Ling Li

Importance: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19), but further data from randomized clinical trials are needed. Objective: To evaluate the efficacy and adverse effects of convalescent plasma therapy for patients with COVID-19. Design, Setting, and Participants: Open-label, multicenter, randomized clinical trial performed in 7 medical centers in Wuhan, China, from February 14, 2020, to April 1, 2020, with final follow-up April 28, 2020. The trial included 103 participants with laboratory-confirmed COVID-19 that was severe (respiratory distress and/or hypoxemia) or life-threatening (shock, organ failure, or requiring mechanical ventilation). The trial was terminated early after 103 of a planned 200 patients were enrolled. Intervention: Convalescent plasma in addition to standard treatment (n = 52) vs standard treatment alone (control) (n = 51), stratified by disease severity. Main Outcomes and Measures: Primary outcome was time to clinical improvement within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale (ranging from 1 [discharge] to 6 [death]). Secondary outcomes included 28-day mortality, time to discharge, and the rate of viral polymerase chain reaction (PCR) results turned from positive at baseline to negative at up to 72 hours. Results: Of 103 patients who were randomized (median age, 70 years; 60 [58.3%] male), 101 (98.1%) completed the trial. Clinical improvement occurred within 28 days in 51.9% (27/52) of the convalescent plasma group vs 43.1% (22/51) in the control group (difference, 8.8% [95% CI, -10.4% to 28.0%]; hazard ratio [HR], 1.40 [95% CI, 0.79-2.49]; P = .26). Among those with severe disease, the primary outcome occurred in 91.3% (21/23) of the convalescent plasma group vs 68.2% (15/22) of the control group (HR, 2.15 [95% CI, 1.07-4.32]; P = .03); among those with life-threatening disease the primary outcome occurred in 20.7% (6/29) of the convalescent plasma group vs 24.1% (7/29) of the control group (HR, 0.88 [95% CI, 0.30-2.63]; P = .83) (P for interaction = .17). There was no significant difference in 28-day mortality (15.7% vs 24.0%; OR, 0.59 [95% CI, 0.22-1.59]; P = .30) or time from randomization to discharge (51.0% vs 36.0% discharged by day 28; HR, 1.61 [95% CI, 0.88-2.95]; P = .12). Convalescent plasma treatment was associated with a negative conversion rate of viral PCR at 72 hours in 87.2% of the convalescent plasma group vs 37.5% of the control group (OR, 11.39 [95% CI, 3.91-33.18]; P < .001). Two patients in the convalescent plasma group experienced adverse events within hours after transfusion that improved with supportive care. Conclusion and Relevance: Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days. Interpretation is limited by early termination of the trial, which may have been underpowered to detect a clinically important difference. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000029757.

An epidemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread unexpectedly in Wuhan, Hubei Province, China, since December 2019. There are few reports about asymptomatic contacts of infected patients identified as positive for SARS-CoV-2 through screening. We studied the epidemiological and clinical outcomes in 55 asymptomatic carriers who were laboratory confirmed to be positive for SARS-CoV-2 through nucleic acid testing of pharyngeal swab samples. The asymptomatic carriers seldom occurred among young people (aged 18-29 years) who had close contact with infected family members. In the majority of patients, the outcome was mild or ordinary 2019 novel coronavirus disease during hospitalization.

