Coronavirus disease 2019 (COVID-19) is known to cause multi-organ dysfunction 1 – 3 during acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some patients experiencing prolonged symptoms, termed post-acute sequelae of SARS-CoV-2 (refs. 4 , 5 ). However, the burden of infection outside the respiratory tract and time to viral clearance are not well characterized, particularly in the brain 3 , 6 – 14 . Here we carried out complete autopsies on 44 patients who died with COVID-19, with extensive sampling of the central nervous system in 11 of these patients, to map and quantify the distribution, replication and cell-type specificity of SARS-CoV-2 across the human body, including the brain, from acute infection to more than seven months following symptom onset. We show that SARS-CoV-2 is widely distributed, predominantly among patients who died with severe COVID-19, and that virus replication is present in multiple respiratory and non-respiratory tissues, including the brain, early in infection. Further, we detected persistent SARS-CoV-2 RNA in multiple anatomic sites, including throughout the brain, as late as 230 days following symptom onset in one case. Despite extensive distribution of SARS-CoV-2 RNA throughout the body, we observed little evidence of inflammation or direct viral cytopathology outside the respiratory tract. Our data indicate that in some patients SARS-CoV-2 can cause systemic infection and persist in the body for months.

Background: Effective therapeutics to treat COVID-19 are urgently needed. Remdesivir is a nucleotide prodrug with in vitro and in vivo efficacy against coronaviruses. Here, we tested the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection. Methods:To evaluate the effect of remdesivir treatment on SARS-CoV-2 disease outcome, we used the recently established rhesus macaque model of SARS-CoV-2 infection that results in transient lower respiratory tract disease. Two groups of six rhesus macaques were infected with SARS-CoV-2 and treated with intravenous remdesivir or an equal volume of vehicle solution once daily. Clinical, virological and histological parameters were assessed regularly during the study and at necropsy to determine treatment efficacy. Results:In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs. Virus titers in bronchoalveolar lavages were significantly reduced as early as 12hrs after the first treatment was administered. At necropsy on day 7 after inoculation, lung viral loads of remdesivir-treated animals were significantly lower and there was a clear reduction in damage to the lung tissue. Conclusions: Therapeutic remdesivir treatment initiated early during infection has a clear clinical benefitin SARS-CoV-2-infected rhesus macaques. These data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to severe pneumonia.

medRxiv preprint Dear editor, 10The unprecedented pandemic of COVID-19 has created worldwide shortages of personal protective 11 equipment, in particular respiratory protection such as N95 respirators(1). SARS-CoV-2 transmission is 12 frequently occurring in hospital settings, with numerous reported cases of nosocomial transmission 13 highlighting the vulnerability of healthcare workers(2). The environmental stability of SARS-CoV-2 14 underscores the need for rapid and effective decontamination methods. In general, N95 respirators are 15 designed for single use prior to disposal. Extensive literature is available for decontamination procedures 16 for N95 respirators, using either bacterial spore inactivation tests, bacteria or respiratory viruses (e.g. 17 influenza A virus)(3-6). Effective inactivation methods for these pathogens and surrogates include UV, 18 ethylene oxide, vaporized hydrogen peroxide (VHP), gamma irradiation, ozone and dry heat(3-7). The 19 filtration efficiency and N95 respirator fit has typically been less well explored, but suggest that both 20 filtration efficiency and N95 respirator fit can be affected by the decontamination method used (7, 8). For 21 a complete list of references see supplemental information. 23Here, we analyzed four different decontamination methods -UV radiation (260 -285 nm), 70ºC dry heat, 24 70% ethanol and vaporized hydrogen peroxide (VHP) -for their ability to reduce contamination with 25 infectious SARS-CoV-2 and their effect on N95 respirator function. For each of the decontamination 26 methods, we compared the normal inactivation rate of SARS-CoV-2 on N95 filter fabric to that on 27 stainless steel, and we used quantitative fit testing to measure the filtration performance of the N95 28 respirators after each decontamination run and 2 hours of wear, for three consecutive decontamination 29 and wear sessions (see supplemental information). VHP and ethanol yielded extremely rapid inactivation 30 both on N95 and on stainless steel ( Figure 1A). UV inactivated SARS-CoV-2 rapidly from steel but more 31 slowly on N95 fabric, likely due its porous nature. Heat caused more rapid inactivation on N95 than on 32 steel; inactivation rates on N95 were comparable to UV. 33 34 for use under a CC0 license.Quantitative fit tests showed that the filtration performance of the N95 respirator was not markedly 35 reduced after a single decontamination for any of the four decontamination methods ( Figure 1B). 36Subsequent rounds of decontamination caused sharp drops in filtration performance of the ethanol-treated 37 masks, and to a slightly lesser degree, the heat-treated masks. The VHP and UV treated masks retained 38 comparable filtration performance to the control group after two rounds of decontamination, and 39 maintained acceptable performance after three rounds. 41Taken together, our findings show that VHP treatment exhibits the best combination of rapid inactivation 42 of SARS-CoV-2 and preservation of N95 respirator integrity, under the experimental conditions used here 43 (...

ChAdOx1 nCoV-19/AZD1222 is an approved adenovirus-based vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) currently being deployed globally. Previous studies in rhesus macaques revealed that intramuscular vaccination with ChAdOx1 nCoV-19/AZD1222 provided protection against pneumonia but did not reduce shedding of SARS-CoV-2 from the upper respiratory tract. Here, we investigated whether intranasally administered ChAdOx1 nCoV-19 reduces detection of virus in nasal swabs after challenging vaccinated macaques and hamsters with SARS-CoV-2 carrying a D614G mutation in the spike protein. Viral loads in swabs obtained from intranasally vaccinated hamsters were decreased compared to control hamsters, and no viral RNA or infectious virus was found in lung tissue after a direct challenge or after direct contact with infected hamsters. Intranasal vaccination of rhesus macaques resulted in reduced virus concentrations in nasal swabs and a reduction in viral loads in bronchoalveolar lavage and lower respiratory tract tissue. Intranasal vaccination with ChAdOx1 nCoV-19/AZD1222 reduced virus concentrations in nasal swabs in two different SARS-CoV-2 animal models, warranting further investigation as a potential vaccination route for COVID-19 vaccines.