COVID-19 severity appears to be reduced in spring/summer.

BACKGROUND: because of different human behaviours, SARS-CoV-2 spread may be lower in spring/summer. On the contrary, it is not clearly known whether the clinical course/severity of hospitalized patients infected by SARS-CoV-2 can be different in the various seasons.. OBJECTIVES: to understand whether there were differences in severity of COVID-19 in patients who had contracted the infection in winter versus those infected in spring/summer. DESIGN: observational retrospective cohort study. SETTING AND PARTICIPANTS: from the administrative database of the SARS-CoV-2 surveillance system and that of hospital discharge, a cohort of patients (8,221, 653 of which were hospitalized) who tested positive to the RT-PCR test for SARS-CoV-2 between 01.12.2020 and 31.07.2021 in the Grosseto province (Tuscany Region, Central Italy) was selected and analysed. MAIN OUTCOME MEASURES: hospitalization rate and length, continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV) use, Intensive Care Unite (ICU) admissions, intra-hospital mortality and PaO2/FiO2 values were measured and compared between subjects infected in winter and those who developed COVID-19 in spring/summer. Viral load (cycle threshold, Ct), vitamin D, serum ferritin, IL-6, procalcitonin, D-dimer, and C-reactive protein measured in the two periods were also compared. RESULTS: in the considered months, the hospitalization rate among 8,221 patients with COVID-19 was 8%: 370 (8.5%) individuals were hospitalized in winter and 283 (7,3%; p=0.31) in spring/summer; 62 (16.8%), 88 (23.8%), and 63 (17%) in winter and 28 (9.9%), 40 (14.1%), and 36 (12.7%) in spring/summer were admitted in ICU (p=0.01), used CPAP/NIV (p=0.002) and died (p=0.13), respectively. Hospitalization days were 14.5±11.6 in winter and 10.3±8.84 in spring/summer (p=0.001), while minimum PaO2/FiO2, measured during hospital stays was 123.2±38.6 in spring/summer and 112.6±40.8 in winter (p=0.054). Multivariate analysis (adjusted for all confounding factors) also confirmed reduced risks of having ICU admissions (0.53; 95%CI 0.32;0.88; p=0.01) and of using CPAP/NIV (0.48; 95%CI 0.32;0.75; p=0.001) in spring/summer when compared to winter. Hospitalization days and minimum PaO2/FiO2 were also lower in spring/summer (ß= -3.9; 95%CI -5.5;-2.2; p=0.001) and winter (ß= -17; 95%CI -0.93;35; p=0.06), respectively. The adjusted hazard ratio of mortality in winter, obtained with a Cox model, was higher of about 38% compared to spring/summer. No Ct values (viral load) differences were found either in winter (19.45±6.18) or spring/summer (20.3±6.7; p=0.343). IL-6, ferritin, procalcitonin, D-dimer were similar. Conversely, CRP was lower whereas vitamin D was higher in the warmer seasons. CONCLUSIONS: COVID-19 may be less severe during spring/summer in hospitalized patients. This does not seem to be influenced by different SARS-CoV-2 viral load in the different periods considered. C-reactive protein was found to be lower whereas vitamin D higher in the warmer months. It can be hypothesized that higher levels of vitamin D in spring/summer, compared to winter, may be associated to a positive modulation of COVID-19 induced inflammation with a possible disease severity reduction during spring/summer.

Safety and Efficacy of Outpatient Treatments for COVID-19: Real-Life Data from a Regionwide Cohort of High-Risk Patients in Tuscany, Italy (the FEDERATE Cohort).

Early COVID-19 treatments can prevent progression to severe disease. However, real-life data are still limited, and studies are warranted to monitor the efficacy and tolerability of these drugs. We retrospectively enrolled outpatients receiving early treatment for COVID-19 in 11 infectious diseases units in the Tuscany region of Italy between 1 January and 31 March 2022, when Omicron sublineages BA.1 and BA.2 were circulating. Eligible COVID-19 patients were treated with sotrovimab (SOT), remdesivir (RMD), nirmatrelvir/ritonavir (NRM/r), or molnupiravir (MOL). We gathered demographic and clinical features, 28-day outcomes (hospitalization or death), and drugs tolerability. A total of 781 patients (median age 69.9, 66% boosted for SARS-CoV-2) met the inclusion criteria, of whom 314 were treated with SOT (40.2%), 205 with MOL (26.3%), 142 with RMD (18.2%), and 120 with NRM/r (15.4%). Overall, 28-day hospitalization and death occurred in 18/781 (2.3%) and 3/781 (0.3%), respectively. Multivariable Cox regression showed that patients receiving SOT had a reduced risk of meeting the composite outcome (28-day hospitalization and/or death) in comparison to the RMD cohort, while no significant differences were evidenced for the MOL and NRM/r groups in comparison to the RMD group. Other predictors of negative outcomes included cancer, chronic kidney disease, and a time between symptoms onset and treatment administration > 3 days. All treatments showed good safety and tolerability, with only eight patients (1%) whose treatment was interrupted due to intolerance. In the first Italian multicenter study presenting real-life data on COVID-19 early treatments, all regimens demonstrated good safety and efficacy. SOT showed a reduced risk of progression versus RMD. No significant differences of outcome were observed in preventing 28-day hospitalization and death among patients treated with RMD, MOL, and NRM/r.