The effect of different high pressure homogenization energy input parameters on mean diameter droplet size (MDS) and droplets with > 5 μm of lipid injectable emulsions were evaluated. All emulsions were prepared at different water bath temperatures or at different rotation speeds and rotor-stator system times, and using different homogenization pressures and numbers of high-pressure system recirculations. The MDS and polydispersity index (PI) value of the emulsions were determined using the dynamic light scattering (DLS) method, and large-diameter tail assessments were performed using the light-obscuration/single particle optical sensing (LO/SPOS) method. Using 1000 bar homogenization pressure and seven recirculations, the energy input parameters related to the rotor-stator system will not have an effect on the final particle size results. When rotor-stator system energy input parameters are fixed, homogenization pressure and recirculation will affect mean particle size and large diameter droplet. Particle size will decrease with increasing homogenization pressure from 400 bar to 1300 bar when homogenization recirculation is fixed; when the homogenization pressure is fixed at 1000 bar, the particle size of both MDS and percent of fat droplets exceeding 5 μm (PFAT5) will decrease with increasing homogenization recirculations, MDS dropped to 173 nm after five cycles and maintained this level, volume-weighted PFAT5 will drop to 0.038% after three cycles, so the “plateau” of MDS will come up later than that of PFAT5, and the optimal particle size is produced when both of them remained at plateau. Excess homogenization recirculation such as nine times under the 1000 bar may lead to PFAT5 increase to 0.060% rather than a decrease; therefore, the high-pressure homogenization procedure is the key factor affecting the particle size distribution of emulsions. Varying storage conditions (4–25°C) also influenced particle size, especially the PFAT5.

BACKGROUND: The lack of effective treatments against the 2019 coronavirus disease (COVID-19) has led to the exploratory use of convalescent plasma for treating COVID-19. Case reports and case series have shown encouraging results. This study investigated SARS-CoV-2 antibodies and epidemiological characteristics in convalescent plasma donors, to identify criteria for donor selection. METHODS: Recovered COVID-19 patients, aged 18-55 years, who had experienced no symptoms for more than 2 weeks, were recruited. Donor characteristics such as disease presentations were collected and SARS-CoV-2 N-specific IgM, IgG, and S-RBD-specific IgG levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Whereas levels of N-specific IgM antibody declined after recovery, S-RBD-specific and N-specific IgG antibodies increased after 4 weeks from the onset of symptoms, with no significant correlation to age, sex, or ABO blood type. Donors with the disease presentation of fever exceeding 38.5°C or lasting longer than 3 days exhibited higher levels of S-RBD-specific IgG antibodies at the time of donation. Of the 49 convalescent plasma donors, 90% had an S-RBD-specific IgG titer of ≥1:160 and 78% had a titer of ≥1:640 at the time of plasma donation. Of the 30 convalescent plasma donors, who had donated plasma later than 28 days after the onset of symptoms and had a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C, 100% had an S-RBD-specific IgG titer of ≥1:160 and 93% had a titer of ≥1:640. CONCLUSION: This study indicates that the S-RBD-specific IgG antibody reaches higher levels after 4 weeks from the onset of COVID-19 symptoms. We recommend the following selection criteria for optimal donation of COVID-19 convalescent plasma: 28 days after the onset of symptoms and with a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C. Selection based on these criteria can ensure a high likelihood of achieving sufficiently high S-RBD-specific IgG titers.

BACKGROUND: COVID-19 has caused a global pandemic and the death toll is increasing. However, there is no definitive information regarding the type of clinical specimens that is the best for SARS-CoV-2 detection, the antibody levels in patients with different duration of disease, and the relationship between antibody level and viral load. METHODS: Nasopharyngeal swabs, anal swabs, saliva, blood, and urine specimens were collected from patients with a course of disease ranging from 7 to 69 days. Viral load in different specimen types was measured using droplet digital PCR (ddPCR). Meanwhile, anti-nucleocapsid protein (anti-N) IgM and IgG antibodies and anti-spike protein receptor-binding domain (anti-S-RBD) IgG antibody in all serum samples were tested using ELISA. RESULTS: The positive detection rate in nasopharyngeal swab was the highest (54.05%), followed by anal swab (24.32%), and the positive detection rate in saliva, blood, and urine was 16.22%, 10.81%, and 5.41%, respectively. However, some patients with negative nasopharyngeal swabs had other specimens tested positive. There was no significant correlation between antibody level and days after symptoms onset or viral load. CONCLUSIONS: Other specimens could be positive in patients with negative nasopharyngeal swabs, suggesting that for patients in the recovery period, specimens other than nasopharyngeal swabs should also be tested to avoid false negative results, and anal swabs are recommended. The antibody level had no correlation with days after symptoms onset or the viral load of nasopharyngeal swabs, suggesting that the antibody level may also be affected by other factors.