By Christian Hoffmann &
Bernd S. Kamps
Chu H, Chan JF, Wang Y, et al. Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the pathogenesis of COVID-19. Clin Infect Dis. 2020 Apr 9. pii: 5818134. PubMed: https://pubmed.gov/32270184 . Full-text: https://doi.org/10.1093/cid/ciaa410
Cell experiments on replication capacity and immune activation profile of SARS-CoV-2 and SARS-CoV infection in human lung tissues. Both viruses were similar in cell tropism, with both targeting types I and II pneumocytes, and alveolar macrophages. SARS-CoV-2 generated 3.20 folds more infectious virus particles than SARS-CoV from the infected lung tissues.
Cao X. COVID-19: immunopathology and its implications for therapy. Nat Rev Immunol. 2020 Apr 9. pii: 10.1038/s41577-020-0308-3. PubMed: https://pubmed.gov/32273594 . Full-text: https://doi.org/10.1038/s41577-020-0308-3
Some thoughts on the immunopathological changes in patients with COVID-19 and how this may provide potential targets for drug discovery and may be important for clinical management.
Wang Q, Zhang Y, Wu L, et al. Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2. Cell. 2020 Apr 7. pii: S0092-8674(20)30338-X. PubMed: https://pubmed.gov/32275855 . Full-text: https://doi.org/10.1016/j.cell.2020.03.045
Atomic details of the crystal structure of the C-terminal domain of SARS-CoV-2 spike protein in complex with human ACE2 are presented. hACE2-binding mode of SARS-CoV-2 seems to be similar to SARS-CoV, but some key residue substitutions slightly strengthen the interaction and lead to higher affinity for receptor binding. Antibody experiments indicated notable differences in antigenicity between SARS-CoV and SARS-CoV-2.
Guo ZD, Wang ZY, Zhang SF, et al. Aerosol and Surface Distribution of Severe Acute Respiratory Syndrome Coronavirus 2 in Hospital Wards, Wuhan, China, 2020. Emerg Infect Dis. 2020 Apr 10;26(7). PubMed: https://pubmed.gov/32275497 . Full-text: https://doi.org/10.3201/eid2607.200885
In hospitals, the virus is everywhere. SARS-CoV-2 was widely distributed in the air and on object surfaces in both the intensive care units and general wards, implying a potentially high infection risk for medical staff. Contamination was greater in ICU. Virus was found on floors, computer mice, trash cans, and sickbed handrails and was detected in air approximately 4 m from patients.
Rossman H, Keshet A, Shilo S, et al. A framework for identifying regional outbreak and spread of COVID-19 from one-minute population-wide surveys. Nat Med. 2020 Apr 9. pii: 10.1038/s41591-020-0857-9. PubMed: https://pubmed.gov/32273611 . Full-text: https://doi.org/10.1038/s41591-020-0857-9
Coronavirus infection spreads in clusters, and early identification of these clusters is critical for slowing down the spread of the virus. Short daily population-wide online surveys that assess the development of symptoms could serve as a strategic and valuable tool for identifying such clusters and informing epidemiologists, public-health officials and policymakers.
Guo WL, Jiang Q, Ye F, et al. Effect of throat washings on detection of 2019 novel coronavirus. Clin Infect Dis. 2020 Apr 9. pii: 5818370. PubMed: https://pubmed.gov/32271374 . Full-text: https://doi.org/10.1093/cid/ciaa416
Throat washing may be used for monitoring due to its noninvasive and reliability. Throat washing was harvested by asking patient to oscillate over posterior pharyngeal wall with 20 ml sterile normal saline. After 5-10 seconds, they had to spit out normal saline from their throat to a sterile container. In 24 paired throat washings and nasopharyngeal swabs specimens, positive testing rate of throat washing was much higher than that of swabs.
Xiao AT, Tong YX, Zhang S. False-negative of RT-PCR and prolonged nucleic acid conversion in COVID-19: Rather than recurrence. J Med Virol. 2020 Apr 9. PubMed: https://pubmed.gov/32270882 . Full-text: https://doi.org/10.1002/jmv.25855
Negative does not mean absolutely negative. Among 70 COVID-19 patients, 15 (21%) experienced a “turn positive” of SARS-CoV-2 PCR after two consecutive negative results (up to 45 days after symptom onset).
Mao L, Jin H, Wang M, et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020 Apr 10. pii: 2764549. PubMed: https://pubmed.gov/32275288 . Full-text: https://doi.org/10.1001/jamaneurol.2020.1127
This retrospective, observational case series found 78/214 patients (36%) with neurologic manifestations, ranging from fairly specific symptoms (loss of sense of smell or taste, myopathy, and stroke) to more nonspecific symptoms (headache, low consciousness, dizziness, or seizure). Whether these more nonspecific symptoms are manifestations of the disease itself remains to be seen.
Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr 9. PubMed: https://pubmed.gov/32271988 . Full-text: https://doi.org/10.1111/jth.14830
Among 81 severe COVID-19 patients, incidence of venous thromboembolism (VTE) was 25%. A significant increase of D-dimer was a good index for identifying high-risk groups of VTE.
Ferner RE, Aronson JK. Chloroquine and hydroxychloroquine in covid-19. BMJ. 2020 Apr 8;369:m1432. PubMed: https://pubmed.gov/32269046 . Full-text: https://doi.org/10.1136/bmj.m1432
In the year 1925, the BMJ cautiously endorsed Moellgaard’s gold treatment for tuberculosis, although it found his pharmacological reasoning “both interesting and instructive”. In 2020, BMJ is similarly cautious about hydroxyl/chloroquine treatment for SARS-CoV-2. In cell and animal studies, the effects on avian influenza, Epstein-Barr, chikungunya or Zika have been variable. Wide use of these drugs will expose patients to rare but potentially fatal harms, including serious cutaneous adverse reactions, fulminant hepatic failure, and ventricular arrhythmias (especially when prescribed with azithromycin).