Background: The role of convalescent plasma (COPLA) for the treatment of severely ill Corona Virus Disease-2019 is under investigation. We compared the efficacy and safety of convalescent plasma with fresh frozen plasma (FFP) in severe COVID-19 patients. Methods and findings: This was an open-label, single-centre phase II RCT on 29 patients with severe COVID-19 from India. One group received COPLA with standard medical care (SMC) (n=14), and another group received FFP with SMC (n=15). A total of 29 patients were randomized in the two treatment groups. Eleven out of 14 (78.5%) patients remained free of ventilation at day seven in the intervention arm while the proportion was 14 out of 15 (93.3 %) in the control arm (p= 0.258). The median reductions in RR per min at 48-hours in COPLA-group and FFP group were -6.5 and -3 respectively [p=0.004] and at day seven were -14.5 and -10 respectively (p=0.008). The median improvements in percentage O2 saturation at 48-hours were 6.5 and 2 respectively [p=0.001] and at day seven were 10 and 7.5 respectively (p=0.026). In the COPLA-group, the median improvement in PaO2/FiO2 was significantly superior to FFP at 48-hours [41.94 and 231.15, p=0.009], and also at day-7 [5.55 and 77.01 p<0.001]. We did not find significant differences in hospitalization duration between the groups (0.08). Conclusion: COPLA therapy resulted in rapid improvement in respiratory parameters and shortened time to clinical recovery, although no significant reduction in mortality was observed in this pilot trial. We need larger trials to draw conclusive evidence on the use of Convalescent plasma in COVID-19.

Chromoblastomycosis (CBM) is a chronic, progressive, cutaneous and subcutaneous fungal infection following the traumatic implantation of certain dematiaceous fungi. The disease has worldwide prevalence with predominant cases reported from humid tropical and subtropical regions of America, Asia, and Africa. Diagnosis is often delayed or misdirected either due to poor degree of clinical suspicions or clinical simulation of dermatological conditions. The infection is not uncommon in India and several case reports from the sub-Himalayan belt and western and eastern coasts of India have been published; however, very few have reviewed the cases. We reviewed 169 cases published in English literature from India during 1957 through May 2016, including 2 recent cases from our institute. A tremendous increase in the number of reported cases was noticed since 2012, since which, more than 50% of the cases had been published. A majority of the patients (74.1%) were involved in various agricultural activities directly or indirectly. The mean age at presentation was 43.3 years ± 16.0, with male to female ratio of 4.2:1. The duration of disease at the time of presentation varied from 20 days to 35 years. Any history of trauma was recalled only in 33.8% of the studied cases. The lower extremity was the most common site afflicted, followed by the upper extremity. The culture was positive in 80.3% of the cases with Fonsecaea pedrosoi, isolated as the most common fungal pathogen, followed by Cladophialophora carrionii. Although all the commercially available antifungals were prescribed in these cases, itraconazole and terbinafine were the most commonly used, either alone or in combination with other drugs/physical methods, with variable degrees of outcome. Combinations of different treatment modalities (chemotherapy and physical methods) yielded a cure rate of 86.3%. CBM is refractory to treatment and no single antifungal agent or regimen has demonstrated satisfactory results. Increased awareness with early clinical suspicion of the disease and adequate therapy are necessary to improve the outcome. However, depending upon the causative agent, disease severity, and the choice of antifungals, variable outcomes can be observed.

Background Corona virus disease 2019 (COVID-19) which initially started as a cluster of pneumonia cases in the Wuhan city of China has now become a full-blown pandemic. Timely diagnosis of COVID-19 is the key in containing the pandemic and breaking the chain of transmission. In low-and middle-income countries availability of testing kits has become the major bottleneck in testing. Novel methods like pooling of samples are the need of the hour. Objective We undertook this study to evaluate a novel protocol of pooling of RNA samples/elutes in performance of PCR for SARS CoV-2 virus. Study design Extracted RNA samples were randomly placed in pools of 8 on a 96 well plate. Both individual RNA (ID) and pooled RNA RT-qPCR for the screening E gene were done in the same plate and the positivity for the E gene was seen. Results The present study demonstrated that pool testing with RNA samples can easily detect even up to a single positive sample with Ct value as high as 38. The present study also showed that the results of pool testing is not affected by number of positive samples in a pool. Conclusion Pooling of RNA samples can reduce the time and expense, and can help expand diagnostic capabilities, especially during constrained supply of reagents and PCR kits for the diagnosis of SARS-CoV-2 infection.

