https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1006&context=covid19

SARS-CoV-2

Background While the leading symptoms during coronavirus disease 2019 (COVID-19) are acute and the majority of patients fully recover, a significant fraction of patients now increasingly experience long-term health consequences. However, most data available focus on health-related events after severe infection and hospitalisation. We present a longitudinal, prospective analysis of health consequences in patients who initially presented with no or minor symptoms of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection. Hence, we focus on mild COVID-19 in non-hospitalised patients. Methods 958 Patients with confirmed SARS-CoV-2 infection were observed from April 6th to December 2nd 2020 for long-term symptoms and SARS-CoV-2 antibodies. We identified anosmia, ageusia, fatigue or shortness of breath as most common, persisting symptoms at month 4 and 7 and summarised presence of such long-term health consequences as post-COVID syndrome (PCS). Predictors of long-term symptoms were assessed using an uni- and multivariable logistic regression model. Findings We observed 442 and 353 patients over four and seven months after symptom onset, respectively. Four months post SARS-CoV-2 infection, 8•6% (38/442) of patients presented with shortness of breath, 12•4% (55/442) with anosmia, 11•1% (49/442) with ageusia and 9•7% (43/442) with fatigue. At least one of these characteristic symptoms was present in 27•8% (123/442) and 34•8% (123/353) at month 4 and 7 post-infection, respectively. A lower baseline level of SARS-CoV-2 IgG, anosmia and diarrhoea during acute COVID-19 were associated with higher risk to develop long-term symptoms. Interpretation The on-going presence of either shortness of breath, anosmia, ageusia or fatigue as long-lasting symptoms even in non-hospitalised patients was observed at four and seven months post-infection and summarised as post-COVID syndrome (PCS). The continued assessment of patients with PCS will become a major task to define and mitigate the socioeconomic and medical long-term effects of COVID-19. Funding COVIM:„NaFoUniMedCovid19"(FKZ: 01KX2021)

Post-COVID syndrome in non-hospitalised patients with COVID-19: a longitudinal prospective cohort study.

Abstract Introduction This study aims to examine the worldwide prevalence of post COVID-19 condition, through a systematic review and meta-analysis. Methods PubMed, Embase, and iSearch were searched on July 5, 2021 with verification extending to March 13, 2022. Using a random effects framework with DerSimonian-Laird estimator, we meta-analyzed post COVID-19 condition prevalence at 28+ days from infection. Results 50 studies were included, and 41 were meta-analyzed. Global estimated pooled prevalence of post COVID-19 condition was 0.43 (95% CI: 0.39,0.46). Hospitalized and non-hospitalized patients have estimates of 0.54 (95% CI: 0.44,0.63) and 0.34 (95% CI: 0.25,0.46), respectively. Regional prevalence estimates were Asia— 0.51 (95% CI: 0.37,0.65), Europe— 0.44 (95% CI: 0.32,0.56), and North America— 0.31 (95% CI: 0.21,0.43). Global prevalence for 30, 60, 90, and 120 days after infection were estimated to be 0.37 (95% CI: 0.26,0.49), 0.25 (95% CI: 0.15,0.38), 0.32 (95% CI: 0.14,0.57) and 0.49 (95% CI: 0.40,0.59), respectively. Fatigue was the most common symptom reported with a prevalence of 0.23 (95% CI: 0.17,0.30), followed by memory problems (0.14 [95% CI: 0.10,0.19]). Discussion This study finds post COVID-19 condition prevalence is substantial; the health effects of COVID-19 appear to be prolonged and can exert stress on the healthcare system.

Global Prevalence of Post COVID-19 Condition or Long COVID: A Meta-Analysis and Systematic Review

Abstract Background This study aims to examine the worldwide prevalence of post-coronavirus disease 2019 (COVID-19) condition, through a systematic review and meta-analysis. Methods PubMed, Embase, and iSearch were searched on July 5, 2021 with verification extending to March 13, 2022. Using a random-effects framework with DerSimonian-Laird estimator, we meta-analyzed post-COVID-19 condition prevalence at 28+ days from infection. Results Fifty studies were included, and 41 were meta-analyzed. Global estimated pooled prevalence of post-COVID-19 condition was 0.43 (95% confidence interval [CI], .39–.46). Hospitalized and nonhospitalized patients had estimates of 0.54 (95% CI, .44–.63) and 0.34 (95% CI, .25–.46), respectively. Regional prevalence estimates were Asia (0.51; 95% CI, .37–.65), Europe (0.44; 95% CI, .32–.56), and United States of America (0.31; 95% CI, .21–.43). Global prevalence for 30, 60, 90, and 120 days after infection were estimated to be 0.37 (95% CI, .26–.49), 0.25 (95% CI, .15–.38), 0.32 (95% CI, .14–.57), and 0.49 (95% CI, .40–.59), respectively. Fatigue was the most common symptom reported with a prevalence of 0.23 (95% CI, .17–.30), followed by memory problems (0.14; 95% CI, .10–.19). Conclusions This study finds post-COVID-19 condition prevalence is substantial; the health effects of COVID-19 seem to be prolonged and can exert stress on the healthcare system. 

