 + 40 control. Dosage: 400 mL AB0 compatible.
 

Late administration of convalescent plasma in critically ill COVID-19 patients has only limited benefits. Improvement in some clinical parameters was observed but overal outcome (mortality) was poor. Sample size: 5. Dosage: 400 mL (3 patients), 1,200 mL (2 patients) (Ab titer >1:640).

no difference in mortality, hospital stay or day-15 disease severity in comparison to standard of care