COVID -19 is an acute infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Human surfactant protein D (SP-D) is known to interact with spike protein of SARS-CoV, but its immune-surveillance against SARS-CoV-2 is not known.The study aimed to examine the potential of a recombinant fragment of human SP-D (rfhSP-D) as an inhibitor of replication and infection of SARS-CoV-2. The interaction of rfhSP-D with spike protein of SARS-CoV-2 and hACE-2 receptor was predicted via docking analysis.The inhibition of interaction between spike protein and ACE-2 by rfhSP-D was confirmed using direct and indirect ELISA. The effect of rfhSP-D on replication and infectivity of SARS-CoV-2 from clinical samples was studied by measuring the expression of RdRp gene of the virus using qPCR. In-silico interaction studies indicated that three amino acid residues in the RBD of spike of SARS-CoV-2 were commonly involved in interacting with rfhSP-D and ACE-2. Studies using clinical samples of SARS-CoV-2 positive cases (asymptomatic, n=7 and symptomatic, n=8 and negative controls n=15) demonstrated that treatment with 1.67 µM rfhSP-D inhibited viral replication by ~5.5 fold and was more efficient than Remdesivir (100 µM). Approximately, a 2-fold reduction in viral infectivity was also observed after treatment with 1.67 µM rfhSP-D. These results conclusively demonstrate that the calcium independent rfhSP-D mediated inhibition of binding between the receptor binding domain of the S1 subunit of the SARS-CoV-2 spike protein and human ACE-2, its host cell receptor, and a significant reduction in SARS-CoV-2 infection and replication invitro.

ImportanceNo proven treatment is available for severely ill COVID-19. Therapeutic use of COVID-19 convalescent plasma (COPLA) is under investigation.ObjectiveTo compare the efficacy of COPLA with standard medical therapy (SMT) alone in severe COVID-19 patients.Design, setting and participantsA multicentric, open-labelled, phase-III randomised controlled trial conducted at two treatment centres with COPLA collected at the third dedicated centre in North-India, the coordinating centre during trial from June 2020 to December 2020. The study population comprised 400 participants in the ratio of 1:1 in each treatment group.InterventionOne group received COPLA with SMT (n=200), and another group received SMT only (n=200).Main outcome measuresPrimary outcome was time to clinical improvement measured by a two-point reduction in the ordinal scale. Secondary outcomes included duration of O2 therapy, the proportion of patients on mechanical ventilation at day-7, mortality, SARS-CoV-2 antibody levels, cytokine levels and incidence of adverse events.ResultsThe median time to a two-point reduction in the ordinal scale in both groups was 9 days (IQR=7–13) (p=0.328). The median duration of O2 therapy was 8 days (IQR=6–12) in COPLA and 10 days (IQR=6–12) in SMT group (p=0.64). The PaO2/FiO2 ratio showed significant improvement at 7 days in COPLA group(p=0.036). There was no difference in mortality till 28 days in both groups (p=0.62). However, if COPLA was given within 3 days of hospital admission, a significant reduction in ordinal scale was observed (p=0.04). Neutralising antibody titres in COPLA group (80 (IQR 80–80)) were higher than SMT group (0 (IQR 0–80)) at 48 hours (p=0.001). COPLA therapy led to a significant reduction in TNF-α levels at 48 hours (p=0.048) and D-dimer at 7 days (p=0.02). Mild allergic reactions were observed in 3 (1.5%) patients in COPLA group.Conclusion and relevanceConvalescent plasma with adequate antibody titres should be transfused in COVID-19 patients along with SMT in the initial 3 days of hospitalisation for better clinical outcomes.Trial registration numberNCT04425915.

BackgroundWe report the findings of a large follow-up, community-based, cross-sectional serosurvey and correlate it with the coronavirus disease (COVID-19) test-positivity rate and the caseload observed between the peaks of the first and the second wave of the COVID-19 pandemic in Delhi, India. MethodologyIndividuals aged five and above were recruited from 274 wards of the state (population approximately 19.6 million) from January 11 to January 22, 2021. A total of 100 participants each were included from all wards for a net sample size of approximately 28,000. A multistage sampling technique was employed to select participants for the household serosurvey. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin (IgG) antibodies were detected by using the VITROS® (Ortho Clinical Diagnostics, Raritan, NJ, USA) assay (90% sensitivity, 100% specificity). ResultsAntibody positivity was observed in 14,298 (50.76%) of 28,169 samples. The age, sex, and district population-weighted seroprevalence of the SARS-CoV-2 IgG was 50.52% (95% confidence interval [CI] = 49.94-51.10), and after adjustment for assay characteristics, it was 56.13% (95% CI = 55.49-56.77). On adjusted analysis, participants aged ≥50 years, of female gender, housewives, having ever lived in containment zones, urban slum dwellers, and diabetes or hypertensive patients had significantly higher odds of SARS-CoV-2 antibody positivity.The peak infection rate and the test-positivity rate since October 2020 were initially observed in mid-November 2020, with a subsequent steep declining trend, followed by a period of persistently low case burden lasting until the first week of March 2021. This was followed by a steady increase followed by an exponential surge in infections from April 2021 onward culminating in the second wave of the pandemic. ConclusionsThe presence of infection-induced immunity from SARS-CoV-2 even in more than one in two people can be ineffective in protecting the population. Despite such high seroprevalence, population susceptibility to COVID-19 can be accentuated by variants of concern having the ability for rapid transmission and depletion of antibody levels with the threat of recurrent infections, signifying the need for mass vaccination.

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