Efficacy of Licensed Monoclonal Antibodies and Antiviral Agents against the SARS-CoV-2 Omicron Sublineages BA.1 and BA.2

Newly emerging SARS-CoV-2 variants may escape monoclonal antibodies (mAbs) and antiviral drugs. By using live virus assays, we assessed the ex vivo inhibition of the B.1 wild-type (WT), delta and omicron BA.1 and BA.2 lineages by post-infusion sera from 40 individuals treated with bamlanivimab/etesevimab (BAM/ETE), casirivimab/imdevimab (CAS/IMD), and sotrovimab (SOT) as well as the activity of remdesivir, nirmatrelvir and molnupiravir. mAbs and drug activity were defined as the serum dilution (ID50) and drug concentration (IC50), respectively, showing 50% protection of virus-induced cytopathic effect. All pre-infusion sera were negative for SARS-CoV-2 neutralizing activity. BAM/ETE, CAS/IMD, and SOT showed activity against the WT (ID50 6295 (4355–8075) for BAM/ETE;18,214 (16,248–21,365) for CAS/IMD;and 456 (265–592) for SOT) and the delta (14,780 (ID50 10,905–21,020) for BAM/ETE;63,937 (47,211–79,971) for CAS/IMD;and 1103 (843–1334) for SOT). Notably, only SOT was active against BA.1 (ID50 200 (37–233)), whereas BA.2 was neutralized by CAS/IMD (ID50 174 (134–209) ID50) and SOT (ID50 20 (9–31) ID50), but not by BAM/ETE. No significant inter-variant IC50 differences were observed for molnupiravir (1.5 ± 0.1/1.5 ± 0.7/1.0 ± 0.5/0.8 ± 0.01 μM for WT/delta/BA.1/BA.2, respectively), nirmatrelvir (0.05 ± 0.02/0.06 ± 0.01/0.04 ± 0.02/0.04 ± 0.01 μM) or remdesivir (0.08 ± 0.04/0.11 ± 0.08/0.05 ± 0.04/0.08 ± 0.01 μM). Continued evolution of SARS-CoV-2 requires updating the mAbs arsenal, although antivirals have so far remained unaffected.

Efficacy of Licensed Monoclonal Antibodies and Antiviral Agents against the SARS-CoV-2 Omicron Sublineages BA.1 and BA.2.

Newly emerging SARS-CoV-2 variants may escape monoclonal antibodies (mAbs) and antiviral drugs. By using live virus assays, we assessed the ex vivo inhibition of the B.1 wild-type (WT), delta and omicron BA.1 and BA.2 lineages by post-infusion sera from 40 individuals treated with bamlanivimab/etesevimab (BAM/ETE), casirivimab/imdevimab (CAS/IMD), and sotrovimab (SOT) as well as the activity of remdesivir, nirmatrelvir and molnupiravir. mAbs and drug activity were defined as the serum dilution (ID50) and drug concentration (IC50), respectively, showing 50% protection of virus-induced cytopathic effect. All pre-infusion sera were negative for SARS-CoV-2 neutralizing activity. BAM/ETE, CAS/IMD, and SOT showed activity against the WT (ID50 6295 (4355-8075) for BAM/ETE; 18,214 (16,248-21,365) for CAS/IMD; and 456 (265-592) for SOT) and the delta (14,780 (ID50 10,905-21,020) for BAM/ETE; 63,937 (47,211-79,971) for CAS/IMD; and 1103 (843-1334) for SOT). Notably, only SOT was active against BA.1 (ID50 200 (37-233)), whereas BA.2 was neutralized by CAS/IMD (ID50 174 (134-209) ID50) and SOT (ID50 20 (9-31) ID50), but not by BAM/ETE. No significant inter-variant IC50 differences were observed for molnupiravir (1.5 ± 0.1/1.5 ± 0.7/1.0 ± 0.5/0.8 ± 0.01 µM for WT/delta/BA.1/BA.2, respectively), nirmatrelvir (0.05 ± 0.02/0.06 ± 0.01/0.04 ± 0.02/0.04 ± 0.01 µM) or remdesivir (0.08 ± 0.04/0.11 ± 0.08/0.05 ± 0.04/0.08 ± 0.01 µM). Continued evolution of SARS-CoV-2 requires updating the mAbs arsenal, although antivirals have so far remained unaffected.

Spontaneous abdominal bleeding associated with SARS-CoV-2 infection: causality or coincidence?

Authors present 6 cases of abdominal bleeding associated with COVID-19, representing 1.35% of all hospitalized COVID-19 patients and hypothesize that there could be, although not very frequently, a relationship between SARS-CoV2 and bleeding. They excluded a side effect of the low molecular weight heparin therapy that all patients underwent during the course of the disease or other possible causes. Alterations of the coagulation state or a weakness of the vascular wall due toa presumed endotheliitis SARS-CoV-2 infection induced, are hypothesized by the authors. Investigation and follow-up for possible hemorrhagic problems in patients with COVID-19 is recommended. In particular, clinicians should be vigilant about retroperitoneal hemorrhage in COVID-19 patients. In addition to the fact that these patients are being treated with anticoagulants, anemia and abdominal pain are the signs that should lead us to suspect this type of haemorrhage. More studies are needed to understand if COVID-19 can be directly associated with bleeding. (www.actabiomedica.it)