Copy-editor: Rob Camp
Immunology
Paper of the Day
Tang J, Ravichandran S, Lee Y, et al. Antibody affinity maturation and plasma IgA associate with clinical outcome in hospitalized COVID-19 patients. Nat Commun 12, 1221 (February 22, 2021). Full-text: https://www.nature.com/articles/s41467-021-21463-2
A comprehensive longitudinal antibody analysis on 25 SARS-CoV-2 PCR-confirmed hospitalized COVID-19 patients. In more severe COVID-19 patients, even though they could generate high binding and neutralizing antibody titers, there was a block to antibody affinity maturation that may be linked to deficiency in CD4 cells, and especially T follicular helper cell subsets, which are required for entry into the germinal center. Sustained high levels of proinflammatory cytokines (IL-6 and IL-8), high serum IgA, and blunted affinity maturation against the pre-fusion spike protein were predictive of the worst outcome for hospitalized patients. An elevated inflammatory response may be augmented by low-affinity antibodies that are not efficient in controlling SARS-CoV-2 replication.
Epidemiology
Zimmerman FJ, Anderson NW. Association of the Timing of School Closings and Behavioral Changes With the Evolution of the Coronavirus Disease 2019 Pandemic in the US. JAMA Pediatr February 22, 2021. https://jamanetwork.com/journals/jamapediatrics/fullarticle/2776608
This cross-sectional study used US COVID-19 data (March to May 2020) and anonymized cell phone as well as internet data. The main findings: voluntary behavioral changes, such as reductions in time spent at work, had an association with COVID-19 incidence and mortality that was 3 times stronger than that of school closures. According to Nathaniel W. Anderson and Frederick J. Zimmerman, their findings suggest that less harmful ways of preventing SARS-CoV-2 transmission are available than mandatory school closures (note: this is based on data prior to the occurrence of more transmittable variants).
Gold JA, Gettings JR, Kimball A, et al. Clusters of SARS-CoV-2 Infection Among Elementary School Educators and Students in One School District — Georgia, December 2020–January 2021. MMWR Morb Mortal Wkly Rep. ePub: 22 February 2021. Full-text: http://dx.doi.org/10.15585/mmwr.mm7008e4
Vaccinate and test the teachers! This investigation in a Georgia school district from December 1, 2020 to January 22, 2021, identified nine clusters of COVID-19 cases involving 13 educators and 32 students at six elementary schools. Consistent with findings from international studies, the report found that initial infections among educators played a substantial role in in-school SARS-CoV-2 transmission and subsequent chains of infection to other educators, students, and households, highlighting the importance of preventing infections among educators in particular.
Virology
Bullock HA, Goldsmith CS, Zaki SR, Martines RB, Miller SE. Difficulties in differentiating coronaviruses from subcellular structures in human tissues by electron microscopy. Emerg Infect Dis, February 18, 2021 Apr [date cited]. https://wwwnc.cdc.gov/eid/article/27/4/20-4337_article
In attempts to attribute pathology directly to tissue damage caused by SARS-CoV-2, investigators have inaccurately reported subcellular structures, including coated vesicles, multivesicular bodies, and vesiculating rough endoplasmic reticulum, as coronavirus particles. Hannah A. Bullock from Atlanta and colleagues describe some morphologic features of coronavirus that distinguish it from subcellular structures.
Clinical
Dai CL, Kornilov SA, Roper RT, et al. Characteristics and Factors Associated with COVID-19 Infection, Hospitalization, and Mortality Across Race and Ethnicity. Clin Infect Dis. 2021 Feb 20:ciab154. PubMed: https://pubmed.gov/33608710. Full-text: https://doi.org/10.1093/cid/ciab154
This retrospective cohort study examining 629,953 patients tested for SARS-CoV-2 in a large US health system, Hispanics who tested positive at a higher rate required excess hospitalization and mechanical ventilation and had higher odds of in-hospital mortality despite younger age.
Long COVID-19
Klein H, Asseo K, Karni N, et al. Onset, duration and unresolved symptoms, including smell and taste changes, in mild COVID-19 infections. A cohort study in Israeli patients. Clin Microbiol Infect. 2021 Feb 16:S1198-743X(21)00083-5. PubMed: https://pubmed.gov/33607252. Full-text: https://doi.org/10.1016/j.cmi.2021.02.008
Of 103 patients with mild COVID-19, 46% had at least one unresolved symptom at six months, most commonly fatigue (22%), smell and taste changes (15% and 8%, respectively), and breathing difficulties (8%).
Logue JK, Franko NM, McCulloch D, et al. Sequelae in Adults at 6 Months After COVID-19 Infection. JAMA Netw Open, February 19, 2021;4(2):e210830. Full-text: https://doi.org/10.1001/jamanetworkopen.2021.0830
A longitudinal prospective cohort of adults with COVID-19 (11 asymptomatic, 150 outpatients with mild disease, 16 with severe illness) was compared with a concurrent cohort of healthy patients. Between 3 and 9 months after onset of illness, the most common persistent symptoms were fatigue (14%) and loss of sense of smell or taste (14%). Notably, 14 participants, including 9 non-hospitalized individuals, reported negative impacts on activity of daily living after infection. With > 60 million cases worldwide, even a small incidence of long-term debility could have enormous health and economic consequences.
Zhou M, Wong CK, Un KC, et al. Cardiovascular sequalae in uncomplicated COVID-19 survivors. PLoS One. 2021 Feb 11;16(2):e0246732. PubMed: https://pubmed.gov/33571321. Full-text: https://doi.org/10.1371/journal.pone.0246732
Cardiac abnormality is common (but mostly self-limiting) among COVID survivors with mild disease: a systematic cardiac screening was performed among 97 consecutive COVID-19 survivors (mean age 46 years, all with non-severe disease), including treadmill exercise test and cardiac magnetic resonance imaging (CMR). Median duration from discharge to screening was 11 days. Cardiac abnormalities were detected in 42.3% including sinus bradycardia (29.9%), newly detected T-wave abnormality (8.2%) and elevated troponin level (6.2%). For COVID-19 survivors with persistent elevation of troponin levels after discharge or newly detected T wave abnormalities, echocardiography and CMR did not reveal any evidence of infarct, myocarditis, or left ventricular systolic dysfunction.
Collateral damage
Ghafil C, Matsushima K, Henry R, et al. Trends in Trauma Admissions During the COVID-19 Pandemic in Los Angeles County, California. JAMA Netw Open. February 22, 2021;4(2):e211320. Full-text: https://doi.org/10.1001/jamanetworkopen.2021.1320
Less accidents (for a few weeks) but more gunshots? In this retrospective cohort study of 6777 trauma admissions in Los Angeles County from January 1 to June 7, 2020, overall volume transiently decreased but quickly returned to baseline. Mechanisms of injury were significantly different, with a steady increase in admissions for “penetrating” injuries (in other words: mainly gunshots).
Treatment
Hunt BJ, De Paula EV, McLintock C, Dumantepe M. Prophylactic anticoagulation for patients in hospital with covid-19. BMJ. 2021 Feb 19;372:n487. PubMed: https://pubmed.gov/33608304. Full-text: https://doi.org/10.1136/bmj.n487
The risk of hospital-associated venous thromboembolism for medical in-patients is greatest in the first 90 days post-discharge, and many units are using unlicensed extended thromboprophylaxis with LMWH or direct acting oral anticoagulants for patients discharged after COVID-19. Recent retrospective data showing low rates of hospital-associated venous thromboembolism post-discharge are reassuring, but according to this editorial, randomized trials formally evaluating the need for extended thromboprophylaxis are now required.