OUP accepted manuscript

Characteristics and predictors of acute and chronic post-COVID syndrome: A systematic review and meta-analysis

SARS-CoV-2 is a recently emerged s-coronavirus. Here we present the current knowledge on its epidemiologic features. Non-systematic review. SARS-CoV-2 replicates in the upper and lower respiratory tract. It is mainly transmitted by droplets and aerosols from asymptomatic and symptomatic infected subjects. The consensus estimate for the basis reproduction number (R0) is between 2 and 3, and the median incubation period is 5.7 (range 2–14) days. Similar to SARS and MERS, superspreading events have been reported, the dispersion parameter (kappa) is estimated at 0.1. Most infections are uncomplicated, and 5–10% of patients are hospitalized, mainly due to pneumonia with severe inflammation. Complications are respiratory and multiorgan failure; risk factors for complicated disease are higher age, hypertension, diabetes, chronic cardiovascular, chronic pulmonary disease and immunodeficiency. Nosocomial and infections in medical personnel have been reported. Drastic reductions of social contacts have been implemented in many countries with outbreaks of SARS-CoV-2, leading to rapid reductions. Most interventions have used bundles, but which of the measures have been more or less effective is still unknown. The current estimate for the infection’s fatality rate is 0.5–1%. Using current models of age-dependent infection fatality rates, upper and lower limits for the attack rate in Germany can be estimated between 0.4 and 1.6%, lower than in most European countries. Despite a rapid worldwide spread, attack rates have been low in most regions, demonstrating the efficacy of control measures.

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Epidemiology of SARS-CoV-2

COVID-19 is a syndrome caused by the recently emerged SARS-CoV-2. We collected clinical and epidemiologic data in an almost complete cohort of SARS-CoV-2 positive individuals from Regensburg, Germany, from March 2020 to May 2020. Analysis of a retrospectively documented cohort of consecutive COVID-19 cases recorded between March 7, 2020 and May 24, 2020 as part of an infection control investigation program, with prospective follow-up interviews gathering information on type and duration of symptoms and COVID-19 risk factors until June 26, 2020. Of 1089 total cases, 1084 (99.5%) cases were included. The incidence during the time period was 315.4/100,000, lower than in the superordinate government district Oberpfalz (468.5/100,000) and the overall state of Bavaria (359.7/100,000). The case fatality ratio (CFR) was 2.1%. Among fatal cases, the mean age was 74.4 years and 87% presented with known risk factors, most commonly chronic heart disease, chronic lung disease, kidney disease, and diabetes mellitus. 897 cases (82.7%) showed at least one symptom, most frequently cough (45%) and fever (41%). Further, 18% of cases suffered from odour/taste disorder. 17% of total cases reported no symptoms. The median duration of general illness was 10 days. During follow-up, 8.9% of 419 interviewed cases reported at least one symptom lasting at least 6 weeks, and fatigue was the most frequent persistent symptom. We report data on type and duration of symptoms, and clinical severity of nearly all (99.5%) patients with SARS-CoV-2 recorded from March 2020 to May 2020 in Regensburg. A broad range of symptoms and symptom duration was seen, some of them lasting several weeks in a considerable number of cases. The case-fatality ratio was 2.1%. Asymptomatic cases may be underrepresented due to the nature of the study.

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Clinical and epidemiological data of COVID-19 from Regensburg, Germany: a retrospective analysis of 1084 consecutive cases.

