Suthar MS, Zimmerman MG, Kauffman RC, et al. Rapid generation of neutralizing antibody responses in COVID-19 patients. Cell Rep Med June 05, 2020. Full-text: https://doi.org/10.1016/j.xcrm.2020.100040
A robust humoral immune response occurs early during severe or moderate COVID-19 infections: in this cross-sectional study of 44 hospitalized COVID-19 patients, receptor-binding domain (RBD)-specific IgG responses became detectable in all patients 6 days after PCR confirmation. Neutralizing antibody titers were detectable in 40/44 cases, mostly within 20 days of symptom onset. Of note, RBD-specific IgG titers seemed to correlate with the neutralizing potency, indicating that RBD-specific IgG titers could be used as a surrogate of neutralization activity against SARS-CoV-2 infection.
Seydoux E, Homad LJ, MacCamy AJ, et al. Analysis of a SARS-CoV-2 infected individual reveals development of potent neutralizing antibodies to distinct epitopes with limited somatic mutation. Immunity June 05, 2020. Full-text: https://doi.org/10.1016/j.immuni.2020.06.001
Authors have isolated B cells specific for the SARS-CoV-2 envelope glycoprotein spike (S) from a COVID-19-infected subject. Main findings: The 45 S-specific monoclonal antibodies that could be generated had undergone minimal somatic mutation, with limited clonal expansion. Most anti-S antibodies that were generated in this patient during the first weeks of COVID-19 infection were non-neutralizing and target epitopes outside the RBD. Neutralizing antibodies targeting the interaction of the S protein with ACE2 were minimally mutated.
Gutierrez L, Beckford J, Alachkar H. Deciphering the TCR repertoire to solve the COVID-19 mystery. Trends Pharmacol Sci. June 03, 2020. Full-text: https://doi.org/10.1016/j.tips.2020.06.001
Outstanding article on unresolved questions. Why do some patients develop severe disease, while others do not; and what roles do genetic variabilities play in the individual immune response to this viral infection? Authors discuss the critical role T-cells play in the orchestration of the antiviral response underlying the pathogenesis of COVID-19. They highlight the scientific rationale for that analyzing TCR repertoire would reveal important findings that may explain the outcome disparity.
Subbarao K, Mahanty S. Respiratory Virus Infections: Understanding COVID-19. Immunity. 2020 May 20:S1074-7613(20)30212-0. PubMed: https://pubmed.gov/32497522 . Full-text: https://doi.org/10.1016/j.immuni.2020.05.004
Nice review about the immune response to respiratory viruses. What happens when the virus reaches the respiratory mucosa? What are the consequences of infection in the host?
Wang H, Zhang Y, Huang B, et al. Development of an inactivated vaccine candidate, BBIBP-CorV, with potent protection against SARS-CoV-2. Cell 2020, June 06. Full-text: https://doi.org/10.1016/j.cell.2020.06.008
Will this be the first vaccine? Compared with the adenovirus-vectored and the DNA vaccine, inactivated vaccine development and production is a conventional and mature technology (main pro: large amounts of vaccine doses can be easily manufactured, main con: safety issues, including an antibody-dependent worsening of the infection). BBIBP-CorV, an inactivated SARS-CoV-2 vaccine, induced high levels of neutralizing antibody in several animal models, including 8 rhesus macaques, protecting them against SARS-CoV-2 infection. There was no observable antibody-dependent infection enhancement or immunopathological exacerbation. A Phase I clinical trial of BBIBP-CorV is currently in progress and a Phase II clinical trial has recently been initiated.
Xu X, Sun J, Nie S, et al. Seroprevalence of immunoglobulin M and G antibodies against SARS-CoV-2 in China. Nat Med. 2020 Jun 5. PubMed: https://pubmed.gov/32504052 . Full-text: https://doi.org/10.1038/s41591-020-0949-6
To estimate the cumulative prevalence, authors evaluated IgM and IgG antibodies in 17,368 individuals from Wuhan, China. The seropositivity in Wuhan was low, varying between 3.2% and 3.8% in different sub-cohorts. As seen in other studies, an early and a higher level of IgG response was observed, compared to IgM.
Ucciferri C, Auricchio A, Di Nicola M, et al. Canakinumab in a subgroup of patients with COVID-19. Lancet Rheumatology, June 4, 2020. https://doi.org/10.1016/S2665-9913(20)30167-3
Canakinumab is human monoclonal antibody against IL-1β, approved for the treatment of juvenile rheumatoid arthritis and other chronic autoinflammatory syndromes. In a pilot trial, 10 patients with hyperinflammation (defined as CRP ≥ 50 mg/L) and respiratory failure showed a rapid improvement in serum inflammatory biomarkers and an improvement in oxygenation.
Toubiana J, Poirault C, Corsia A, et al. Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study. BMJ. 2020 Jun 3;369:m2094. PubMed: https://pubmed.gov/32493739 . Full-text: https://doi.org/10.1136/bmj.m2094
Of 21 children and adolescents (3.7-16.6 years, 19 with recent SARS-CoV-2 infection) with features of Kawasaki disease who were admitted between 27 April and 11 May 2020, 12 (57%) presented with Kawasaki disease shock syndrome and 16 (76%) with myocarditis. 17 (81%) required intensive care support. All 21 patients had noticeable gastrointestinal symptoms and high levels of inflammatory markers. All 21 patients received intravenous immunoglobulin and 10 (48%) also received corticosteroids. The clinical outcome was favourable in all patients.
Sun SH, Chen Q, Gu HJ, et al. A Mouse Model of SARS-CoV-2 Infection and Pathogenesis. Cell Host Microbe. 2020 May 27:S1931-3128(20)30302-4. PubMed: https://pubmed.gov/32485164 . Full-text: https://doi.org/10.1016/j.chom.2020.05.020
Human ACE2 knockin mice were generated by using CRISPR-Cas9 technology. Bottom line: SARS-CoV-2 led to robust replication in the lung, trachea, and brain. SARS-CoV-2 caused interstitial pneumonia and elevated cytokines. A high dose of virus could establish infection via an intragastric route.
Davies NG, Kucharski ADJ, Eggo RM, et al. Effects of non-pharmaceutical interventions on COVID-19 cases, deaths, and demand for hospital services in the UK: a modelling study. Lancet, June 02, 2020. Full-text: https://doi.org/10.1016/S2468-2667(20)30133-X
Herd immunity? Forget it. Using a stochastic age-structured transmission model to explore a range of intervention scenarios, tracking 66 million people in England, Wales, Scotland, and Northern Ireland, the authors projected a median unmitigated burden of 23 million (95% prediction interval 13–30) clinical cases and 350,000 deaths (170,000–480, 000) due to COVID-19 in the UK by December, 2021. Bad news because extreme measures are probably required to bring the epidemic under control.
Hao S, Lian J, Lu Y, et al. Decreased B cells on admission was associated with prolonged viral RNA shedding from respiratory tract in Coronavirus Disease 2019: a case control study. J Infect Dis. 2020 May 31. PubMed: https://pubmed.gov/32474608 . Full-text: https://doi.org/10.1093/infdis/jiaa311
In 104 patients, a decrease in B cells was independently associated with prolonged viral RNA shedding. The viral RNA shedding from respiratory tract in patients with normal B cell count was significantly shorter than patients with decreased B cell on admission (median 11 vs 16 days). This is good news, because these observations may help to individualize monitoring of COVID-19 patients.
Shen B, Yi X, Sun Y, et al. Proteomic and Metabolomic Characterization of COVID-19 Patient Sera. Cell May 27, 2020. DOI: https://doi.org/10.1016/j.cell.2020.05.032. Full-text: https://www.sciencedirect.com/science/article/pii/S0092867420306279
Molecular insights into the pathogenesis of SARS-CoV-2 infection. Authors applied proteomic and metabolomic technologies to analyze the proteome and metabolome of sera from COVID-19 patients and several control groups. Pathway analyses and network enrichment analyses of the 93 differentially expressed proteins showed that 50 of these proteins belong to three major pathways, namely activation of the complement system, macrophage function and platelet degranulation. 80 significantly changed metabolites were found to be also involved in the three biological processes revealed in the proteomic analysis.
Park A, Iwasaki A. Type I and Type III Interferons – Induction, Signaling, Evasion, and Application to Combat COVID-19. Cell Host Microbe 2020, May 27. DOI:https://doi.org/10.1016/j.chom.2020.05.008. Full-text: https://www.sciencedirect.com/science/article/abs/pii/S1931312820302900
The interferon (IFN) response constitutes the major first line of defence against viruses. This complex host defence strategy can, with accurate understanding of its biology, be translated into safe and effective antiviral therapies. In their comprehensive review, the authors describe the recent progress in our understanding of both type I and type III IFN-mediated innate antiviral responses against human coronaviruses and discuss the potential use of IFNs as treatment strategy.
Randolph HE, Barreiro LB. Herd Immunity: Understanding COVID-19. Immunity Volume 52, ISSUE 5, P737-741, 2020. Full-text: https://doi.org/10.1016/j.immuni.2020.04.012
Overview on the basic concepts of herd immunity and its implications. There is no straightforward, ethical path to reach herd immunity, as the societal consequences of achieving it are devastating. Instead, an emphasis should be placed on policies that protect the most vulnerable groups in the hopes that herd immunity will eventually be achieved as a “byproduct” of such measures, although not the primary objective itself.
Gartshteyn Y, Askanase AD, Schmidt NM, et al. COVID-19 and systemic lupus erythematosus: a case series. Published: May 26, 2020. Full-text: https://doi.org/10.1016/S2665-9913(20)30161-2
Of 18 SLE patients with COVID-19, most recovered. Previous intake of immunosuppressants before admission to hospital did not seem to influence the severity of infection.
Remy KE, Brakenridge SC, Francois B, et al. Immunotherapies for COVID-19: lessons learned from sepsis. Lancet Respir Med. 2020 Apr 28. PubMed: https://pubmed.gov/32444269. Full-text: https://doi.org/10.1016/S2213-2600(20)30217-4
The hypothesis that quelling the cytokine storm with anti-inflammatory therapies directed at reducing interleukin-6 (IL-6), IL-1, or even tumour necrosis factor α (TNFα) might be beneficial has led to several ongoing trials. The authors are less enthusiastic and urge caution. Past attempts to block the cytokine storm associated with other microbial infections and with sepsis have not been successful and, in some cases, have worsened outcomes. Moreover, there is concern that suppressing the innate and adaptive immune system to address increased cytokine concentrations, could enable unfettered viral replication, suppress adaptive immunity, and delay recovery processes. There is growing recognition that potent immunosuppressive mechanisms are also prevalent in such patients. Giving immunosuppressive agents seems not to be a good idea.