Borna disease virus 1 (BoDV-1) causes rare but often fatal encephalitis in humans. Late diagnosis prohibits an experimental therapeutic approach. Here, we report a recent case of fatal BoDV-1 infection diagnosed on day 12 after hospitalization by detection of BoDV-1 RNA in the cerebrospinal fluid. In a retrospective analysis, we detect BoDV-1 RNA 1 day after hospital admission when the cell count in the cerebrospinal fluid is still normal. We develop a new ELISA using recombinant BoDV-1 nucleoprotein, phosphoprotein, and accessory protein X to detect seroconversion on day 12. Antibody responses are also shown in seven previously confirmed cases. The individual BoDV-1 antibody profiles show variability, but the usage of three different BoDV-1 antigens results in a more sensitive diagnostic tool. Our findings demonstrate that early detection of BoDV-1 RNA in cerebrospinal fluid and the presence of antibodies against at least two different viral antigens contribute to BoDV-1 diagnosis. Physicians in endemic regions should consider BoDV-1 infection in cases of unclear encephalopathy and initiate appropriate diagnostics at an early stage. 

http://www.cell.com/article/S2666379121003761/pdf

Antibodies against viral nucleo-, phospho-, and X protein contribute to serological diagnosis of fatal Borna disease virus 1 infections

Background: We analyzed the epidemiology of COVID-19 in Regensburg after the first wave ended in June 2020 and compared it with patients' characteristics and symptoms in late summer/early autumn 2020. Methods: Retrospective analysis of epidemiological data from Regensburg (city/county) on age and initial symptoms as reported during case investigation for containment. Observed periods: March 7, 2020 to June 6, 2020 and August 12, 2020 to October 9, 2020. Results: The proportion of asymptomatic persons who tested positive for SARS-COV-2 in the second period was 55% (286 of 520 cases), whereas during the first wave from March to June 2020 this percentage was 14.4% (169 of 1,170 cases). A comparison of typical symptoms shows that the most common symptoms of COVID-19 in the first wave (cough, fever and generally feeling ill) were less often reported in the second period: cough 14% vs. 42%, fever 17% vs. 38%, general signs of illness 14% vs. 22% in the second vs. first period, respectively overall cases were younger in the second period, the median age of asymptomatic cases was comparable in both periods. The case fatality rate for the first period was 2.1%, in the second it was 0.2%. Discussion: The epidemiological situation in the second period is different from that during the first wave. We observed a considerable proportion of questionable cases in August/September 2020 (asymptomatic cases, high ct values, often only detection of one gene). False positive cases/non-contagious cases have to be taken into account for this period. On-demand or free-of-charge testing for asymptomatic persons will lower the positive predictive value of tests and place a high burden on finite capacities.

Changing epidemiology of COVID-19.

SARS-CoV‑2 („severe acute respiratory syndrome coronavirus 2“) hat sich seit Dezember 2019 rasch weltweit ausgebreitet. Eine erste Welle ist bis Ende Juni 2020 in vielen Regionen sichtbar. Wir stellen hier das aktuelle Wissen zur Epidemiologie und Pravention dar. SARS-CoV‑2 wird v. a. durch Tropfchen und Aerosole ubertragen und repliziert uberwiegend im oberen und unteren Respirationstrakt. Die Basisreproduktionszahl R0 liegt zwischen 2 und 3, die Inkubationszeit betragt im Median 6 (2–14) Tage. Wie bei den verwandten Coronaviren SARS-CoV und MERS(„Middle East respiratory syndrome“)-CoV spielen Superspreading-Ereignisse bei der Ausbreitung eine wichtige Rolle. Eine hohe Rate von Infektionen verlauft unkompliziert, moderate bis schwere Verlaufe treten bei 5–10 % der Infizierten auf. Pneumonien, kardiale Beteiligung und Thromboembolien sind die haufigsten zur Hospitalisierung fuhrenden Manifestationen. Risikofaktoren fur einen komplizierten Verlauf sind hoheres Alter, Hypertonie, Diabetes mellitus und chronische Herz- und Lungenerkrankungen sowie Immundefekte. Derzeit liegt die Schatzung fur die IFR („infection fatality rate“) uber alle Altersgruppen zwischen 0,5 und 1 %. Mit Bundeln verschiedener Masnahmen zur Reduktion sozialer Kontakte wurden Ausbruche in vielen Regionen begrenzt. Fur Deutschland wird fur die erste Welle eine Befallsrate von 0,4–1,8 % geschatzt, eine Ubersterblichkeit konnte dabei nicht beobachtet werden.

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Benedikt M J Lampl

Papers

Epidemiology of SARS-CoV-2

Clinical and epidemiological data of COVID-19 from Regensburg, Germany: a retrospective analysis of 1084 consecutive cases.

Antibodies against viral nucleo-, phospho-, and X protein contribute to serological diagnosis of fatal Borna disease virus 1 infections

Changing epidemiology of COVID-19.

[SARS-CoV-2/COVID-19-epidemiology and prevention].